This article has Open Peer Review reports available.
Epithelioid sarcoma with multiple lesions on the left arm: a case report
© The Author(s). 2016
Received: 25 January 2016
Accepted: 4 October 2016
Published: 24 October 2016
Epithelioid sarcoma is a rare, high-grade malignant tumor of the soft tissue. The incidence of local recurrence, regional lymph node involvement, and distant metastases is high. Epithelioid sarcoma is most often seen in adolescents and young adults. In the early stage before the development of full clinical features, epithelioid sarcoma is often misdiagnosed as a benign disease such as granuloma.
We report a case of a 74-year-old Japanese woman whose epithelioid sarcoma was initially misdiagnosed as fungal infection. Rebiopsy revealed the proliferation of atypical polygonal or oval epithelioid cells in the dermis and lymphocyte infiltration through the dermis. Immunohistochemically, the tumor cells were positive for vimentin, cell adhesion molecule 5.2, epithelial membrane antigen, and E26-related gene. The nuclear expression of integrase interactor 1 was lost in the tumor cells.
We encountered a rare case of epithelioid sarcoma and had difficulty in making the correct diagnosis. We suggest that in patients whose lesions are resistant to conventional treatments, repeat biopsy and immunohistochemical studies should be considered to rule out rare epithelioid sarcoma.
Epithelioid sarcoma (ES), first described by Enzinger in 1970 , is a rare sarcoma localized to deep or superficial soft tissue. It is the most common soft tissue sarcoma of the hand and wrist, followed by alveolar rhabdomyosarcoma and synovial sarcoma. ES can develop at any age but is rarely seen in children and the elderly. Because it is very rare and appears to be a benign lesion in the early stage, ES is often misdiagnosed as a benign disease such as granuloma. We report a case of a patient with ES on the hand and forearm with multiple satellite cutaneous lesions.
ES, a rare and highly malignant soft tissue tumor, shows a high tendency for local recurrence, regional lymph node involvement, and distant metastases . ES constitutes less than 1 % of all soft tissue sarcomas . It is characterized clinically by a firm and slow-growing tumor with a predilection for the hands, fingers, and forearms. Fifty-four percent of cases arise in the distal upper extremities . Pain or tenderness is rarely a prominent symptom, unless large nerves are affected by the tumor. ES is commonly seen in young patients; the peak incidence is in the third decade of life, and it is rare in children and the elderly.
Clinical features of previously reported cases and our patient
Reported cases 
Male sex, %
Female sex, %
Mean age at first symptoms, years
Mean symptom duration before diagnosis, months
Local recurrence, %
Lymph node metastases, %
Distant metastases, %
A new subtype, a proximal variant of ES, has been proposed . This subtype exhibits more aggressive clinical behavior, and its histopathological appearance is distinct. Clinically, the proximal subtype differs from the classical type by its multinodular growth pattern, its more frequent occurrence in older patients, its more proximal/axial distribution, its more deep-seated location, and its more aggressive clinical behavior from the outset. Histologically, it is characterized by predominantly large cells, epithelioid cytomorphology, marked cytological atypia, the frequent manifestation of rhabdoid features, and the absence of a granuloma-like pattern in most patients. On the basis of our clinical and histological findings, we considered the ES in our patient to be of the conventional distal type.
The cellular elements of ES range from large ovoid or polygonal cells with deeply eosinophilic cytoplasm to plump, spindle-shaped cells . Consequently, ES is often misdiagnosed as one of numerous benign and malignant disorders, and proper treatment is delayed. The median interval between the initial diagnosis and the start of treatment is 3.5 months (range 1–6 months) . Nishimura et al.  reported a patient with ES masquerading as an intractable wound for more than 18 years. We correctly diagnosed our patient 4 months after her initial presentation.
Immunohistochemical examination is essential to making a diagnosis of ES. Characteristically, it shows expression of vimentin and low-molecular-weight cytokeratins such as those recognized by the monoclonal antibody CAM5.2 [8, 9], and 85–96 % of cases are EMA-positive . The staining pattern suggests that ES is a neoplasm of mesenchymal origin with epithelial dedifferentiation. Vimentin is rarely negative. CD34, expressed in approximately 50 % of ES lesions, is used as an additional diagnostic marker in vimentin-negative cases. The INI1 gene is a member of the adenosine triphosphate-dependent SWI/SWF chromatin-remodeling complex and thus a candidate as a tumor suppressor gene. Loss of the INI1 gene is seen in some patients with malignant rhabdoid tumors; its loss is 93 % sensitive for a diagnosis of ES .
ERG, a member of the erythroblast transformation-specific family of transcription factors, is a marker of endothelial differentiation . Kohashi et al. , who analyzed the expression of ERG in INI1-deficient tumors, including ES, reported that ERG was expressed in 13 of 24 conventional distal type lesions and 5 of 20 patients with proximal-type ES. All of their patients with malignant rhabdoid tumors had negative test results for ERG, suggesting that ERG may be a useful marker to distinguish ES from malignant rhabdoid tumors with loss of INI1.
Cancer antigen 125 (CA-125) is a high-molecular-weight glycoprotein commonly used for the identification of epithelial ovarian carcinomas; it has also been detected in various neoplasms, including carcinomas of the breast, lung, and colon, and in patients with lymphoma. Kato et al.  documented that 10 (91 %) of 11 patients with ES had positive test results for CA-125; 10 manifested the classical type and the other had the proximal type of the disease. In other soft tissue tumors, including synovial sarcomas, clear cell sarcomas, leiomyosarcomas, rhabdomyosarcomas, liposarcomas, malignant peripheral nerve sheath tumors, malignant fibrous histiocytomas, desmoid tumors, cutaneous squamous cell carcinomas, and rheumatoid nodules, CA-125 was negative. Other authors [8, 9] have suggested that CA-125 immunoreactivity in the presence of an elevated serum CA-125 level could be a useful tumor marker for the diagnosis of ES and for monitoring the clinical course of patients with ES.
ES is very rare and appears to be a benign lesion in the early stage, and it is often misdiagnosed as a benign disease such as granuloma. We encountered a rare case of ES and had difficulty in making the correct diagnosis. We suggest that in patients whose lesions are resistant to conventional treatments, repeat biopsy and immunohistochemical studies should be considered to rule out rare ES.
We sincerely thank our patient for allowing us to publish this case report.
No funding agency was involved in our patient’s treatment or our preparation of the manuscript.
Availability of data and materials
The dataset supporting the conclusions of this case report is included within the case report (images and laboratory parameters).
RN, YH, and TK carried out medical management and the writing of the manuscript. YG and MH performed the histological examination of the patient’s skin biopsy. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
Consent for publication
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
Ethics approval and consent to participate
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Enzinger FM. Epithelioid sarcoma: a sarcoma simulating a granuloma or a carcinoma. Cancer. 1970;26:1029–41.View ArticlePubMedGoogle Scholar
- Chase DR, Enzinger FM. Epithelioid sarcoma: diagnosis, prognostic indicators, and treatment. Am J Surg Pathol. 1985;9:241–63.View ArticlePubMedGoogle Scholar
- Enzinger FM, Weiss SW. Malignant soft tissue tumors of uncertain type. In: Weiss SW, Goldblum JR, editors. Enzinger and Weiss’s soft tissue tumors. 4th ed. St. Louis, MO: Mosby-Year Book; 2001. p. 1521–38.Google Scholar
- Coates SJ, Ogunrinade O, Lee HJ, Desman GJ. Epidermotropic metastatic epithelioid sarcoma: a potential diagnostic pitfall. Cutan Pathol. 2014;41(8):672–6.View ArticleGoogle Scholar
- Guillou L, Wadden C, Coindre JM, Krausz T, Fletcher CD. “Proximal-type” epithelioid sarcoma, a distinctive aggressive neoplasm showing rhabdoid features: clinicopathologic, immunohistochemical, and ultrastructural study of a series. Am J Surg Pathol. 1997;21:130–46.View ArticlePubMedGoogle Scholar
- de Visscher SA, van Ginkel RJ, Wobbes T, Veth RP, Ten Heuvel SE, Suurmeijer AJ, et al. Epithelioid sarcoma: still an only surgically curable disease. Cancer. 2006;107(3):606–12.View ArticlePubMedGoogle Scholar
- Nishimura Y, Yamaguchi Y, Tomita Y, Hamada K, Maeda A, Morita A, et al. Epithelioid sarcoma on the foot masquerading as an intractable wound for > 18 years. Clin Exp Dermatol. 2010;35(3):263–8.View ArticlePubMedGoogle Scholar
- Lynch MC, Graber EM, Johnson TS, Clarke LE. Epithelioid sarcoma resembling benign fibrous histiocytoma. Cutis. 2015;95(2):83–6.PubMedGoogle Scholar
- Armah HB, Parwani AV. Epithelioid sarcoma. Arch Pathol Lab Med. 2009;133(5):814–9.PubMedGoogle Scholar
- Hornick JL, Dal Cin P, Fletcher CD. Loss of INI1 expression is characteristic of both conventional and proximal-type epithelioid sarcoma. Am J Surg Pathol. 2009;33(4):542–50.View ArticlePubMedGoogle Scholar
- Martens JH. Acute myeloid leukemia: a central role for the ETS factor ERG. Int J Biochem Cell Biol. 2011;43(10):1413–6.View ArticlePubMedGoogle Scholar
- Kohashi K, Yamada Y, Hotokebuchi Y, Yamamoto H, Taguchi T, Iwamoto Y, et al. ERG and SALL4 expressions in SMARCB1/INI1-deficient tumors: A useful tool for distinguishing epithelioid sarcoma from malignant rhabdoid tumor. Hum Pathol. 2015;46(2):225–30.View ArticlePubMedGoogle Scholar
- Kato H, Hatori M, Kokubun S, Watanabe M, Smith RA, Hotta T, et al. CA125 expression in epithelioid sarcoma. Jpn J Clin Oncol. 2004;34(3):149–54.View ArticlePubMedGoogle Scholar