6018 Background: Mediators of access to medical care, such as geographic isolation, rurality and socioeconomic status, have been associated with stage at diagnosis, treatment, clinical trial involvement and prognosis for various cancers. For melanoma, little is known about the relationship between mediators of access and various outcome measures. We hypothesize that Breslow depth at diagnosis is related to the distance patients travel to reach their diagnosing providers. Methods: An IRB-approved secondary data analysis was performed of all incident cases of invasive cutaneous melanoma in 2000 from a 42 county ascertainment area. Patients and physicians were geocoded to street address; Euclidian distances between patients and providers were calculated. The outcome variable, Breslow depth at diagnosis, was logged for analysis. Simple and multiple linear regression were used to test associations between Breslow depth and distance to provider, age, gender, census tract poverty rate, rurality and availability of local dermatologists. Results: Of 655 eligible cases, 6% were excluded for missing histopathologic data. Median Breslow depth was 0.6mm (mean 1.1±1.6; range 0.1–20.0mm). Median distance to provider was 8 miles (mean 15±31; range 0–386 miles). For every ten mile increase in distance, Breslow depth increased by 6% (p=0.002). For every 10% increase in poverty rate, the Breslow depth increased by 10% (p=0.041). The relationship between Breslow depth and age wasn’t linear: depth was 17% greater for patients 51–80 than for those ≤50 (p=0.016), while depth was 74% greater for patients >80 than for those ≤50 (p<0.001). Gender, rurality, and availability of local dermatologists were not significantly associated with Breslow depth. On multivariate analysis, the associations between Breslow depth at diagnosis and distance to provider (p=0.002) and age (p<0.015) were significant. Conclusions: Distance to provider may be a significant measure of access to melanoma care that captures different information than proxy measures of rurality, poverty, and local availability of providers. Further research is needed to elucidate factors that mediate how far patients travel to reach their diagnosing providers. No significant financial relationships to disclose.

We provide documentation of the onset of 3 invasive superficial spreading melanomas arising from clinically normal skin and correlation with histologic lack of nevus association. Clinical, dermoscopic, and pathologic features of these “de novo” melanomas, which became invasive while small in diameter and had few clinical criteria for diagnosis, are reported.

The RAS/RAF/MAPK pathway likely mediates critical cell proliferation and survival signals in melanoma. BRAF mutations have been found in a high percentage of melanoma cell lines and metastases; however, only a few studies with a limited number of specimens have focused on primary melanomas. We examined BRAF exon 15 mutational status in 37 primary invasive melanomas of varying thicknesses, which had undergone a standardized pathology review. BRAF mutational status was determined using direct manual sequencing of PCR products, followed by resequencing separately amplified DNA aliquots to confirm each mutation. BRAF exon 15 mutations were found in 17 of 37 (46%) primary melanomas. Tumor-specific tandem mutations, encoding either V599K, V599R, or V599E, were found in 5 of 17 (29%) melanomas with BRAF exon 15 mutations. Cloning of BRAF double base-pair substitutions confirmed that both base changes were on the same allele and can result in a positive charge at codon 599. BRAF mutations, including tandem mutations, were frequently found in both thin and thick primary melanomas, implying that these mutations can occur early in the progression of melanoma. The finding of tandem mutations in thin melanomas makes it more likely that they arise as a simultaneous rather than sequential event.

A novel homeobox-containing cDNA from the developing human brain has been cloned and sequenced. The transcript is most closely related to the Distal-less (Dll) homeogene of Drosophila melanogaster and to the Dlx genes in the mouse, specifically to Dlx-2. As such, it is the first report of a human Dll-like gene.

Bilateral diaphragmatic paralysis is rare. We describe a patient with bilateral diaphragmatic paralysis who died 18 months after initial presentation and who was found to have renal cell carcinoma. At autopsy, no intrathoracic tumor was found that would explain the diaphragmatic paralysis. We believe that this may represent a paraneoplastic syndrome caused by renal cell carcinoma.