Sinonasal NK/T-cell Lymphomas in the United States

Abstract

Sinonasal natural killer (NK)/T-cell lymphomas are common in Asia and areas of South and Central America but are rarely seen in the United States, where they have not been as well characterized. Fifteen cases diagnosed in Southern California were studied with respect to histologic features, immunophenotype, Epstein-Barr virus EBER in-situ hybridization (EBV EBER-ISH), and T-cell receptor gamma chain (TCR-gamma) gene rearrangement. Although ethnic background was available for only seven patients, six were of Asian or Hispanic descent with only one non-Hispanic white known. Twelve presented as sinonasal lesions, but three were limited to the oropharynx. Most cases (11 of 15) demonstrated both necrosis and an angiodestructive pattern. All cases demonstrated cytoplasmic CD3 positivity (15 of 15), and were positive for both TIA-1 and granzyme B (14 of 14). Perforin was positive in 5 of 14. CD56 was expressed in 10 of 15 and CD8 in 3 of 15. EBV EBER-ISH was positive in 14 of 14 and TCR-gamma gene rearrangement was detected in 1 of 14 cases. None (0 of 14) were positive for CD16 or CD57. Although CD16-positive histiocytes were abundant, double-label EBER-ISH/IHC failed to identify CD16 expression on EBV-positive tumor cells. Three cases with pleomorphic large cell morphology showed focal CD30 positivity, raising the differential diagnosis of anaplastic large cell lymphoma, but all were ALK-1-negative and otherwise similar to the other cases of NK/T-cell lymphoma. Sinonasal NK/T-cell lymphomas in the United States most often occur in ethnic groups from areas of reported high frequency (Asia, Central and South America), although less commonly than in endemic populations, and are otherwise similar phenotypically. A combined approach, including immunohistochemistry, EBV EBER-ISH, and TCR gene rearrangement studies, is most helpful to arrive at the correct diagnosis.

Nasal-type extranodal natural killer/T-cell lymphomas: a clinicopathologic and genotypic study of 42 cases in Singapore

“…The nasal-type NK/TCL in this study showed clinicopathologic findings similar to those of previous studies in Asian and Western countries. 8,15,19,20 In all, 82% of our cases presented with stage I and II disease, while 18% had stage III and IV disease at presentation. The sites of initial involvement included upper aerodigestive tract, skin, gastrointestinal tract, liver, spleen, bone marrow, testis, lung, brain and soft tissue.…”

“…However, a minority of these tumors with indistinguishable clinical, histologic and immunophenotypic features may express a T-cell phenotype and show monoclonal T-cell receptor gene rearrangement. 1,2,6,19 A recent study described the presence of restricted killer immunoglobulin-like receptor repertoire and monoclonal T-cell receptor gene rearrangement in six out of 15 cases of sinonasal lymphomas, suggesting a mixed NK/T-cell differentiation in a subset of these tumors. 32 The cell lineage of NK/TCL has been evaluated in several studies using molecular genetic techniques.…”

“…14 In this study, we describe the clinicopathologic and genotypic findings of 42 cases of nasal-type NK/ TCL in Singapore, which is a multiracial society populated predominantly by Asians, and compared our findings with those of other series reported in the Eastern 8,[15][16][17][18] and Western populations. [19][20][21][22] We analyzed the clonality of T-cell receptor-g gene using both traditional agarose gel electrophoresis and highly sensitive capillary electrophoresis in order to determine the proportion of NK/TCL that are of true NK derivation and compared these tumors with their T-cell counterparts with regards to their histologic features and clinical behavior. To investigate the prognostic importance and role of p53 in the pathogenesis of NK/TCL, we studied the immunohistochemical expression of p53 and evaluated the functional status of the overexpressed protein by correlating with the expression of its downstream target protein, p21.…”

Epstein-Barr Virus Nuclear Antigen (EBNA)-1 Carboxy-Terminal and EBNA-4 Sequence Polymorphisms in Nasal Natural Killer/T-Cell Lymphoma in the United States

“…The features of these cases have been previously reported with regard to clinical presentation, histology, immunophenotype, in situ hybridization for EBV-encoded RNA (EBER-ISH), and T-cell receptor gamma chain gene rearrangement (Gaal et al, 2000). All cases were positive for EBV EBER-ISH.…”

“…NL occur uncommonly in the U.S. but share identical morphologic, immunohistochemical, and molecular features with their more frequent counterparts in Asia and certain South and Central American populations (Arber et al, 1993;Gaal et al, 2000;Jaffe et al, 1996). Characterization of EBV polymorphisms to assess for tumorigenic strains or association with specific tumor types has been more extensively studied in other EBV-associated malignancies.…”