Definition/General

Introduction:
-Endometrial Leiomyoma, commonly called uterine fibroid, is a benign smooth muscle tumor of the uterus
-It arises from the myometrium but may extend into or indent the endometrial cavity
-Submucosal fibroids directly affect the endometrium
-They are the most common gynecological tumors.
Origin:
-Arises from smooth muscle cells of the myometrium
-Results from monoclonal proliferation
-Estrogen and progesterone promote growth
-Growth factors and extracellular matrix involved
-May originate from vascular smooth muscle
-Genetic predisposition exists.
Classification:
-Submucosal: Projects into endometrial cavity
-Intramural: Within myometrial wall
-Subserosal: Projects from uterine surface
-Pedunculated: On a stalk
-Intraligamentary: Between broad ligament layers
-Cervical: In cervical stroma.
Epidemiology:
-Extremely common: 70-80% of women by age 50
-Peak incidence in 4th-5th decades
-Higher prevalence in African American women
-Associated with reproductive years
-Estrogen-dependent growth
-Often multiple (70-80% cases).

Clinical Features

Presentation:
-Heavy menstrual bleeding (most common symptom)
-Pelvic pressure and bulk symptoms
-Urinary frequency
-Constipation
-Infertility (submucosal type)
-Recurrent pregnancy loss
-Asymptomatic (50% of cases).
Symptoms:
-Menorrhagia (70-80% of symptomatic cases)
-Pelvic pain and pressure
-Urinary symptoms (frequency, urgency)
-Bowel symptoms (constipation)
-Abdominal distension
-Dyspareunia
-Fatigue (due to anemia).
Risk Factors:
-Age (reproductive years)
-African American ethnicity
-Nulliparity
-Early menarche
-Family history
-Obesity
-Hypertension
-Red meat consumption
-Vitamin D deficiency.
Screening:
-Pelvic examination
-Transvaginal ultrasound (first-line imaging)
-MRI (for surgical planning)
-Hysteroscopy (submucosal fibroids)
-Complete blood count (anemia assessment)
-Endometrial biopsy (if indicated).

Master Leiomyoma Pathology with RxDx

Access 100+ pathology videos and expert guidance with the RxDx app

Get it on Google Play Download on the App Store

Gross Description

Appearance:
-Well-circumscribed, firm masses
-Gray-white cut surface with whorled pattern
-Rubbery consistency
-May show calcification
-Cystic degeneration possible
-Hemorrhage and necrosis in degenerating fibroids
-Pseudocapsule present.
Characteristics:
-Smooth, lobulated external surface
-Whorled, fascicular cut surface pattern
-Firm to hard consistency
-Distinct borders from surrounding myometrium
-May contain calcifications
-Variable sizes
-Multiple nodules common.
Size Location:
-Size ranges from millimeters to >20cm
-Submucosal: Indents endometrial cavity
-Intramural: Within myometrial wall
-Subserosal: Projects from serosa
-May be pedunculated
-Multiple locations common
-Fundal predominance.
Multifocality:
-Multiple fibroids in 70-80% of cases
-Variable sizes
-Different locations and types
-May show different degrees of degeneration
-Satellite nodules possible
-Dominant fibroid often present.

Microscopic Description

Histological Features:
-Interlacing fascicles of smooth muscle cells
-Spindle-shaped cells with eosinophilic cytoplasm
-Cigar-shaped nuclei
-Low mitotic activity (<5 mitoses/10 HPF)
-Hyalinized areas
-Thick-walled blood vessels
-Pseudocapsule.
Cellular Characteristics:
-Uniform spindle cells
-Elongated, blunt-ended nuclei
-Eosinophilic, fibrillar cytoplasm
-Indistinct cell borders
-No nuclear atypia
-Minimal mitotic activity
-Longitudinal striations visible
-Well-differentiated appearance.
Architectural Patterns:
-Fascicular arrangement
-Interlacing bundles
-Whorled pattern
-Pushing borders
-Compressed surrounding tissue
-May contain entrapped glands
-Hyalinization and calcification
-Cystic degeneration.
Grading Criteria:
-Benign leiomyoma: <5 mitoses/10 HPF, no atypia
-Cellular leiomyoma: Increased cellularity, <5 mitoses/10 HPF
-Mitotically active: 5-9 mitoses/10 HPF, no atypia
-Atypical leiomyoma: Moderate atypia, <10 mitoses/10 HPF
-Assessment of size, mitoses, and atypia.

Immunohistochemistry

Positive Markers:
-Smooth muscle actin (diffusely positive)
-Desmin (positive)
-Caldesmon (positive)
-Calponin (positive)
-ER positive (usually strong)
-PR positive
-WT1 negative
-h-Caldesmon (specific).
Negative Markers:
-Cytokeratin negative
-S-100 negative
-CD10 negative
-Inhibin negative
-Chromogranin negative
-CD117 negative
-DOG1 negative (versus GIST).
Diagnostic Utility:
-Smooth muscle actin confirms smooth muscle origin
-h-Caldesmon specific for smooth muscle
-ER/PR shows hormone responsiveness
-Desmin supports muscle differentiation
-CD117 negative excludes GIST
-Cytokeratin negative excludes carcinoma.
Molecular Subtypes:
-Conventional leiomyoma
-Cellular leiomyoma
-Epithelioid leiomyoma
-Myxoid leiomyoma
-Lipoleiomyoma
-Atypical leiomyoma
-Mitotically active leiomyoma.

Molecular/Genetic

Genetic Mutations:
-MED12 mutations (70% of leiomyomas)
-HMGA2 rearrangements
-FH mutations (hereditary leiomyomatosis)
-Chromosomal aberrations
-del(7q)
-t(12;14)
-Clonal origin.
Molecular Markers:
-Estrogen receptor expression
-Progesterone receptor expression
-Growth factors (IGF, EGF)
-Extracellular matrix proteins
-Collagen overproduction
-TGF-β expression
-VEGF expression.
Prognostic Significance:
-Excellent prognosis for benign leiomyomas
-Malignant transformation extremely rare (<0.1%)
-Growth during pregnancy
-Regression after menopause
-Size and location affect symptoms
-Recurrence after myomectomy possible.
Therapeutic Targets:
-Hormonal therapy: GnRH agonists
-Selective progesterone receptor modulators (SPRMs)
-Aromatase inhibitors
-Myomectomy
-Uterine artery embolization
-Focused ultrasound
-Hysterectomy (definitive).

Differential Diagnosis

Similar Entities:
-Leiomyosarcoma
-Endometrial stromal sarcoma
-Adenomyosis
-GIST
-Undifferentiated sarcoma
-Metastatic sarcoma
-Smooth muscle tumor of uncertain malignant potential (STUMP).
Distinguishing Features:
-Leiomyoma: <5 mitoses/10 HPF, no atypia
-Leiomyosarcoma: >10 mitoses/10 HPF, atypia, necrosis
-ESS: CD10 positive, spiral arteries
-GIST: CD117 positive, DOG1 positive
-Adenomyosis: Endometrial glands present.
Diagnostic Challenges:
-Distinguishing atypical leiomyoma from leiomyosarcoma
-Cellular leiomyoma versus sarcoma
-Smooth muscle tumor of uncertain malignant potential
-Degenerative changes
-Sampling adequacy
-Size criteria application.
Rare Variants:
-Epithelioid leiomyoma
-Myxoid leiomyoma
-Cellular leiomyoma
-Hemorrhagic cellular leiomyoma
-Lipoleiomyoma
-Angioleiomyoma
-Bizarre leiomyoma (pleomorphic).

Sample Pathology Report

Template Format

Sample Pathology Report

Complete Report: This is an example of how the final pathology report should be structured for this condition.

Patient Information

Name: [Patient Name]\nAge: [X] years\nMRN: [Medical Record Number]\nDate of Procedure: [Date]

Clinical History

Clinical indication: [Heavy menstrual bleeding/Pelvic pressure/Bulk symptoms/Infertility/Asymptomatic]\nSymptoms: [Menorrhagia/Pelvic pain/Urinary frequency/Constipation/None]\nImaging: [Ultrasound/MRI findings]\nProcedure: [Myomectomy/Total hysterectomy/Other]

Specimen Received

Specimen type: [Myomectomy specimen/Hysterectomy with leiomyomas]\nNumber of tumors: [Single/Multiple] ([X] total)\nLargest tumor size: [X] cm\nFixative: 10% neutral buffered formalin

Gross Examination

[Myomectomy: The specimen consists of a well-circumscribed, firm, [single/multiple] nodular mass(es) measuring [X] cm in greatest dimension. The external surface is smooth and shows a thin pseudocapsule.]\n[Hysterectomy: The uterus contains [single/multiple] well-circumscribed, firm intramural/submucosal/subserosal nodule(s) measuring up to [X] cm.]\nCut surface reveals a gray-white, whorled appearance with a rubbery consistency. [Calcification/Cystic degeneration/Hemorrhage/Necrosis] is [present/absent]. The tumor appears [well-circumscribed/encapsulated] with [clear/indistinct] margins from surrounding myometrium.

Microscopic Examination

Sections show a benign smooth muscle tumor composed of interlacing fascicles of uniform spindle cells. The cells have elongated, blunt-ended nuclei with fine chromatin and eosinophilic, fibrillar cytoplasm. Nuclear atypia is [absent/minimal]. Mitotic activity is low with [X] mitoses per 10 high power fields (normal <5/10 HPF). [Tumor necrosis is absent/present]. [Hyalinization/Calcification/Cystic degeneration] is [present/absent]. The tumor shows [well-defined/infiltrative] borders with [compressed surrounding myometrium/clear margins]. [Associated degenerative changes include: specify if present].

Immunohistochemistry (if performed)

Smooth Muscle Actin: [Diffusely positive]\nDesmin: [Positive]\nh-Caldesmon: [Positive]\nEstrogen Receptor: [Positive/Negative]\nProgesterone Receptor: [Positive/Negative]\nKi-67 proliferation index: [Low (<5%)]

Final Diagnosis

BENIGN LEIOMYOMA (UTERINE FIBROID)\n\nSize: [X] cm in greatest dimension\nLocation: [Intramural/Submucosal/Subserosal/Pedunculated]\nNumber: [Single/Multiple]\nMitotic count: [X] per 10 HPF\nNecrosis: [Absent/Present]\nMargins: [Clear/Not applicable for hysterectomy]

Comments

• Benign smooth muscle tumor with excellent prognosis.\n• Malignant transformation to leiomyosarcoma is extremely rare (<0.1%).\n• Tumors are estrogen and progesterone responsive.\n• May grow during pregnancy and regress after menopause.\n• [Complete excision achieved - recurrence unlikely for myomectomy specimens.]\n• Clinical correlation with symptoms recommended.

Reported By

Dr. [Pathologist Name], MD\nConsultant Pathologist\nDate: [Report Date]