REGUB Path - Uterus (ii)

Carcinoma

epithelial derived

2 subsets

type 1: oestrogen dependent

younger patients (40s-60s, but even 30s)

better prognosis

preexisting hyperplasia

microsat instability, mutations in KRAS, PTEN, beta-catenin

type 2: non-oestrogen dependent

worse prognosis

older women

P53 mutations, LOH of several chromo

endometrioid adenocarc

most common

usually low grade + stage - good prognosis - surgery usually curative

affects perimenopausal women (40-60)

grading based on gland architecture (more aggressive tumours have less glands + are increasingly solid) + nuclear features

a/w squamous metaplasia

clear cell carc - related to endometrioid, but more mutations - worse prognosis

serous carc

most have papillary architecture

high grade pleomorphic nuclei - SMUDGE CELLS

serious - worse prognosis - rapid spread along tubes

consider drop down mets (ovarian primary - or there could be simply 2 primaries)

60+ y/o

often on surface of polyps

mucinous carc (rare)

a/w PTEN

tumour suppressor gene

chromo 10q33

regulates cell prolif + apoptosis

normal endometrium: high levels in prolif phase, absent in mid-late secretory phase

lost in 97% of cancers

isolated -ve glands may be earliest precursors

Carcinosarcoma

Malignant mixed mullerian tumour

epithelial (glands) + non-epithelial (mesenchymal - spindle cells [cart/muscle]) elements

malignant stroma between glands

particularly aggressive

usually polypoid

common in elderly patients with hx of radiation (e.g. for cervical cancer) 10-15 yrs ago

Staging

depth of invasion

if tumour invades outer 1/2 of myometrium, worse prognosis due to access to blood vessels

involvement of other organs (e.g. cervix)

Leiomyoma

fibroid

benign smooth muscle tumour (of myometrium)

clonal abnormalities

DOES NOT TRANSFORM TO A LEIOMYOSARCOMA

round, well-circumscribed, unencapsulated, white, whorled myometrial mass(es)

intramural, submucosal or subserosal

no haemorrhage or necrosis

grow slowly

tx: cannula in fem art - PVA (poly vinyl alcohol) beads to try shrink them) - giant cell reaction

Leiomyosarcoma

haemorrhage/necrosis

mitoses, necrosis, atypia, pleomorphism

NO PRECURSOR - starts malignant

round, intramural

usually 40-60 y/o

recur + met (lung, bone, brain)

single large mass >5cm, usually >10cm, irregular, infiltrating

not white

outgrows its blood supply - necrosis in centre

Stromal tumours

pure stroma

yellow - potentially hormone-producing

stromal nodule: benign, well-circumscribed

stromal sarcoma: infiltrative margin, lymphatic invasion, may recur in approx 11-12 yrs

undifferentiated endometrial sarcoma: aggressive