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Uterus (excludes Cervix)

Stromal tumors

Leiomyoma

Reviewer: Mohamed Mokhtar Desouki, MD, PhD (see Reviewers page)
Revised: 15 March 2012, last major update August 2011
Copyright: (c) 2002-2012, PathologyOutlines.com, Inc.

General
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● Extremely common tumor
● At autopsy, present in uterus in 77% of females; 84% of tumors are multicentric

Terminology
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● Also called fibroid, myofibroma, fibromyoma, leiomyofibroma, fibroma, myoma

Epidemiology
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● Present in 25% of women during reproductive years
● More common in blacks than whites; usually multiple in blacks
● Clinically apparent lesions are more common in nulliparous, postmenopausal women

Etiology
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● May be due to xenoestrogens, a diverse set of environmental compounds which exist naturally (genistein) or are synthetic (diethylstilbestrol/DES) and bind to estrogen receptor (ER) in myometrium
● Somatic mutations and molecular alterations in X chromosome must occur for initiation and subsequent development of myomas
● Oral contraceptives and progestin-only injectables are associated with a reduced risk, particularly with prolonged use of oral contraceptives
● Meat consumption may be a risk factor and green vegetables a protective factor (Obstet Gynecol 1999;94:395)

Clinical features
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● Typically asymptomatic, but up to 30% of women experience abnormal uterine bleeding or lower abdomen pressure-related symptoms
● May interfere with pregnancy or block ureters if large
● Rarely associated with polycythemia, which regresses when the tumor is excised
● Estrogen responsive, may regress after menopause or castration, and enlarge during pregnancy
● Difficult to diagnose from D & C since resembles superficial myometrium

Treatment
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● If symptomatic, treat with myomectomy, leuprolide acetate depot, or GNRH analog that shrinks the tumor; asymptomatic tumors do not require treatment

Gross description
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● Sharply circumscribed, round, firm, gray-white, “raw silk”, and whorled cut surface
● Often shells out
● Bulging and trabeculated cut surface
● Usually within myometrium (intramural), may be submucosal or subserosal
● May be multiple
● Sampling: sample myxoid areas extensively to rule out myxoid leiomyosarcoma; sample all leiomyomas that lack the classic gross appearance of leiomyomas and 3 largest tumors

Gross images
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Submucosal leiomyoma


Submucosal, intramural and subserosal leiomyomata


Hysterectomy specimen containing two leiomyomas: the tumor at the apex shows the typical, well-demarcated, firm, white, whorled cut surface and is in subserosal location. Projecting into the endometrial cavity is a submucous leiomyoma that is soft and gray, but nonetheless proved to be benign

Micro description
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● Whorled (fascicular) pattern of smooth muscle bundles separated by well vascularized connective tissue
● Smooth muscle cells are elongated with eosinophilic or occasional fibrillar cytoplasm and distinct cell membranes
● May develop areas of degeneration if large including hyaline or mucoid change, calcification, cystic change or fatty metamorphosis
● Usually non-infiltrative, thick-walled arteries throughout and cleft-like spaces
● May have extensive hyaline necrosis if protrudes into endometrial cavity
● Variable lymphocytes and mast cells
● Usually less than 5 mitotic figures per 10 high power fields in most mitotically active area, no significant atypia
● Rarely has focal skeletal muscle differentiation (Hum Pathol 1999;30:356) or tubules / glands
● Post-lupron treatment: initially edema and necrosis, then hyalinization and mild lymphocytic infiltrate

● Smooth muscle proliferations with unusual growth patterns: disseminated peritoneal leiomyomatosis; benign metastasizing leiomyoma; intravenous leiomyomatosis; lymphangioleiomyomatosis

Micro images
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Various images


Classic leiomyoma consists of whorled fascicles of smooth muscle cells separated by a fibrovascular stroma


Intersecting bands of small, uniform smooth muscle cells that are separated by a fibrous stroma with focal hyalinization


Small spindle cells with uniform nuclei that are spindled, have blunt ends and are normochromatic with generally inconspicuous nucleoli

   
Bland smooth muscle cells are entrapped and isolated within extensive fields of hyalinized stroma


Sharp demarcation of large field of hyalinization from more typical leiomyoma suggests a healed infarct


Vasular leiomyoma resembling hemangioma

               

       

Embolized leiomyoma: contributed by Dr. Mowafak Hamodat, Eastern Health of Newfoundland and Labrador, St. John’s, Canada

Positive stains
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● Smooth muscle actin, muscle specific actin, desmin, h-caldesmon, vimentin
● Focal cytokeratin in 25-30%, especially epithelioid cases
● Occasionally focal CD10

Negative stains
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● Keratin (usually), EMA (usually)

EM description
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● Smooth muscle cells with varying degrees of differentiation
● In central regions, cells are characterized by filaments sporadically located in the cytoplasm and well-developed organelles
● In outer layer, myocytes are more mature and resemble normal myometrial cells

Molecular description
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● 40% have non-random tumor-specific chromosomal abnormalities; other 60% have normal chromosomal profiles
● Most common chromosomal rearrangements are t(12;14)(q14-q15;q23-q24), deletion (7)(q22q32), rearrangement of 6-6p21 (Cancer Genet Cytogenet 2005;158:1)
● Less common are karyotypic abnormal rearrangements of 1p36, 3q, 10q22, 13q21-22, trisomy 12 and X chromosome
● Increase in transforming growth factor-beta in leiomyomata tissue
● Patients with germline mutations in fumarate hydratase have increased risk for developing leiomyomas, as well as uterine leiomyosarcomas

Differential Diagnosis
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● Endometrial, stromal sarcoma with smooth muscle metaplasia; leiomyosarcoma

End of Uterus > Stromal tumors > Leiomyoma

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