Primary Cutaneous NK/T-cell Lymphoma, Nasal Type and CD56-positive Peripheral T-cell Lymphoma

Abstract

Primary cutaneous, extranodal natural killer/T-cell lymphoma, nasal type (PC-ENKTL), is a rare Epstein-Barr virus (EBV)-associated neoplasm with poorly defined clinicopathologic features. We performed a multinational retrospective study of PC-ENKTL and CD56-positive EBV-negative peripheral T-cell lymphoma (PC-CD56+PTCL) in Asia in an attempt to elucidate their clinicopathologic features. Using immunohistochemistry for T-cell receptors (TCRs), in situ hybridization for EBV, and TCR gene rearrangement, we classified 60 tumors into 51 with PC-ENKTL (20 of NK-cell, 17 T-cell, and 14 indeterminate lineages) and 9 with PC-CD56+PTCL. Tumors of T-cell origin accounted for 46% of PC-ENKTLs with half of these cases being TCR-silent. As compared with T-lineage tumors, PC-ENKTLs of NK-cell lineage had more frequent involvement of regional lymph nodes and more frequently CD8-negative and CD56-positive. Cases of PC-ENKTL showed more frequent tumor necrosis, younger age, and a higher frequency of CD16 and CD30 expression than cases of PC-CD56+PTCL. CD56-positive T-lineage PC-ENKTL tumors (n=8) had more localized disease in the TNM (tumor-node-metastasis) staging and were more often of γδ T-cell origin compared with cases of PC-CD56+PTCL (n=9). PC-ENKTLs and PC-CD56+PTCLs were equally aggressive, with a 5-year overall survival rate of 25%. Tumor necrosis and CD16 expression may serve as useful surrogates for differentiating PC-ENKTL from PC-CD56+PTCL. A single lesion, an elevated lactate dehydrogenase level, and the presence of B symptoms were independent poor prognostic factors for PC-ENKTL in multivariate analysis. Further studies with more cases are warranted to delineate the clinicopathologic features and significance of EBV in these rare lymphomas.

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

“…In the eight cases positive for TCR, the αβ T-cell and γδ T-cell tumors were equal in number. 7 In agreement with these data from Takata et al, 50% of the T-lineage ENKTLs lacked TCR in the present study. Absence of TCR expression might be a common phenomenon in T-cell lymphoma and was also reported in EATL.…”

“…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. On the other hand, a lack of further analysis of PCR products can produce false-positive results.…”

“…7,8,10,20 Rodriguez-Pinilla et al 10 showed that ENKTLs primarily affecting the skin or subcutaneous tissue (n = 11) were all negative for TCR-γ. Pongpruttipan et al 8 analyzed 67 cases of ENKTL by immunohistochemistry and found that TCR types including βF1, γ, and δ were negative in 70% of cases, positive in only 9%, and indeterminate in 21%.…”

“…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. 7,8 In addition to gene rearrangement analysis, TCR protein detection in tumor cells is useful to distinguish cellular lineages in cases of ENKTL. After completion of productive TCR gene rearrangement, a primary transcript is synthesized that incorporates the constant domain gene, which allows translation of the full-length protein for the TCR chain.…”

“…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.…”