Pathologie Simone Münst

Endometrial Neoplasms

PathoBasic 10.03.2015

Endometrial Neoplasms

• Endometrial Carcinoma

- Variants

- Precursors

• Endometrial Sarcomas

• MMMT

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

Endometrial Carcinoma

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Endometrioid EC

Grade 1 Grade 2 Grade 2 Grade 3

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Endometrioid EC

Grade 2

Endometrioid EC

Grade 2

Endometrioid EC

Grade 3

Mucinous EC

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Secretory EC

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Clear Cell EC

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Serous EC

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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)

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Hyperplasia without atypia

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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!

Atypical Hyperplasia/EIN

EIN

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Atypical Hyperplasia/EIN

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Treated AEH/EIN

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Telescoping

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Serous endometrial intraepithelial carcinoma (SEIC)

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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»

SEIC

p53

cave: null phenotype! https://ebooks.amirsys.com/

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

Low grade ESS

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Low grade ESS

CD10 https://ebooks.amirsys.com/

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 +++

High grade ESS

Cyclin D-1

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Undifferentiated uterine sarcoma

• High-grade sarcoma lacking specific differentiation

• No resemblance to endometrial stroma!

• No t(10;17)

UUS

p53

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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

MMMT

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