Diagnosis
Diagnosis
Extranodal NK/T-cell lymphoma
Discussion
Extranodal NK/T-cell lymphoma (ENKTL) is an Epstein-Barr virus (EBV)-associated lymphoma of NK-cell or cytotoxic T-cell lineage. ENKTL is more common in East Asia and Latin America and is classified into nasal and non-nasal forms based on the site of the primary tumor. The nasal form is the most common and typically involves the nasal cavity, nasopharynx, and upper aerodigestive tract. Locally destructive growth may result in erosion of the nasal floor and hard palate, leading to the historic designation "lethal midline granuloma." The non-nasal form most commonly involves the skin, gastrointestinal tract, soft tissue, and testis.
Histologically, ENKTL is characterized by a dense atypical lymphoid infiltrate, frequently accompanied by ulceration, extensive necrosis, and a prominent inflammatory background. The neoplastic cells are typically medium-sized with irregular nuclear contours, granular chromatin, and moderate amounts of pale cytoplasm. A characteristic feature is an angiocentric and angiodestructive growth pattern, with tumor cells infiltrating and damaging blood vessel walls, resulting in ischemia, coagulative necrosis, and ulceration. These findings may closely mimic infectious, inflammatory, or vasculitic processes, particularly in small or necrotic biopsies. The neoplastic cells typically express CD2, cytoplasmic CD3ε, CD56, and cytotoxic markers including TIA-1, granzyme B, and perforin, and demonstrate EBV infection by EBER in situ hybridization.
This diagnostic pitfall was illustrated in the present case. The initial skin biopsies were interpreted as medium-vessel vasculitis in an appropriate clinical setting. Following the diagnosis of ENKTL in the sinonasal lesion, retrospective immunohistochemical evaluation of the original skin biopsies demonstrated expression of CD56, cytotoxic markers, and EBER within the lesional lymphoid cells, confirming that the cutaneous lesions represented early involvement by ENKTL rather than primary vasculitis.
Resources
- WHO Classification of Tumours Editorial Board: Haematolymphoid Tumours, 5th ed, 2024
- de Leval L, Feldman AL, Pileri S, Nakamura S, Gaulard P. Extranodal T- and NK-cell lymphomas. Virchows Arch. 2023;482(1):245-264. PMID: 36336765; PMCID: PMC9852223
- Quintanilla-Martinez L, Swerdlow SH, Tousseyn T, Barrionuevo C, Nakamura S, Jaffe ES. New concepts in EBV-associated B, T, and NK cell lymphoproliferative disorders. Virchows Arch. 2023;482(1):227-244. PMID: 36216980; PMCID: PMC9852222