Clinical overview
The pathology of heavy menstrual bleeding (HMB) is the pathology of the FIGO PALM-COEIN causes. This chapter complements heavy-menstrual-bleeding-management by drilling into the histology and mechanism for each cause. Understanding the pathology is what turns the registrar from someone who follows a flowchart into someone who can predict which treatment will succeed and which is likely to fail.
Core knowledge
Structural PALM causes alter the endometrium or myometrium through polyps, adenomyosis, submucosal fibroids and hyperplasia.
Polyp (P)
Pathology:
- Localised endometrial overgrowth with fibrovascular stroma; covered by endometrial epithelium.
- Sessile or pedunculated.
- Glandular pattern within polyp may be inactive, functional, or hyperplastic; rarely malignant (<5% in postmenopausal symptomatic polyps; <1% in premenopausal).
Clinical correlate:
- HMB and IMB through ulceration of polyp surface, asynchronous bleeding from polyp tissue.
- Often asymptomatic; sometimes presents with PMB.
- Removed for symptoms or to exclude malignancy.
Adenomyosis (A)
Pathology:
- Endometrial glands and stroma within myometrium.
- Surrounded by smooth muscle hypertrophy; junctional zone disordered.
- Cyclical bleeding within myometrial islands → inflammation, fibrosis, microhaemorrhages.
- Disturbed myometrial contractility.
Clinical correlate:
- Bulky, tender, boggy uterus.
- HMB and dysmenorrhoea (progressive over years).
- Often misdiagnosed as fibroids. See endometriosis-pathophysiology for detail and MUSA criteria for diagnosis (endometriosis-staging).
Leiomyoma (L) — fibroids
Pathology:
- Monoclonal benign smooth muscle tumour.
- Whorled bundles of smooth muscle cells.
- Pseudocapsule of compressed adjacent myometrium.
- Variable vascularity; may undergo degenerations: hyaline (most common), cystic, red (in pregnancy — ischaemic), calcific, sarcomatous (rare, <0.5%).
- FIGO classification 0–8: 0 (pedunculated intracavitary) → 8 (extrauterine pedunculated).
Mechanism of HMB:
- Increased endometrial surface area.
- Abnormal vasculature (increased capillary density, altered angiogenesis).
- Impaired myometrial contraction (in submucosal/intramural disease).
- Ulceration of submucosal fibroid surface.
Clinical correlate:
- HMB, dysmenorrhoea, pressure symptoms (urinary, bowel), bulk symptoms.
- Submucosal (FIGO 0–2) most relevant to HMB.
- See fibroids for full coverage.
Malignancy and hyperplasia (M)
Endometrial hyperplasia:
- Without atypia — overcrowded glands with cytologically benign appearance; ~1–3% lifetime malignancy risk.
- With atypia (endometrial intraepithelial neoplasia, EIN) — cytologic atypia, complex architecture; ~30% concurrent or progression to cancer.
- Driven by unopposed oestrogen (PCOS, obesity, HRT without progestogen, oestrogen-secreting tumours).
Endometrial cancer:
- Type 1 (endometrioid, 80%): oestrogen-driven, lower grade, better prognosis.
- Type 2 (serous, clear cell): not oestrogen-driven; aggressive; often older women.
- See endometrial-carcinoma.
Clinical correlate:
- HMB, IMB, PMB, persistent abnormal bleeding patterns.
- Risk factors: obesity, diabetes, nulliparity, late menopause, PCOS, tamoxifen, Lynch syndrome.
Coagulopathy (C)
- Von Willebrand disease (most common inherited bleeding disorder, ~1% population; ~5–20% women with HMB).
- Platelet function disorders.
- Thrombocytopenia (ITP, marrow disease).
- Acquired (liver disease, renal disease, anticoagulants).
Pathology:
- Normal endometrial vascular response but impaired haemostatic plug formation.
- vWD: deficient vWF → impaired platelet adhesion + factor VIII deficiency.
Clinical correlate:
- HMB since menarche.
- Personal/family bleeding history (epistaxis, gum bleeding, easy bruising, PPH).
Ovulatory dysfunction (O)
Pathology:
- Anovulation → no progesterone → unopposed oestrogen → endometrium proliferates without secretory transformation → eventually outgrows blood supply → asynchronous breakdown → irregular and often heavy bleeding.
- PCOS: hyperandrogenism, insulin resistance, anovulation.
- Hypothyroidism: alters TBG, SHBG, prolactin; affects gonadotropin pulsatility.
- Hyperprolactinaemia: suppresses GnRH.
- Perimenopause: declining ovarian reserve → erratic ovulation.
Clinical correlate:
- Irregular, often unpredictable cycles.
- Often coexist with HMB during ovulatory cycles or with heavy unpredictable bleeding during anovulatory cycles.
- Endometrial hyperplasia/cancer risk increased if persistent anovulation (need progestogen protection).
Endometrial (E) — primary
A diagnosis of exclusion: HMB with no structural pathology, ovulatory cycles, normal coagulation, no iatrogenic cause. Postulated mechanisms:
- Disordered local haemostasis (altered platelet plug formation in endometrium).
- Altered local fibrinolysis (excess plasmin activity in HMB — basis for tranexamic acid efficacy).
- Disordered prostaglandin synthesis (excess PGE2/PGF2α — basis for NSAID efficacy).
- Endothelin imbalance.
Iatrogenic (I)
- IUDs (especially copper IUD — heavier menses); LNG-IUS typically reduces.
- Anticoagulants (warfarin, DOACs, LMWH).
- Antiplatelets.
- Hormonal contraception breakthrough bleeding.
- Some chemotherapy agents (capecitabine, methotrexate).
Not otherwise classified (N)
- AV malformations (rare; pulsatile vessels in myometrium; require imaging diagnosis).
- Caesarean scar niche (isthmocele) — pooling of menstrual blood in a CS scar defect → prolonged spotting and HMB.
- Chronic endometritis.
- Tuberculosis of endometrium.
Assessment
Pathology-driven assessment is described in heavy-menstrual-bleeding-management. From a pathology lens:
- Sonographic features → suspect P, A, L, M.
- Hysteroscopy/SIS → identify cavity lesions.
- Endometrial biopsy → identify hyperplasia, atypia, malignancy.
- Coagulation screen + vWD panel → identify C.
- Cycle history + endocrine workup → identify O.
- Drug history → identify I.
Management
Specific to underlying pathology — see heavy-menstrual-bleeding-management for the stepped approach.
Red flags / pitfalls
- Calling all HMB "DUB" — that term is obsolete; use PALM-COEIN.
- Missing endometrial hyperplasia/cancer — biopsy threshold appropriately low.
- Ignoring von Willebrand disease in young women — refer haematology.
- Treating IUD-induced bleeding by removing the IUD without exploring whether the bleeding pattern would improve with time.
- Missing isthmocele as cause in a woman with prior CS and prolonged postmenstrual spotting.
- Failing to test for coagulopathy in adolescent HMB.
Evidence anchors
- FIGO PALM-COEIN classification (Munro MG et al., 2011, 2018 update).
- NICE NG88 — Heavy Menstrual Bleeding.
- RCOG GTG 67 — Endometrial Hyperplasia.
- WHO Classification of Female Genital Tumours, 5th edition.
- Munro MG. Practical aspects of the two FIGO classification systems for AUB. Best Pract Res Clin Obstet Gynaecol.
- NICE NG12 — Suspected cancer: recognition and referral.
- South African EML / NDoH Standard Treatment Guidelines.