Question

A middle-aged woman from Assam presents with chronic cough, fever, weight loss and cavitary lung lesions. Lung biopsy shows granulomatous inflammation with caseous necrosis and histiocyte-rich infiltrates. Which of the following should be strongly considered in the differential diagnosis?

• A. Sarcoidosis
• B. Aspergillosis
• C. Histoplasmosis
• D. Granulomatosis with polyangiitis

Hint:

An endemic dimorphic fungus of North-East India that grows inside histiocytes and mimics TB.

Answer 1

The Correct Option is C

Step 1: Recognise the clinical syndrome.
Chronic cough, fever, weight loss and cavitary lesions in a patient from Assam (North-East India) is a classic tuberculosis-mimic picture. The histology - granulomas with caseous necrosis and abundant histiocytes - raises an endemic dimorphic fungus.

Step 2: Geographic and histological clue.
North-East India (Assam, Manipur) is an endemic focus for histoplasmosis. Histoplasma capsulatum is an intracellular dimorphic yeast that proliferates inside histiocytes/macrophages, producing histiocyte-rich, necrotising granulomas that closely mimic tuberculosis. The small intracellular yeasts are seen on GMS/PAS stains.

Step 3: Why the other options are less fitting.
• Sarcoidosis - gives non-caseating granulomas; caseous necrosis argues against it.
• Aspergillosis - typically an aspergilloma in a pre-existing cavity or angio-invasive disease with septate acute-angle hyphae, not histiocyte-rich caseating granulomas.
• Granulomatosis with polyangiitis - necrotising vasculitis with geographic necrosis and giant cells, usually with sinonasal/renal involvement, not the histiocyte-rich endemic-fungus picture.

Key fact: An Assam patient with TB-like caseating, histiocyte-rich granulomas should prompt strong consideration of histoplasmosis.