Low-Grade Appendiceal Mucinous Neoplasm

Low grade appendiceal mucinous neoplasm (LAMN) is a mucin-producing epithelial tumor of the appendix with low-grade cytological atypia, a villous or flat architecture, loss of the muscularis mucosae and a pushing, not infiltrative, pattern of invasion. It is the commonest mucinous appendiceal tumor, found in about 0.3 to 1% of appendectomy specimens, with peak incidence at 50 to 65 years. About half are diagnosed on pathology after surgery for presumed appendicitis.

Molecular features: KRAS mutations in about 60 to 70%, and GNAS mutations in about 30 to 50%. The disease follows an indolent course. Confined to the appendix with intact wall, cure rate after appendectomy is close to 100%. If the wall is perforated or mucin extends outside the appendix, the risk of peritoneal recurrence depends on whether the mucin contains epithelial cells.

The cells implant on peritoneal surfaces and produce pseudomyxoma peritonei over years. Lymph node metastasis is very rare (under 1%) and lymphadenectomy is not needed. Complications: perforation, peritoneal dissemination, recurrence at the appendiceal stump and a synchronous colonic neoplasm in 15 to 20%.

• Often asymptomatic, found on imaging or at operation
• Right iliac fossa pain mimicking appendicitis, or a palpable mass
• Chronic abdominal distension, ovarian mass, or new hernia if mucin has spread
• Red flags: increasing abdominal girth, ascites, a peritoneal mass, and bowel obstruction

1. CT with intravenous contrast: a dilated appendix with a thin wall, mural calcification and internal mucin attenuation. Free mucin shows low-density ascites with scalloping of the liver margin, and peritoneal nodules.
2. MRI: better delineation of mucin and peritoneal disease.
3. Histology is the definitive step. Pathology must report the grade, the depth of invasion, the status of the appendiceal base margin, perforation, and the presence of acellular or cellular mucin outside the appendix. Express these in descriptive terms.
4. Tumor markers: carcinoembryonic antigen, CA 19-9 and CA 125 as a baseline for follow-up.
5. Colonoscopy for synchronous neoplasia.

Differentials: mucinous adenocarcinoma, simple mucocele, appendicitis, ovarian mucinous neoplasm, Crohn disease.

1. Confined to the appendix, negative base margin, no mucin outside: appendectomy alone is curative. Remove the appendix intact within a retrieval bag. Surveillance with CT or MRI and tumor markers annually for 5 years.
2. Positive base margin, with no mucin in the peritoneum: a cecectomy or right hemicolectomy to clear the margin.
3. Acellular mucin outside the appendix: surveillance with imaging and tumor markers every 6 months for 2 years and then annually to 5 years, since the risk of peritoneal disease is low (under 5%).
4. Cellular mucin or peritoneal implants: referral to a specialist centre for cytoreductive surgery with heated intraperitoneal chemotherapy (see the details below as the standard regimen): mitomycin C 30 mg/m2 as a single intraperitoneal perfusion at 41 to 42 degrees Celsius for 90 minutes, after complete removal of visible disease.
5. Perioperative prophylaxis: cefazolin 2 g IV as a single dose before incision (3 g if over 120 kg), with metronidazole 500 mg IV as a single dose, and enoxaparin 40 mg SC once daily for 7 days (28 days after cancer surgery).
6. Spillage at laparoscopy: irrigate with saline, aspirate mucin, and send cytology.
7. Complications: anastomotic leak, ileus, adhesions, and peritoneal recurrence of 5 to 10% after limited spill.

Follow-up in the first 5 years includes imaging and markers, and colonoscopy at 3 to 5 years. Counsel on symptoms of recurrence such as distension and new hernia.