Review of high-risk features of cutaneous squamous cell carcinoma and discrepancies between the American Joint Committee on Cancer and NCCN Clinical Practice Guidelines In Oncology.

Cutaneous squamous cell carcinoma (SCC) is a malignancy that arises from epidermal keratinocytes. Although the majority of cutaneous SCC cases are easily treated without further complication, some behave more aggressively and carry a poor prognosis. These "high-risk" cutaneous SCCs commonly originate in the head and neck and have an increased tendency toward recurrence, local invasion, and distant metastasis. Factors for high-risk cutaneous SCC include large size (>2 cm), a deeply invasive lesion (>2 mm), incomplete excision, high-grade/desmoplastic lesions, perineural invasion (PNI), lymphovascular invasion, immunosuppression, and high-risk anatomic locations. Both the National Comprehensive Cancer Network® (NCCN® ) and the American Joint Committee on Cancer (AJCC) identify several of these high-risk features of cutaneous SCC. The purpose of this article was to review the high-risk features included in these guidelines, as well as their notable discrepancies and omissions. We also provide a brief overview of current prophylactic measures, surgical options, and adjuvant therapies for high-risk cutaneous SCC. © 2016 Wiley Periodicals, Inc. Head Neck 39: 578-594, 2017.

The importance of serum albumin and phosphorous as predictors of mortality in ESRD patients.

Secondary hyperparathyroidism and abnormal calcium/phosphate balance are common complications of ESRD and significant cardiovascular risk factors. It has also been demonstrated that malnourished dialysis patients have a much higher mortality than well-nourished patients. There is a lack of research looking at combined mortality with altered mineral metabolism and a low serum albumin. Using our renal database, we analyzed outcomes on 1,007 chronic dialysis patients, commencing dialysis between January 1990 and December 2004. The association between median values of serum phosphate, calcium, albumin (between three and six months post-commencement of dialysis), and long-term survival was examined. Cox proportional hazards models were used to determine the combined effects of these variables on patient outcome. The results showed that 18% of patients had serum phosphorous >1.8 mmol/L (5.5 g/dL), and the five-year survival of these patients was 48.4% compared with 58.6% for those with a serum phosphorous <1.8 mmol/L (p = 0.047). For serum albumin, 34.9% had a value <35 g/L, and this group also had a highly significant risk of increased mortality (p < 0.001). When combined with corrected calcium, 40.9% of patients reached all three target levels and had the greatest long-term survival (five-year survival of 62.5% for all three targets reached, compared to 30.7% for 0 or 1 targets reached). Poor control of calcium/phosphorous balance appears to have long-term deleterious effects on patient survival in ESRD patients. This risk of death is increased by poor serum albumin levels reflecting inadequate nutrition.

Association of methylenetetrahydrofolate reductase polymorphism and the risk of squamous cell carcinoma in renal transplant patients.

The relative risk of developing cutaneous squamous cell carcinoma (SCC) is significantly increased after organ transplantation. We investigated the genetic association of SCC in two pathways associated with cancer risks, with the potential for modification by vitamin supplementation. A total of 367 renal transplant recipients (117 with SCC and 250 without any skin cancer) were genotyped for key polymorphisms in the folate pathway (methylene tetrahydrofolate reductase; MTHFR:C677T), and the vitamin D pathway (vitamin D receptor: Intron8G/T;). Individuals carrying the MTHFR 677T allele had a marked increase in risk of SCC (adjusted odds ratio=2.54, P=0.002, after adjustment for age, ender, skin type, sun exposure score, and immunosuppression duration; lower 95% confidence boundary odds ratio of 1.41). In contrast, vitamin D receptor polymorphisms were not significantly associated. Folate-sensitive pathways may play a critical role in the elevated rate of SCC in renal transplant recipients.

Genetic factors associated with skin cancer in renal transplant patients.

BACKGROUND: Non-melanoma skin cancer represents a significant cause of morbidity and mortality among renal transplant recipients. Established risk factors that increase susceptibility to skin cancer after transplantation include skin type, sun exposure and level of immunosuppression. METHODS: A comprehensive literature review was carried out to discuss relevant genetic polymorphism for the development of skin cancer in organ transplant recipients. These include genetic polymorphisms in glutathione S-transferase, interleukin-10, retinoblastoma and p53 genes. We also discuss genetic polymorphisms in the folate pathway, melanocortin 1 receptor and vitamin D receptor recently discovered in our group. RESULTS: No single factor is causative in cutaneous carcinogenesis in transplant recipients. Interactions of some of the above mechanisms with known environmental factors lead to increased risk. CONCLUSION: Polymorphisms in methylenetetrahydrofolate reductase are potentially correctable with folic acid supplementation; however, further evaluation is required in adequately powered prospective clinical trials. Avoidance of known oncogenic environmental factors and genetic risk evaluation may improve outcomes in transplant patients.