Background

A 56-year-old female presented with postmenopausal bleeding. MRI pelvis showed bulky uterus with large myometrial fibroid having cystic degeneration. Total abdominal hysterectomy was done. Sections from the myometrial mass.

Microscopy

Fig.12a; H&E; 5x

Fig.12b; H&E; 10x

Fig.12c; H&E; 10x

Fig.12d; H&E; 20x

Fig.12e; H&E; 10x

Fig.12f; H&E; 10x

Images show areas of high-grade spindle cell sarcoma in fascicles and sheets [Fig.12a] with focal areas of myogenic differentiation [Fig.12b]. Many multinucleated tumor cells are seen [Fig.12c] along with sheets of epithelioid cells in myxoid background [Fig.12d]. Areas of heterologous differentiation in the form of osteosarcoma [Fig.12e] and chondroid differentiation [Fig.12f] are also noted.

No epithelial component is readily identified.

Fig.12g; CK

Fig.12h; SMA

Fig.12i; Desmin

On Immunohistochemistry, tumor cells are diffusely negative for CK [Fig.12g]. Areas with myogenic differentiation show positivity for SMA [Fig.12h] and Desmin [Fig.12i].

Final Impression: High Grade Leiomyosarcoma With Heterologus (Osteosarcoma/Chondrosarcoma) Differentiation.

POINTS TO REMEMBER

• Uterine leiomyosarcoma is a malignant mesenchymal tumor derived from smooth muscle cells
• Age of presentation: 4^th-5^th decade of life
• Location: Uterine corpus (common), cervix
• Germline mutation in Fumarate Hydratase⇒ increased risk of developing uterine leiomyosarcoma
• Genetic alteration: Frequently mutated genes:
  • TP53
  • ATRX
  • MED12
• Subtypes:

• Essential diagnostic criteria:

• Rare cases with osseous and chondro-osseous differentiation have been reported in literature
• Immunohistochemistry (Positive stains):
  • Desmin, h-caldesmon, SMA, CD10
  • EMA, CK (epithelioid leiomyosarcoma)
  • ER, PR, p16, p53 overexpression (Spindle cell leiomyosarcoma)
• Differential diagnosis:
  • Smooth muscle tumor of uncertain malignant potential (Criteria):
    • Tumor cell necrosis: absent, focal moderate atypia, ≥5 mitosis/10HPF or,
    • Tumor cell necrosis: absent, diffuse severe to moderate atypia, 5-9 mitosis/10HPF or,
    • Tumor cell necrosis: present, none to mild atypia, <10 mitosis/10HPF
  • Atypical leiomyoma (Criteria):
    • Tumor cell necrosis- Absent
    • Focal moderate to severe atypia
    • <5mitosis/10HPF
  • Mitotically active leiomyoma (Criteria):
    • Tumor cell necrosis- Absent
    • None to mild atypia
    • ≥5mitosis/10HPF
  • Undifferentiated endometrial sarcoma:
    • Endometrium and myometrium location
    • Negative for Desmin, caldesmon and Actin
  • Rhabdomyosarcoma:
    • Rare in uterus
    • Search for rhabdomyoblast.
    • Positive for Desmin and Myogenin
    • Negative for caldesmon
• Prognosis:
  • Aggressive, even with tumor confined to uterus
  • Recurrence (50-70%) occur in lung and in pelvis
  • Progression depends on stage
  • Size of neoplasm < 5cm (in Stage I tumor) and premenopausal women have more favourable outcome as seen in some studies
• Treatment:
  • Postmenopausal women: Early-stage: TAH and BSO
  • Removal of ovary and lymph node is controversial, as metastasis to these organs occur in small percentage of cases
  • Premenopausal women: therapy is controversial
  • In stage I and II cases, role of adjuvant systemic therapy or radiotherapy on survival is uncertain
  • Some patients respond to hormonal therapy

Contributed by: Dr Sunil Pasricha

Compiled by: Dr Diksha Karki

In case of queries, email us at: kumar.ankur@rgcirc.org

Female genital tract Heterologous differentiation Leiomyosarcoma Smooth muscle tumor Soft tissue tumors

Last modified: 28/06/2021