Epstein-Barr virus-negative Hodgkin's lymphoma after mycosis fungoides: molecular evidence for distinct clonal origin.
The association of mycosis fungoides (MF) and Hodgkin's lymphoma is a relatively frequent occurrence, but the potential clonal relationship of the two neoplasms is still controversial. We report a case of a patient with a history of MF in Clinical Stage 1A who developed retroperitoneal lymphadenopathy 9 years after the initial diagnosis of MF. A bone marrow biopsy obtained at this time showed nodular involvement by a mixed cellular infiltrate with large, atypical cells consistent with Hodgkin and Reed-Sternberg (RS) cells. These atypical cells were positive for CD30 and CD15 and did not express B- or T-cell markers. In addition, they lacked evidence of infection by Epstein-Barr virus, both by immunohistochemical staining for latent membrane protein 1 and by in situ hybridization for EBER1/2. The background population consisted mainly of small T cells without morphological or phenotypical signs of malignancy. Review of the skin biopsy obtained 9 years before showed the typical features of MF. Polymerase chain reaction analysis of the T-cell receptor T-gene confirmed the presence of a clonal T-cell rearrangement in the skin specimen. The bone marrow biopsy, however, showed a polyclonal pattern both for the T-cell receptor gamma-gene, as well as for immunoglobulin heavy chain genes. Isolation of RS cells stained for CD30 was performed by laser capture microdissection. Polymerase chain reaction analysis of several groups of RS cells showed a reproducible biallelic rearrangement of IgH genes, which was confirmed by cloning and sequencing of polymerase chain reaction products. To our knowledge, this is the first case in which a distinct clonal origin of MF and Hodgkin's lymphoma arising in the same patient is clearly demonstrated, based on molecular analysis of microdissected RS cells.
Institute of Pathology, Technical University Munich, Germany.
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M
Kremer
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Sandherr
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Geist
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AD
Cabras
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Höfler
F
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Fend
D014408:Biomarkers, Tumor / Q000032:analysis; D001854:Bone Marrow Cells / Q000737:chemistry / Q000473:pathology; D002999:Clone Cells; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor / Q000235:genetics; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification; D006689:Hodgkin Disease / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000150:complications* / Q000473:pathology; D016133:Polymerase Chain Reaction; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics; D016539:Reed-Sternberg Cells / Q000737:chemistry / Q000473:pathology; D012878:Skin Neoplasms / Q000150:complications* / Q000473:pathology
D014408:Biomarkers, Tumor; D017931:DNA Primers; D004273:DNA, Neoplasm; D007143:Immunoglobulin Heavy Chains; D016692:Receptors, Antigen, T-Cell, gamma-delta