A 43-year-old Hispanic man with a history of lepromatous leprosy presented with lymphadenopathy. Biopsy was performed to exclude lymphoproliferative disorder. Histologic examination showed lymphoid tissue containing clustered histiocytes with vacuolated, “lipid-like” cytoplasm. Within vacuoles, there was eosinophilic, flocculent debris (panel A; hematoxylin and eosin stain, original magnification ×1000). CD68 immunohistochemistry stain highlighted histiocytes (panel B; original magnification ×400). Ziehl-Neelsen stain was negative (panel C; original magnification ×1000) for acid-fast bacilli (AFB); however, given the clinical history, a Fite stain was performed, highlighting numerous AFB, or “red snappers” (panel D; original magnification ×1000 [inset, ×2000]).

Mycobacterium leprae is weakly acid-fast as the result of a thinner mycolic acid coat than is seen in other Mycobacterium, such as Mycobacterium tuberculosis. As a result, xylene exposure will more rapidly remove dyes from weakly acid-fast organisms. This explains the Ziehl-Neelsen stain negativity in this case, whereas Fite stain is positive. The Fite stain uses xylene with peanut oil to limit exposure of mycolic acid to xylene, allowing retention of dye and microscopic positivity. This case emphasizes both the importance of understanding biologic properties of organisms and ordering appropriate stains based on that knowledge and the importance of communication between the clinician and pathologist in arriving at the correct diagnosis. Although relatively rare, pathologists should consider M leprae infection when interpreting cases showing collections of histiocytes, particularly when Ziehl-Neelsen stain is negative.