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

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.

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

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.

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.