A new evidence-based risk stratification system for cutaneous squamous cell carcinoma into low, intermediate, and high risk groups with implications for management.

Most primary cutaneous squamous cell carcinomas are cured with surgery. A subset, however, may develop local and nodal metastasis that may eventuate in disease-specific; death. This subset has been variably termed high risk. Herein, we review; an emerging body of data on the risks of these outcomes and propose an evidence-based; risk stratification for low-, intermediate-, and high-risk tumors that takes into; account both tumor and patient characteristics. Finally, we discuss a framework for; management of these tumors on the basis of data, when available, and our; recommendations when data are sparse.

Incidence and Trends of Basal Cell Carcinoma and Cutaneous Squamous Cell Carcinoma: A Population-Based Study in Olmsted County, Minnesota, 2000 to 2010.

OBJECTIVE: To determine population-based incidence estimates of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). PATIENTS AND METHODS: We reviewed the medical records of a population-based cohort diagnosed with nonmelanoma skin cancer between January 2, 2000, and December 31, 2010. The age- and sex-adjusted incidence rates were calculated and compared with estimates from previous periods. RESULTS: The age-adjusted BCC incidence (cases per 100,000 person-years) was 360.0 (95% CI, 342.5-377.4) in men and 292.9 (95% CI, 278.6-307.1) in women. The age-adjusted cSCC incidence (cases per 100,000 person-years) was 207.5 (95% CI, 193.9-221.1) in men and 128.8 (95% CI, 119.4-138.2) in women. From years 1976 to 1984 to years 2000 to 2010, the age- and sex-adjusted incidence (cases per 100,000 person-years) of BCC increased from 222.0 (95% CI, 204.5-239.5) to 321.2 (95% CI, 310.3-332.2) and that of cSCC from 61.8 (95% CI, 52.3-71.4) to 162.5 (95% CI, 154.6-170.3). Over time, the anatomical distribution of BCC shifted from the head and neck to the torso and that of cSCC shifted from the head and neck to the extremities. CONCLUSION: The incidences of BCC and cSCC are increasing, with a disproportionate increase in cSCC relative to BCC. There is also a disproportionate increase in the incidence of both tumors in women, as well as a shift of anatomical distributions.

Upstaging From Melanoma in Situ to Invasive Melanoma on the Head and Neck After Complete Surgical Resection.

BACKGROUND: Melanoma in situ (MIS) diagnosed from a subtotal biopsy may be upstaged to invasive melanoma after resection. The frequency of this phenomenon is markedly variable. OBJECTIVE: To quantify the rate of upstaging MIS on the head and neck after resection at this institution, characterize the location of the invasive component relative to the clinically evident lesion, and determine the rate of upstaging with time. MATERIALS AND METHODS: The authors retrospectively reviewed clinical records of adult patients with a preoperative diagnosis of MIS on the head and neck from January 1994 to August 2012. Patient and tumor characteristics were recorded. RESULTS: In total, 624 patients met the inclusion criteria and 24 (4%) were upstaged after resection. Four patients had invasive disease beyond the clinically evident lesion. The annual percentage of upstaged lesions seemed to show an increasing trend with time. CONCLUSION: Upstaging of MIS on the head and neck occurs at a relatively low rate that may be increasing with time. Invasive components of lentigo maligna melanoma may exist beyond the clinically evident margins. Histological examination of the maximal amount of the surgical specimen is paramount for optimal staging and treatment of MIS.

Cutaneous manifestations of pediatric granulomatosis with polyangiitis: a clinicopathologic and immunopathologic analysis.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is a rare systemic vasculitis associated with variable cutaneous manifestations and histopathologic findings. It is less frequent in children than adults and is often positive for cytoplasmic antineutrophil cytoplasmic antibody (ANCA) or proteinase 3-ANCA. OBJECTIVE: We sought to better define and correlate the clinical, histopathologic, and immunopathologic characteristics of cutaneous GPA in pediatric patients. METHODS: We retrospectively reviewed clinical records and cutaneous histopathologic specimens of patients 17 years or younger with cutaneous manifestations of GPA who were seen at our institution from 1990 to 2013. RESULTS: Of the 52 patients identified with GPA, cutaneous involvement occurred in 36.5% and was the initial manifestation of disease in 7.7%. Of the 19 patients with cutaneous involvement, 26.3% developed acneiform and folliculitis-like papules; 84.2% were cytoplasmic ANCA positive; and 78.9% were proteinase 3-ANCA positive. Histopathologic features included leukocytoclastic vasculitis, granulomatous inflammation, acneiform and perifollicular inflammation, granulomatous vasculitis, and palisading granulomas. LIMITATIONS: Our study was limited because of its retrospective design. CONCLUSION: Pediatric patients with cutaneous GPA most commonly have palpable purpura, leukocytoclastic vasculitis, and positive cytoplasmic ANCA or proteinase 3-ANCA serologic results. Cutaneous manifestations and histopathologic findings vary, but acneiform lesions may be a cutaneous manifestation of the disease unique to this age group.

Novel vitamin D hydroxyderivatives inhibit melanoma growth and show differential effects on normal melanocytes.

BACKGROUND/AIMS: To test the activity of novel hydroxyvitamin D(3) analogs (20(OH)D(3), 20,23(OH)(2)D and 1,20(OH)(2)D(3)) on normal and malignant melanocytes in comparison to 1,25(OH)(2)D(3). MATERIALS AND METHODS: Human epidermal melanocytes and human and hamster melanoma cells were used to measure effects on proliferation and colony formation in monolayer and soft agar. Cell morphology and melanogenesis were also analyzed. QPCR was used to measure gene expression. RESULTS: Novel secosteroids inhibited proliferation and colony formation by melanoma cells in a similar fashion to 1,25(OH)(2)D(3), having no effect on melanogenesis. These effects were accompanied by ligand-induced translocation of VDR to the nucleus. In normal melanocytes 1α-hydroxyderivatives (1,25(OH)(2)D(3) and 1,20(OH)(2)D(3)) had stronger anti-proliferative effects than 20(OH)D(3) and 20,23(OH)(2)D(3), and inhibited dendrite formation. The cells tested expressed genes encoding VDR and enzymes that activate or inactivate vitamin D(3). CONCLUSION: Novel secosteroids show potent anti-melanoma activity in vitro with 20(OH)D(3) and 20,23(OH)(2)D(3) being excellent candidates for pre-clinical testing.