Leiomyoma

Epidemiology:

• 20-30% of women over 30y of age
• 4^th and 5^th decades usually
• Hereditary:
• Younger presentation
• Leiomyomatosis and renal cancer syndrome:
• FH mutation (fumarate hydratase) (1q43)
• AD
• Uterine leiomyomas
• Cutaneous leiomyomas
• Renal cell carcinomas
• Mitotically active leiomyoma
• Reproductive age group
• Hormonee therapy associated sometimes
• Benign metastasizing leiomyoma:
• History of (typical) leiomyoma resection
• Median 15 years after hysterectomy
• Absence of primary smooth muscle malignancy in any extrauterine site

Common sites:

• Uterus
• Parasitic leiomyoma (detachment of a subserosal leiomyoma from its pedicle)
• Lungs (most common extrauterine location
• Leiomyomatosis peritonealis disseminate (uncommon)
• Cardiovascular involvement (rare, intravenous lyomyomatosis)
• Other sites (rare)

Gross features:

• Multiple (> 75%)
• sharply circumscribed, round, firm, gray-white tumour
• characteristic whorled pattern on cut section
• may have areas of yellow-brown to red softening (red degeneration, associated with pregnancy)
• infarction, sometimes with hemorrhage (common)
• cystic change occasionally
• diffuse leiomyomatosis (rare)
• numerous ill-defined often confluent small nodules within the myometrium
• intravenous leiomyomatosis:
• worm-like plugs protruding from myometrial or broad ligament veins
• small number of vessels (usually), or extensive (occasionally)

Histologic features:

• intersecting fascicles of spindle cells
• scarce mitotic figures (< 5 per 10 hpf) (may have more in young or pregnant women)
• cells are uniform in size and shape (some exceptions)
• characteristic oval nucleus to cigar-shaped
• small nucleoli
• long, slender bipolar cytoplasmic processes
• indistinct borders
• eosinophilic fibrillary cytoplasm
• thick-walled vessels
• mitoses infrequent
• may see hyaline necrosis:
• zone of eosinophilic collagen interposed between viable and necrotic cells
• inconspicuous or absent ghost nuclei
• may have zone of granulation tissue between necrotic cells and hyaline band
• infarct-type necrosis maybe:
• band of granulation tissue between viable and non-viable tumour
• associated hemorrhage maybe
• associated fibrosis maybe
• mummified appearance of non-viable areas
• single or groups of apoptotic cells with pyknotic nuclei in early stage
• may see inflammatory necrosis in submucosal leiomyoma (due to ulceration):
• acute inflammatory cells
• peripheral repairative process
• inconspicuous or absent ghost nuclei
• may also see cystic degeneration, myxoid degeneration, mucinous degeneration
• prominent hyalinization maybe
• calcification rarely
• variants:
• highly cellular leiomyoma
• more cellular than usual (mimic EST)
• diffuse or in fascicles (at the periphery)
• irregular border usually
• thick-walled vessels commonly
• cleft-like spaces commonly
• lack nuclear atypia
• rare mitoses
• Leiomyoma with bizarre nuclei / atypical leiomyoma / symplastic leiomyoma
• mod to severe atypia
• typically focal
• MI low typically (< 10/10 HPF)
• Karyorrhectic nuclei may mimic atypical mitotic figures
• Absent tumour cell necrosis (infarct-type necrosis maybe seen)
• Mitotically active leiomyoma
• MI often 10-20/10 hpf
• May be cellular
• Lacks cytologic atypia
• Bland grossly
• No tumour cell necrosis
• Epithelioid leiomyoma
• Composed predominantly or completely of nonspindled, rounded cells with an epithelioid appearance
• Clear or eosinophilic cytoplasm
• MI < 5/10 hpf
• None to mild atypia
• No tumour necrosis
• No convincing glands
• Hydropic leiomyoma
• Conspicuous zonal, watery oedema
• Hyalinization maybe
• Leiomyoma with apoplectic change (associated with progesterone therapy)
• Zones of hemoorhagic infarction surrounded by hypercellular areas
• Increased mitoses often
• Myxoid change sometimes
• Lipoleiomyoma
• Mixture of mature adipocytes and smooth muscle cells
• Mitotically inactive
• Cotyledonoid dissecting leiomyoma
• Irregular dissection of bland smooth muscle cells within the myometrium
• Extension outside of uterus maybe
• Conspicuous hydropic changes sometimes
• Neurilemoma-like leiomyoma
• Hyalinized leiomyoma where nuclei are lined up simulating the palisading pattern of schwannoma
• Myxoid leiomyoma
• Be suspicious for leiomyosarcoma

1. mitotic index may be misleading
2. look for myometrial and vascular invasion, cellular atypia

• Islands of collagenated spindle cells in a sea of edematous connective tissue
• Smooth muscle differentiation not apparent
• Large vessels suspended in these myxoid areas
• Bland nuclei
• Circumscribed margins with no infiltration of myometrium
• Mitotically inactive
• Diffuse leiomyomatosis
• Histological pattern mimicking infiltration – small islands of hypercellular, bland smooth muscle interspersed with areas of normally cellular smooth muscle
• Meets all criteria for leiomyoma
• Lacks atypical features
• Disseminated peritoneal leiomyomatosis
• Multiple peritoneal nodules composed of an admixture of fibroblasts and bland smooth muscle cells
• Nodules usually < 2cm
• Associated with pregnancy and other hormonal states
• Regresses post-partum
• Benign metastasizing leiomyoma
• Benign extrauterine smooth muscle deposits (usually lungs)
• Entrapment of bronchioalveolar epithelium is often seen
• Parasitic leiomyoma
• Subserosal leiomyoma which detaches and attaches to another pelvic site
• Intravascular leiomyomatosis and leiomyoma with vascular intrusion
• Bland smooth muscle within vascular channels, outside the confines of the leiomyoma (seen grossly)
• Free floating or attached to the vessel wall
• Outside the confines of the leiomyoma (If within the confines of a leiomyoma, it is called leiomyoma with vascular intrusion)
• May have morphological variance from usual smooth muscle appearance (hydropic commonly)
• But rarely has the appearance of another leiomyoma variant
• Must remain within blood vessels or cardiac chambers
• Bland cells usually
• No tumour necrosis
• Rare mitoses (MI < 5/10 hpf)
• Leiomyomatosis and renal cancer syndrome:
• Multiple leiomyomas
• Increased cellularity frequently
• Multinucleated and atypical nuclei frequently
• Prominent red to orange nucleoli surrounded by a clear halo
• Haemangiopericytoma-like vessels
• Histologic changes associated with GnRH-agonists:
• Anti-fibrinolytic agents:
• Thrombosis and infarction maybe

Immunophenotype:

Marker:	Sensitivity:	Specificity:
h-caldesmon
Desmin
Muscle-specific actin
smooth muscle actin
Histone deacetylase 8
Smooth muscle myosin heavy chain
Oxytocin receptor
ER
PR
WT1
CD10 (neg)	Positive in up to 40% of highly cellular leiomyomas
EMA (neg)	usually
p53	Often positive in leiomyomas with bizarre nuclei	Not helpful in DDx of LMS
P16	Often positive in leiomyomas with bizarre nuclei	Not helpful in DDx of LMS

Molecular features:

• Leiomyomatosis and renal cancer syndrome:
• FH mutation (fumarate hydratase) (1q43)

Other features:

• Intravenous leiomyomatosis can recur (< 5%) up to 15 years after hysterectomy
• IVC or cardiac involvement usually
• Benign metastasizing leiomyoma
• Indolent clinical course
• Tumours may continue to grow and eventually result in respiratory failure
• Epithelioid leiomyomas may recur locally even with relatively low mitotic activity and cytologic atypia
• hormonally responsive
• may increase in size with:

• estrogen therapy
• progestins, progesterone
• hormone replacement therapy
• clomiphene
• pregnancy

• these also may cause hemorrhagic degeneration
• GnRH agonists usually decrease the size
• Symptoms:
• Asymptomatic
• Menorrhagia
• Pelvic pain / pressure
• Ascites (less common)
• erythrocytosis (uncommon, EPO production)

References:

• Kurman RJ, et al. (eds.) WHO Classification of Tumours of Female Reproductive Organs. (2014)