title: Splenic marginal-zone lymphoma: one or more entities? A histologic, immunohistochemical, and molecular study of 42 cases.
abstract: We analyzed 42 splenic marginal-zone lymphoma (SMZL) cases diagnosed on splenectomy specimens after established World Health Organization criteria. A predominantly nodular growth pattern was observed in 24 cases; the remainder showed predominantly (11/42) or exclusively (7/42) diffuse infiltration. Twenty-one cases showed the "classic" biphasic appearance; 13 cases exhibited marginal-zone morphology; finally, 8 cases were composed predominantly of small cells. CD21 and CD35 were expressed by 12/42 and 17/38 cases, respectively. DBA.44 was detected in 24/42 cases. Seventeen of 37 cases were surface IgD (SIgD)-positive. Twenty-one of 22 analyzed cases were SIgM-positive (12/21 coexpressed SIgD). Five of 37 cases were SIgG-positive. CD27 staining was observed in 21/35 cases; 7/18 CD27-positive cases coexpressed SIgD; 7/14 CD27-negative cases were SIgD-positive. Forty IGHV-D-J rearrangements were amplified in 34/42 cases: the IGHV4-34 gene predominated, followed by IGHV1-2. Using the 98% homology cut-off, 25/40 (62.5%) IGHV sequences were considered as "mutated": 10/11 cases with monomorphous, marginal-zone morphology were IGHV-mutated; in contrast, 4/6 cases with monomorphous, small-cell morphology were IGHV-unmutated. Five of 7 cases expressing IGHV1 subgroup genes had biphasic morphology, whereas 6/9 IGHV3-expressing cases had monomorphous, marginal-zone morphology. Most IGHV-mutated cases (14/20; 70%) were SIgD-negative; in contrast, 8/11 IGHV-unmutated cases expressed SIgD. CD27 was detected in 10/17 IGHV-mutated and 6/10 IGHV-unmutated cases. Seven of 11 CD27-negative cases were IGHV-mutated; 5/7 CD27-negative/IGHV-mutated cases expressed DBA.44. These results confirm the considerable histologic, immunohistochemical, and molecular heterogeneity of SMZL and indicate an origin from the diverse resident B-cell populations of the normal SMZ.
authors.affiliation: Hemopathology Department, Evangelismos Hospital, Athens, Greece.
authors.forename: Theodora
authors.initials: T
authors.lastname: Papadaki
authors.forename: Kostas
authors.initials: K
authors.lastname: Stamatopoulos
authors.forename: Chrysoula
authors.initials: C
authors.lastname: Belessi
authors.forename: Evi
authors.initials: E
authors.lastname: Pouliou
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Parasi
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Douka
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Laoutaris
authors.forename: Athanasios
authors.initials: A
authors.lastname: Fassas
authors.forename: Achilles
authors.initials: A
authors.lastname: Anagnostopoulos
authors.forename: Dimitra
authors.initials: D
authors.lastname: Anagnostou
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000235:genetics; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain / Q000235:genetics; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics; D016130:Immunophenotyping; D008223:Lymphoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012334:RNA, Neoplasm / Q000032:analysis; D013154:Spleen / Q000473:pathology*; D013156:Splenectomy; D013160:Splenic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D012334:RNA, Neoplasm