What is the recommended treatment for a patient with a low-grade mucinous (mucin-producing) neoplasm of the appendix that has metastasized to the ovary?

Treatment of Low-Grade Mucinous Neoplasm of Appendix with Metastasis to Ovary

For a patient with low-grade mucinous neoplasm of the appendix metastatic to the ovary, the recommended treatment is complete cytoreductive surgery including appendectomy, total abdominal hysterectomy with bilateral salpingo-oophorectomy, omentectomy, and comprehensive surgical staging, followed by consideration of gastrointestinal regimen chemotherapy such as 5-FU/leucovorin/oxaliplatin or capecitabine/oxaliplatin. 1

Diagnostic Considerations

Before proceeding with treatment, it's essential to confirm the origin of the mucinous tumor:

• Distinguish between primary ovarian mucinous carcinoma and metastatic appendiceal neoplasm
• Additional workup should include:
  • Gastrointestinal tract evaluation
  • CEA level measurement
  • PAX8 immunostaining (may help distinguish primary vs. metastatic disease) 1

Surgical Management

The cornerstone of treatment is complete surgical resection:

1. Comprehensive surgical staging with:

   • Vertical incision for adequate exposure 1
   • Cytologic evaluation of ascites or peritoneal washings
   • En-bloc removal of tumor
   • Total abdominal hysterectomy and bilateral salpingo-oophorectomy
   • Appendectomy (critical even if appendix appears normal) 1
   • Infracolic omentectomy
   • Examination of all peritoneal surfaces with biopsy of suspicious areas
   • Pelvic and para-aortic lymph node assessment 1

2. Extent of surgery depends on disease spread:

   • For limited disease: Complete resection of all visible disease
   • For extensive peritoneal involvement: Cytoreductive surgery with consideration of hyperthermic intraperitoneal chemotherapy (HIPEC) 2

Adjuvant Therapy

Postoperative treatment options for stage II-IV mucinous carcinomas include:

1. Gastrointestinal regimen chemotherapy (preferred due to similarity to gastrointestinal tumors):

   • 5-FU/leucovorin/oxaliplatin (FOLFOX)
   • Capecitabine/oxaliplatin (CAPOX) 1

2. Alternative option:

   • Standard epithelial ovarian cancer chemotherapy regimens (carboplatin/paclitaxel or carboplatin/docetaxel) 1

Prognostic Factors and Follow-up

• Patients with metastatic low-grade mucinous appendiceal neoplasms generally have better prognosis than high-grade tumors 2
• Surveillance should include:
  • Regular clinical examinations
  • Tumor marker monitoring (CEA)
  • Periodic imaging (CT scans of chest, abdomen, and pelvis)

Special Considerations

• Molecular testing: Consider next-generation sequencing for KRAS and GNAS mutations, as concurrent mutations strongly support appendiceal origin when the primary site is unclear 3
• Risk of pseudomyxoma peritonei: Low-grade appendiceal mucinous neoplasms can lead to peritoneal spread with mucinous ascites, requiring aggressive surgical management 4, 5
• Fertility preservation: Not typically an option given the need for complete resection of reproductive organs in metastatic disease 1

Common Pitfalls to Avoid

• Misdiagnosis: Low-grade appendiceal mucinous neoplasms are often misdiagnosed as primary ovarian tumors 3, 6
• Incomplete staging: Failure to perform appendectomy in patients with mucinous ovarian tumors can miss the primary site 1
• Inadequate surgery: Incomplete cytoreduction leads to poorer outcomes and higher risk of pseudomyxoma peritonei 2

The management of low-grade mucinous neoplasm of the appendix with metastasis to the ovary requires a specialized approach with thorough surgical staging and appropriate adjuvant therapy to optimize patient outcomes and survival.