Appendiceal Carcinoma

In 1867, four case reports by Rokitansky described carcinoma of the appendix. However, microscopic diagnosis was not provided at that time. The first microscopically confirmed case of appendiceal carcinoma was published in 1882 by Beger.

Etiology

• Develop via adenoma-to-carcinoma sequence like colorectal adenocarcinomas
• Mutations in KRAS oncogene
• Affects males more than females
• Average age of 60 years old
• Types
  • Epithelial
    • Mucinous adenocarcinoma → proliferation of mucin-containing cells
      • Low-grade appendiceal mucinous neoplasms (LAMNs) → earliest form of mucinous tumor, not inherently malignant, mucin-containing cells are confined to epithelium, low grade of atypia with few mitotic figures
      • High-grade appendiceal mucinous neoplasms (HAMN) → display higher-grade atypical cells, more numerous cells, and cribriform growth, don’t have infiltrative invasion
      • Mucinous adenocarcinoma → presence of infiltrating invasion at least into submucosa; most common source of pseudomyxoma peritonei
    • Nonmucinous adenocarcinoma
      • Adenocarcinoma (colorectal-type)
      • Goblet cell adenocarcinoma →
        • Arise from intestinal crypt base stem cells 
        • Tumor composed of goblet-like mucinous cells, neuroendocrine, and Paneth cells
        • Behave more like adenocarcinomas as opposed to neuroendocrine
    • Note: presence of signet rings is associated with more aggressive cancer and can be found in both mucinous and nonmucinous adenocarcinoma 
  • Nonepithelial
    • Neuroendocrine tumors (NETs)
      • Previously known as “carcinoid tumor” → tumors that metastasize to the liver can cause carcinoid syndrome and present with symptoms such as flushing, diarrhea, bronchoconstriction, and valvular heart disease
      • Most common appendiceal neoplasm, and most common site for carcinoid tumor
      • Monitored for recurrence every 6-12 months with biochemical (e.g., 5-HIAA) and imaging (e.g., CT, MRI)
    • Lymphoma
    • Sarcoma
    • Gastrointestinal stromal tumors (GIST)
    • Mesenchymal tumors

Epidemiology

• Rare, 1 per 1,000,000 population
• 1% of all neoplasms of intestinal tract

Pathogenesis

• Various cell types of appendix from which neoplasms can arise
  • Epithelial
    • Adenocarcinoma
  • Nonepithelial
    • Neuroendocrine tumors
    • Lymphoma
    • Sarcoma
    • Gastrointestinal stromal tumors (GIST)
    • Mesenchymal tumors

Presentation

• Presents the same way as acute appendicitis
• Right lower quadrant pain
• Fever
• Nausea
• Diagnosed incidentally after appendectomy for appendicitis

Staging

Treatment

• Indications for surgery
  • Incidental finding of abnormal-appearing appendix during exploration during a separate surgery
  • Incidental pathologic diagnosis made after surgery for appendicitis
  • Appendiceal cancer is suspected prior to surgery (e.g., bulky mesenteric adenopathy, biopsy-proven adenocarcinoma)
• Surgical treatment after appendectomy depends on pathology and clinical findings at the time of surgery
• Surgical approach
  • Acute appendicitis → standard preparation for appendectomy
  • Known diagnosis of mucinous neoplasm → complete clinical staging
    • CT chest, abdomen, and pelvis
    • Colonoscopy
    • Obtain CEA, CA19-9, and CA-125
    • If right colectomy is planned, mechanical and antibiotic bowel prep should be utilized
• Surgical technique
  • Appendectomy
  • Indications for right hemicolectomy
    • Nonmucinous adenocarcinoma
      • Due to high rate of lymph node metastasis with appendiceal adenocarcinoma
      • Risk is highest for colorectal-type adenocarcinoma compared to mucinous
    • Mucinous adenocarcinoma if
      • Moderate to poor differentiation
      • Not completely resected
      • Ruptured
    • Carcinoid tumor
    • Consider right hemicolectomy if tumor if positive margin at base of appendix for HAMN
    • Neuroendocrine tumor >2 cm in size – may perform right colectomy in neuroendocrine tumor 1-2 cm in size depending on patient presentation and tumor characteristics
• Multimodal therapy
  • No adjuvant therapy indicated for LAMN or HAMN
  • High-risk tumors (e.g., lymph node involvement, evidence of perforation, signet cell histology, poor differentiation) → consider 5-fluorouracil-based adjuvant chemotherapy

Relevant Information

• 2% of all appendectomy specimens harbor an appendiceal neoplasm
• Can be found incidentally during colonoscopy