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

Enzinger first characterized a peculiar sarcoma with epithelioid features, arising from tendons and aponeuroses. 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%). 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. 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. 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) and ifosfamide (9,000 mg/m) 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. A third case of sciatic nerve involvement was probably an EMS due to its S-100 positivity. Indeed, like EES, EMS and EMPNST stain positively for vimentin and epithelial markers (cytokeratin or EMA), but they also show S-100 positivity. 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 INI-1 and S-100. Nevertheless, diagnosis of EES remains one of exclusion due to the lack of a specific immunohistochemical marker. This report confirms that nerves may also be affected primarily by EES. We emphasize the possibility of a malignant origin of isolated foot drop and the importance of early diagnosis and intervention.