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PA29.{2-3,9} | Endometrial Hyperplasia, Carcinoma & Uterine Smooth Muscle Tumors — SDL Guide (Part 2)

Endometrial Carcinoma — Type II Serous (Non-Estrogen-Driven)

Type II endometrial carcinoma — predominantly the serous (papillary serous) subtype — accounts for only ~10% of endometrial carcinomas but causes a disproportionate share of deaths because of its aggressive biology.

Contrast with Type I:

Feature	Type I Endometrioid	Type II Serous
Age at presentation	Perimenopausal (55–65 yr)	Older postmenopausal (65–75 yr)
Estrogen dependence	Yes	No
Precursor lesion	Atypical hyperplasia / EIN	Serous Endometrial Intraepithelial Carcinoma (SEIC)
Key mutation	PTEN, MSI, KRAS	TP53 (> 90%)
Grade	Low (Grade 1–2)	High (Grade 3 by default)
Background endometrium	Hyperplastic / thick	Atrophic
Prognosis	Good	Poor

TP53 mutation is the driver event in serous carcinoma, arising in an atrophic endometrium through SEIC (non-invasive serous carcinoma in surface epithelium or glands).

Histology: Complex papillary architecture with fibrovascular cores, lined by cells with marked nuclear pleomorphism, hyperchromatic nuclei, prominent nucleoli, and numerous atypical mitoses. Characteristically, cells with bulging apical cytoplasm appear to be falling into gland lumens ("hobnail" cells in some variants).

A three-panel educational diagram shows high-power serous endometrial carcinoma histology with papillary fronds, high-grade nuclei, and mitoses, plus early peritoneal spread and the clinical diagnostic pathway. — **Panel A:** 40x histology showing complex papillary architecture, fibrovascular cores, high-grade pleomorphic hyperchromatic nuclei, prominent nucleoli, and atypical mitotic figure. **Panel B:** Simplified uterus and peritoneal cavity showing small serous carcinoma focus, transtubal or peritoneal spread, and peritoneal implants. **Panel C:** Clinical pathway showing postmenopausal bleeding, TVS endometrial thickness threshold, endometrial sampling methods, and MRI pelvis for staging.

Why serous kills: Despite arising in small foci (even SEIC), serous carcinoma spreads early to peritoneal surfaces (analogous to ovarian serous carcinoma) — stage for stage, it carries a far worse prognosis than endometrioid.

Endometrial Carcinoma — Presentation, Diagnosis, and Clinical Approach

Clinical presentation:

Postmenopausal bleeding (PMB) — the cardinal symptom. Occurs in 90% of symptomatic cases. Any PMB (bleeding > 12 months after last period) mandates investigation.
Premenopausal: abnormal uterine bleeding, menorrhagia, or intermenstrual bleeding — often misattributed to fibroids or dysfunction.
Pelvic pain is a late feature, suggesting parametrial or nodal involvement.
Rarely: pyometra (distension of the uterine cavity with pus) in elderly women with cervical stenosis.

Diagnostic pathway:

1. Transvaginal ultrasound (TVS) — endometrial thickness ≥ 4 mm in a postmenopausal woman is abnormal and warrants sampling (sensitivity ~96% for carcinoma).
2. Endometrial sampling:
• Pipelle biopsy (outpatient, 90% sensitivity for carcinoma)
• Dilatation and curettage (D&C) — more complete, used if Pipelle is inadequate
• Hysteroscopy + directed biopsy — best for focal lesions
3. MRI pelvis — most accurate for assessing depth of myometrial invasion and cervical involvement (critical for staging and surgical planning).
4. CT chest/abdomen/pelvis or PET-CT — distant staging, especially for high-grade histology.

Longitudinally cut uterus showing an exophytic endometrial tumour from the posterior fundal wall invading the myometrium, with labels and clinical sampling cues. — **Panel A:** Longitudinal cut uterus showing tumour mass, posterior fundal wall, myometrial invasion, endometrial cavity, myometrium, cervix, and endocervical canal.. **Panel B:** Magnified posterior fundal wall cross-section showing endometrium, exophytic tumour, myometrium, and depth of myometrial invasion.. **Panel C:** Clinical pearl panel showing postmenopausal bleeding, TVS endometrial thickness threshold, endometrial sampling, and Lynch syndrome/MMR IHC alert..

CLINICAL PEARL

Postmenopausal bleeding = carcinoma until histology says otherwise.

Only 10% of women with PMB have endometrial carcinoma — but 90% of women with endometrial carcinoma present with vaginal bleeding. The asymmetry is everything: you cannot reassure without tissue.

TVS threshold: In a postmenopausal woman NOT on hormone replacement, an endometrial thickness of ≤ 3–4 mm has a negative predictive value of ~99% for carcinoma and may avoid biopsy. Any thickness > 4 mm, irregular echo texture, or inhomogeneity mandates endometrial sampling regardless of symptom severity.

Lynch syndrome alert: In a woman < 50 presenting with endometrial carcinoma, always consider Lynch syndrome (hereditary non-polyposis colorectal cancer — HNPCC). Reflex immunohistochemistry for mismatch repair proteins (MLH1, MSH2, MSH6, PMS2) should be performed on all endometrial carcinoma specimens under 60 — this has direct implications for colorectal cancer screening of the patient and her family.

Grading, FIGO Staging, Myometrial Invasion, and Routes of Spread

Histological grading (FIGO/WHO for endometrioid carcinoma):

Grade	Architecture	Nuclear Atypia
Grade 1	≤ 5% solid non-squamous growth	Mild
Grade 2	6–50% solid growth	Moderate
Grade 3	> 50% solid growth	Severe (upgrades G1 → G2 if severe atypia)

Serous and clear cell carcinomas are Grade 3 by definition.

FIGO Staging (2023 revised):

Stage	Definition
IA	Tumour confined to endometrium or invades < ½ myometrium
IB	Invades ≥ ½ myometrium
II	Invades cervical stroma (not just surface epithelium)
IIIA	Serosa or adnexal involvement
IIIB	Vaginal or parametrial involvement
IIIC1	Pelvic lymph node metastasis
IIIC2	Para-aortic lymph node metastasis
IVA	Bladder or bowel mucosa invasion
IVB	Distant metastasis (lung, liver, bone)

Schematic coronal pelvis diagram showing FIGO endometrial carcinoma stages IA, IB, II, IIIA, IIIC, and IVA by depth and direction of tumor spread. — **Panel A:** Coronal overview of uterus and pelvis with endometrium, myometrium, cervix, serosa, adnexa, bladder, bowel/rectum, pelvic lymph nodes, para-aortic lymph nodes, and color-coded FIGO stage spread.. **Panel B:** Stage IA with tumor confined to endometrium or invading less than half of the myometrium.. **Panel C:** Stage IB with tumor invading one half or more of the myometrium without serosal extension.. **Panel D:** Stage II with tumor extension into cervical stroma.. **Panel E:** Stage IIIA with tumor involving uterine serosa and/or adnexa including ovary or fallopian tube.. **Panel F:** Stage IIIC with metastatic pelvic and/or para-aortic lymph nodes.. **Panel G:** Stage IVA with tumor invasion into bladder mucosa and/or bowel or rectal mucosa..

Myometrial invasion is the single most important prognostic factor in Stage I disease. Depth correlates directly with lymphovascular invasion, nodal metastasis risk, and recurrence.

Routes of spread:
• Direct extension — to cervix, vagina, parametrium, bladder, rectum
• Lymphatic — to pelvic lymph nodes (obturator, internal iliac, external iliac), then para-aortic nodes (via ovarian lymphatics from the fundus)
• Transtubal (transcoelomic) — especially serous subtype — peritoneal seeding via fallopian tube
• Haematogenous — lungs, liver, bone (late stage)

SELF-CHECK

Histopathology of a hysterectomy specimen shows a Grade 2 endometrioid adenocarcinoma with invasion of exactly half the myometrial thickness. No cervical stromal involvement. No nodal or adnexal disease. What is the FIGO stage?

A. Stage IA

B. Stage IB

C. Stage II

D. Stage IIIA

Reveal Answer

Answer: B. Stage IB

Stage IB is defined as myometrial invasion of ≥ ½ the myometrial thickness with disease still confined to the uterine corpus. Stage IA is < ½ invasion. Stage II requires cervical stromal involvement. Stage IIIA requires serosa or adnexal spread. Since invasion is exactly half (≥ ½), this is Stage IB.