Endometrial cancer (mechanism of disease)

ERRATA: Type 1 is more associated with PTEN; Type 2 with p53. Thanks, @jl9774.

This is a mechanism of disease flowchart for endometrial cancer, covering the etiology, pathophysiology, and manifestations.

ADDITIONAL TAGS:
Pharmacology / toxicity
Infectious / microbial
Biochem / molecular bio
Mutation
Signs / symptoms
Labs / tests / imaging results
Endometrial cancer
Core concepts
Social determinants of
health / risk factors
Hormone changes
Genetics / hereditary
Mass effect
Pathophysiology
Etiology
Manifestations
Mutation, such as:
-Loss of function or null mutation in tumor suppressor gene (p53 [Type I] or PTEN [Type II])
-Increase in activity of oncogene (Her2/neu)
Long term exposure to ↑ estrogen levels
Genetic predisposition
Nulliparity
Early menarche
Late menopause
↑ fat cells contain aromatase
↑ insulin
Production of extraovarian estrogen
Metabolic syndrome (obesity, DM2)
↑ IGF-2 → proliferation of endometrial cells
Unopposed estrogen replacement therapy, such as for menopause symptoms, without added progestin
Tamoxifen treatment
History of breast cancer
Hereditary nonpolyposis colorectal cancer (Lynch syndrome)
Older
Post-menopausal
African American
Type I, estrogen-dependant
Type II
estrogen-independent,
endometrial atrophy
↑ progesterone
Multiparity
Combined OCPs
Lifelong soy diet
Regular exercise
↑ androgen
x
x
Protective factors
Smoking
x
Abnormal uterine bleeding
-Postmenopausal: anything
-Pre-/perimenopausal: heavy, irregular, intermenstrual
+/- enlarged uterus
Contiguous spread, regional extension
Metastatic spread
Pelvic pain
Vaginal mass
Weight loss
Lethargy
Pleural effusion
Cough
Anemia
TVUS: endometrial thickness 4 mm
Biopsy: Endometrial hyperplasia with atypia +/- concomitant adenocarcinoma
Abdominal distension
Abnormal cervix