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

Abstract

We studied the clinicopathologic features of 42 cases of nasal-type extranodal natural killer (NK)/T-cell lymphoma in Singapore and compared our findings with other series reported in the Asian and Western populations. A panel of immunohistochemical stains, which included CD2, CD3, CD4, CD8, CD56, T-cell intracellular Antigen-1 and granzyme B, and in situ hybridization for Epstein-Barr virus encoded RNA (EBER) were performed. Polymerase chain reaction for T-cell receptor-gamma gene rearrangement using both gel and capillary electrophoresis were evaluated to determine the proportion of tumors which are of true T-cell lineage. We also studied the functional status of the overexpressed p53 protein in these lymphomas by correlating p53 expression with its downstream target protein, p21. In all, 31 out of 42 cases presented in the upper aerodigestive tract. The other sites of involvement included gastrointestinal tract, skin, soft tissue, testis, liver, spleen, bone marrow and brain. The tumors displayed characteristic morphologic features. In situ hybridization for EBER was detected in 41 out of 42 cases (97.6%). The only significant adverse prognostic factor identified was an International Prognostic Index of two or more. A significantly higher proportion of the tumors (27%), compared to previous studies, demonstrated monoclonal T-cell receptor-gamma gene rearrangement. There was, however, no difference in survival or clinicopathologic features between the true NK-cell tumors and their T-cell counterparts. Overexpression of p53 was present in 40% of the cases, but no significant difference in survival rate was detected in patients with p53 overexpression and there was no association between p53 overexpression with large cell morphology, and advanced stage of disease. These findings suggest that molecular aberrations other than those of the p53 pathway may be operative in the pathogenesis of this malignancy.

Nasal-type NK/T-cell lymphomas are more frequently T rather than NK lineage based on T-cell receptor gene, RNA, and protein studies: lineage does not predict clinical behavior

“…1,17 Gene rearrangement analysis for T-cell genes is a useful test to identify clonal T-cell proliferation. In cases of ENKTL, previous studies applying conventional PCR techniques showed wide ranges of T-cell clonality ranging from 0 to 71.4%, 5,6,18,19 while T-cell clonality ranged from 0 to 26% by BIOMED-2 multiplex PCR analysis. 7,8,10,20 The traditional PCR design with a few consensus primers to detect TCR gene rearrangement yields frequent falsenegative results because the primers cannot cover extensive sequence variations.…”

“…11 There have been only few reports on the clinical impact of cellular lineage for cases of ENKTL. Ng et al 5 failed to observe any difference in patient survival or clinicopathologic features between true NK-cell tumors and their T-cell counterparts. Takata et al 7 reported that NK-cell cutaneous ENKTLs more frequently showed lymph node involvementusually CD8-negative and CD56-positive-but no significant difference in overall patient survival was seen between NK-and T-cell lineages.…”

“…4 TCR gene rearrangement analysis using Southern blot hybridization or nested polymerase chain reaction (PCR) analyses disclosed variable T-cell clonality in ENKTLs ranging from 0 to 27%. 5,6 The BIOMED-2 Concerted Action protocol using multiplex PCR primers has now replaced conventional PCR in assaying gene rearrangements and has higher sensitivity than conventional PCR analyses that use fewer primer sets. Using this technology, monoclonal TCR-γ gene rearrangements were described in 8 of 27 cases of primary cutaneous ENKTLs, which did not express for TCR protein.…”

Immunohistochemical expression and clinical significance of P‐glycoprotein in previously untreated extranodal NK/T‐cell lymphoma, nasal type

“…This lymphoma is rare in the Western countries, but is relatively common in East Asia and Latin America. Nasal cavity is the most common site involved by this distinct clinicopathological entity [2,3]. The pathogenesis of extranodal NK/T-cell lymphoma, nasal type, remains uncertain.…”

Peripheral T cell lymphoma in Asia

“…The percentage of ENKL, nasal type, of T-cell origin, according to PCR-based research, ranges 0-38 % [86]. One phenotype study reported that ENKL, nasal type, was of NK origin (70 %), TCRcd?…”