“Malignant” foot drop: Enzinger epithelioid sarcoma of the common fibular nerve

Abstract

Enzinger first characterized a peculiar sarcoma with epithelioid features, arising from tendons and aponeuroses. 1 Enzinger epithelioid sarcoma (EES) has an indolent and unpredictable behavior. Its prognosis is difficult to establish, distant metastases may occur, and long-term follow-up is necessary (overall 5-year survival is 45%). 2 EES is a very rare tumor of still unknown histogenesis. On immunohistochemical staining, it is positive for vimentin, cytokeratin, and epithelial membrane antigen (EMA), whereas staining is negative with the neural derived S-100 protein and the nuclear antigen INI-1. The latter is maintained in most epithelioid tumors that mimic EES, such as epithelioid vascular tumors, metastatic carcinomas, and melanomas. 3-5 On the other hand, epithelioid malignant peripheral nerve sheath tumors (EMPNSTs) and epithelioid malignant schwannomas (EMSs) frequently lose INI-1, but they always stain positively with S-100. 5,6 The possible origin of EES from nerve is still controversial. We report a unique observation of a well-characterized EES rising from the common fibular nerve.A 50-year-old, healthy man came to our attention due to a 3-month history of left foot drop with a positive Tinel sign at the fibular head. Knee MRI showed a nodular lesion with inhomogeneous contrast enhancement involving the common fibular nerve. On surgical exploration a malignant infiltrating mass was found inside the nerve. Careful microscopic dissection allowed complete removal of the lesion, sparing about 30% of nerve fascicles and achieving an end-to-side neurorrhaphy of the amputated fascicles. Histologic examination revealed a malignant, infiltrating lesion sparing regional and inguinal lymph nodes. Immunohistochemical stains were positive for vimentin, cytokeratin, EMA, and CD34, whereas INI-1, S-100, endothelial markers (CD31, FLI-1), podoplanin, desmin, and glial fibrillary acidic protein were absent. Such an immunophenotype was consistent with a diagnosis of EES. A total body computed tomography (CT) scan did not reveal any other localization. One year later, follow-up CT scan revealed tumor recurrence in lumboaortic lymph nodes, confirmed by biopsy. The patient underwent 5 courses of epirubicin (105 mg/m 2 ) and ifosfamide (9,000 mg/m 2 ) therapy, combined with radiotherapy (60 Gy), resulting in complete regression of the tumor. At last follow-up, 5 years after diagnosis, the patient had a stable foot drop (MRC 2-3/5) and no clinical or radiological sign of disease recurrence.Two previous reports described possible EES involving nerves (sciatic and median), but they lacked complete characterization. 7,8 A third case of sciatic nerve involvement was probably an EMS due to its S-100 positivity. 9 Indeed, like EES, EMS and EMPNST stain positively for vimentin and epithelial markers (cytokeratin or EMA), but they also show S-100 positivity. 6,10-12 EES should be distinguished from other epithelioid malignant neoplasms of nerves (EMS and EMPNST) showing a loss of INI-1, and its core feature is the absence of both I...