Plexiform schwannoma in schwannomatosis
SV Shinde1, DK Tyagi2, HV Sawant2, GV Puranik1,
1 Department of Pathology, B.Y.L Nair Hospital, Mumbai, India
2 Department of Neurosurgery, B.Y.L Nair Hospital, Mumbai, India
S V Shinde
Department of Pathology, B.Y.L Nair Hospital, Mumbai
|How to cite this article:|
Shinde S V, Tyagi D K, Sawant H V, Puranik G V. Plexiform schwannoma in schwannomatosis.J Postgrad Med 2009;55:206-207
|How to cite this URL:|
Shinde S V, Tyagi D K, Sawant H V, Puranik G V. Plexiform schwannoma in schwannomatosis. J Postgrad Med [serial online] 2009 [cited 2020 Sep 26 ];55:206-207
Available from: http://www.jpgmonline.com/text.asp?2009/55/3/206/57406
A 32 year-old female presented with quadriparesis, diffuse abdominal pain, and left lumbar mass of two months' duration. Magnetic resonance imaging (MRI) revealed multiple intradural masses at C1, T1-2, T 7-8, and T12-L4 levels. These were isointense in T1 images, hyperintense in T2 images, and homogenously contrast-enhancing, suggesting nerve sheath tumors [Figure 1]. On T2 imaging, there were multiple, lobulated, hyperintense retroperitoneal masses in extension with intradural masses. These showed areas of necrosis and calcification that raised a suspicion of degenerative or malignant change in the neurogenic tumor [Figure 2]. The patient had a past history of generalized seizure seven years ago when she was seven months pregnant. A computerized tomography (CT) scan revealed a uniformly isodense, fronto-parietal meningioma and trigeminal schwannoma [Figure 3]; no vestibular schwannoma (VS) was detected. The child was aborted and no further management was done for the meningioma. Since then, the patient had also complained of a gradually increasing left gluteal swelling. In the present admission, the patient was operated for the gluteal subcutaneous mass and laminectomy was done for three intradural masses. The patient was unwilling to be investigated invasively for the retroperitoneal masses. The present MRI did not reveal any change in the meningioma or in the appearance of VS. The patient had no family history for similar masses.
We received a 7 x 4 cm gluteal subcutaneous mass with an overlying skin flap. The mass showed a multinodular appearance of yellowish, soft, myxoid nodules typical of plexiform schwannoma (PS) [Figure 4]. The three intradural masses were seen to be encapsulated, glistening, yellowish, and soft. Microscopy of the gluteal mass showed a typical plexiform pattern of PS with Antoni A (cellular with elongated spindle cells with serpentine nuclei; Verocay bodies were seen) and Antoni B areas (hypocellular with hyalinized vessels showing thrombi.) Degenerative atypia was seen but no mitoses or geographic necrosis was noted. The three intradural masses showed an appearance of benign schwannomas. The patient has not developed any new lesion in the past 14 months of follow-up.
We have described multiple neurogenic tumors, both central and peripheral in location. These can be found in neurofibromatosis 1 (NF-1), neurofibromatosis 2 (NF-2), and in schwannomatosis. The diagnostic criteria for NF-1 include at least two of the following: Cafe-au-lait spots, plexiform neurofibroma (PN) or more than two neurofibromas, optic glioma, Lisch nodules, and sphenoid dysplasia.  Definite criteria for NF-2 include bilateral VS or first-degree family members of NF-2 plus (1) unilateral VS below age 30 years or (2) any two of meningioma, glioma, or schwannomas.  Definitive criteria for schwannomatosis include two or more pathologically proven schwannomas plus the lack of radiographic evidence of VS above 18 years of age.  Revised criteria stress on the patient's age being above 30 years, the absence of first-degree relatives with NF-2, and the lack of NF-2 mutations. 
Generally, schwannomatosis is a sporadic, nonfamilial condition that presents in older age groups (mean age: 45 years) with longer life expectancy. NF-2 is generally familial with autosomal dominant inheritance and younger age (mean: 28 years). NF-2 and schwannomatosis share mutations in the NF-2 gene on chromosome 22q. NF-2 patient have germline mutations with high penetrance where as schwannomatosis patients have somatic mutations with incomplete penetrance. , Young patients who present with multiple peripheral schwannomas should have undergo high-quality MRI of the head and spine, a thorough ophthalmologic examination, and constitutional NF2 mutation testing to rule out NF-2. 
The differing clinical implications for PS and PN stress the importance of specifying the terminology in light microscopy examinations. PS is a rare variant, forming 5% of benign schwannomas; its plexiform and multinodular growth pattern mimics PN. PN lacks Antoni A and B areas of schwannoma  and shows weak, patchy S-100 positivity. On the other hand, PS shows diffuse and strong positivity with immunohistochemical markers like S-100, laminin and collagen type IV.  PN is pathognomonic of NF-1 and has a capacity for malignant transformation, in sharp contrast to PS.  PS has no association with neurofibromatosis-1 (NF-1), but shows up to 5% association with NF-2 and schwannomatosis. ,, A curious case of coexistent schwannoma and PN was found to be unassociated with schwannomatosis or NF-2. Spinner et al. found loss of merlin and neurofibromin expression in both tumors, whereas only PN showed chromosome 22q deletions, thus suggestive of mosaicism.  Both schwannoma and neurofibroma are isointense in T1, hyperintense in T2, and variably enhancing on contrast.  Thus, the onus lies with the pathologist to distinguish them on microscopy.
PS shows no propensity for malignant transformation in spite of worrisome cellularity and mitotic activity. ,, Subtotal resection can result in local recurrence. , Absence of mitotic activity commensurate with cellularity, absence of geographic necrosis, and diffuse S-100 positivity favor benign lesion.  Deep-seated PS in retroperitoneum that is unassociated with NF-2 or schwannomatosis shows a female preponderance and focal necrosis.  Benign neurogenic tumors with cyst/hemorrhage/calcification or necrotic degenerations may mimic malignant change on MRI.  Our case showed such changes in the retroperitoneal mass. The patient denied us further interventional investigations to confirm the suspicion of degenerative change versus malignancy.
Solitary meningioma has been described with schwannomatosis. ,,, Sporadic and familial meningiomas show mutation of chromosome 22. Hence, coexistent PS and meningioma can be regarded as forme fruste of NF-2 with a dominant peripheral manifestation. 
|1||Enzinger FM, Weiss SW. Benign tumors of peripheral nerves. In: Enzinger FM, Weiss SW, editors. Soft tissue tumors. 4 th ed. St. Louis: Mosby; 2001. p. 1111-207.|
|2||Baser ME, Friedman JM, Evans GR. Increasing the specificity of diagnostic criteria for schwannomatosis. Neurology 2006;66:730-2.|
|3||King A, Gutmann DH. The question of familial meningiomas and schwannomatosis: NF2B or not to be? Neurology 2000;54:4-5.|
|4||Agaram NP, Prakash S, Antonescu CR. Deep-seated plexiform schwannoma: A pathologic study of 16 cases and comparative analysis with the superficial variety. Am J Surg Pathol 2005;29:1042-8.|
|5||Ishida T, Kuroda M, Motoi T, Oka T, Imamura T, Machinami R. Phenotypic diversity of neurofibromatosis 2: Association with plexiform schwannoma. Histopathology 1998;32:264-70.|
|6||Berg JC, Scheithauer BW, Spinner RJ, Allen CM, Koutlas IG. Plexiform schwannoma: A clinicopathologic overview with emphasis on the head and neck region. Hum Pathol 2008;39:633-40.|
|7||Spinner RJ, Scheithauer BW, Perry A, Amrani KK, Emnett R, Gutmann DH. Colocalised cellular schwannoma and plexiform neurofibroma in the absence of neurofibromatosis: Case report. J Neurosurg 2007;107:435-9.|
|8||Osborn AG. Diagnostic neuroradiology. 1 st ed. St.Louis: Mosby;1994.|
|9||Antinheimo J, Sankila R, Carpen O, Pukkala E, Sainio M, Jaaskelainen J. Population-based analysis of sporadic and type 2 neurofibromatosis-associated meningiomas and schwannomas. Neurology 2000;54:71-6.|