Granulomatous Lesions in the Head and Neck Region: A Clinicopathological, Histochemical, and Molecular Diagnostic Study

<b>Background/Objectives</b>: Granulomatous lesions of the head and neck arise from diverse infectious and non-infectious causes, with tuberculosis (TB) being a predominant etiology. This retrospective study analyzed 42 cases from the archives of university of Baghdad, College of Dentistry (1975-2025). This study aimed to characterize the clinicopathological features of these lesions and to assess the diagnostic performance of histochemical stains and real-time PCR in identifying infectious etiologies-particularly <i>Mycobacterium tuberculosis</i>-in formalin-fixed, paraffin-embedded (FFPE) tissue samples. <b>Methods</b>: Definitive diagnoses included 25 TB cases confirmed through clinical, microbiological, and therapeutic follow-up at the Baghdad Tuberculosis Institute, and 17 non-TB cases classified by predefined clinicopathological criteria supported by relevant clinical data. Zieh-Neelsen (ZN), Periodic acid-Schiff (PAS), and Grocott methenamine silver (GMS) stains were employed to identify acid-fast bacilli and fungal organisms. Statistical analysis was performed using SPSS version 26, with significance set at <i>p</i> ≤ 0.05. <b>Results</b>: The mean patient age was 36.28 years (SD = 20.6), with a female predominance (59.5%). Necrotizing granulomas were identified in 69% of cases and were strongly associated with tuberculosis, which was detected in 59.5% of specimens. ZN staining showed a sensitivity of 16.7% for tuberculosis, while PCR sensitivity was highly dependent on sample age. The detection rate was 33.3% in samples archived for less than 10 years but only 10% in older samples, resulting in an overall sensitivity of 24.0% for tuberculous cases. Langhans-type giant cells were significantly more frequent in necrotizing granulomas and strongly associated with tuberculosis infection (<i>p</i> = 0.001). Fungal infections, predominantly aspergillosis, were confirmed by PAS and GMS in 11.9% and 9.5% of cases, respectively, and were confined to non-necrotizing granulomas. The mandible was the most commonly affected site, and soft tissue lesions were significantly associated with necrotizing granulomas (<i>p</i> = 0.004). <b>Conclusions</b>: These findings underscore the complementary role of histopathology, histochemical stains, and molecular diagnostics in improving the evaluation and diagnosis of granulomatous inflammation in head and neck lesions.