Post-transplantation lymphoproliferative disorders in Mexico: an aggressive clonal disease associated with Epstein-Barr virus type A.
Post-transplantation lymphoproliferative disorders (PT-LPDs) are a complication of immunosuppression with variable clinical behavior and frequent Epstein-Barr virus (EBV) association. There is geographic variation in the association of EBV with certain tumors and a lack of studies of PT-LPDs from developing countries, so we decided to study in detail a series of PT-LPDs from Mexico to identify similarities and differences between populations in Mexico and those in Europe and the United States. We used paraffin-embedded tissue from eight PT-LPDs (six from men, two from women) that arose after renal transplantation. Clinical data, morphologic features, and clonality on the basis of immunoglobulin (Ig) light chain restriction, as well as polymerase chain reaction (PCR) for Ig heavy chain genes, were studied. The presence of EBV was investigated with PCR, immunohistochemical analysis for latent membrane protein (LMP)-1, and in situ hybridization for EBV early RNA transcripts. In addition, the subtype of EBV based on the EBNA 2A and 2B genes and the presence of a 30-bp deletion in the LMP-1 gene were investigated by PCR. Seven (87.5%) of eight cases presented with gastrointestinal involvement; five patients died. Three cases were polymorphic PT-LPDs, four were monomorphic large cell lymphomas (one diffuse large cell, three immunoblastic), and one was unclassifiable. All showed a B-cell phenotype, with a clonal population demonstrated in seven of the eight cases. Tumor cells expressed EBERs in all of the cases and LMP-1 in six of seven evaluable cases. Seven of seven cases showed EBV subtype A. Two (25%) of eight cases had the 30-bp LMP-1 deletion. This study shows that PT-LPDs in Mexico are clonal disorders associated with EBV subtype A. In contrast to series from Europe and the United States, our cases showed a significantly higher incidence of gastrointestinal tract involvement (P < .001), and a lower incidence of the 30-bp LMP-1 deletion, although this was not statistically significant (P < .28).
Quintanilla-Martínez
L
L
Department of Pathology, Instituto Nacional de la Nutrición, Mexico City, Mexico. leticiaq@box1.nih.gov
Lome-Maldonado
C
C
Schwarzmann
F
F
Gredler
E
E
Reyes
E
E
Angeles-Angeles
A
A
Fend
F
F
D000328:Adult; D000956:Antigens, Viral / Q000032:analysis; D005260:Female; D006566:Herpesviridae Infections / Q000235:genetics / Q000473:pathology / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D016867:Immunocompromised Host; D016130:Immunophenotyping; D007414:Intestinal Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology*; D016030:Kidney Transplantation / Q000009:adverse effects*; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000473:pathology / Q000821:virology; D008232:Lymphoproliferative Disorders / Q000145:classification / Q000235:genetics / Q000473:pathology / Q000821:virology*; D008297:Male; D008800:Mexico; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000032:analysis; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology / Q000821:virology; D012367:RNA, Viral / Q000032:analysis; D014412:Tumor Virus Infections / Q000235:genetics / Q000473:pathology / Q000821:virology*; D014763:Viral Matrix Proteins / Q000235:genetics
D000956:Antigens, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D009856:Oncogene Proteins, Viral; D012367:RNA, Viral; D014763:Viral Matrix Proteins