Need for an improved molecular/genetic classification for CD30+ lymphomas involving the skin.
BACKGROUND
The spectrum of diseases that constitute the CD30+ lymphomas, with lymphomatoid papulosis (LyP) at one end, and anaplastic large-cell lymphoma (ALCL) at the other end, shows variable morphology, immunophenotype, and clinical behavior. The border between these diseases is sometimes difficult to establish and there are many grey zones in their classification.


METHODS
We reviewed the clinical and research literature and guided by our experiences attempted to discern molecular and phenotypic criteria to improve the classification and identify molecular targets for therapy of CD30-positive cutaneous lymphomas.


RESULTS
Functional studies of ALCL cell lines clonally derived from LyP have revealed loss of growth inhibition by transforming growth factor beta (TGF-beta), due to TGF-beta receptor mutations. Studies of genetic variants of the CD30 promoter showed distinct microsatellite alleles associated with development of LyP and lymphoma progression. Studies of LyP and cutaneous ALCL tissues and cell lines suggest a dual role for CD30/CD30 ligand interactions in regression of LyP and progression to lymphoma. CD30 signaling activates NF-kappaB in cell lines derived from cutaneous ALCL but not anaplastic lymphoma kinase (ALK)-positive systemic ALCL in which growth arrest occurs through cell cycle inhibitor p21WAF1/Cip1. Other likely biomarkers of disease progression include differential expression of Bcl-2, fascin, cutaneous lymphocyte antigen, and T-cell receptor clonality. These may lead to improved classification, diagnoses, and therapeutic targets.


CONCLUSIONS
The current clinicopathologic classification of CD30+ cutaneous lymphoproliferative disorders is insufficient. Incorporating genetic and molecular criteria would better define the borders between benign/ malignant and aggressive/nonaggressive disorders.
Droc
Claudia
C
Hematopathology and Laboratory Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA.
Cualing
Hernani D
HD
Kadin
Marshall E
ME
D015870:Gene Expression; D019254:Genes, bcl-2; D006801:Humans; D017728:Lymphoma, Large-Cell, Anaplastic / Q000145:classification / Q000235:genetics / Q000473:pathology*; D008967:Molecular Biology; D010641:Phenotype; D011379:Prognosis; D012878:Skin Neoplasms / Q000145:classification / Q000235:genetics / Q000473:pathology*