Background

These tumors are derived from schwann cells. These cells produce myelin, which insulates nerves facilitating neural transmission. These tumors have been associated with neurofibromatosis. Malignant change is very rare.

OUTLINE

Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Differential Diagnosis
Prognosis
Treatment
Commonly Used Terms
Internet Links

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
VARIANTS
BONE
Intraosseous schwannoma of the humerus. Mutema GK, Sorger J. Department of Pathology, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267, USA,	Skeletal Radiol 2002 Jul;31(7):419-21 Abstract quote Intraosseous schwannomas are rare benign neoplasms of the bone, of which fewer than 200 cases have been described in the world literature. These tumors are well-defined, lytic lesions, rarely associated with pathologic fracture. The mandible is the most frequently involved bone. We present only the third case of an intraosseous schwannoma involving the humerus.
BRAINSTEM (ACOUSTIC NEUROMAS)
Natural history of acoustic neuromas. Rosenberg SI. Florida Ear and Sinus Center, Sarasota, USA.	Laryngoscope 2000 Apr;110(4):497-508 Abstract quote OBJECTIVES/HYPOTHESIS: 1) Develop a computerized technique to accurately compare acoustic neuroma size on routine computed tomography and magnetic resonance imaging (MRI) scans; 2) use this technique to determine the growth pattern in a large series of patients with acoustic neuroma who were conservatively managed; 3) describe the natural history of patients with acoustic neuromas who did not receive surgical intervention and those who underwent subtotal resection; 4) correlate the size and growth rate of acoustic neuromas to clinical presentation and auditory and vestibular testing; and 5) recommend guidelines for the management of patients with acoustic neuromas. STUDY DESIGN: A retrospective study from 1974 to 1999 of patients with unilateral acoustic neuromas who had conservative treatment by serial imaging studies (80 patients) or subtotal resection (49 patients). METHODS: All patient charts were evaluated for presenting symptoms, reasons for the type of management given, and clinical outcome. Charts were also reviewed with respect to serial audiological assessment, electronystagmography, and brainstem auditory evoked response. Imaging studies were analyzed using a computer technique so that serial studies could be compared to determine growth rates. RESULTS: Rigorous computer analysis of tumor size and growth rate was statistically the same as the radiologist's description of the tumor size and growth rate. Of 70 patients who were older than 65 years of age old at the time their tumor was discovered, 4 (5.7%) required intervention and 18 (26%) were dead of unrelated causes. These patients had a mean follow-up of 4.8 years (range, 0.01-17.2 y). Overall, growth rate for nonsurgical patients was 0.91 mm per year. Nonsurgical tumors did not grow or regressed in 42%. Overall postoperative growth rate for surgical subtotal resection patients was 0.35 mm per year. Surgical tumors did not grow or regressed after subtotal resection of acoustic neuroma in 68.5% of patients. Three patients (6.1%) required revision surgery because of tumor growth or the development of symptoms. Neither auditory nor vestibular testing was a reliable measure for determining tumor growth. CONCLUSION: Measurement of the maximal tumor diameter on MRI scans is a reliable method for following acoustic neuroma growth. There is no need to perform a rigorous analysis of tumor size to determine whether the tumor is growing significantly. The vast majority of patients older than 65 years with acoustic neuromas do not require intervention. The indications for intervention should be based on a combination of rapid tumor growth with the development of symptoms.
COLON
Schwannomas in the Colon and Rectum A Clinicopathologic and Immunohistochemical Study of 20 Cases Markku Miettinen, M.D.; Kris M. Shekitka, M.D.; Leslie H. Sobin, M.D. From the Department of Soft Tissue Pathology (M.M.) and the Division of Gastrointestinal Pathology (K.M.S., L.H.S.), Armed Forces Institute of Pathology, Washington, DC, U.S.A.	Am J Surg Pathol 2001;25:846-855 Abstract quote Schwannomas of the colon and rectum are uncommon and incompletely characterized tumors, and only a small number of cases have been reported. This study was undertaken to determine the clinicopathologic profile of such tumors. A total of 20 colorectal schwannomas were identified and analyzed in a review of 600 mesenchymal tumors of the colon and rectum from the files of the Armed Forces Institute of Pathology. The schwannomas occurred equally in men (n = 9) and women (n = 11) in a wide age range (18–87 years; median age 65 years). The most common location was cecum (n = 7), followed by sigmoid and rectosigmoid (n = 6), transverse colon (n = 3), descending colon (n = 2), and rectum (n = 1); the location of one tumor had not been specified. The tumors commonly presented as polypoid intraluminal lesions, often with mucosal ulceration. Rectal bleeding, colonic obstruction, and abdominal pain were the most common presenting symptoms. The most common histologic variant (n = 15) was a spindle cell schwannoma with a trabecular pattern and vague or no Verocay bodies. These tumors ranged from 0.5 to 5.5 cm in diameter. A lymphoid cuff with germinal centers typically surrounded these tumors and focal nuclear atypia was often present, but mitotic activity never exceeded 5 per 50 HPF. All four epithelioid schwannomas occurred in the descending colon or sigmoid, three of them as small submucosal tumors. There was one plexiform schwannoma in the sigmoid composed of multiple nodules of prominently palisading schwann cells similar to those seen in conventional soft tissue schwannomas. All tumors studied were strongly positive for S-100 protein and also for low affinity nerve growth factor receptor (p75), collagen IV, and GFAP. Three tumors had CD34-positive cells, but all were negative for CD117 (KIT), neurofilament proteins, smooth muscle actin, and desmin. The percentage of MIB-1-positive cells was usually less than 1% and never higher than 3%. Colorectal schwannomas behaved in a benign fashion with no evidence of aggressive behavior or connection with neurofibromatosis 1 or 2, based on follow-up information on 18 patients.
HEAD AND NECK
Obstructive supraglottic schwannoma: a case report and review of the literature. Rosen FS, Pou AM, Quinn FB Jr. Department of Otolaryngology, University of Texas Medical Branch, Galveston 77555-0521, USA.	Laryngoscope 2002 Jun;112(6):997-1002 Abstract quote OBJECTIVE: At the conclusion of the current presentation, the participants should be able to describe the etiology, presentation, histopathologic identification, and treatment options for schwannoma of the larynx. OBJECTIVES: Nerve sheath tumors rarely occur within the larynx. The goal of the current report is to acquaint the clinician with the presentation and treatment options for this disease. STUDY DESIGN: Retrospective case report and review of the literature. METHODS: We report one case of schwannoma of the supraglottic larynx at the Department of Otolaryngology, University of Texas Medical Branch (Galveston, TX). In addition, we review English-language publications regarding laryngeal nerve sheath tumors. RESULTS: Laryngeal nerve sheath tumors have an insidious course, commonly involve the supraglottic larynx, and can lead to upper airway obstruction. Cure is achieved by complete surgical excision. CONCLUSIONS: Median thyrotomy has proven to be safe and successful in the treatment of supraglottic schwannoma.
Extracranial head and neck schwannomas: a review of 8 years experience. Leu YS, Chang KC. Department of Otolaryngology, Mackay Memorial Hospital, Taipei, Taiwan.	Acta Otolaryngol 2002 Jun;122(4):435-7 Abstract quote Schwannomas of the head and neck are uncommon tumors that arise from cranial, peripheral or autonomic nerves. In this study we review a series of 52 cases of schwannoma originating in the head and neck region over an 8-year period. All the tumors were benign, with the exception of one malignant schwannoma. The age range of the patients studied was 13-76 years and there was a predilection for males. Twenty-five schwannomas occurred in the scalp, face and external ear canal, 9 in the oral or nasal cavity and 18 in the neck. Seven cases of neck schwannoma originating from the major nerve system were found in the parapharyngeal space, all of which were located in the post-styloid compartment. Cervical plexus schwannomas originated either in the peripheral nerves or in an unidentified area of the nervous system; seven tumors were found in the posterior triangle of the neck and two in the anterior triangle. Two of the tumors originating in the brachial plexus were located in the posterior neck and one in the anterior neck. Tumors originating in the vagus nerve or sympathetic chain were all located in the anterior triangle of the neck.
PANCREAS
Cystic schwannoma of the pancreas. Tan G, Vitellas K, Morrison C, Frankel WL.	Ann Diagn Pathol. 2003 Oct;7(5):285-91 Abstract quote.   Intrapancreatic schwannoma is a rare neoplasm. We report a case of a 46-year-old man with a cystic schwannoma in the head of the pancreas. This tumor, based on clinical manifestations and radiologic features, was initially suspected to be a cystic mucinous tumor of the pancreas or a pseudocyst. Histologically, the tumor was a typical schwannoma with cyst formation caused by degenerative changes. Immunostaining showed the tumor cells to be strongly and diffusely positive for S-100 protein, vimentin, and CD56, and negative for cytokeratin AE1/AE3, desmin, smooth muscle myosin specific, CD34, and CD117, which support the diagnosis of schwannoma. Cystic schwannoma is a rare neoplasm occurring in the pancreas and should be considered in the differential diagnoses for patients presenting with pancreatic cystic lesions.
SINUS
Cystic schwannoma of the maxillary sinus. Sarioglu S, Ozkal S, Guneri A, Ada E, Sis B, Kemal Erdag T, Ugur Pabuccuoglu H. Department of Pathology, School of Medicine, Dokuz Eylul University, 35340 Inciralti/, Izmir, Turkey	Auris Nasus Larynx 2002 Jul;29(3):297 Abstract quote OBJECTIVE: Although 25-45% of all schwannomas are reported to occur in the head and neck region, nasal cavity and paranasal sinus involvement is rare, with 32 such cases described till 1999. Of these cases, only three were cystic. Herein we present a cystic schwannoma of the maxillary sinus of a 66-year-old, otherwise healthy male patient. METHODS: The tumor tissue was routinely processed, embedded in paraffin, and stained with H&E. Immunostaining was performed for S-100 protein, epithelial membrane antigen (EMA) and cytokeratin. RESULTS: A mass with sudden enlargement, inhomogenous enhancement with cystic areas, S-100 positive membrane-like structures lining the cystic cavity of an otherwise classical schwannoma were the main features encountered in our case. CONCLUSION: We recommend that cystic schwannoma should be kept in mind in the differential diagnosis of cystic masses of the maxilla.

 

HISTOLOGICAL TYPES	CHARACTERIZATION
VARIANTS
EPITHELIOID
Benign cutaneous epithelioid Schwannoma: case report and review of the literature. Saad AG, Mutema GK, Mutasim DF. Department of Pathology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0592, USA.	Am J Dermatopathol. 2005 Feb;27(1):45-7. Abstract quote   Benign peripheral nerve sheath tumors are relatively common. They are mostly characterized by the presence of delicate S-shaped spindle cells and myxoid stroma. Although variants with epithelioid foci can be present, the pure epithelioid variant of benign cutaneous schwannoma is extremely rare. It was first reported as cutaneous epithelial schwannoma by Kindblom et al in 1998. Since then, only six cases have been reported. Care should be taken not to misdiagnose them as malignant neoplasms. Their diagnosis can be problematic as their histopathologic features may overlap with those of other soft-tissue and melanocytic tumors. We report a case of cutaneous epithelioid schwannoma and review of the literature.
Benign Epithelioid Peripheral Nerve Sheath Tumors of the Soft Tissues: Clinicopathologic Spectrum of 33 Cases. Laskin WB, Fetsch JF, Lasota J, Miettinen M. From the *Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL; and the daggerDepartment of Soft Tissue Pathology, Armed Forces Institute of Pathology, Washington, DC.	Am J Surg Pathol. 2005 Jan;29(1):39-51. Abstract quote Benign epithelioid peripheral nerve sheath tumors (BEPNSTs) have not been fully characterized, and their relationship to conventional schwannoma and neurofibroma has not been satisfactorily established. Herein, we detail the clinicopathologic features of 33 examples of BEPNST. The study included 22 females and 11 males ranging in age from 2 to 68 years (median, 31.5 years). Only one patient probably has neurofibromatosis type 1. The tumors were predominantly dermal/subcutaneous in location (85%) and involved the lower limb (n = 15), upper limb (n = 11), trunk (n = 4), and head/neck (n = 3). The lesions ranged in size from 0.3 to 6.8 cm (median, 1.1 cm). Microscopically, the tumors were generally well-circumscribed, uninodular, or multinodular masses. Twenty-six lesions were encapsulated. Tumors consisted of trabeculae, loosely arranged nodules, and cohesive nests of epithelioid tumor cells immersed in collagenous, myxohyaline, or chiefly myxoid stroma. A bland spindled cell component comprising 5% to 40% of the tumor was noted in 15 cases. Mitotic activity ranged from 0 to 6 mitoses/50 high power fields (mean, 1.5 mitoses/50 high power fields) with no abnormal division figures identified. Five lesions were considered atypical based on presence of focal nuclear/nucleolar enlargement and hyperchromasia. Immunohistochemical reactivity for Schwann cell-related markers in tumor cells included S-100 protein (20 of 20 cases), collagen type IV (10 of 10), laminin (8 of 8), nerve growth factor receptor, p75(7 of 8), CD57 (6 of 9), and glial fibrillary acidic protein (8 of 15). CD34-positive fibroblast-like cells were identified in all 12 neoplasms tested. Anti-epithelial membrane antigen highlighted perineurial cells in 9 of the 11 encapsulated tumors. Anti-neurofilament protein did not identify intralesional neuraxons in the 10 tumors evaluated. Eighteen tumors were subtyped as epithelioid neurofibromas. The remaining 15 cases showed some histologic features suggestive of schwannoma, but their uniform cellularity, absence of nuclear palisading, and presence of a significant CD34-positive spindled cell population in 5 cases led to their classification as "BEPNST of indeterminate histogenesis." Evaluation for loss of heterozygosity in 2 cases demonstrated deletion of genetic material on chromosome 22q and 17q involving NF2 and NF1 loci. However, sequencing of NF2 coding sequences revealed no mutations. Follow-up for 18 patients (median interval, 13.5 years), including 4 patients with tumors exhibiting cytologic atypia, revealed a nondestructive recurrence or persistent disease in 3 patients whose tumors lacked atypia, but no evidence of metastatic spread or tumor-related death. BEPNSTs are usually small neoplasms located in superficial soft tissue and have an excellent prognosis after complete local excision. Accurate subclassification of some of these lesions is difficult based on currently available techniques.
Expanding the Spectrum of Malignant Change in Schwannomas Epithelioid Malignant Change, Epithelioid Malignant Peripheral Nerve Sheath Tumor, and Epithelioid Angiosarcoma: A Study of 17 Cases Máirín E. McMenamin, M.B., M.R.C.P.I., M.R.C.Path.; Christopher D. M. Fletcher, M.D., F.R.C.Path. From the Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, U.S.A.	Am J Surg Pathol 2001;25:13-25 Abstract quote Schwannomas (neurilemmomas) rarely undergo malignant change, most often in the form of either malignant peripheral nerve sheath tumor (MPNST) or angiosarcoma. We characterize the clinical features and the histopathologic spectrum of 17 schwannomas with evidence of malignant change. The study group comprised 7 males and 10 females with an age range of 16 to 76 years, (median, 40 yrs). None of the patients had neurofibromatosis. Lesions ranged in size from 0.6 to 10.5 cm (median, 4.0 cm) and arose mainly in the limbs/limb girdles (7 cases) or head and neck region (7 cases). All tumors contained areas of conventional benign schwannoma. Four cases of pure epithelioid malignant peripheral nerve sheath tumor (EMPNST) were identified, three of which showed immunopositivity for S-100 protein. Four angiosarcomas were identified, predominantly epithelioid-type. Ten schwannomas had an appearance that we have designated epithelioid malignant change (EMC) and, in one of these, EMC coexisted with EMPNST. Large epithelioid cells with abundant eosinophilic cytoplasm, vesicular chromatin, and prominent nucleoli (morphologically similar to cells of EMPNST) were distributed throughout the schwannoma—singly, in clusters, and in one case a microscopic nodule of such cells was also present. These large epithelioid cells were strongly positive for S-100 protein. Although follow-up data so far are limited, 1 of 5 patients with EMC in whom meaningful follow up was available developed repeated local recurrence (median follow up, 21 mos), one patient each with EMPNST and angiosarcoma died of local and metastatic disease. Pure EMPNST is rare; however, we confirm the tendency of MPNST to show epithelioid cytomorphology when arising in a benign schwannoma. We also confirm the distinctive (albeit infrequent) tendency of angiosarcoma to arise in schwannomas. We describe EMC in schwannomas and suggest that this represents a putative precursor lesion of EMPNST. At this time, we do not have an explanation for the tendency of schwannomas to show epithelioid cytomorphology when they undergo malignant change.
LIPOBLASTIC
Lipoblastic nerve sheath tumors: report of a distinctive variant of neural soft tissue neoplasm with adipocytic differentiation. Plaza JA, Wakely PE Jr, Suster S. Department of Pathology, Division of Anatomic Pathology, Ohio State University, Columbus, OH.	Am J Surg Pathol. 2006 Mar;30(3):337-44. Abstract quote   Benign nerve sheath tumors of soft tissue can occasionally adopt unusual or unfamiliar morphologic appearances that may introduce difficulties for diagnosis, such as multinucleation, bizarre nuclei, intranuclear vacuoles, and other degenerative changes. Tumor cells adopting a signet-ring or lipoblast-like configuration, however, are mostly associated with epithelial malignancies, liposarcoma and melanoma, and have been only rarely observed in spindle cell tumors of soft tissue. We report 5 cases of benign nerve sheath neoplasms that displayed prominent signet-ring cells with lipoblast-like features. The cases presented as solitary soft tissue masses in the groin, thigh, retroperitoneum, and shoulder in 4 men and 1 woman between the ages of 31 to 57 years. Four tumors predominantly showed features of schwannoma and one of neurofibroma; however, intimately admixed with the spindle cell population, there were also numerous scattered mature adipocytes as well as lipoblast-like cells displaying a signet-ring cell appearance. Immunohistochemical studies showed strong S-100 protein positivity in the spindle cells as well as in the signet-ring lipoblast-like cells and the mature adipocytes. The signet-ring cells were negative for mucin stains, cytokeratin, EMA, CEA, and several other differentiation markers. Ultrastructural examination was performed in 2 cases. The signet-ring cells contained large cytoplasmic lipid droplets that displaced the nuclei to the periphery, consistent with lipoblastic differentiation, whereas complex, interdigitating cytoplasmic processes covered by basal lamina material characteristic of nerve sheath differentiation could be identified in the spindle cells. Four patients for whom follow-up was available were alive and well with no evidence of recurrence over a period of 28 to 116 months (median follow-up, 50 months). The presence of mature fat and signet-ring lipoblast-like cells within a nerve sheath neoplasm is quite rare and may signify a process of aberrant differentiation. Neurogenic tumors should be added in the differential diagnosis of spindle cell tumors capable of displaying prominent signet-ring cell features.
MELANOTIC
Multiple melanotic schwannoma. cUlhaci N, Dikicioglu E, Meteoglu I, Boylu S.	Ann Diagn Pathol. 2003 Aug;7(4):254-8 Abstract quote Melanotic schwannoma is a rare pigmented neural tumor most commonly occurring in the paraspinal region. In a small minority of instances, melanotic schwannoma may have multiple nodules. Here, a 52-year-old woman is presented with multiple melanotic schwannomas of paraspinal region.
NEUROBLASTOMA-LIKE (ROSETOID)
Rosetoid schwannoma (neuroblastoma-like) in association with an anetoderma. Velez D, Reina Duran T, Perez-Gala S, Fernandez JF.	J Cutan Pathol. 2006 Aug;33(8):573-6. Abstract quote We report an additional case of an extremely uncommon but distinctive histological variant of benign schwannoma, which was previously designated as neuroblastoma-like schwannoma by Goldblum et al. A 29-year-old woman referred to a 6-year-history of an atrofic macule. Its clinical appearance was similar to that of an anetoderma. A cutaneous biopsy showed findings consistent with a neuroblastoma-like schwannoma with the following peculiar features: (i) Being fully composed of rosette-like structures. (ii) Association to an anetoderma. Because neither the histological pattern nor the type of tumor allows a differential diagnosis with neuroblastoma, we propose the descriptive term of rosetoid schwannoma. And to our knowledge, this will be the first case reported of rosetoid schwannoma associated to anetoderma.
Schwannoma with Neuroblastoma-Like Rosettes: An Unusual Morphologic Variant. Lewis ZT, Geisinger KR, Pichardo R, Sangueza OP. From the *Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, North Carolina; and daggerDepartment of Dermatology, Wake Forest University School of Medicine, Winston-Salem, North Carolina.	Am J Dermatopathol. 2005 Jun;27(3):243-246. Abstract quote   In the past ten years, seven cases of schwannomas with giant fibrillar rosettes or perivascular rosettes have been reported. As these unusual variants of schwannomas had areas with hyperchromatic, small round cells recapitulating the appearance of a neuroblastoma, they received the descriptive name of neuroblastoma-like schwannomas. We herein report two additional cases of this unique variant of schwannoma and provide differential diagnostic considerations.
Neuroblastoma-like schwannoma: a case report and review of the literature. Somerhausen Nde S, Valaeys V, Geerts M, Andre J.	Am J Dermatopathol 2003 Feb;25(1):32-4 Abstract quote We report a case of schwannoma (neurilemmoma) predominantly composed of small cells arranged in rosettes around central collagenous cores and discuss the differential diagnosis of this unusual variant. Schwannoma with giant rosettes, previously designated as neuroblastoma-like schwannoma by Goldblum et al., must be differentiated from neuroblastoma, peripheral neuroectodermal tumors, and malignant change in a schwannoma.
PERINEURIOMA
Hybrid peripheral nerve sheath tumors: Schwannoma-perineurioma and neurofibroma-perineurioma. A report of three cases in extradigital locations. Kazakov DV, Pitha J, Sima R, Vanecek T, Shelekhova K, Mukensnabl P, Michal M. Sikl's Department of Pathology, Charles University, Medical Faculty Hospital, 30460 Pilsen, Czech Republic.	Ann Diagn Pathol. 2005 Feb;9(1):16-23. Abstract quote   We present three cases of subcutaneous tumors with hybrid features of schwannoma-perineurioma (one case) and neurofibroma-perineurioma (two cases), which occurred in two women aged 50 and 52 years and one man aged 52. Locations included the scapular area, skin overlying breast and knee area. The tumors were 1.5, 4 and 5 cm in largest diameter. None of the patients had signs of neurofibromatosis. All tumors were surgically removed, and patients remained disease-free for 1 to 4 years. The classification of the lesion into schwannoma-perineurioma and neurofibroma-perineurioma rested on histopathological and immunohistochemical findings. An ultrastructural study was performed in one case of neurofibroma-perineurioma. All cases were studied for mutation of the NF2 gene, and in one case (neurofibroma-perineurioma) a point mutation was detected in exon 15 of the gene.
PLEXIFORM
Plexiform schwannoma: a clinicopathologic overview with emphasis on the head and neck region. Berg JC, Scheithauer BW, Spinner RJ, Allen CM, Koutlas IG. Department of Pathology, Mayo Clinic, Rochester, MN 55905, USA.	Hum Pathol. 2008 May;39(5):633-40. Abstract quote Plexiform schwannoma is a rare variant of Schwann cell tumor. Occurring in either conventional or cellular type, they are characterized either grossly or histologically by a plexiform pattern of intraneural growth often with multinodularity. Ordinary as well as plexiform schwannoma typically arise in superficial soft tissues and show a predilection for the head and neck region. Infrequent examples arise in the setting of neurofibromatosis type 2 or schwannomatosis. The purpose of this study was to assess the frequency of plexiform schwannoma by location, to determine their syndromic association, and to analyze the clinicopathologic features of tumors affecting the head and neck region. It was found, in this not entirely random population, that plexiform schwannoma represented 4.3% of all schwannomas, 23% of head and neck region examples, 15% of cutaneous schwannomas, and lastly, 2% of 322 oral nerve sheath tumors made separately available for review. Furthermore, the association with neurofibromatosis type 2 and with schwannomatosis was 5% each.
Plexiform Epithelioid Schwannoma:: A Case Report. Gao Z, Palleschi SM, Chen S. From the *Department of Pathology; and daggerDepartment of Surgery, Albert Einstein College of Medicine Long Island Jewish Medical Center, New Hyde Park, NY.	Am J Dermatopathol. 2007 Feb;29(1):56-58. Abstract quote Epithelioid schwannoma is rare but may pose a challenge in histopathologic diagnosis. In the present report, we describe a plexiform variant of epithelioid schwannoma in the skin of the breast of a 47-year-old woman.
Deep-seated plexiform schwannoma: a pathologic study of 16 cases and comparative analysis with the superficial variety. Agaram NP, Prakash S, Antonescu CR. From the Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY.	Am J Surg Pathol. 2005 Aug;29(8):1042-8. Abstract quote   Plexiform schwannoma (PS) is one of the least common histologic variants of schwannoma. It shows a plexiform growth pattern and typically occurs in the dermis and subcutaneous tissue. Morphologically, PS can display a conventional, cellular, or mixed appearance. However, the frequent cellular morphology associated with hyperchromatic nuclei, increased mitoses, and plexiform growth can suggest a malignant process, mainly a high-grade malignant peripheral nerve sheath tumor (MPNST). The purpose of this study was to analyze the clinicopathologic features of deep-seated PS and compare them with the superficial counterparts. Sixteen deep-seated PSs were analyzed clinicopathologically, immunohistochemically, and ultrastructurally, and compared with 8 superficial (5 dermal and 3 subcutaneous) PSs. There were 12 females and 4 males, ranging from 5 months to 61 years of age. Fifteen tumors were located in the deep somatic soft tissue (extremities, 8; retroperitoneum/pelvis, 3; trunk, 2; parotid, 1; vulva, 1) and 1 tumor was located in the thoracic esophagus. None of the patients had stigmata of neurofibromatosis. Local recurrence was noted in half of the patients with clinical information available, but none had evidence of disease at last follow-up. Worrisome morphologic features included: increased cellularity (68%), mild to moderate pleomorphism (50%), and mitotic activity (93%) ranging from 1 to 10 MF/10 high power fields (HPFs). Focal necrosis was seen in 12% and myxoid change was identified in 18% of cases. Immunohistochemical stains for S-100 protein showed strong and diffuse positivity on all cases tested. Ultrastructurally, findings characteristic of schwannian differentiation were identified in the cases analyzed. The 8 superficial PSs showed increased cellularity and mild to moderate pleomorphism in 62% of cases but lacked tumor necrosis. Deep-seated PS is a rare, underrecognized PNST of deep soft tissue, typically not associated with neurofibromatosis. Although commonly occurring in the extremities, they can be seen in other locations including the viscera. In contrast with the more common superficial (dermal and subcutaneous) tumors, deep PSs have a predilection for females, can occur in congenital settings, and can show necrosis and myxoid change. Common worrisome histologic features seen in both groups include increased cellularity and mitoses. It is important to differentiate these tumors from plexiform neurofibromas and MPNSTs as they follow a benign clinical course, with complete surgical excision being curative.
Congenital and childhood plexiform (multinodular) cellular schwannoma: a troublesome mimic of malignant peripheral nerve sheath tumor. Woodruff JM, Scheithauer BW, Kurtkaya-Yapicier O, Raffel C, Amr SS, LaQuaglia MP, Antonescu CR.	Am J Surg Pathol. 2003 Oct;27(10):1321-9. Abstract quote   SUMMARY: We present six cases of a plexiform nerve sheath tumor of childhood that previously had been designated a form of malignant peripheral nerve sheath tumor (MPNST), and we provide evidence that such tumors are in fact benign plexiform cellular schwannomas. At presentation, the four girls and two boys ranged in age from 2 to 15 months with tumors of the leg (four), deep groin and upper thigh (one), and pelvis (one). Of the six lesions, five were congenital and none was associated with type 1 neurofibromatosis. Tumor sizes ranged from 2.0 to 9 cm, with three larger than 5 cm. Three tumors were well circumscribed, two were purely infiltrative, and one had a mixed circumscribed and infiltrative growth pattern. Peripheral nerve involvement was evident in two cases. Grossly, the tumors were multinodular or plexiform in configuration and, on sectioning, lobulated and homogeneously tan without necrosis. Characteristic histologic features included hypercellularity, composition of cells spindle in shape with elongate hyperchromatic nuclei, and indistinct cellular outlines. Their nuclei varied minimally in size and shape but were at least three times the size of typical neurofibroma nuclei. Mitoses were seen in every tumor and in the areas of greatest proliferative activity ranged from 4 to 31/10 high power fields. MIB-1 staining of at least 30% of the cells was noted in three cases. In five cases in which p53 immunoreactions were performed, no nuclear staining was evident. That the tumors are schwannomas was evident from their uniform strong staining for S-100 protein and an ultrastructure in all five cases showing only differentiated neoplastic Schwann cells. Architecturally, the tumors differed from conventional schwannoma and nonplexiform cellular schwannomas by their lack of both well-formed capsules and degenerative changes. Follow-up was available in all cases and ranged from 2 to 13.6 years. All tumors recurred locally and were treated by local resections. With the exception of one child lost to follow-up at 25 months, all the children are alive and free of disease. Our data combined with cases previously reported by Meis-Kindblom and Enzinger show a childhood peripheral nerve tumor unassociated with type 1 neurofibromatosis, occurring most commonly in infants, often presenting as a congenital tumor and, though prone to local recurrence, having no metastatic potential. The behavior is that of a benign tumor, although its often rapid growth, hypercellularity and increased mitotic activity, sometimes locally aggressive behavior, and difficulties encountered in obtaining tumor-free margins are unsettling to pathologist and clinician alike. These features may lead to a misdiagnosis of malignancy, which could result in harmful overtreatment.
PSEUDOGLANDULAR ELEMENTS
Benign cutaneous pseudoglandular schwannoma: a case report. Deng A, Petrali J, Jaffe D, Sina B, Gaspari A. Department of Dermatology, University of Maryland, Baltimore, Maryland 21201, USA.	Am J Dermatopathol. 2005 Oct;27(5):432-5. Abstract quote   Schwannoma is a common peripheral neural neoplasm that could present as a primary skin lesion. In addition to typical schwannoma with classic Antoni A and Antoni B areas, many variant types have been described, such as plexiform, cellular, epithelioid, and ancient schwannomas. Glandular schwannoma is a rare variant characterized by the presence of glands in an otherwise typical schwannoma. There are also a few reported cases in the literature of pseudoglandular schwannoma from central nervous system, eye, submandible, and shoulder, in which the gland-like structures were lined by Schwann cells. We report here a patient with a benign cutaneous schwannoma composed of predominantly gland-like spaces that contained mucinous material and were lined by Schwann cells confirmed by immunohistochemistry and ultrastructural studies. The tumor was well circumscribed and showed minimal cytologic atypia, indicating benignity. We report this unusual case of benign cutaneous pseudoglandular schwannoma to further awareness of the morphologic diversity of schwannoma.
Pseudoglandular elements in schwannomas. Robinson CA, Curry B, Rewcastle NB. Department of Pathology, University of Calgary and Foothills Medical Center, Calgary, Alberta, Canada.	Arch Pathol Lab Med. 2005 Sep;129(9):1106-12 Absract quote   CONTEXT: Uncommon examples of schwannomas are seen in which a coexisting glandular component is present. The pseudoglandular schwannoma is a relatively recently described variant in which cystic spaces are lined by pseudocolumnar or cuboidal-like neoplastic Schwann cells exhibiting an epithelial-like appearance. OBJECTIVES: To determine the incidence of pseudoglandular elements in schwannomas, to describe the variable morphology of the schwannomas that may contain pseudoglandular elements, and to discuss the potential mechanisms of development and biological significance of these elements. DESIGN: We screened 202 schwannomas from any anatomic site for the presence of pseudoglandular elements and examined these with light microscopy, immunohistochemistry, and electron microscopy. RESULTS: Sixteen (7.9%) of the schwannomas contained pseudoglandular elements, which ranged from poorly to well organized in appearance and which were found in schwannomas exhibiting a wide range of morphologic appearances. The Schwann cell nature of the cells composing these elements was apparent both immunohistochemically and ultrastructurally. The frequency of proliferative activity within these elements was no greater than that observed throughout the remainder of the respective schwannomas. CONCLUSIONS: Our observations suggest that, rather than representing a distinct phenotypic schwannoma variant, pseudoglandular elements likely arise as a response to a degenerative phenomenon, perhaps reflecting the propensity that the Schwann cell has to palisade formation. Such elements may be found within a variety of schwannoma variants and do not appear to possess a unique growth potential.
SIGNET RING
Signet ring cell gastric schwannoma: report of a new distinctive morphological variant. Tozbikian Rulong Shen G, Suster S. Department of Pathology, The Ohio State University Medical Center, Arthur G. James Cancer Center, Columbus, OH.	Ann Diagn Pathol. 2008 Apr;12(2):146-52. Abstract quote An 89-year-old woman was seen for indigestion, light chest pain, and melanotic stools. Endoscopic examination revealed 2 submucosal gastric masses. A subtotal gastrectomy showed 2 submucosal masses in the stomach: one infiltrating through the muscularis propria into the serosa, the second one, a well-circumscribed submucosal nodule. Histologic examination showed large tumor cells infiltrating diffusely through the muscularis propria into the subserosa. On higher magnification, numerous signet ring cells were present against a myxoid stroma, in addition to large vacuolated epithelioid cells. There was no evidence of invasion, necrosis, nuclear pleomorphism, or mitotic activity. Initial diagnostic considerations based on the histology included signet ring cell carcinoma, malignant melanoma, and a myxoid mesenchymal tumor, including gastrointestinal stromal tumor. A panel of immunohistochemical stains showed diffuse strong positivity for S-100 protein and negative reaction for CD117, bcl-2, cytokeratin AE1/AE3, Melan-A, HMB45, smooth muscle antigen, and other differentiation markers. Electron microscopic examination revealed elongated, complex, and interdigitating cell processes covered by a thin layer of continuous basement membrane material characteristic of peripheral nerve sheath differentiation. The presentation of this tumor was significant in that it was multifocal and infiltrative, mimicking a malignant neoplasm. The extensive myxoid/signet ring cell change represents a heretofore-unreported histologic variant of gastric schwannoma.

 

SPECIAL STAINS/ IMMUNOPEROXIDASE/ OTHER	CHARACTERIZATION
Special stains
Immunoperoxidase	S100 positive
EPIDERMAL GROWTH FACTOR RECEPTOR
Epidermal growth factor receptor is not amplified in schwannomas. Prayson RA, Yoder BJ, Barnett GH. Department of Anatomic Pathology (L25), Cleveland Clinic Foundation, Cleveland, OH 44195, USA.	Ann Diagn Pathol. 2007 Oct;11(5):326-9. Abstract quote Epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor of the ErbB family. This family of receptors plays an active role in cellular growth and mitogenesis. It is well established that the overexpression of ErbB receptors in human cancers, most commonly because of true genomic amplification, correlates with a more aggressive clinical course. There is limited data published on the expression and amplification of EGFR in schwannomas. Both neurofibromas and schwannomas are capable of progression to malignant peripheral nerve sheath tumors (MPNSTs). A subset of human MPNSTs, both NF-1-related and sporadic, overexpress EGFR via true genomic amplification of the short arm of chromosome 7 (7p12). The goal of this study is to assess whether EGFR is expressed and/or amplified in human schwannomas. Twenty schwannomas in 12 women and 8 men (mean age, 51 years) were analyzed for EGFR expression via immunohistochemistry and fluorescence in situ hybridization. None of the 20 cases were positive for EGFR expression via immunohistochemistry; 3 tumors showed focal nonspecific Golgi staining. None of the cases demonstrated true genomic amplification of the EGFR region via fluorescence in situ hybridization. The mitogenic signaling for schwannomas is unlikely to be related to overexpression or amplification of EGFR; however, acquiring this signaling pathway might contribute to the progression of a subset of benign peripheral nerve sheath tumors to MPNST.
KERATIN
Keratin expression in schwannoma; a study of 115 retroperitoneal and 22 peripheral schwannomas. Fanburg-Smith JC, Majidi M, Miettinen M. 1Department of Soft Tissue Pathology, Armed Forces Institute of Pathology, Washington, DC, USA.	Mod Pathol. 2006 Jan;19(1):115-21 Abstract quote.   Schwannomas have been variably observed to be glial fibrillary acid protein (GFAP) and occasionally keratin positive, with antibodies reacting with multiple keratins (pankeratins, keratin cocktail (CK), but specific keratin polypeptides (K) have not been examined for in schwannoma. Since we observed CK positivity in retroperitoneal schwannomas, we wanted to study a large group of retroperitoneal and peripheral schwannomas with GFAP, CK and Ks to explore the frequency and biologic background of this finding. We immunohistochemically evaluated a large number of retroperitoneal (n=115) and peripheral schwannomas (n=22) for GFAP, 16 individual K and AE1/AE3 keratin cocktail. The great majority (104/115, 90%) of retroperitoneal schwannomas were positive for GFAP, and 72/104 (69%) cases were positive for AE1/AE3, often extensively. Both markers highlighted the cellular Antoni A areas, particularly adjacent to the capsule, myxoid or degenerative areas, and perivascularly. Most cases 87/104 (84%) stained for both AE1/AE3 and GFAP at least focally. No tumors stained for keratins that were GFAP negative. None of the immunostains for individual K showed positivity comparable to that obtained with AE1/AE3 CK. However, 62% were focally positive for high molecular weight K1 and 8/61 (13%) for K7. None of the retroperitoneal schwannomas were positive for other keratins including K2, 4, 5, 8, 9, 10 and K14-20. Peripheral schwannomas showed GFAP-positivity in only three of 22 cases (14%), and all were negative for keratins, both cocktail and individual K. We conclude that crossreactivity of AE1/AE3 with other intermediate filament proteins, such as GFAP, as previously observed in brain and glioma tissue, probably accounts for the extensive keratin-positivity seen in some retroperitoneal schwannomas. However, focal expression of K1 and K7 cannot be ruled out. Keratin-positive schwannomas should not be confused with other keratin-positive tumors, such as sarcomatoid carcinoma, mesothelioma, and synovial sarcoma.

 

PROGNOSIS AND TREATMENT	CHARACTERIZATION
Treatment	Excision
BRAINSTEM TUMORS
Management of bilateral acoustic neuroma. Glasscock ME 3rd, Hart MJ, Vrabec JT. Otology Group, Vanderbilt Medical Center North, Nashville, Tennessee.	Otolaryngol Clin North Am 1992 Apr;25(2):449-69 Abstract quote This article has reviewed the genetic disorder, neurofibromatosis 2. The history, nomenclature, genetic etiology, epidemiology, diagnostic criteria, pathogenesis, and presentation of neurofibromatosis 2 have been given. A related but distinctly different disorder, neurofibromatosis 1, has also been described. The diagnostic evaluation of neurofibromatosis 2 has been discussed with an emphasis on the importance of early diagnosis. An analysis of the surgical treatment of bilateral acoustic neuromas as well as nonsurgical therapeutic alternatives has been presented. The results and complications in the operative management of 86 acoustic tumors in 49 patients with neurofibromatosis 2 have been described in detail. The poor immediate hearing results and the even poorer long-term hearing results have been examined in light of the invasive histopathology of these tumors. It has been emphasized that patients with neurofibromatosis 2 and asymptomatic family members require comprehensive, multidisciplined, long-term management.
A review of facial nerve outcome in 100 consecutive cases of acoustic tumor surgery. McElveen JT Jr, Belmonte RG, Fukushima T, Bullard DE. Carolina Ear and Hearing Clinic, PC, Raleigh, North Carolina 27609, USA.	Laryngoscope 2000 Oct;110(10 Pt 1):1667-72 Abstract quote OBJECTIVE: To determine the facial nerve outcomes at a tertiary neurotological referral center specializing in acoustic neuroma and skull base surgery. STUDY DESIGN: Retrospective review of 100 consecutive patients in whom acoustic neuromas were removed using all of the standard surgical approaches. METHODS: Functional facial nerve outcomes were independently assessed using the House-Brackmann facial nerve grading system. RESULTS: The tumors were categorized as small, medium, large, and giant. If one excludes the three patients with preoperative facial palsies, 100% of the small tumors, 98.6% of the medium tumors, 100% of the large tumors, and 71% of the giant tumors had facial nerve function grade I-II/VI after surgery. CONCLUSION: Facial nerve results from alternative nonsurgical treatments must be compared with facial nerve outcomes from experienced surgical centers. Based on the facial nerve outcomes from our 100 consecutive patients, microsurgical resection remains the preferred treatment modality for acoustic tumors.
Radiosurgery of residual and recurrent vestibular schwannomas. Unger F, Walch C, Papaefthymiou G, Feichtinger K, Trummer M, Pendl G. Department of Neurosurgery, Karl-Franzens University, Graz, Austria.	Acta Neurochir (Wien) 2002 Jul;144(7):671-7 Abstract quote SUMMARY:Radiosurgery is either a primary or an adjunctive management approach used to treat patients with vestibular schwannomas. We sought to determine outcomes measuring the potential benefits against the neurological risks in patients who underwent radiosurgery after previous microsurgical subtotal resection or recurrence of the tumour after total resection. Gamma Knife radiosurgery was applied as an adjunctive treatment modality for 86 patients with vestibular schwannomas from April 1992 to August 2001. We evaluated the results of 50 patients who had a follow-up of at least 3.5 years (median 75 months, range 42-114 months). In 16 patients a recurrence of disease was observed after previous total resection. The median treatment volume was 3.4 ccm with a median dose to the tumour margin of 13 Gy. Tumour control rate was 96%. Two tumours progressed after adjunctive radiosurgery. Useful hearing (Gardner-Robertson II) (4 patients (8%)) and residual hearing (Gardner-Roberson III) (10 patients (20%)) remained unchanged in all patients, who presented with it before radiosurgery, respectively. Clinical neurological improvement was observed in 24 patients (46%). Adverse effects comprised transient neurological symptoms and signs (incomplete facial palsy, House-Brackman II/III) in five cases (recovered completely), mild trigeminal neuropathy in four cases, and morphological changes displaying rapid enlargement of a pre-existing macrocyst in one patient and tumour growth in another one. No permanent new cranial nerve deficit was observed. Radiosurgery appears to be an effective adjunctive method for growth control of vestibular schwannomas and is associated with both a low mortality rate and a good quality of life. Accordingly, radiosurgery is a rewarding therapeutic approach for the preservation of cranial nerve function in the management of patients with vestibular schwannoma in whom prior microsurgical resection failed.

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Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
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Antoni A and B-This describes 2 histologic patterns commonly present in these tumors. Antoni A refers to a more cellular pattern while Antoni B is less cellular with more myxoid changes.

Neurofibromatosis

Verocay bodies-A pattern with nuclear palisading, commonly present in Antoni A areas.

Soft Tissue Tumors

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Last Updated May 20, 2008

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