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Uterine Fibroids (Leiomyomas) - Full Breakdown
What Are They?
A uterine fibroid (leiomyoma, myoma) is a benign monoclonal smooth muscle tumor arising from the myometrium. They are the most common tumor in women, present in up to 40% of reproductive-age women and up to 70-80% by age 50. They are also the most common reason hysterectomy is performed (~240,000 per year in the US).
- Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 937
- Berek & Novak's Gynecology, p. 497
Pathogenesis & Molecular Biology
Fibroids are monoclonal tumors - each one arises from a single smooth muscle cell. Key molecular points:
| Feature | Detail |
|---|---|
| MED12 mutation | Found in ~70% of fibroids. MED12 encodes a subunit of the Mediator complex, which bridges transcription factors to RNA polymerase |
| HMGC / HMGIY | Rearrangements of chromosomes 12q14 and 6p; these encode chromatin-regulating DNA-binding factors |
| Fumarate hydratase (FH) | Germline mutations cause HLRCC syndrome (hereditary leiomyoma + renal cell carcinoma); somatic FH mutations occur in sporadic fibroids too |
| Hormonal dependence | Require estrogen AND progesterone for growth; shrink after menopause; can grow rapidly in early pregnancy |
Fibroids contain large aggregations of extracellular matrix - collagen, elastin, fibronectin, and proteoglycan - in addition to smooth muscle. This explains their firm, rubbery texture.
Risk Factors
| Factor | Effect |
|---|---|
| Black/African American race | 2.9x higher risk vs. white women; earlier onset, more numerous, larger, more symptomatic |
| Family history | 2.5x increased risk in first-degree relatives |
| Obesity | 21% increased risk per 10 kg weight gain; obesity raises biologically available estrogen via increased androgen-to-estrone conversion + decreased SHBG |
| Nulliparity | Increasing parity is protective - postpartum uterine remodeling may cause fibroid involution |
| Red meat/processed meat diet | Associated with increased risk |
| Physical activity | Women with >7 hrs/week of exercise significantly less likely to have fibroids |
| OCP use | No definitive relationship with fibroid formation or growth |
- Berek & Novak's Gynecology, p. 500-502
Classification - FIGO System
The FIGO system categorizes fibroids 0-8 based on location relative to the endometrium and serosa:
| Type | Location | Surgical Approach |
|---|---|---|
| 0 | Intracavitary (pedunculated, entirely in cavity) | Vaginal or hysteroscopic |
| 1 | Submucosal, <50% in myometrium | Hysteroscopic |
| 2 | Submucosal, ≥50% in myometrium | Hysteroscopic or open/lap |
| 3 | Abuts endometrium, no intracavitary component | Open or laparoscopic |
| 4 | Entirely intramural | Open or laparoscopic |
| 5 | Subserosal, ≥50% intramural | Open or laparoscopic |
| 6 | Subserosal, <50% intramural | Open or laparoscopic |
| 7 | Pedunculated subserosal (stalk-attached) | Open or laparoscopic |
| 8 | Extrauterine (cervical, parasitic, broad ligament) | Open or laparoscopic |
Transmural fibroids span both surfaces and are described with both relationships (e.g., "2-5").
- Sabiston Textbook of Surgery, p. (Table 120.5)
- Berek & Novak's Gynecology, p. 506
Morphology (What They Look Like)
Gross:
- Sharply circumscribed, discrete, round, firm, gray-white tumors
- Classic whorled pattern of smooth muscle bundles on cut section
- Range from tiny nodules to massive pelvic tumors
- Large tumors may develop areas of yellow-brown to red softening (degeneration)
Microscopic:
- Bundles of smooth muscle cells resembling normal myometrium
- Uniform cells with oval nucleus, long bipolar cytoplasmic processes
- Scarce mitotic figures (key differentiator from leiomyosarcoma)
- Variants include: leiomyoma with bizarre nuclei, cellular leiomyoma - both benign if low mitotic index
Rare variants:
-
Intravenous leiomyomatosis - extends into vessels, may reach vena cava/right atrium; considered benign
-
Disseminated peritoneal leiomyomatosis - multiple peritoneal nodules; benign despite appearance
-
Robbins, Cotran & Kumar, p. 937
Symptoms
Most fibroids are asymptomatic. When symptomatic, location matters more than size:
| Symptom | Mechanism / Notes |
|---|---|
| Abnormal uterine bleeding (menorrhagia) | Submucosal fibroids are most responsible - distort endometrial cavity |
| Pelvic pressure / bulk symptoms | Large or multiple fibroids pressing on adjacent structures |
| Urinary frequency | Bladder compression |
| Constipation | Posterior fibroid pressure on rectum |
| Dysmenorrhea / dyspareunia | Broad ligament or cervical fibroids |
| Acute pelvic pain | Degeneration (loss of blood supply) or torsion of pedunculated fibroid |
| Infertility / recurrent miscarriage | Submucosal fibroids have the strongest effect; intramural may slightly reduce fertility |
| "Fibroid expulsion" pain | A submucous pedunculated fibroid causes uterine contractions like labor, with cramping + hemorrhage |
There is no strong correlation between the degree of pain and fibroid volume or number. Do not assume a large fibroid = more pain.
Fibroid Degeneration Types
When fibroids outgrow their blood supply, they degenerate:
| Type | Appearance / Notes |
|---|---|
| Hyaline | Most common; fibrotic change |
| Cystic | Liquefaction of hyaline areas |
| Myxoid | Mucoid degeneration |
| Red (carneous) | Common in pregnancy; hemorrhagic infarction; causes acute pain |
| Calcific | Dystrophic calcification, often postmenopausal |
Diagnosis
| Modality | Use |
|---|---|
| Pelvic exam | Enlarged, irregular, firm, non-tender uterus. Works well even for BMI >30 |
| Pelvic ultrasound | First line; differentiates fibroids from adnexal masses; less good for submucosal |
| Saline infusion sonography (SIS) | Better for submucosal fibroids |
| MRI | Gold standard for mapping - most precise for number, size, and position including cavity proximity |
| Hysteroscopy | Directly visualizes and allows treatment of submucosal fibroids |
A definitive diagnosis of submucous fibroids requires SIS, hysteroscopy, or MRI. - Berek & Novak's Gynecology, p. 506
Fibroids & Fertility
A critical clinical pearl:
-
Submucosal fibroids - reduce fertility; removal increases fertility
-
Subserosal fibroids - do NOT affect fertility; removal does NOT increase fertility
-
Intramural fibroids - may slightly reduce fertility; removal does NOT clearly increase fertility
-
Berek & Novak's Gynecology, p. 497
Fibroids in Pregnancy
Most fibroids do not grow during pregnancy despite the hormonal milieu. Complications are possible:
- Increased risk of cesarean section (23% vs 12%)
- Increased risk of preterm delivery (~19% vs 13%)
- Placenta previa (3.5% vs 1.8%)
- Postpartum hemorrhage (8.3% vs 2.9%)
- Fetal malpresentation, uterine inertia
- Red degeneration - painful but self-limiting, treated conservatively
Uterine rupture after myomectomy: Risk during trial of labor is ~0.47% (similar to post-cesarean). Risk is higher if laparoscopic myomectomy was done without proper multilayered closure.
- Berek & Novak's Gynecology, p. 513
- Creasy & Resnik's Maternal-Fetal Medicine
Management
Watchful Waiting
- Appropriate for asymptomatic or mildly symptomatic women
- As women approach menopause, watchful waiting is reasonable - fibroids shrink after menopause and bleeding stops
Medical Treatment
| Drug | Mechanism | Notes |
|---|---|---|
| GnRH agonists (leuprolide) | Hypoestrogenic state causes fibroid shrinkage | Short-term only (bone loss); used preop to shrink fibroids |
| GnRH antagonists (elagolix, relugolix) | Same but oral; given with add-back estradiol + norethindrone to preserve bone | Elagolix 300 mg BID, relugolix 40 mg OD |
| Mifepristone (anti-progesterone) | Reduces fibroid size and symptoms | 5 mg/day x 6 months or 10 mg/day x 3 months; benefits often transient |
| Ulipristal acetate (SPRM) | Selective progesterone receptor modulator | 5-10 mg/day x 13 weeks |
| NSAIDs (naproxen, mefenamic acid) | Symptomatic relief of pain/heavy bleeding | |
| Combined OCPs / progestins / LNG-IUS | Reduce bleeding | Do not significantly shrink fibroids |
Surgical Treatment
| Procedure | Indication | Notes |
|---|---|---|
| Hysteroscopic myomectomy | Submucosal fibroids (Type 0, 1, 2) | Preserves fertility; preferred for cavity fibroids |
| Laparoscopic myomectomy | Subserosal / intramural, fertility-preserving | Needs meticulous multilayer closure |
| Abdominal myomectomy | Large/multiple fibroids, fertility desired | Safe alternative to hysterectomy even for very large uteri |
| Hysterectomy | Definitive; for women not desiring fertility | Can be abdominal, vaginal, or laparoscopic |
| Uterine artery embolization (UAE) | Good option when surgery not desired | Myomectomy has better outcomes than UAE for fertility; 17.5% need subsequent hysterectomy after UAE |
| Focused ultrasound surgery (FUS) | Noninvasive; for selected patients | |
| Laparoscopic radiofrequency ablation | Minimally invasive option |
Power morcellation during laparoscopic myomectomy is restricted due to risk of disseminating occult malignancy.
- Goldman-Cecil Medicine, p. treatment section
- Sabiston Textbook of Surgery, Table 120.5
Malignant Transformation
Transformation to leiomyosarcoma is extremely rare (roughly 1 in 1000-1500 women under 45). Fibroids are not premalignant lesions. A rapidly enlarging uterus almost never indicates sarcoma in a premenopausal woman - sarcomas are more typical in postmenopausal women presenting with pain and bleeding.
Quick Summary Table
| Feature | Key Point |
|---|---|
| Most common tumor in women | Up to 80% by age 50 |
| Origin | Monoclonal smooth muscle cell |
| Key mutation | MED12 (~70%) |
| Hormone dependence | Estrogen + progesterone; shrink after menopause |
| Most symptomatic location | Submucosal (menorrhagia, infertility) |
| Best imaging | MRI for mapping; U/S for initial eval |
| Fertility impact | Only submucosal removal clearly improves fertility |
| Degeneration in pregnancy | Red (carneous) degeneration - painful, conservative |
| Malignant transformation | Extremely rare |
| Definitive treatment | Hysterectomy; fertility-sparing = myomectomy |
Sources used:
- Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 937
- Berek & Novak's Gynecology, pp. 497-513
- Sabiston Textbook of Surgery, Table 120.5
- Goldman-Cecil Medicine, treatment section
- Creasy & Resnik's Maternal-Fetal Medicine
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