Question

Uterine sarcoma:
Immunohistochemical (IH and molecular profiles of leiomyosarcoma and endometrial stromal sarcoma.

Hint:

Differentiating between LMS and ESS is crucial for treatment decisions, as they have distinct IHC and molecular profiles.

Answer 1

Leiomyosarcoma (LMS) and Endometrial Stromal Sarcoma (ESS) are both types of uterine sarcomas but have distinct immunohistochemical (IHC) and molecular profiles.

Step 1: IHC Profile of Leiomyosarcoma

• Positive Markers: LMS typically expresses smooth muscle markers such as α-Smooth Muscle Actin (α-SM, Desmin, and H-caldesmon.
• Negative Markers: It is usually negative for markers of endometrial stromal differentiation like CD10, WT1, and Estrogen Receptor (ER).

Step 2: IHC Profile of Endometrial Stromal Sarcoma

• Positive Markers: ESS often shows positivity for CD10, WT1, and sometimes ER.
• Negative Markers: ESS is typically negative for Desmin and α-SMA, distinguishing it from leiomyosarcoma.

Step 3: Molecular Profiles

• Leiomyosarcoma: LMS often has complex genomic alterations, including mutations in TP53, and sometimes alterations in MDM2 and CDK4, which lead to cell cycle dysregulation.
• Endometrial Stromal Sarcoma: ESS is characterized by specific genetic translocations such as the JAZF1-SUZ12 fusion gene in low-grade ESS and PHF1 rearrangement in high-grade ESS.