uterine endometrioid adenocarcinoma, FIGO grade 1

Definition: Relatively indolent tumors that arise in background of endometrial hyperplasia.

According to one definition, when endometrial glands show a confluent pattern occupying at least 2x2 mm focus, the diagnosis of adenocarcinoma can be made. Smaller foci are labeled "complex endometrial hyperplasia".

The diagnosis of endometrioid adenocarcinoma can also be made if there is extensive papillary pattern or infiltrative glands with desmoplastic response.

The glands are well-differentiated and show angulation or branching. Cytologic atypia is minimal.

The grading system currently used for endometrioid adenocarcinomas is the one proposed by International Federation of Gynecology and Obstetrics (FIGO).

If the tumor contains no more than 5% of solid, non-morular component, it is Grade 1. Grade 1 tumors make up approximately 50% of endometrial adenocarcinomas.

The glands are well-differentiated and show minimal cytologic atypia.

FIGO Grading system is based on the growth pattern of cancer - relative proportions of glandular vs solid components. It also takes into account cytologic atypia.

If a tumor with Grade 1 architectural pattern has severe cytologic atypia, it is classified as Grade 2. Such cases are rare and serous carcinoma should be ruled out.

Images

 http://www.webpathology.com/image.asp?case=569&n=3

Microscopy

 Back to back endometrial-type glands of varying differentiation/atypia with no intervening stroma
 May occasionally show a villoglandular pattern
 Stroma present is usually desmoplastic, may have foamy cells due to tumor necrosis (not specific for carcinoma, derived from stroma not histiocytes; fat positive, mucin negative)
 Adjacent endometrium often exhibits EIN or atypical hyperplasia
 Vascular invasion is associated with chronic inflammation around lymphatics
 May have trophoblastic differentiation with hCG+ cells
 Commonly has squamous metaplasia

FIGO grading

 Well differentiated (FIGO grade 1)

• Extensive, complex epithelial growth pattern with little intervening stroma
• Usually budding and branching of large glands causing papillary structures
• May be villoglandular on low power
• May have true papillae (DD: clear cell carcinoma, serous carcinoma), but without atypia
• Mild to moderate atypia is allowed or only focal; if atypia is more severe, FIGO grade is increased to moderate (FIGO grade 2)
• Some are myoinvasive
• Often has benign squamous differentiation (adenoacanthoma), focal mucinous, secretory or ciliated features
• Usually stage 1, with 95% relapse-free survival rate

 Moderately differentiated (FIGO grade 2)

• 6%-50% of non-squamous tumor is composed of sheet-like tumor cells without glandular features
• Tumor cells have moderate pleomorphism, prominent nucleoli

 Poorly differentiated (FIGO grade 3)

• >50% of nonsquamous tumor is composed of sheet-like tumor cells without glandular features
• Tumor cells have high grade features
• Glands poorly formed when present
• May contain malignant squamous cells
• Angiolymphatic invasion common

Myometrial invasion

Myometrial invasion is an independent prognostic parameter of the endometrioid carcinomas which correlates with the risk of metastasis to pelvic and/or paraaortic lymph nodes.

Recognition of myometrial invasion is sometimes difficult. In fact, myoinvasion is overdiagnosed in routine practice in as many as 25% of the cases. Recently, it has been observed that tumor-associated macrophages stimulate angiogenesis and promote cancer dissemination.

There is a link between increased microvessel proliferation to stromal macrophage infiltrate and suggest that enhanced tumor angiogenesis, triggered by stromal macrophages, regulates the progression of endometrioid carcinomas.

The identical stroma microenvironment found in the primary and the corresponding metastatic tumor suggests that tumor stroma response is determined by the intrinsic biology of the tumor.

Predisposition

 polycystic ovary disease

• In patients with history of polycystic ovary disease, excessive estrogenic stimulation of the endometrium increases their risk of developing endometrial hyperplasia and carcinoma.
• Most endometrial carcinomas arising in this setting are well-differentiated and less likely to invade myometrium or metastasize.

Differential diagnosis

 Ciliary metaplasia
 Papillary change
 Progesterone treatment related changes
 Shedding endometrium with papillary syncytial metaplasia
 Villoglandular endometrioid carcinoma
 Well differentiated tumors: atypical hyperplasia / EIN (Mod Pathol 2000;13:309)
 Poorly differentiated tumors: serous carcinoma

References

 Myometrial invasion and lymph node metastasis in endometrioid carcinomas: tumor-associated macrophages, microvessel density, and HIF1A have a crucial role. Espinosa I, José Carnicer M, Catasus L, Canet B, D’angelo E, Zannoni GF, Prat J. Am J Surg Pathol. 2010 Nov;34(11):1708-14. PMID: 20962622