Sarcomas of the mediastinum with epithelioid morphology

Our plain-English summary of Sarcomas of the mediastinum with epithelioid morphology, by K.D. Perry, J. Montecalvo, A.M. Perry (Mediastinum, 2021).

The study

• Authors: K.D. Perry, J. Montecalvo, A.M. Perry
• Journal: Mediastinum
• Published: 2021;5:4
• Type of article: Review
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

While soft tissue sarcomas typically have a spindled or pleomorphic appearance, a subset of malignant soft tissue neoplasms can have a prominent epithelioid morphology. In complex anatomic sites such as the mediastinum, such tumors can often be mistaken for a carcinoma or mesothelioma. Frequent expression of cytokeratin staining can further confound the diagnostic process and familiarity with these entities can help prevent an erroneous diagnosis. Particular entities that have been reported to occur in the mediastinum with such features include dedifferentiated liposarcoma, pleomorphic liposarcoma, malignant peripheral nerve sheath tumor, synovial sarcoma, SMARCA4-deficient thoracic sarcoma, alveolar soft part sarcoma and clear cell sarcoma. Many of these tumors exhibit unique clinical, genetic, molecular or immunohistochemical features which allow for accurate characterization. For example, pleomorphic liposarcoma contains bizarre appearing lipoblasts and dedifferentiated liposarcoma exhibits MDM2 gene amplification that is typically confirmed by fluorescence in-situ hybridization. Malignant peripheral nerve sheath tumor will often arise in association with a nerve or neurofibroma. Synovial sarcoma consistently exhibits rearrangements involving the SS18 gene and SMARCA4-deficient thoracic sarcoma shows loss of SMARCA4 staining in the tumor cells. Alveolar soft part sarcoma demonstrates an ASPL-TFE3 fusion transcript. Clear cell sarcoma often shows an EWSR1-ATF1 fusion transcript. When encountering a sarcoma of the mediastinum with epithelioid features, familiarity with these and other characteristics can help insure a correct diagnosis.

2021 Mediastinum. All rights reserved.

In plain English

This article was a review, not a study of patients or of asbestos exposure. It gave an overview of sarcomas (cancers of soft tissues such as fat, blood vessels and nerves) that can arise in the mediastinum, the central chest space, and whose cells look "epithelioid", resembling the cells of carcinomas. The authors explained that in the mediastinum such sarcomas are much more likely to be mistaken for carcinoma or mesothelioma, partly because they often stain for cytokeratins or EMA, markers usually linked to epithelial tumors. The review described several tumor types, including liposarcomas, vascular tumors, synovial sarcoma, SMARCA4-deficient thoracic sarcoma, alveolar soft part sarcoma and clear cell sarcoma. For most of these it described identifying genetic or staining findings, such as MDM2 gene amplification or SS18-SSX gene fusions. Pleomorphic liposarcoma, by contrast, lacks a characteristic genetic abnormality and is diagnosed mainly by its appearance. The review noted that the TLE-1 stain is of little help in confirming synovial sarcoma in the mediastinum because almost all mesotheliomas are TLE-1 positive. The authors concluded that a holistic approach and familiarity with these features can help assure accurate diagnosis. They said this matters because sarcomas and carcinomas are treated differently.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review article
• Who was studied: No patient group was studied. The review covered published reports on sarcoma types with epithelioid features occurring in the mediastinum.
• Exposure: Not applicable. The article does not study asbestos or any other exposure.
• Main results:
  • The review stated that in the mediastinum, sarcomas with epithelioid features are more likely to be mistaken for carcinoma or mesothelioma.
  • The review stated that these sarcomas often stain for broad-spectrum cytokeratins or epithelial membrane antigen (EMA), which makes them resemble carcinomas.
  • Citing earlier reports, the review stated that mesenchymal tumors make up about 5% of primary tumors in the mediastinum.
  • The review stated that the TLE-1 stain gives little help in confirming synovial sarcoma in the mediastinum, because almost all mesotheliomas are TLE-1 positive.
  • The review described distinguishing genetic features: MDM2 gene amplification by FISH helps confirm dedifferentiated liposarcoma, and synovial sarcomas carry SS18-SSX1 or SS18-SSX2 gene fusions.
  • The review stated that pleomorphic liposarcoma lacks a characteristic genetic abnormality such as MDM2 amplification. Once dedifferentiated liposarcoma has been excluded, its diagnosis rests mainly on its microscopic appearance.
  • For SMARCA4-deficient thoracic sarcoma, the review stated that SMARCA4 and SMARCA2 are lost in the tumor cells. It reported that a paper by Rekhtman et al. proposed these tumors are actually undifferentiated or dedifferentiated carcinomas rather than primary sarcomas.
  • The review stated that clear cell sarcoma shows an EWSR1-ATF1 fusion, but that this fusion is not specific to that tumor.
• The authors' conclusion: The authors concluded that a holistic diagnostic approach and familiarity with the specific microscopic, staining and molecular findings of these tumors can help assure accurate diagnosis. They considered this clinically relevant because sarcomas and carcinomas typically have different treatment regimens.
• Limitations the authors state:
  • The authors noted that, because angiosarcomas are rare in the mediastinum, there is limited documentation of how these tumors behave in that location.
  • The authors noted that clear cell sarcoma occurs too rarely in the mediastinum to allow a prognosis specific to that site.

Topics

Medical terms in this study, explained in our Lexicon: Sarcoma, Mediastinum, Epithelioid, Pleomorphic, Neoplasm, Carcinoma, Mesothelioma, Synovial Sarcoma.

Related studies

• A biphasic tumor of the mediastinum with features of synovial sarcoma. A report of four cases — G.B. Witkin, M. Miettinen, et al. (1989)
• A Rare Case of Pleural Epithelioid Mesothelioma With a Prominent Myxoid Stroma Reported With Morphology, Fluorescent In Situ Hybridization, and Ultrastructural Findings — H. Sonobe, R. Omote, et al. (2024)
• Epithelioid sarcoma. A clinical and pathologic study of nine cases — H. Santiago, L.K. Feinerman, et al. (1972)
• Metastatic proximal epithelioid sarcoma in pleural effusion: cytopathologic findings and differential diagnosis — H. Guan, F. Haque, et al. (2013)
• A case of pleural epithelioid sarcoma of proximal type presenting as malignant pleural mesothelioma — G.A. Madsen, T.R. Rasmussen, et al. (2013)
• Pulmonary tumor diagnosed as an undifferentiated sarcoma with epithelioid features: a case report — M.R. El Ochi, M.M. El Hammoumi, et al. (2016)

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