Microcystic/reticular schwannoma: a distinct variant with predilection for visceral locations

Schwannomas are benign, generally nonrecurring tumors most frequently arising in the subcutaneous tissue of adults with no sex predilection. Herein we report 10 cases of a distinctive morphologic variant of schwannoma with predominantly microcystic-reticular morphology and characterize the clinicopathologic spectrum. The age at presentation ranged from 11 to 93 years (median age 63 y). The tumor size ranged from 0.4 to 23 cm (median size 4.3 cm). Five tumors arose in the gastrointestinal tract, most often in the submucosa. Two cases arose in subcutaneous tissue and 1 case each in the upper respiratory tract, the adrenal gland, and deep soft tissue. None of the patients had features of neurofibromatosis type 1 or type 2 (NF1, NF2). Histologically 8 tumors were circumscribed but unencapsulated and 2 cases located in the subcutaneous fat were circumscribed and encapsulated. At visceral locations, focally pushing margins and microscopic foci of infiltration into surrounding parenchyma were seen. All cases showed a striking microcystic and reticular lesional growth pattern with anastomosing and intersecting strands of spindle cells with eosinophilic cytoplasm distributed around islands of myxoid or collagenous/hyalinized stroma. The nuclei were round, oval, and tapered and showed inconspicuous nucleoli. Three cases had smaller areas resembling conventional schwannoma. Mitotic activity did not exceed more than 3 mitoses/50 high-power fields (HPF) (median 1/30 HPF). Pleomorphism and necrosis were absent. All tumors showed strong nuclear and cytoplasmic positivity for S-100 and variably strong glial fibrillary acidic protein staining. A surrounding tumor capsule was highlighted with epithelial membrane antigen in 2 out of 10 cases. Smooth muscle actin, Desmin, Pan-CK, AE/AE3, Cam5.2, and p-63 were negative in all cases evaluated. Neurofilament protein highlighted axons in one out of 7 cases investigated. CD117 showed weak focal positivity in 1 out of 4 cases. Follow-up data were available in 7 cases (median duration 15 mo). None has recurred to date. Microcystic schwannoma represents a distinctive morphologic variant of schwannoma with predilection for visceral locations. Recognition of this distinct entity is essential to avoid confusion with malignant tumors, especially in the gastrointestinal and upper respiratory tracts.