- Email: [email protected]
Diffuse Large B Cell Lymphoma Presented as Trigeminal Neuralgia: 2 Cases Reported and Literature Review
Accepted Manuscript Diffuse Large B Cell Lymphoma presented as trigeminal neuralgia: two cases reported and literatures review Hua Zhao, Jin Zhu, Xin Zhang, Yin-da Tang, Shi-ting Li PII:
S1878-8750(18)32776-1
DOI:
https://doi.org/10.1016/j.wneu.2018.11.217
Reference:
WNEU 10901
To appear in:
World Neurosurgery
Received Date: 5 November 2018 Revised Date:
24 November 2018
Accepted Date: 26 November 2018
Please cite this article as: Zhao H, Zhu J, Zhang X, Tang Y-d, Li S-t, Diffuse Large B Cell Lymphoma presented as trigeminal neuralgia: two cases reported and literatures review, World Neurosurgery (2019), doi: https://doi.org/10.1016/j.wneu.2018.11.217. 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.
ACCEPTED MANUSCRIPT
Diffuse Large B Cell Lymphoma presented as trigeminal neuralgia: two cases reported and literatures review (Hua Zhao, Jin Zhu, Xin Zhang, Yin-da Tang, Shi-ting Li)
RI PT
Department of Neurosurgery, Xinhua hospital affiliated to Shanghai Jiaotong University School of Medicine
Jin Zhu: medzhujin@12：.com Xin Zhang: zhangxin：010@12：.com
M AN U
Yin-da Tang: [email protected]
SC
Hua Zhao: zhaohuaziyu@1：3.com
Hua Zhao and Jin Zhu are first co-authors.
Correspondence: [email protected]
TE D
Department of Neurosurgery, Xinhua hospital affiliated to Shanghai Jiaotong University School of Medicine, 1：：5# Kongjiang Road,
EP
Yangpu district, Shanghai, China.
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Run title: Diffuse Large B Cell Lymphoma presented as trigeminal neuralgia
1
ACCEPTED MANUSCRIPT Diffuse Large B-Cell Lymphoma Presented as Trigeminal Neuralgia: Report of Two Cases and Literature Review Abstract
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Objective: Extra-axial lymphoma involving the trigeminal nerve, an uncommon condition that presents as a trigeminal schwannoma, resulted in misdiagnosis and a flawed surgical strategy. We report two cases: a primary lymphoma of Meckel’s cave
SC
and a metastasis lymphoma in the prepontine cistern arising from the supraclavicular
M AN U
lymph node.
Cases report: The first patient presented with a 3-month history of persistent, sharp facial pain across the area innervated by the V2 nerve. She was misdiagnosed with primary trigeminal
neuralgia and
underwent
microvascular
decompression.
TE D
Intraoperatively, the trigeminal nerve was swollen to a large extent and surrounded by red granuloma-like tissue. The second case was a 75-year-old woman; she had a history of a malignant lymphoma of the of the supraclavicular lymph node and
EP
presented with right facial pain. Magnetic resonance imaging revealed that the
AC C
cisternal portion of the right trigeminal nerve was swollen. A specimen was taken from the two patients, and histopathological examinations revealed a diffuse large B-cell lymphoma.
Conclusion: The diagnosis of a malignant lymphoma should be considered for lesions in the trigeminal region. Extracting a specimen for biopsy is the most suitable surgical strategy. Our report indicates that postoperative adjuvant chemotherapy for malignant lymphomas is essential.
2
ACCEPTED MANUSCRIPT Keywords: Biopsy; Malignant lymphoma; Neuropathic pain Introduction Primary central nervous system lymphoma (CNSL) usually originates from the brain 1,2
. Although primary CNSL is an
RI PT
parenchyma, particularly the white matter
uncommon brain neoplasm, its incidence is rising in some groups due to an increase in immunocompromised patients with acquired immunodeficiency syndrome3.
4-7
. We report two cases of diffuse large B-cell lymphoma in the trigeminal
M AN U
condition
SC
However, extra-axial lymphoma arising in the trigeminal region is a less common
region: a primary lymphoma and a metastasis lymphoma arising from the supraclavicular lymph node. The clinical and radiological features conformed to those of trigeminal neurinoma. This study was approved by the Xinhua Hospital
TE D
Institutional Ethics Committee, and the protocol adhered to approved institutional guidelines and regulations.
Case 1
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Clinical Presentation
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A 55-year-old women presented with a 3-month history of persistent, sharp facial pain distributed across the area innervated by the right V2 nerve. Though the pain was initially restricted to the nostril, it progressed to include numbness across the cheek. On physical examination, she was found to exhibit right facial numbness. Further cranial nerve examinations revealed no abnormalities or other neurological deficits. Family and social history were noncontributory. Magnetic resonance imaging (MRI) revealed the right trigeminal nerve to be thicker than the contralateral trigeminal
3
ACCEPTED MANUSCRIPT nerve (Figure 1A). The patient was misdiagnosed with primary trigeminal neuralgia and underwent microvascular decompression (MVD). Intraoperatively, the trigeminal nerve was swollen and surrounded by red granuloma-like tissue (Figure1B). A
RI PT
specimen was resected from the granuloma-like tissue. The patient underwent enhanced MRI on the third postoperative day. The MRI indicated that the right trigeminal nerve was swollen at its cisternal portion and at the Meckel cave (Figure 2). specimen
was
analyzed
The
hematoxylin-eosin
(HE)
latter revealed
a
staining
and
tumor consisting of
M AN U
immunohistochemistry (IHC).
via
SC
The
medium-to-large sized lymphoid cells with multi-lobulated nuclei of a B-cell phenotype (CD 20 positive). The cells were LCA positive, CD56 negative, and featured a high Ki-67 labeling index of 78% (Figure 3), indicating a diffuse large
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B-cell lymphoma. The patient underwent R-MPV therapy (rituximab, methotrexate, prednisone, vincristine), after which the intracranial mass lesion was almost undetectable via MRI. She had not experienced recurrence by the 2-year follow-up
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Case 2
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(Figure4); however, she still exhibited facial numbness.
A 75-year-old women presented with a 2-month history of right facial pain in all three divisions of the trigeminal nerve. Her past medical history included a malignant lymphoma of the supraclavicular lymph node; the administration of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) therapy for eight cycles had completely resolved her condition. A neurological examination indicated hypoesthesia in all divisions of the trigeminal nerve as well as a diminished
4
ACCEPTED MANUSCRIPT right corneal reflex. MRI revealed that the cisternal portion of the right trigeminal nerve was swollen. The right trigeminal nerve, isointense on T1-and T2-weighted MRI, was homogeneously enhanced with gadolinium. Thin-slice temporal bone
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computed tomographic (CT) images showed no notable pathologic changes in the bone (Figure 5). We made an initial diagnosis of a malignant lymphoma of the trigeminal nerve. The patient underwent an operation via a suboccipital retrosigmoid
SC
approach for histopathological confirmation. Intraoperatively, the trigeminal nerve
M AN U
was swollen and pink (Figure 6). A biopsy was taken from the trigeminal nerve; the subsequent analysis of the frozen section indicated the presence of a diffuse large B-Cell Lymphoma. The permanent histological findings agreed with the findings from the frozen section (Figure 7). The patient was treated with R-CHOP
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chemotherapy.
Discussion
The present report describes a primary lymphoma and a metastatic lymphoma at
EP
trigeminal nerve adjacent to the skull base, a rare location of for primary CNS
AC C
lymphoma to present. To the best of our knowledge, only 11 patients with lymphoma-induced trigeminal neuralgia have been hitherto reported (Table 1)
4-14
.
Including the women presented in this report, the mean age and the male-to-female ratio of the 13 patients are 56.15 years (range, 44-70 years) and 8:5, respectively. Diagnosis of malignant lymphoma in the trigeminal region The literature lacks a unified understanding of the diagnosis of malignant lymphoma in the trigeminal region, thereby confounding correct diagnosis at the
5
ACCEPTED MANUSCRIPT initial stage of treatment. Based on our experience, we suggest that the following observations can help to inform a correct diagnosis of malignant lymphoma. 1) Clinical characteristics are atypical: ① the average duration of symptoms indicative
RI PT
of lymphoma is relatively shorter than those corresponding to other presumptive lesions, ② the absence of the trigger-point phenomenon; and ③ persistent pain. 2) Numbness in the ipsilateral face is apparent. 3) The MRI findings reveal a swollen
SC
trigeminal nerve is swollen, and T1-weighted MRI with gadolinium enhancement
M AN U
indicates that the nerve is enhanced along its long axis. 4) The medical history includes organ transplantations, acquired immunodeficiency syndrome, or lymphoma in other parts of the body.
Differential diagnosis in the trigeminal region
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Multiple types of mass lesions can occur in the cerebellopontine angle (CPA) of Meckel’s cave12. The clinical features of malignant lymphoma of the trigeminal region, including trigeminal neuralgia, facial hypesthesia, and diplopia, coincide with
EP
those caused by other trigeminal-nerve and cavernous-sinus lesions. The MRI features
AC C
of extranodal non-Hodgkin lymphoma of the skull base are similar to those associated with meningioma and other more common neoplasms of this region. Han et al15. attempted to determine radiological criteria for non-Hodgkin’s cranial base lymphoma . The study identified three aspects that distinguish a lymphoma from a meningioma: 1) bone enhancement without periosteal reaction; 2) cavernous-sinus invasion without narrowing of the internal carotid; and 3) the absence of the “dural tail” sign from the T1-weighted MRI with gadolinium enhancement.
6
ACCEPTED MANUSCRIPT Complete resection or Biopsy? When neurosurgeons suspect a mass lesion in the trigeminal region to be a lymphoma, complex surgical approach to resect the entire lesion should be avoided
RI PT
pending biopsy confirmation of the lesion. Abdel et al. reported a case of a tumor for which the first presumptive diagnosis was trigeminal schwannoma in Meckel’s cave5. The neurosurgeon chose to perform a frontotemporal craniotomy in tandem with an
SC
orbitozygomatic osteotomy and anterior petrosectomy to extract the mass lesion.
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Postoperatively, the patient suffered from series of complications, such as left ophthalmoparesis and diminished visual acuity in the left eye. However, the post-operation histological diagnosis was confirmed as B-cell lymphoma. We recommend that biopsies of lesions in Meckel’s cave be performed via a
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percutaneous-needle biopsy through the foramen ovale, a strategy that adopts a needle-insertion technique used in percutaneous stereotactic rhizotomy. This approach
complications.
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allows for the sufficient differentiation among lesions while reducing the incidence of
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Postoperative adjuvant chemotherapy Although there are various treatment options for primary CNS lymphoma, its
prognosis is poor. Deangelis et al16 reported that radiotherapy alone did not work well but provided long-time survival when combined with chemotherapy. The preferred chemotherapy entails high dose methotrexate (MTX), R-CHOP, and R-MPV. In Case 1, the patient accepted the whole-brain radiation therapy after R-MPV therapy. At the 2-year follow-up, no recurrent tumors were observed on MRI. For the second patient,
7
ACCEPTED MANUSCRIPT on account of the tumor having recurred after R-CHOP administration, we also selected R-MPV therapy in tandem with whole brain irradiation. Conclusion
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We have reported two cases of CNS lymphoma of the trigeminal nerve. When neurosurgeons suspect a mass lesion in the trigeminal region to be a lymphoma, complex surgical approach to resect the entire lesion should be avoided. Postoperative
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SC
adjuvant chemotherapy to remove the malignant lymphoma is essential.
References
1
Chiavazza C, Pellerino A, Ferrio F. Primary CNS lymphomas: Challenges in
diagnosis and monitoring. Biomed Res Int 2018; 2018:3606970. Bower K and Shah N. Primary cns burkitt lymphoma: A case report of a
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2
55-year-old cerebral palsy patient. Case Rep Oncol Med 2018; 2018:5869135. 3
Adhikari N, Biswas A, Bakhshi S, et al. A rare case of paediatric primary central
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nervous system lymphoma treated with high-dose methotrexate and rituximab-based
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chemoimmunotherapy and whole brain radiotherapy followed by tumour bed boost with three-dimensional conformal radiation technique. Childs Nerv Syst 2018. 4
Nakatomi H, Sasaki T, Kawamoto S, et al. Primary cavernous sinus malignant
lymphoma treated by gamma knife radiosurgery: Case report and review of the literature. Surg Neurol 1996; 46:272-278. 5
Abdel Aziz KM and van Loveren HR. Primary lymphoma of meckel's cave
mimicking trigeminal schwannoma: Case report. Neurosurgery 1999; 44:859-862.
8
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Kinoshita M, Izumoto S, Oshino S. Primary malignant lymphoma of the
trigeminal region treated with rapid infusion of high-dose mtx and radiation: Case report and review of the literature. Surg Neurol 2003; 60:343-348. Bulsara KR, Kadri PA, Husain M. Malignant lymphoma of the trigeminal region.
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Case illustration. J Neurooncol 2005; 73:279-280. 8
Iplikcioglu AC, Dinc C, Bikmaz K. Primary lymphoma of the trigeminal nerve.
Akaza M, Tsunemi T, Sanjo N. Malignant lymphoma presented as left trigeminal
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9
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Br J Neurosurg 2006; 20:103-105.
neuralgia. Rinsho Shinkeigak 2009; 49:432-436.
10 Tanaka T, Kato N, Itoh K. Long-term survival of diffuse large b cell lymphoma of the trigeminal region extending to the meckel's cave treated by chaser therapy:
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Case report. Neurol Med Chir (Tokyo) 2014; 54:677-680.
11 Perera C, Fitt G, Kalnins R. Lymphoma of the trigeminal nerve--the need for histological diagnosis. Br J Neurosurg 2014; 28:278-280.
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12 Jack AS, McDougall CM, Findlay JM. Primary lymphoma isolated to the
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trigeminal nerve. Can J Neurol Sci 2014; 41:103-105. 13 Ogiwara T, Horiuchi T, Sekiguchi N. Primary malignant lymphoma of the trigeminal nerve: Case report and literature review. World Neurosurg 2015; 84:592 e593-597.
14 Ang JW, Khanna A, Walcott BP. Central nervous system lymphoma presenting as trigeminal neuralgia: A diagnostic challenge. J Clin Neurosci 2015; 22:1188-1190.
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ACCEPTED MANUSCRIPT 15 Han MH, Chang KH, Kim IO. Non-hodgkin lymphoma of the central skull base: Mr manifestations. J Comput Assist Tomogr 1993; 17:567-571. 16 DeAngelis LM. Neuro-oncology: Primary CNS lymphoma treatment--the devil is
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in the details. Nat Rev Neurol 2015; 11:314-315.
Figure legends
Figure 1. Preoperative imaging and intraoperative photo. (A) T2-weighted MRI show
SC
that the trigeminal nerve(arrow) is thicken than the contralateral trigeminal nerve. (B)The trigeminal nerve was swollen and encased by the pinkish. V: trigeminal nerve
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Figure 2. Postoperative T1-weighted MRI pictures. The picture shows swelling of the bilateral trigeminal nerve (small arrow) and heterogeneously enhancing tumor enhancing lesion with gadolinium along the bilateral cavernous and infratemporal fossa (thick arrow) extending to the foramen ovale.
Fgure3. Histopathological findings revealing diffuse large B cell lymphomas.
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(A)Nuclei with atypia and mitosis were present. H&E stain×100. (B)Many of tumor cells were positive for CD20, LCA and Ki-67 antibody. (C) Many of tumor cells were positive for LCA. (D) Many of tumor cells were positive for Ki-67. LCA: Leukocyte common antigen;
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Figure4. (A)Two years later after operation, no recurrent tumors were present observed on T1-weighted MRI with gadolinium enhancement.
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Figure5. Preoperative radiological imaging. (A) T2-weighted MRI shows that the right trigeminal nerve swollen. (B) MRI axial presents that the right trigeminal nerve enhanced in CP-angle. (C) MRI coronal scanning presents the right trigeminal nerve enhanced in CP-angle. (D) Computed tomography scans shows no notable pathologic changes of bone. Figure 6 Intraoperative view. Swollen trigeminal nerve was identified. V
trigeminal
nerve; VIII: acoustic nerve Figure 7 Pathological pictures revealing diffuse large B cell lymphomas. (A) Nuclei with atypia and mitosis were present. H&E stain×100. (B) Nuclei with atypia and 10
ACCEPTED MANUSCRIPT mitosis were present. H&E stain ×400. (C)Many of tumor cells were positive for
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SC
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CD20 antibody. (D) Many of tumor cells were positive for Ki-67 antibody.
11
ACCEPTED MANUSCRIPT Table 1 Clinical summary of the 13 cases of Malignant Lymphoma of the trigeminal region
Age/sex
First
location
presenting
First
Surgical
diagnosis
removal
Meningioma
Lateral
symptoms Nakatomi(199：’
77/M
Facial
Lt. PA-CS
dysesth Abdel(1999’
40/F
Facial
Schwannoma
Subtemporal
CHOP+RT
N.D.
Facial
Lt. MC-IF
N.D.
pain
Lateral
MTX+RT
Death
Bulsara(2005’
52/F
Facial
Mass
N.D.
suboccipital Lt. MC-FR
50/M
Facial
Rt. PC-CS
pain Akaza(2009’
：0/M
Facial
52/M
Facial
Subtemporal
N.D.
Lateral
resetction
MTX+RT
C.R.
suboccipital
Lt. PA-MC
Schwannoma
Biopsy
MTX+RT
C.R.
Lt. PA-MC
N.D.
Lateral
CHASER+RT
C.R.
pain Tanaka(2013’
N.D.
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pain Iplikcioglu(200：’
SC
55/M
result
Death
pain Kinosita(2003’
Clinical
RT+MTX+PSL
suboccipital Lt. MC-CS
Chemotherapy
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authors
pain
suboccipital
55/F
Diplopia
Rt. MC
Meningioma
Transsphenoidal
N.D.
N.D.
Jack(2014’
57/M
Facial
Lt. PA-MC
N.D.
Lateral
R-MPV
C.R.
R-MPV
C.R.
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Perera(2014’
pain Toshihiro
47/M (2015’
Lt. CS-IF
N.D.
pain 55/M
Facial
EP
Ang(2015’
Facial
suboccipital Lateral suboccipital
Lt. CS-IF
Schwannoma
Biopsy
CHOP+RT
C.R.
Lt. MC-CS
Schwannoma
Biopsy
R-MPV
C.R.
Lt. PA
Lymphomas
Biopsy
R-MPV
N.D.
pain
Present case 1
55/F
Facial
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pain
Present case 2
75/F
Facial
pain
F: female; M: male; PA: prepontine cistern; CS: cavernous sinus; MC: Meckel s cave; IF
infratemporal fossa; FR: foramen rotundum; N.D: not
described; C.R: complete remission; RT; radiation; MTX: methotrexate; CHOP:
ACCEPTED MANUSCRIPT
cyclophosphamide, doxorubicin, vincristine, and prednisolone; PSL: prednisolone; CHASER: cyclophosphamide, high dose, cytarabine, dexamethasone, etoposide, and rituximab; R-MPV: rituximab,
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EP
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SC
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methotrexate, prednisone, vincristine
AC C
EP
TE D
M AN U
SC
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ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
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ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
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ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
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ACCEPTED MANUSCRIPT
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EP
TE D
M AN U
SC
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ACCEPTED MANUSCRIPT
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EP
TE D
M AN U
SC
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ACCEPTED MANUSCRIPT
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EP
TE D
M AN U
SC
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ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT Central nervous system lymphoma Magnetic resonance imaging Microvascular decompression Hematoxylin-eosin Immunohistochemistry
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EP
TE D
M AN U
SC
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CNSL MRI MVD HE IHC
S1878-8750(18)32776-1
DOI:
https://doi.org/10.1016/j.wneu.2018.11.217
Reference:
WNEU 10901
To appear in:
World Neurosurgery
Received Date: 5 November 2018 Revised Date:
24 November 2018
Accepted Date: 26 November 2018
Please cite this article as: Zhao H, Zhu J, Zhang X, Tang Y-d, Li S-t, Diffuse Large B Cell Lymphoma presented as trigeminal neuralgia: two cases reported and literatures review, World Neurosurgery (2019), doi: https://doi.org/10.1016/j.wneu.2018.11.217. 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.
ACCEPTED MANUSCRIPT
Diffuse Large B Cell Lymphoma presented as trigeminal neuralgia: two cases reported and literatures review (Hua Zhao, Jin Zhu, Xin Zhang, Yin-da Tang, Shi-ting Li)
RI PT
Department of Neurosurgery, Xinhua hospital affiliated to Shanghai Jiaotong University School of Medicine
Jin Zhu: medzhujin@12：.com Xin Zhang: zhangxin：010@12：.com
M AN U
Yin-da Tang: [email protected]
SC
Hua Zhao: zhaohuaziyu@1：3.com
Hua Zhao and Jin Zhu are first co-authors.
Correspondence: [email protected]
TE D
Department of Neurosurgery, Xinhua hospital affiliated to Shanghai Jiaotong University School of Medicine, 1：：5# Kongjiang Road,
EP
Yangpu district, Shanghai, China.
AC C
Run title: Diffuse Large B Cell Lymphoma presented as trigeminal neuralgia
1
ACCEPTED MANUSCRIPT Diffuse Large B-Cell Lymphoma Presented as Trigeminal Neuralgia: Report of Two Cases and Literature Review Abstract
RI PT
Objective: Extra-axial lymphoma involving the trigeminal nerve, an uncommon condition that presents as a trigeminal schwannoma, resulted in misdiagnosis and a flawed surgical strategy. We report two cases: a primary lymphoma of Meckel’s cave
SC
and a metastasis lymphoma in the prepontine cistern arising from the supraclavicular
M AN U
lymph node.
Cases report: The first patient presented with a 3-month history of persistent, sharp facial pain across the area innervated by the V2 nerve. She was misdiagnosed with primary trigeminal
neuralgia and
underwent
microvascular
decompression.
TE D
Intraoperatively, the trigeminal nerve was swollen to a large extent and surrounded by red granuloma-like tissue. The second case was a 75-year-old woman; she had a history of a malignant lymphoma of the of the supraclavicular lymph node and
EP
presented with right facial pain. Magnetic resonance imaging revealed that the
AC C
cisternal portion of the right trigeminal nerve was swollen. A specimen was taken from the two patients, and histopathological examinations revealed a diffuse large B-cell lymphoma.
Conclusion: The diagnosis of a malignant lymphoma should be considered for lesions in the trigeminal region. Extracting a specimen for biopsy is the most suitable surgical strategy. Our report indicates that postoperative adjuvant chemotherapy for malignant lymphomas is essential.
2
ACCEPTED MANUSCRIPT Keywords: Biopsy; Malignant lymphoma; Neuropathic pain Introduction Primary central nervous system lymphoma (CNSL) usually originates from the brain 1,2
. Although primary CNSL is an
RI PT
parenchyma, particularly the white matter
uncommon brain neoplasm, its incidence is rising in some groups due to an increase in immunocompromised patients with acquired immunodeficiency syndrome3.
4-7
. We report two cases of diffuse large B-cell lymphoma in the trigeminal
M AN U
condition
SC
However, extra-axial lymphoma arising in the trigeminal region is a less common
region: a primary lymphoma and a metastasis lymphoma arising from the supraclavicular lymph node. The clinical and radiological features conformed to those of trigeminal neurinoma. This study was approved by the Xinhua Hospital
TE D
Institutional Ethics Committee, and the protocol adhered to approved institutional guidelines and regulations.
Case 1
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Clinical Presentation
AC C
A 55-year-old women presented with a 3-month history of persistent, sharp facial pain distributed across the area innervated by the right V2 nerve. Though the pain was initially restricted to the nostril, it progressed to include numbness across the cheek. On physical examination, she was found to exhibit right facial numbness. Further cranial nerve examinations revealed no abnormalities or other neurological deficits. Family and social history were noncontributory. Magnetic resonance imaging (MRI) revealed the right trigeminal nerve to be thicker than the contralateral trigeminal
3
ACCEPTED MANUSCRIPT nerve (Figure 1A). The patient was misdiagnosed with primary trigeminal neuralgia and underwent microvascular decompression (MVD). Intraoperatively, the trigeminal nerve was swollen and surrounded by red granuloma-like tissue (Figure1B). A
RI PT
specimen was resected from the granuloma-like tissue. The patient underwent enhanced MRI on the third postoperative day. The MRI indicated that the right trigeminal nerve was swollen at its cisternal portion and at the Meckel cave (Figure 2). specimen
was
analyzed
The
hematoxylin-eosin
(HE)
latter revealed
a
staining
and
tumor consisting of
M AN U
immunohistochemistry (IHC).
via
SC
The
medium-to-large sized lymphoid cells with multi-lobulated nuclei of a B-cell phenotype (CD 20 positive). The cells were LCA positive, CD56 negative, and featured a high Ki-67 labeling index of 78% (Figure 3), indicating a diffuse large
TE D
B-cell lymphoma. The patient underwent R-MPV therapy (rituximab, methotrexate, prednisone, vincristine), after which the intracranial mass lesion was almost undetectable via MRI. She had not experienced recurrence by the 2-year follow-up
AC C
Case 2
EP
(Figure4); however, she still exhibited facial numbness.
A 75-year-old women presented with a 2-month history of right facial pain in all three divisions of the trigeminal nerve. Her past medical history included a malignant lymphoma of the supraclavicular lymph node; the administration of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) therapy for eight cycles had completely resolved her condition. A neurological examination indicated hypoesthesia in all divisions of the trigeminal nerve as well as a diminished
4
ACCEPTED MANUSCRIPT right corneal reflex. MRI revealed that the cisternal portion of the right trigeminal nerve was swollen. The right trigeminal nerve, isointense on T1-and T2-weighted MRI, was homogeneously enhanced with gadolinium. Thin-slice temporal bone
RI PT
computed tomographic (CT) images showed no notable pathologic changes in the bone (Figure 5). We made an initial diagnosis of a malignant lymphoma of the trigeminal nerve. The patient underwent an operation via a suboccipital retrosigmoid
SC
approach for histopathological confirmation. Intraoperatively, the trigeminal nerve
M AN U
was swollen and pink (Figure 6). A biopsy was taken from the trigeminal nerve; the subsequent analysis of the frozen section indicated the presence of a diffuse large B-Cell Lymphoma. The permanent histological findings agreed with the findings from the frozen section (Figure 7). The patient was treated with R-CHOP
TE D
chemotherapy.
Discussion
The present report describes a primary lymphoma and a metastatic lymphoma at
EP
trigeminal nerve adjacent to the skull base, a rare location of for primary CNS
AC C
lymphoma to present. To the best of our knowledge, only 11 patients with lymphoma-induced trigeminal neuralgia have been hitherto reported (Table 1)
4-14
.
Including the women presented in this report, the mean age and the male-to-female ratio of the 13 patients are 56.15 years (range, 44-70 years) and 8:5, respectively. Diagnosis of malignant lymphoma in the trigeminal region The literature lacks a unified understanding of the diagnosis of malignant lymphoma in the trigeminal region, thereby confounding correct diagnosis at the
5
ACCEPTED MANUSCRIPT initial stage of treatment. Based on our experience, we suggest that the following observations can help to inform a correct diagnosis of malignant lymphoma. 1) Clinical characteristics are atypical: ① the average duration of symptoms indicative
RI PT
of lymphoma is relatively shorter than those corresponding to other presumptive lesions, ② the absence of the trigger-point phenomenon; and ③ persistent pain. 2) Numbness in the ipsilateral face is apparent. 3) The MRI findings reveal a swollen
SC
trigeminal nerve is swollen, and T1-weighted MRI with gadolinium enhancement
M AN U
indicates that the nerve is enhanced along its long axis. 4) The medical history includes organ transplantations, acquired immunodeficiency syndrome, or lymphoma in other parts of the body.
Differential diagnosis in the trigeminal region
TE D
Multiple types of mass lesions can occur in the cerebellopontine angle (CPA) of Meckel’s cave12. The clinical features of malignant lymphoma of the trigeminal region, including trigeminal neuralgia, facial hypesthesia, and diplopia, coincide with
EP
those caused by other trigeminal-nerve and cavernous-sinus lesions. The MRI features
AC C
of extranodal non-Hodgkin lymphoma of the skull base are similar to those associated with meningioma and other more common neoplasms of this region. Han et al15. attempted to determine radiological criteria for non-Hodgkin’s cranial base lymphoma . The study identified three aspects that distinguish a lymphoma from a meningioma: 1) bone enhancement without periosteal reaction; 2) cavernous-sinus invasion without narrowing of the internal carotid; and 3) the absence of the “dural tail” sign from the T1-weighted MRI with gadolinium enhancement.
6
ACCEPTED MANUSCRIPT Complete resection or Biopsy? When neurosurgeons suspect a mass lesion in the trigeminal region to be a lymphoma, complex surgical approach to resect the entire lesion should be avoided
RI PT
pending biopsy confirmation of the lesion. Abdel et al. reported a case of a tumor for which the first presumptive diagnosis was trigeminal schwannoma in Meckel’s cave5. The neurosurgeon chose to perform a frontotemporal craniotomy in tandem with an
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orbitozygomatic osteotomy and anterior petrosectomy to extract the mass lesion.
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Postoperatively, the patient suffered from series of complications, such as left ophthalmoparesis and diminished visual acuity in the left eye. However, the post-operation histological diagnosis was confirmed as B-cell lymphoma. We recommend that biopsies of lesions in Meckel’s cave be performed via a
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percutaneous-needle biopsy through the foramen ovale, a strategy that adopts a needle-insertion technique used in percutaneous stereotactic rhizotomy. This approach
complications.
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allows for the sufficient differentiation among lesions while reducing the incidence of
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Postoperative adjuvant chemotherapy Although there are various treatment options for primary CNS lymphoma, its
prognosis is poor. Deangelis et al16 reported that radiotherapy alone did not work well but provided long-time survival when combined with chemotherapy. The preferred chemotherapy entails high dose methotrexate (MTX), R-CHOP, and R-MPV. In Case 1, the patient accepted the whole-brain radiation therapy after R-MPV therapy. At the 2-year follow-up, no recurrent tumors were observed on MRI. For the second patient,
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ACCEPTED MANUSCRIPT on account of the tumor having recurred after R-CHOP administration, we also selected R-MPV therapy in tandem with whole brain irradiation. Conclusion
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We have reported two cases of CNS lymphoma of the trigeminal nerve. When neurosurgeons suspect a mass lesion in the trigeminal region to be a lymphoma, complex surgical approach to resect the entire lesion should be avoided. Postoperative
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adjuvant chemotherapy to remove the malignant lymphoma is essential.
References
1
Chiavazza C, Pellerino A, Ferrio F. Primary CNS lymphomas: Challenges in
diagnosis and monitoring. Biomed Res Int 2018; 2018:3606970. Bower K and Shah N. Primary cns burkitt lymphoma: A case report of a
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2
55-year-old cerebral palsy patient. Case Rep Oncol Med 2018; 2018:5869135. 3
Adhikari N, Biswas A, Bakhshi S, et al. A rare case of paediatric primary central
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nervous system lymphoma treated with high-dose methotrexate and rituximab-based
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chemoimmunotherapy and whole brain radiotherapy followed by tumour bed boost with three-dimensional conformal radiation technique. Childs Nerv Syst 2018. 4
Nakatomi H, Sasaki T, Kawamoto S, et al. Primary cavernous sinus malignant
lymphoma treated by gamma knife radiosurgery: Case report and review of the literature. Surg Neurol 1996; 46:272-278. 5
Abdel Aziz KM and van Loveren HR. Primary lymphoma of meckel's cave
mimicking trigeminal schwannoma: Case report. Neurosurgery 1999; 44:859-862.
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Kinoshita M, Izumoto S, Oshino S. Primary malignant lymphoma of the
trigeminal region treated with rapid infusion of high-dose mtx and radiation: Case report and review of the literature. Surg Neurol 2003; 60:343-348. Bulsara KR, Kadri PA, Husain M. Malignant lymphoma of the trigeminal region.
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Case illustration. J Neurooncol 2005; 73:279-280. 8
Iplikcioglu AC, Dinc C, Bikmaz K. Primary lymphoma of the trigeminal nerve.
Akaza M, Tsunemi T, Sanjo N. Malignant lymphoma presented as left trigeminal
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Br J Neurosurg 2006; 20:103-105.
neuralgia. Rinsho Shinkeigak 2009; 49:432-436.
10 Tanaka T, Kato N, Itoh K. Long-term survival of diffuse large b cell lymphoma of the trigeminal region extending to the meckel's cave treated by chaser therapy:
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Case report. Neurol Med Chir (Tokyo) 2014; 54:677-680.
11 Perera C, Fitt G, Kalnins R. Lymphoma of the trigeminal nerve--the need for histological diagnosis. Br J Neurosurg 2014; 28:278-280.
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12 Jack AS, McDougall CM, Findlay JM. Primary lymphoma isolated to the
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trigeminal nerve. Can J Neurol Sci 2014; 41:103-105. 13 Ogiwara T, Horiuchi T, Sekiguchi N. Primary malignant lymphoma of the trigeminal nerve: Case report and literature review. World Neurosurg 2015; 84:592 e593-597.
14 Ang JW, Khanna A, Walcott BP. Central nervous system lymphoma presenting as trigeminal neuralgia: A diagnostic challenge. J Clin Neurosci 2015; 22:1188-1190.
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ACCEPTED MANUSCRIPT 15 Han MH, Chang KH, Kim IO. Non-hodgkin lymphoma of the central skull base: Mr manifestations. J Comput Assist Tomogr 1993; 17:567-571. 16 DeAngelis LM. Neuro-oncology: Primary CNS lymphoma treatment--the devil is
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in the details. Nat Rev Neurol 2015; 11:314-315.
Figure legends
Figure 1. Preoperative imaging and intraoperative photo. (A) T2-weighted MRI show
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that the trigeminal nerve(arrow) is thicken than the contralateral trigeminal nerve. (B)The trigeminal nerve was swollen and encased by the pinkish. V: trigeminal nerve
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Figure 2. Postoperative T1-weighted MRI pictures. The picture shows swelling of the bilateral trigeminal nerve (small arrow) and heterogeneously enhancing tumor enhancing lesion with gadolinium along the bilateral cavernous and infratemporal fossa (thick arrow) extending to the foramen ovale.
Fgure3. Histopathological findings revealing diffuse large B cell lymphomas.
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(A)Nuclei with atypia and mitosis were present. H&E stain×100. (B)Many of tumor cells were positive for CD20, LCA and Ki-67 antibody. (C) Many of tumor cells were positive for LCA. (D) Many of tumor cells were positive for Ki-67. LCA: Leukocyte common antigen;
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Figure4. (A)Two years later after operation, no recurrent tumors were present observed on T1-weighted MRI with gadolinium enhancement.
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Figure5. Preoperative radiological imaging. (A) T2-weighted MRI shows that the right trigeminal nerve swollen. (B) MRI axial presents that the right trigeminal nerve enhanced in CP-angle. (C) MRI coronal scanning presents the right trigeminal nerve enhanced in CP-angle. (D) Computed tomography scans shows no notable pathologic changes of bone. Figure 6 Intraoperative view. Swollen trigeminal nerve was identified. V
trigeminal
nerve; VIII: acoustic nerve Figure 7 Pathological pictures revealing diffuse large B cell lymphomas. (A) Nuclei with atypia and mitosis were present. H&E stain×100. (B) Nuclei with atypia and 10
ACCEPTED MANUSCRIPT mitosis were present. H&E stain ×400. (C)Many of tumor cells were positive for
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CD20 antibody. (D) Many of tumor cells were positive for Ki-67 antibody.
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ACCEPTED MANUSCRIPT Table 1 Clinical summary of the 13 cases of Malignant Lymphoma of the trigeminal region
Age/sex
First
location
presenting
First
Surgical
diagnosis
removal
Meningioma
Lateral
symptoms Nakatomi(199：’
77/M
Facial
Lt. PA-CS
dysesth Abdel(1999’
40/F
Facial
Schwannoma
Subtemporal
CHOP+RT
N.D.
Facial
Lt. MC-IF
N.D.
pain
Lateral
MTX+RT
Death
Bulsara(2005’
52/F
Facial
Mass
N.D.
suboccipital Lt. MC-FR
50/M
Facial
Rt. PC-CS
pain Akaza(2009’
：0/M
Facial
52/M
Facial
Subtemporal
N.D.
Lateral
resetction
MTX+RT
C.R.
suboccipital
Lt. PA-MC
Schwannoma
Biopsy
MTX+RT
C.R.
Lt. PA-MC
N.D.
Lateral
CHASER+RT
C.R.
pain Tanaka(2013’
N.D.
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pain Iplikcioglu(200：’
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55/M
result
Death
pain Kinosita(2003’
Clinical
RT+MTX+PSL
suboccipital Lt. MC-CS
Chemotherapy
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authors
pain
suboccipital
55/F
Diplopia
Rt. MC
Meningioma
Transsphenoidal
N.D.
N.D.
Jack(2014’
57/M
Facial
Lt. PA-MC
N.D.
Lateral
R-MPV
C.R.
R-MPV
C.R.
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Perera(2014’
pain Toshihiro
47/M (2015’
Lt. CS-IF
N.D.
pain 55/M
Facial
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Ang(2015’
Facial
suboccipital Lateral suboccipital
Lt. CS-IF
Schwannoma
Biopsy
CHOP+RT
C.R.
Lt. MC-CS
Schwannoma
Biopsy
R-MPV
C.R.
Lt. PA
Lymphomas
Biopsy
R-MPV
N.D.
pain
Present case 1
55/F
Facial
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pain
Present case 2
75/F
Facial
pain
F: female; M: male; PA: prepontine cistern; CS: cavernous sinus; MC: Meckel s cave; IF
infratemporal fossa; FR: foramen rotundum; N.D: not
described; C.R: complete remission; RT; radiation; MTX: methotrexate; CHOP:
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cyclophosphamide, doxorubicin, vincristine, and prednisolone; PSL: prednisolone; CHASER: cyclophosphamide, high dose, cytarabine, dexamethasone, etoposide, and rituximab; R-MPV: rituximab,
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methotrexate, prednisone, vincristine
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ACCEPTED MANUSCRIPT Central nervous system lymphoma Magnetic resonance imaging Microvascular decompression Hematoxylin-eosin Immunohistochemistry
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CNSL MRI MVD HE IHC