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.

Primary Cutaneous Diffuse Large B-cell Lymphoma, Leg Type in an Elderly Man with Human Immunodeficiency Virus Encephalopathy

“…with a poor prognosis due to frequent spread of the disease to lymph nodes and internal organs (14,15). PCLBCL-LT with Bcl-2 positive is characterized by a poor prognosis and requires etTective therapies (4). The cutaneous lesion in our case completely healed after therapy, w ith no evidence of recurrence during the follow ing 7 years.…”

“…In this classification, primary cutaneous B-cell lymphomas (PCBCLs) were divided into the following three main groups: primary cutaneous follicular centre lymphoma, primary cutaneous diffuse large B-cell iymphoma. leg type (PCLBCL-LT) and primary cutaneous marginal zone B-cell lymphoma (4). PCLBCL-LT shows positive staining for the Bcl-2 protein.…”

Managing Patients with Cutaneous B-Cell and T-Cell Lymphomas Other Than Mycosis Fungoides

“…Immunohistochemistry reveals pan-B-cell markers CD19 and CD20, with coexpression of BCL6. Other germinal center B-cell markers are also often expressed including CD10 and human germinal center –associated lymphoma (HGAL) 73 Unlike nodal follicular lymphoma, in which BCL2 expression is a hallmark that reflects a t(14;18)(q32;q21) translocation, PCFCL is characteristically negative for BCL2. However, in examples that are follicular, especially when predominantly small cleaved cells, BCL2 is expressed in approximately 40% of cases.…”

Best Practices in Diagnostic Immunohistochemistry: Workup of Cutaneous Lymphoid Lesions in the Diagnosis of Primary Cutaneous Lymphoma

“…42 IgM and HGAL as markers to aid in the differentiation between these 2 entities have been reported. [50][51][52] FOXP1 is shown to be expressed in most DLBCLs, leg type. 53 Primary Cutaneous Diffuse Large B-Cell Lymphoma, Other…”

“…While CD10 is a commonly used marker and shows positivity in a subset of cases 49 with a follicular pattern, it may be lost in a good portion of PCFLCs and those with a diffuse growth. Other markers, including BCL6, human germinal center-associated lymphoma (HGAL also known as GCET2) antigen, 50 or GCET1, may be used as alternatives.…”