October 2023 – Gynecological Pathology and Surgical Pathology

Beta-catenin (nuclear and membranous staining).

This is an example of a corded and hyalinized variant of endometrioid endometrial carcinoma (CHEC), in which neoplastic cells are arranged in cords or small clusters and set within a hyalinized stromal background. Other morphologic clues to this variant include extensive squamous metaplasia, osseous metaplasia, or spindle cell proliferations. Patients with CHEC also tend to be younger than those with conventional endometrioid adenocarcinoma, with a mean age of less than 50 years at presentation.¹ This pattern is also clinically important, as CHEC tend to have low-grade morphology and overall favorable outcomes, though some high-grade CHEC have been reported.^2,3 Furthermore, CHEC-pattern changes have also been reported in endometrial hyperplasia and extrauterine sites such as ovarian primary endometrioid carcinoma, where they may cause diagnostic confusion.^2,4 CHEC characteristically harbor a mutation in CTNNB1, which is immunohistochemically manifested as diffuse, nuclear and membranous reactivity for beta-catenin.

The corded growth pattern in CHEC could raise the possibility of sex cord-like tumors of the uterus, such as uterine tumor resembling ovarian sex cord tumor (UTROSCT). UTROSCT can show positivity for sex cord markers such as inhibin or calretinin, whereas CHEC should not have such expression.

In any neoplasm of the gynecologic tract with a squamoid component, cervical carcinomas should also at least be considered. Given that many of them are HPV-driven, they classically would show diffuse, “block” positivity with p16 staining.

Lastly, carcinosarcoma represents a major pitfall in the diagnosis of CHEC, as the spindled or metaplastic components in CHEC might resemble a malignant mesenchymal component of carcinosarcoma. However, carcinosarcomas have both a high-grade epithelial and a high-grade mesenchymal component, as opposed to the low-grade morphology typically seen in CHEC.¹ Carcinosarcoma patients tend to be of older age—presenting in their 8^th decade-and nearly all contain TP53 mutations, which can be reflected in diffusely positive or completely negative immunohistochemical staining for p53.⁵

References

1. Travaglino et al. Corded and hyalinized endometrioid carcinoma: Summary of clinical, histological, immunohistochemical and molecular data. Pathol Res Pract. 2023 Jul;247:154515. doi:10.1016/j.prp.2023.154515. Epub 2023 May 8. PMID: 37209572.
2. Pors et al. The Evolving Spectrum of Endometrial Glandular Proliferations With Corded and Hyalinized Features. Am J Surg Pathol. 2023 Sep 1;47(9):1067-1076. doi:10.1097/PAS.0000000000002078. Epub 2023 Jul 27. PMID: 37493099.
3. Ladwig et al. Corded and Hyalinized Endometrioid Adenocarcinoma (CHEC) of the Uterine Corpus are Characterized by CTNNB1 Mutations and Can Show Adverse Clinical Outcomes. Int J Gynecol Pathol. 2021 Mar 1;40(2):103-115. doi:10.1097/PGP.0000000000000671. PMID: 32909971.
4. Talia and McCluggage. The diverse morphology and immunophenotype of ovarian endometrioid carcinomas. Pathology. 2023 Apr;55(3):269-286. doi:10.1016/j.pathol.2023.01.003. Epub 2023 Jan 21. PMID: 36759286.
5. WHO Classification of Tumours Editorial Board. Female genital tumours [Internet]. Lyon (France): International Agency for Research on Cancer; 2020 [cited 2023 Aug 23]. (WHO classification of tumours series, 5th ed.; vol. 4). Available from: https://tumourclassification.iarc.who.int/chapters/34.