Solid organ transplant recipients (SOTR) are at significantly increased risk for the development of cutaneous squamous cell carcinomas (cSCCs). Based on previously published data, our Columbia University Cutaneous Oncology Group has developed novel clinical management guidelines aimed at reducing the development of cSCCs in SOTR. Currently published data contain the following broad recommendations that may reduce development of cSCCs in SOTR: 1) Use of mTOR inhibitors, particularly sirolimus, in conjunction with mycophenolate, compared to alternative immunosuppressants; 2) Chemoprevention with acitretin and niacinamide (limited data is available for the use of niacinamide in immunocompromised patients); 3) Use of capecitabine (small case series have shown reduction of cSCCs in SOTR). Based on the above data, our group proposes the following algorithm: 1) Considering the excellent safety profile of niacinamide, all SOTR with risk factors for skin cancers should start niacinamide; 2) For SOTR with 1 low-risk cSCC/year, AJCC/BWH stage T1, continue niacinamide and consider adding acitretin. 3) For 2-10 low-risk cSCCs/year, add acitretin and consider immunosuppression modification. 4) For >10 low-risk cSCCs/year, consider adding capecitabine. 5) For SOTR with 1 high-risk cSCC, AJCC T3 or BWH stage T2B, continue niacinamide, add acitretin, and consider immunosuppression modification. 6) For ≥2 high-risk cSCCs, reduce immunosuppression and consider adding capecitabine. Niacinamide is efficacious in immunocompetent patients and has an excellent safety profile. Therefore, our group proposes early administration of niacinamide in SOTR, recognizing the need for additional investigation and dedicated trials focused on niacinamide in this population. Our institutional guidelines allow for an algorithmic and standardized approach to the current preventative paradigm for cSCCs in SOTR, and enable the building of a unified platform for future studies.

Follicular mucinosis (FM) is a cutaneous disorder arising from the pilosebaceous unit that is most strongly associated with folliculotropic mycosis fungoides (FMF), an aggressive form of mycosis fungoides (MF). Demodicidosis is a cutaneous infection caused by Demodex, an ectoparasitic mite that permanently resides in or near the pilosebaceous unit of mammalian hair follicles. Demodicidosis can have a variety of presentations including rosacea-like demodicidosis, pityriasis folliculorum, and demodicidosis gravis.

Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of lymphoproliferative disorders derived from skin-homing memory T cells. Mycosis fungoides (MF) and Sezary syndrome (SS) are the most common subtypes. Aberrant cytokine expression in the MF/SS tumor microenvironment (TME) is a major factor in disease pathogenesis and progression. We have previously shown that MF/SS malignant lymphocytes produce high levels of IL-13, which acts as an autocrine factor for tumor cells and suppresses tumor-cell immunosurveillance. Furthermore, our studies indicate that IL-13 synergizes with IL-4 in inducing SS cell growth and implicate IL-13 signaling via the Signal Transducer and Activator of Transcription-6 (STAT-6), an up-stream mediator common to both IL-4 and IL-13 signaling. Significantly, we found high numbers of activated STAT-6+ cells in the affected skin of MF patients, particularly in advanced stages, implicating STAT-6 as a critical signaling mediator in MF/SS lymphocytes. To investigate the underlying molecular mechanism, we combined genome-wide transcriptional profiling with STAT-6 inhibition to identify the STAT-6-regulated genes in advanced-stage MF/SS tumors. In malignant lymphocytes, we found that STAT-6 regulates the expression of genes associated with control of cell cycle progression and genomic stability, and its inhibition decreased proliferation. Furthermore, we showed that STAT-6 enhances expression of Th2 cytokines in malignant and reactive T cells by up-regulating the expression of GATA-3. Finally, we demonstrated that STAT-6 contributes to the pro-tumoral M2-like phenotype of macrophages in the TME of advanced-stage MF by up-regulating the expression of genes associated with immunosuppression, chemotaxis, and tumor matrix remodeling. Thus, STAT-6 contributes to MF/SS malignancy by several mechanisms including enhancing proliferation of tumor lymphocytes and promoting an immunosuppressive and pro-tumoral microenvironment that favors tumor growth and invasion.

Actinic keratoses (AKs) are premalignant cutaneous lesions, with a small percentage (<5%) eventually developing into squamous cell carcinomas (SCCs). SCC is generally curable except a subset of aggressive SCCs characterized by increased tendency for recurrence and metastasis. Currently, there is no test for identifying high-risk AKs and aggressive SCC subtypes. Biomarker-based molecular testing represents a promising tool for risk stratifying these cutaneous lesions to guide clinical diagnosis and treatment.

Squamous cell carcinomas (SCCs) and pre-malignant actinic keratoses (AKs) are thought to develop secondary to ultraviolet radiation (UV) damage. However, only ∼10% of AKs progress and become SCCs. We use RNA NanoString nCounter® analysis to validate a novel, 80-gene UV radiation-associated biomarker panel for stratification of skin cancer risk. Based on our previous study, we selected 80 of the 125 highly conserved UV-responsive genes to validate for clinical utility as a biomarker panel for detecting cancer-prone skin lesions. We enrolled patients with clinically evident AKs adjacent to NS or cutaneous SCCs adjacent to NS undergoing Mohs micrographic surgery (MMS). Diagnosis was confirmed histopathologically. RNA was isolated and NanoString nCounter® flex system was used on matched samples to quantify expression of the 80 biomarker genes. Dendrogram and supervised hierarchical clustering heat map of SCCs and AKs based on differential expression of the selected UV biomarker genes between each AK/SCC and their respective NS pair. Dot plots were created highlighting differential expression of selected biomarker genes for each AK/SCC and their respective NS pair based on fold-change. Results identified 33/80 selected UV responsive genes as consistently dysregulated in more than 50% of human primary SCC samples. Results showed hierarchical clustering of SCCs into two subgroups, with one more strongly corroborated with the UV signature. The AKs form a distinctive cluster showing an intermediate level of UV biomarker gene expression, except two outliers. The genes selected for this UV-biomarker panel corroborate the theory that AKs exist on a continuum with SCCs and their UV gene signature may allow for better risk stratification. The finding of two SCC subgroups also suggests that there may be two different major molecular pathways, one of which is more highly UV-dependent, underpinning SCC pathogenesis.

Background The lip and surrounding perioral region are susceptible to non-melanoma skin cancer, but the distribution of basal cell and squamous cell carcinoma on the cutaneous and vermilion lips has not been fully elucidated. Objective To investigate the distribution of cutaneous and vermilion lip non-melanoma skin cancer and to better describe risk factors, anatomic location, treatment characteristics and oncologic outcomes. Methods A retrospective comparative case series of patients undergoing Mohs micrographic surgery (MMS) at a single academic centre for lip and perioral basal cell and squamous cell carcinoma was performed over a 5-year period. Demographics, medical comorbidities, surgical characteristics and recurrence status were extracted. Results Forty-five vermilion and 116 cutaneous lip cancers were identified. Basal cell carcinoma (BCC) was more common in the cutaneous perioral region, while squamous cell carcinoma (SCC) was more common on the vermilion lip (P < 0.001). BCCs were more common on the upper vermilion lip and SCCs were more common on the lower vermilion lip (P < 0.001). Within the cutaneous perioral region, both BCCs and SCCs were more common on the upper perioral surface (P = 0.002). Male gender was associated with lower lip SCC (P = 0.015). Smoking, immunosuppression, anticoagulant use and hydrochlorothiazide use were not associated with cancer type or location. Recurrences were rare, but more common in vermilion lip cancers (6.6%) compared to perioral cutaneous cancers (0.8%). Outcomes for all groups were similar; BCCs of the vermilion lip had significantly greater mean MMS stages (P < 0.001) as did SCCs (P = 0.05). Conclusion Basal cell carcinoma is more commonly encountered on the cutaneous lip, whereas SCC is more common on the vermilion lip. Within the vermilion lip, BCC favours the upper lip, while SCC favours the lower lip. Within the cutaneous perioral region, both BCC and SCC favour the upper cutaneous tissue. Early stage lip cancers are curable by Mohs micrographic surgery with rare recurrences.

The incidence of melanoma has increased dramatically in recent years. Over-the-counter sunscreen use in childhood has been shown to lower the lifetime risk of melanoma in Australia, but previous studies in the U.S. have failed to demonstrate benefit. We hypothesize that short follow-up and a failure to take into account inappropriate sunscreen application practices may contribute to the lack of positive findings. Here, we created a predictive model for the impact of different regimens of sunscreen use on melanoma incidence in the pediatric New York State Medicaid population. A Markov model was developed to analyze ideal use conditions (almost daily), some use (50% of ideal), and none. Total sunscreen use for children was estimated at about 15-20 ml per application, with the number of applications depending on time of year. The model population was based on SEER data and published literature. The model incorporated various salient population characteristics including gender, ethnicity (white, non-white), and sunbed use. The model time frame was 79 years, the average life expectancy in the U.S. Our model found that compared to no sunscreen use, ideal sunscreen application is associated with a significant 43% risk reduction of lifetime melanoma development, while some sunscreen application is associated with a 17.5% risk reduction. These findings suggest that in order to demonstrate reduction in melanoma incidence, it is important to ensure appropriate sunscreen application conditions and also to look at long-term follow-up.