Uterus
Smooth muscle tumors
Leiomyoma-general


Minor changes: 13 April 2021

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PubMed search: leiomyoma[title] uterus review[ptyp]

Léonie Alran, B.S.
Sabrina Croce, M.D., Ph.D.
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Cite this page: Alran L, Rychlik A, Croce S. Leiomyoma-general. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/uterusleiomyoma.html. Accessed May 16th, 2021.
Definition / general
Essential features
  • Benign mesenchymal tumor derived from smooth muscle
  • 90% of leiomyomas are the conventional type:
    • Conventional / usual leiomyoma:
      • Monotonous spindle cells with indistinct borders arranged in intersecting fascicles
      • Mitoses: rare (in general < 5/10 high power fields)
    • Subtypes:
      • Cellular
      • Bizarre nuclei
      • Fumarate hydratase (FH) deficient
      • Mitotically active
      • Hydropic
      • Apoplectic
      • Lipoleiomyoma
      • Epithelioid
      • Myxoid
      • Dissecting leiomyoma
      • Diffuse leiomyomatosis
ICD coding
  • ICD-O: 8890/0 - leiomyoma, NOS
  • ICD-11: 2E86.0 - leiomyoma of uterus
Epidemiology
Sites
  • Uterine corpus; less common in vulva, vagina, cervix, broad ligament, ovary
Pathophysiology
  • Leiomyomas have a clonal origin
  • Several alterations identified (Table 1) (Clin Obstet Gynecol 2016;59:25)
  • Risk decreased by oral contraceptives
  • May occur in hereditary leiomyomatosis and renal cancer syndrome (HLRCC) and Alport syndrome
Etiology
  • Mitotically active leiomyoma: associated ischemia or hormonal stimulation (endogenous or exogenous) (Am J Surg Pathol 2016;40:563)
  • Apoplectic leiomyoma: progesterone (or analogues) exposure (contraception or pregnancy and postpartum)
Diagrams / tables

Contributed by Sabrina Croce, M.D., Ph.D.

Table 1: molecular alterations



Table 2: differential diagnosis in uterine spindle cell smooth muscle lesions
Tumor cell necrosis
Atypia
Mitoses*
Diagnosis
- + ≥ 10 Leiomyosarcoma
+ + ≥ 10
+ + < 10
- - > 15** Smooth muscle tumor of
uncertain malignant
potential (STUMP)
- + < 10
+ - < 10
- - ≥ 6 and ≤ 15** Mitotically active leiomyoma
* Mitoses/10 high power fields
** > 15 or ≥ 15, cutoff value varies according to the references


Table 3: differential diagnosis in uterine myxoid smooth muscle lesions
Myxoid leiomyoma
Myxoid STUMP
Myxoid leiomyosarcoma
Infiltrative borders - -
1 or more of these criteria:
  • Mitoses: ≥ 2
  • Tumor cell necrosis
  • Atypia
Atypia - -
Tumor cell necrosis - -
Mitoses* - 1
* Mitoses/10 high power fields


Table 4: differential diagnosis in uterine epithelioid smooth muscle lesions
Epithelioid leiomyoma
Epithelioid STUMP
Epithelioid leiomyosarcoma
Atypia - - 1 or more of these criteria:
  • Mitoses: ≥ 4
  • Tumor cell necrosis
  • Atypia
Tumor cell necrosis - -
Mitoses* < 2 ≥ 2 and < 4
* Mitoses/10 high power fields
Clinical features
  • 25% symptomatic; remainder asymptomatic
  • Symptoms depend on size and location
  • Menorrhagia and pelvic pain in 33% of patients
  • Reference: Nat Rev Dis Primers 2016;2:16043
Diagnosis
  • Can be established by resection of the whole uterus (hysterectomy), by resection of the leiomyoma if accessible by curetting (if submucosal) or by myomectomy (if subserosal)
  • Ultrasound or MRI guided core biopsy of the leiomyoma is a promising new procedure (Int J Gynecol Cancer 2020;30:A113)
Prognostic factors
  • Uterine leiomyomas are benign tumors that may recur, especially after myomectomy; fumarate hydratase deficient leiomyomas recur more frequently
    • For fumarate hydratase deficient leiomyomas, genetic counseling should be recommended
Case reports
Treatment
  • Asymptomatic: does not require therapy
  • Symptomatic leiomyoma:
    • Surgery (hysterectomy or myomectomy)
    • Hysteroscopic resection
    • Medical treatment - progestins / levonorgestrel intrauterine system, gonadotropin releasing hormone (GnRH) analogs or aromatase inhibitors
      • Ulipristal acetate; widely used in conservative treatment of uterine fibromas but rejected by the FDA due to risk of liver toxicity
    • Interventional treatments - uterine artery embolization or radiofrequency myolysis
  • Reference: J Obstet Gynaecol Can 2015;37:157
Gross description
  • Location in the uterus: intramural, submucosal and subserosal
  • Often multiple
  • Typically well circumscribed but nonencapsulated
  • On cut surface: white or tan-white, whorled, firm, bulging
  • Hemorrhage and infarction can be present in large tumors
  • Calcifications can be present
  • Apoplectic change (foci of hemorrhage) associated with progesterone therapy
  • Extensive sampling (to exclude malignancy)
    • Especially in leiomyomas that lack the classic gross appearance
    • Myxoid areas to exclude myxoid leiomyosarcoma
  • Reference: Mod Pathol 2016;29:S104
Gross images

Contributed by Sabrina Croce, M.D., Ph.D.

Submucosal leiomyoma

Intramural leiomyoma

Subserosal leiomyomas

Apoplectic leiomyoma

Conventional / usual leiomyoma

Microscopic (histologic) description
  • Conventional / usual leiomyoma (spindle):
    • Well defined borders
    • Normocellular
    • Intersecting fascicles of monotonous spindle cells with indistinct borders, eosinophilic cytoplasm, cigar shaped nuclei (with tapered ends) and small nucleoli
    • Atypia: absent or mild
    • Mitoses: rare (in general < 5/10 high power fields)
    • Blood vessels with thick walls
    • With or without infarct type necrosis, hyalinization, calcification, cystic change
  • Subtypes:
    • Cellular
      • Increased cellularity (more cellular than background myometrium)
      • Scant cytoplasm without increased mitotic activity and atypia
      • May have irregular borders
    • Bizarre nuclei:
    • Fumarate hydratase deficient leiomyoma:
      • Alveolar edema
      • Staghorn or hemangiopericytoma-like vessels
      • Chain-like growth of tumor cells
      • Spindle or epithelioid cells with ovoid nuclei and prominent eosinophilic nucleoli surrounded by perinucleolar halos
      • Rhabdoid / eosinophilic cytoplasmic inclusions
      • May include multinucleated cells and cells with bizarre nuclei
    • Mitotically active:
      • Spindle cell leiomyoma without atypia or tumor cell necrosis
      • Increased mitotic activity (the mitotic cutoff varies according to the authors 6 - 14 mitoses/10 high power fields or 6 - 15 mitoses/10 high power fields)
    • Hydropic:
      • Tumor cells separated by watery or eosinophilic and proteinaceous fluid, resulting in a trabecular, nested architecture
    • Apoplectic:
      • Central zone of hemorrhage and necrosis with increased mitotic activity in its periphery or myxoid changes (zonation phenomenon)
      • Usual appearance away from the central necrosis
    • Lipoleiomyoma:
      • Tumor composed of smooth muscle cells mixed with mature adipocytes (variable quantity)
    • Epithelioid:
      • Round or polygonal cells with eosinophilic or clear cytoplasm (in general, ≥ 50% of tumor cells)
      • Nested or trabecular architecture
      • No cytologic atypia or tumor cell necrosis
      • Mitotic count is < 2 mitoses/10 high power fields
    • Myxoid:
      • Hypocellular tumor
      • Cells separated by myxoid matrix composed of glycosaminoglycan (Alcian blue+) occupying ≥ 50% of the overall tumor volume
      • Well circumscribed borders (most important criteria)
      • No cytologic atypia, mitoses or tumor cell necrosis
    • Dissecting leiomyoma:
      • Nodules of smooth muscle cells dissecting the myometrium; occasionally hydropic changes and intravenous extension can be seen
      • Called cotyledonoid leiomyoma if extends outside the uterus
    • Diffuse leiomyomatosis:
      • Diffuse, poorly circumscribed, innumerable tumor nodules in the myometrium
      • No atypia and tumor cell necrosis
      • Low mitotic count
Microscopic (histologic) images

Contributed by Sabrina Croce, M.D., Ph.D.

Conventional / usual leiomyoma

Cellular leiomyoma


FH deficient leiomyoma


Leiomyoma with bizarre nuclei


Hydropic leiomyoma

Apoplectic leiomyoma

Epithelioid leiomyoma


Myxoid leiomyoma

Lipoleiomyoma

Virtual slides

Images hosted on other servers:

Leiomyoma

Leiomyoma with bizarre nuclei

Highly cellular leiomyoma

Lipoleiomyoma

Positive stains
Negative stains
  • p16 negative or patchy (except in leiomyomas with bizarre nuclei, where it can be diffusely positive)
  • p53 typically wildtype (except in leiomyomas with bizarre nuclei, where it can show aberrant expression)
Molecular / cytogenetics description
Sample pathology report
  • Uterus, total hysterectomy:
    • Conventional leiomyoma: 5.0 cm (see comment)
    • Comment: Microscopic examination reveals a smooth muscle tumor composed of spindle, cigar shaped cells arranged in fascicular pattern without cytologic atypia and tumor cell necrosis. Mitoses are rare (4 mitoses/10 high power fields). Tumor borders are well circumscribed. By immunohistochemistry the tumor cells are positive for desmin, h-caldesmon, ER and PR.
Differential diagnosis
Board review style question #1

A 23 year old woman with multiple recurrent leiomyomas is diagnosed with a FH deficient leiomyoma. Which of the following is true?

  1. FH deficiency is a risk factor for uterine leiomyosarcoma
  2. Staghorn vessels, alveolar oedema, macronuclei with perinucleolar halos and cytoplasmic eosinophilic globules are typical morphologic features of FH deficient leiomyoma
  3. Bizarre nuclei and FH deficient leiomyoma are mutually exclusive
  4. All FH deficient leiomyomas are 2SC positive and FH negative
  5. All FH deficient leiomyomas are associated with a germline mutation
Board review style answer #1
B. Staghorn vessels, alveolar oedema, macronuclei with perinucleolar halos and cytoplasmic eosinophilic globules are typical morphologic features of FH deficient leiomyoma

Comment Here

Reference: Leiomyoma-general
Board review style question #2

A 44 year old woman presents with 4 cm leiomyoma with bizarre nuclei. Which of the following is true?

  1. The presence of atypia alone is a sufficient criterion warrant the diagnosis of leiomyosarcoma
  2. Significant number of leiomyomas with bizarre nuclei harbor FH biallelic inactivation
  3. Leiomyomas with bizarre nuclei are malignant
  4. p16 staining is a reliable marker of leiomyomas with bizarre nuclei
  5. Arteriolarization of vessels is a typical feature of bizarre nuclei leiomyoma
Board review style answer #2
B. Significant number of leiomyomas with bizarre nuclei harbor FH biallelic inactivation

Comment Here

Reference: Leiomyoma-general
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