title: Expression of HGAL in primary cutaneous large B-cell lymphomas: evidence for germinal center derivation of primary cutaneous follicular lymphoma.
abstract: The classification of primary cutaneous large B-cell lymphoma (PCLBCL) is based on standard morphology, immunohistochemistry, and clinical presentation. There are two major subtypes in the current WHO-EORTC classification: follicle center lymphoma and diffuse large B-cell lymphoma, leg-type (DLBCL-LT). The goals of this study were to examine a series of DLBCLs to determine (1) whether the immunohistochemical paradigm of germinal center B-cell and non-germinal center B-cell types of systemic DLBCL could be applied to PCLBCL; (2) whether application of the newly described germinal center B-cell marker, human germinal center-associated lymphoma (HGAL) also discriminates between these types as a further support for germinal center B-cell origin for primary cutaneous center lymphoma; and (3) whether any of these biologic markers were of prognostic significance. To this end, 32 cases of diffuse PCLBCL (22 primary cutaneous follicular center lymphomas and 10 DLBCL-LT) were classified based on the WHO-EORTC criteria and studied for expression of CD20, BCL2, BCL6, CD10, MUM-1, and HGAL by immunohistochemistry. Results were correlated with clinical features. HGAL and BCL6 expression and germinal center B-cell phenotype were associated with primary cutaneous follicular center lymphoma. The combination of HGAL and BCL6 positivity had the highest sensitivity (88%) and specificity (100%) for predicting subtype compared to either marker alone. Both HGAL and BCL6 were associated with the germinal center B-cell phenotype. The correlation of HGAL expression with the germinal center B-cell phenotype demonstrates the role of this marker in the classification of cutaneous large B-cell lymphomas. BCL6 expression was the only immunohistochemical marker associated with overall survival. Characterizing PCLBCLs with markers of B-cell maturation stage is a useful framework for studying, classifying, and clinically stratifying these lymphomas.
authors.affiliation: Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Xiuyan
authors.initials: X
authors.lastname: Xie
authors.forename: Uma
authors.initials: U
authors.lastname: Sundram
authors.forename: Yaso
authors.initials: Y
authors.lastname: Natkunam
authors.forename: Sabine
authors.initials: S
authors.lastname: Kohler
authors.forename: Richard T
authors.initials: RT
authors.lastname: Hoppe
authors.forename: Youn H
authors.initials: YH
authors.lastname: Kim
authors.forename: James R
authors.initials: JR
authors.lastname: Cook
authors.forename: Jefferey
authors.initials: J
authors.lastname: Hammel
authors.forename: Steven H
authors.initials: SH
authors.lastname: Swerdlow
authors.forename: Juan
authors.initials: J
authors.lastname: Guitart
authors.forename: Marc D
authors.initials: MD
authors.lastname: Smith
authors.forename: David
authors.initials: D
authors.lastname: Bosler
authors.forename: Catherine
authors.initials: C
authors.lastname: Listinsky
authors.forename: Izidore S
authors.initials: IS
authors.lastname: Lossos
authors.forename: Eric D
authors.initials: ED
authors.lastname: Hsi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D005260:Female; D018858:Germinal Center / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D050835:Interferon Regulatory Factors / Q000096:biosynthesis; D047908:Intracellular Signaling Peptides and Proteins; D053208:Kaplan-Meier Estimate; D008224:Lymphoma, Follicular / Q000145:classification* / Q000378:metabolism / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000145:classification* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008840:Microfilament Proteins; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D015260:Neprilysin / Q000096:biosynthesis*; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051560:Proto-Oncogene Proteins c-bcl-6; D012878:Skin Neoplasms / Q000145:classification* / Q000378:metabolism / Q000473:pathology; D000099218:Interferon Regulatory Factor-4
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D050835:Interferon Regulatory Factors; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D015260:Neprilysin; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D000099218:Interferon Regulatory Factor-4; C084103:BCL6 protein, human; C476824:GCSAM protein, human