Immunohistochemical Evaluation of S100 and CD163 in Leprosy with Emphasis on Polar Leprosy

Background: Leprosy (Hansen’s disease), caused by Mycobacterium leprae , manifests as an immunopathologic spectrum from tuberculoid (TT) to lepromatous (LL) leprosy. Histopathological diagnosis is essential for accurate classification. S100 immunostaining highlights nerve fibers within granulomas and CD163 identifies M2 macrophages, both offering diagnostic and pathogenetic insights beyond routine hematoxylin-eosin (H and E) staining. Aims: The aim of the study was to evaluate the pattern of S100 immunostaining and CD163 expression across different histopathological types of leprosy and correlate these with clinicopathological features. Materials and Methods: This hospital-based, cross-sectional study (August 2022–August 2024) included 33 adults, treatment-naïve, biopsy-proven leprosy cases. Skin biopsies were stained with H and E, Fite-Faraco, S100 (EP32), and CD163 (EP324) immunostains. S100 nerve patterns and CD163 grading were correlated with histopathological type. Results: Mean age was 40.2 years (male: female = 3.1:1). Lepromatous leprosy was the most common (33.3%). Fragmented S100 pattern (51.5%) predominated. S100 positive nerves were within the infiltrate in 83.3% of paucibacillary cases versus outside in 66.6% of multibacillary cases ( P = 0.009). CD163 was significantly associated with histopathological type ( P = 0.01), with Grade 4 positivity in 63.6% of LL cases. S100 enabled nerve visualization in 18% of cases where nerve fibers were difficult to identify on H and E alone. Conclusions: S100 immunostaining is a valuable adjunct in diagnosing and subtyping leprosy. CD163 correlates significantly with the lepromatous pole, reflecting M2 macrophage predominance, with future therapeutic implications.