Introduction: This is a report on FHL describing a family with five children of whom three were HLA class I genotype identical. Within a period of six years, these three siblings (one girl and two boys) were diagnosed with Epstein-Barr virus (EBV)-positive Hodgkin lymphoma (HL). Methods: In-situ hybridisation for EBV-encoded small nuclear RNAs 1 and 2 (EBER-ISH) was performed by standard non-isotopic technique. Germline mutation analysis was performed on peripheral blood lymphocytes. Results: Two of the siblings were diagnosed at age 12, the other at age 5. All three cases were localised at diagnosis i.e. Ann Arbor stage IA (two cases) and IIA (one case), without evidence of bulky disease. All three were treated with chemo- and/or radiotherapy. Two are in a still ongoing complete remission (CR) at 3 and 8 years after end of treatment. One experienced a late relapse, but has now completed her second year in CR after ending second line treatment. The presence of EBV in tumour cells was demonstrated by EBER-ISH and immunohistochemical staining for latent membrane protein 1. The three siblings were also found to be HLA class I genotype identical (A26,B38zA9,B5). A genetic analysis performed on peripheral blood samples of all family members (the five siblings and their parents) did not reveal germline mutations. None of the children had overt immunodeficiency or autoimmune disease. Conclusions: Genetic factors may be involved in HL. In fact, FHL cases may share HLA haplotypes and siblings with the autoimmune lymphoproliferative syndrome have a 50-fold increased risk of developing HL. Moreover, a polymorphism in the HLA class I subregion is associated with an increased susceptibility to develop EBV-positive HL. The present cases contribute to a further characterisation of FHL and to the hypothesis of a role played by HLA class 1 antigens, intratoumoral EBV genome and/or a combination of the two in the pathogenesis of at least some cases of HL.
Annals of Oncology, 2005, Issue (Suppl. 5)
Main Research Area:
9th International Conference on Malignant Lymphoma, 2005