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

Abstract

Extranodal natural killer (NK)/T-cell lymphoma (ENKTL), nasal type, comprises NK or cytotoxic T cells. We evaluated the clinical impact of cell type and the usefulness of T-cell receptor (TCR) gene transcripts in distinguishing cell lineage. One hundred and eight cases of ENKTL were analyzed for TCR gene rearrangements using the BIOMED-2 protocol and for TCR gene expression using immunohistochemistry for TCR-βF1 and TCR-cγM1, and RNA in situ hybridization for TCR gene transcripts. Prognostic factors were analyzed. Among the 108 cases, 44 were monoclonal for a TCR rearrangement (40%) while 64 (60%) were undefinable. The monoclonal cases expressed TCR-βF1 in 14 out of 40 cases (35%) and TCR-cγM1 in 1 out of 44 cases (2%). The 64 undetermined cases expressed TCR-βF1 in 15 cases (23%) and TCR-cγM1 in 1 (2%). Thirteen of 40 TCR-β constant gene transcript-positive cases (33%) expressed TCR-βF1 and one of nine TCR-γ constant gene transcript-positive cases (11%) expressed TCR-cγM1. TCR gene transcripts were not useful in the distinction of cell lineages. TCR gene transcripts were positive in ENKTLs as well as in normal B cells and aggressive NK-cell leukemia. Based on gene rearrangements and immunohistochemistry for TCR, there were 60 T-cell type cases (56%), 32 NK-cell type cases (30%), and 16 cases with an undetermined cell type (14%). TCR protein was expressed in 30/60 T-ENKTLs (50%) in a variable fraction of tumor cells. There were no significant differences in clinical findings or overall patient survival between T-or NK-cell types of ENKTL, although those with a T-cell type tended to show a better prognosis for those with localized nasal lymphomas. Univariate and multivariate analysis showed that a non-nasal ENKTL, age 460 years, high level of lactate dehydrogenase, bone marrow involvement, and the absence of radiotherapy were independent prognostic factors.

Diagnosis and management of extranodal NK/T cell lymphoma nasal type

“…9,10 It is also unclear if these cases were predominantly of alpha/beta or gamma/delta derivation. 9,10 However, whether the lymphoma cells are of putative NK-cell or T-cell origin has no impact on the clinical behaviour and outcome. 9,10 In the current World Health Organization (WHO) JAK/STAT pathway, and hence might be important in lymphomagenesis.…”

“…9,10 However, whether the lymphoma cells are of putative NK-cell or T-cell origin has no impact on the clinical behaviour and outcome. 9,10 In the current World Health Organization (WHO) JAK/STAT pathway, and hence might be important in lymphomagenesis. Although later studies failed to define a high incidence of JAK3 mutation, mutations of STAT3 and STAT5B…”

“…9,10 The exact proportion of cases of T-cell lineage has been reported to vary from 10-40%. 9,10 It is also unclear if these cases were predominantly of alpha/beta or gamma/delta derivation.…”

“…9,10 The exact proportion of cases of T-cell lineage has been reported to vary from 10-40%. 9,10 It is also unclear if these cases were predominantly of alpha/beta or gamma/delta derivation. 9,10 However, whether the lymphoma cells are of putative NK-cell or T-cell origin has no impact on the clinical behaviour and outcome.…”

Extranodal NK/T-cell lymphoma: a review of literature and case report

“…В других про-спективных исследованиях прогностическое значение NK-PI было опровергнуто [26,27]. Впоследствии корейскими исследователями на основании анализа 108 случаев ЭНКТЛ была опубликована работа об от-сутствии существенных различий ОВ в зависимости от линейной принадлежности опухолевых клеток [28]. Проведенное международное исследование показало, что экстраназальный тип, чаще встречающийся в Азии, характеризуется более короткой продолжительностью жизни в сравнении с назальным типом [6].…”