Indian Journal of Dermatopathology and Diagnostic Dermatology

: 2021  |  Volume : 8  |  Issue : 1  |  Page : 13--16

Primary cutaneous primitive neuroectodermal tumor/Ewing sarcoma: A rare case with an unusual presentation

Shobhna Sharma1, Deepa Goel1, Paritosh Gupta2,  
1 Department of Histopathology, Lab Medicine, Artemis Hospitals, Gurugram, Haryana, India
2 Department of General, MI & Bariatric Surgery, Artemis Hospitals, Gurugram, Haryana, India

Correspondence Address:
Shobhna Sharma
Department of Histopathology, Lab Medicine, Artemis Hospitals, Sector 51, Gurugram 122 001, Haryana.


Primitive neuroectodermal tumors (PNET)/Ewing sarcomas (ES) are a group of malignant tumors composed of small round cells of neuroectodermal origin, that affect soft tissue and bone, primarily in children and young adults. About 10%–20% of all cases are extraskeletal, out of which primary cutaneous and superficial cases are rare. We report a case of primary cutaneous PNET/ES in a 57-year-old diabetic man without osseous or other extraskeletal involvement. Differential diagnosis of this rare entity includes other cutaneous malignant round cell tumors such as lymphoma, melanoma, malignant glomus tumor, Merkel cell carcinoma, and malignant cutaneous adnexal neoplasms. The correct diagnosis is important for managing these chemosensitive tumors, which can be achieved with the help of special stains and immunohistochemistry. This case report aims to increase the awareness about rarer clinical presentation of this rare entity with emphasis on histomorphological differential diagnosis.

How to cite this article:
Sharma S, Goel D, Gupta P. Primary cutaneous primitive neuroectodermal tumor/Ewing sarcoma: A rare case with an unusual presentation.Indian J Dermatopathol Diagn Dermatol 2021;8:13-16

How to cite this URL:
Sharma S, Goel D, Gupta P. Primary cutaneous primitive neuroectodermal tumor/Ewing sarcoma: A rare case with an unusual presentation. Indian J Dermatopathol Diagn Dermatol [serial online] 2021 [cited 2022 Aug 14 ];8:13-16
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Primary primitive neuroectodermal tumor (PNET)/Ewing sarcoma (ES) of the skin is a very rare malignant tumor which typically arises in children and young adults with a female predilection. Lower and upper limbs are the common sites of involvement.[1] Histomorphology shows malignant small round cell tumor in the dermis and subcutaneous tissue with vague pseudorosetting. Because of its rarity and morphological similarity to other cutaneous round cell tumors, PNET/ES involving the skin is at risk of being misdiagnosed clinically and pathologically. The correct diagnosis can be achieved with the help of special stains, immunohistochemistry (IHC), and other ancillary techniques such as cytogenetics and molecular genetics of translocations. The treatment includes surgical resection and chemotherapy with or without radiotherapy. Cutaneous and superficial PNET/ES has a better prognosis than their counterparts in deep soft tissue and bone. This case report presents a rare case of primary cutaneous PNET/ES in an unusual clinical setting with emphasis on histomorphological differential diagnosis.

 Case Report

A 57-year-old male diabetic patient presented to the surgery outpatient department of our hospital with a chief complaint of a small painless nodular swelling over the abdominal wall in the right hypochondrium region for 2 weeks. On clinical examination, a nontender solitary subcutaneous soft nodule of ~2.0 cm × 2.0 cm size was observed. A clinical diagnosis of sebaceous cyst was considered and local excision was performed. Gross examination of the excised specimen showed single partly skin-lined gray-brown soft-tissue piece measuring 2.5 cm × 1.5 cm × 1.0 cm with overlying skin flap measuring 1.8 cm × 0.5 cm. Cut sections showed a gray-white partly cystic lesion measuring 2.0 cm × 1.0 cm × 1.0 cm, reaching close to the skin and deep soft-tissue cut margins. Microscopic examination showed a well-circumscribed highly cellular round cell tumor, located in the dermis and subcutaneous tissue with unremarkable epidermis [Figure 1]A and B. The tumor was composed of sheets of mitotically active monomorphic small round cells with a vague pseudorosette pattern [Figure 1]C. The tumor cells showed round nuclei with fine chromatin, inconspicuous nucleoli, and scant eosinophilic to clear cytoplasm [Figure 1]D. Periodic acid–Schiff stain demonstrated intracytoplasmic glycogen, which was diastase degradable [Figure 1]E and F. On performing IHC, the tumor cells showed strong diffuse membranous expression of CD99 [Figure 2]A and diffuse nuclear immunoreactivity for antibodies against FLI1 [Figure 2]B. Focal immunoreactivity for PanCK [Figure 2]D, synaptophysin [Figure 2]E, and S100 [Figure 2]F was observed with ~70% Ki67 [Figure 2]C. The cells were nonimmunoreactive for leukocyte common antigen (LCA), CK7, CK20, CK5/6, P63, epithelial membrane antigen (EMA), CD31, CD34, smooth muscle actin (SMA), chromogranin, CD56, and HMB45. Final diagnosis of primary cutaneous PNET/ES was rendered. Positron emission tomography–computed tomography examination further to this did not reveal any evidence of systemic or bony disease elsewhere in the body. The patient then underwent surgery for revision of resection margins, which did not reveal any residual disease. Afterward, the patient received the standard five-drug chemotherapy regimen for ES family of tumors, comprising vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide for the duration of 48 weeks. No local recurrence or distant metastasis was observed on follow-up after 15 months of surgery and 3 months of completion of chemotherapy.{Figure 1} {Figure 2}


ES family of tumors encompasses ES and PNET. They are now regarded as the same entity in view of the similar morphology, immunohistochemical staining patterns, and characteristic chromosomal translocations involving the EWS gene, namely t(11;22)(q24;q22).[2] Extraskeletal cases commonly involve deep soft tissue of children and young adults, but only rarely the skin, either as a primary tumor[3] or as a metastasis.[4] Cutaneous PNET/ES most commonly affects younger population with a female predilection.[5],[6],[7] Extremities are the common sites of involvement.[1],[5],[6] Primary cutaneous PNET/ES on the abdominal wall is quite rare with only a few previously published cases,[3],[8],[9] highly unusual in the older age group.[9] The differential diagnosis of cutaneous and superficial PNET/ES in an elderly includes a wide variety of primary and metastatic malignant round cell tumors, such as malignant cutaneous adnexal tumors, Merkel cell carcinoma, metastatic neuroendocrine carcinoma, malignant glomus tumor, non-Hodgkin lymphoma, and melanoma. A panel of immunohistochemical stains is essential for definite diagnosis due to these histomorphological mimics. Malignant cutaneous adnexal tumors with eccrine differentiation are the common and close differential diagnosis, having similar well-circumscribed dermal basophilic lobules of small round cells with scant clear cytoplasm, sometimes mimicking rosette arrangement. Focal immunoreactivity for cytokeratin was observed in our case, raising the possibility of adnexal tumor. Based on this, more epithelial immunostains were attempted which turned out to be negative and ruled out cutaneous adnexal tumors. We would like to emphasize here that cytokeratin expression, a manifestation of epithelial differentiation, is well documented in the literature in as many as 20% of ES/PNET in either a diffuse or focal pattern.[10] Merkel cell carcinoma, a highly aggressive neuroendocrine cutaneous neoplasm, is another very close mimic in view of similar histomorphology and overlapping immunohistochemical results including patchy cytokeratin and synaptophysin staining. Focal S100 and synaptophysin immunoreactivity, a manifestation of neuroectodermal differentiation, commonly seen in PNET/ES, was observed in our case also. Nonimmunoreactivity for chromogranin, CD56, and CK20 ruled out Merkel cell carcinoma and metastatic neuroendocrine carcinoma. Malignant glomus tumor, vascular tumor, melanoma, and cutaneous lymphoma were ruled out due to nonimmunoreactivity for SMA, CD34/CD31, HMB45, and LCA, respectively.

To conclude, primary cutaneous PNET/ES is an extremely rare malignancy in old age which can be misdiagnosed as a variety of other small round cell tumors of skin if the histopathologist is not familiar with the unusual clinical presentation of this rare entity. The correct diagnosis can be achieved with the help of special stains, IHC, and/or molecular studies. The prognosis of cutaneous PNET/ES appears to be more favorable than its more common extracutaneous counterparts. The current management of cutaneous PNET/ES includes surgery and chemotherapy with or without radiotherapy. However, in order to determine the prognosis and the most appropriate management, more such cases with extended follow up should be reported.

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Conflicts of interest

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