Dedifferentiated Liposarcoma With Epithelioid/Epithelial Features

Our plain-English summary of Dedifferentiated Liposarcoma With Epithelioid/Epithelial Features, by N. Makise, A. Yoshida, M. Komiyama, et al (The American Journal of Surgical Pathology, 2017).

The study

• Authors: N. Makise, A. Yoshida, M. Komiyama, F. Nakatani, K. Yonemori, A. Kawai, M. Fukayama, N. Hiraoka
• Journal: The American Journal of Surgical Pathology
• Published: 2017;41(11):1523-1531
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Dedifferentiated liposarcoma (DDLPS) demonstrates a variety of growth patterns, and their histologic resemblance to other spindle cell mesenchymal tumors has been widely recognized. However, epithelioid morphology in DDLPS has only rarely been documented. Here, we report 6 cases of DDLPS with striking epithelioid/epithelial features. The patients were 5 men and 1 woman with a median age of 61 years. All tumors were located in the internal trunk. During follow-up of 1 to 41 months, local recurrence, distant metastases, and tumor-related death occurred in 4, 2, and 4 patients, respectively. Beside well-differentiated liposarcoma component and conventional high-grade spindle cell morphology, all tumors focally exhibited growth comprising small or large epithelioid cells in diffuse or sheet-like proliferation. Rhabdoid cells were present in 2 cases. All 5 tumors tested harbored MDM2 amplification. Cytokeratin and/or epithelial membrane antigen were at least focally positive in all 5 tumors tested. One case contained a small focus of novel heterologous epithelial differentiation with acinar structures, wherein cytokeratin, MOC31, and claudin-4 were diffusely expressed and H3K27me3 expression was lost. DDLPS with epithelioid/epithelial features may lead to misdiagnosis of carcinoma or mesothelioma, and their diagnosis should be based on correlation with clinicopathologic and molecular findings. The epithelioid morphology in DDLPS may suggest an aggressive behavior based on this small series. In addition, we document 2 cases of MDM2-amplified undifferentiated neoplasm with epithelioid features in the internal trunk that lacked association with well-differentiated liposarcoma histology and showed rapid clinical course. Whether these latter tumors belong to DDLPS with epithelioid features requires further study.

In plain English

This was a case series from the pathology records of the National Cancer Center Hospital in Tokyo. It concerned dedifferentiated liposarcoma (DDLPS), a fat-tissue cancer, whose cells looked epithelioid, meaning like the cells that line body surfaces. The article does not study asbestos. Mesothelioma appears only as a disease these tumors can be mistaken for. Of 156 DDLPS cases from 2008 to 2016, the authors found 6 (3.8%) whose epithelioid areas closely resembled carcinoma or mesothelioma. In 2 of these 6, such a diagnosis was seriously considered at first. All 5 tumors tested had MDM2 gene amplification, and all 5 were at least partly positive for the epithelial markers cytokeratin and/or EMA. Over 1 to 41 months of follow-up, 4 of the 6 patients died of the disease. The authors also described 2 further retroperitoneal tumors that may have been the same disease but could not be confirmed. Both of those patients died within 1 to 2 months. The authors concluded that this pattern is a diagnostic pitfall. They said further study is needed to judge whether it signals a worse outlook, noting the series was small.

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: Retrospective case series: a search of one hospital's pathology database with slide review, immunohistochemistry (tissue staining for markers) and FISH testing for MDM2 gene amplification
• Who was studied: Cohort 1: 6 patients (5 men, 1 woman, aged 51 to 66, median 61) with dedifferentiated liposarcoma with epithelioid/epithelial features, selected from 156 DDLPS cases at the National Cancer Center Hospital, Tokyo, Japan, from 2008 to 2016. Cohort 2: 2 men (aged 53 and 60) with MDM2-amplified undifferentiated epithelioid tumors of the retroperitoneum and no well-differentiated liposarcoma component, analyzed separately.
• Exposure: None studied. The article does not examine asbestos or any other exposure; mesothelioma is discussed only as a disease these tumors can be mistaken for under the microscope.
• Main results:
  • Epithelioid features resembling carcinoma or mesothelioma were found in 6 of 156 DDLPS cases (3.8%), based on cohort 1.
  • In cohort 1, all tumors were in the internal trunk: 5 in the retroperitoneum and 1 in the obturator space.
  • In 2 of the 6 cohort 1 cases, carcinoma, mesothelioma or lymphoma was seriously considered at the original diagnosis.
  • In cohort 1, all 5 tumors tested were at least focally positive for cytokeratin (AE1/AE3) and/or EMA, and all 5 tested by FISH showed high-level MDM2 amplification.
  • In cohort 1, during follow-up of 1 to 41 months (median 10 months), 4 of the 6 patients had local recurrence, 2 had distant metastases, and 4 died of the disease.
  • The marker claudin-4 was negative in the epithelioid areas except in case 2. The authors noted this can help separate these tumors from carcinomas but will not help separate them from mesotheliomas.
  • One cohort 1 case (case 2, a 52-year-old man) contained a 1 cm focus of epithelial differentiation not previously documented in DDLPS. In that focus, H3K27me3 staining was completely lost.
  • None of the 7 cases tested (5 in cohort 1, 2 in cohort 2) showed loss of SMARCB1, SMARCA4 or SMARCA2. One case showed mildly reduced SMARCA2 staining.
  • In cohort 2, both patients (men aged 53 and 60, both with retroperitoneal tumors) died of the disease within 1 to 2 months.
• The authors' conclusion: The authors concluded that DDLPS with epithelioid features is a diagnostic pitfall that must be distinguished from carcinomas and mesotheliomas. They said diagnosis should rest on clinical context, microscopic appearance, immunohistochemistry and molecular findings taken together, and that further study is needed to know whether this appearance signals a poor prognosis.
• Limitations the authors state:
  • The authors described the series as small, so its suggestion of aggressive behavior is tentative.
  • The identity of the 2 cohort 2 tumors could not be settled, because a small subset of carcinomas and mesotheliomas can also carry MDM2 amplification. The authors said a larger series is needed.

Topics

Medical terms in this study, explained in our Lexicon: Epithelioid, Spindle Cell, Mesenchymal Tumor, Well-Differentiated, Rhabdoid, Epithelial Membrane Antigen (EMA), Acinar, Claudin-4.

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