- Email: [email protected]
Magnetic resonance imaging diagnosis of brain tumors in dogs
Accepted Manuscript Title: Magnetic resonance imaging diagnosis of brain tumors in dogs Author: R. Timothy Bentley PII: DOI: Reference:
S1090-0233(15)00043-X http://dx.doi.org/doi: 10.1016/j.tvjl.2015.01.025 YTVJL 4411
To appear in:
The Veterinary Journal
Accepted date:
24-1-2015
Please cite this article as: R. Timothy Bentley, Magnetic resonance imaging diagnosis of brain tumors in dogs, The Veterinary Journal (2015), http://dx.doi.org/doi: 10.1016/j.tvjl.2015.01.025. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
Review
Magnetic resonance imaging diagnosis of brain tumors in dogs R. Timothy Bentley a,* a
Department of Veterinary Clinical Sciences, Purdue University, West Lafayette, IN 479072026, USA
* Corresponding author. Tel.: +1 765 494 1107. E-mail address: [email protected]
Page 1 of 42
17
Highlights
18
Magnetic resonance imaging (MRI) features of brain tumors from dogs are described.
19
Groups include meningeal or ventricular masses, intra-axial enhancing to non-
20
enhancing lesions, and multifocal lesions.
21
Guidance for differential diagnoses is provided.
22
MRI features need to be interpreted with available clinical information.
23 24
Abstract
25
A great deal of information is now available regarding the range of magnetic
26
resonance imaging (MRI) features of many primary and secondary brain tumors from dogs. In
27
this review, these canine neoplasms are grouped into meningeal masses, ventricular masses,
28
intra-axial enhancing lesions, intra-axial mildly to non-enhancing lesions, and multifocal
29
lesions. For each of these patterns, the major and sporadic neoplastic differential diagnoses
30
are provided, and guidance on how to rank differential diagnoses for each individual patient is
31
presented. The implication of MRI features such as contrast-enhancement, signal intensities
32
and location is discussed. However, the information garnered from MRI must be correlated
33
with all available clinical information and with epidemiological data before creating a
34
differential diagnosis.
35 36
Keywords: Magnetic Resonance Imaging; Meningioma; Glioma; Canine; Diagnosis; Central
37
nervous system.
Page 2 of 42
38
Introduction
39
Brain tumors in adult dogs are a substantial cause of clinical disease and a major cause
40
of death (Song et al., 2013). Although surgery and ante-mortem histology are becoming
41
routine, not all lesions are safely accessible and expense may be prohibitive. Confidence in
42
the magnetic resonance imaging (MRI) diagnosis of brain tumors is needed prior to selecting
43
options such as euthanasia, radiation therapy without histology, or surgery.
44 45
Considerable information exists regarding what MRI features to expect knowing the
46
tumor type. However, clinical practice works in the opposite direction: when the MRI features
47
are available the clinician must predict whether a brain tumor is present, which type or types
48
is or are most likely, and if other tumors and non-neoplastic lesions are also reasonably
49
possible.
50 51
This review describes five broad MRI patterns of brain tumors in adult dogs: (1)
52
meningeal masses, (2) ventricular masses, (3) intra-axial enhancing lesions, (4) intra-axial
53
mildly or non-enhancing lesions, and (5) multifocal lesions. For each pattern, the common
54
and sporadic tumor types plus the major non-neoplastic differential diagnoses are provided.
55
MRI features are presented such that they can be used to increase or decrease the index of
56
suspicion for a particular tumor type, although they cannot be used to rule in or rule out
57
particular diagnoses.
58 59
The imaging features can be used to re-order the differential diagnoses, when
60
combined with clinical characteristics for that patient, such as signalment, history,
61
cerebrospinal fluid (CSF) analysis, evidence of extra-neural disease etc., and epidemiological
62
information. It may be possible to give a provisional diagnosis of a brain tumor based on all
Page 3 of 42
63
these data, or histology may still be an absolute pre-requisite to forming treatment
64
recommendations. One limitation is that the distinction between extra-axial and intra-axial is
65
occasionally challenging. Occasionally, both meningeal-based (e.g. meningioma) and intra-
66
axial masses (e.g. superficial glioma) must be retained in the differential diagnoses.
67
Oligodendroglioma in particular can be hard to differentiate from an intra-ventricular tumor.
68 69
Solitary meningeal masses: Extra-axial, non-ventricular, non-pituitary mass lesions
70
Description
71
The term solitary meningeal masses refers to lesions arising from the meninges,
72
interior to the skull and exterior to the brain tissue, the archetypal example being meningioma
73
although many other neoplastic and non-neoplastic masses arise in this location (Table 1).
74
Only lesions typically located within the cranial vault are covered here as information on
75
neoplastic invasion into the cranial vault (e.g. nasal adenocarcinoma, multilobular tumor of
76
bone, peripheral nerve sheath tumors, etc.) is readily available elsewhere (see, for example,
77
Lipsitz et al., 2001; Agthe et al., 2009; Wessmann et al., 2013).
78 79
For masses associated with the pituitary gland or nearby optic chiasm, the differential
80
diagnosis will include pituitary adenoma or adenocarcinoma, germ cell tumor,
81
craniopharyngioma and ependymoma (Eckersley et al., 1991; Valentine et al., 1988; Borrelli
82
et al., 2009; Seruca et al., 2010; Wisner et al., 2011), as well many neoplasms discussed
83
below, such as meningioma, lymphoma, granular cell tumor, gliomatosis cerebri (GC) and
84
metastatic carcinoma (Nielsen et al., 2008; Anwer et al., 2013; Gutierrez-Quintana et al.,
85
2013; Song et al., 2013; Bentley et al., 2014).
86
Page 4 of 42
87
The pachymeninges exist outside of the blood brain barrier (BBB) and almost any
88
tumor or granuloma arising here will contrast-enhance. Contrast-enhancement of extra-axial
89
tumors such as meningioma, histiocytic sarcoma (HS), granular cell tumor and
90
hemangioblastoma is almost universal (Kraft et al., 1997; Sharkey et al., 2004; Cherubini et
91
al., 2005; Sturges et al., 2008; Tamura et al., 2009; Ródenas et al., 2011; Singh et al., 2011;
92
Mishra et al., 2012; Anwer et al., 2013; Liebel et al., 2013). A meningeal sarcoma was a rare
93
exception (Ródenas et al., 2011).
94 95
Influence upon the subarachnoid space informs whether the mass is extra-axial or
96
intra-axial. Extra-axial lesions may widen the subarachnoid space. A T2-hyperintense line
97
(CSF or edematous brain) can delineate the margin of a meningioma with the brain. In
98
contrast, CSF adjacent to intra-axial masses may be pushed away from the brain and towards
99
the skull.
100 101
An extra-axial mass should have no normal brain tissue between the mass and the
102
contour of the fused dura mater-skull periosteum, or the mass may only contact the dura mater
103
(e.g. falcine meningiomas with no skull contact). Dural contact and extra-axial origin are
104
significant predictors of neoplasia, as is the ‘dural tail sign’ (Cherubini et al., 2005; Young et
105
al., 2014). A dural tail is a linear enhancement of thickened dura mater adjacent to an extra-
106
axial mass on T1-weighted (T1W) post-contrast images (Graham et al., 1998). In one study
107
(Young et al., 2014), it was noted in brain tumors only (meningiomas and sporadic other
108
neoplasms). However, in the author’s personal observation, and as reported by several groups
109
dural tails have occurred in HS, adenocarcinoma, choroid plexus tumor (CPT), fungal and
110
protozoal granulomas (Graham et al., 1998; Tamura et al., 2009; Baron et al., 2011; Ródenas
111
et al., 2011; Bentley et al., 2015). Broad-based dural contact and the dural tail sign may
Page 5 of 42
112
confirm that a lesion is extra-axial but do not allow a definitive diagnosis. Meningiomas,
113
other meningeal tumors and granulomas all display these features.
114 115
Features of mass effect include displacement of normal structures, midline shift,
116
distortion of ventricles and brain herniations. Unless they are small, meningiomas typically
117
cause a noticeable mass effect.
118 119
After meningioma, HS is often the most common solitary meningeal-based contrast-
120
enhancing mass lesion (Fig. 1) (Tamura et al., 2009; Ide et al., 2011; Song et al., 2013). On
121
MRI, HS is often found to be very similar to meningioma (Tamura et al., 2009), although
122
reduced enhancement might be more common (Wisner et al., 2011). Less commonly, there
123
may be invasion from the meninges to the parenchyma, a diffuse meningeal disease, mixed
124
intra-axial and extra-axial features or an intra-axial lesion (Snyder et al., 2006; Kang et al.,
125
2009; Tamura et al., 2009; Ide et al., 2011; Moore, 2014). Intracranial HS is frequently
126
primary (Kang et al., 2009; Tamura et al., 2009; Ide et al., 2011; Song et al., 2013; Moore,
127
2014) and the absence of extra-neural disease does not rule out HS. There are no MRI
128
guidelines to definitively differentiate meningioma and sub-dural HS. Disseminated HS
129
(malignant histiocytosis) rarely affects the brain (Chandra and Ginn, 1999; Thio et al., 2006).
130 131
Cystic regions
132
Cystic regions are isointense to CSF on T1W (i.e. dark) and T2-weighted (T2W) (i.e.
133
bright), and hypointense to normal gray matter on T2W fluid attenuation inversion recovery
134
(FLAIR), often isointense to CSF (James et al., 2012). Around one-quarter of meningiomas
135
are cystic or polycystic (Sturges et al., 2008; James et al., 2012). Neither single eccentric
136
cysts, nor intra-tumoral fluid accumulation(s) predict meningioma grade or subtype (Sturges
Page 6 of 42
137
et al., 2008). Their importance lies in adjusting the differential diagnoses. Well-defined cystic
138
regions have not yet been reported for HS, granular cell tumors, lymphoma, meningeal
139
sarcoma or hemangioblastoma (Sharkey et al., 2004; Snyder et al., 2006; Tamura et al., 2009;
140
Ródenas et al., 2011; Anwer et al., 2013; Liebel et al., 2013). However, cyctic regions have
141
been found to occur in meningeal carcinomatosis (Lipsitz et al., 1999; Mateo et al., 2010) and
142
brain invasion by pituitary tumors, nasal tumors and olfactory neuroblastoma (Kraft et al.,
143
1997; Kitagawa et al., 2006; Ródenas et al., 2011).
144 145
Identifying cystic regions in solitary meningeal masses could increase the suspicion of
146
meningioma over other neoplasms. Non-neoplastic extra-axial cystic lesions include
147
arachnoid diverticula, respiratory epithelial cyst, epidermoid cyst, dermoid cyst,
148
adenohypophyseal cyst, ependymal cyst and intracranial extension of nasal mucocele
149
(Sessums and Lane, 2008; Wyss-Fluehmann et al., 2008; MacKillop, 2011; De Decker et al.,
150
2012; Molín et al., 2014).
151 152 153
Tumor borders Meningiomas typically have borders well-defined with the brain; borders may be
154
smooth or irregular (Hathcock, 1996; Kraft et al., 1997) but are sharply defined in nearly 90%
155
of cases (Sturges et al., 2008). The margins of one hemangioblastoma (Liebel et al., 2013) and
156
most granular cell tumors (Higgins et al., 2001; Mishra et al., 2012; Anwer et al., 2013) were
157
also well-defined. Defined margins and a regular shape are significant predictors of neoplasia
158
(Cherubini et al., 2005; Young et al., 2014).
159 160 161
Fungal lesions frequently have indistinct borders (Sykes et al., 2010; Bentley et al., 2015) and lymphoma often has an irregular or indistinct margin (see below). Noting a poorly
Page 7 of 42
162
defined border or parenchymal invasion can increase the suspicion of a lesion other than a
163
meningioma, perhaps especially a round cell tumor or a granuloma.
164 165 166
Location Around three-quarters of meningiomas are supratentorial, especially fronto-olfactory
167
(Hathcock, 1996; Kraft et al., 1997; Sturges et al., 2008; Motta et al., 2012). Fronto-olfactory
168
tumors periodically include granular cell tumors (Higgins et al., 2001; Anwer et al., 2013),
169
hemangioblastoma (Fig. 2) (Liebel et al., 2013) and HS. Meningioma sporadically penetrates
170
the cribriform plate causing confusion with olfactory neuroblastoma (Hathcock, 1996;
171
McDonnell et al., 2007); similarly, with rare exceptions, there is usually a detectable tumor in
172
the nasal passages with an olfactory neuroblastoma (Fig. 3).
173 174
Hemispheric, cerebellar and tentorial meningiomas are usually ovoid or spherical
175
(Hathcock, 1996; Sturges et al., 2008). Plaque-like meningiomas are seen on the skull-base
176
(Fig. 4) (Sturges et al., 2008). Granular cell tumors are usually plaque-like meningeal
177
growths, including hemispheric or falcine tumors (Mishra et al., 2012; Anwer et al., 2013).
178 179 180
Signal intensities T1-hyperintensity increases the suspicion of a granular cell tumor, an otherwise
181
sporadic neoplasm, especially for a plaque-like non-skull-base lesion (Anwer et al., 2013).
182
Meningiomas and most other meningeal masses are usually T1-isointense or hypointense
183
(Hathcock, 1996; Kraft et al., 1997; Sturges et al., 2008; Ródenas et al., 2011).
184 185 186
A T2-isointense or hyperintense signal is non-specific and is observed in the large majority of meningiomas, other extra-axial neoplasms and granulomas (Tamura et al., 2009;
Page 8 of 42
187
Lipitz et al., 2010; Sykes et al., 2010; Ródenas et al., 2011; Thomovsky et al., 2011; Anwer et
188
al., 2013; Liebel et al., 2013; Bentley et al., 2015). T2-hypointensity occurs in just 2% of
189
meningiomas (Sturges et al., 2008) but is also unusual for other tumors, and should stimulate
190
consideration of benign hematoma or hemorrhage within a meningioma (Martin-Vaquero et
191
al., 2010). Peri-lesional edema is seen with meningiomas and many other etiologies.
192 193 194
Bone changes Sclerosis or lysis of the bone may be observed adjacent to meningiomas (Hathcock,
195
1996). Although occasional on computed tomography (CT) (Mercier et al., 2007; Jung et al.,
196
2014), hyperostosis was not detected by MRI in 112 dogs (Sturges et al., 2008). Bony lesions
197
were uncommon in each of neoplastic, inflammatory and vascular diseases, with no statistical
198
significance (Young et al., 2014).
199 200
Non-neoplastic differential diagnoses
201
Granulomas, especially of fungal origin, sporadically form solitary contrast-enhancing
202
meningeal masses within an intact cranial vault (Lipitz et al., 2010; Sykes et al., 2010; Baron
203
et al., 2011; Hecht et al., 2011; Bentley et al., 2015).
204 205
Solitary ventricular masses
206
Description
207
Most solitary ventricular masses are CPTs or ependymomas (Song et al., 2013) (Table
208
2). CPT is usually the leading differential diagnosis; the vast majority of these enhance
209
intensely and they are most common in the fourth ventricle (Westworth et al., 2008). Most
210
CPTs cause ventriculomegaly, either rostral to the mass or rostral and caudal, and peri-
211
ventricular edema (Westworth et al., 2008). CPTs occur as papillomas or carcinomas; a
Page 9 of 42
212
papilliform structure supports papilloma (Westworth et al., 2008). Choroid plexus carcinomas
213
can display ‘drop metastasis’ (transplantation via the CSF) to other ventricular and
214
subarachnoid locations (Westworth et al., 2008) and even cause meningeal carcinomatosis
215
(Lipsitz et al., 1999).
216 217
Location
218
Ventricular masses include all tumors within the lateral ventricles, interventricular
219
foramina, third ventricle, mesencephalic aqueduct, fourth ventricle or lateral apertures. As
220
CPTs are more abundant, any mass replacing the normal choroid plexus is more likely to be a
221
CPT than ependymoma, especially sited in the fourth ventricle.
222 223
If a normal choroid plexus can be identified as a small contrast enhancing area on
224
T1W images, separate from a solitary ventricular mass, that mass is probably not a CPT; the
225
clinician should include ependymoma as a differential diagnosis. Ependymoma has been
226
reported in the rostral horn of the lateral ventricle (distinct from the normal choroid plexus)
227
and might appear to be intra-axial and peri-ventricular (Kraft et al., 1997; Traslavina et al.,
228
2013). Another example assumed a ventral extra-axial location invading the hypophysis
229
(Borrelli et al., 2009). However, one ependymoma was shown to have affected the
230
interventricular foramen, a classic location for CPT (Vural et al., 2006). Contrast-
231
enhancement varied from none to strong.
232 233
Central neurocytoma, spanning both lateral ventricles via the interventricular foramina
234
or originating from the septum pellucidum, were shown to display marked contrast-
235
enhancement on the one MRI reported (Rossmeisl et al., 2012). Williams et al. (2009) found a
Page 10 of 42
236
pineal tumor enhancing within the quadrigeminal cistern of one dog. Parenchymal neoplasms
237
(e.g. oligodendroglioma) may take the appearance of a ventricular mass.
238 239
Signal intensities
240
CPTs are T1-hyperintense much more often than other brain tumors but can also be
241
isointense or hypointense (Kraft et al., 1997; Westworth et al., 2008). Other features are non-
242
specific: they are typically T2-hyperintense with peri-tumoral edema (Westworth et al., 2008).
243
Cystic structures have been seen in CPTs and ependymoma (Kraft et al., 1997; Westworth et
244
al., 2008).
245 246
Occasionally there is difficulty in differentiating a fourth ventricular CPT from a
247
cerebellopontomedullary angle meningioma; one CPT was misdiagnosed as a meningioma
248
(Ródenas et al., 2011). Meningiomas can even originate in the choroid plexus and be
249
completely contained within the fourth ventricle (Salvadori et al., 2011). Overlapping features
250
of these extra-axial neoplasms include marked contrast-enhancement and peri-tumoral edema
251
(Sturges et al., 2008; Westworth et al., 2008). Meningiomas are, however, infrequently T1-
252
hyperintense (Sturges et al., 2008). There will be individual overlap of signalment and CSF
253
results, but these findings are valuable (Snyder et al., 2006; Sturges et al., 2008; Westworth et
254
al., 2008; Song et al., 2013).
255 256
Non-neoplastic differential diagnoses
257
Non-neoplastic ventricular masses are rare. Choroid plexus cyst (Brewer et al., 2010),
258
cholesterol granuloma (Lovett et al., 2012) and epidermoid cyst (De Decker et al., 2012) have
259
all been reported on MRI. The choroid plexus cyst was most akin to a CPT.
260
Page 11 of 42
261
Solitary enhancing intra-axial lesions
262
Description
263
Solitary enhancing intra-axial lesions occur inside the brain parenchyma; normal brain
264
is typically evident between the lesion and the dura mater-skull periosteum (Table 3). Often,
265
the most important differential diagnosis is glioma, including oligodendroglioma, astrocytoma
266
including glioblastoma, and rarer variants such as oligoastrocytoma and undifferentiated
267
glioma (Snyder et al., 2006; Song et al., 2013). Certain MRI features allow partial
268
discrimination of low grade glioma (LGG) vs. high grade glioma (HGG), and of astrocytoma
269
vs. oligodendroglioma. Yet more information is available regarding other intra-axial diseases.
270
Together with clinical and epidemiological data, the differential diagnoses can be adjusted for
271
individual dogs.
272 273
Gliomas have widely varying MRI appearances and have been confused with diseases
274
as diverse as ischemic or hemorrhagic cerebrovascular accident, inflammatory disease,
275
leukoencephalopathy and meningioma (Cervera et al., 2011; Ródenas et al., 2011). Given the
276
substantial variation, the differential diagnoses can be quite different from case to case.
277 278
This section includes both masses and lesions without mass effect. The presence of
279
mass effect informs the differential diagnoses. Mass effect is seen in over 90% of
280
astrocytomas and oligodendrogliomas (Young et al., 2011; Bentley et al., 2013).
281
Oligodendrogliomas usually distort ventricles and failure to do significantly indicates
282
astrocytoma (Bentley et al., 2013). Lymphoma and GC (see final section) may infiltrate
283
without mass effect.
284 285
Contrast-enhancement
Page 12 of 42
286
Strong contrast-enhancement significantly predicts neoplasia over inflammatory,
287
vascular and other lesions (Cherubini et al., 2005; Young et al., 2014). Most enhancing intra-
288
axial neoplasms are gliomas (Snyder et al., 2006). Inflammatory syndromes (infectious and
289
primary) are still a chief differential diagnosis for solitary enhancing lesions; vascular lesions
290
are a sporadic cause.
291 292
Contrast-enhancement is the most repeatable way of distinguishing within gliomas.
293
LGG displays mild to no enhancement significantly more commonly than HGG (Young et al.,
294
2011; Bentley et al., 2013). Nearly every glioblastoma (grade IV astrocytoma) described was
295
enhancing, and mainly specified as moderate or marked (Lipsitz et al., 2003; Snyder et al.,
296
2006; Young et al., 2011; Giri et al., 2011; Bentley et al., 2013). Enhancement in a partial or
297
complete ring occurs in all grades (Bentley et al., 2013).
298 299
Other primary brain tumors cause enhancing intra-axial lesions, including
300
hemangioma (Schoeman et al., 2002; Eichelberger et al., 2011) and primitive
301
neuroectodermal tumor (see below). A neuroblastoma (a distinct entity from olfactory
302
neuroblastoma) was found to be intra-axial (Capucchio, 2003). Metastases (see below) are a
303
prime
304
hemangiosarcoma, lymphoma, carcinoma or melanoma.
consideration
for
a
solitary
lesion
accompanying
known
extra-neural
305 306
Signal intensities
307
The majority of gliomas and other tumors show non-specific signal intensities, and are
308
generally T1-hypointense and T2-hyperintense (Young et al., 2011, 2014; Bentley et al.,
309
2013). Gliomas are frequently heterogenous, especially T2W signals (Bentley et al., 2013),
310
but mixed intensities (particularly T2W FLAIR) are predictive of neoplasia generally (Young
Page 13 of 42
311
et al., 2014). Cystic regions are significantly more common in HGG than LGG (Bentley et al.,
312
2013), but can occur in other neoplasms and diseases.
313 314
The causes of T1-hyperintensity within tumors are narrow, and include melanoma (see
315
below) and hemorrhage. Astrocytomas are significantly more T1-isointense or hyperintense
316
than oligodendrogliomas, despite showing no evidence of increased hemorrhage (Bentley et
317
al., 2013).
318 319
Hemorrhage or T2W gradient echo (GRE) signal voids occur in 30-40% of gliomas
320
and do not discriminate, occurring in both astrocytoma and oligodendroglioma and all grades
321
but perhaps especially HGG (Young et al., 2011; Bentley et al., 2013). Other lesions with
322
hemorrhage or GRE signal voids include hemangiosarcoma, hemorrhagic cerebrovascular
323
accident, hemangioma, hamartoma, melanoma and cerebellar medulloblastoma (Schoeman et
324
al., 2002; MacKillop et al., 2007; Ide et al., 2009; Eichelberger et al., 2011; Tidwell and
325
Robertson, 2011; Wisner et al., 2011; Lowrie et al., 2012; Sebastianelli et al., 2013).
326 327
Peri-lesional edema occurs with many neoplasms. It is significantly more common in
328
glioma than cerebrovascular accident (Cervera et al., 2011). Within gliomas, astrocytomas
329
may have any degree of edema (including extensive), but oligodendrogliomas have
330
significantly less edema (Bentley et al., 2013), typically minimal to moderate (Wisner et al.,
331
2011). Edema adjacent to fungal granulomas can be extensive (Bentley et al., 2015).
332 333
Location
334
Oligodendrogliomas are usually prosencephalic (Young et al., 2011; Bentley et al.,
335
2013). While astrocytomas are also predisposed to the forebrain, nonetheless the majority of
Page 14 of 42
336
caudal fossa gliomas are astrocytic (including glioblastoma) (Lenz et al., 1991; Young et al.,
337
2011).
338 339
The relationship of location with grade and type of glioma is emerging. Surface
340
contact (Young et al., 2011) and ventricular distortion (Bentley et al., 2013) are more
341
common for oligodendroglioma. Involvement of deep structures (e.g. the thalamus) is more
342
common in HGG (Bentley et al., 2013); glioblastomas in thalamic or brainstem locations are
343
numerous (Lipsitz et al., 2003; Snyder et al., 2006).
344 345
For intra-axial cerebellar lesions, medulloblastoma should be considered (see below).
346
Astrocytoma including glioblastoma occasionally occurs here but solitary cerebellar
347
oligodendroglioma is very rare (Snyder et al., 2006; Young et al., 2011).
348 349
Non-neoplastic differential diagnoses
350
Primary inflammatory diseases, including granulomatous meningoencephalomyelitis
351
(GME), produce focal or multifocal lesions that often enhance (Cherubini et al., 2006;
352
Adamo, 2007; Granger et al., 2010). Infectious diseases, including fungal infections, may
353
cause solitary intra-axial contrasting-enhancing masses (Bentley et al., 2011; Bentley et al.,
354
2015).
355 356
Solitary mildly or non-enhancing intra-axial lesions
357
Description
358 359
The differential diagnosis should effectively include all of the tumors above, but poor contrast-enhancement amends the order of the neoplastic differential diagnoses (Table 4). The
Page 15 of 42
360
non-neoplastic differential diagnoses are also reasonably different. As implied above, LGG is
361
a major differential diagnosis (Young et al., 2011; Bentley et al., 2013).
362 363
Minimal contrast-enhancement is characteristic of GC; every intra-axial lesion to date
364
has been non-enhancing or occasionally mildly enhancing and some are solitary (see below).
365
Non-enhancing exceptions of metastatic tumors have been reported (Hanselman et al., 2006;
366
Singh et al., 2012; Gutierrez-Quintana et al., 2013).
367 368
Primitive neuroectodermal tumor (PNET) includes cerebellar medulloblastoma and
369
PNETs elsewhere that are histologically indistinguishable from medulloblastoma (Koestner et
370
al., 1999). The majority of MRI reports involve cerebellar medulloblastomas. These intra-
371
axial cerebellar masses, usually mid-caudal, are none to mildly heterogeneously-enhancing
372
(McConnell et al., 2004; Polizopoulou et al., 2004; MacKillop et al., 2007; Singh et al., 2011;
373
Choi et al., 2012; Patsikas et al., 2014). Lesions can be well demarcated or poorly marginated.
374
Signal intensities are non-specific, being T1-isointense to hypointense and mildly T2-
375
hyperintense, often with multiple regions of high T2 signal. GRE signal voids occurred in one
376
case (MacKillop et al., 2007) and this tumor can be hemorrhagic (Headley et al., 2009). A
377
fronto-olfactory PNET was briefly described as intra-axial, T1-hypointense, T2-hyperintense
378
and strongly ring-enhancing (Glass et al., 2000). Sporadic PNETs traversing the cranial vault
379
are reported to be moderately to strongly enhancing (Katayama et al., 2001; Snyder et al.,
380
2006; Gains et al., 2011).
381 382
Ischemic strokes are a major differential diagnosis for non-enhancing lesions (Cervera
383
et al., 2011). Contrast-enhancement has a predictive value for neoplasia of 74% (Cherubini et
384
al., 2005) and strong enhancement occurs in only 5% of vascular lesions (Young et al., 2014).
Page 16 of 42
385
Contrast-enhancement may occur due to revascularization, so is not typical in the first few
386
days (Tidwell and Robertson, 2011). Likewise, contrast-enhancement does not rule out
387
hemorrhagic cerebrovascular accident, which is possible during peripheral revascularization
388
(Fig. 5) (Tidwell and Robertson, 2011).
389 390
Diffusion weighted imaging (DWI) and apparent diffusion coefficient maps are
391
critical in distinguishing neoplasms from infarcts. Both glioma and (especially) ischemia can
392
cause restricted diffusion. However, hyperintensity on apparent diffusion coefficients is
393
significantly more common for glioma, as is mass effect (Cervera et al., 2011). Wedge-shaped
394
lesions predict cerebrovascular accident. When DWI was provided the rate of misdiagnosis
395
between cerebrovascular accidents and gliomas was much lower. Acute infarcts may have
396
lower apparent diffusion coefficients than neoplasia (Sutherland-Smith et al., 2011).
397 398
In 200 MRIs, GRE allowed the detection of 32 hemangiosarcoma metastases and 35
399
microbleeds unnoticed on T2 and FLAIR sequences (Hodshon et al., 2014). Tumors can be
400
misdiagnosed as cerebrovascular accidents and vice versa, and DWI and GRE sequences are
401
requisite in the author’s experience.
402 403
MRI features should not be over-interpreted and specific pathologies should not be
404
ruled out prematurely. Neoplastic lesions may not enhance while infarction may (Singh et al.,
405
2011) but only 4/29 primary brain tumors failed to enhance in that study: two GC and two
406
gliomas of unspecified grade. Subsequent studies have shown that GC and LGG routinely
407
lack enhancement. All other primary brain tumors enhanced.
408 409
Non-neoplastic differential diagnoses
Page 17 of 42
410 411
Inflammatory lesions including GME and distemper can be non-enhancing (Cherubini et al., 2006; Singh et al., 2011).
412 413
Multifocal lesions
414
Description
415
This includes multifocal lesions in the same region (e.g. two lesions in the same
416
hemisphere), lesions affecting multiple brain compartments, and multifocal meningeal
417
lesions. Both enhancing and non-enhancing lesions are included (Table 5).
418 419
Lymphoma can produce any of the five patterns considered in this review, although
420
ventricular involvement and non-enhancing lesions are atypical. Between primary central
421
nervous system (CNS) lymphoma and secondary CNS lymphoma (including intravascular
422
lymphoma), extreme variation occurs. This includes one to many intra-axial lesions, solitary
423
extra-axial lesions, meningeal enhancement, and concurrent intra and extra-axial lesions
424
(Morozumi et al., 1997; Kent et al., 2001; Bush et al., 2003; Hanselman et al., 2006; Snyder et
425
al., 2006; Nielsen et al., 2008; Ródenas et al., 2011; Thomovsky et al., 2011; Palus et al.,
426
2012).
427 428
Primary CNS lymphoma is well recognized and the absence of known extra-neural
429
disease does not rule out lymphoma (Mellema et al., 2000; Long et al., 2001; Snyder et al.,
430
2006; Palus et al., 2012). Retropharyngeal lymph nodes or temporalis muscles may be
431
abnormal on MRI (Mellema et al., 2000; Thomovsky et al., 2011; Palus et al., 2012).
432
Intravascular lymphoma normally affects the brain (Kent et al., 2001; Bush et al., 2003) and
433
MRI features include multiple lesions, each displaying varying combinations of infarctive,
434
hemorrhagic and neoplastic criteria (Fig. 6).
Page 18 of 42
435 436
Lymphoma has no characteristic MRI appearance; the sensitivity of MRI has been
437
reported to be 0% in some studies (Wolff et al., 2012). CSF analysis generally fails to reveal
438
neoplastic cells and overlaps with other etiologies (Kent et al., 2001; Hanselman et al., 2006;
439
Snyder et al., 2006).
440 441
In order of frequency, common hematogenous metastases are hemangiosarcoma,
442
round cell tumors (particularly lymphoma), carcinoma and melanoma (Snyder et al., 2008;
443
Song et al., 2013). Metastases often affect the cerebrum with or without other intracranial
444
regions (Snyder et al., 2008; Ródenas et al., 2011). The pituitary gland is involved by
445
lymphoma and carcinomas, sporadically by HS and melanoma, and negligibly by
446
hemangiosarcoma (Kent et al., 2001; Tamura et al., 2007; Snyder et al., 2008; Gutierrez-
447
Quintana et al., 2013).
448 449
Metastasis usually causes multifocal MRI lesions (Wisner et al., 2011). While
450
metastasis is an important consideration for a solitary lesion, most MRI reports specify
451
multifocal lesions (Appendix A; Supplementary material). In people, solitary metastasis is a
452
major differential diagnosis for HGG (Hakyemez et al., 2010). Minimal information is
453
available to assist in differentiating canine primary brain tumors from metastases by MRI
454
alone, highlighting the importance of considering the dog as a whole (Fig. 7).
455 456
GC may cause focal lesions, multifocal lesions, spread down white matter,
457
periventricular and subpial lesions, or sporadic diffuse meningeal enhancement (Porter et al.,
458
2003; Gruber et al., 2006; Galán et al., 2010; Ródenas et al., 2011; Fukuoka et al., 2012;
459
Martin-Vaquero et al., 2012; Canal et al., 2013; Bentley et al., 2014).
Page 19 of 42
460 461
Dogs are occasionally affected by two unrelated tumors, usually a meningioma or
462
glioma with another tumor (Stacy et al., 2003; Alves et al., 2006; Snyder et al., 2006;
463
MacKillop et al., 2007; McDonnell et al., 2007; Sturges et al., 2008; Espino et al., 2009).
464
Multifocal oligodendroglioma occurred in three dogs (Koch et al., 2011) and
465
oligodendroglioma can spread via the CSF (Koestner et al., 1999). Two dogs with diffuse
466
low-grade astrocytoma had non-enhancing lesions (Kraft et al., 1990).
467 468 469
Contrast enhancement This is a key discriminating feature. The most repeatable characteristic of lymphoma
470
is contrast-enhancement. With the exception of only one dog (Hanselman et al., 2006),
471
enhancement occurred in every report of primary, secondary and intravascular lymphoma
472
including a case with ventricular enhancement (Morozumi et al., 1997; Kent et al., 2001;
473
Bush et al., 2003; Snyder et al., 2006; Nielsen et al., 2008; Ródenas et al., 2011; Thomovsky
474
et al., 2011; Palus et al., 2012). Contrast-enhancement is absent in only 1% of humans with
475
primary CNS lymphoma (Batchelor and Loeffler, 2006). With rare exceptions, metastatic
476
lesions also usually enhance (Wisner et al., 2011) (Appendix: Supplementary material).
477 478
In contrast, GC lesions rarely enhance. Every reported intra-axial GC lesion was
479
minimally or non-enhancing, although extra-axial masses and diffuse meningeal lesions can
480
enhance (Porter et al., 2003; Gruber et al., 2006; Galán et al., 2010; Singh et al., 2011;
481
Fukuoka et al., 2012; Martin-Vaquero et al., 2012; Plattner et al., 2012; Canal et al., 2013;
482
Bentley et al., 2014).
483 484
Signal intensities
Page 20 of 42
485
Melanin is T1-hyperintense but melanomas themselves vary. In humans, there are
486
increasing rates of T1-hyperintensity from amelanotic to highly melanotic histologic subtypes
487
of metastases (Isiklar et al., 1995). Melanin and hemorrhage share many features including
488
GRE signal voids (Fig. 8); in the same study 12% of melanoma metastases displayed features
489
consistent with hematoma. Canine intracranial metastasis MRI has not been reported, but
490
ocular and nasal melanomas are inconsistently T1-hyperintense and T2-hypointense (Kato et
491
al., 2005; Miwa et al., 2005; Hicks and Fidel, 2006). Human melanoma metastases typically
492
contrast-enhance (Isiklar et al., 1995) and there might be much overlap in the MRI features of
493
canine glioma, hemangiosarcoma and melanoma.
494 495
Signal intensities are otherwise generally non-specific, being mostly T1-isointense to
496
hypointense and T2-hyperintense for lymphoma, gliomatosis cerebri and many other lesions
497
(Hanselman et al., 2006; Snyder et al., 2006; Ródenas et al., 2011; Palus et al., 2012; Bentley
498
et al., 2014). T1-hyperintensities were shown to have occurred in one dog with multiple
499
infarcts secondary to intravascular lymphoma (Kent et al., 2001).
500 501
Some lymphomas and numerous GC and metastatic lesions have vague borders
502
(Snyder et al., 2006; Thomovsky et al., 2011; Wisner et al., 2011; Ródenas et al., 2011; Palus
503
et al., 2012; Bentley et al., 2014). MRI might be within normal limits with lymphoma,
504
multifocal oligodendroglioma or especially GC (Koch et al., 2011; Plattner et al., 2012;
505
Bentley et al., 2014; Young et al., 2014).
506 507
Mass effect
508
Lymphoma and particularly GC are archetypal examples of diffuse infiltration of
509
neoplastic cells with negligible mass effect. While most cases of lymphoma have a mass
Page 21 of 42
510
effect (Ródenas et al., 2011; Thomovsky et al., 2011; Palus et al., 2012), some do not
511
(Hanselman et al., 2006). Many GC cases exhibit single or multiple parenchymal T2-
512
hyperintensities with minimal mass effect; less commonly, mass lesions are seen with or
513
without concurrent infiltrative disease (Porter et al., 2003; Galán et al., 2010; Fukuoka et al.,
514
2012; Plattner et al., 2012; Bentley et al., 2014).
515 516
Multifocal or diffuse meningeal lesions
517
Lymphoma is a major cause of multifocal or diffuse meningeal enhancement
518
(Mellema et al., 2000; Palus et al., 2012). Often accompanying other lesions, there may be
519
subtle enhancement of the meninges of one region, enhancing meninges adjacent to an extra-
520
axial mass, or strong multifocal-diffuse meningeal enhancement (Mellema et al., 2000; Bush
521
et al., 2003; Thomovsky et al., 2011; Palus et al., 2012).
522 523
Other neoplasms sporadically exhibiting multifocal to diffuse meningeal enhancement
524
include HS (Tamura et al., 2009), leukemia (Mellema et al., 2000; Vernau et al., 2000), GC
525
(Canal et al., 2013), granular cell tumor (Mishra et al., 2012) and meningeal carcinomatosis
526
(e.g. mammary carcinoma or choroid plexus carcinoma) (Lipsitz et al., 1999; Behling-Kelly et
527
al., 2010; Mateo et al., 2010). Diffuse-multifocal meningeal enhancement, with or without
528
other lesions, can increase the suspicion of round cell tumors and inflammatory disease.
529 530
Non-neoplastic differential diagnoses
531
For multifocal lesions, a major consideration is inflammatory disease including GME,
532
necrotizing encephalitides (Granger et al., 2010) and fungal, neosporosis, viral and tick-borne
533
infectious diseases (Bathen-Noethen et al., 2008; Garosi et al., 2010; Lipitz et al., 2010; Sykes
Page 22 of 42
534
et al., 2010; Parzefall et al., 2014). Other causes include thiamine deficiency (Garosi et al.,
535
2003).
536 537
Post-ictal changes are reversible MRI abnormalities in seizing dogs (Mellema et al.,
538
1999). Such changes may overlap in appearance with infiltrating neoplasia, occurring
539
unilaterally or bilaterally in the parenchyma of the pyriform-temporal lobe and elsewhere, and
540
showing non-specific signal intensities and variable contrast-enhancement. It is noteworthy
541
that neoplasia is the most common cause of secondary epilepsy (Pákozdy et al., 2008).
542 543
Conclusions
544
Much information is available to create a comprehensive differential diagnosis (and to
545
rank it appropriately) for dogs with brain tumors undergoing MRI. However, the features
546
garnered from MRI must be correlated with all available clinical information and with
547
epidemiological data. When MRI lesions are first categorized as meningeal masses,
548
ventricular masses, intra-axial enhancing lesions, intra-axial mildly to non-enhancing lesions
549
or multifocal lesions, then a more specific list of differential diagnoses can be developed for
550
each individual patient. This is imperative in selecting therapies without or prior to the
551
availability of histopathology data.
552 553 554 555
Conflict of interest statement The author of this paper has no financial or personal relationship with other people or organisations that could inappropriately influence or bias the content of the paper.
556 557
Acknowledgements
Page 23 of 42
558 559
The author thanks the diagnostic imaging service of the Purdue University Veterinary Teaching Hospital for acquiring images used in this article.
560 561 562 563
Appendix: Supplementary material Supplementary data associated with this article can be found in the online version, at doi….setters please insert doi number
564 565
References
566 567
Adamo, P., 2007. Granulomatous meningoencephalomyelitis in dogs. Compendium: Continuing Education for Veterinarians 29, 678–90.
568 569 570
Agthe, P., Caine, A.R., Gear, R.N., Dobson, J.M., Richardson, K.J., Herrtage, M.E., 2009. Prognostic significance of specific magnetic resonance imaging features in canine nasal tumours treated by radiotherapy. Journal of Small Animal Practice 50, 641–648.
571 572 573
Alves, A., Prada, J., Almeida, J.M., Pires, I., Queiroga, F., Platt, S.R., Varejão, A.S.P., 2006. Primary and secondary tumors occurring simultaneously in the brain of a dog. Journal of Small Animal Practice 47, 607–610.
574 575 576
Anwer, C.C., Vernau, K.M., Higgins, R.J., Dickinson, P.J., Sturges, B.K., LeCouteur, R.A., Bentley, R.T., Wisner, E.R., 2013. Magnetic resonance imaging features of intracranial granular cell tumors in six dogs. Veterinary Radiology and Ultrasound 54, 271–277.
577 578 579
Baron, M.L., Hecht, S., Westermeyer, H.D., Mankin, J.M., Novak, J.M., Donnell, R.L., 2011. Intracranial extension of retrobulbar blastomycosis (Blastomyces dermatitidis) in a dog. Veterinary Ophthalmology 14, 137–141.
580 581
Batchelor, T., Loeffler, J.S., 2006. Primary CNS lymphoma. Journal of Clinical Oncology 24, 1281–1288.
582 583 584
Bathen-Noethen, A., Stein, V.M., Puff, C., Baumgaertner, W., Tipold, A., 2008. Magnetic resonance imaging findings in acute canine distemper virus infection. Journal of Small Animal Practice 49, 460–467.
585 586 587
Behling-Kelly, E., Petersen, S., Muthuswamy, A., Webb, J.L., Young, K.M., 2010. Neoplastic pleocytosis in a dog with metastatic mammary carcinoma and meningeal carcinomatosis. Veterinary Clinical Pathology 39, 247–252.
588 589
Bentley, R.T., Burcham, G.N., Heng, H.G., Levine, J.M., Longshore, R., Carrera-Justiz, S., Cameron, S., Kopf, K., Miller, M.A., 2014. A comparison of clinical, magnetic
Page 24 of 42
590 591 592
resonance imaging and pathological findings in dogs with gliomatosis cerebri, focusing on cases with minimal magnetic resonance imaging changes. Veterinary and Comparative Oncology doi: 10.1111/vco.12106
593 594 595
Bentley, R.T., Faissler, D., Sutherland-Smith, J., 2011. Successful management of an intracranial phaeohyphomycotic fungal granuloma in a dog. Journal of the American Veterinary Medical Association 239, 480–485.
596 597 598 599
Bentley, R.T., Heng, H.G., Thompson, C., Lee, C.S., Kroll, R.A., Roy, M.E., Marini, L., Heo, J., Wigle, W.L., 2015. Magnetic resonance imaging features and outcome for solitary central nervous system Coccidioides granulomas in 11 dogs and cats. Veterinary Radiology and Ultrasound. In press, 2015.
600 601 602 603
Bentley, R.T., Ober, C.P., Anderson, K.L., Feeney, D.A., Naughton, J.F., Ohlfest, J.R., O’Sullivan, M.G., Miller, M.A., Constable, P.D., Pluhar, G.E., 2013. Canine intracranial gliomas: relationship between magnetic resonance imaging criteria and tumor type and grade. The Veterinary Journal 198, 463–471.
604 605 606
Borrelli, A., Mattiazzi, L., Capucchio, M.T., Biolatti, C., Cagnasso, A., Gianella, P., D’Angelo, A., 2009. Cachexia secondary to intracranial anaplastic (malignant) ependymoma in a boxer dog. Journal of Small Animal Practice 50, 554–557.
607 608 609
Brewer, D.M., Cerda-Gonzalez, S., Dewey, C.W., Coates, J.R., 2010. Diagnosis and surgical resection of a choroid plexus cyst in a dog. Journal of Small Animal Practice 51, 169– 172.
610 611 612
Bush, W.W., Throop, J.L., McManus, P.M., Kapatkin, A.S., Vite, C.H., Van Winkle, T.J., 2003. Intravascular lymphoma involving the central and peripheral nervous systems in a dog. Journal of the American Animal Hospital Association 39, 90–96.
613 614
Canal, S., Bernardini, M., Pavone, S., Mandara, M.T., 2013. Primary diffuse leptomeningeal gliomatosis in 2 dogs. Canadian Veterinary Journal 54, 1075–1079.
615 616
Capucchio, M., 2003. Histological and immunohistochemical study of a neuroblastoma in a dog. Clinical Neuropathology 22, 176–179.
617 618 619
Cervera, V., Mai, W., Vite, C.H., Johnson, V., Dayrell-Hart, B., Seiler, G.S., 2011. Comparative magnetic resonance imaging findings between gliomas and presumed cerebrovascular accidents in dogs. Veterinary Radiology and Ultrasound 52, 33–40.
620 621
Chandra, A.M., Ginn, P.E., 1999. Primary malignant histiocytosis of the brain in a dog. Journal of Comparative Pathology 121, 77–82.
622 623 624
Chang, S.C., Liao, J.W., Lin, Y.C., Liu, C.I., Wong, M.L., 2007. Pancreatic acinar cell carcinoma with intracranial metastasis in a dog. The Journal of Veterinary Medical Science 69, 91–93.
625 626 627
Cherubini, G.B., Mantis, P., Martinez, T.A., Lamb, C.R., Cappello, R., 2005. Utility of magnetic resonance imaging for distinguishing neoplastic from non-neoplastic brain lesions in dogs and cats. Veterinary Radiology and Ultrasound 46, 384–387.
Page 25 of 42
628 629 630
Cherubini, G.B., Platt, S.R., Anderson, T.J., Rusbridge, C., Lorenzo, V., Mantis, P., Cappello, R., Al, H., Highland, W., 2006. Characteristics of magnetic resonance images of granulomatous meningoencephalomyelitis in 11 dogs. Veterinary Record 159, 110–115.
631 632 633
Choi, U.S., Philippe, L., Alleman, A.R., Kim, M.S., Lee, K.C., 2012. Cytologic and immunohistochemical characterization of a primitive neuroectodermal tumor in the brain of a dog. Veterinary Clinical Pathology 41, 153–157.
634 635 636
De Decker, S., Davies, E., Benigni, L., Wilson, H., Pelligand, L., Rayner, E.L., Shihab, N., Volk, H.A., 2012. Surgical treatment of an intracranial epidermoid cyst in a dog. Veterinary Surgery 41, 766–771.
637 638
Eckersley, G., Geel, J., Kriek, N., 1991. A craniopharyngioma in a seven-year-old dog. Journal of the South African Veterinary Association 62, 65–67.
639 640 641
Eichelberger, B.M., Kraft, S.L., Halsey, C.H.C., Park, R.D., Miller, M.D., Klopp, L., 2011. Imaging diagnosis-magnetic resonance imaging findings of primary cerebral hemangioma. Veterinary Radiology and Ultrasound 52, 188–191.
642 643 644
Espino, L., Suarez, M., Santamarina, G., Vila, M., Miño, N., Lopez-Peña, M., 2009. First report of the simultaneous occurrence of choroid plexus papilloma and meningioma in a dog. Acta Veterinaria Hungarica 57, 389–397.
645 646 647
Fernández, T., Díez-Bru, N., Rios, A., Gómez, L., Pumarola, M., 2001. Intracranial metastases from an ovarian dysgerminoma in a 2-year-old dog. Journal of the American Animal Hospital Association 37, 553–556.
648 649 650
Fukuoka, H., Sasaki, J., Kamishina, H., Sato, R., Yasuda, J., Katayama, M., Tohyama, K., Ohshida, M., Goryo, M., 2012. Gliomatosis Cerebelli in a Saint Bernard Dog. Journal of Comparative Pathology 147, 37–41.
651 652
Gains, M.J., Leclerc, M., Bédard, C., 2011. A primitive neuroectodermal tumor with extension into the cranial vault in a dog. Canadian Veterinary Journal 52, 1232–1236.
653 654 655
Galán, A., Guil-Luna, S., Millán, Y., Martín-Suárez, E.M., Pumarola, M., de Las Mulas, J.M., 2010. Oligodendroglial gliomatosis cerebri in a Poodle. Veterinary and Comparative Oncology 8, 254–262.
656 657 658 659
Garosi, L., Dawson, A., Couturier, J., Matiasek, L., Stefani, A. De, Davies, E., Jeffery, N., Smith, P., 2010. Necrotizing cerebellitis and cerebellar atrophy caused by Neospora caninum infection: magnetic resonance imaging and clinicopathologic findings in seven dogs. Journal of Veterinary Internal Medicine 24, 571–578.
660 661 662
Garosi, L.S., Dennis, R., Platt, S.R., Corletto, F., de Lahunta, A., Jakobs, C., 2003. Thiamine deficiency in a dog: clinical, clinicopathologic, and magnetic resonance imaging findings. Journal of Veterinary Internal Medicine 17, 719–723.
663 664 665
Giri, D.K., Aloisio, F., Ajithdoss, D.K., Ambrus, A., Lidbury, J.A., Hein, H.E., Porter, B.F., 2011. Giant cell glioblastoma in the cerebrum of a pembroke welsh corgi. Journal of Comparative Pathology 144, 324–327.
Page 26 of 42
666 667 668
Glass, E., Kapatkin, A., Vite, C., Steinberg, S., 2000. A modified bilateral transfrontal sinus approach to the canine frontal lobe and olfactory bulb: surgical technique and five cases. Journal of the American Animal Hospital Association 36, 43–50.
669 670 671
Graham, J.P., Newell, S.M., Voges, A.K., Roberts, G.D., Harrison, J.M., 1998. The dural tail sign in the diagnosis of meningiomas. Veterinary Radiology and Ultrasound 39, 297– 302.
672 673 674
Granger, N., Smith, P.M., Jeffery, N.D., 2010. Clinical findings and treatment of noninfectious meningoencephalomyelitis in dogs: a systematic review of 457 published cases from 1962 to 2008. The Veterinary Journal 184, 290–297.
675 676
Gruber, A., Leschnik, M., Kneissl, S., Schmidt, P., 2006. Gliomatosis cerebri in a dog. Journal of Veterinary Medicine A 53, 435–438.
677 678 679 680
Gutierrez-Quintana, R., Carrera, I., Dobromylskyj, M., Patterson-Kane, J., Ortega, M., Wessmann, A., 2013. Pituitary Metastasis of Pancreatic Origin in a Dog Presenting with Acute-Onset Blindness. Journal of the American Animal Hospital Association 49, 403– 406.
681 682 683
Hakyemez, B., Erdogan, C., Gokalp, G., Dusak, A., Parlak, M., 2010. Solitary metastases and high-grade gliomas: radiological differentiation by morphometric analysis and perfusionweighted MRI. Clinical Radiology 65, 15–20.
684 685 686
Hanselman, B., Kruth, S., Poma, R., Nykamp, S., 2006. Hypernatremia and hyperlipidemia in a dog with central nervous system lymphosarcoma. Journal of Veterinary Internal Medicine 20, 1029–1032.
687 688
Hathcock, J.T., 1996. Low field magnetic resonance imaging characteristics of cranial vault meningiomas in 13 dogs. Veterinary Radiology and Ultrasound 37, 257–263.
689 690 691
Headley, S.A., Koljonen, M., Gomes, L.A., Sukura, A., 2009. Central primitive neuroectodermal tumor with ependymal differentiation in a dog. Journal of Comparative Pathology 140, 80–83.
692 693 694
Hecht, S., Adams, W.H., Smith, J.R., Thomas, W.B., 2011. Clinical and imaging findings in five dogs with intracranial blastomycosis (Blastomyces dermatiditis). Journal of the American Animal Hospital Association 47, 241–249.
695 696
Hicks, D.G., Fidel, J.L., 2006. Intranasal malignant melanoma in a dog. Journal of the American Animal Hospital Association 42, 472–476.
697 698 699
Higgins, R.J., Lecouteur, R.A., Vernau, K.M., Sturges, B.K., Obradovich, J.E., Bollen, A.W., 2001. Granular cell tumor of the canine central nervous system: two cases. Veterinary Pathology 38, 620–627.
700 701 702
Hodshon, A.W., Hecht, S., Thomas, W.B., 2014. Use of the T2*-Weighted Gradient Recalled Echo Sequence for Magnetic Resonance Imaging of the Canine and Feline Brain. Veterinary Radiology and Ultrasound doi: 10.1111/vru.12164
Page 27 of 42
703 704 705
Ide, T., Uchida, K., Kagawa, Y., Suzuki, K., Nakayama, H., 2011. Pathological and immunohistochemical features of subdural histiocytic sarcomas in 15 dogs. Journal of Veterinary Diagnostic Investigation 23, 127–132.
706 707 708
Ide, T., Uchida, K., Morozumi, M., Nakayama, H., 2009. Hamartoma in the medulla oblongata with marked mineral deposits in a dog. The Journal of Veterinary Medical Science 71, 1097–1100.
709 710 711
Isiklar, I., Leeds, N., Fuller, G., Kumar, A., 1995. Intracranial metastatic melanoma: correlation between MR imaging characteristics and melanin content. American Journal of Roentgenology 165, 1503–1512.
712 713 714
James, F.M.K., da Costa, R.C., Fauber, A., Peregrine, A.S., McEwen, B., Parent, J.M., Bergman, R., 2012. Clinical and MRI findings in three dogs with polycystic meningiomas. Journal of the American Animal Hospital Association 48, 331–338.
715 716 717
Jung, H., Lee, H., Kim, J., Jang, H., Moon, J., Sur, J., Jeongim, H., Jung, D., 2014. Imatinib mesylate plus hydroxyurea chemotherapy for cerebellar meningioma in a Belgian Malinois dog. The Journal of Veterinary Medical Science doi: 10.1292/jvms.14-0001
718 719 720
Kang, B., Park, C., Yoo, J., Gu, S., Jang, D., Kim, Y., 2009. 18F-fluorodeoxyglucose positron emission tomography and magnetic resonance imaging findings of primary intracranial histiocytic sarcoma in a dog. The Journal of Veterinary Medical Science 71, 1397–1401.
721 722 723
Katayama, K.I., Kuroki, K., Uchida, K., Nakayama, H., Sakai, M., Mochizuki, M., Nishimura, R., Sasaki, N., Doi, K., 2001. A case of canine primitive neuroectodermal tumor (PNET). The Journal of Veterinary Medical Science 63, 103–105.
724 725 726
Kato, K., Nishimura, R., Sasaki, N., Matsunaga, S., Mochizuki, M., Nakayama, H., Ogawa, H., 2005. Magnetic resonance imaging of a canine eye with melanoma. The Journal of Veterinary Medical Science 67, 179–182.
727 728
Kent, M., Delahunta, A., Tidwell, A.S., 2001. MR imaging findings in a dog with intravascular lymphoma in the brain. Veterinary Radiology and Ultrasound 42, 504–510.
729 730 731
Kitagawa, M., Okada, M., Yamamura, H., Kanayama, K., Sakai, T., 2006. Diagnosis of olfactory neuroblastoma in a dog by magnetic resonance imaging. Veterinary Record 159, 288–289.
732 733
Koch, M.W., Sánchez, M.D., Long, S., 2011. Multifocal oligodendroglioma in three dogs. Journal of the American Animal Hospital Association 47, e77–e85.
734 735 736
Koestner, A., Bilzer, T., Fatzer, R., Summers, B., Van Winkle, T., 1999. Histologic classification of tumors of the nervous system of domestic animals 2nd ed., Washington, DC: Armed Forces Institute of Pathology.
737 738 739
Kraft, S.L., Gavin, P.R., DeHaan, C., Moore, M., Wendling, L.R., Leathers, C.W., 1997. Retrospective review of 50 canine intracranial tumors evaluated by magnetic resonance imaging. Journal of Veterinary Internal Medicine 11, 218–225.
Page 28 of 42
740 741 742
Kraft, S.L., Gavin, P.R., Leathers, C.W., Wendling, L.R., Frenier, S., Dorn, R. V, 1990. Diffuse cerebral and leptomeningeal astrocytoma in dogs: MR features. Journal of Computer Assisted Tomography 14, 555–560.
743 744
Lenz, S.D., Janovitz, E.B., Lockridge, K., 1991. An anaplastic astrocytoma (glioblastoma) in the cerebellum of a dog. Veterinary Pathology 28, 250–252.
745 746 747
Liebel, F.X., Summers, B.A., Lowrie, M., Smith, P., Garosi, L., 2013. Imaging diagnosismagnetic resonance imaging features of a cerebral hemangioblastoma in a dog. Veterinary Radiology and Ultrasound 54, 164–167.
748 749 750
Lipitz, L., Rylander, H., Forrest, L.J., Foy, D.S., 2010. Clinical and magnetic resonance imaging features of central nervous system blastomycosis in 4 dogs. Journal of Veterinary Internal Medicine 24, 1509–1514.
751 752 753
Lipsitz, D., Higgins, R.J., Kortz, G.D., Dickinson, P.J., Bollen, A.W., Naydan, D.K., LeCouteur, R.A., 2003. Glioblastoma multiforme: clinical findings, magnetic resonance imaging, and pathology in five dogs. Veterinary Pathology 40, 659–669.
754 755 756
Lipsitz, D., Levitski, R.E., Berry, W.L., 2001. Magnetic resonance imaging features of multilobular osteochondrosarcoma in 3 dogs. Veterinary Radiology and Ultrasound 42, 14–19.
757 758 759
Lipsitz, D., Levitski, R., Chauvet, A., 1999. Magnetic resonance imaging of a choroid plexus carcinoma and meningeal carcinomatosis in a dog. Veterinary Radiology and Ultrasound 40, 246–250.
760 761 762
Long, S.N., Johnston, P.E., Anderson, T.J., 2001. Primary T-cell lymphoma of the central nervous system in a dog. Journal of the American Veterinary Medical Association 218, 719–722.
763 764 765
Lovett, M.C., Fenner, W.R., Watson, A.T., Hostutler, R.A., 2012. Imaging diagnosis-MRI characteristics of a fourth ventricular cholesterol granuloma in a dog. Veterinary Radiology and Ultrasound 53, 650–654.
766 767 768
Lowrie, M., De Risio, L., Dennis, R., Llabrés-Díaz, F., Garosi, L., 2012. Concurrent medical conditions and long-term outcome in dogs with nontraumatic intracranial hemorrhage. Veterinary Radiology and Ultrasound 53, 381–388.
769 770
MacKillop, E., 2011. Magnetic resonance imaging of intracranial malformations in dogs and cats. Veterinary Radiology and Ultrasound 52, S42–S51.
771 772 773
MacKillop, E., Thrall, D.E., Ranck, R.S., Linder, K.E., Munana, K.R., 2007. Imaging diagnosis-synchronous primary brain tumors in a dog. Veterinary Radiology and Ultrasound 48, 550–553.
774 775 776
Martin-Vaquero, P., da Costa, R.C., Aeffner, F., Oglesbee, M.J., Echandi, R.L., 2010. Imaging diagnosis-hemorrhagic meningioma. Veterinary Radiology and Ultrasound 51, 165–167.
Page 29 of 42
777 778 779
Martin-Vaquero, P., da Costa, R.C., Wolk, K.E., Premanandan, C., Oglesbee, M.J., 2012. MRI features of gliomatosis cerebri in a dog. Veterinary Radiology and Ultrasound 53, 189–192.
780 781 782
Mateo, I., Lorenzo, V., Muñoz, A., Molín, J., 2010. Meningeal carcinomatosis in a dog: magnetic resonance imaging features and pathological correlation. Journal of Small Animal Practice 51, 43–48.
783 784 785
McConnell, J.F., Platt, S., Smith, K.C., 2004. Magnetic resonance imaging findings of an intracranial medulloblastoma in a Polish Lowland Sheepdog. Veterinary Radiology and Ultrasound 45, 17–22.
786 787 788
McDonnell, J.J., Kalbko, K., Keating, J.H., Sato, A.F., Faissler, D., 2007. Multiple meningiomas in three dogs. Journal of the American Animal Hospital Association 43, 201–208.
789 790 791
Mellema, L., Koblik, P., Kortz, G., LeCouteur, R., Chechowitz, M., Dickinson, P., 1999. Reversible magnetic resonance imaging abnormalities in dogs following seizures. Veterinary Radiology and Ultrasound 40, 588–595.
792 793 794
Mellema, L.M., Samii, V.F., Vernau, K.M., LeCouteur, R. a, 2000. Meningeal enhancement on magnetic resonance imaging in 15 dogs and 3 cats. Veterinary Radiology and Ultrasound 43, 10–15.
795 796 797
Mercier, M., Barnes Heller, H.L., Bischoff, M.G., Looper, J., Bacmeister, C.X., 2007. Imaging diagnosis-hyperostosis associated with meningioma in a dog. Veterinary Radiology and Ultrasound 48, 421–423.
798 799
Mishra, S., Kent, M., Haley, A., Platt, S., Sakamoto, K., 2012. Atypical meningeal granular cell tumor in a dog. Journal of Veterinary Diagnostic Investigation 24, 192–197.
800 801 802
Miwa, Y., Matsunaga, S., Kato, K., Ogawa, H., Nakayama, H., Tsujimoto, S., Sasaki, N., 2005. Choroidal melanoma in a dog. The Journal of Veterinary Medical Science 67, 821–823.
803 804 805
Molín, J., Rentmeister, K., Matiasek, K., 2014. Caudal fossa respiratory epithelial cyst in a dog: clinical, magnetic resonance imaging, and histopathologic findings. Journal of Veterinary Internal Medicine 28, 1336–1340.
806 807
Moore, P.F., 2014. A review of histiocytic diseases of dogs and cats. Veterinary Pathology 51, 167–184.
808 809 810
Morozumi, M., Miyahara, K., Sato, M., Hirose, T., 1997. Computed tomography and magnetic resonance findings in two dogs and a cat with intracranial lesions. The Journal of Veterinary Medical Science 59, 807–810.
811 812
Motta, L., Mandara, M.T., Skerritt, G.C., 2012. Canine and feline intracranial meningiomas: an updated review. The Veterinary Journal 192, 153–165.
Page 30 of 42
813 814 815
Nielsen, L., Thompson, H., Hammond, G.J., Chang, Y., Ramsey, I.K., 2008. Central diabetes insipidus associated with primary focal B cell lymphoma in a dog. Veterinary Record 162, 124–126.
816 817 818
Pákozdy, A., Leschnik, M., Tichy, A.G., Thalhammer, J.G., 2008. Retrospective clinical comparison of idiopathic versus symptomatic epilepsy in 240 dogs with seizures. Acta Veterinaria Hungarica 56, 471–483.
819 820
Palus, V., Volk, H.A., Lamb, C.R., Targett, M.P., Cherubini, G.B., 2012. MRI features of CNS lymphoma in dogs and cats. Veterinary Radiology and Ultrasound 53, 44–49.
821 822 823
Parzefall, B., Driver, C.J., Benigni, L., Davies, E., 2014. Magnetic resonance imaging characteristics in four dogs with central nervous system neosporosis. Veterinary Radiology and Ultrasound 55, 539–546.
824 825 826 827
Patsikas, M., Jakovljevic, S Papadopoulou, P., Polizopoulou, Z., Kazakos, G., Tontis, D., Soultani, C., Charitanti, A., Chrissogonidis, I., Tsifountoudis, I., 2014. Magnetic resonance imaging features of cerebellar vermis medulloblastoma in an adult canine patient. Journal of Biological Regulators and Homeostatic Agents 28, 341–347.
828 829 830
Plattner, B.L., Kent, M., Summers, B., Platt, S.R., Freeman, A.C., Blas-Machado, U., Clemans, J., Cheville, N.F., Garcia-Tapia, D., 2012. Gliomatosis cerebri in two dogs Journal of the American Animal Hospital Association 48, 359–365.
831 832 833
Polizopoulou, Z.S., Koutinas, A.F., Souftas, V.D., Kaldrymidou, E., Kazakos, G., Papadopoulos, G., 2004. Diagnostic correlation of CT-MRI and histopathology in 10 dogs with brain neoplasms. Journal of Veterinary Medicine A 51, 226–231.
834 835
Porter, B., DeLahunta, A., Summers, B., 2003. Gliomatosis cerebri in six dogs. Veterinary Pathology 40, 97–102.
836 837 838
Ródenas, S., Pumarola, M., Gaitero, L., Zamora, A., Añor, S., 2011. Magnetic resonance imaging findings in 40 dogs with histologically confirmed intracranial tumors. The Veterinary Journal 187, 85–91.
839 840 841
Rossmeisl, J., Pineyro, P., Sponenberg, D., Garman, R., Jortner, B.S., 2012. Clinicopathologic features of intracranial central neurocytomas in 2 dogs. Journal of Veterinary Internal Medicine 26, 186–191.
842 843 844
Salvadori, C., Pintore, M.D., Ricci, E., Konar, M., Tartarelli, C.L., Gasparinetti, N., Cantile, C., 2011. Microcystic meningioma of the fourth ventricle in a dog. The Journal of Veterinary Medical Science 73, 367–370.
845 846 847
Schoeman, J.P., Stidworthy, M.F., Penderis, J., Kafka, U., 2002. Magnetic resonance imaging of a cerebral cavernous haemangioma in a dog. Journal of the South African Veterinary Association 73, 207–210.
848 849 850
Sebastianelli, M., Mandara, M.T., Pavone, S., Canal, S., Bernardini, M., 2013. Thalamic astrocytic hamartoma and associated meningoangiomatosis in a German shepherd dog. Research in Veterinary Science 94, 644–647.
Page 31 of 42
851 852 853
Seruca, C., Ródenas, S., Leiva, M., Peña, T., Añor, S., 2010. Acute postretinal blindness: ophthalmologic, neurologic, and magnetic resonance imaging findings in dogs and cats (seven cases). Veterinary Ophthalmology 13, 307–314.
854 855
Sessums, K.B., Lane, S.B., 2008. Imaging diagnosis: intracranial mucocele in a dog. Veterinary Radiology and Ultrasound 49, 564–566.
856 857
Sharkey, L.C., McDonnell, J.J., Alroy, J., 2004. Cytology of a mass on the meningeal surface of the left brain in a dog. Veterinary Clinical Pathology 33, 111–114.
858 859 860
Singh, J.B., Oevermann, A., Henke, D., Segard, E., Gorgas, D., 2012. Imaging diagnosis-lack of contrast enhancement in metastatic cerebral adenocarcinoma. Veterinary Radiology and Ultrasound 53, 193–196.
861 862 863 864
Singh, J.B., Oevermann, A., Lang, J., Vandevelde, M., Doherr, M., Henke, D., Gorgas, D., 2011. Contrast media enhancement of intracranial lesions in magnetic resonance imaging does not reflect histopathologic findings consistently. Veterinary Radiology and Ultrasound 52, 619–626.
865 866 867
Snyder, J.M., Lipitz, L., Skorupski, K. a, Shofer, F.S., Van Winkle, T.J., 2008. Secondary intracranial neoplasia in the dog: 177 cases (1986-2003). Journal of Veterinary Internal Medicine 22, 172–177.
868 869 870
Snyder, J.M., Shofer, F.S., Winkle, T.J. Van, Massicotte, C., 2006. Canine intracranial primary neoplasia: 173 cases (1986–2003). Journal of Veterinary Internal Medicine 20, 669–675.
871 872 873
Song, R.B., Vite, C.H., Bradley, C.W., Cross, J.R., 2013. Postmortem evaluation of 435 cases of intracranial neoplasia in dogs and relationship of neoplasm with breed, age, and body weight. Journal of Veterinary Internal Medicine 27, 1143–1152.
874 875 876
Stacy, B.A., Stevenson, T.L., Lipsitz, D., Higgins, R.J., 2003. Simultaneously occurring oligodendroglioma and meningioma in a dog. Journal of Veterinary Internal Medicine 17, 357–359.
877 878 879 880
Sturges, B.K., Dickinson, P.J., Bollen, A.W., Koblik, P.D., Kass, P.H., Kortz, G.D., Vernau, K.M., Knipe, M.F., Lecouteur, R.A., Higgins, R.J., 2008. Magnetic resonance imaging and histological classification of intracranial meningiomas in 112 dogs. Journal of Veterinary Internal Medicine 22, 586–595.
881 882 883
Sutherland-Smith, J., King, R., Faissler, D., Ruthazer, R., Sato, A., 2011. Magnetic resonance imaging apparent diffusion coefficients for histologically confirmed intracranial lesions in dogs. Veterinary Radiology and Ultrasound 52, 142–148.
884 885 886 887
Sykes, J.E., Sturges, B.K., Cannon, M.S., Gericota, B., Higgins, R.J., Trivedi, S.R., Dickinson, P.J., Vernau, K.M., Meyer, W., Wisner, E.R., 2010. Clinical signs, imaging features, neuropathology, and outcome in cats and dogs with central nervous system cryptococcosis from California. Journal of Veterinary Internal Medicine 24, 1427–1438.
Page 32 of 42
888 889 890
Tamura, S., Tamura, Y., Nakamoto, Y., Ozawa, T., Uchida, K., 2009. MR imaging of histiocytic sarcoma of the canine brain. Veterinary Radiology and Ultrasound 50, 178– 181.
891 892 893
Tamura, S., Tamura, Y., Suzuoka, N., Ohoka, A., Hasegawa, T., Uchida, K., 2007. Multiple metastases of thyroid cancer in the cranium and pituitary gland in two dogs. Journal of Small Animal Practice 48, 237–239.
894 895
Thio, T., Hilbe, M., Grest, P., Pospischil, A., 2006. Malignant histiocytosis of the brain in three dogs. Journal of Comparative Pathology 134, 241–244.
896 897 898
Thomovsky, S.A., Packer, R.A., Burcham, G.N., Heng, H.G., 2011. Imaging diagnosismagnetic resonance imaging features of metastatic cerebral lymphoma in a dog. Veterinary Radiology and Ultrasound 52, 192–195.
899 900
Tidwell, A.S., Robertson, I.D., 2011. Magnetic resonance imaging of normal and abnormal brain perfusion. Veterinary Radiology and Ultrasound 52, S62–S71.
901 902 903
Traslavina, R.P., Kent, M.S., Mohr, F.C., Dickinson, P.J., Vernau, K.M., Bollen, A.W., Higgins, R.J., 2013. Clear cell ependymoma in a dog. Journal of Comparative Pathology 149, 53–56.
904 905 906
Valentine, B., Summers, B., de Lahunta, A., White, C., Kuhajda, F., 1988. Suprasellar germ cell tumors in the dog: a report of five cases and review of the literature. Acta Neuropathologica 76, 94–100.
907 908 909
Vernau, K.M., Terio, K., LeCouteur, R.A., Berry, W., Vernau, W., Moore, P.F., Samii, V.F., 2000. Acute B-cell lymphoblastic leukemia with meningeal metastasis causing primary neurologic dysfunction in a dog. Journal of Veterinary Internal Medicine 14, 110–115.
910 911
Vural, S.A., Besalti, O., Ilhan, F., Ozak, A., Haligur, M., 2006. Ventricular ependymoma in a German Shepherd dog. The Veterinary Journal 172, 185–187.
912 913 914
Wessmann, A., Hennessey, A., Goncalves, R., Benigni, L., Hammond, G., Volk, H.A., 2013. The association of middle ear effusion with trigeminal nerve mass lesions in dogs. Veterinary Record 173, 449
915 916 917
Westworth, D., Dickinson, P., Vernau, W., Johnson, E., Bollen, A., Kass, P., Sturges, B., Vernau, K., Lecouteur, R., Higgins, R., 2008. Choroid Plexus Tumors in 56 Dogs (1985 –2007). Journal of Veterinary Internal Medicine 22, 1157–1165.
918 919
Williams, J.M., Michal, U., Botteron, C., Skerritt, G., Hetzel, U., 2009. Papillary tumor of the pineal region of a dog. Journal of Veterinary Diagnostic Investigation 21, 910–914.
920 921
Wisner, E.R., Dickinson, P.J., Higgins, R.J., 2011. Magnetic resonance imaging features of canine intracranial neoplasia. Veterinary Radiology and Ultrasound 52, S52–S61.
922 923
Wolff, C.A., Holmes, S.P., Young, B.D., Chen, A. V, Kent, M., Platt, S.R., Savage, M.Y., Schatzberg, S.J., Fosgate, G.T., Levine, J.M., 2012. Magnetic resonance imaging for the
Page 33 of 42
924 925
differentiation of neoplastic, inflammatory, and cerebrovascular brain disease in dogs. Journal of Veterinary Internal Medicine 26, 589–597.
926 927
Wyss-Fluehmann, G., Konar, M., Jaggy, A., Vandevelde, M., Oevermann, A., 2008. Cerebellar ependymal cyst in a dog. Veterinary Pathology 45, 910–913.
928 929 930 931
Young, B.D., Fosgate, G.T., Holmes, S.P., Wolff, C.A., Chen-Allen, A. V, Kent, M., Platt, S.R., Savage, M.Y., Schatzberg, S.J., Levine, J.M., 2014. Evaluation of standard magnetic resonance characteristics used to differentiate neoplastic, inflammatory, and vascular brain lesions in dogs. Veterinary Radiology and Ultrasound 55, 399–406.
932 933 934 935
Young, B.D., Levine, J.M., Porter, B.F., Chen-Allen, A. V, Rossmeisl, J.H., Platt, S.R., Kent, M., Fosgate, G.T., Schatzberg, S.J., 2011. Magnetic resonance imaging features of intracranial astrocytomas and oligodendrogliomas in dogs. Veterinary Radiology and Ultrasound 52, 132–141.
936 937
Page 34 of 42
938 939 940 941 942 943 944 945 946 947 948 949 950 951 952 953 954 955 956 957 958 959 960 961 962 963 964 965 966 967 968 969 970 971 972 973 974 975 976 977 978 979 980 981 982 983 984 985 986 987
Figure legends Fig. 1. Extra-axial fronto-olfactory meningioma (upper) and histiocytic sarcoma (lower): sagittal T2W (A), T1W (B) and post-contrast T1W (C) images. With extra-axial mass lesions, it may be possible to observe faint T2-hyperintense lines continuous with the subarachnoid space (arrows), helping to support an extra-axial location. These lines, at the margin of the brain and the tumor, represent CSF or edematous brain. Both masses are mainly T2-isointense and T1-isointense, and strongly contrast-enhancing, either homogenously (upper) or heterogeneously (lower). Both masses have a broad based origin from the dura mater-skull periosteum. It is impossible to definitively differentiate meningioma and histiocytic sarcoma on MRI alone. The upper case was a 9.5 year-old dog and a provisional diagnosis of meningioma was given after MRI. Note the sharply defined border with the brain on the postcontrast image. The lower case was a 5 year-old dog, and round cell tumors including histiocytic sarcoma were given as a possible differential diagnosis, along with meningioma, other neoplasms, and granuloma. Fig. 2. Hemangioblastoma. A, T1W; B, T2W; C, post-contrast T1W transverse images; D, coronal post-contrast fat saturation T1W image. Hemangioblastomas are a sporadic differential diagnosis for a fronto-olfactory, extra-axial, T2-hyperintense, markedly enhancing mass lesion in an older dog, and can be impossible to differentiate from meningioma based on MRI alone. Note the distinct borders with the brain. Fig. 3. Meningeal-based neoplasms displaying shared MRI features with meningioma: olfactory neuroblastoma (esthesioneuroblastoma) (upper) and granular cell tumor (lower). A, T1W post-contrast; B, T2W dorsal images of olfactory neuroblastoma. This markedly contrast-enhancing mass is meningeal-based, attached to the falx cerebri of the frontal lobe and olfactory bulb. Note the absence of any detectable changes in the nasal passages, a rare finding for this tumor. This lesion is similar to a small meningioma. C, T1W transverse; D, T1W post-contrast dorsal images of granular cell tumor. There is a broad-based origin from the falx cerebri. Note the mild pre-contrast T1-hyperintensity in A, a feature much more typical of granular cell tumor than meningioma. Note the plaque-like growth along the falx cerebri (D). Plaque-like meningiomas are usually in a skull-base location. Fig. 4. T1W post-contrast images of a skull-base meningioma exhibiting plaque-like growth. A, transverse image at the level of the diencephalon; B, transverse image at the level of the rostral medulla; C, parasagittal image. This is a classic location for a plaque-like meningioma. Note the sharply defined borders of the mass. The basilar artery is present as a midline hypointense circle within the dorsal aspect of the mass in B, confirming the arachnoid-dural origin of the mass. A small dural tail is present caudal to the mass (arrow, C). Fig. 5. High grade oligodendroglioma (upper) and hemorrhagic cerebrovascular accident (lower). A, T1W transverse; B, T2W transverse; C, T2*-weighted gradient echo transverse; D, T1W post-contrast dorsal images. Both lesions have T1-hyperintense regions pre-contrast and a heterogeneously T2-hyperintense signal. Signal voids are present on gradient echo; note the rim on the lower image. Both lesions show peripheral contrast-enhancement. It can be impossible to definitively differentiate a chronic hematoma from neoplasia using MRI alone. Note the ventricular distortion and lack of peri-tumoral edema in the upper images, which can be used to support oligodendroglioma over astrocytoma, but does not aid in differentiating neoplasia from benign lesions.
Page 35 of 42
988 989 990 991 992 993 994 995 996 997 998 999 1000 1001 1002 1003 1004 1005 1006 1007 1008 1009 1010 1011 1012 1013 1014 1015
Fig. 6. Intravascular lymphoma. Transverse images at the level of the caudal medulla (upper) and rostral midbrain (lower). T2W (A), gradient echo (B and D) and post-contrast T1W (C). A caudal medulla unilateral T2-hyperintense lesion (A) with no mass effect had no GRE signal void (B); this lesion displayed no contrast enhancement. Multifocal areas of contrastenhancement were noted elsewhere (arrows, C). The most medial of these is dorsal to a small T1-hypointense area which displayed a gradient echo signal void (arrow, D). The MRI lesions display confusing combinations of infarctive, hemorrhagic and neoplastic criteria. At necropsy, variable lesions associated with intravascular lymphoma were detected, including ischemic regions, thrombosed vasculature, invasion of neoplastic lymphocytes from blood vessels into the brain parenchyma, and pathological hemorrhages. Fig. 7. Solitary metastasis, caudal parietal lobe (A, T2W; B, T1W; C, T1W post-contrast). The MRI features are indistinguishable from a glioma, although the location is unusual. Note T2-hyperintensity, mild T1-hypointensity, mass effect (distortion of lateral ventricle) and marked contrast-enhancement. Surface contact is noted, but the subarachnoid space dorsal and medial to the mass is narrowed, supporting intra-axial location. Metastasis of systemic lymphoma. Fig. 8. Solitary intra-axial oral melanoma metastatic lesion. A, T2W; B, T2*W GRE; C, T1W and D, T1W post-contrast transverse images. Compared to normal grey matter, the lesion is T2-hyperintense and faintly T1-hyperintense. On T2* gradient echo, a signal void is present ventro-medially. The lesion is homogenously contrast-enhancing and well demarcated. The caudal lesion location, the occipital lobe, is unusual for glioma. While astrocytomas in particular can be T1-hyperintense, and high grade gliomas in particular can be hemorrhagic, the imaging characteristics combined with the history of oral melanoma are highly suggestive of a melanotic metastasis. At necropsy, histology confirmed melanoma metastasis with varying levels of melanin production; concurrent bilateral otitis media was also noted.
1016 1017
Table 1
1018
Reported solitary meningeal-based (non-pituitary) masses Major neoplastic differential diagnosis
Meningioma
Significant neoplastic differential diagnoses
Histiocytic sarcoma Choroid plexus tumor (cerebellopontomedullary angle)
Sporadic neoplasms
Lymphoma – solitary variant Granular cell tumor Metastasis e.g. carcinoma – solitary variant Hemangioblastoma Meningeal sarcoma Gliomatosis cerebri – extra-axial variant Olfactory neuroblastoma (rare variant with no tumor evident in nasal passages)
Significant non-
Granuloma, especially fungal
Page 36 of 42
neoplastic differential diagnoses
Various anomalous and acquired benign cystic lesions Hematoma
Cystic extra-axial neoplasms
Meningioma – common Nasal carcinoma (extending through cribriform plate) Olfactory neuroblastoma (typically extending through cribriform plate) Meningeal carcinomatosis (diffuse meningeal lesions)
1019 1020
Page 37 of 42
1021
Table 2
1022
Reported solitary ventricular masses
1023
Major neoplastic differential diagnoses
Choroid plexus papilloma Choroid plexus carcinoma
Significant neoplastic differential diagnoses
Ependymoma Meningioma (cerebellopontomedullary angle)
Sporadic neoplasms
Central neurocytoma Glioma, especially oligodendroglioma, can appear ventricular or spread down CSF Papillary tumor of the pineal region (within quadrigeminal cistern) Meningioma (within choroid plexus) Lymphoma (to date, not reported as a solitary lesion)
Sporadic nonneoplastic differential diagnoses
Choroid plexus cyst Cholesterol granuloma Epidermoid cyst
Non-enhancing Ependymoma (variable enhancement) neoplasms CSF, cerebrospinal fluid
1024
Page 38 of 42
1025 1026
Table 3 Reported solitary enhancing intra-axial lesions Major neoplastic differential diagnoses
Glioma, especially HGG (high grade oligodendroglioma, high grade astrocytoma including glioblastoma)
Significant neoplastic differential diagnoses
Metastasis (hemangiosarcoma, round cell tumor, carcinoma, melanoma) – solitary variant Primary CNS lymphoma – solitary variant
Sporadic neoplasms
PNET (non-cerebellar) Cerebellar medulloblastoma – strongly enhancing variant Histiocytic sarcoma – intra-axial variant Hemangioma Neuroblastoma* Ependymoma (can appear intra-axial, adjacent to ventricle)
Significant nonneoplastic differential diagnoses
Primary inflammatory syndromes including granulomatous meningoencephalomyelitis Infection especially fungal granuloma Ischemic cerebrovascular accident (enhancement after first few days) Hemorrhagic cerebrovascular accident (enhancement after first few days) Hamartoma
Glioma – all grades, especially HGG Hemangiosarcoma Hemorrhagic cerebrovascular accident Hamartoma Cerebellar medulloblastoma Melanoma (melanin causes a GRE signal void) Hemangioma * MRI of neuroblastoma was not fully described. Note that this tumor is a separate entity to olfactory neuroblastoma. Hemorrhagic lesions/T2* GRE signal voids
1027 1028 1029 1030 1031
CNS, central nervous system; GRE, gradient echo; HGG, high grade glioma; PNET, primitive neuroectodermal tumor
Page 39 of 42
1032 1033
Table 4 Reported solitary mildly or non-enhancing intra-axial lesions Major neoplastic differential diagnoses
Low grade glioma (low grade astrocytoma, low grade oligodendroglioma)
Significant neoplastic differential diagnosis
Cerebellar medulloblastoma Gliomatosis cerebri
Sporadic neoplasms
High grade glioma – poorly enhancing variant Metastasis (e.g. carcinoma) – rare poorly enhancing variant Lymphoma – rare poorly enhancing variant Ependymoma (may appear intra-axial)
Significant nonneoplastic differential diagnoses
Ischemic cerebrovascular accident Hemorrhagic cerebrovascular accident Inflammatory syndromes including granulomatous meningoencephalomyelitis and distemper
1034 1035
Page 40 of 42
1036 1037
Table 5 Reported multifocal lesions Major neoplastic differential diagnoses
Lymphoma – primary and secondary including intravascular (usually enhancing) Metastasis, especially hemangiosarcoma, carcinoma and melanoma (usually enhancing) Gliomatosis cerebri (usually non-enhancing)
Significant neoplastic differential diagnosis
Choroid plexus carcinoma with drop metastasis
Sporadic neoplasms
Meningioma or glioma combined with an unrelated neoplasm Oligodendroglioma – multifocal variant Diffuse low grade astrocytoma – variant (non-enhancing) Malignant histiocytosis (disseminated histiocytic sarcoma)*
Significant nonneoplastic differential diagnoses
Primary inflammatory syndromes including granulomatous meningoencephalomyelitis and necrotizing encephalitis Infectious including fungal, neosporosis, viral, tick-borne Reversible post-ictal changes Thiamine deficiency
Diffuse/multifocal meningeal tumors
1038
Lymphoma Histiocytic sarcoma – variant Granular cell tumor – variant Gliomatosis cerebri – variant Meningeal carcinomatosis Leukemia metastasis Meningioma – multiple meningioma variant * Primary or secondary; no MRI reports available to date
1039
Page 41 of 42
1040 1041 1042
Supplementary material
1043
Appendix. Metastatic MRI lesions.
1044
Page 42 of 42
S1090-0233(15)00043-X http://dx.doi.org/doi: 10.1016/j.tvjl.2015.01.025 YTVJL 4411
To appear in:
The Veterinary Journal
Accepted date:
24-1-2015
Please cite this article as: R. Timothy Bentley, Magnetic resonance imaging diagnosis of brain tumors in dogs, The Veterinary Journal (2015), http://dx.doi.org/doi: 10.1016/j.tvjl.2015.01.025. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
Review
Magnetic resonance imaging diagnosis of brain tumors in dogs R. Timothy Bentley a,* a
Department of Veterinary Clinical Sciences, Purdue University, West Lafayette, IN 479072026, USA
* Corresponding author. Tel.: +1 765 494 1107. E-mail address: [email protected]
Page 1 of 42
17
Highlights
18
Magnetic resonance imaging (MRI) features of brain tumors from dogs are described.
19
Groups include meningeal or ventricular masses, intra-axial enhancing to non-
20
enhancing lesions, and multifocal lesions.
21
Guidance for differential diagnoses is provided.
22
MRI features need to be interpreted with available clinical information.
23 24
Abstract
25
A great deal of information is now available regarding the range of magnetic
26
resonance imaging (MRI) features of many primary and secondary brain tumors from dogs. In
27
this review, these canine neoplasms are grouped into meningeal masses, ventricular masses,
28
intra-axial enhancing lesions, intra-axial mildly to non-enhancing lesions, and multifocal
29
lesions. For each of these patterns, the major and sporadic neoplastic differential diagnoses
30
are provided, and guidance on how to rank differential diagnoses for each individual patient is
31
presented. The implication of MRI features such as contrast-enhancement, signal intensities
32
and location is discussed. However, the information garnered from MRI must be correlated
33
with all available clinical information and with epidemiological data before creating a
34
differential diagnosis.
35 36
Keywords: Magnetic Resonance Imaging; Meningioma; Glioma; Canine; Diagnosis; Central
37
nervous system.
Page 2 of 42
38
Introduction
39
Brain tumors in adult dogs are a substantial cause of clinical disease and a major cause
40
of death (Song et al., 2013). Although surgery and ante-mortem histology are becoming
41
routine, not all lesions are safely accessible and expense may be prohibitive. Confidence in
42
the magnetic resonance imaging (MRI) diagnosis of brain tumors is needed prior to selecting
43
options such as euthanasia, radiation therapy without histology, or surgery.
44 45
Considerable information exists regarding what MRI features to expect knowing the
46
tumor type. However, clinical practice works in the opposite direction: when the MRI features
47
are available the clinician must predict whether a brain tumor is present, which type or types
48
is or are most likely, and if other tumors and non-neoplastic lesions are also reasonably
49
possible.
50 51
This review describes five broad MRI patterns of brain tumors in adult dogs: (1)
52
meningeal masses, (2) ventricular masses, (3) intra-axial enhancing lesions, (4) intra-axial
53
mildly or non-enhancing lesions, and (5) multifocal lesions. For each pattern, the common
54
and sporadic tumor types plus the major non-neoplastic differential diagnoses are provided.
55
MRI features are presented such that they can be used to increase or decrease the index of
56
suspicion for a particular tumor type, although they cannot be used to rule in or rule out
57
particular diagnoses.
58 59
The imaging features can be used to re-order the differential diagnoses, when
60
combined with clinical characteristics for that patient, such as signalment, history,
61
cerebrospinal fluid (CSF) analysis, evidence of extra-neural disease etc., and epidemiological
62
information. It may be possible to give a provisional diagnosis of a brain tumor based on all
Page 3 of 42
63
these data, or histology may still be an absolute pre-requisite to forming treatment
64
recommendations. One limitation is that the distinction between extra-axial and intra-axial is
65
occasionally challenging. Occasionally, both meningeal-based (e.g. meningioma) and intra-
66
axial masses (e.g. superficial glioma) must be retained in the differential diagnoses.
67
Oligodendroglioma in particular can be hard to differentiate from an intra-ventricular tumor.
68 69
Solitary meningeal masses: Extra-axial, non-ventricular, non-pituitary mass lesions
70
Description
71
The term solitary meningeal masses refers to lesions arising from the meninges,
72
interior to the skull and exterior to the brain tissue, the archetypal example being meningioma
73
although many other neoplastic and non-neoplastic masses arise in this location (Table 1).
74
Only lesions typically located within the cranial vault are covered here as information on
75
neoplastic invasion into the cranial vault (e.g. nasal adenocarcinoma, multilobular tumor of
76
bone, peripheral nerve sheath tumors, etc.) is readily available elsewhere (see, for example,
77
Lipsitz et al., 2001; Agthe et al., 2009; Wessmann et al., 2013).
78 79
For masses associated with the pituitary gland or nearby optic chiasm, the differential
80
diagnosis will include pituitary adenoma or adenocarcinoma, germ cell tumor,
81
craniopharyngioma and ependymoma (Eckersley et al., 1991; Valentine et al., 1988; Borrelli
82
et al., 2009; Seruca et al., 2010; Wisner et al., 2011), as well many neoplasms discussed
83
below, such as meningioma, lymphoma, granular cell tumor, gliomatosis cerebri (GC) and
84
metastatic carcinoma (Nielsen et al., 2008; Anwer et al., 2013; Gutierrez-Quintana et al.,
85
2013; Song et al., 2013; Bentley et al., 2014).
86
Page 4 of 42
87
The pachymeninges exist outside of the blood brain barrier (BBB) and almost any
88
tumor or granuloma arising here will contrast-enhance. Contrast-enhancement of extra-axial
89
tumors such as meningioma, histiocytic sarcoma (HS), granular cell tumor and
90
hemangioblastoma is almost universal (Kraft et al., 1997; Sharkey et al., 2004; Cherubini et
91
al., 2005; Sturges et al., 2008; Tamura et al., 2009; Ródenas et al., 2011; Singh et al., 2011;
92
Mishra et al., 2012; Anwer et al., 2013; Liebel et al., 2013). A meningeal sarcoma was a rare
93
exception (Ródenas et al., 2011).
94 95
Influence upon the subarachnoid space informs whether the mass is extra-axial or
96
intra-axial. Extra-axial lesions may widen the subarachnoid space. A T2-hyperintense line
97
(CSF or edematous brain) can delineate the margin of a meningioma with the brain. In
98
contrast, CSF adjacent to intra-axial masses may be pushed away from the brain and towards
99
the skull.
100 101
An extra-axial mass should have no normal brain tissue between the mass and the
102
contour of the fused dura mater-skull periosteum, or the mass may only contact the dura mater
103
(e.g. falcine meningiomas with no skull contact). Dural contact and extra-axial origin are
104
significant predictors of neoplasia, as is the ‘dural tail sign’ (Cherubini et al., 2005; Young et
105
al., 2014). A dural tail is a linear enhancement of thickened dura mater adjacent to an extra-
106
axial mass on T1-weighted (T1W) post-contrast images (Graham et al., 1998). In one study
107
(Young et al., 2014), it was noted in brain tumors only (meningiomas and sporadic other
108
neoplasms). However, in the author’s personal observation, and as reported by several groups
109
dural tails have occurred in HS, adenocarcinoma, choroid plexus tumor (CPT), fungal and
110
protozoal granulomas (Graham et al., 1998; Tamura et al., 2009; Baron et al., 2011; Ródenas
111
et al., 2011; Bentley et al., 2015). Broad-based dural contact and the dural tail sign may
Page 5 of 42
112
confirm that a lesion is extra-axial but do not allow a definitive diagnosis. Meningiomas,
113
other meningeal tumors and granulomas all display these features.
114 115
Features of mass effect include displacement of normal structures, midline shift,
116
distortion of ventricles and brain herniations. Unless they are small, meningiomas typically
117
cause a noticeable mass effect.
118 119
After meningioma, HS is often the most common solitary meningeal-based contrast-
120
enhancing mass lesion (Fig. 1) (Tamura et al., 2009; Ide et al., 2011; Song et al., 2013). On
121
MRI, HS is often found to be very similar to meningioma (Tamura et al., 2009), although
122
reduced enhancement might be more common (Wisner et al., 2011). Less commonly, there
123
may be invasion from the meninges to the parenchyma, a diffuse meningeal disease, mixed
124
intra-axial and extra-axial features or an intra-axial lesion (Snyder et al., 2006; Kang et al.,
125
2009; Tamura et al., 2009; Ide et al., 2011; Moore, 2014). Intracranial HS is frequently
126
primary (Kang et al., 2009; Tamura et al., 2009; Ide et al., 2011; Song et al., 2013; Moore,
127
2014) and the absence of extra-neural disease does not rule out HS. There are no MRI
128
guidelines to definitively differentiate meningioma and sub-dural HS. Disseminated HS
129
(malignant histiocytosis) rarely affects the brain (Chandra and Ginn, 1999; Thio et al., 2006).
130 131
Cystic regions
132
Cystic regions are isointense to CSF on T1W (i.e. dark) and T2-weighted (T2W) (i.e.
133
bright), and hypointense to normal gray matter on T2W fluid attenuation inversion recovery
134
(FLAIR), often isointense to CSF (James et al., 2012). Around one-quarter of meningiomas
135
are cystic or polycystic (Sturges et al., 2008; James et al., 2012). Neither single eccentric
136
cysts, nor intra-tumoral fluid accumulation(s) predict meningioma grade or subtype (Sturges
Page 6 of 42
137
et al., 2008). Their importance lies in adjusting the differential diagnoses. Well-defined cystic
138
regions have not yet been reported for HS, granular cell tumors, lymphoma, meningeal
139
sarcoma or hemangioblastoma (Sharkey et al., 2004; Snyder et al., 2006; Tamura et al., 2009;
140
Ródenas et al., 2011; Anwer et al., 2013; Liebel et al., 2013). However, cyctic regions have
141
been found to occur in meningeal carcinomatosis (Lipsitz et al., 1999; Mateo et al., 2010) and
142
brain invasion by pituitary tumors, nasal tumors and olfactory neuroblastoma (Kraft et al.,
143
1997; Kitagawa et al., 2006; Ródenas et al., 2011).
144 145
Identifying cystic regions in solitary meningeal masses could increase the suspicion of
146
meningioma over other neoplasms. Non-neoplastic extra-axial cystic lesions include
147
arachnoid diverticula, respiratory epithelial cyst, epidermoid cyst, dermoid cyst,
148
adenohypophyseal cyst, ependymal cyst and intracranial extension of nasal mucocele
149
(Sessums and Lane, 2008; Wyss-Fluehmann et al., 2008; MacKillop, 2011; De Decker et al.,
150
2012; Molín et al., 2014).
151 152 153
Tumor borders Meningiomas typically have borders well-defined with the brain; borders may be
154
smooth or irregular (Hathcock, 1996; Kraft et al., 1997) but are sharply defined in nearly 90%
155
of cases (Sturges et al., 2008). The margins of one hemangioblastoma (Liebel et al., 2013) and
156
most granular cell tumors (Higgins et al., 2001; Mishra et al., 2012; Anwer et al., 2013) were
157
also well-defined. Defined margins and a regular shape are significant predictors of neoplasia
158
(Cherubini et al., 2005; Young et al., 2014).
159 160 161
Fungal lesions frequently have indistinct borders (Sykes et al., 2010; Bentley et al., 2015) and lymphoma often has an irregular or indistinct margin (see below). Noting a poorly
Page 7 of 42
162
defined border or parenchymal invasion can increase the suspicion of a lesion other than a
163
meningioma, perhaps especially a round cell tumor or a granuloma.
164 165 166
Location Around three-quarters of meningiomas are supratentorial, especially fronto-olfactory
167
(Hathcock, 1996; Kraft et al., 1997; Sturges et al., 2008; Motta et al., 2012). Fronto-olfactory
168
tumors periodically include granular cell tumors (Higgins et al., 2001; Anwer et al., 2013),
169
hemangioblastoma (Fig. 2) (Liebel et al., 2013) and HS. Meningioma sporadically penetrates
170
the cribriform plate causing confusion with olfactory neuroblastoma (Hathcock, 1996;
171
McDonnell et al., 2007); similarly, with rare exceptions, there is usually a detectable tumor in
172
the nasal passages with an olfactory neuroblastoma (Fig. 3).
173 174
Hemispheric, cerebellar and tentorial meningiomas are usually ovoid or spherical
175
(Hathcock, 1996; Sturges et al., 2008). Plaque-like meningiomas are seen on the skull-base
176
(Fig. 4) (Sturges et al., 2008). Granular cell tumors are usually plaque-like meningeal
177
growths, including hemispheric or falcine tumors (Mishra et al., 2012; Anwer et al., 2013).
178 179 180
Signal intensities T1-hyperintensity increases the suspicion of a granular cell tumor, an otherwise
181
sporadic neoplasm, especially for a plaque-like non-skull-base lesion (Anwer et al., 2013).
182
Meningiomas and most other meningeal masses are usually T1-isointense or hypointense
183
(Hathcock, 1996; Kraft et al., 1997; Sturges et al., 2008; Ródenas et al., 2011).
184 185 186
A T2-isointense or hyperintense signal is non-specific and is observed in the large majority of meningiomas, other extra-axial neoplasms and granulomas (Tamura et al., 2009;
Page 8 of 42
187
Lipitz et al., 2010; Sykes et al., 2010; Ródenas et al., 2011; Thomovsky et al., 2011; Anwer et
188
al., 2013; Liebel et al., 2013; Bentley et al., 2015). T2-hypointensity occurs in just 2% of
189
meningiomas (Sturges et al., 2008) but is also unusual for other tumors, and should stimulate
190
consideration of benign hematoma or hemorrhage within a meningioma (Martin-Vaquero et
191
al., 2010). Peri-lesional edema is seen with meningiomas and many other etiologies.
192 193 194
Bone changes Sclerosis or lysis of the bone may be observed adjacent to meningiomas (Hathcock,
195
1996). Although occasional on computed tomography (CT) (Mercier et al., 2007; Jung et al.,
196
2014), hyperostosis was not detected by MRI in 112 dogs (Sturges et al., 2008). Bony lesions
197
were uncommon in each of neoplastic, inflammatory and vascular diseases, with no statistical
198
significance (Young et al., 2014).
199 200
Non-neoplastic differential diagnoses
201
Granulomas, especially of fungal origin, sporadically form solitary contrast-enhancing
202
meningeal masses within an intact cranial vault (Lipitz et al., 2010; Sykes et al., 2010; Baron
203
et al., 2011; Hecht et al., 2011; Bentley et al., 2015).
204 205
Solitary ventricular masses
206
Description
207
Most solitary ventricular masses are CPTs or ependymomas (Song et al., 2013) (Table
208
2). CPT is usually the leading differential diagnosis; the vast majority of these enhance
209
intensely and they are most common in the fourth ventricle (Westworth et al., 2008). Most
210
CPTs cause ventriculomegaly, either rostral to the mass or rostral and caudal, and peri-
211
ventricular edema (Westworth et al., 2008). CPTs occur as papillomas or carcinomas; a
Page 9 of 42
212
papilliform structure supports papilloma (Westworth et al., 2008). Choroid plexus carcinomas
213
can display ‘drop metastasis’ (transplantation via the CSF) to other ventricular and
214
subarachnoid locations (Westworth et al., 2008) and even cause meningeal carcinomatosis
215
(Lipsitz et al., 1999).
216 217
Location
218
Ventricular masses include all tumors within the lateral ventricles, interventricular
219
foramina, third ventricle, mesencephalic aqueduct, fourth ventricle or lateral apertures. As
220
CPTs are more abundant, any mass replacing the normal choroid plexus is more likely to be a
221
CPT than ependymoma, especially sited in the fourth ventricle.
222 223
If a normal choroid plexus can be identified as a small contrast enhancing area on
224
T1W images, separate from a solitary ventricular mass, that mass is probably not a CPT; the
225
clinician should include ependymoma as a differential diagnosis. Ependymoma has been
226
reported in the rostral horn of the lateral ventricle (distinct from the normal choroid plexus)
227
and might appear to be intra-axial and peri-ventricular (Kraft et al., 1997; Traslavina et al.,
228
2013). Another example assumed a ventral extra-axial location invading the hypophysis
229
(Borrelli et al., 2009). However, one ependymoma was shown to have affected the
230
interventricular foramen, a classic location for CPT (Vural et al., 2006). Contrast-
231
enhancement varied from none to strong.
232 233
Central neurocytoma, spanning both lateral ventricles via the interventricular foramina
234
or originating from the septum pellucidum, were shown to display marked contrast-
235
enhancement on the one MRI reported (Rossmeisl et al., 2012). Williams et al. (2009) found a
Page 10 of 42
236
pineal tumor enhancing within the quadrigeminal cistern of one dog. Parenchymal neoplasms
237
(e.g. oligodendroglioma) may take the appearance of a ventricular mass.
238 239
Signal intensities
240
CPTs are T1-hyperintense much more often than other brain tumors but can also be
241
isointense or hypointense (Kraft et al., 1997; Westworth et al., 2008). Other features are non-
242
specific: they are typically T2-hyperintense with peri-tumoral edema (Westworth et al., 2008).
243
Cystic structures have been seen in CPTs and ependymoma (Kraft et al., 1997; Westworth et
244
al., 2008).
245 246
Occasionally there is difficulty in differentiating a fourth ventricular CPT from a
247
cerebellopontomedullary angle meningioma; one CPT was misdiagnosed as a meningioma
248
(Ródenas et al., 2011). Meningiomas can even originate in the choroid plexus and be
249
completely contained within the fourth ventricle (Salvadori et al., 2011). Overlapping features
250
of these extra-axial neoplasms include marked contrast-enhancement and peri-tumoral edema
251
(Sturges et al., 2008; Westworth et al., 2008). Meningiomas are, however, infrequently T1-
252
hyperintense (Sturges et al., 2008). There will be individual overlap of signalment and CSF
253
results, but these findings are valuable (Snyder et al., 2006; Sturges et al., 2008; Westworth et
254
al., 2008; Song et al., 2013).
255 256
Non-neoplastic differential diagnoses
257
Non-neoplastic ventricular masses are rare. Choroid plexus cyst (Brewer et al., 2010),
258
cholesterol granuloma (Lovett et al., 2012) and epidermoid cyst (De Decker et al., 2012) have
259
all been reported on MRI. The choroid plexus cyst was most akin to a CPT.
260
Page 11 of 42
261
Solitary enhancing intra-axial lesions
262
Description
263
Solitary enhancing intra-axial lesions occur inside the brain parenchyma; normal brain
264
is typically evident between the lesion and the dura mater-skull periosteum (Table 3). Often,
265
the most important differential diagnosis is glioma, including oligodendroglioma, astrocytoma
266
including glioblastoma, and rarer variants such as oligoastrocytoma and undifferentiated
267
glioma (Snyder et al., 2006; Song et al., 2013). Certain MRI features allow partial
268
discrimination of low grade glioma (LGG) vs. high grade glioma (HGG), and of astrocytoma
269
vs. oligodendroglioma. Yet more information is available regarding other intra-axial diseases.
270
Together with clinical and epidemiological data, the differential diagnoses can be adjusted for
271
individual dogs.
272 273
Gliomas have widely varying MRI appearances and have been confused with diseases
274
as diverse as ischemic or hemorrhagic cerebrovascular accident, inflammatory disease,
275
leukoencephalopathy and meningioma (Cervera et al., 2011; Ródenas et al., 2011). Given the
276
substantial variation, the differential diagnoses can be quite different from case to case.
277 278
This section includes both masses and lesions without mass effect. The presence of
279
mass effect informs the differential diagnoses. Mass effect is seen in over 90% of
280
astrocytomas and oligodendrogliomas (Young et al., 2011; Bentley et al., 2013).
281
Oligodendrogliomas usually distort ventricles and failure to do significantly indicates
282
astrocytoma (Bentley et al., 2013). Lymphoma and GC (see final section) may infiltrate
283
without mass effect.
284 285
Contrast-enhancement
Page 12 of 42
286
Strong contrast-enhancement significantly predicts neoplasia over inflammatory,
287
vascular and other lesions (Cherubini et al., 2005; Young et al., 2014). Most enhancing intra-
288
axial neoplasms are gliomas (Snyder et al., 2006). Inflammatory syndromes (infectious and
289
primary) are still a chief differential diagnosis for solitary enhancing lesions; vascular lesions
290
are a sporadic cause.
291 292
Contrast-enhancement is the most repeatable way of distinguishing within gliomas.
293
LGG displays mild to no enhancement significantly more commonly than HGG (Young et al.,
294
2011; Bentley et al., 2013). Nearly every glioblastoma (grade IV astrocytoma) described was
295
enhancing, and mainly specified as moderate or marked (Lipsitz et al., 2003; Snyder et al.,
296
2006; Young et al., 2011; Giri et al., 2011; Bentley et al., 2013). Enhancement in a partial or
297
complete ring occurs in all grades (Bentley et al., 2013).
298 299
Other primary brain tumors cause enhancing intra-axial lesions, including
300
hemangioma (Schoeman et al., 2002; Eichelberger et al., 2011) and primitive
301
neuroectodermal tumor (see below). A neuroblastoma (a distinct entity from olfactory
302
neuroblastoma) was found to be intra-axial (Capucchio, 2003). Metastases (see below) are a
303
prime
304
hemangiosarcoma, lymphoma, carcinoma or melanoma.
consideration
for
a
solitary
lesion
accompanying
known
extra-neural
305 306
Signal intensities
307
The majority of gliomas and other tumors show non-specific signal intensities, and are
308
generally T1-hypointense and T2-hyperintense (Young et al., 2011, 2014; Bentley et al.,
309
2013). Gliomas are frequently heterogenous, especially T2W signals (Bentley et al., 2013),
310
but mixed intensities (particularly T2W FLAIR) are predictive of neoplasia generally (Young
Page 13 of 42
311
et al., 2014). Cystic regions are significantly more common in HGG than LGG (Bentley et al.,
312
2013), but can occur in other neoplasms and diseases.
313 314
The causes of T1-hyperintensity within tumors are narrow, and include melanoma (see
315
below) and hemorrhage. Astrocytomas are significantly more T1-isointense or hyperintense
316
than oligodendrogliomas, despite showing no evidence of increased hemorrhage (Bentley et
317
al., 2013).
318 319
Hemorrhage or T2W gradient echo (GRE) signal voids occur in 30-40% of gliomas
320
and do not discriminate, occurring in both astrocytoma and oligodendroglioma and all grades
321
but perhaps especially HGG (Young et al., 2011; Bentley et al., 2013). Other lesions with
322
hemorrhage or GRE signal voids include hemangiosarcoma, hemorrhagic cerebrovascular
323
accident, hemangioma, hamartoma, melanoma and cerebellar medulloblastoma (Schoeman et
324
al., 2002; MacKillop et al., 2007; Ide et al., 2009; Eichelberger et al., 2011; Tidwell and
325
Robertson, 2011; Wisner et al., 2011; Lowrie et al., 2012; Sebastianelli et al., 2013).
326 327
Peri-lesional edema occurs with many neoplasms. It is significantly more common in
328
glioma than cerebrovascular accident (Cervera et al., 2011). Within gliomas, astrocytomas
329
may have any degree of edema (including extensive), but oligodendrogliomas have
330
significantly less edema (Bentley et al., 2013), typically minimal to moderate (Wisner et al.,
331
2011). Edema adjacent to fungal granulomas can be extensive (Bentley et al., 2015).
332 333
Location
334
Oligodendrogliomas are usually prosencephalic (Young et al., 2011; Bentley et al.,
335
2013). While astrocytomas are also predisposed to the forebrain, nonetheless the majority of
Page 14 of 42
336
caudal fossa gliomas are astrocytic (including glioblastoma) (Lenz et al., 1991; Young et al.,
337
2011).
338 339
The relationship of location with grade and type of glioma is emerging. Surface
340
contact (Young et al., 2011) and ventricular distortion (Bentley et al., 2013) are more
341
common for oligodendroglioma. Involvement of deep structures (e.g. the thalamus) is more
342
common in HGG (Bentley et al., 2013); glioblastomas in thalamic or brainstem locations are
343
numerous (Lipsitz et al., 2003; Snyder et al., 2006).
344 345
For intra-axial cerebellar lesions, medulloblastoma should be considered (see below).
346
Astrocytoma including glioblastoma occasionally occurs here but solitary cerebellar
347
oligodendroglioma is very rare (Snyder et al., 2006; Young et al., 2011).
348 349
Non-neoplastic differential diagnoses
350
Primary inflammatory diseases, including granulomatous meningoencephalomyelitis
351
(GME), produce focal or multifocal lesions that often enhance (Cherubini et al., 2006;
352
Adamo, 2007; Granger et al., 2010). Infectious diseases, including fungal infections, may
353
cause solitary intra-axial contrasting-enhancing masses (Bentley et al., 2011; Bentley et al.,
354
2015).
355 356
Solitary mildly or non-enhancing intra-axial lesions
357
Description
358 359
The differential diagnosis should effectively include all of the tumors above, but poor contrast-enhancement amends the order of the neoplastic differential diagnoses (Table 4). The
Page 15 of 42
360
non-neoplastic differential diagnoses are also reasonably different. As implied above, LGG is
361
a major differential diagnosis (Young et al., 2011; Bentley et al., 2013).
362 363
Minimal contrast-enhancement is characteristic of GC; every intra-axial lesion to date
364
has been non-enhancing or occasionally mildly enhancing and some are solitary (see below).
365
Non-enhancing exceptions of metastatic tumors have been reported (Hanselman et al., 2006;
366
Singh et al., 2012; Gutierrez-Quintana et al., 2013).
367 368
Primitive neuroectodermal tumor (PNET) includes cerebellar medulloblastoma and
369
PNETs elsewhere that are histologically indistinguishable from medulloblastoma (Koestner et
370
al., 1999). The majority of MRI reports involve cerebellar medulloblastomas. These intra-
371
axial cerebellar masses, usually mid-caudal, are none to mildly heterogeneously-enhancing
372
(McConnell et al., 2004; Polizopoulou et al., 2004; MacKillop et al., 2007; Singh et al., 2011;
373
Choi et al., 2012; Patsikas et al., 2014). Lesions can be well demarcated or poorly marginated.
374
Signal intensities are non-specific, being T1-isointense to hypointense and mildly T2-
375
hyperintense, often with multiple regions of high T2 signal. GRE signal voids occurred in one
376
case (MacKillop et al., 2007) and this tumor can be hemorrhagic (Headley et al., 2009). A
377
fronto-olfactory PNET was briefly described as intra-axial, T1-hypointense, T2-hyperintense
378
and strongly ring-enhancing (Glass et al., 2000). Sporadic PNETs traversing the cranial vault
379
are reported to be moderately to strongly enhancing (Katayama et al., 2001; Snyder et al.,
380
2006; Gains et al., 2011).
381 382
Ischemic strokes are a major differential diagnosis for non-enhancing lesions (Cervera
383
et al., 2011). Contrast-enhancement has a predictive value for neoplasia of 74% (Cherubini et
384
al., 2005) and strong enhancement occurs in only 5% of vascular lesions (Young et al., 2014).
Page 16 of 42
385
Contrast-enhancement may occur due to revascularization, so is not typical in the first few
386
days (Tidwell and Robertson, 2011). Likewise, contrast-enhancement does not rule out
387
hemorrhagic cerebrovascular accident, which is possible during peripheral revascularization
388
(Fig. 5) (Tidwell and Robertson, 2011).
389 390
Diffusion weighted imaging (DWI) and apparent diffusion coefficient maps are
391
critical in distinguishing neoplasms from infarcts. Both glioma and (especially) ischemia can
392
cause restricted diffusion. However, hyperintensity on apparent diffusion coefficients is
393
significantly more common for glioma, as is mass effect (Cervera et al., 2011). Wedge-shaped
394
lesions predict cerebrovascular accident. When DWI was provided the rate of misdiagnosis
395
between cerebrovascular accidents and gliomas was much lower. Acute infarcts may have
396
lower apparent diffusion coefficients than neoplasia (Sutherland-Smith et al., 2011).
397 398
In 200 MRIs, GRE allowed the detection of 32 hemangiosarcoma metastases and 35
399
microbleeds unnoticed on T2 and FLAIR sequences (Hodshon et al., 2014). Tumors can be
400
misdiagnosed as cerebrovascular accidents and vice versa, and DWI and GRE sequences are
401
requisite in the author’s experience.
402 403
MRI features should not be over-interpreted and specific pathologies should not be
404
ruled out prematurely. Neoplastic lesions may not enhance while infarction may (Singh et al.,
405
2011) but only 4/29 primary brain tumors failed to enhance in that study: two GC and two
406
gliomas of unspecified grade. Subsequent studies have shown that GC and LGG routinely
407
lack enhancement. All other primary brain tumors enhanced.
408 409
Non-neoplastic differential diagnoses
Page 17 of 42
410 411
Inflammatory lesions including GME and distemper can be non-enhancing (Cherubini et al., 2006; Singh et al., 2011).
412 413
Multifocal lesions
414
Description
415
This includes multifocal lesions in the same region (e.g. two lesions in the same
416
hemisphere), lesions affecting multiple brain compartments, and multifocal meningeal
417
lesions. Both enhancing and non-enhancing lesions are included (Table 5).
418 419
Lymphoma can produce any of the five patterns considered in this review, although
420
ventricular involvement and non-enhancing lesions are atypical. Between primary central
421
nervous system (CNS) lymphoma and secondary CNS lymphoma (including intravascular
422
lymphoma), extreme variation occurs. This includes one to many intra-axial lesions, solitary
423
extra-axial lesions, meningeal enhancement, and concurrent intra and extra-axial lesions
424
(Morozumi et al., 1997; Kent et al., 2001; Bush et al., 2003; Hanselman et al., 2006; Snyder et
425
al., 2006; Nielsen et al., 2008; Ródenas et al., 2011; Thomovsky et al., 2011; Palus et al.,
426
2012).
427 428
Primary CNS lymphoma is well recognized and the absence of known extra-neural
429
disease does not rule out lymphoma (Mellema et al., 2000; Long et al., 2001; Snyder et al.,
430
2006; Palus et al., 2012). Retropharyngeal lymph nodes or temporalis muscles may be
431
abnormal on MRI (Mellema et al., 2000; Thomovsky et al., 2011; Palus et al., 2012).
432
Intravascular lymphoma normally affects the brain (Kent et al., 2001; Bush et al., 2003) and
433
MRI features include multiple lesions, each displaying varying combinations of infarctive,
434
hemorrhagic and neoplastic criteria (Fig. 6).
Page 18 of 42
435 436
Lymphoma has no characteristic MRI appearance; the sensitivity of MRI has been
437
reported to be 0% in some studies (Wolff et al., 2012). CSF analysis generally fails to reveal
438
neoplastic cells and overlaps with other etiologies (Kent et al., 2001; Hanselman et al., 2006;
439
Snyder et al., 2006).
440 441
In order of frequency, common hematogenous metastases are hemangiosarcoma,
442
round cell tumors (particularly lymphoma), carcinoma and melanoma (Snyder et al., 2008;
443
Song et al., 2013). Metastases often affect the cerebrum with or without other intracranial
444
regions (Snyder et al., 2008; Ródenas et al., 2011). The pituitary gland is involved by
445
lymphoma and carcinomas, sporadically by HS and melanoma, and negligibly by
446
hemangiosarcoma (Kent et al., 2001; Tamura et al., 2007; Snyder et al., 2008; Gutierrez-
447
Quintana et al., 2013).
448 449
Metastasis usually causes multifocal MRI lesions (Wisner et al., 2011). While
450
metastasis is an important consideration for a solitary lesion, most MRI reports specify
451
multifocal lesions (Appendix A; Supplementary material). In people, solitary metastasis is a
452
major differential diagnosis for HGG (Hakyemez et al., 2010). Minimal information is
453
available to assist in differentiating canine primary brain tumors from metastases by MRI
454
alone, highlighting the importance of considering the dog as a whole (Fig. 7).
455 456
GC may cause focal lesions, multifocal lesions, spread down white matter,
457
periventricular and subpial lesions, or sporadic diffuse meningeal enhancement (Porter et al.,
458
2003; Gruber et al., 2006; Galán et al., 2010; Ródenas et al., 2011; Fukuoka et al., 2012;
459
Martin-Vaquero et al., 2012; Canal et al., 2013; Bentley et al., 2014).
Page 19 of 42
460 461
Dogs are occasionally affected by two unrelated tumors, usually a meningioma or
462
glioma with another tumor (Stacy et al., 2003; Alves et al., 2006; Snyder et al., 2006;
463
MacKillop et al., 2007; McDonnell et al., 2007; Sturges et al., 2008; Espino et al., 2009).
464
Multifocal oligodendroglioma occurred in three dogs (Koch et al., 2011) and
465
oligodendroglioma can spread via the CSF (Koestner et al., 1999). Two dogs with diffuse
466
low-grade astrocytoma had non-enhancing lesions (Kraft et al., 1990).
467 468 469
Contrast enhancement This is a key discriminating feature. The most repeatable characteristic of lymphoma
470
is contrast-enhancement. With the exception of only one dog (Hanselman et al., 2006),
471
enhancement occurred in every report of primary, secondary and intravascular lymphoma
472
including a case with ventricular enhancement (Morozumi et al., 1997; Kent et al., 2001;
473
Bush et al., 2003; Snyder et al., 2006; Nielsen et al., 2008; Ródenas et al., 2011; Thomovsky
474
et al., 2011; Palus et al., 2012). Contrast-enhancement is absent in only 1% of humans with
475
primary CNS lymphoma (Batchelor and Loeffler, 2006). With rare exceptions, metastatic
476
lesions also usually enhance (Wisner et al., 2011) (Appendix: Supplementary material).
477 478
In contrast, GC lesions rarely enhance. Every reported intra-axial GC lesion was
479
minimally or non-enhancing, although extra-axial masses and diffuse meningeal lesions can
480
enhance (Porter et al., 2003; Gruber et al., 2006; Galán et al., 2010; Singh et al., 2011;
481
Fukuoka et al., 2012; Martin-Vaquero et al., 2012; Plattner et al., 2012; Canal et al., 2013;
482
Bentley et al., 2014).
483 484
Signal intensities
Page 20 of 42
485
Melanin is T1-hyperintense but melanomas themselves vary. In humans, there are
486
increasing rates of T1-hyperintensity from amelanotic to highly melanotic histologic subtypes
487
of metastases (Isiklar et al., 1995). Melanin and hemorrhage share many features including
488
GRE signal voids (Fig. 8); in the same study 12% of melanoma metastases displayed features
489
consistent with hematoma. Canine intracranial metastasis MRI has not been reported, but
490
ocular and nasal melanomas are inconsistently T1-hyperintense and T2-hypointense (Kato et
491
al., 2005; Miwa et al., 2005; Hicks and Fidel, 2006). Human melanoma metastases typically
492
contrast-enhance (Isiklar et al., 1995) and there might be much overlap in the MRI features of
493
canine glioma, hemangiosarcoma and melanoma.
494 495
Signal intensities are otherwise generally non-specific, being mostly T1-isointense to
496
hypointense and T2-hyperintense for lymphoma, gliomatosis cerebri and many other lesions
497
(Hanselman et al., 2006; Snyder et al., 2006; Ródenas et al., 2011; Palus et al., 2012; Bentley
498
et al., 2014). T1-hyperintensities were shown to have occurred in one dog with multiple
499
infarcts secondary to intravascular lymphoma (Kent et al., 2001).
500 501
Some lymphomas and numerous GC and metastatic lesions have vague borders
502
(Snyder et al., 2006; Thomovsky et al., 2011; Wisner et al., 2011; Ródenas et al., 2011; Palus
503
et al., 2012; Bentley et al., 2014). MRI might be within normal limits with lymphoma,
504
multifocal oligodendroglioma or especially GC (Koch et al., 2011; Plattner et al., 2012;
505
Bentley et al., 2014; Young et al., 2014).
506 507
Mass effect
508
Lymphoma and particularly GC are archetypal examples of diffuse infiltration of
509
neoplastic cells with negligible mass effect. While most cases of lymphoma have a mass
Page 21 of 42
510
effect (Ródenas et al., 2011; Thomovsky et al., 2011; Palus et al., 2012), some do not
511
(Hanselman et al., 2006). Many GC cases exhibit single or multiple parenchymal T2-
512
hyperintensities with minimal mass effect; less commonly, mass lesions are seen with or
513
without concurrent infiltrative disease (Porter et al., 2003; Galán et al., 2010; Fukuoka et al.,
514
2012; Plattner et al., 2012; Bentley et al., 2014).
515 516
Multifocal or diffuse meningeal lesions
517
Lymphoma is a major cause of multifocal or diffuse meningeal enhancement
518
(Mellema et al., 2000; Palus et al., 2012). Often accompanying other lesions, there may be
519
subtle enhancement of the meninges of one region, enhancing meninges adjacent to an extra-
520
axial mass, or strong multifocal-diffuse meningeal enhancement (Mellema et al., 2000; Bush
521
et al., 2003; Thomovsky et al., 2011; Palus et al., 2012).
522 523
Other neoplasms sporadically exhibiting multifocal to diffuse meningeal enhancement
524
include HS (Tamura et al., 2009), leukemia (Mellema et al., 2000; Vernau et al., 2000), GC
525
(Canal et al., 2013), granular cell tumor (Mishra et al., 2012) and meningeal carcinomatosis
526
(e.g. mammary carcinoma or choroid plexus carcinoma) (Lipsitz et al., 1999; Behling-Kelly et
527
al., 2010; Mateo et al., 2010). Diffuse-multifocal meningeal enhancement, with or without
528
other lesions, can increase the suspicion of round cell tumors and inflammatory disease.
529 530
Non-neoplastic differential diagnoses
531
For multifocal lesions, a major consideration is inflammatory disease including GME,
532
necrotizing encephalitides (Granger et al., 2010) and fungal, neosporosis, viral and tick-borne
533
infectious diseases (Bathen-Noethen et al., 2008; Garosi et al., 2010; Lipitz et al., 2010; Sykes
Page 22 of 42
534
et al., 2010; Parzefall et al., 2014). Other causes include thiamine deficiency (Garosi et al.,
535
2003).
536 537
Post-ictal changes are reversible MRI abnormalities in seizing dogs (Mellema et al.,
538
1999). Such changes may overlap in appearance with infiltrating neoplasia, occurring
539
unilaterally or bilaterally in the parenchyma of the pyriform-temporal lobe and elsewhere, and
540
showing non-specific signal intensities and variable contrast-enhancement. It is noteworthy
541
that neoplasia is the most common cause of secondary epilepsy (Pákozdy et al., 2008).
542 543
Conclusions
544
Much information is available to create a comprehensive differential diagnosis (and to
545
rank it appropriately) for dogs with brain tumors undergoing MRI. However, the features
546
garnered from MRI must be correlated with all available clinical information and with
547
epidemiological data. When MRI lesions are first categorized as meningeal masses,
548
ventricular masses, intra-axial enhancing lesions, intra-axial mildly to non-enhancing lesions
549
or multifocal lesions, then a more specific list of differential diagnoses can be developed for
550
each individual patient. This is imperative in selecting therapies without or prior to the
551
availability of histopathology data.
552 553 554 555
Conflict of interest statement The author of this paper has no financial or personal relationship with other people or organisations that could inappropriately influence or bias the content of the paper.
556 557
Acknowledgements
Page 23 of 42
558 559
The author thanks the diagnostic imaging service of the Purdue University Veterinary Teaching Hospital for acquiring images used in this article.
560 561 562 563
Appendix: Supplementary material Supplementary data associated with this article can be found in the online version, at doi….setters please insert doi number
564 565
References
566 567
Adamo, P., 2007. Granulomatous meningoencephalomyelitis in dogs. Compendium: Continuing Education for Veterinarians 29, 678–90.
568 569 570
Agthe, P., Caine, A.R., Gear, R.N., Dobson, J.M., Richardson, K.J., Herrtage, M.E., 2009. Prognostic significance of specific magnetic resonance imaging features in canine nasal tumours treated by radiotherapy. Journal of Small Animal Practice 50, 641–648.
571 572 573
Alves, A., Prada, J., Almeida, J.M., Pires, I., Queiroga, F., Platt, S.R., Varejão, A.S.P., 2006. Primary and secondary tumors occurring simultaneously in the brain of a dog. Journal of Small Animal Practice 47, 607–610.
574 575 576
Anwer, C.C., Vernau, K.M., Higgins, R.J., Dickinson, P.J., Sturges, B.K., LeCouteur, R.A., Bentley, R.T., Wisner, E.R., 2013. Magnetic resonance imaging features of intracranial granular cell tumors in six dogs. Veterinary Radiology and Ultrasound 54, 271–277.
577 578 579
Baron, M.L., Hecht, S., Westermeyer, H.D., Mankin, J.M., Novak, J.M., Donnell, R.L., 2011. Intracranial extension of retrobulbar blastomycosis (Blastomyces dermatitidis) in a dog. Veterinary Ophthalmology 14, 137–141.
580 581
Batchelor, T., Loeffler, J.S., 2006. Primary CNS lymphoma. Journal of Clinical Oncology 24, 1281–1288.
582 583 584
Bathen-Noethen, A., Stein, V.M., Puff, C., Baumgaertner, W., Tipold, A., 2008. Magnetic resonance imaging findings in acute canine distemper virus infection. Journal of Small Animal Practice 49, 460–467.
585 586 587
Behling-Kelly, E., Petersen, S., Muthuswamy, A., Webb, J.L., Young, K.M., 2010. Neoplastic pleocytosis in a dog with metastatic mammary carcinoma and meningeal carcinomatosis. Veterinary Clinical Pathology 39, 247–252.
588 589
Bentley, R.T., Burcham, G.N., Heng, H.G., Levine, J.M., Longshore, R., Carrera-Justiz, S., Cameron, S., Kopf, K., Miller, M.A., 2014. A comparison of clinical, magnetic
Page 24 of 42
590 591 592
resonance imaging and pathological findings in dogs with gliomatosis cerebri, focusing on cases with minimal magnetic resonance imaging changes. Veterinary and Comparative Oncology doi: 10.1111/vco.12106
593 594 595
Bentley, R.T., Faissler, D., Sutherland-Smith, J., 2011. Successful management of an intracranial phaeohyphomycotic fungal granuloma in a dog. Journal of the American Veterinary Medical Association 239, 480–485.
596 597 598 599
Bentley, R.T., Heng, H.G., Thompson, C., Lee, C.S., Kroll, R.A., Roy, M.E., Marini, L., Heo, J., Wigle, W.L., 2015. Magnetic resonance imaging features and outcome for solitary central nervous system Coccidioides granulomas in 11 dogs and cats. Veterinary Radiology and Ultrasound. In press, 2015.
600 601 602 603
Bentley, R.T., Ober, C.P., Anderson, K.L., Feeney, D.A., Naughton, J.F., Ohlfest, J.R., O’Sullivan, M.G., Miller, M.A., Constable, P.D., Pluhar, G.E., 2013. Canine intracranial gliomas: relationship between magnetic resonance imaging criteria and tumor type and grade. The Veterinary Journal 198, 463–471.
604 605 606
Borrelli, A., Mattiazzi, L., Capucchio, M.T., Biolatti, C., Cagnasso, A., Gianella, P., D’Angelo, A., 2009. Cachexia secondary to intracranial anaplastic (malignant) ependymoma in a boxer dog. Journal of Small Animal Practice 50, 554–557.
607 608 609
Brewer, D.M., Cerda-Gonzalez, S., Dewey, C.W., Coates, J.R., 2010. Diagnosis and surgical resection of a choroid plexus cyst in a dog. Journal of Small Animal Practice 51, 169– 172.
610 611 612
Bush, W.W., Throop, J.L., McManus, P.M., Kapatkin, A.S., Vite, C.H., Van Winkle, T.J., 2003. Intravascular lymphoma involving the central and peripheral nervous systems in a dog. Journal of the American Animal Hospital Association 39, 90–96.
613 614
Canal, S., Bernardini, M., Pavone, S., Mandara, M.T., 2013. Primary diffuse leptomeningeal gliomatosis in 2 dogs. Canadian Veterinary Journal 54, 1075–1079.
615 616
Capucchio, M., 2003. Histological and immunohistochemical study of a neuroblastoma in a dog. Clinical Neuropathology 22, 176–179.
617 618 619
Cervera, V., Mai, W., Vite, C.H., Johnson, V., Dayrell-Hart, B., Seiler, G.S., 2011. Comparative magnetic resonance imaging findings between gliomas and presumed cerebrovascular accidents in dogs. Veterinary Radiology and Ultrasound 52, 33–40.
620 621
Chandra, A.M., Ginn, P.E., 1999. Primary malignant histiocytosis of the brain in a dog. Journal of Comparative Pathology 121, 77–82.
622 623 624
Chang, S.C., Liao, J.W., Lin, Y.C., Liu, C.I., Wong, M.L., 2007. Pancreatic acinar cell carcinoma with intracranial metastasis in a dog. The Journal of Veterinary Medical Science 69, 91–93.
625 626 627
Cherubini, G.B., Mantis, P., Martinez, T.A., Lamb, C.R., Cappello, R., 2005. Utility of magnetic resonance imaging for distinguishing neoplastic from non-neoplastic brain lesions in dogs and cats. Veterinary Radiology and Ultrasound 46, 384–387.
Page 25 of 42
628 629 630
Cherubini, G.B., Platt, S.R., Anderson, T.J., Rusbridge, C., Lorenzo, V., Mantis, P., Cappello, R., Al, H., Highland, W., 2006. Characteristics of magnetic resonance images of granulomatous meningoencephalomyelitis in 11 dogs. Veterinary Record 159, 110–115.
631 632 633
Choi, U.S., Philippe, L., Alleman, A.R., Kim, M.S., Lee, K.C., 2012. Cytologic and immunohistochemical characterization of a primitive neuroectodermal tumor in the brain of a dog. Veterinary Clinical Pathology 41, 153–157.
634 635 636
De Decker, S., Davies, E., Benigni, L., Wilson, H., Pelligand, L., Rayner, E.L., Shihab, N., Volk, H.A., 2012. Surgical treatment of an intracranial epidermoid cyst in a dog. Veterinary Surgery 41, 766–771.
637 638
Eckersley, G., Geel, J., Kriek, N., 1991. A craniopharyngioma in a seven-year-old dog. Journal of the South African Veterinary Association 62, 65–67.
639 640 641
Eichelberger, B.M., Kraft, S.L., Halsey, C.H.C., Park, R.D., Miller, M.D., Klopp, L., 2011. Imaging diagnosis-magnetic resonance imaging findings of primary cerebral hemangioma. Veterinary Radiology and Ultrasound 52, 188–191.
642 643 644
Espino, L., Suarez, M., Santamarina, G., Vila, M., Miño, N., Lopez-Peña, M., 2009. First report of the simultaneous occurrence of choroid plexus papilloma and meningioma in a dog. Acta Veterinaria Hungarica 57, 389–397.
645 646 647
Fernández, T., Díez-Bru, N., Rios, A., Gómez, L., Pumarola, M., 2001. Intracranial metastases from an ovarian dysgerminoma in a 2-year-old dog. Journal of the American Animal Hospital Association 37, 553–556.
648 649 650
Fukuoka, H., Sasaki, J., Kamishina, H., Sato, R., Yasuda, J., Katayama, M., Tohyama, K., Ohshida, M., Goryo, M., 2012. Gliomatosis Cerebelli in a Saint Bernard Dog. Journal of Comparative Pathology 147, 37–41.
651 652
Gains, M.J., Leclerc, M., Bédard, C., 2011. A primitive neuroectodermal tumor with extension into the cranial vault in a dog. Canadian Veterinary Journal 52, 1232–1236.
653 654 655
Galán, A., Guil-Luna, S., Millán, Y., Martín-Suárez, E.M., Pumarola, M., de Las Mulas, J.M., 2010. Oligodendroglial gliomatosis cerebri in a Poodle. Veterinary and Comparative Oncology 8, 254–262.
656 657 658 659
Garosi, L., Dawson, A., Couturier, J., Matiasek, L., Stefani, A. De, Davies, E., Jeffery, N., Smith, P., 2010. Necrotizing cerebellitis and cerebellar atrophy caused by Neospora caninum infection: magnetic resonance imaging and clinicopathologic findings in seven dogs. Journal of Veterinary Internal Medicine 24, 571–578.
660 661 662
Garosi, L.S., Dennis, R., Platt, S.R., Corletto, F., de Lahunta, A., Jakobs, C., 2003. Thiamine deficiency in a dog: clinical, clinicopathologic, and magnetic resonance imaging findings. Journal of Veterinary Internal Medicine 17, 719–723.
663 664 665
Giri, D.K., Aloisio, F., Ajithdoss, D.K., Ambrus, A., Lidbury, J.A., Hein, H.E., Porter, B.F., 2011. Giant cell glioblastoma in the cerebrum of a pembroke welsh corgi. Journal of Comparative Pathology 144, 324–327.
Page 26 of 42
666 667 668
Glass, E., Kapatkin, A., Vite, C., Steinberg, S., 2000. A modified bilateral transfrontal sinus approach to the canine frontal lobe and olfactory bulb: surgical technique and five cases. Journal of the American Animal Hospital Association 36, 43–50.
669 670 671
Graham, J.P., Newell, S.M., Voges, A.K., Roberts, G.D., Harrison, J.M., 1998. The dural tail sign in the diagnosis of meningiomas. Veterinary Radiology and Ultrasound 39, 297– 302.
672 673 674
Granger, N., Smith, P.M., Jeffery, N.D., 2010. Clinical findings and treatment of noninfectious meningoencephalomyelitis in dogs: a systematic review of 457 published cases from 1962 to 2008. The Veterinary Journal 184, 290–297.
675 676
Gruber, A., Leschnik, M., Kneissl, S., Schmidt, P., 2006. Gliomatosis cerebri in a dog. Journal of Veterinary Medicine A 53, 435–438.
677 678 679 680
Gutierrez-Quintana, R., Carrera, I., Dobromylskyj, M., Patterson-Kane, J., Ortega, M., Wessmann, A., 2013. Pituitary Metastasis of Pancreatic Origin in a Dog Presenting with Acute-Onset Blindness. Journal of the American Animal Hospital Association 49, 403– 406.
681 682 683
Hakyemez, B., Erdogan, C., Gokalp, G., Dusak, A., Parlak, M., 2010. Solitary metastases and high-grade gliomas: radiological differentiation by morphometric analysis and perfusionweighted MRI. Clinical Radiology 65, 15–20.
684 685 686
Hanselman, B., Kruth, S., Poma, R., Nykamp, S., 2006. Hypernatremia and hyperlipidemia in a dog with central nervous system lymphosarcoma. Journal of Veterinary Internal Medicine 20, 1029–1032.
687 688
Hathcock, J.T., 1996. Low field magnetic resonance imaging characteristics of cranial vault meningiomas in 13 dogs. Veterinary Radiology and Ultrasound 37, 257–263.
689 690 691
Headley, S.A., Koljonen, M., Gomes, L.A., Sukura, A., 2009. Central primitive neuroectodermal tumor with ependymal differentiation in a dog. Journal of Comparative Pathology 140, 80–83.
692 693 694
Hecht, S., Adams, W.H., Smith, J.R., Thomas, W.B., 2011. Clinical and imaging findings in five dogs with intracranial blastomycosis (Blastomyces dermatiditis). Journal of the American Animal Hospital Association 47, 241–249.
695 696
Hicks, D.G., Fidel, J.L., 2006. Intranasal malignant melanoma in a dog. Journal of the American Animal Hospital Association 42, 472–476.
697 698 699
Higgins, R.J., Lecouteur, R.A., Vernau, K.M., Sturges, B.K., Obradovich, J.E., Bollen, A.W., 2001. Granular cell tumor of the canine central nervous system: two cases. Veterinary Pathology 38, 620–627.
700 701 702
Hodshon, A.W., Hecht, S., Thomas, W.B., 2014. Use of the T2*-Weighted Gradient Recalled Echo Sequence for Magnetic Resonance Imaging of the Canine and Feline Brain. Veterinary Radiology and Ultrasound doi: 10.1111/vru.12164
Page 27 of 42
703 704 705
Ide, T., Uchida, K., Kagawa, Y., Suzuki, K., Nakayama, H., 2011. Pathological and immunohistochemical features of subdural histiocytic sarcomas in 15 dogs. Journal of Veterinary Diagnostic Investigation 23, 127–132.
706 707 708
Ide, T., Uchida, K., Morozumi, M., Nakayama, H., 2009. Hamartoma in the medulla oblongata with marked mineral deposits in a dog. The Journal of Veterinary Medical Science 71, 1097–1100.
709 710 711
Isiklar, I., Leeds, N., Fuller, G., Kumar, A., 1995. Intracranial metastatic melanoma: correlation between MR imaging characteristics and melanin content. American Journal of Roentgenology 165, 1503–1512.
712 713 714
James, F.M.K., da Costa, R.C., Fauber, A., Peregrine, A.S., McEwen, B., Parent, J.M., Bergman, R., 2012. Clinical and MRI findings in three dogs with polycystic meningiomas. Journal of the American Animal Hospital Association 48, 331–338.
715 716 717
Jung, H., Lee, H., Kim, J., Jang, H., Moon, J., Sur, J., Jeongim, H., Jung, D., 2014. Imatinib mesylate plus hydroxyurea chemotherapy for cerebellar meningioma in a Belgian Malinois dog. The Journal of Veterinary Medical Science doi: 10.1292/jvms.14-0001
718 719 720
Kang, B., Park, C., Yoo, J., Gu, S., Jang, D., Kim, Y., 2009. 18F-fluorodeoxyglucose positron emission tomography and magnetic resonance imaging findings of primary intracranial histiocytic sarcoma in a dog. The Journal of Veterinary Medical Science 71, 1397–1401.
721 722 723
Katayama, K.I., Kuroki, K., Uchida, K., Nakayama, H., Sakai, M., Mochizuki, M., Nishimura, R., Sasaki, N., Doi, K., 2001. A case of canine primitive neuroectodermal tumor (PNET). The Journal of Veterinary Medical Science 63, 103–105.
724 725 726
Kato, K., Nishimura, R., Sasaki, N., Matsunaga, S., Mochizuki, M., Nakayama, H., Ogawa, H., 2005. Magnetic resonance imaging of a canine eye with melanoma. The Journal of Veterinary Medical Science 67, 179–182.
727 728
Kent, M., Delahunta, A., Tidwell, A.S., 2001. MR imaging findings in a dog with intravascular lymphoma in the brain. Veterinary Radiology and Ultrasound 42, 504–510.
729 730 731
Kitagawa, M., Okada, M., Yamamura, H., Kanayama, K., Sakai, T., 2006. Diagnosis of olfactory neuroblastoma in a dog by magnetic resonance imaging. Veterinary Record 159, 288–289.
732 733
Koch, M.W., Sánchez, M.D., Long, S., 2011. Multifocal oligodendroglioma in three dogs. Journal of the American Animal Hospital Association 47, e77–e85.
734 735 736
Koestner, A., Bilzer, T., Fatzer, R., Summers, B., Van Winkle, T., 1999. Histologic classification of tumors of the nervous system of domestic animals 2nd ed., Washington, DC: Armed Forces Institute of Pathology.
737 738 739
Kraft, S.L., Gavin, P.R., DeHaan, C., Moore, M., Wendling, L.R., Leathers, C.W., 1997. Retrospective review of 50 canine intracranial tumors evaluated by magnetic resonance imaging. Journal of Veterinary Internal Medicine 11, 218–225.
Page 28 of 42
740 741 742
Kraft, S.L., Gavin, P.R., Leathers, C.W., Wendling, L.R., Frenier, S., Dorn, R. V, 1990. Diffuse cerebral and leptomeningeal astrocytoma in dogs: MR features. Journal of Computer Assisted Tomography 14, 555–560.
743 744
Lenz, S.D., Janovitz, E.B., Lockridge, K., 1991. An anaplastic astrocytoma (glioblastoma) in the cerebellum of a dog. Veterinary Pathology 28, 250–252.
745 746 747
Liebel, F.X., Summers, B.A., Lowrie, M., Smith, P., Garosi, L., 2013. Imaging diagnosismagnetic resonance imaging features of a cerebral hemangioblastoma in a dog. Veterinary Radiology and Ultrasound 54, 164–167.
748 749 750
Lipitz, L., Rylander, H., Forrest, L.J., Foy, D.S., 2010. Clinical and magnetic resonance imaging features of central nervous system blastomycosis in 4 dogs. Journal of Veterinary Internal Medicine 24, 1509–1514.
751 752 753
Lipsitz, D., Higgins, R.J., Kortz, G.D., Dickinson, P.J., Bollen, A.W., Naydan, D.K., LeCouteur, R.A., 2003. Glioblastoma multiforme: clinical findings, magnetic resonance imaging, and pathology in five dogs. Veterinary Pathology 40, 659–669.
754 755 756
Lipsitz, D., Levitski, R.E., Berry, W.L., 2001. Magnetic resonance imaging features of multilobular osteochondrosarcoma in 3 dogs. Veterinary Radiology and Ultrasound 42, 14–19.
757 758 759
Lipsitz, D., Levitski, R., Chauvet, A., 1999. Magnetic resonance imaging of a choroid plexus carcinoma and meningeal carcinomatosis in a dog. Veterinary Radiology and Ultrasound 40, 246–250.
760 761 762
Long, S.N., Johnston, P.E., Anderson, T.J., 2001. Primary T-cell lymphoma of the central nervous system in a dog. Journal of the American Veterinary Medical Association 218, 719–722.
763 764 765
Lovett, M.C., Fenner, W.R., Watson, A.T., Hostutler, R.A., 2012. Imaging diagnosis-MRI characteristics of a fourth ventricular cholesterol granuloma in a dog. Veterinary Radiology and Ultrasound 53, 650–654.
766 767 768
Lowrie, M., De Risio, L., Dennis, R., Llabrés-Díaz, F., Garosi, L., 2012. Concurrent medical conditions and long-term outcome in dogs with nontraumatic intracranial hemorrhage. Veterinary Radiology and Ultrasound 53, 381–388.
769 770
MacKillop, E., 2011. Magnetic resonance imaging of intracranial malformations in dogs and cats. Veterinary Radiology and Ultrasound 52, S42–S51.
771 772 773
MacKillop, E., Thrall, D.E., Ranck, R.S., Linder, K.E., Munana, K.R., 2007. Imaging diagnosis-synchronous primary brain tumors in a dog. Veterinary Radiology and Ultrasound 48, 550–553.
774 775 776
Martin-Vaquero, P., da Costa, R.C., Aeffner, F., Oglesbee, M.J., Echandi, R.L., 2010. Imaging diagnosis-hemorrhagic meningioma. Veterinary Radiology and Ultrasound 51, 165–167.
Page 29 of 42
777 778 779
Martin-Vaquero, P., da Costa, R.C., Wolk, K.E., Premanandan, C., Oglesbee, M.J., 2012. MRI features of gliomatosis cerebri in a dog. Veterinary Radiology and Ultrasound 53, 189–192.
780 781 782
Mateo, I., Lorenzo, V., Muñoz, A., Molín, J., 2010. Meningeal carcinomatosis in a dog: magnetic resonance imaging features and pathological correlation. Journal of Small Animal Practice 51, 43–48.
783 784 785
McConnell, J.F., Platt, S., Smith, K.C., 2004. Magnetic resonance imaging findings of an intracranial medulloblastoma in a Polish Lowland Sheepdog. Veterinary Radiology and Ultrasound 45, 17–22.
786 787 788
McDonnell, J.J., Kalbko, K., Keating, J.H., Sato, A.F., Faissler, D., 2007. Multiple meningiomas in three dogs. Journal of the American Animal Hospital Association 43, 201–208.
789 790 791
Mellema, L., Koblik, P., Kortz, G., LeCouteur, R., Chechowitz, M., Dickinson, P., 1999. Reversible magnetic resonance imaging abnormalities in dogs following seizures. Veterinary Radiology and Ultrasound 40, 588–595.
792 793 794
Mellema, L.M., Samii, V.F., Vernau, K.M., LeCouteur, R. a, 2000. Meningeal enhancement on magnetic resonance imaging in 15 dogs and 3 cats. Veterinary Radiology and Ultrasound 43, 10–15.
795 796 797
Mercier, M., Barnes Heller, H.L., Bischoff, M.G., Looper, J., Bacmeister, C.X., 2007. Imaging diagnosis-hyperostosis associated with meningioma in a dog. Veterinary Radiology and Ultrasound 48, 421–423.
798 799
Mishra, S., Kent, M., Haley, A., Platt, S., Sakamoto, K., 2012. Atypical meningeal granular cell tumor in a dog. Journal of Veterinary Diagnostic Investigation 24, 192–197.
800 801 802
Miwa, Y., Matsunaga, S., Kato, K., Ogawa, H., Nakayama, H., Tsujimoto, S., Sasaki, N., 2005. Choroidal melanoma in a dog. The Journal of Veterinary Medical Science 67, 821–823.
803 804 805
Molín, J., Rentmeister, K., Matiasek, K., 2014. Caudal fossa respiratory epithelial cyst in a dog: clinical, magnetic resonance imaging, and histopathologic findings. Journal of Veterinary Internal Medicine 28, 1336–1340.
806 807
Moore, P.F., 2014. A review of histiocytic diseases of dogs and cats. Veterinary Pathology 51, 167–184.
808 809 810
Morozumi, M., Miyahara, K., Sato, M., Hirose, T., 1997. Computed tomography and magnetic resonance findings in two dogs and a cat with intracranial lesions. The Journal of Veterinary Medical Science 59, 807–810.
811 812
Motta, L., Mandara, M.T., Skerritt, G.C., 2012. Canine and feline intracranial meningiomas: an updated review. The Veterinary Journal 192, 153–165.
Page 30 of 42
813 814 815
Nielsen, L., Thompson, H., Hammond, G.J., Chang, Y., Ramsey, I.K., 2008. Central diabetes insipidus associated with primary focal B cell lymphoma in a dog. Veterinary Record 162, 124–126.
816 817 818
Pákozdy, A., Leschnik, M., Tichy, A.G., Thalhammer, J.G., 2008. Retrospective clinical comparison of idiopathic versus symptomatic epilepsy in 240 dogs with seizures. Acta Veterinaria Hungarica 56, 471–483.
819 820
Palus, V., Volk, H.A., Lamb, C.R., Targett, M.P., Cherubini, G.B., 2012. MRI features of CNS lymphoma in dogs and cats. Veterinary Radiology and Ultrasound 53, 44–49.
821 822 823
Parzefall, B., Driver, C.J., Benigni, L., Davies, E., 2014. Magnetic resonance imaging characteristics in four dogs with central nervous system neosporosis. Veterinary Radiology and Ultrasound 55, 539–546.
824 825 826 827
Patsikas, M., Jakovljevic, S Papadopoulou, P., Polizopoulou, Z., Kazakos, G., Tontis, D., Soultani, C., Charitanti, A., Chrissogonidis, I., Tsifountoudis, I., 2014. Magnetic resonance imaging features of cerebellar vermis medulloblastoma in an adult canine patient. Journal of Biological Regulators and Homeostatic Agents 28, 341–347.
828 829 830
Plattner, B.L., Kent, M., Summers, B., Platt, S.R., Freeman, A.C., Blas-Machado, U., Clemans, J., Cheville, N.F., Garcia-Tapia, D., 2012. Gliomatosis cerebri in two dogs Journal of the American Animal Hospital Association 48, 359–365.
831 832 833
Polizopoulou, Z.S., Koutinas, A.F., Souftas, V.D., Kaldrymidou, E., Kazakos, G., Papadopoulos, G., 2004. Diagnostic correlation of CT-MRI and histopathology in 10 dogs with brain neoplasms. Journal of Veterinary Medicine A 51, 226–231.
834 835
Porter, B., DeLahunta, A., Summers, B., 2003. Gliomatosis cerebri in six dogs. Veterinary Pathology 40, 97–102.
836 837 838
Ródenas, S., Pumarola, M., Gaitero, L., Zamora, A., Añor, S., 2011. Magnetic resonance imaging findings in 40 dogs with histologically confirmed intracranial tumors. The Veterinary Journal 187, 85–91.
839 840 841
Rossmeisl, J., Pineyro, P., Sponenberg, D., Garman, R., Jortner, B.S., 2012. Clinicopathologic features of intracranial central neurocytomas in 2 dogs. Journal of Veterinary Internal Medicine 26, 186–191.
842 843 844
Salvadori, C., Pintore, M.D., Ricci, E., Konar, M., Tartarelli, C.L., Gasparinetti, N., Cantile, C., 2011. Microcystic meningioma of the fourth ventricle in a dog. The Journal of Veterinary Medical Science 73, 367–370.
845 846 847
Schoeman, J.P., Stidworthy, M.F., Penderis, J., Kafka, U., 2002. Magnetic resonance imaging of a cerebral cavernous haemangioma in a dog. Journal of the South African Veterinary Association 73, 207–210.
848 849 850
Sebastianelli, M., Mandara, M.T., Pavone, S., Canal, S., Bernardini, M., 2013. Thalamic astrocytic hamartoma and associated meningoangiomatosis in a German shepherd dog. Research in Veterinary Science 94, 644–647.
Page 31 of 42
851 852 853
Seruca, C., Ródenas, S., Leiva, M., Peña, T., Añor, S., 2010. Acute postretinal blindness: ophthalmologic, neurologic, and magnetic resonance imaging findings in dogs and cats (seven cases). Veterinary Ophthalmology 13, 307–314.
854 855
Sessums, K.B., Lane, S.B., 2008. Imaging diagnosis: intracranial mucocele in a dog. Veterinary Radiology and Ultrasound 49, 564–566.
856 857
Sharkey, L.C., McDonnell, J.J., Alroy, J., 2004. Cytology of a mass on the meningeal surface of the left brain in a dog. Veterinary Clinical Pathology 33, 111–114.
858 859 860
Singh, J.B., Oevermann, A., Henke, D., Segard, E., Gorgas, D., 2012. Imaging diagnosis-lack of contrast enhancement in metastatic cerebral adenocarcinoma. Veterinary Radiology and Ultrasound 53, 193–196.
861 862 863 864
Singh, J.B., Oevermann, A., Lang, J., Vandevelde, M., Doherr, M., Henke, D., Gorgas, D., 2011. Contrast media enhancement of intracranial lesions in magnetic resonance imaging does not reflect histopathologic findings consistently. Veterinary Radiology and Ultrasound 52, 619–626.
865 866 867
Snyder, J.M., Lipitz, L., Skorupski, K. a, Shofer, F.S., Van Winkle, T.J., 2008. Secondary intracranial neoplasia in the dog: 177 cases (1986-2003). Journal of Veterinary Internal Medicine 22, 172–177.
868 869 870
Snyder, J.M., Shofer, F.S., Winkle, T.J. Van, Massicotte, C., 2006. Canine intracranial primary neoplasia: 173 cases (1986–2003). Journal of Veterinary Internal Medicine 20, 669–675.
871 872 873
Song, R.B., Vite, C.H., Bradley, C.W., Cross, J.R., 2013. Postmortem evaluation of 435 cases of intracranial neoplasia in dogs and relationship of neoplasm with breed, age, and body weight. Journal of Veterinary Internal Medicine 27, 1143–1152.
874 875 876
Stacy, B.A., Stevenson, T.L., Lipsitz, D., Higgins, R.J., 2003. Simultaneously occurring oligodendroglioma and meningioma in a dog. Journal of Veterinary Internal Medicine 17, 357–359.
877 878 879 880
Sturges, B.K., Dickinson, P.J., Bollen, A.W., Koblik, P.D., Kass, P.H., Kortz, G.D., Vernau, K.M., Knipe, M.F., Lecouteur, R.A., Higgins, R.J., 2008. Magnetic resonance imaging and histological classification of intracranial meningiomas in 112 dogs. Journal of Veterinary Internal Medicine 22, 586–595.
881 882 883
Sutherland-Smith, J., King, R., Faissler, D., Ruthazer, R., Sato, A., 2011. Magnetic resonance imaging apparent diffusion coefficients for histologically confirmed intracranial lesions in dogs. Veterinary Radiology and Ultrasound 52, 142–148.
884 885 886 887
Sykes, J.E., Sturges, B.K., Cannon, M.S., Gericota, B., Higgins, R.J., Trivedi, S.R., Dickinson, P.J., Vernau, K.M., Meyer, W., Wisner, E.R., 2010. Clinical signs, imaging features, neuropathology, and outcome in cats and dogs with central nervous system cryptococcosis from California. Journal of Veterinary Internal Medicine 24, 1427–1438.
Page 32 of 42
888 889 890
Tamura, S., Tamura, Y., Nakamoto, Y., Ozawa, T., Uchida, K., 2009. MR imaging of histiocytic sarcoma of the canine brain. Veterinary Radiology and Ultrasound 50, 178– 181.
891 892 893
Tamura, S., Tamura, Y., Suzuoka, N., Ohoka, A., Hasegawa, T., Uchida, K., 2007. Multiple metastases of thyroid cancer in the cranium and pituitary gland in two dogs. Journal of Small Animal Practice 48, 237–239.
894 895
Thio, T., Hilbe, M., Grest, P., Pospischil, A., 2006. Malignant histiocytosis of the brain in three dogs. Journal of Comparative Pathology 134, 241–244.
896 897 898
Thomovsky, S.A., Packer, R.A., Burcham, G.N., Heng, H.G., 2011. Imaging diagnosismagnetic resonance imaging features of metastatic cerebral lymphoma in a dog. Veterinary Radiology and Ultrasound 52, 192–195.
899 900
Tidwell, A.S., Robertson, I.D., 2011. Magnetic resonance imaging of normal and abnormal brain perfusion. Veterinary Radiology and Ultrasound 52, S62–S71.
901 902 903
Traslavina, R.P., Kent, M.S., Mohr, F.C., Dickinson, P.J., Vernau, K.M., Bollen, A.W., Higgins, R.J., 2013. Clear cell ependymoma in a dog. Journal of Comparative Pathology 149, 53–56.
904 905 906
Valentine, B., Summers, B., de Lahunta, A., White, C., Kuhajda, F., 1988. Suprasellar germ cell tumors in the dog: a report of five cases and review of the literature. Acta Neuropathologica 76, 94–100.
907 908 909
Vernau, K.M., Terio, K., LeCouteur, R.A., Berry, W., Vernau, W., Moore, P.F., Samii, V.F., 2000. Acute B-cell lymphoblastic leukemia with meningeal metastasis causing primary neurologic dysfunction in a dog. Journal of Veterinary Internal Medicine 14, 110–115.
910 911
Vural, S.A., Besalti, O., Ilhan, F., Ozak, A., Haligur, M., 2006. Ventricular ependymoma in a German Shepherd dog. The Veterinary Journal 172, 185–187.
912 913 914
Wessmann, A., Hennessey, A., Goncalves, R., Benigni, L., Hammond, G., Volk, H.A., 2013. The association of middle ear effusion with trigeminal nerve mass lesions in dogs. Veterinary Record 173, 449
915 916 917
Westworth, D., Dickinson, P., Vernau, W., Johnson, E., Bollen, A., Kass, P., Sturges, B., Vernau, K., Lecouteur, R., Higgins, R., 2008. Choroid Plexus Tumors in 56 Dogs (1985 –2007). Journal of Veterinary Internal Medicine 22, 1157–1165.
918 919
Williams, J.M., Michal, U., Botteron, C., Skerritt, G., Hetzel, U., 2009. Papillary tumor of the pineal region of a dog. Journal of Veterinary Diagnostic Investigation 21, 910–914.
920 921
Wisner, E.R., Dickinson, P.J., Higgins, R.J., 2011. Magnetic resonance imaging features of canine intracranial neoplasia. Veterinary Radiology and Ultrasound 52, S52–S61.
922 923
Wolff, C.A., Holmes, S.P., Young, B.D., Chen, A. V, Kent, M., Platt, S.R., Savage, M.Y., Schatzberg, S.J., Fosgate, G.T., Levine, J.M., 2012. Magnetic resonance imaging for the
Page 33 of 42
924 925
differentiation of neoplastic, inflammatory, and cerebrovascular brain disease in dogs. Journal of Veterinary Internal Medicine 26, 589–597.
926 927
Wyss-Fluehmann, G., Konar, M., Jaggy, A., Vandevelde, M., Oevermann, A., 2008. Cerebellar ependymal cyst in a dog. Veterinary Pathology 45, 910–913.
928 929 930 931
Young, B.D., Fosgate, G.T., Holmes, S.P., Wolff, C.A., Chen-Allen, A. V, Kent, M., Platt, S.R., Savage, M.Y., Schatzberg, S.J., Levine, J.M., 2014. Evaluation of standard magnetic resonance characteristics used to differentiate neoplastic, inflammatory, and vascular brain lesions in dogs. Veterinary Radiology and Ultrasound 55, 399–406.
932 933 934 935
Young, B.D., Levine, J.M., Porter, B.F., Chen-Allen, A. V, Rossmeisl, J.H., Platt, S.R., Kent, M., Fosgate, G.T., Schatzberg, S.J., 2011. Magnetic resonance imaging features of intracranial astrocytomas and oligodendrogliomas in dogs. Veterinary Radiology and Ultrasound 52, 132–141.
936 937
Page 34 of 42
938 939 940 941 942 943 944 945 946 947 948 949 950 951 952 953 954 955 956 957 958 959 960 961 962 963 964 965 966 967 968 969 970 971 972 973 974 975 976 977 978 979 980 981 982 983 984 985 986 987
Figure legends Fig. 1. Extra-axial fronto-olfactory meningioma (upper) and histiocytic sarcoma (lower): sagittal T2W (A), T1W (B) and post-contrast T1W (C) images. With extra-axial mass lesions, it may be possible to observe faint T2-hyperintense lines continuous with the subarachnoid space (arrows), helping to support an extra-axial location. These lines, at the margin of the brain and the tumor, represent CSF or edematous brain. Both masses are mainly T2-isointense and T1-isointense, and strongly contrast-enhancing, either homogenously (upper) or heterogeneously (lower). Both masses have a broad based origin from the dura mater-skull periosteum. It is impossible to definitively differentiate meningioma and histiocytic sarcoma on MRI alone. The upper case was a 9.5 year-old dog and a provisional diagnosis of meningioma was given after MRI. Note the sharply defined border with the brain on the postcontrast image. The lower case was a 5 year-old dog, and round cell tumors including histiocytic sarcoma were given as a possible differential diagnosis, along with meningioma, other neoplasms, and granuloma. Fig. 2. Hemangioblastoma. A, T1W; B, T2W; C, post-contrast T1W transverse images; D, coronal post-contrast fat saturation T1W image. Hemangioblastomas are a sporadic differential diagnosis for a fronto-olfactory, extra-axial, T2-hyperintense, markedly enhancing mass lesion in an older dog, and can be impossible to differentiate from meningioma based on MRI alone. Note the distinct borders with the brain. Fig. 3. Meningeal-based neoplasms displaying shared MRI features with meningioma: olfactory neuroblastoma (esthesioneuroblastoma) (upper) and granular cell tumor (lower). A, T1W post-contrast; B, T2W dorsal images of olfactory neuroblastoma. This markedly contrast-enhancing mass is meningeal-based, attached to the falx cerebri of the frontal lobe and olfactory bulb. Note the absence of any detectable changes in the nasal passages, a rare finding for this tumor. This lesion is similar to a small meningioma. C, T1W transverse; D, T1W post-contrast dorsal images of granular cell tumor. There is a broad-based origin from the falx cerebri. Note the mild pre-contrast T1-hyperintensity in A, a feature much more typical of granular cell tumor than meningioma. Note the plaque-like growth along the falx cerebri (D). Plaque-like meningiomas are usually in a skull-base location. Fig. 4. T1W post-contrast images of a skull-base meningioma exhibiting plaque-like growth. A, transverse image at the level of the diencephalon; B, transverse image at the level of the rostral medulla; C, parasagittal image. This is a classic location for a plaque-like meningioma. Note the sharply defined borders of the mass. The basilar artery is present as a midline hypointense circle within the dorsal aspect of the mass in B, confirming the arachnoid-dural origin of the mass. A small dural tail is present caudal to the mass (arrow, C). Fig. 5. High grade oligodendroglioma (upper) and hemorrhagic cerebrovascular accident (lower). A, T1W transverse; B, T2W transverse; C, T2*-weighted gradient echo transverse; D, T1W post-contrast dorsal images. Both lesions have T1-hyperintense regions pre-contrast and a heterogeneously T2-hyperintense signal. Signal voids are present on gradient echo; note the rim on the lower image. Both lesions show peripheral contrast-enhancement. It can be impossible to definitively differentiate a chronic hematoma from neoplasia using MRI alone. Note the ventricular distortion and lack of peri-tumoral edema in the upper images, which can be used to support oligodendroglioma over astrocytoma, but does not aid in differentiating neoplasia from benign lesions.
Page 35 of 42
988 989 990 991 992 993 994 995 996 997 998 999 1000 1001 1002 1003 1004 1005 1006 1007 1008 1009 1010 1011 1012 1013 1014 1015
Fig. 6. Intravascular lymphoma. Transverse images at the level of the caudal medulla (upper) and rostral midbrain (lower). T2W (A), gradient echo (B and D) and post-contrast T1W (C). A caudal medulla unilateral T2-hyperintense lesion (A) with no mass effect had no GRE signal void (B); this lesion displayed no contrast enhancement. Multifocal areas of contrastenhancement were noted elsewhere (arrows, C). The most medial of these is dorsal to a small T1-hypointense area which displayed a gradient echo signal void (arrow, D). The MRI lesions display confusing combinations of infarctive, hemorrhagic and neoplastic criteria. At necropsy, variable lesions associated with intravascular lymphoma were detected, including ischemic regions, thrombosed vasculature, invasion of neoplastic lymphocytes from blood vessels into the brain parenchyma, and pathological hemorrhages. Fig. 7. Solitary metastasis, caudal parietal lobe (A, T2W; B, T1W; C, T1W post-contrast). The MRI features are indistinguishable from a glioma, although the location is unusual. Note T2-hyperintensity, mild T1-hypointensity, mass effect (distortion of lateral ventricle) and marked contrast-enhancement. Surface contact is noted, but the subarachnoid space dorsal and medial to the mass is narrowed, supporting intra-axial location. Metastasis of systemic lymphoma. Fig. 8. Solitary intra-axial oral melanoma metastatic lesion. A, T2W; B, T2*W GRE; C, T1W and D, T1W post-contrast transverse images. Compared to normal grey matter, the lesion is T2-hyperintense and faintly T1-hyperintense. On T2* gradient echo, a signal void is present ventro-medially. The lesion is homogenously contrast-enhancing and well demarcated. The caudal lesion location, the occipital lobe, is unusual for glioma. While astrocytomas in particular can be T1-hyperintense, and high grade gliomas in particular can be hemorrhagic, the imaging characteristics combined with the history of oral melanoma are highly suggestive of a melanotic metastasis. At necropsy, histology confirmed melanoma metastasis with varying levels of melanin production; concurrent bilateral otitis media was also noted.
1016 1017
Table 1
1018
Reported solitary meningeal-based (non-pituitary) masses Major neoplastic differential diagnosis
Meningioma
Significant neoplastic differential diagnoses
Histiocytic sarcoma Choroid plexus tumor (cerebellopontomedullary angle)
Sporadic neoplasms
Lymphoma – solitary variant Granular cell tumor Metastasis e.g. carcinoma – solitary variant Hemangioblastoma Meningeal sarcoma Gliomatosis cerebri – extra-axial variant Olfactory neuroblastoma (rare variant with no tumor evident in nasal passages)
Significant non-
Granuloma, especially fungal
Page 36 of 42
neoplastic differential diagnoses
Various anomalous and acquired benign cystic lesions Hematoma
Cystic extra-axial neoplasms
Meningioma – common Nasal carcinoma (extending through cribriform plate) Olfactory neuroblastoma (typically extending through cribriform plate) Meningeal carcinomatosis (diffuse meningeal lesions)
1019 1020
Page 37 of 42
1021
Table 2
1022
Reported solitary ventricular masses
1023
Major neoplastic differential diagnoses
Choroid plexus papilloma Choroid plexus carcinoma
Significant neoplastic differential diagnoses
Ependymoma Meningioma (cerebellopontomedullary angle)
Sporadic neoplasms
Central neurocytoma Glioma, especially oligodendroglioma, can appear ventricular or spread down CSF Papillary tumor of the pineal region (within quadrigeminal cistern) Meningioma (within choroid plexus) Lymphoma (to date, not reported as a solitary lesion)
Sporadic nonneoplastic differential diagnoses
Choroid plexus cyst Cholesterol granuloma Epidermoid cyst
Non-enhancing Ependymoma (variable enhancement) neoplasms CSF, cerebrospinal fluid
1024
Page 38 of 42
1025 1026
Table 3 Reported solitary enhancing intra-axial lesions Major neoplastic differential diagnoses
Glioma, especially HGG (high grade oligodendroglioma, high grade astrocytoma including glioblastoma)
Significant neoplastic differential diagnoses
Metastasis (hemangiosarcoma, round cell tumor, carcinoma, melanoma) – solitary variant Primary CNS lymphoma – solitary variant
Sporadic neoplasms
PNET (non-cerebellar) Cerebellar medulloblastoma – strongly enhancing variant Histiocytic sarcoma – intra-axial variant Hemangioma Neuroblastoma* Ependymoma (can appear intra-axial, adjacent to ventricle)
Significant nonneoplastic differential diagnoses
Primary inflammatory syndromes including granulomatous meningoencephalomyelitis Infection especially fungal granuloma Ischemic cerebrovascular accident (enhancement after first few days) Hemorrhagic cerebrovascular accident (enhancement after first few days) Hamartoma
Glioma – all grades, especially HGG Hemangiosarcoma Hemorrhagic cerebrovascular accident Hamartoma Cerebellar medulloblastoma Melanoma (melanin causes a GRE signal void) Hemangioma * MRI of neuroblastoma was not fully described. Note that this tumor is a separate entity to olfactory neuroblastoma. Hemorrhagic lesions/T2* GRE signal voids
1027 1028 1029 1030 1031
CNS, central nervous system; GRE, gradient echo; HGG, high grade glioma; PNET, primitive neuroectodermal tumor
Page 39 of 42
1032 1033
Table 4 Reported solitary mildly or non-enhancing intra-axial lesions Major neoplastic differential diagnoses
Low grade glioma (low grade astrocytoma, low grade oligodendroglioma)
Significant neoplastic differential diagnosis
Cerebellar medulloblastoma Gliomatosis cerebri
Sporadic neoplasms
High grade glioma – poorly enhancing variant Metastasis (e.g. carcinoma) – rare poorly enhancing variant Lymphoma – rare poorly enhancing variant Ependymoma (may appear intra-axial)
Significant nonneoplastic differential diagnoses
Ischemic cerebrovascular accident Hemorrhagic cerebrovascular accident Inflammatory syndromes including granulomatous meningoencephalomyelitis and distemper
1034 1035
Page 40 of 42
1036 1037
Table 5 Reported multifocal lesions Major neoplastic differential diagnoses
Lymphoma – primary and secondary including intravascular (usually enhancing) Metastasis, especially hemangiosarcoma, carcinoma and melanoma (usually enhancing) Gliomatosis cerebri (usually non-enhancing)
Significant neoplastic differential diagnosis
Choroid plexus carcinoma with drop metastasis
Sporadic neoplasms
Meningioma or glioma combined with an unrelated neoplasm Oligodendroglioma – multifocal variant Diffuse low grade astrocytoma – variant (non-enhancing) Malignant histiocytosis (disseminated histiocytic sarcoma)*
Significant nonneoplastic differential diagnoses
Primary inflammatory syndromes including granulomatous meningoencephalomyelitis and necrotizing encephalitis Infectious including fungal, neosporosis, viral, tick-borne Reversible post-ictal changes Thiamine deficiency
Diffuse/multifocal meningeal tumors
1038
Lymphoma Histiocytic sarcoma – variant Granular cell tumor – variant Gliomatosis cerebri – variant Meningeal carcinomatosis Leukemia metastasis Meningioma – multiple meningioma variant * Primary or secondary; no MRI reports available to date
1039
Page 41 of 42
1040 1041 1042
Supplementary material
1043
Appendix. Metastatic MRI lesions.
1044
Page 42 of 42