Recently my partner biopsied a verrucous papule from the face of a young boy, without being confident of his clinical impression. Histologically, I knew I was looking at a malignant lesion, but could not identify it. I sent the slide for a second opinion – the consensus of the group was that they were not sure either; the lesion was then referred to the pathology department at the Children’s Hospital of Philadelphia, where a very broad panel of immunoperoxidase studies was performed. A positive CD99 suggested the diagnosis of a primary cutaneous Ewing sarcoma (PCES). The patient was subsequently referred to surgical oncology.
Barreau et al presented the case of a 64 year-old woman with an exophytic, firm keratotic tumor of her right sole, with no visceral disease. Histology demonstrated a proliferation of small basophilic round cells of the the dermis and subcutaneous tissue, staining positive for CD99 and FISH (fluorescence in situ hybridization) revealing a EWSR1 translocation, confirming the diagnosis of PCES. Following chemotherapy and a forefoot amputation, she was free of disease after ten months of follow-up (1).
Ewing sarcoma (ES) is a primitive neuroectodermal tumor that classically affects bone. It may rarely affect soft tissues as a primary tumor, including the skin and adipose tissue. It usually affects young people in the second decade of life with a female/male ratio of 2/1 (2). There have been 7 reported cases in adults > 50 years old. Lesions may appear anywhere on the body. They have variable clinical appearances, ranging from pink to brown nodules that may have a keratotic surface (1). It is doubtful that the diagnosis would ever be considered clinically.
There have only been 3 reported cases of metastases from PCES, with two deaths. The prognosis for PCES is much more favorable than for ES of bone or other soft tissues, presumably because of the lesion being diagnosed earlier, being smaller and more superficial. Treatment is surgical, with the decision to add adjunctive chemotherapy or radiation depending upon the size and location of the tumor (2).
The onus of diagnosing PCES is on the dematopathologist. The histologic differential diagnosis falls under the realm of “small round blue cell tumors”, including (but not limited to) Merkel cell carcinoma, lymphoblastic lymphomas, rhabdomyosarcoma, synovial sarcoma, and melanoma. Aside from CD99 and FISH studies for EWSR1, newer studies such as expression of NKX2-2 can assist in diagnosing PCES, as it was recently shown to be a sensitive, but imperfectly specific test, being positive in 37/40 cases of ES (3).
It is difficult to reach any conclusions having confronted with a lesion that I will perhaps see once in my entire career. While I’m pleased, of course, that I at least recognized that it was malignant, knew my limitations, and sought appropriate consultations, the real lesson here is that dermatology, and dermatopathology in particular, is a humbling profession. Keep looking for answers from those with more expertise.
1. Barreau M, et al. An unusual case of primary cutaneous Ewing sarcoma in an adult. Int J Dermatol 2016; 55: 906-8.
2. de Oliveira Filho J, et al. Primary cutaneous Ewing sarcoma – case report. An Bras Dermatol 2014; 89: 501-3.
3. Hung YP, et al. Evaluation of NKX2-2 expression in round cell sarcomas and other tumors with EWSR1 rearrangement: imperfect specificity for Ewing sarcoma. Mod Pathol 2016; 29: 370-80.