Expression of HGAL in primary cutaneous large B-cell lymphomas: evidence for germinal center derivation of primary cutaneous follicular lymphoma.
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.
Xie
Xiuyan
X
Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH 44195, USA.
Sundram
Uma
U
Natkunam
Yaso
Y
Kohler
Sabine
S
Hoppe
Richard T
RT
Kim
Youn H
YH
Cook
James R
JR
Hammel
Jefferey
J
Swerdlow
Steven H
SH
Guitart
Juan
J
Smith
Marc D
MD
Bosler
David
D
Listinsky
Catherine
C
Lossos
Izidore S
IS
Hsi
Eric D
ED
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
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