title: Detection of L265P MYD-88 mutation in a series of clonal B-cell lymphocytosis of marginal zone origin (CBL-MZ).
abstract: Clonal B-cell lymphocytosis of marginal zone origin (CBL-MZ) is a recently described entity characterized by the presence of clonal B cells in the blood and/or bone marrow (BM) with morphologic and immunophenotypic features consistent with marginal zone derivation in otherwise healthy individuals. CBL-MZ is commonly associated with paraproteinemia, usually immunoglobulin M (IgM), raising diagnostic difficulties from Waldenstrom macroglobulinemia (WM). The aim of the present study was to determine the presence of MYD-88 L265P mutation in a well-characterized series of CBL-MZ to identify cases that may in fact represent WM. Fifty-three CBL-MZ cases were retrospectively evaluated. MYD-88 L265P mutation was determined by allele-specific polymerase chain reaction in blood and/or BM mononuclear cells. Almost half of the CBL-MZ cases (49%) were associated with paraproteinemia mainly of the IgM type (65%). MYD-88 L265P mutation was identified in 10 cases (19%). These cases may truly represent WM, whereas 43 cases (81%) are still classified as CBL-MZ. Mutated cases were all associated with paraproteinemia compared with 37% of the nonmutated ones (P < .0001). In addition, mutated cases displayed more frequently CD38 and CD25 positivity (P = .002 and P = .005, respectively). Moreover, cases without paraproteinemia presented more frequently with lymphocytosis, irrespective of the presence of the MYD-88 mutation (P = .02). The present study demonstrates that MYD-88 L265P mutation may represent the only sensitive marker for the differentiation of CBL-MZ from probable WM. However, further studies are warranted to better define the biological significance of MYD-88 L265P mutation and to clarify whether the presence of the mutation establishes WM diagnosis or that it can also be present in borderline cases associated with paraproteinemia.
authors.affiliation: Department of Haematology, University of Crete, Heraklion, Crete, Greece.
authors.forename: Christina
authors.initials: C
authors.lastname: Kalpadakis
authors.affiliation: Department of Haematology, Athens Medical Center Psychikon Branch, Athens, Greece.
authors.forename: Gerassimos A
authors.initials: GA
authors.lastname: Pangalis
authors.affiliation: Department of Haematology, Laikon General Hospital, University of Athens, Athens, Greece.
authors.forename: Theodoros P
authors.initials: TP
authors.lastname: Vassilakopoulos
authors.affiliation: 1st Department of Propedeutics, Laikon General Hospital, University of Athens, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Roumelioti
authors.affiliation: Department of Haematology, Athens Medical Center Psychikon Branch, Athens, Greece.
authors.forename: Sotirios
authors.initials: S
authors.lastname: Sachanas
authors.affiliation: 1st Department of Anatomic Pathology, University of Athens, Athens, Greece.
authors.forename: Penelope
authors.initials: P
authors.lastname: Korkolopoulou
authors.affiliation: Department of Haematology, Athens Medical Center Psychikon Branch, Athens, Greece.
authors.forename: Efstathios
authors.initials: E
authors.lastname: Koulieris
authors.affiliation: Department of Haematology, Athens Medical Center Psychikon Branch, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Moschogiannis
authors.affiliation: Department of Haematology, Athens Medical Center Psychikon Branch, Athens, Greece.
authors.forename: Xanthi
authors.initials: X
authors.lastname: Yiakoumis
authors.affiliation: Department of Haematology, Athens Medical Center Psychikon Branch, Athens, Greece.
authors.forename: Pantelis
authors.initials: P
authors.lastname: Tsirkinidis
authors.affiliation: Department of Haematology, University of Crete, Heraklion, Crete, Greece.
authors.forename: Charalampos
authors.initials: C
authors.lastname: Pontikoglou
authors.affiliation: Department of Anatomic Pathology, Evangelismos Hospital of Athens, Athens, Greece.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Rondoyianni
authors.affiliation: Department of Haematology, University of Crete, Heraklion, Crete, Greece.
authors.forename: Helen A
authors.initials: HA
authors.lastname: Papadaki
authors.affiliation: 1st Department of Propedeutics, Laikon General Hospital, University of Athens, Athens, Greece.
authors.forename: Panayiotidis
authors.initials: P
authors.lastname: Panayiotidis
authors.affiliation: Department of Haematology, Laikon General Hospital, University of Athens, Athens, Greece.
authors.forename: Maria K
authors.initials: MK
authors.lastname: Angelopoulou
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000473:pathology*; D005260:Female; D006801:Humans; D008218:Lymphocytosis / Q000235:genetics* / Q000473:pathology; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88
keywords: MYD-88 L265P mutation; clonal B-cell lymphocytosis