title: Primary cutaneous follicle center cell lymphomas and large B cell lymphomas of the leg descend from germinal center cells. A single cell polymerase chain reaction analysis.
abstract: Primary cutaneous B cell lymphomas are defined as non-Hodgkin lymphomas that occur in the skin without extracutaneous involvement for 6 mo after diagnosis. They are characterized by a less aggressive course and better prognosis than their nodal counterparts. According to the European Organization for Research and Treatment of Cancer classification, the major subentities of primary cutaneous B cell lymphoma are follicle center cell lymphomas, immunocytomas, and large B cell lymphomas of the leg, which differ considerably regarding their clinical behavior, the former two being indolent, the latter being of intermediate malignancy. In this study, we applied a single cell polymerase chain reaction approach to analyze immunoglobulin V(H)/V(L) genes in 532 individual B lymphocytes from histologic sections of four follicle center cell lymphomas localized on the head and trunk, and four large B cell lymphomas on the leg. We found: (i) in six of eight patients a clonal heavy chain, and in seven of eight patients a clonal light chain rearrangement, all being potentially productive; (ii) no bias in VH gene usage, in four of seven light chain rearrangements the V kappa germline gene IGVK3-20*1 was used; (iii) no biallelic rearrangements; (iv) all V(H)/V(L) genes are extensively mutated (mutation rate 5.4-16.3%); (v) intraclonal diversity in six of eight cases (three of each group); and (vi) low replacement vs silent mutation ratios in framework regions indicating preservation of antigen-receptor structure, as in normal B cells selected for antibody expression. Our data indicate a germinal center cell origin of primary cutaneous follicle center cell lymphomas and large B cell lymphomas independent of those belonging to one of these subentities.
authors.affiliation: Department of Dermatology, Medical Faculty (Charité), Humboldt University, Berlin, Germany. sylke.gellrich@charite.de
authors.forename: S
authors.initials: S
authors.lastname: Gellrich
authors.forename: S
authors.initials: S
authors.lastname: Rutz
authors.forename: S
authors.initials: S
authors.lastname: Golembowski
authors.forename: C
authors.initials: C
authors.lastname: Jacobs
authors.forename: M
authors.initials: M
authors.lastname: von Zimmermann
authors.forename: P
authors.initials: P
authors.lastname: Lorenz
authors.forename: H
authors.initials: H
authors.lastname: Audring
authors.forename: M
authors.initials: M
authors.lastname: Muche
authors.forename: W
authors.initials: W
authors.lastname: Sterry
authors.forename: S
authors.initials: S
authors.lastname: Jahn
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D001706:Biopsy; D002999:Clone Cells; D004252:DNA Mutational Analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D015322:Gene Rearrangement, B-Lymphocyte / Q000235:genetics; D018858:Germinal Center / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007866:Leg; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000473:pathology*; D008224:Lymphoma, Follicular / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology*
chemical_list: D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D012333:RNA, Messenger