Endometrial hyperplasia and atypia — structured SAQ (15 marks)

(a) WHO 2014 classification and the role of atypia (3 marks)

One mark per point. [1][3]

• The revised 2014 WHO classification separates endometrial hyperplasia into two groups based on the presence of cytological atypia: (i) hyperplasia without atypia and (ii) atypical hyperplasia (AH), also termed endometrial intraepithelial neoplasia (EIN).[1][3]
• Cytologic atypia (nuclear enlargement, pleomorphism, hyperchromasia, prominent nucleoli, loss of polarity) — not architectural complexity alone — is the dominant predictor of progression. Kurman 1985: progression in 1.6 percent of hyperplasia without atypia (2 of 122) versus 23 percent of atypical hyperplasia (11 of 48); complex atypical hyperplasia 29 percent (10 of 35).
• The 2014 system replaces the 1994 four-tier schema (simple/complex x non-atypical/atypical) because architectural complexity alone is a weak discriminator.

(b) Concurrent carcinoma risk and first-line management (4 marks)

One mark per point, maximum four. [2][3]

• The GOG prospective cohort (Trimble 2006) found a 42.6 percent rate of concurrent endometrial carcinoma at hysterectomy within 12 weeks of an AH biopsy; 30.9 percent of those were myoinvasive.[2]
• A community diagnosis of AH also has high pathology discordance: central GOG re-review down-graded 25.6 percent to less than AH and up-graded 29.1 percent to frank carcinoma.
• First-line management for this 54-year-old is total hysterectomy (BSO because she is postmenopausal), laparoscopic preferred — because of the risk of concurrent or future invasive malignancy.
• Refer to gynaecological oncology, consent for cancer surgery (possible intra-operative staging), and avoid morcellation to prevent upstaging occult carcinoma.

(c) Fertility-sparing surveillance pathway (5 marks)

One mark per point, maximum five. [3][4]

• For a woman with AH wishing to preserve fertility or unfit for surgery: first-line LNG-IUS, oral progestogens second-line.[3]
• Endometrial biopsy every 3 months until two consecutive negative biopsies are obtained.
• After regression, biopsy every 6 to 12 months until a hysterectomy is performed.
• Once fertility is no longer required, hysterectomy should be offered in view of the high risk of disease progression and relapse (Gallos 2013: relapse 13.7 percent LNG-IUS, 30.3 percent oral progestogen).
• Refer to a fertility specialist; achieve regression on at least one biopsy before attempting conception; counsel clearly on the concurrent-cancer risk.

(d) Oral progestogen regimen and cyclical avoidance (3 marks)

One mark per point. [3]

• Continuous oral progestogens: medroxyprogesterone acetate 10–20 mg/day (or an equivalent continuous progestogen such as norethisterone), for women who decline the LNG-IUS.[3]
• Minimum 6 months treatment to induce histological regression.
• Cyclical progestogens are not used because they are less effective than continuous oral progestogens or the LNG-IUS at inducing regression.