Distinguishing Lymphoma, Disseminated TB, Sarcoidosis, Histoplasmosis, and Brucellosis

Epidemiologic and Exposure History

The American College of Physicians suggests that geographic and occupational exposures are diagnostic anchors for distinguishing between conditions such as histoplasmosis, tuberculosis, brucellosis, and sarcoidosis, with histoplasmosis being endemic to Ohio and Mississippi River valleys 1
Recent travel to TB-endemic regions significantly increases dissemination risk, according to the Centers for Disease Control and Prevention 1
Occupational exposure to livestock, unpasteurized dairy products, or endemic regions is a risk factor for brucellosis, as stated by the World Health Organization 1
The American Thoracic Society notes that sarcoidosis has a higher incidence in northern Europeans and African Americans, with no specific exposure pattern 2

The American College of Rheumatology states that constitutional symptoms such as fever, night sweats, weight loss, and extreme fatigue are common in disseminated TB and histoplasmosis, lasting weeks to months 1
Brucellosis is characterized by an undulating fever pattern, profound sweats, and arthralgias, according to the Infectious Diseases Society of America 1
Lymphoma often presents with B symptoms, including fever, night sweats, and weight loss, as well as painless lymphadenopathy, as noted by the American Society of Clinical Oncology 3
Sarcoidosis may be asymptomatic or present with Löfgren's syndrome, characterized by bilateral hilar adenopathy with erythema nodosum and/or periarticular arthritis, according to the American Thoracic Society 4, 5

The American College of Radiology suggests that chest CT patterns are diagnostically powerful, with sarcoidosis typically showing bilateral hilar adenopathy with perilymphatic nodules, and disseminated TB or histoplasmosis showing necrotizing granulomas with cavitation 1, 4
Lymphoma often presents with bulky mediastinal adenopathy and extranodal masses, as stated by the American Society of Clinical Oncology 3

The American Society for Clinical Pathology notes that granuloma characteristics are the gold standard for diagnosis, with tuberculosis showing robust necrotizing granulomas, histoplasmosis showing large acellular necrotizing granulomas, and sarcoidosis showing well-formed, non-necrotizing granulomas 1, 4, 6
Brucellosis is characterized by non-caseating granulomas, similar to sarcoidosis, but with positive cultures or serology, as stated by the Centers for Disease Control and Prevention 1
Lymphoma is diagnosed by the presence of a monoclonal B-cell population on immunohistochemistry, as noted by the American Society of Clinical Oncology 3

The American Thoracic Society recommends a step-wise approach to laboratory testing, starting with mycobacterial and fungal testing to rule out infection, followed by sarcoidosis-specific testing, and finally lymphoma evaluation 1, 4, 5
The Infectious Diseases Society of America suggests that mycobacterial testing should include sputum AFB smear and culture, as well as interferon-gamma release assay or tuberculin skin test 1
Fungal testing should include histoplasma urine/serum antigen, fungal cultures, and serology, as stated by the Centers for Disease Control and Prevention 1
Lymphoma evaluation should include complete blood count with differential, serum LDH, flow cytometry, and tissue biopsy with immunohistochemistry, as noted by the American Society of Clinical Oncology 3, 7