Disseminated Histoplasmosis Masquerading as Metastatic Malignancy: A Diagnostic Odyssey in an Immunocompromised Host

Disseminated histoplasmosis is a rare systemic fungal infection caused by Histoplasma capsulatum, typically reported in immunocompromised individuals. Bilateral adrenal involvement, though a recognized but uncommon manifestation, frequently presents a formidable diagnostic challenge owing to its striking radiologic resemblance to disseminated malignancy. We report a case of a 46-year-old male farmer from India presenting with abdominal pain, a progressive paraumbilical lump, low-grade fever, and weight loss. Contrast-enhanced CT revealed large bilateral adrenal masses, widespread abdominal soft tissue deposits, and hypodense splenic lesions. Although these appearances most closely favored disseminated malignancy of unknown primary, they were nonspecific, and a disseminated infective etiology was retained within the radiologic differential. The patient had an untreated asymptomatic hepatitis C virus (HCV) infection and type 2 diabetes mellitus. Fine-needle aspiration cytology (FNAC) of the bilateral adrenal masses and a core-needle biopsy of the paraumbilical nodule, with histopathological examination using periodic acid-Schiff (PAS) staining, revealed intracellular and extracellular fungal forms with narrow-based budding morphology, consistent with H. capsulatum. Morning serum cortisol was preserved at 10.80 µg/dL despite massive bilateral adrenal infiltration. Urine Histoplasma galactomannan antigen was negative, underscoring the limitations of serologic tests in non-HIV-associated immunosuppression. This case suggests, rather than establishes, that non-HIV-associated immunosuppression from HCV infection and diabetes mellitus may act as predisposing substrates for invasive fungal disease; a causal role cannot be inferred from a single report and warrants confirmation in larger series.