Superficial primitive neuroectodermal tumor/Ewing sarcoma (PN/ES): same tumor as deep PN/ES or new entity?

Primitive neuroectodermal tumor/Ewing sarcoma (PN/ES) is a single clinical, morphologic, and molecular small round cell tumor entity. These are generally found in deep soft tissue or bone of young male patients, with poor behavior. Location in dermis is unexpected; only rare cases are reported. Cases coded as "dermal," "cutaneous," or "skin" PN/ES were retrieved from our consultation files. Only primary dermal cases were included. Those otherwise diagnosed or with incomplete material were excluded. There were 13 dermal PN/ES cases, consisting of 10 women and 3 men. Ages ranged from 2 to 67 years (mean, 28 years). Locations included groin or thigh (4), back or shoulder (3), neck (1), chest (1), scalp (1), forehead (1), hand (1), and foot (1). Most cases were small (0.5-2.3 centimeters) and painful, and persisted for less than 1 year. All were located within the dermis. Three caused pedunculation; 9 also involved superficial subcutis. All but 1 of the metastasizing tumors were round and encapsulated. All were composed of round to oval cells with a vague rosetting pattern, slightly overlapping nuclei, finely stippled chromatin, clear to eosinophilic cytoplasm, and collagenous stroma. Median mitotic activity was 8 per 10 high-power fields. Necrosis was present in three cases. All had globular periodic acid Schiff positivity and distinctive cytoplasmic membrane CD99 reactivity. One case studied was positive for Fli-1. All were negative for leukocyte common antigen, Tdt, CD3, CD20, CD79, CK20, pankeratin, epithelial membrane antigen, chromogranin, neurofilament protein, carcinoembryonic antigen, desmin, actin, diffuse S100 protein, and HMB45. Nine cases with material for reverse transcription-polymerase chain reaction revealed 1 positive type 2 translocation (EWS exon 7 to Fli-1 exon 5), 4 negative, and 4 "unable to amplify." Treatment was by wide excision; 9 received chemotherapy and 6 radiation. Follow-up of 11 (85%) cases revealed the following: 1 metastasis to stomach and death at 3 years; 10 years without disease (median, 9.0 years). Cutaneous PN/ES is a superficial round cell tumor in older women, with better prognosis than deep PN/ES. These may have a hitherto unrecognized variant genetic abnormality.