Slender finger-like villi are lined by pseudostratified columnar cells.
The neoplastic cells are morphologically similar those found in the usual type endometrioid adenocarcinoma, with columnar shapes and ovoid or rounded nuclei.
In this particular case, the tumor was deeply myoinvasive.
ER staining was diffusely positive.
Interestingly, this case demonstrated strong p16 positivity, which is usually seen in serous endometrial carcinomas or endocervical HPV-related adenocarcinomas.
Moderate p53 staining was also seen. Note that an IHC panel consisting of ER/PR/p53/p16 can often aid in distinguishing between adenocarcinomas of endocervical or endometrial origin. Typical serous endometrial carcinomas are: p53 diffuse+/p16 diffuse+/ER-/PR-. Typical endometrial endometrioid carcinomas are: p53- or patchy+/p16 patchy+/ER+/PR+ Typical endocervical adenocarcinomas are: p16 diffuse+/p53-/ER-/PR- (Yemelyanova). Thus, the IHC profile for this particular VGA does not perfectly fit into any of the 3 categories. The p53 and p16 staining is more strongly reactive than expected for an endometrioid endometrial carcinoma and resembles that seen in a serous endometrial adenocarcinoma, however, ER positivity is retained which is uncommon in a serous tumor. Either way, I will refrain from further speculation -- this case demonstrates the complex nature of classifying tumors.
Papillary formations often occur in endometrial carcinomas involving the various cells types (endometrioid, clear cell, mucinous, serous). Classifying endometrial tumors containing papillary structures has been fraught with difficulty and furthermore, there are conflicting data on the prognosis of these tumors. Here is our attempt to simply matters.
Basically, type I (endometrioid) adenocarcinomas that contain finger-like papillary projections are called villoglandular adenocarcinomas (VGA). VGA are considered a variant with conventional type endometrioid adenocarcinomas with similar clinical features and prognosis. Type II (serous) adenocarcinomas that contain papillary structures are called papillary serous adenocarcinomas of the uterus -- these tumors behave in an aggressive manner.
VGA is the second most common variant of endometrioid adenocarcinomas, following the adenosquamous variant, and is seen in approximately 15-30% of endometrioid adenocarcinomas. Microscopically, long slender finger-like projections are lined by columnar cells that resemble those found in endometrioid adenocarcinomas. The neoplastic cells are often pseudostratified and the papillary projections blend in with glandular formations.
Some published studies have found improved survival for VGA, especially VGA that occurs in the uterine cervix. Other studies, however, have found a poorer prognosis in VGA of the endometrium (Ambros). This may reflect differences between pathologists on how the definition of VGA is applied. The current consensus is to treat VGA tumor as a variant of endometrioid adenocarcinoma.
In a study of 61 VGA tumors, Zaino and colleagues found no significant differences between VGA and conventional type endometrial carcinomas. The two patient populations were similar in age, depth of tumor invasion and nodal spread. The disease-specific survival rate at 3 years was 94% for VGA and 88% for conventional type endometrial adenocarcinomas (Zaino).
(1) Villoglandular adenocarcinoma of the endometrium is now considered a variant of endometrioid endometrial adenocarcinoma with similar clinical features and prognosis.
(2) VGA often co-exists with more usual type endometrioid adenocarcinoma.
1 Nucci MR, Oliva Esther. Gynecologic Pathology: Foundations in Diagnostic Pathology. Philadelphia, PA: Elsevier: 2009: 244.
2 Zaino RJ, Kurman RJ, Brunetto VL et al. Villoglandular adenocarcinoma of the endometrium: a clinicopathologic study of 61 cases: a gynecologic oncology group study. Am J Surg Pathol. 1998 Nov;22(11):1379-85.
3 Ambros RA, Ballouk F, Malfetano JH et al. Significance of papillary (villoglandular) differentiation in endometrioid carcinoma of the uterus. Am J Surg Pathol. 1994 Jun;18(6):569-75.
4 Yemelyanova A, Ji H, Shih IeM et al. Utility of p16 expression for distinction of uterine serous carcinomas from endometrial endometrioid and endocervical adenocarcinomas: immunohistochemical analysis of 201 cases. Am J Surg Pathol. 2009 Oct;33(10):1504-14.