Brain Pathology Case of the Month - July 2007

FINAL DIAGNOSIS :   CELLULAR SCHWANNOMA

DISCUSSION:

Schwannoma is infrequently located intracranially, forming approximately 8% of all primary intracranial neoplasms with an affinity for the cerebellopontine angle region [1]. Cellular schwannoma, described by Woodruff in 1981 [2], is considered a variant of schwannoma and comprising about 10% of all schwannomas [1].

The most common location of cellular schwannoma is the paravertebral region with the sacral site constituting 64% of all neoplasms [3]. The intracranial location accounts for 8% of all cellular schwannomas. The retrobulbar region is an extremely uncommon site for this tumor and to the best our knowledge, our current case forms the fourth case after those described by Casadei et al [3] and Huang et al [4].

Cellular schwannoma is generally encapsulated and sometimes associated with a nerve [3]. On histology, unlike classical schwannoma, cellular schwannoma discloses a markedly increase in cellularity, comprising fascicles of spindle cells which can occasionally be associated with herringbone or storiform pattern. Compact and hypercellular fascicles recapitulating Antoni-A areas can be identified. Although classical Verocay bodies are seldom identified, there may be occasional suggestion of palisades [3-6]. Antoni-B areas are, however, not prominently featured [3]. The spindle cells may exhibit mild nuclear atypia [4, 6]. Thick-walled blood vessels usually displayed in classic schwannoma are also present in the cellular variant [3-4]. Microscopic areas of necrosis may be observed in cellular schwannoma, but geographic necrosis seen in malignant peripheral nerve sheath tumor (MPNST) is absent [3,6,7]. Mitotic activity usually does not exceed 4 per 10 high power fields [3-5] although in plexiform cellular schwannoma in childhood, a mitotic index of up to 31 per 10 high power fields has been reported [8].

Cellular schwannoma is strongly positive for S100 protein and vimentin [3]. Glial fibrillary acidic protein (GFAP) is variably positive [3-6]. The striking feature seen ultrastructurally is the presence of numerous tightly packed intertwined cell processes [3] as identified in our case. Primitive intercellular junctions and cell membranes abutting stroma and covered by well developed continuous and occasionally duplicated basement membranes, are also present. Luse bodies may be absent.

In the retrobulbar region, a diagnosis of meningioma may be considered, since the tumor cells in a cellular schwannoma may form whorls [3]. However the presence of areas resembling Antoni A in association with a negative staining for EMA militates against a diagnosis of meningioma. Glial tumors enter the differential diagnosis given the findings of GFAP positivity within the tumor. However careful discernment of Antoni A-like areas and ultrastructural findings on electron microscopy in conjunction with the clinical and radiological findings favor a diagnosis of cellular schwannoma in our case.

Cellular schwannoma may be mistaken for malignant peripheral nerve sheath tumor (MPNST) due to its association with increased cellularity, nuclear atypia, mitotic activity, necrotic foci, bony erosion, and tumor recurrence [3-6]. However, a MPNST [7] is usually more cellular, associated usually with a higher degree of anaplasia, lacks the thick walled hyalinised blood vessels and usually demonstrates only focal S-100 positivity on immunohistochemistry. In the orbital region, a solitary fibrous tumor has been confused for a schwannoma [9].

While metastases and death have not been described in cellular schwannoma [3-6], recurrences in incompletely resected cellular schwannoma have been documented, especially in sites where complete tumor resection is difficult to achieve (e.g. intraspinal or intracranial) [3, 4]. In such instances, mitotic count significantly correlates with the incidence of tumor recurrence [3] and close follow up is advocated.

References

1. Lantos PL, Louis DN, Rosenblum MK, Kleihues P. Tumours of the nervous system. In : Greenfield's neuropathology. Graham DI, Lantos PL, eds. 7th ed. London : Arnold, 2002:898-902
2. Woodruff JM, Susin M, Godwin TA, Martini N, Erlandson RA. Cellular schwannoma : a variety of schwannoma sometimes mistaken for a malignant tumor. Am J Surg Pathol 1981;5:733-744
3. Casadei GP,Scheithauer BW, Hirose T, Manfrini M, Wood MB. Cellular schwannoma - a clinicopathologic, DNA flow cytometric, and proliferation markers study of 70 patients. Cancer 1995;75:1109-1119
4. Huang WT, Chen WJ, Hsu HC, Cheng YF, Eng HL. Retrobulbar cellular schwannoma. Two cases report and review of the literature. Pathol Res Pract 2003;199:171-174
5. Fletcher CDM, Davies SE, McKee PH. Cellular schwannoma: a distinct pseudosarcomatous entity. Histopathology 1987;11:21-35
6. White W, Shiu MH, Rosenblum MK, Erlandson RA, Woodruff JM. Cellular schwannoma, a clinicopathologic study of 57 patients and 58 tumours. Cancer 1990;66:1266-1275
7. Hruban RH, Shiu MH, Senie RT, Woodruff JM. Malignant peripheral nerve sheath tumours of the buttock and lower extremity. A study of 43 cases. Cancer 1990;66: 1253-1265
8. Woodruff JM, Scheithauer BW, Kurtkaya-Yapicier O, Raffel C, Amr SS, LaQuaglia MP, Antonescu C. Congenital and childhood plexiform (multinodular) cellular schwannoma. A troublesome mimic of malignant peripheral nerve sheath tumor. Am J Surg Pathol 2003;27:1321-1329
9. Polito E, Tosi GM, Toti P, Schurfeld k, Caporossi A. Orbital solidarity fibrous tumor with aggressive behaviour. Three cases and review of literature. Graefe's Arch Clin Exp Ophthalmol 2002;240:570-574

Contributed by Hong Wui Tan, MRCPath, Seng Geok Nicholas Goh, FRCPA, Wai Ming Yap, FRCPath, Khoon Leong Chuah, FRCPA

International Society of Neuropathology