Itch and pain intensity in skin cancer: Why should dermatologic surgeons assess it?

Nonmelanoma skin cancer is the most common type of cancer in the United States. Due to its rising incidence, better screening modalities assessing patient symptomatology are imperative. We reviewed the literature regarding pain and pruritus as presenting clinical manifestations of cutaneous malignancies and elucidate the clinical presentations among skin cancer subtypes. Multiple studies have indicated a higher prevalence of reported pain for squamous cell carcinoma than basal cell carcinoma, but no statistically significant difference was found between these subtypes for itch. Transplant patients, a subset of patients commonly affected with aggressive nonmelanoma skin cancers, ranked the severity of their pain higher in comparison to nontransplant patients. The following cutaneous tumors: keratoacanthomas, infiltration sclerosing BCCs, morpheaform BCCs types and those with perineural invasion, were reported as eliciting the most pain. With the increasing incidence of skin cancer, it is important to recognize the associated presenting clinical manifestations of pruritus and pain, which are shown to be useful in the identification of undiagnosed cutaneous malignancies. Implementation of a numerical rating scale should be considered when evaluating patients with a history of skin cancer or those at high risk, such as transplant recipients.

Genetic dissection of the Gpnmb network in the eye.

PURPOSE: To use a systematic genetics approach to investigate the regulation of Gpnmb, a gene that contributes to pigmentary dispersion syndrome (PDS) and pigmentary glaucoma (PG) in the DBA/2J (D2) mouse. METHODS: Global patterns of gene expression were studied in whole eyes of a large family of BXD mouse strains (n = 67) generated by crossing the PDS- and PG-prone parent (DBA/2J) with a resistant strain (C57BL/6J). Quantitative trait locus (eQTL) mapping methods and gene set analysis were used to evaluate Gpnmb coexpression networks in wild-type and mutant cohorts. RESULTS: The level of Gpnmb expression was associated with a highly significant cis-eQTL at the location of the gene itself. This autocontrol of Gpnmb is likely to be a direct consequence of the known premature stop codon in exon 4. Both gene ontology and coexpression network analyses demonstrated that the mutation in Gpnmb radically modified the set of genes with which Gpnmb expression is correlated. The covariates of wild-type Gpnmb are involved in biological processes including melanin synthesis and cell migration, whereas the covariates of mutant Gpnmb are involved in the biological processes of posttranslational modification, stress activation, and sensory processing. CONCLUSIONS: These results demonstrated that a systematic genetics approach provides a powerful tool for constructing coexpression networks that define the biological process categories within which similarly regulated genes function. The authors showed that the R150X mutation in Gpnmb dramatically modified its list of genetic covariates, which may explain the associated ocular pathology.