Mesothelioma differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Parminder Dhingra, M.D. [2], Sujit Routray, M.D. [3]

Overview

Mesothelioma must be differentiated from pleural effusion, lung cancer, pulmonary tuberculosis, peritoneal tuberculosis, pseudomyxoma peritonei, constrictive pericarditis, ovarian cystadenoma, and mesothelial hyperplasia of the testis.

Differentiating Mesothelioma from other Diseases

Differentiating Pleural Mesothelioma from other Diseases

Pleural mesothelioma must be differentiated from:

• Pleural effusion
• Benign asbestos-related pleural disease
• Peripheral bronchogenic carcinoma
• Pleural fibrosis from infective/inflammatory source (e.g. actinomycetes, tuberculosis)
• Primary pleural tumors

• Solitary fibrous tumor of the pleura
• Pleural fibrosarcoma
• Pleural liposarcoma
• Primary pleural lymphoma
• Pleural synovial sarcoma

• Secondary lesions that can involve the pleura

• Pleural metastases
• Thymoma with pleural invasion
• Pericardial tumors with pleural invasion
• Ewing sarcoma of chest wall with pleural invasion

Differentiating Peritoneal Mesothelioma from other Diseases

Peritoneal mesothelioma must be differentiated from:

• Peritoneal carcinomatosis
• Pseudomyxoma peritonei
• Lymphoma with peritoneal involvement
• Peritoneal involvement with tuberculosis
• Mesenteric panniculitis
• Primary peritoneal adenomatoid tumor
• Primary peritoneal papillary serous carcinoma
• Primary peritoneal serous borderline tumor
• Diffuse peritoneal leiomyomatosis
• Desmoplastic small round cell tumor arising from the peritoneum
• Solitary fibrous tumor arising the peritoneum
• Peritoneal lymphangioma
• Peritoneal inclusion cyst
• Spontaneous bacterial peritonitis (SBP)

Differentiating Pericardial Mesothelioma from other Diseases

Pericardial mesothelioma must be differentiated from:

• Heart failure
• Coronary heart disease
• Constrictive pericarditis
• Cardiomyopathy
• Tuberculosis pericarditis
• Cardiac tamponade
• Intra-atrial myxoma

Differentiating Multicystic Mesothelioma from other Diseases

Multicystic mesothelioma must be differentiated from:

• Abdominopelvic cystic lymphangioma
• Ovarian cystadenoma
• Ovarian cystadenocarcinoma
• Endometriosis
• Cystic teratoma
• Cystic mucinous tumor of pancreas

Differentiating Tunica Vaginalis Testis Mesothelioma from other Diseases

Tunica vaginalis testis mesothelioma must be differentiated from:

• Mesothelial hyperplasia of the testis
• Adenomatoid tumor of the testis
• Rete testis adenocarcinoma
• Serous papillary tumors of the testis and epididymis
• Pleomorphic rhabdomyosarcoma
• Malignant fibrous histiocytoma
• Germ cell tumors of the testis

Differentiating peritoneal Mesothelioma from other Diseases

Differentiating peritoneal mesothelioma from other causes of peritonitis

Disease		Prominent clinical findings	Lab tests	Tratment
Primary peritonitis	Spontaneous bacterial peritonitis	Absence of GI perforation, most closely associated with cirrhosis and advanced liver disease. Presents with abrupt onset of fever, abdominal pain, distension, and rebound tenderness.	Most have clinical and biochemical manifestations of advanced cirrhosis or nephrosis like leukocytosis,hypoalbuminemia, Prolonged prothrombin time. SAAG >1.1 g/dL, increased serum lactic acid level, or a decreased ascitic fluid pH (< 7.31) supports the diagnosis. Gram staining reveals bacteria in only 25% of cases. Diagnosed by analysis of the ascitic fluid which reveals WBC > 500/ML, and PMN >250cells/ml. Culture of ascitic fluid inoculated immediately into blood culture media at the bedside usually reveals a single enteric organism, most commonly Escherichia coli, Klebsiella, or streptococci.	Once diagnosed,it is treated with Ceftriaxone.
	Tuberculous peritonitis	Seen in 0.5% of new cases of tuberculosis particularly in young women in endemic areas as a primary infection. Presents with abdominal pain and distension, fever, night sweats, weight loss, and altered bowel habits.	Ascites is present in about half of cases. Abdominal mass may be felt in a third of cases. The peritoneal fluid is characterized by a protein concentration > 3 g/dL with < 1.1 g/dL SAAG and lymphocyte predominance of WBC. Definitive diagnosis in 80% of cases is by culture. Most patients presenting acutely are diagnosed only by laparotomy.	Combination antituberculosis chemotherapy is preferred in chronic cases.
	Continuous Ambulatory Peritoneal Dialysis (CAPD peritonitis)	Peritonitis is one of the major complications of peritoneal dialysis & 72.6% occurred within the first six months of peritoneal dialysis. Historically, coagulase-negative staphylococci were the most common cause of peritonitis in CAPD, presumably due to touch contamination or infection via the pericatheter route. Treatment for peritoneal dialysis-associated peritonitis consists of antimicrobial therapy, in some cases catheter removal is also warranted. Additional therapies for relapsing or recurrent peritonitis may include fibrinolytic agents and peritoneal lavage. Most episodes of peritoneal dialysis-associated peritonitis resolve with outpatient antibiotic treatment.	Majority of peritonitis cases are caused by bacteria (50%-due to gram positive organisms, 15% to gram negative organisms,20% were culture negative.2% of cases are caused by fungi, mostly Candida species. Polymicrobial infection in 4%.Exit-site infection was present in 13% and a peritoneal fluid leak in 3 % and M.tuberculosis 0.1%.	Initial empiric antibiotic coverage for peritoneal dialysis-associated peritonitis consists of coverage for gram-positive organisms (by vancomycin or a first-generation cephalosporin) and gram-negative organisms (by a third-generation cephalosporin or an aminoglycoside). Subsequently, the regimen should be adjusted based on culture and sensitivity data. Cure rates are approximately 75%.
Secondary peritonitis	Acute bacterial secondary peritonitis	Occurs after perforating, penetrating, inflammatory, infectious, or ischemic injuries of the GI or GU tracts. Most often follows disruption of a hollow viscus?chemical peritonitis?bacterial peritonitis(polymicrobial, includes aerobic gram negative {E coli, Klebsiella, Enterobacter, Proteus mirabilis} and gram positive { Enterococcus, Streptococcus} and anaerobes {Bacteroides, clostridia}). Presents with abdominal pain, tenderness, guarding or rigidity, distension, free peritoneal air, and diminished bowel sounds. Signs that reflect irritation of the parietal peritoneum resulting ileus. Systemic findings include fever, chills or rigors, tachycardia, sweating, tachypnea, restlessness, dehydration, oliguria, disorientation, and, ultimately, refractory shock.		Peritoneal lavage, Laparoscopy are the treatment of choice.
	Biliary peritonitis	Most often seen in cases of rupture of pathological gallbladder or bile duct or cholangitic abscess or secondary to obstruction of the biliary tract. Seen in alcoholic patients with ascites.
Tertiary peritonitis		Persistence or recurrence of intraabdominal infection following apparently adequate therapy of primary or secondary peritonitis. Associated with high mortality due to multi organ dysfunction. It presents in a similar way as other peritonitis but is recognized as an adverse outcome with poor prognosis.	Enterococcus, Candida, Staphylococcus epidermidis, and Enterobacter being the most common organisms.	Characterized by lack of response to appropriate surgical and antibiotic therapy due to disturbance in the hosts immune response.
Familial Mediterranean fever (periodic peritonitis, familial paroxysmal polyserositis)		Rare genetic condition which affects individuals of Mediterranean genetic background. Etiology is unclear. Presents with recurrent bouts of abdominal pain and tenderness along with pleuritic or joint pain. Fever and leukocytosis are common.		Colchicine prevents but does not treat acute attacks.
Granulomatous peritonitis		A rare condition caused by disposable surgical fabrics or food particles from a perforated ulcer, eliciting a vigorous granulomatous (delayed hypersensitivity) response in some patients 2-6 weeks after laparotomy. Presents with abdominal pain, fever, nausea and vomiting, ileus, and systemic complaints, mild and diffuse abdominal tenderness.	Diagnosed by the demonstration of diagnostic Maltese cross pattern of starch particles.	The disease is self-limiting. Treated with corticosteroids or anti-inflammatory agents.
Sclerosing encapsulating peritonitis		Seen in conditions associated with long term peritoneal dialysis, shunts like VP shunts, history of abdominal surgeries, liver transplantation. Symptoms include nausea, abdominal pain, diarrhea, anorexia, bloody ascites.
Intraperitoneal abscesses		Most common etiologies being Gastrointestinal perforations, postoperative complications, and penetrating injuries. Signs and symptoms depend on the location of the abscess within the peritoneal cavity and the extent of involvement of the surrounding structures. Diagnosis is suspected in any patient with a predisposing condition. In a third of cases it occurs as a sequela of generalized peritonitis. The pathogenic organisms are similar to those responsible for peritonitis, but anaerobic organisms occupy an important role. The mortality rate of serious intra-abdominal abscesses is about 30%.	Diagnosed best by CT scan of the abdomen.	Treatment consists of prompt and complete CT or US guided drainage of the abscess, control of the primary cause, and adjunctive use of effective antibiotics. Open drainage is reserved for abscesses for which percutaneous drainage is inappropriate or unsuccessful.
Peritoneal mesothelioma		Arises from the mesothelium lining the peritoneal cavity. Its incidence is approximately 300-500 new cases being diagnosed in the United States each year. As with pleural mesothelioma, there is an association with an asbestos exposure. Most commonly affects men at the age of 50-69 years. Patients most often present with abdominal pain and later increased abdominal girth and ascites along with anorexia, weight loss and abdominal pain. Mean time from diagnosis to death is less than 1 year without treatment.	CT with intravenous contrast typically demonstrates the thickening of the peritoneum. Laparoscopy with tissue biopsy or CT guided tissue biopsy with immunohistochemical staining for calretinin, cytokeratin 5/6, mesothelin, and Wilms tumor 1 antigen remain the gold standard for diagnosis.	At laparotomy the goal is cytoreduction with excision. Debulking surgery and intraperitoneal chemotherapy improves survival in some cases.
peritoneal carcinomatosis		Associated with a history of ovarian or GI tract malignancy. Symptoms include ascites, abdominal pain, nausea, vomiting.

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