To the Editor:

Cells that have altered or absent DNA repair mechanisms may be more susceptible to genetic alteration and, thus, neoplastic transformation. Alteration in the integrity of the DNA mismatch repair mechanism can be measured by documenting microsatellite instability (MSI). Microsatellite alterations may not affect the phenotype of the cell, but are a sensitive measure of defective DNA mismatch repair which in some cells is a precursor event to neoplastic transformation. Accordingly, patients with Lynch syndrome, a hereditary disorder of DNA mismatch repair, have an increased frequency of carcinomas.1 In addition, MSI has been implicated in the oncogenesis of at least 16 different types of sporadic carcinomas.2 

In contrast to carcinomas, we and others have documented MSI in a cohort of B- and T-cell lymphomas arising in immunosuppressed hosts.3,4 We have also shown that microsatellite analysis is an effective means of determining the recipient/donor origin of the tumor when it arises in allograft recipients. We have extended our previous studies by analyzing a group of six natural killer cell–like T-cell lymphomas (NKTCL), of which three arose in allograft recipients and three arose in immunocompetent hosts.5 

We examined six microsatellite loci in each case as previously described3 (Table 1). Microsatellite instability was detected in five of the six microsatellite loci in one NKTCL arising in an allograft recipient. In contrast, MSI was not detected at any of the six loci in three NKTCL arising in immunocompetent hosts. Furthermore, one of the three NKTCL arising in allograft recipients was of donor origin and did not have MSI. Loss of heterozygosity was not observed in any case.

Table 1.

Summary of Analysis on NK-TCL and PTLD

LymphomaNo. of CasesMSIDonor OriginHost Origin
NK-TCL 
Allograft recipient 
Immunocompetent NA NA 
All PTLD 
Cases studied for MSI NA NA 
Cases studied for donor/host origin 39 NA 32 
LymphomaNo. of CasesMSIDonor OriginHost Origin
NK-TCL 
Allograft recipient 
Immunocompetent NA NA 
All PTLD 
Cases studied for MSI NA NA 
Cases studied for donor/host origin 39 NA 32 

Abbreviations: NK-TCL, Natural killer–like T-cell lymphoma; PTLD, posttransplant lymphoproliferative disorder; MSI, microsatellite instability; NA, not applicable.

Thirty-nine cases of posttransplant lymphoproliferative disorders (PTLD), including those reported here, have been studied for the host/donor origin in allograft recipients3 6 (Table 1). Seven tumors (18%) have been reported as donor origin and 32 were of recipient origin (82%). Interestingly, one case of NKTCL arising in an allograft recipient was donor in origin, and represents the first reported case with these findings.

Nine cases of PTLD, including the cases in this report, have now been analyzed; of which two cases have MSI. Both cases were T-cell cases of recipient origin. This limited series of NKTCL is consistent with the concept that microsatellite instability plays a role in the pathogenesis of a minority of cases of lymphomas arising in immunocompromised hosts.

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HFA
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Jager FCA
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