title: The morphologic and molecular genetic categories of posttransplantation lymphoproliferative disorders are clinically relevant.
abstract: BACKGROUND
  Posttransplantation lymphoproliferative disorders (PT-LPDs) are a well-known complication of immunosuppression associated with solid organ transplantation. The clinical course of PT-LPDs is unpredictable; some patients experience regression of all lesions with a reduction in immunosuppression, whereas other patients, despite chemotherapy, radiation therapy, or surgery, rapidly die of their disease. In this study, the authors attempted to establish whether the previously described morphologic and molecular genetic categories of PT-LPD--plasmacytic hyperplasia (PH), polymorphic PT-LPD (polymorphic), and malignant lymphoma/multiple myeloma (ML/MM)--are clinically relevant and helpful in predicting the clinical outcome of patients who develop these lesions.
  
  
  METHODS
  To determine the clinical significance of the morphologic and molecular genetic categories of PT-LPDs, the clinical characteristics of 32 solid organ transplant recipients (26 heart, 5 kidney, and 1 lung), including age, time from transplantation to development of PT-LPD, stage of disease, and clinical outcome, were compared with the morphologic and molecular genetic features of the 41 PT-LPDs that they developed (15 PH in 12 patients, 19 polymorphic in 16 patients, and 7 ML/MM in 6 patients). Clinical outcome was defined by the following categories: 1) regression (after a reduction in immunosuppression) and surgical resolution (by surgical excision, with or without a reduction in immunosuppression); 2) medical resolution (by chemotherapy and/or radiation therapy); and 3) no response.
  
  
  RESULTS
  Although there was no difference in the time from transplantation to PT-LPD development among patients belonging to the three morphologic and molecular genetic categories, there was a significant difference in patient age at the time of PT-LPD development (P < 0.0098). Younger patients developed PH (mean age of 19 years), whereas older patients developed polymorphic PT-LPD (mean age of 35 years) and ML/MM (mean age of 56 years). Patients with PH presented with lower stages of disease (Stages I-II) than patients with ML/MM (P < 0.0004). Furthermore, there was a statistically significant trend between morphologic and molecular genetic category and clinical outcome, with decreased likelihood that lesions categorized as PH, polymorphic, or ML/MM would regress with a reduction in immunosuppression or be resolved by surgery, whereas those classified as ML/MM were more likely to exhibit no response to aggressive clinical intervention (P < 0.00006). Furthermore, no patients with PH died, whereas 20% with polymorphic PT-LPD and 67% with ML/MM died as a direct result of their PT-LPDs.
  
  
  CONCLUSIONS
  This study strongly suggests that classification of PT-LPDs into the morphologic and molecular genetic categories PH, polymorphic, PT-LPD and ML/MM is clinically relevant.
authors.affiliation: Department of Pathology, Cornell University Medical College, New York, New York 10021, USA.
authors.forename: A
authors.initials: A
authors.lastname: Chadburn
authors.forename: J M
authors.initials: JM
authors.lastname: Chen
authors.forename: D T
authors.initials: DT
authors.lastname: Hsu
authors.forename: G
authors.initials: G
authors.lastname: Frizzera
authors.forename: E
authors.initials: E
authors.lastname: Cesarman
authors.forename: T J
authors.initials: TJ
authors.lastname: Garrett
authors.forename: J G
authors.initials: JG
authors.lastname: Mears
authors.forename: S D
authors.initials: SD
authors.lastname: Zangwill
authors.forename: L J
authors.initials: LJ
authors.lastname: Addonizio
authors.forename: R E
authors.initials: RE
authors.lastname: Michler
authors.forename: D M
authors.initials: DM
authors.lastname: Knowles
mesh_terms: D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005260:Female; D016027:Heart Transplantation / Q000009:adverse effects*; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006801:Humans; D006965:Hyperplasia / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects*; D016040:Lung Transplantation / Q000009:adverse effects*; D016393:Lymphoma, B-Cell / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic; D012698:Serologic Tests; D015996:Survival Rate; D016896:Treatment Outcome