Serous endometrial intraepithelial carcinoma (EIC) exhibits very high-grade nuclear atypia. Dehiscence is typical, as seen with the cells sloughing into the glanduloar lumen on the upper left. A benign endometrial gland is seen on the right.
Glandular involvement by serous intraepithelial carcinoma. Note the numerous mitotic figures.
Serous EIC is characterized by marked nuclear atypia, similar to that found in invasive papillary serous endometrial carcinoma. There is a loss of orientation and polarity. The nuclei pile up into a cribriform/pseudo-papillary structure, imparting a complex architecture to the gland.
The nuclei exhibit significant pleomorphism as demonstrated by the obvious size and shape variation. The nuclei are hyperchromatic, overlapping with prominent nucleoli.
Serous endometrial intraepithelial carcinoma (serous EIC) is the in situ correlate of invasive papillary serous-type (type 2) endometrial adenocarcinoma. It is thought that serous EIC accompanies, rather than precedes, invasive papillary serous endometrial adenocarcinoma. There is some difficult in the concept of "intraepithelial" in type 2 endometrial carcinoma, as this lesion is notorious for extensive metastasis without evidence of myometrial invasion.
Remember than type 1 endometrioid endometrial carcinoma is associated with prolonged estrogen exposure and a thickened endometrial stripe on ultrasound, and follows a hyperplasia-dysplasia-carcinoma sequence. In contrast, type 2 serous endometrial carcinoma is estrogen-independent, associated with atrophic endometrium and does not follow the hyperplasia-dysplasia-carcinoma sequence. Type 2 presents as a high-grade aggressive lesion, with a significantly poorer prognosis than type 1 carcinomas.
Although the pathway of oncogenesis has not yet been clearly established for type 2 endometrial carcinomas, 'precursor' lesions have been identified that exhibit the cytogenetic aberrations characteristic of type 2 carcinomas such as p53 mutation, increase in Ki-67 and LOH at multiple chromosomal loci such as 17p and 1p. These precursor lesions include serous endometrial intraepithelial carcinoma and serous endometrial gland dysplasia (serous EmGD), which exhibits a morphology and IHC pattern that lies at the midpoint between normal glands and serous EIC.1
It is important to impart to the surgeon that serous EIC may not actually be confined to the uterus These lesions are notorious for peritoneal spread and metastasis, despite lack of myometrial invasion. Thus, appropriate staging may be necessary even though the myometrium appears uninvolved grossly.1
1 Bishop JW, Maksem JA. Endometrial Intraepithelial carcinoma (EIC)/Serous (Type 2) Surface Cancer. Pathology Case Reviews 2007;12:166-169.
2 Fletcher CDM, ed. Diagnostic Histopathology of Tumors. 3rd Ed. Philadelphia, PA: Elsevier; 2007: 660.