Leiomyosarcoma

Leiomyosarcoma
Diagnosis in short
Leiomyosarcoma. H&E stain.
LM	fasciclar arrangement (characteristic of smooth muscle), features of malignancy (usually need 2 of 3): † (1) nuclear atypia, (2) tumour cell necrosis, (3) mitoses - variable & definitions suffer from HPFitis
Subtypes	major: spindled leiomyosarcoma (leiomyosarcoma NOS), epithelioid leiomyosarcoma, myxoid leiomyosarcoma; minor: leiomyosarcoma with prominent intravascular growth, leiomyosarcoma with osteoclast-type cells, leiomyosarcoma with clear cells, leiomyosarcoma with xanthoma-type cells
LM DDx	pleomorphic undifferentiated sarcoma, atypical fibroxanthoma (skin only), EBV-associated smooth muscle tumour, carcinosarcoma, smooth muscle tumour of uncertain malignant potential (STUMP), endometrial stromal sarcoma, atypical leiomyoma (symplastic leiomyoma)
Gross	"fleshy" appearance, necrosis, large size
Site	uterus, skin, others
Prevalence	uncommon
Prognosis	poor

Leiomyosarcoma is a malignant tumour of smooth muscle. It is seen in various places including the uterus and skin.

General

• Poor prognosis.
• Do not (generally) arise from leiomyomas.
• Often singular, i.e. one tumour; unlike leiomyomas (which are often multiple).

Gross

Features:

• "Fleshy" appearance.
• Necrosis.
• Large size.
• Often singular, i.e. one lesion; leiomyomata are often multiple.

Microscopic

Features:

• Usually a cellular lesion.
• Fasciclar arrangement:
  • Whorled look at low power.
  • Groups of spindle cells cut peripendicular to their long axis adjacent to groups of spindle cells cut in the plane of their long axis.
• Features of malignancy (usually need 2 of 3): †
  1. Nuclear atypia.
  2. Tumour cell necrosis.
     • Should be patchy/multifocal.
       • Zonal necrosis is suggestive of vascular cause.
  3. Mitoses - key feature - definitions suffer from HPFitis:
     • >=10 mitoses/HPF - if spindled.
     • >=5 mitoses/HPF - if epithelioid.
     • >=2 mitoses/HPF - if myxoid.
     • >=1 mitosis/HPF - if cutaneous.
• +/-Heterologous elements, e.g. malignant cartilage or bone.

Notes:

• † In deep soft tissue. 1 of 3 criteria is considered enough.
• Leiomyosarcoma de facto trumps other sarcomas.
• Mitotic rate seems to be a relatively weak predictor; modest rate may be malignant and a high rate benign.

DDx:

• Pleomorphic undifferentiated sarcoma.
• EBV-associated smooth muscle tumour - rare, immunoincompetent individuals.
• Carcinosarcoma.
• Smooth muscle tumour of uncertain malignant potential (STUMP).
• Endometrial stromal sarcoma.
• Atypical leiomyoma.

Images

Uterine:

• 

  Uterine leiomyosarcoma 1 (WC)

• 

  Uterine leiomyosarcoma 2 (WC)

Cutaneous:

• 

  Cutaneous leiomyosarcoma - intermed. mag. - shows fascicular pattern (WC)

• 

  Cutaneous leiomyosarcoma - intermed. mag. (WC)

• 

  Cutaneous leiomyosarcoma - high mag. (WC)

• 

  Cutaneous leiomyosarcoma - very high mag. (WC)

www:

• Cutaneous leiomyosarcoma (upmc.edu).

Subtypes

Major variants:

• Spindled leiomyosarcoma (leiomyosarcoma NOS) - see above.
• Epithelioid leiomyosarcoma.
• Myxoid leiomyosarcoma.

Minor variants:

• Leiomyosarcoma with prominent intravascular growth.
• Leiomyosarcoma with osteoclast-type cells.
• Leiomyosarcoma with clear cells.
• Leiomyosarcoma with xanthoma-type cells.

Epithelioid leiomyosarcoma

Features:

• >50% epithelial appearance.
• >=5 mitoses/HPF - definition suffers from HPFitis.

Image:

• Epithelioid leiomyosarcoma (webpathology.com).

Myxoid leiomyosarcoma

Features:

• >=2 mitoses/HPF - definition suffers from HPFitis.
• May have minimal nuclear atypia.

IHC

Features:

• Positive for SMC markers.
  • Desmin - present in all three types of muscle.
  • H-caldesmon.
  • Smooth muscle myosin.
• CD10 -ve.
  • May be +ve.
  • Some use in the context of uterine lesions -- CD10 +ve in endometrial stromal sarcoma.

Others:

• ER, PR, AR +ve -- 30-40% of the time.
• CD117 +ve/-ve.
• p53 +ve.
• MIB1 high.
• Kertins usu. -ve -- more often +ve in epithelioid variant.

See also

• Soft tissue lesions.
• Uterine tumours.
• Leiomyoma.