Lymphoproliferative disorders in children with primary immunodeficiencies:immunological status may be more predictive of the outcome than other criteria

Aims: Lymphoproliferative disorders (LPDs) are a severe complication in pri mary immunodeficiency and post-transplant patients. In primary immunodefici ency patients, LPDs are not well-known and, thus, we tried to evaluate thei r distinctive features and to determine prognostic factors predictive of cl inical outcome by comparison with LPDs in post-transplant children. Methods and results: Clinical records and histopathology of 18 LPDs occurri ng in primary immunodeficiency children were compared with those of 10 LPDs in posttransplant children, together with results of in-situ hybridization for the detection of Epstein-Barr virus (EBV)-RNA and molecular biological techniques. LPDs were frequently extranodal, EBV-associated, and were more commonly pleomorphic in primary immunodeficiency than in post-transplant p atients. A low T-cell count and abnormal T-cell function indicated bad prog nosis in both groups, Polymorphic LPDs (PLPDs) were most frequent (n = 19), whereas lymphomas were rare (n = 7), and pseudo-tumoral lymphoid hyperplas ias (n = 2) were observed only in primary immunodeficiency. Comparative p53 /bcl-2 staining revealed a p53 overexpression in lymphomas compared with PL PDs; CD20/CD79a showed a similar staining in lymphomas, whereas PLPD expres sed mainly CD20, TCR and IgH rearrangements did not help in distinguishing PLPDs from lymphomas, but detection of IgH clonality by Southern blot indic ated poor prognosis, whereas oligoclonality by Southern blot regardless of PCR clonality and especially a polyclonal profile by Southern blot and PCR indicated a relatively good prognosis. Conclusions: This study documents the pleomorphism of LPDs in primary immun odeficiency compared to post-transplant children, even if some LPDs are sim ilar in both groups (PLPDs). No criteria are useful enough to ascertain the diagnosis of malignancy in this series. Some molecular biological criteria help to predict the clinical outcome which, nevertheless, seems to depend more on the degree of immunosuppression and on T-lymphocyte presence and fu nction.