What is the recommended treatment approach for a patient with grade 2 endometrioid carcinoma, Pax8 and WT1 (Wilms Tumor 1) negativity, and CK7 (Cytokeratin 7), Vimentin, ER (Estrogen Receptor), and PR (Progesterone Receptor) positivity?

Treatment Approach for Grade 2 Endometrioid Carcinoma with Specific Immunohistochemical Profile

For a patient with grade 2 endometrioid carcinoma showing PAX8 and WT1 negativity with CK7, vimentin, ER, and PR positivity, hormone therapy is the preferred front-line systemic therapy due to the hormone receptor-positive status.

Immunohistochemical Profile Interpretation

The immunohistochemical profile provides important diagnostic and prognostic information:

• PAX8 negativity: Unusual for endometrial carcinoma as PAX8 is typically positive in endometrial adenocarcinomas 1. This negative result is atypical but doesn't change the primary diagnosis.
• WT1 negativity: Expected in endometrioid carcinomas. WT1 is typically positive in serous ovarian carcinomas but negative in endometrial endometrioid carcinomas 2.
• CK7, vimentin positivity: Consistent with endometrial origin 3.
• ER, PR positivity: Favorable prognostic markers that predict response to hormone therapy 2.

Treatment Algorithm Based on Disease Stage

For Early-Stage Disease (Stage I-II):

1. Primary surgical management:

   • Total hysterectomy with bilateral salpingo-oophorectomy
   • Comprehensive surgical staging including pelvic and para-aortic lymph node assessment

2. Adjuvant therapy based on risk stratification:

   • Stage IA/IB, grade 2 (low-intermediate risk): Consider observation without adjuvant therapy 2
   • Stage IC, grade 2 (intermediate risk): Adjuvant pelvic radiotherapy to reduce locoregional recurrence 2
   • Stage II: Adjuvant pelvic radiotherapy with or without intravaginal brachytherapy 2

For Advanced Disease (Stage III-IV):

1. Maximal surgical cytoreduction when feasible 2

2. Systemic therapy options:

   • First choice: Hormone therapy with progestogens (MPA 200 mg or MA 160 mg daily) due to ER/PR positivity and grade 2 histology 2
   • Alternative options if rapid disease progression or visceral involvement:
     • Chemotherapy with carboplatin/paclitaxel 2

Hormone Therapy Considerations

• Efficacy: Grade 2 endometrioid tumors have approximately 23% response rate to progestogen therapy 2
• Predictive factors: ER/PR positivity increases likelihood of response (25-37% response rates) 2
• Recommended agents:
  • First-line: Medroxyprogesterone acetate (MPA) 200 mg daily 2
  • Second-line options: Tamoxifen, aromatase inhibitors (anastrozole, letrozole), or fulvestrant 2

Monitoring and Follow-up

• Regular clinical examinations
• Consider re-biopsy of any recurrent disease as hormone receptor status may change over time (23% of primary tumors vs. 76% of metastatic lesions show PR loss) 2
• Transvaginal ultrasound for surveillance

Important Caveats

• PAX8 negativity is unusual for endometrial carcinoma and warrants consideration of other entities, though the overall immunophenotype still supports endometrioid carcinoma
• Avoid hormone therapy if there is:
  • Rapidly progressive disease
  • Visceral involvement
  • High-grade components (though not applicable in this grade 2 case)
• Consider genetic testing as Lynch syndrome can be associated with endometrioid carcinomas 2

Treatment Response Assessment

• Clinical examination and imaging every 2-3 months
• If no response to hormone therapy after 2-3 months, consider switching to chemotherapy
• For patients with stable disease on hormone therapy, continue treatment until progression