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 Table of Contents  
CASE REPORT
Year : 2021  |  Volume : 8  |  Issue : 1  |  Page : 13-16

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


1 Department of Histopathology, Lab Medicine, Artemis Hospitals, Gurugram, Haryana, India
2 Department of General, MI & Bariatric Surgery, Artemis Hospitals, Gurugram, Haryana, India

Date of Submission23-Aug-2020
Date of Decision27-Oct-2020
Date of Acceptance08-Feb-2021
Date of Web Publication11-Aug-2021

Correspondence Address:
Shobhna Sharma
Department of Histopathology, Lab Medicine, Artemis Hospitals, Sector 51, Gurugram 122 001, Haryana.
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijdpdd.ijdpdd_97_20

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  Abstract 

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.

Keywords: Cutaneous, Ewing sarcoma, primitive neuroectodermal tumor, round cell tumor


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;8:13-6

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 2021 Dec 7];8:13-6. Available from: https://www.ijdpdd.com/text.asp?2021/8/1/13/323708




  Introduction Top


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 Top


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: (A) Lower dermis showing primitive neuroectodermal tumor/Ewing sarcoma composed of small round blue cells (H and E, ×20). (B) Well-circumscribed primitive neuroectodermal tumor/Ewing sarcoma in the subcutaneous tissue (H and E, ×20). (C) Primitive neuroectodermal tumor/Ewing sarcoma with vague pseudorosette pattern (H and E, ×100). (D) Primitive neuroectodermal tumor/Ewing sarcoma cells showing round nuclei with fine chromatin, scant eosinophilic cytoplasm, and mitosis (H and E, ×400). (E) Primitive neuroectodermal tumor/Ewing sarcoma cells with intracytoplasmic glycogen (periodic acid–Schiff, ×400). (F) Loss of intracytoplasmic glycogen after predigestion with diastase (periodic acid–Schiff diastase, ×400)

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Figure 2: (A) Diffuse strong membranous immunoreactivity for CD99 (immunohistochemistry, ×200). (B) Diffuse strong nuclear immunoreactivity for FLI1 (immunohistochemistry, ×200). (C) High (~70%) Ki67 (immunohistochemistry, ×200). (D) Focal patchy immunoreactivity for PanCK (immunohistochemistry, ×200). (E) Focal patchy immunoreactivity for synaptophysin (immunohistochemistry, ×200). (F) Focal patchy immunoreactivity for S100 (immunohistochemistry, ×200)

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  Discussion Top


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.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Patel RM, Scolyer RA. Ewing sarcoma. In: Elder DE, Massi D, Scolyer RA, Willemze R, editors. WHO Classification of Skin Tumours. 4th ed. Lyon: IARC; 2018. p. 375.  Back to cited text no. 1
    
2.
Dehner LP. Primitive neuroectodermal tumor and Ewing’s sarcoma. Am J Surg Pathol 1993;17:1-3.  Back to cited text no. 2
    
3.
Somers GR, Shago M, Zielenska M, Chan HS, Ngan BY. Primary subcutaneous primitive neuroectodermal tumor with aggressive behavior and an unusual karyotype: Case report. Pediatr Dev Pathol 2004;7:538-45.  Back to cited text no. 3
    
4.
Izquierdo MJ, Pastor MA, Carrasco L, Requena C, Fariña MC, Martín L, et al. Cutaneous metastases from Ewing’s sarcoma: Report of two cases. Clin Exp Dermatol 2002;27:123-8.  Back to cited text no. 4
    
5.
Shingde MV, Buckland M, Busam KJ, McCarthy SW, Wilmott J, Thompson JF, et al. Primary cutaneous Ewing sarcoma/primitive neuroectodermal tumour: A clinicopathological analysis of seven cases highlighting diagnostic pitfalls and the role of FISH testing in diagnosis. J Clin Pathol 2009;62:915-9.  Back to cited text no. 5
    
6.
Ehrig T, Billings SD, Fanburg-Smith JC. Superficial primitive neuroectodermal tumor/Ewing sarcoma (PN/ES): Same tumor as deep PN/ES or new entity? Ann Diagn Pathol 2007;11:153-9.  Back to cited text no. 6
    
7.
Di Giannatale A, Frezza AM, Le Deley MC, Marec-Bérard P, Benson C, Blay JY, et al. Primary cutaneous and subcutaneous Ewing sarcoma. Pediatr Blood Cancer 2015;62:1555-61.  Back to cited text no. 7
    
8.
Soma S, Shetty SK, Bhat S. PNET of the abdominal wall: A rare presentation. J Clin Diagn Res 2015;9:XD01-2.  Back to cited text no. 8
    
9.
Betal D, Shaygi B, Babu R, Jamil K, Sainsbury RJ. Primitive Neuroectodermal Tumour (PNET) in subcutaneous abdominal wall: A case report. Int Semin Surg Oncol 2009;6:10.  Back to cited text no. 9
    
10.
Gu M, Antonescu CR, Guiter G, Huvos AG, Ladanyi M, Zakowski MF. Cytokeratin immunoreactivity in Ewing’s sarcoma: Prevalence in 50 cases confirmed by molecular diagnostic studies. Am J Surg Pathol 2000;24:410-6.  Back to cited text no. 10
    


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