Peritoneal washings reveal cytologic clues to aggressive pilomatrix-like endometrioid carcinoma

A rare and aggressive variant of endometrial cancer has now been characterized under the microscope in a way that may help pathologists recognize it earlier. Pilomatrix-like high-grade endometrioid carcinoma, abbreviated PiMHEC, is a variant of endometrioid carcinoma marked by basaloid high-grade morphology, shadow cells, and aberrant β-catenin expression.

The researchers retrospectively identified five histologically confirmed PiMHECs that had peritoneal washing specimens available. Four of these contained malignant cells on review and were included in the cytomorphologic analysis. Concurrent cervicovaginal liquid-based cytology was available in two cases. For each case, the team also reviewed the corresponding surgical specimens, immunostains, and targeted next-generation sequencing results, allowing the cytologic findings to be correlated directly with tissue-level and molecular features.

The peritoneal washings were malignant in all four cases, while both cervicovaginal specimens were negative. The tumor cells appeared in several distinct patterns: as loose single cells, as sheets and trabeculae, as papillary and three-dimensional clusters, and as palisaded clusters. This combination of architectural patterns, particularly the palisading, forms part of the recognizable cytologic signature the authors describe.

Under high magnification, the malignant cells were small to medium sized with scant cytoplasm and high nuclear-to-cytoplasmic ratios. Their nuclei were round to angulated, with coarse to vesicular chromatin, variable nucleoli, and visible mitoses, and apoptotic debris was also present.

Notably, the degree of atypia visible in the washings varied between cases. In two cases, the peritoneal washings showed only low-grade papillary structures without high-grade tumor cells, and the corresponding tissue sections showed only focal mild nuclear pleomorphism. In the other two cases, keratinization, dyskeratotic cells, or overt keratin pearl formation was present in the washings, and these findings correlated with abrupt keratinization and shadow-cell formation in the tissue sections.

The immunohistochemical profile of the basaloid component was distinctive. It showed aberrant nuclear and cytoplasmic β-catenin expression together with diffuse CDX2 expression, while the hormone receptors ER and PR and the marker PAX8 were lost. This combination of aberrant β-catenin, diffuse CDX2, and loss of ER, PR, and PAX8 provides a concrete immunophenotypic fingerprint that can be checked against cytologic material in conjunction with histology.

Molecular testing added further definition. All tumors were mismatch repair proficient, p53 wild type, and microsatellite stable, and all were POLE and TP53 wild type. Every tumor harbored a CTNNB1 exon 3 mutation, consistent with the aberrant β-catenin staining pattern. The authors emphasize that these molecular correlates should be considered alongside the cytologic and immunophenotypic findings when PiMHEC is suspected.

The clinical course of the patients underscores the aggressive nature of this variant. Three of the patients developed recurrent or metastatic disease. Because the series is small, comprising four cytologically analyzed cases, the findings should be interpreted as an initial characterization rather than a definitive diagnostic standard, and the authors note that the cytologic features of this tumor remain an area requiring further study.

Nevertheless, the study concludes that PiMHEC can show recognizable cytologic clues in serous fluid specimens. According to the authors, a high-grade basaloid and discohesive carcinoma with peripheral palisading, brisk apoptosis or mitotic activity, and keratinization or keratin pearl formation should prompt consideration of PiMHEC, followed by correlation with histology, the β-catenin and CDX2 immunophenotype, and CTNNB1 status. For cytologists evaluating peritoneal washings, the message is that a distinctive constellation of features, rather than any single finding, may flag this rare and aggressive tumor.

Subject of Research: Cytologic features of pilomatrix-like high-grade endometrioid carcinoma of the uterine corpus in peritoneal washing specimens

Article Title: Cytologic features of Pilomatrix-like high-grade endometrioid carcinoma of the uterine corpus: a four-case series and review of the literature

Article References: Qin, L., Xu, W., Zhou, X., Wang, Y., Lin, W., & Zhou, F. (2026). Cytologic features of Pilomatrix-like high-grade endometrioid carcinoma of the uterine corpus: a four-case series and review of the literature. Diagnostic Pathology. https://doi.org/10.1186/s13000-026-01859-8

Image Credits: AI Generated

DOI: 10.1186/s13000-026-01859-8

Keywords: pilomatrix-like endometrioid carcinoma, peritoneal washing cytology, endometrial cancer, shadow cells, beta-catenin, CTNNB1 mutation, CDX2, basaloid carcinoma, Diagnostic Pathology, case series, immunohistochemistry, gynecologic pathology