What is the differential diagnosis for pseudomyxoma peritonei?

Differential Diagnosis of Pseudomyxoma Peritonei

The differential diagnosis of pseudomyxoma peritonei must distinguish between primary mucinous neoplasms (most commonly appendiceal adenomas/adenocarcinomas), secondary peritoneal carcinomatoses from other gastrointestinal or gynecologic malignancies, and non-neoplastic conditions that can mimic the clinical presentation.

Primary Mucinous Neoplasms

Appendiceal Origin (Most Common)

• Appendiceal mucinous adenoma is the most common source, accounting for approximately 60% of cases, presenting as disseminated peritoneal adenomucinosis (DPAM) with bland mucinous epithelium and abundant extracellular mucin 1
• Appendiceal mucinous adenocarcinoma represents 27.5% of cases, manifesting as peritoneal mucinous carcinomatosis (PMCA) with cytologic and architectural features of carcinoma 1
• Intermediate forms exist where well-differentiated appendiceal adenocarcinomas produce peritoneal lesions with both DPAM and focal carcinoma features 1

Other Gastrointestinal Sources

• Mucinous neoplasms of the colon, stomach, pancreas, and small bowel can produce similar mucinous peritoneal dissemination 2, 3
• These typically present as peritoneal carcinomatosis rather than true pseudomyxoma peritonei 1

Gynecologic Sources

• Ovarian mucinous tumors are frequently misdiagnosed as the primary source but are often secondary involvement from appendiceal primaries 3
• Endocervical, fallopian tube, and uterine mucinous neoplasms are rare causes 3
• In women with right pelvic masses and mucinous ascites, appendiceal tumors should be strongly considered in the differential 3

Secondary Peritoneal Carcinomatoses

Common Primary Sites

• Breast, colon, gastric, pancreatic, and ovarian cancers are the most common origins of peritoneal carcinomatosis that can mimic pseudomyxoma peritonei 2
• Gastric cancer with peritoneal metastases occurs in 12.9-26.5% of cases at diagnosis, often presenting with mucinous or signet ring cell histology 4

Distinguishing Features

• True pseudomyxoma peritonei shows characteristic "jelly belly" appearance with redistribution phenomenon (mucin accumulates in dependent areas and omentum) 5
• Secondary carcinomatoses typically show solid peritoneal nodules rather than gelatinous mucin collections 2
• Histopathology reveals abundant extracellular mucin with scant epithelium in DPAM versus more cellular carcinomatous implants in secondary disease 1

Non-Neoplastic Mimics

Infectious Conditions

• Tuberculous peritonitis requires tissue biopsy showing caseating granulomas and acid-fast bacilli, with diagnostic yield of 84-100% 2
• This presents with ascites but lacks the characteristic gelatinous mucin of pseudomyxoma peritonei 2

Rare Peritoneal Conditions

• Mucinous cysts of the spleen, urachus, urinary bladder, and breast can rarely cause mucinous peritoneal collections 3

Diagnostic Approach to Differentiate

Initial Assessment

• Measure CA-125, CEA, and CA19-9 before any intervention; elevated CEA and CA19-9 with normal or mildly elevated CA-125 suggests appendiceal origin 2
• In young women, measure alpha-fetoprotein and beta-HCG to exclude germ cell tumors 2
• History of previous malignancy is critical as breast, colon, gastric, pancreatic, and ovarian cancers commonly metastasize to peritoneum 2

Imaging Characteristics

• CT demonstrates low-attenuation gelatinous material with scalloping of liver and spleen surfaces in pseudomyxoma peritonei 3, 6
• Ultrasound shows hyperechoic echogenicity of mucinous ascites with 97% sensitivity for omental involvement 2
• CT sensitivity for peritoneal disease is only 28-51% despite 97-99% specificity, so negative imaging does not exclude diagnosis 2

Definitive Diagnosis

• Laparoscopy with peritoneal cytology and biopsy provides 85% sensitivity and 100% specificity for peritoneal disease 2
• Paracentesis with cytology has 96.7% sensitivity when three samples are sent immediately, but negative cytology does not exclude low-volume disease 2
• Histopathology distinguishes DPAM (bland mucinous epithelium with abundant mucin) from PMCA (carcinomatous epithelium) and secondary carcinomatoses 1

Critical Pitfalls to Avoid

• Do not assume ovarian origin in women with pelvic masses and mucinous ascites without excluding appendiceal primary 3
• Never rely solely on CT for diagnosis given its low sensitivity; proceed to laparoscopy in surgical candidates 2
• Recognize that negative ascitic cytology does not exclude peritoneal carcinomatosis, especially in early or low-volume disease 2
• Avoid routine PET-CT as it has limited utility, particularly in mucinous tumors which have low FDG uptake 2

Prognostic Implications of Correct Classification

• DPAM carries 75% 5-year and 68% 10-year survival versus 14% 5-year and 3% 10-year survival for PMCA 7
• Intermediate forms (PMCA-I/D) have 50% 5-year and 21% 10-year survival 7
• Accurate pathologic classification is essential as it fundamentally changes prognosis and treatment approach 1, 7