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Endometrial endometrioid adenocarcinoma with a malignant squamous component: is the unusual metastatic pattern unique of these tumors?

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Abstract

The FIGO scheme is currently applied for tumor grading of endometrioid adenocarcinoma. The current report presents a series of ten cases of endometrioid carcinomas that when applying the FIGO grading does not fully convey the true biological nature of the disease. The squamous component of these tumors is malignant; it constitutes the predominant invasive component, and it often metastasizes to unconventional sites. Half of the cohort developed distant disease recurrence within 2 years, even those with early-stage disease. Somatic mutations were analyzed, targeting 101 genes in all ten cases, and mutations in PTEN, MMR, PIK3CA, ATM, RB1, and TP53 genes were detected, often multiple mutations in the same case. None of the cases revealed unique molecular signatures or previously unreported gene mutations. Immunohistochemical staining for beta-catenin showed aberrant nuclear staining in eight of ten cases and remaining two showed cytoplasmic and membranous staining. Aggressive behavior and unusual sites of metastases are observed in this series even in low-grade tumor. The FIGO grading on smaller samples may be deceptive for these cases. Even if FIGO is applied, the pathology report should emphasize the malignant squamous component and its potential significance so that the gynecologic oncology team can formulate appropriate adjuvant treatment upfront. This case series argues that this histology should be regarded as a high-grade endometrioid carcinoma and can show unusual metastatic patterns. Further research is needed with more cases within this histologic subtype to guide recommendations on adjuvant therapies for this aggressive tumor type.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Women & Infants Hospital, Warren Alpert Medical School of Brown University, 101 Dudley Street, Providence, RI, 02905, USA

    M. Ruhul Quddus, Renan Ribeiro e Ribeiro, C. James Sung & Kamaljeet Singh

  2. Laboratório Cicap–Hospital Alemão Oswaldo Cruz, São Paulo, and Instituto do Câncer do Estado de São Paulo (ICESP), São Paulo, SP, Brazil

    Renan Ribeiro e Ribeiro

  3. Department of Women’s Oncology, Women & Infants Hospital, Warren Alpert Medical School of Brown University, Providence, RI, USA

    Jessica B. DiSilvestro

Authors
  1. M. Ruhul Quddus
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  2. Renan Ribeiro e Ribeiro
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  3. Jessica B. DiSilvestro
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  4. C. James Sung
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  5. Kamaljeet Singh
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Contributions

MRQ: conceptualize, case collection and case review, manuscript write up, literature review, and overall supervision

RRR: case review, literature review, result interpretation, manuscript editing

JBD: survival data collection, patient management, and manuscript editing

CJS: sequencing help, manuscript editing

KS: manuscript editing, literature review, organizing data

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Correspondence to M. Ruhul Quddus.

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Quddus, M.R., Ribeiro, R.R., DiSilvestro, J.B. et al. Endometrial endometrioid adenocarcinoma with a malignant squamous component: is the unusual metastatic pattern unique of these tumors?. Virchows Arch (2024). https://doi.org/10.1007/s00428-024-03828-2

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  • DOI: https://doi.org/10.1007/s00428-024-03828-2

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