Soft Tissue Tumors 3 - Leiomyosarcoma

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Soft Tissue Tumors Part 3

Muscle, Vascular, Nerve, Other

Leiomyosarcoma-general

Author: Nat Pernick, M.D, PathologyOutlines.com, Inc.

Revised: 12 August 2009, last major update - August 2009

Leiomyosarcoma: general, cutaneous, epithelioid, myxoid, pleomorphic, rhabdoid features

Definition

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● Smooth muscle tumor with atypia plus either mitotic activity, tumor cell necrosis or size > 10 cm

● 10% of adult soft tissue sarcomas

● Variants are described separately above

Epidemiology

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● Skin/subcutis: see cutaneous variants above; better survival than retroperitoneal tumors

● Retroperitoneum: third most common retroperitoneal sarcoma after liposarcoma and MFH; usually women, 5 year survival is only 29%

● Immunocompromised patients: associated with EBV in HIV patients; may be multifocal

Sites

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● Usually extremities

● Often arises from large vessels (AJSP 2002;26:14), most commonly inferior vena cava, saphenous vein, femoral vein, pulmonary artery, femoral artery

● Also occurs in retroperitoneum, superficial or deep soft tissues

Case reports

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● 26 year old man with EBV+ tumor after heart transplantation (AJSP 2000;24:614)

● 54 year old man with tumor of inferior vena cava (Archives 2003;127:e423)

● 69 year old man with tumor of internal jugular vein (World J Surg Oncol 2008;6:113)

Treatment and prognosis

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● Excision with clear margins (enucleation is inadequate treatment)

● Often recurs locally or metastasizes

● Lung is common site of metastasis, lymph nodes are uncommon site

● Poor prognostic factors: retroperitoneal, mesenteric or other deep location, size > 5 cm, age > 62 years, high grade, tumor disruption by prior incisional biopsy or incomplete excision (Cancer 2007;109:282), possibly nuclear c-myc expression (Mod Pathol 2009 Jul 24 [Epub ahead of print])

● In extremities, poor prognostic factors are large size and high mitotic rate; best treatment is wide surgical excision plus adjuvant radiation therapy (Eur J Surg Oncol 2004;30:565)

Clinical images

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12 cm tibial tumor

Gross description

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● Large, soft, often necrosis, hemorrhage and cystic degeneration

● May project into lumen of major vessels or be intramural

Gross images

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Recurrent tumor Fusiform tumor of arm Tumor of popliteal vein

with cystic cavity

Images: leg tumor #1; #2; retroperitoneal tumor; thigh tumor; necrotic tumor within skeletal muscle

Micro description

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● Fascicular growth pattern (bundles intersect at right angles)

● Tumor cells merge with blood vessel walls

● Palisading of spindle cells with eosinophilic fibrillary cytoplasm, focal granularity

● Nuclei are cigar-shaped and blunt-ended with variable atypia, often with cytoplasmic vacuoles at both ends of nuclei (unlike neural lesions)

● Mitotic figures are common

● May have hemangiopericytoma-like vasculature, nuclear palisading, myxoid change, osteoclast-like giant cells

● Often infiltrates into adjacent tissue
● See also variants above

Malignant criteria by site

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● Soft tissue: 1-2 MF/10 HPF and deep

● Skin/subcutaneous: 2 MF/10 HPF is definitive, 1 MF/10 HPF if consistent in all fields

● Retroperitoneum: 5 MF/10 HPF is definitive, or 1-4 MF/10 HPF plus necrosis plus size > 7.5 cm

● Vascular: 1-4 MF/10 HPF plus large size plus necrosis

● Diagnosis as tumor of uncertain malignant potential (UMP) if mitotic figures are fewer than above or focal

Micro images

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Malignant based on Pleomorphism and smooth

low power pleomorphism muscle differentiation are evident

Markedly pleomorphic, little evidence Multinucleated giant cells

of smooth muscle differentiation

Tumor of inferior vena cava - cytology, Intravenous tumor

H&E and smooth muscle actin

H&E and h-caldesmon

Retroperitoneum: smooth muscle morphology Marked pleomorphism

and no identifiable smooth muscle

Uncertain malignant potential: 8 cm retroperitoneal tumor with bland cells and < 1 MF/10 HPF

Tumor cells are intimately associated with vessels: Hemangiopericytoma-like

H&E and smooth muscle actin growth pattern

Hereditary retinoblastoma patients: Coagulative tumor MIB index is 35-40%

cell necrosis

Cytology description

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● Fascicles with an mixture of dispersed cells or stripped nuclei

● Most cells are spindled with elongated, blunt-ended, segmented or fusiform nuclei or round/polygonal with round or indented nuclei

● Also pleomorphic cells, occasionally intranuclear vacuoles, mitoses and osteoclast-like giant cells (Diagn Cytopathol 2006;34:597)

Positive stains

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● HHF-35 (90%), alpha-smooth muscle actin (90%), vimentin, desmin (75%) (Cancer 2009 Jul 22 [Epub ahead of print])

● H-caldesmon (Am J Clin Pathol 2000;113:663)

● PTAH (stains myofibrils), keratin (30%), ER (usually in uterine and female retroperitoneal tumors), S100 (occasionally weak staining), EMA (may be focal)

Negative stains

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● CD117

Electron microscopy

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● Some smooth muscle features, including cytoplasmic filaments with focal densities (also present in myofibroblasts), pinocytotic vesicles, thick basal lamina

Molecular / cytogenetics

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● Often complex karyotypes with no consistent aberrations

Differential Diagnoses

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● Leiomyoma - no/rare mitotic activity, no/minimal atypia, small size, no hemorrhage, no necrosis

● Dedifferentiated liposarcoma - usually trunk, better prognosis, well differentiated component present, MDM2 and CDK4 amplification (AJSP 2007;31:1557)

End of Soft Tissue Tumors Part 3 - Muscle, Vascular, Nerve, Other > Leiomyosarcoma

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