Malignant squamous differentiation in endometrioid carcinoma marked aggressive disease

Design

Retrospective single-institution case series with central review and targeted sequencing

Population

9 malignant squamous cases among 3,696 endometrioid endometrial carcinomas

Primary outcome

Clinicopathological, immunohistochemical and molecular features

Effect

Associated with deep invasion, extensive LVSI and nodal metastasis; all four molecular subtypes represented

A retrospective review of 3,696 endometrioid endometrial carcinomas diagnosed between 2020 and 2025 identified nine with malignant squamous differentiation by predefined criteria. All underwent central review, an immunohistochemical panel and targeted sequencing, with FIGO 2023 staging and molecular classification.

These tumours showed deep myometrial invasion, extensive lymphovascular space invasion and frequent nodal metastasis. The malignant squamous component sat mainly at the invasive front and in metastatic deposits, and consistently lost hormone receptor expression. Preoperative biopsy and curettage often underestimated or misclassified it. The tumours spanned all four molecular subtypes, with recurrent PI3K/AKT pathway alterations.

This is a very small series, so the findings describe a pattern rather than set a risk estimate. The practical point is that molecular class alone did not flag this phenotype, so careful morphology of the invasive front still matters.

• Distinguish malignant from benign-appearing squamous differentiation in endometrioid carcinoma, and report it.
• Sample the invasive front and check lymphovascular space invasion carefully when a malignant squamous component is present.
• Consider hormone receptor staining of the squamous component, which lost expression in this series.
• Do not rely on a biopsy or curettage to exclude it; preoperative sampling often missed it.

Why it matters

Molecular classification did not capture this aggressive phenotype, so morphology remains the only way to see it.

Don't overread it

Nine cases — the associations are descriptive and not a validated prognostic factor.

The statistics, in plain English

Nine cases among nearly 3,700 is a rate of about 0.2%, so this is a rare finding. With so few cases, no reliable risk estimate is possible, only a description of what these tumours had in common.

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