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Spindle cell oncocytoma of the adenohypophysis: Report of a rare case and review of literature
Clinical Neurology and Neurosurgery 114 (2012) 267–271
Contents lists available at SciVerse ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Case report
Spindle cell oncocytoma of the adenohypophysis: Report of a rare case and review of literature Geetika Singh a , Shipra Agarwal a , Mehar Chand Sharma a,∗ , Vaishali Suri a , Chitra Sarkar a , Ajay Garg b , Shashank Sharad Kale c a
Department of Pathology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India Department of Neuroradiology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India c Department of Neurosurgery, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India b
a r t i c l e
i n f o
Article history: Received 14 July 2010 Received in revised form 12 August 2011 Accepted 11 October 2011 Available online 8 November 2011 Keywords: Sellar–suprasellar tumors Pituitary gland Spindle cell oncocytoma
1. Introduction Spindle cell oncocytoma of the adenohypophysis was first described by Roncaroli et al. in 2002, in their multi-institutional series of 5 cases [1]. Since then ten reports of thirteen cases of this tumor have been published in literature bringing the total number of reported cases to eighteen [2–11]. This new entity was included in the WHO classification of tumors of the Central Nervous System in 2007 [12]. In nearly all the cases presentation was akin to a non functioning pituitary adenoma in an elderly patient, however the behaviour of these tumors varied as seven of the eighteen published cases showed recurrence with or without morphological features of anaplasia in the form of nuclear pleomorphism, frequent mitoses, high Ki-67 index and/or foci of necrosis [2–8]. We report the nineteenth case of spindle cell oncocytoma (SCO) in a 68-year-old male patient and review the available English literature till date on this tumor. 2. Case report This 68-year old male presented to the Neurosurgery Outpatient Department in July 2009 with complaints of visual diminution in the left eye of one year duration and headache for
∗ Corresponding author. Tel.: +91 11 26593371; fax: +91 11 26588663. E-mail address: [email protected] (M.C. Sharma). 0303-8467/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.clineuro.2011.10.014
6 months. Computerised tomography (CT) of head showed a large sellar–suprasellar mass measuring 31 mm × 29 mm × 30 mm which was isodense to brain parenchyma (Fig. 1a and b). The sella was not enlarged (Fig. 1c). No areas of calcification or hemorrhage were seen within the mass. A partial decompression of the tumor was done through sublabial transsphenoidal approach with a clinical diagnosis of non functional pituitary adenoma. Per operatively the tumor was firm, vascular and located in the sellar and suprasellar region. There was no evidence of invasion into adjacent structures. 2.1. Pathological examination Haematoxylin and eosin stained sections showed a tumor composed of spindle cells arranged in short intersecting fascicles. The individual cells had plump oval to spindle shaped nuclei, vesicular chromatin, inconspicuous nucleoli and abundant eosinophilic cytoplasm with indistinct cytoplasmic borders giving the cells an ‘oncocytic’ appearance (Fig. 2a). Mild nuclear pleomorphism was noted but mitosis or necrosis was not seen. A part of the normal pituitary gland identified at the periphery of the tumor was not infiltrated by the tumor. A panel of immunohistochemical stains was applied (Fig. 2b–d). The tumor cells were strongly and diffusely immunopositive for vimentin (Novocastra, dil 1:100), S-100 (Dako Denmark, dil 1:1000) and showed granular cytoplasmic reactivity for epithelial membrane antigen (EMA) (Dako Denmark, dil 1:100), but were immunonegative for cytokeratin (Dako Denmark, dil 1:100), chromogranin (NeoMarker, dil 1:100), synaptophysin
268
G. Singh et al. / Clinical Neurology and Neurosurgery 114 (2012) 267–271
Fig. 1. (a and b) Non-contrast enhanced CT scan showed a large sellar–suprasellar mass, isodense to brain parenchyma; (c) the sella is not enlarged.
(NeoMarker, dil 1:100), smooth muscle actin (Dako Denmark, dil 1:100), growth hormone (NeoMarker, dil 1:500), prolactin (NeoMarker, 1:100), adrenocorticotropic hormone (NeoMarker, 1:100), leutinizing hormone (NeoMarker, dil 1:500), follicular stimulating hormone (NeoMarker, dil 1:500), thyroid stimulating hormone (NeoMarker, dil 1:100), glial fibrillary acidic protein (GFAP) (Dako, Denmark, 1:1000), bcl-2 (NeoMarker, dil 1:50) and p53 (SantaCruz, USA dil 1:50). The MIB-1 labeling index was less than 1% (Fig. 3). Based on the morphology and immunohistochemical panel the differential diagnoses considered were fibroblastic meningioma and spindle cell oncocytoma. For confirmation, ultrastructural examination was planned and the tumor tissue was retrieved from the paraffin block and processed. Ultra-thin sections were double stained with uranyl acetate and lead citrate and examined under a transmission electron microscope (TEM, Morgagni 268, Holland). The tissue was sub-optimally preserved however revealed numerous mitochondria in the
cytoplasm along with few electron dense neurosecretory granules varying from 120 to 200 nm in diameter. Due to lack of proper fixation the internal structure of the mitochondria was not discernable. In addition smooth endoplasmic reticulum and intermediate filaments were seen (Fig. 3). No basal lamina, desmosomes or interdigitating cell processes were identified. This confirmed the diagnosis of spindle cell oncocytoma. The postoperative period was uneventful and the patient was discharged on the seventh postoperative day. Unfortunately, he expired untimely due to unrelated cause after a month at home and autopsy could not be performed. 3. Discussion Spindle cell oncocytoma is a recently described entity in the WHO Classification of tumors of the Central Nervous System 2007 [12] and is now an important differential diagnosis to consider in
Fig. 2. Photomicrographs show a spindle cell tumor arranged in short intersecting fascicles. The tumor cells have abundant eosinophilic cytoplasm and indistinct borders (a, H&E ×200). The immunohistochemical panel characteristic for SCO is seen in the form of moderate granular cytoplasmic reactivity to epithelial membrane antigen (b, ×200), moderate and diffuse nuclear reactivity to S 100 (c, ×200) and strong and diffuse cytoplasmic immunopositivity to vimentin and (d, ×200).
G. Singh et al. / Clinical Neurology and Neurosurgery 114 (2012) 267–271
269
Fig. 3. Electron photomicrographs showing a tumor cell with abundant swollen mitochondria in the cytoplasm (a, ×1800, b, ×8000); along with occasional electron dense secretory granules {diameter 123 nm} (c, ×8000); numerous intermediate filaments were also identified (d, ×6300).
cases of spindle cell lesions of the sellar–suprasellar region. Based on current literature its presentation is usually in the 6th–8th decades of life without any sex predilection [2–11]. Dahiya et al. reported the youngest case of a 26 year old male [3]. Most common presenting symptoms are of visual defects and headache similar to large non-functioning pituitary adenomas. On radiology, it appears as a sellar mass with suprasellar extension and cannot be distinguished from a pituitary adenoma. Rarely these tumors have been reported to involve the cavernous sinus [4], destroy the sellar floor or clivus and extend into the sphenoid sinus [2,5]. The differential diagnoses on morphology include (I) oncocytic tumors of the sellar suprasellar region, pituitary adenomas with oncocytic change (null cell adenoma), meningioma with oncocytic change; and (II) spindle cell tumors of the sellar suprasellar region: fibroblastic meningioma, pituicytoma, schwannoma, solitary fibrous tumor (SFT) and, (III) others, including granular cell tumor and paraganglioma. An exhaustive immunohistochemical panel comprising of chromogranin, synaptophysin, pituitary hormones, EMA, vimentin, S-100, GFAP, cytokeratin, CD 34, bcl 2 and
galectin 3 is advised to arrive at a definitive diagnosis (Table 1). The co-expression of EMA, vimentin and S-100 along with galectin 3 is classical for a spindle cell oncocytoma [1]. Rodriguez et al. [13] have shown that although galectin-3 positivity is a key feature of the immunophenotype of spindle cell oncocytoma, its consistent expression in other morphologically similar tumors (meningioma, pituicytoma, nerve sheath tumors, granular cell tumor, metastases) makes it of little use in the differential diagnoses of sellar region tumors, a setting in which it should be discouraged. Overlapping immunoreactivities have been reported by Vajtai et al. in the form of diffuse staining for ␣-crystallin and focally for GFAP [4]; and Kloub et al. who reported weak or equivocal GFAP reactivity in the initial tumor (which was later absent in the recurrent tumor) [2]. This can lead to diagnostic confusion with pituicytoma, an important differential diagnosis [14]. Milka et al. have recently reported nuclear reactivity for thyroid transcription factor-1 (TTF-1) in their case which is a specific marker for pituicytes [10]. Therefore for a definite diagnosis electron microscopy is required and SCOs show presence of numerous swollen
Table 1 The immunohistochemical profile of sellar–suprasellar tumors.
SCO Oncocytic pituitary adenoma Oncocytic meningioma Pituicytoma Schwannoma Solitary fibrous tumor Granular cell tumor Paraganglioma
GFAP
Vim
EMA
S-100
CK
CG
Syn
CD 34
Bcl 2
TTF-1
− − − + − − − −
+ − + + + + + +
+ − + − − − − −
+ − −a + + − + +b
− +/− − − − − − −
− + − − − − − +
− + − − − − − +
− − − − − + − −
+/− − − − − + − −
+/− − − + − − − −
Abbreviations: CG, chromogranin; CK, cytokeratin; EMA, epithelial membrane antigen; GFAP, glial fibrillary acidic protein; Syn, synaptophysin; TTF-1, thyroid transcription factor-1; Vim, vimentin. a Positive in fibroblastic variant of meningioma. b Positive in sustentacular cells.
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G. Singh et al. / Clinical Neurology and Neurosurgery 114 (2012) 267–271
Table 2 Summary of the published cases of spindle cell oncocytoma. Case no.
Ref no.
Age (yrs)
Sex
Nu pleo
Mitosis
Necrosis
MIB-1 LI
Treatment
Follow up
Recurrences at
1–5
1
61.6 (mean)
M:F = 3:2
–
<1/10 hpf
3% (1–5%)
TS-GTR
2 2
71 76
F M
– Mild
– Increased
18%a 20%a
8 9 10 11
3 3 4 5
26 55 48 55
M F F F
– – – <1/10 hpf
– – – –
1% 8% <1% 2%
12
6
63
F
Mild Mild Mild Marked at places –
Subtotal debulking TS surgery, RT after first recurrence STR followed by RT TS-GTR TS-GTR TS-PR followed by RT
35 mo (2–68 mo) 11 yrs 10 yrs
–
6 7
Present in 1 case – Focal
–
–
9%, 13–15%a
13 14 15 16 17 18 19
7 8 9 9 10 11 Present
59 70 63 65 45 55 68
M F F F F F M
– – Focal mild – – – Mild
– – Rare Rare 1/10 hpf – –
– – – – – – –
2–3% 3.2%, 3.5%a 5% 1%, 1%a NA 1.5–2% <1%
Selective TS surgery, RT following recurrence TS-GTR TS-GTR TS surgery Frontal craniotomy TS-GTR TS surgery TS-PR
7 yrs 6 mo 16 yrs 30 mo
3 yrs 3 yrs and 10 yrs
5 mo
– – – Slow regrowth over 30 mo 5 mo
9 mo 13 yrs 28 mo 5 yrs 3 mo NA Died
9 mo 13 yrs – 3 yrs – NA –
Abbreviations: –, absent; F, female; GTR, gross total resection; M, male; MIB-1 LI, MIB-1 labeling index; mo, months; NA, not available; Nu pleo, nuclear pleomorphism; PR, partial resection; RT, radiotherapy; STR, subtotal resection; yrs, years, TS, transsphenoidal. a MIB-1 LI in the recurrent tumor.
mitochondria in the cytoplasm of the tumor cells along with bundles of intermediate filaments entrapping lysosomes and rough endoplasmic reticulum [1]. Roncaroli et al. [1] and Borges et al. [8] also reported well formed desmosomes and intermediate junctions and absence of secretory granules. In contrast, Dahiya et al. [3] and Kloub et al. [2] reported an occasional dense core secretory granule in their cases without any desmosomes/intercellular junctions, similar to the present case. In addition, Coiré et al. [6] recently reported the formation of pituitary follicle-like structures in the cytoplasm of the tumor. There has been a shift in the understanding of the biologic behaviour of SCO, with the initial impression of a WHO grade I tumor being challenged in subsequent reports. Of the thirteen cases reported after Roncaroli’s initial series there were recurrences in seven tumors and the time to recurrence ranged from 5 months to 13 years after the initial surgery (Table 2). No definite predictors of aggressive behaviour have been found. Most cases have shown minimal to moderate degree of nuclear pleomorphism as seen in the present case also. Mitotic activity has ranged from none to less than 1 per 10 hpf [1–8] except for the report by Kloub et al. [2] in which one of their cases of SCO harbored an increased mitotic activity, however this was at recurrence. The prognostic value of MIB-1 LI is also still debatable with tumors recurring despite having low MIB-1 indices of 2–3% [5,7]. Necrosis, another morphological marker of aggressiveness, is reported only in two cases of SCO, on of which showed repeated recurrences [1,2]. The mainstay of treatment of SCO remains transsphenoidal resection along with radiotherapy in the recurrent cases. In the case reported by Dahiya et al. [3], radiotherapy was given soon after a subtotal resection and the patient did not report any recurrence after a 7 year follow up period. Contrasting this, a second recurrence was seen in one of the cases reported by Kloub et al. [2] even after receiving radiotherapy. Therefore it still remains to be determined whether these tumors are radiosensitive or not. The cell of origin of this tumor is also debatable. Ulm et al. hypothesized that the similarities seen in several pituitary tumors including adenomas, pituicytomas and spindle cell oncocytomas may be due to divergent neoplastic transformation of a single progenitor cell [15]. The presence of neurosecretory granules along with the focal GFAP reactivity noted in the tumor cells adds credence to this hypothesis [4]. Roncaroli et al. proposed that SCO originate from folliculostellate cell (FSC) based on the common
immunoreactivity for S-100, EMA, vimentin and galectin 3 as well as similar ultrastructural findings including cell–cell junctional complexes [1]. The recent report by Vajtai et al. [11] also supports this hypothesis. 4. Conclusion The present case highlights the difficulty in diagnosing SCO as it has a variety of histological mimics in the sellar–suprasellar region. A combination of histopathological, immunohistochemical and ultrastructural examination is required to reach a definite diagnosis. In the absence of any known definitive morphological or other predictive prognostic factors, a long and regular follow-up along with an aggressive treatment protocol is required in these patients. References [1] Roncaroli F, Scheithauer BW, Cenacchi G, Horvath E, Kovacs K, Lloyd RV, et al. ‘Spindle cell oncocytoma’ of the adenohypophysis: a tumor of folliculostellate cells? Am J Surg Pathol 2002;26:1048–55. [2] Kloub O, Perry A, Tu PH, Lipper M, Lopes MB. Spindle cell oncocytoma of the adenohypophysis: report of two recurrent cases. Am J Surg Pathol 2005;29:247–53. [3] Dahiya S, Sarkar C, Hedley-Whyte ET, Sharma MC, Zervas NT, Sridhar E, et al. Spindle cell oncocytoma of the adenohypophysis: report of two cases. Acta Neuropathol 2005;110:97–9. [4] Vajtai I, Sahli R, Kappeler A. Spindle cell oncocytoma of the adenohypophysis: report of a case with a 16-year follow-up. Pathol Res Pract 2006;202:745–50. [5] Borota OC, Scheithauer BW, Fougner SL, Hald JK, Ramm-Pettersen J, Bollerslev J. Spindle cell oncocytoma of the adenohypophysis: report of a case with marked cellular atypia and recurrence despite adjuvant treatment. Clin Neuropathol 2009;28:91–5. [6] Coiré CI, Horvath E, Smyth HS, Kovacs K. Rapidly recurring folliculostellate cell tumor of the adenohypophysis with the morphology of a spindle cell oncocytoma: case report with electron microscopic studies. Clin Neuropathol 2009;28:303–8. [7] Demssie YN, Joseph J, Dawson T, Roberts G, de Carpentier J, Howell S. Recurrent spindle cell oncocytoma of the pituitary, a case report and review of literature. Pituitary 2009 [Epub ahead of print]. [8] Borges MT, Lillehei KO, Kleinschmidt-Demasters BK. Spindle cell oncocytoma with late recurrence and unique neuroimaging characteristics due to recurrent subclinical intratumoral bleeding. J Neurooncol 2011;101((January) 1):145–54. ´ [9] Matyja E, Maksymowicz M, Grajkowska W, Olszewski W, Zielinski G, Bonicki W. Spindle cell oncocytoma of the adenohypophysis – a clinicopathological and ultrastructural study of two cases. Folia Neuropathol 2010;48:175–84. [10] Mlika M, Azouz H, Chelly I, Saïd IB, Jemel H, Haouet S, et al. Spindle cell oncocytoma of the adenohypophysis in a woman: a case report and review of the literature. J Med Case Rep 2011;5:64. [11] Vajtai I, Beck J, Kappeler A, Hewer E. Spindle cell oncocytoma of the pituitary gland with follicle-like component: organotypic differentiation to
G. Singh et al. / Clinical Neurology and Neurosurgery 114 (2012) 267–271 support its origin from folliculo-stellate cells. Acta Neuropathol 2011;122: 253–8. [12] Fuller G, Scheithauer BW, Roncaroli F, Wesseling P. Spindle cell oncocytoma of the adenohypophysis. In: Louis DN, Ohgaki H, Wiestler OD, Cavanee WK, editors. WHO classification of tumours of the central nervous system. 4th ed. Lyon: IARC; 2007. p. 245–6. [13] Rodriguez FJ, Scheithauer BW, Roncaroli F, Silva AI, Kovacs K, Brat DJ, et al. Galectin-3 expression is ubiquitous in tumors of the sellar region, nervous
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system, and mimics: an immunohistochemical and RT-PCR study. Am J Surg Pathol 2008;32:1344–52. [14] Wesseling P, Brat DJ, Fuller GN. Pituicytoma. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, editors. WHO classification of tumours of the central nervous system. 4th ed. Lyon: IARC; 2007. p. 243–4. [15] Ulm AJ, Yachnis AT, Brat DJ, Rhoton AL. Pituicytoma: report of two cases and clues regarding pathogenesis. Neurosurgery 2004;54:753–8.
Contents lists available at SciVerse ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Case report
Spindle cell oncocytoma of the adenohypophysis: Report of a rare case and review of literature Geetika Singh a , Shipra Agarwal a , Mehar Chand Sharma a,∗ , Vaishali Suri a , Chitra Sarkar a , Ajay Garg b , Shashank Sharad Kale c a
Department of Pathology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India Department of Neuroradiology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India c Department of Neurosurgery, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India b
a r t i c l e
i n f o
Article history: Received 14 July 2010 Received in revised form 12 August 2011 Accepted 11 October 2011 Available online 8 November 2011 Keywords: Sellar–suprasellar tumors Pituitary gland Spindle cell oncocytoma
1. Introduction Spindle cell oncocytoma of the adenohypophysis was first described by Roncaroli et al. in 2002, in their multi-institutional series of 5 cases [1]. Since then ten reports of thirteen cases of this tumor have been published in literature bringing the total number of reported cases to eighteen [2–11]. This new entity was included in the WHO classification of tumors of the Central Nervous System in 2007 [12]. In nearly all the cases presentation was akin to a non functioning pituitary adenoma in an elderly patient, however the behaviour of these tumors varied as seven of the eighteen published cases showed recurrence with or without morphological features of anaplasia in the form of nuclear pleomorphism, frequent mitoses, high Ki-67 index and/or foci of necrosis [2–8]. We report the nineteenth case of spindle cell oncocytoma (SCO) in a 68-year-old male patient and review the available English literature till date on this tumor. 2. Case report This 68-year old male presented to the Neurosurgery Outpatient Department in July 2009 with complaints of visual diminution in the left eye of one year duration and headache for
∗ Corresponding author. Tel.: +91 11 26593371; fax: +91 11 26588663. E-mail address: [email protected] (M.C. Sharma). 0303-8467/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.clineuro.2011.10.014
6 months. Computerised tomography (CT) of head showed a large sellar–suprasellar mass measuring 31 mm × 29 mm × 30 mm which was isodense to brain parenchyma (Fig. 1a and b). The sella was not enlarged (Fig. 1c). No areas of calcification or hemorrhage were seen within the mass. A partial decompression of the tumor was done through sublabial transsphenoidal approach with a clinical diagnosis of non functional pituitary adenoma. Per operatively the tumor was firm, vascular and located in the sellar and suprasellar region. There was no evidence of invasion into adjacent structures. 2.1. Pathological examination Haematoxylin and eosin stained sections showed a tumor composed of spindle cells arranged in short intersecting fascicles. The individual cells had plump oval to spindle shaped nuclei, vesicular chromatin, inconspicuous nucleoli and abundant eosinophilic cytoplasm with indistinct cytoplasmic borders giving the cells an ‘oncocytic’ appearance (Fig. 2a). Mild nuclear pleomorphism was noted but mitosis or necrosis was not seen. A part of the normal pituitary gland identified at the periphery of the tumor was not infiltrated by the tumor. A panel of immunohistochemical stains was applied (Fig. 2b–d). The tumor cells were strongly and diffusely immunopositive for vimentin (Novocastra, dil 1:100), S-100 (Dako Denmark, dil 1:1000) and showed granular cytoplasmic reactivity for epithelial membrane antigen (EMA) (Dako Denmark, dil 1:100), but were immunonegative for cytokeratin (Dako Denmark, dil 1:100), chromogranin (NeoMarker, dil 1:100), synaptophysin
268
G. Singh et al. / Clinical Neurology and Neurosurgery 114 (2012) 267–271
Fig. 1. (a and b) Non-contrast enhanced CT scan showed a large sellar–suprasellar mass, isodense to brain parenchyma; (c) the sella is not enlarged.
(NeoMarker, dil 1:100), smooth muscle actin (Dako Denmark, dil 1:100), growth hormone (NeoMarker, dil 1:500), prolactin (NeoMarker, 1:100), adrenocorticotropic hormone (NeoMarker, 1:100), leutinizing hormone (NeoMarker, dil 1:500), follicular stimulating hormone (NeoMarker, dil 1:500), thyroid stimulating hormone (NeoMarker, dil 1:100), glial fibrillary acidic protein (GFAP) (Dako, Denmark, 1:1000), bcl-2 (NeoMarker, dil 1:50) and p53 (SantaCruz, USA dil 1:50). The MIB-1 labeling index was less than 1% (Fig. 3). Based on the morphology and immunohistochemical panel the differential diagnoses considered were fibroblastic meningioma and spindle cell oncocytoma. For confirmation, ultrastructural examination was planned and the tumor tissue was retrieved from the paraffin block and processed. Ultra-thin sections were double stained with uranyl acetate and lead citrate and examined under a transmission electron microscope (TEM, Morgagni 268, Holland). The tissue was sub-optimally preserved however revealed numerous mitochondria in the
cytoplasm along with few electron dense neurosecretory granules varying from 120 to 200 nm in diameter. Due to lack of proper fixation the internal structure of the mitochondria was not discernable. In addition smooth endoplasmic reticulum and intermediate filaments were seen (Fig. 3). No basal lamina, desmosomes or interdigitating cell processes were identified. This confirmed the diagnosis of spindle cell oncocytoma. The postoperative period was uneventful and the patient was discharged on the seventh postoperative day. Unfortunately, he expired untimely due to unrelated cause after a month at home and autopsy could not be performed. 3. Discussion Spindle cell oncocytoma is a recently described entity in the WHO Classification of tumors of the Central Nervous System 2007 [12] and is now an important differential diagnosis to consider in
Fig. 2. Photomicrographs show a spindle cell tumor arranged in short intersecting fascicles. The tumor cells have abundant eosinophilic cytoplasm and indistinct borders (a, H&E ×200). The immunohistochemical panel characteristic for SCO is seen in the form of moderate granular cytoplasmic reactivity to epithelial membrane antigen (b, ×200), moderate and diffuse nuclear reactivity to S 100 (c, ×200) and strong and diffuse cytoplasmic immunopositivity to vimentin and (d, ×200).
G. Singh et al. / Clinical Neurology and Neurosurgery 114 (2012) 267–271
269
Fig. 3. Electron photomicrographs showing a tumor cell with abundant swollen mitochondria in the cytoplasm (a, ×1800, b, ×8000); along with occasional electron dense secretory granules {diameter 123 nm} (c, ×8000); numerous intermediate filaments were also identified (d, ×6300).
cases of spindle cell lesions of the sellar–suprasellar region. Based on current literature its presentation is usually in the 6th–8th decades of life without any sex predilection [2–11]. Dahiya et al. reported the youngest case of a 26 year old male [3]. Most common presenting symptoms are of visual defects and headache similar to large non-functioning pituitary adenomas. On radiology, it appears as a sellar mass with suprasellar extension and cannot be distinguished from a pituitary adenoma. Rarely these tumors have been reported to involve the cavernous sinus [4], destroy the sellar floor or clivus and extend into the sphenoid sinus [2,5]. The differential diagnoses on morphology include (I) oncocytic tumors of the sellar suprasellar region, pituitary adenomas with oncocytic change (null cell adenoma), meningioma with oncocytic change; and (II) spindle cell tumors of the sellar suprasellar region: fibroblastic meningioma, pituicytoma, schwannoma, solitary fibrous tumor (SFT) and, (III) others, including granular cell tumor and paraganglioma. An exhaustive immunohistochemical panel comprising of chromogranin, synaptophysin, pituitary hormones, EMA, vimentin, S-100, GFAP, cytokeratin, CD 34, bcl 2 and
galectin 3 is advised to arrive at a definitive diagnosis (Table 1). The co-expression of EMA, vimentin and S-100 along with galectin 3 is classical for a spindle cell oncocytoma [1]. Rodriguez et al. [13] have shown that although galectin-3 positivity is a key feature of the immunophenotype of spindle cell oncocytoma, its consistent expression in other morphologically similar tumors (meningioma, pituicytoma, nerve sheath tumors, granular cell tumor, metastases) makes it of little use in the differential diagnoses of sellar region tumors, a setting in which it should be discouraged. Overlapping immunoreactivities have been reported by Vajtai et al. in the form of diffuse staining for ␣-crystallin and focally for GFAP [4]; and Kloub et al. who reported weak or equivocal GFAP reactivity in the initial tumor (which was later absent in the recurrent tumor) [2]. This can lead to diagnostic confusion with pituicytoma, an important differential diagnosis [14]. Milka et al. have recently reported nuclear reactivity for thyroid transcription factor-1 (TTF-1) in their case which is a specific marker for pituicytes [10]. Therefore for a definite diagnosis electron microscopy is required and SCOs show presence of numerous swollen
Table 1 The immunohistochemical profile of sellar–suprasellar tumors.
SCO Oncocytic pituitary adenoma Oncocytic meningioma Pituicytoma Schwannoma Solitary fibrous tumor Granular cell tumor Paraganglioma
GFAP
Vim
EMA
S-100
CK
CG
Syn
CD 34
Bcl 2
TTF-1
− − − + − − − −
+ − + + + + + +
+ − + − − − − −
+ − −a + + − + +b
− +/− − − − − − −
− + − − − − − +
− + − − − − − +
− − − − − + − −
+/− − − − − + − −
+/− − − + − − − −
Abbreviations: CG, chromogranin; CK, cytokeratin; EMA, epithelial membrane antigen; GFAP, glial fibrillary acidic protein; Syn, synaptophysin; TTF-1, thyroid transcription factor-1; Vim, vimentin. a Positive in fibroblastic variant of meningioma. b Positive in sustentacular cells.
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G. Singh et al. / Clinical Neurology and Neurosurgery 114 (2012) 267–271
Table 2 Summary of the published cases of spindle cell oncocytoma. Case no.
Ref no.
Age (yrs)
Sex
Nu pleo
Mitosis
Necrosis
MIB-1 LI
Treatment
Follow up
Recurrences at
1–5
1
61.6 (mean)
M:F = 3:2
–
<1/10 hpf
3% (1–5%)
TS-GTR
2 2
71 76
F M
– Mild
– Increased
18%a 20%a
8 9 10 11
3 3 4 5
26 55 48 55
M F F F
– – – <1/10 hpf
– – – –
1% 8% <1% 2%
12
6
63
F
Mild Mild Mild Marked at places –
Subtotal debulking TS surgery, RT after first recurrence STR followed by RT TS-GTR TS-GTR TS-PR followed by RT
35 mo (2–68 mo) 11 yrs 10 yrs
–
6 7
Present in 1 case – Focal
–
–
9%, 13–15%a
13 14 15 16 17 18 19
7 8 9 9 10 11 Present
59 70 63 65 45 55 68
M F F F F F M
– – Focal mild – – – Mild
– – Rare Rare 1/10 hpf – –
– – – – – – –
2–3% 3.2%, 3.5%a 5% 1%, 1%a NA 1.5–2% <1%
Selective TS surgery, RT following recurrence TS-GTR TS-GTR TS surgery Frontal craniotomy TS-GTR TS surgery TS-PR
7 yrs 6 mo 16 yrs 30 mo
3 yrs 3 yrs and 10 yrs
5 mo
– – – Slow regrowth over 30 mo 5 mo
9 mo 13 yrs 28 mo 5 yrs 3 mo NA Died
9 mo 13 yrs – 3 yrs – NA –
Abbreviations: –, absent; F, female; GTR, gross total resection; M, male; MIB-1 LI, MIB-1 labeling index; mo, months; NA, not available; Nu pleo, nuclear pleomorphism; PR, partial resection; RT, radiotherapy; STR, subtotal resection; yrs, years, TS, transsphenoidal. a MIB-1 LI in the recurrent tumor.
mitochondria in the cytoplasm of the tumor cells along with bundles of intermediate filaments entrapping lysosomes and rough endoplasmic reticulum [1]. Roncaroli et al. [1] and Borges et al. [8] also reported well formed desmosomes and intermediate junctions and absence of secretory granules. In contrast, Dahiya et al. [3] and Kloub et al. [2] reported an occasional dense core secretory granule in their cases without any desmosomes/intercellular junctions, similar to the present case. In addition, Coiré et al. [6] recently reported the formation of pituitary follicle-like structures in the cytoplasm of the tumor. There has been a shift in the understanding of the biologic behaviour of SCO, with the initial impression of a WHO grade I tumor being challenged in subsequent reports. Of the thirteen cases reported after Roncaroli’s initial series there were recurrences in seven tumors and the time to recurrence ranged from 5 months to 13 years after the initial surgery (Table 2). No definite predictors of aggressive behaviour have been found. Most cases have shown minimal to moderate degree of nuclear pleomorphism as seen in the present case also. Mitotic activity has ranged from none to less than 1 per 10 hpf [1–8] except for the report by Kloub et al. [2] in which one of their cases of SCO harbored an increased mitotic activity, however this was at recurrence. The prognostic value of MIB-1 LI is also still debatable with tumors recurring despite having low MIB-1 indices of 2–3% [5,7]. Necrosis, another morphological marker of aggressiveness, is reported only in two cases of SCO, on of which showed repeated recurrences [1,2]. The mainstay of treatment of SCO remains transsphenoidal resection along with radiotherapy in the recurrent cases. In the case reported by Dahiya et al. [3], radiotherapy was given soon after a subtotal resection and the patient did not report any recurrence after a 7 year follow up period. Contrasting this, a second recurrence was seen in one of the cases reported by Kloub et al. [2] even after receiving radiotherapy. Therefore it still remains to be determined whether these tumors are radiosensitive or not. The cell of origin of this tumor is also debatable. Ulm et al. hypothesized that the similarities seen in several pituitary tumors including adenomas, pituicytomas and spindle cell oncocytomas may be due to divergent neoplastic transformation of a single progenitor cell [15]. The presence of neurosecretory granules along with the focal GFAP reactivity noted in the tumor cells adds credence to this hypothesis [4]. Roncaroli et al. proposed that SCO originate from folliculostellate cell (FSC) based on the common
immunoreactivity for S-100, EMA, vimentin and galectin 3 as well as similar ultrastructural findings including cell–cell junctional complexes [1]. The recent report by Vajtai et al. [11] also supports this hypothesis. 4. Conclusion The present case highlights the difficulty in diagnosing SCO as it has a variety of histological mimics in the sellar–suprasellar region. A combination of histopathological, immunohistochemical and ultrastructural examination is required to reach a definite diagnosis. In the absence of any known definitive morphological or other predictive prognostic factors, a long and regular follow-up along with an aggressive treatment protocol is required in these patients. References [1] Roncaroli F, Scheithauer BW, Cenacchi G, Horvath E, Kovacs K, Lloyd RV, et al. ‘Spindle cell oncocytoma’ of the adenohypophysis: a tumor of folliculostellate cells? Am J Surg Pathol 2002;26:1048–55. [2] Kloub O, Perry A, Tu PH, Lipper M, Lopes MB. Spindle cell oncocytoma of the adenohypophysis: report of two recurrent cases. Am J Surg Pathol 2005;29:247–53. [3] Dahiya S, Sarkar C, Hedley-Whyte ET, Sharma MC, Zervas NT, Sridhar E, et al. Spindle cell oncocytoma of the adenohypophysis: report of two cases. Acta Neuropathol 2005;110:97–9. [4] Vajtai I, Sahli R, Kappeler A. Spindle cell oncocytoma of the adenohypophysis: report of a case with a 16-year follow-up. Pathol Res Pract 2006;202:745–50. [5] Borota OC, Scheithauer BW, Fougner SL, Hald JK, Ramm-Pettersen J, Bollerslev J. Spindle cell oncocytoma of the adenohypophysis: report of a case with marked cellular atypia and recurrence despite adjuvant treatment. Clin Neuropathol 2009;28:91–5. [6] Coiré CI, Horvath E, Smyth HS, Kovacs K. Rapidly recurring folliculostellate cell tumor of the adenohypophysis with the morphology of a spindle cell oncocytoma: case report with electron microscopic studies. Clin Neuropathol 2009;28:303–8. [7] Demssie YN, Joseph J, Dawson T, Roberts G, de Carpentier J, Howell S. Recurrent spindle cell oncocytoma of the pituitary, a case report and review of literature. Pituitary 2009 [Epub ahead of print]. [8] Borges MT, Lillehei KO, Kleinschmidt-Demasters BK. Spindle cell oncocytoma with late recurrence and unique neuroimaging characteristics due to recurrent subclinical intratumoral bleeding. J Neurooncol 2011;101((January) 1):145–54. ´ [9] Matyja E, Maksymowicz M, Grajkowska W, Olszewski W, Zielinski G, Bonicki W. Spindle cell oncocytoma of the adenohypophysis – a clinicopathological and ultrastructural study of two cases. Folia Neuropathol 2010;48:175–84. [10] Mlika M, Azouz H, Chelly I, Saïd IB, Jemel H, Haouet S, et al. Spindle cell oncocytoma of the adenohypophysis in a woman: a case report and review of the literature. J Med Case Rep 2011;5:64. [11] Vajtai I, Beck J, Kappeler A, Hewer E. Spindle cell oncocytoma of the pituitary gland with follicle-like component: organotypic differentiation to
G. Singh et al. / Clinical Neurology and Neurosurgery 114 (2012) 267–271 support its origin from folliculo-stellate cells. Acta Neuropathol 2011;122: 253–8. [12] Fuller G, Scheithauer BW, Roncaroli F, Wesseling P. Spindle cell oncocytoma of the adenohypophysis. In: Louis DN, Ohgaki H, Wiestler OD, Cavanee WK, editors. WHO classification of tumours of the central nervous system. 4th ed. Lyon: IARC; 2007. p. 245–6. [13] Rodriguez FJ, Scheithauer BW, Roncaroli F, Silva AI, Kovacs K, Brat DJ, et al. Galectin-3 expression is ubiquitous in tumors of the sellar region, nervous
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system, and mimics: an immunohistochemical and RT-PCR study. Am J Surg Pathol 2008;32:1344–52. [14] Wesseling P, Brat DJ, Fuller GN. Pituicytoma. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, editors. WHO classification of tumours of the central nervous system. 4th ed. Lyon: IARC; 2007. p. 243–4. [15] Ulm AJ, Yachnis AT, Brat DJ, Rhoton AL. Pituicytoma: report of two cases and clues regarding pathogenesis. Neurosurgery 2004;54:753–8.