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: Routine diagnosis of cutaneous lymphomas is based on its characteristic clinical and histopathologic features. However, the broad clinical and histological spectrum of the disease, especially of its early stages and rare variants, often complicates the differentiation between malignant and benign lymphoproliferative disorders. In these cases demonstration of a clonal T- or B-cell population by detection of identically rearranged immune receptor genes provides an adjunct. Using this approach, in combination with standardized PCR techniques according to the BIOMED-2 protocol delivers in most reliable and reproducible results with a high sensitivity. Here, we summarize important pre- and post-analytical aspects of clonality testing, and provide guidelines for interpretation of clonality testing results as well for the primary diagnosis of a cutaneous lymphoma and for staging analysis, e. g. corresponding blood and lymph nodes.

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