A 41-year-old woman presents with worsening abnormal uterine bleeding. An endometrial biopsy returns as hyperplasia with atypia, and the patient undergoes hysterectomy. A uterine mass is identified by gross examination. Representative photomicrographs of the lesion on frozen (figures 1 and 2) and permanent sections (figure 3) are shown.
The correct answer is ...
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 8th decade-and nearly all contain TP53 mutations, which can be reflected in diffusely positive or completely negative immunohistochemical staining for p53.5
Ryan Kendziora, M.D.
Gary Keeney, M.D.
Consultant, Anatomic Pathology
Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science