Case 83

A 83-year-old female with a large uterine mass.

P53 in the biopsy

P53 in the resection

1. What's the interpretation of the overall finding?

   A: Endometrioid carcinoma FIGO3

   B: Mixed endometrioid and serous carcinoma

   C: Mixed endometrioid and giant cell carcinoma

   D: Dedifferentiated carcinoma

   E: Choriocarcinoma

Answer

The p53 showed subclonal expression in the plemorphic cell areas. This is a case of mixed high-grade carcinoma, endometrioid type and giant cell carcinoma.

Histopathological Features

• Composed of bizarre multinucleated and mononucleated giant cells with eosinophilic cytoplasm and prominent nucleoli.

• Grows in a sheet-like or solid pattern; often intermixed with conventional carcinoma components, usually endometrioid or serous.

• No sarcomatous differentiation present.

• ~10–100% of tumor may be composed of giant cells.

• Conventional carcinoma component often lacks clear demarcation from giant cells.

• Numerous atypical mitoses and background necrosis are common.

Immunohistochemical Profile

• Epithelial markers (EMA, AE1/AE3, CK7, CAM5.2): Positive in giant cells and conventional components → confirms epithelial origin.

• PAX8: Positive → supports Müllerian (endometrial) origin.

• Vimentin: Positive in ~50% of cases → co-expression suggests endometrioid-type origin.

• ER/PR: Focally or multifocally positive in most cases.

• p53: Wild-type pattern in ~⅔ of cases. Mutant (aberrant) in ~⅓, including the present case.

• p16: Variably positive; diffusely positive in most but negative in some.

• β-hCG, CD68, p63, Desmin, SMA, MyoD1, Caldesmon, etc.: Negative → helps exclude trophoblastic or sarcomatous origin.

• MMR proteins (MLH1, PMS2, MSH2, MSH6): Retained in all reported cases → MMR-proficient.

• SMARCA4 (BRG1), SMARCB1 (INI1): Retained → rules out SWI/SNF-deficient tumors.

• IMP3: Positive → supports high-grade carcinoma nature.

• WT-1: Focal positivity in some cases (likely from serous component).

  
  

Molecular Classification

Majority fall under “No Specific Molecular Profile (NSMP)”.

A minority show p53-abnormal (copy-number high) features.

No reported cases with POLE mutations or MMR deficiency (MSI).

Differential Diagnosis

• Endometrial Carcinosarcoma (ECS): Biphasic tumor with distinct sarcomatous and carcinomatous components. Sarcomatous areas express muscle markers, absent in EGCC. Often p53-mutant.

  
  

• Undifferentiated/Dedifferentiated Endometrial Carcinoma (UDEC/DDEC):

• UDEC: Uniform, monomorphic cells; lacks giant cell pleomorphism.

• DDEC: Includes low-grade endometrioid and undifferentiated components. Typically shows loss of SMARCA4/SMARCB1, MMR deficiency, or POLE mutations.

  
  

• Choriocarcinoma or EC with Choriocarcinomatous Differentiation:

• Giant cells are syncytiotrophoblastic and express β-hCG, HPL, MelCAM, p63. Patients have elevated serum β-hCG, unlike EGCC.

Reference:

Xiao Tang, Lei Li, Wei Jiang. Endometrial giant cell carcinoma: a case report and review of the literature. European Journal of Gynaecological Oncology. 2025; 46(3): 112-116. doi: 10.22514/ejgo.2025.043.

Case credit: UCSD Pathology

Author: Wangpan Jackson Shi, MD