How to approach the many faces of endometrioid carcinoma

This article reviews the salient features of variants of endometrioid carcinoma (ECa) that can pose a diagnostic challenge and/or are associated with unique clinicopathological findings. Variants with distinct architectural and cytologic features include the following: (1) ECa with a villoglandular pattern (tumor with finger-like papillae lined by bland cells with a tendency for vascular/lymphatic invasion and lymph node metastasis once this pattern is seen within the myoinvasive component); (2) papillary ECa of intermediate grade (grade 2) (tumor that can be mistaken for serous carcinoma, as it contains papillae showing slightly irregular contours, moderately atypical cells, and it is associated with vascular/lymphatic invasion/lymph node metastasis, but with common association with mucinous metaplasia, MELF (microcystic, elongated, and fragmented) pattern of invasion, and wild p53 expression); (3) ECa with non-villous papillae (tumor containing pseudopapillae within glands with bland-appearing cytology commonly associated with abortive squamous differentiation and otherwise not different from usual ECa); (4) ECa with microglandular-like pattern (tumor that mimics microglandular hyperplasia of the cervix, often lacking the typical appearance of microglandular hyperplasia and showing Ki-67 index >10%, strong CD10 expression, and negative PAX-2, p63, and CD34); and (5) ECa with sex cord-like formations and hyalinization (tumor with interconnected cords and nests of bland epithelioid and spindled cells that merge with a typical component of low-grade ECa, usually associated with squamous differentiation and hyalinization). This tumor should be distinguished from carcinosarcoma and, in contrast to the latter, it shows nuclear β-catenin expression, ER/PR and patchy p16 positivity, tends to present at a low stage, and has a favorable prognosis and (6) dedifferentiated ECa (tumor showing a low-grade ECa juxtaposed to an undifferentiated carcinoma-the latter characterized by variably sized monotonous, often non-cohesive cells with brisk mitotic activity and usually arranged in sheets). Undifferentiated carcinoma tends to be negative for PAX8 and ER/PR with variable expression of keratins and can be associated with microsatellite instability (may be part of Lynch syndrome). Variants with distinct cytological features include the following: (1) ECa with clear cells (tumors with clearing due to 'clear' (glycogenated) squamous cells, distinct vacuoles, or not otherwise specified. EC with clear cells should be distinguished from clear cell carcinoma by the absence of the variety of architectural patterns, lack of cuboidal/flattened/hobnail cells, and lack of degree of atypia usually detected in clear cell carcinoma. In addition, they are ER/PR positive and Napsin A and p504S negative in contrast to clear cell carcinoma); (2) ECa with spindle cells (tumor with transition from spindle cells to the glandular component of a low-grade ECa. The spindle cells are keratin, ER/PR, and patchy p16 positive and show wild-type p53 expression); (3) ECa with mucinous differentiation (this tumor can be mistaken for a cervical adenocarcinoma, as they have overlapping features. Expression of ER/PR and vimentin in the context of a negative or patchy p16 positivity and the absence of high-risk HPV allows a correct diagnosis).