endometrial neoplasms - wordpress.com · endometrial carcinoma •most common gynecologic cancer...
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Endometrial Carcinoma
• Most common gynecologic cancer
• Western developed > Southeast Asia
• Increase since the 1970’s
Endometrial Carcinoma
Etiology/Pathogenesis
• Unopposed estrogen stimulation (Anovulation, Obesity, HRT)
• Lynch syndrome, Cowden Syndrome
Endometrial Carcinoma
• Type I: - perimenopausal - non-smokers - endometrioid, mucinous histology, low grade - MIS, PTEN-/KRAS-mutations/accumulation of β-catenin • Type II: - postmenopausal - smokers - serous, clear cell, squamous, undifferentiated histology, high-grade - p53 mutations
DD of EC
Endometrioid EC Serous EC Clear cell EC
ER/PR+ (>90%), Ki-67 low, p53-, p16-
ER/PR +/- (50%), Ki-67 high, p53+++, p16+++*, WT-1-
ER/PR-, Ki-67 ++, p53-, HNF-1β+, P16+ (30%), WT-1+ (30%), E-cadherin-
DD Ovarian serous Ca: WT-1+!
* expression of p16 is unrelated to HPV!!!
Additional EC
• Mixed (minimum 5%)
• Undifferentiated EC (Lynch syndrome!)
• Dedifferentiated EC
(with 2nd G1 or G2
component)
https://ebooks.amirsys.com/
Atypical Hyperplasia/EIN
• EIN diagnostic criteria – At least 1 mm in size
– Glands to stroma ratio exceeds 1:1 (glands comprise > 50% of lesional area)
– Glandular epithelium cytologically distinct from background endometrium
Atypical Hyperplasia/EIN
• May involve endometrial polyp(s) (1/3)
• Metaplasia common: squamous (typically morules), mucinous, tubal, secretory
• PTEN: low sensitivity& specificity!
• No confluent cribriform growth or invasion of myometrium!
SEIC
• atrophic endometrium
• may involve endometrial polyps
• replacement of endometrial glands!
• Ki-67 +++, p53+++
• Carcinoma-may be associated with extensive extrauterine tumor spread!
• «minimal uterine serous carcinoma»
Endometrial sarcomas
• Endometrial stromal nodule (ESN)
• Endometrial stromal tumor (EST)
• Endometrial stromal sarcoma (ESS)
• High-grade ESS
Definitions
• ESN: Endometrial stromal tumor with absent to minimal myometrial invasion (< 3 mm and < 3 protrusions) and no vascular invasion
• EST: More infiltration of adjacent myometrium but no overt permeation or lymphovascular invasion
• ESS: Endometrial stromal tumor with myometrial &/or vascular invasion
IHC
IHC ESS Highly cellular leiomyoma
SMA, Desmin -/+ +
h-Caldesmon - +
CD10 + -/+
ER/PR + +
JAFZ1-JJAZ1 gene fusion 50% -
High grade ESS
• frequently associated with low-grade fibromyxoid endometrial stromal sarcoma
• CD10, ER, and PR negative in high-grade component
• CD117 often positive but DOG1 negative
• t(10;17) (YWHAE-FAM22)
• Cyclin-D1 +++
Undifferentiated uterine sarcoma
• High-grade sarcoma lacking specific differentiation
• No resemblance to endometrial stroma!
• No t(10;17)
Malignant Müllerian Mixed Tumor
• Malignant biphasic tumor composed of carcinomatous and homologous or heterologous sarcomatous elements
• Conversion theory
• L1/V1 and M1 most commonly by carcinoma