Granulomatous variant of extranodal NK/T-cell lymphoma: Mimicking inflammatory or infective lesions.

[OBJECTIVE] A heavy admixture of inflammatory cells is observed in extranodal NK/T-cell lymphoma (ENKTL), but granuloma formation is typically absent. We aimed to describe the clinicopathological features of this rare granulomatous variant of ENKTL.

[METHODS] Four cases of the granulomatous variant of ENKTL were retrospectively analyzed, combined with a review of four cases reported in the literature.

[RESULTS] The four cases in our institution comprised one female and three male patients aged 57-65 years (median: 61 years). One patient had a nasal lesion, while three exhibited extranasal disease. All were diagnosed at stage III/IV. Histopathology showed extensive epithelioid granulomas, but lacked typical features such as angiocentricity and angiodestruction. Scattered atypical lymphoid cells with varying degrees of cytological atypia were observed between granulomas. Immunohistochemistry confirmed T or NK cell lineage with expression of CD3ε and cytotoxic markers. Epstein-Barr virus-encoded small RNA (EBER) in situ hybridization (ISH) confirmed an Epstein-Barr virus (EBV) association in all cases. Three cases were CD56-positive, and two were CD5-negative. Three showed CD4-/CD8-, and one showed CD4-/CD8+. Mutations in DNMT3A, KMT2D, and KMT2A in Case #3 and a B2M mutation in Case #4 were revealed by next-generation sequencing (NGS). Combined with literature, granulomatous ENKTL most frequently involved the skin (6/8 cases). Notably, five of these eight cases were initially misdiagnosed as chronic inflammation.

[CONCLUSIONS] ENKTL encompasses a variety of morphological features and a broad biological spectrum. Heightened awareness of this granulomatous variant is critical for preventing diagnostic delays and ensuring timely therapeutic intervention.