Molecular diagnostic strategies redefine therapies for various skin disorders

Key Points

Molecular diagnostic strategies are redefining the clinical management of a wide range of skin disorders, facilitating diagnosis, staging and prognostication, selection of appropriate therapy, monitoring of treatment response and identification of novel therapeutic targets.

The traditional classification of melanoma into four subtypes (acral lentiginous, superficial spreading, nodular, lentigo maligna) based on clinical-histopathological features is challenged by the results of molecular investigations.

KIT gene mutations are most common in melanomas from acral, mucosal and chronically sun-damaged (head and neck) sites, while BRAF and NRAS gene mutations predominate in melanomas that arise on skin without chronic sun damage, such as the trunk. The identification of somatic gene alterations in melanoma is the basis for a future integrated genomic-morphologic classification scheme and provides a rationale for drug development and more effective targeted therapy.

Molecular technologies can detect subclinical and/or submicroscopic metastases in lymph node and/or peripheral blood samples and may have a role in the staging of patients with melanoma. FISH and DNA microarrays have been used to stratify melanoma patients into prognostically relevant groups and provide biomarkers of treatment response and/or survival in patients with this disease.

Molecular testing may have a role in the identification of individuals at risk for melanoma development (for example, those with germline CDKN2A and/or CDK4 gene mutations) who may benefit from increased surveillance with the potential for early detection of skin cancer.

Surface receptor gene rearrangement analyses are commonly used to evaluate T-cell and B-cell clonality status in an effort to distinguish between benign and malignant cutaneous lymphocytic infiltrates. DNA microarray technology can distinguish cutaneous T-cell lymphoma lymphomas (CTCL) from benign inflammatory dermatoses.

Chromosomal aberrations and/or infection by oncogenic viruses provide opportunities for molecular testing. Take, for example, the t(2;5) translocation in CD30+ anaplastic large cell lymphoma and Epstein-Barr virus (EBV) infection in extranodal NK/T-cell lymphoma, nasal type.

Molecular technologies may be used for staging and prognostic purposes in patients with CTCL and for monitoring response to therapy. A dominant T-cell clone in skin or noncutaneous samples (i.e., lymph node) correlates with a poorer prognosis in CTCL patients.