1. ¹Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH, USA
2. ²Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
3. ³Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA
4. ⁴Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA
5. ⁵Department of Hematopathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
6. ⁶Department of Dermatopathology, Northwestern University, Chicago, IL, USA
7. ⁷William Beaumont Hospital, Royal Oak, MI, USA
8. ⁸Department of Pathology, University Hospital of Cleveland, Cleveland, OH, USA
9. ⁹Division of Hematology-Oncology, Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida, USA

Correspondence: Dr ED Hsi, MD, Section of Hematopathology, Department of Clinical Pathology, L-11, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA. E-mail: hsie@ccf.org

Received 29 May 2007; Revised 8 January 2008; Accepted 8 January 2008; Published online 8 February 2008.

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.