Histopathology 2001, 38, 146±159 Lymphoproliferative disorders in children with primary immunodeficiencies: immunological status may be more predictive of the outcome than other criteria D Canioni, N Jabado, 1 E MacIntyre, 2 N Patey, J F Emile & N Brousse Service d'Anatomie-Pathologique and Universite  Paris V-Rene  Descartes; 1 Unite  d'Immuno-He Âmatologie Pe Âdiatrique, and 2 Service d'He Âmatologie Biologique, Ho Ãpital Necker-Enfants Malades, Paris, France Date of submission 16 November 1999 Accepted for publication 17 May 2000 Canioni D, Jabado N, MacIntyre E, Patey N, Emile J F & Brousse N (2001) Histopathology 38, 146±159 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 primary immunodeficiency and post-transplant patients. In primary immunodeficiency patients, LPDs are not well-known and, thus, we tried to evaluate their distinctive features and to determine prognostic factors predictive of clinical outcome by comparison with LPDs in post-transplant children. Methods and results: Clinical records and histopathol- ogy of 18 LPDs occurring in primary immunodeficieny children were compared with those of 10 LPDs in post- transplant 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 immunodefi- ciency than in post-transplant patients. A low T-cell count and abnormal T-cell function indicated bad prognosis in both groups. Polymorphic LPDs (PLPDs) were most frequent (n  19), whereas lymphomas were rare (n  7), and pseudo-tumoral lymphoid hyperplasias (n  2) were observed only in primary immunodeficiency. Comparative p53/bcl-2 staining revealed a p53 overexpression in lymphomas compared with PLPDs; CD20/CD79a showed a similar staining in lymphomas, whereas PLPD expressed mainly CD20. TCR and IgH rearrangements did not help in distin- guishing PLPDs from lymphomas, but detection of IgH clonality by Southern blot indicated 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 immunodeficiency compared to post-transplant children, even if some LPDs are similar 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 function. Keywords: children, Epstein±Barr virus, lymphomas, lymphoproliferative disorders, primary immunodeficiencies, transplantation Introduction Primary immunodeficiencies and immunosuppression after solid organ or bone marrow transplantation predispose children to the development of neoplasms and especially to lymphoproliferative disorders (LPDs). 1±4 In primary immunodeficiencies, the true incidence of an LPD is difficult to evaluate and has been estimated to be between 1.4% and 24% depending on the type of primary immunodeficiency. 4±6 Their histological spec- trum ranges from non-specific reactive hyperplasia to q 2001 Blackwell Science Limited. Address for correspondence: Dr D Canioni, Service d'Anatomie- Pathologique, Ho Ãpital Necker-Enfants Malades, 149, rue de Se Ávres, 75015, Paris, France.