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Non-Melanoma Skin Cancer

Basal Cell Carcinoma is the most common type of skin cancer, it occurs when basal cells (round cells found in the outer layer of skin) become cancerous. The second most common type of skin cancer is Squamous Cell Carcinoma, this is where squamous cells (the flat, scaly cells on the surface of the skin) become malignant . Cure rates are very high for both basal cell carcinoma and squamous cell carcinoma. In addition there are a number of other, less common cancers starting in the skin including Merkel cell tumours and cutaneous lymphomas and sarcomas (see the sections on sarcoma and lymphoma for more information about these).

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Information for Patients and the Public
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Latest Research Publications
Basal Cell Carcinoma
Squamous Cell Carcinoma
Cutaneous T-cell Lymphoma
Dermatofibrosarcoma Protuberans
Merkel Cell Cancer
Prevention of Skin Cancer
Skin Cancer

Information Patients and the Public (12 links)

Information for Health Professionals / Researchers (9 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Huang C, Lai Z, He M, et al.
Successful surgical treatment for squamous cell carcinoma arising from hidradenitis suppurativa: A case report and literature review.
Medicine (Baltimore). 2017; 96(3):e5857 [PubMed] Free Access to Full Article Related Publications
RATIONALE: Hidradenitis suppurativa (HS) is a disabling inflammatory disease mainly affecting apocrine glands. Marjolin ulcer (MU) is a term used to describe a rare type of squamous cell carcinoma (SCC) arising within sites of chronic wounds or preexisting scars. Chronic HS may result in a rare type of SCC, MU, which has a poor prognosis due to its high metastatic rate.
CONCERNS OF THE PATIENT: Here we reported a 60-year-old male who developed SCC on the right buttock after suffering from HS for 15 years.
INTERVENTIONS: Radical resection with clear margin was performed, after which topical negative pressure (TNP) was applied followed by split-thickness skin grafting.
OUTCOMES: In a 1-year follow-up, there was no recurrence of malignancy.
LESSONS: Cases reported in English literature since 1991 were reviewed to get a general grasp of status quo. The authors conclude that chronic HS lesion especially in the gluteal region should be cautiously observed. Once tumor arisen from HS lesion, immediate radical excision should be performed. With assured clear margin, TNP could be chosen to offer a favorable environment for the survival of skin grafting.

Nguyen AH, Detty SQ, Agrawal DK
Clinical Implications of High-mobility Group Box-1 (HMGB1) and the Receptor for Advanced Glycation End-products (RAGE) in Cutaneous Malignancy: A Systematic Review.
Anticancer Res. 2017; 37(1):1-7 [PubMed] Related Publications
Inflammation and the immune system play a role in the development and progression of melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). The pro-inflammatory and tumor-promoting effects of the high-mobility group box-1 (HMGB1) protein and the receptor for advanced glycation end products (RAGE) have been investigated in these cutaneous malignancies. The clinical implication of these molecules is not fully described. The National Library of Medicine database was searched for articles addressing the clinical relevance of HMGB1 and RAGE in melanoma, BCC, and SCC. This systematic review includes nine articles, with six summarizing RAGE in cutaneous malignancies and three involving HMGB1. RAGE has been found to be up-regulated in SCC lesions, as well as melanoma. Levels of RAGE were highest in stage IV melanomas. Lower levels of soluble RAGE have been associated with poor overall survival in melanoma. Sporadic extracellular expression of HMGB1 was evident in BCC and SCC lesions, which could be released by necrotic tumor cells. HMGB1 was found to be a prognostic marker in melanoma, and HMGB1 levels were elevated in patients who were non-responders to ipilimumab treatment. HMGB1 and RAGE could serve as potential prognostic markers or therapeutic targets in treating melanoma, BCC, and SCC, but further research regarding the clinical utility of the HMGB1-RAGE axis in cutaneous malignancies is warranted.

Handa U, Kundu R, Dimri K
Cutaneous Metastasis: A Study of 138 Cases Diagnosed by Fine-Needle Aspiration Cytology.
Acta Cytol. 2017; 61(1):47-54 [PubMed] Related Publications
BACKGROUND: Cutaneous metastases can occur in a wide variety of internal malignancies and may be the first sign of a clinically silent visceral cancer.
STUDY DESIGN: A retrospective analysis was made of 138 cases diagnosed with cutaneous and subcutaneous metastasis on fine-needle aspiration cytology (FNAC). Primary tumors of the skin/subcutis were excluded.
RESULTS: Of 138 cases, the primary was known in 101 cases and unknown in 37 cases. The age of the patients ranged from 5 to 86 years, and 76 (55.1%) were male and 62 (44.9%) were female. Clinically, the most common lesion was a single nodule (n = 77, 55.8%). The chest wall was the predominant site (n = 53, 38.4%). In males and females, the most common primary sites were the lung (n = 16) and breast (n = 24), respectively. On cytology, the most common diagnosis was metastatic adenocarcinoma (n = 41, 29.7%). Of 37 cases with an unknown primary, FNAC helped to locate the primary site in 17 (45.9%) cases, while in 20 cases it remained undiagnosed.
CONCLUSIONS: FNAC is a rapid and safe technique that can be used as a first line of investigation for confirmation of metastatic lesions of the skin. Critical evaluation of cytomorphological features along with relevant clinical details could help in the localization of an unknown primary site in some cases.

Schweinzer K, Kofler L, Bauer J, et al.
Cytokeratin AE1/AE3 immunostaining and 3D-histology: improvement of diagnosis in desmoplastic squamous cell carcinoma of the skin.
Arch Dermatol Res. 2017; 309(1):43-46 [PubMed] Related Publications
Desmoplastic squamous cell carcinoma (DSCC) as a rare subtype of cutaneous SCC has specific histological features, characterized by columns, bands, and strands of squamoid cells infiltrating a dense collagenous stroma. To decrease the high rates of local recurrence in DSSC, improvement of diagnostic methods is highly demanded. Objective was to evaluate whether immunohistochemistry (IHC) is suited to increase diagnostic accuracy. A total number of 18 patients were included in this study. After recutting of the original paraffin blocks, parallel staining of serial sections with conventionally H&E and cytokeratin AE1/AE3-immunohistochemical staining was performed. Results were evaluated by an experienced dermatohistopathologist. In 55.6% (n = 10), the margins of 3D-histology still showed no evidence of neoplastic lesions in both stainings. In contrast, we found neoplastic lesions in 5 of 18 cases (27.8%) with cytokeratin AE1/AE3 staining, while H&E-staining remained negative. In addition, neoplastic lesions were found in both, H&E as well as cytokeratin AE1/AE3 staining in three cases (16.7%). The data presented show improvement of diagnosis in 27.8% of cases using IHC and 3D-histology. This method is suitable to improve the diagnosis of DSCC.

Newlands C, Currie R, Memon A, et al.
Non-melanoma skin cancer: United Kingdom National Multidisciplinary Guidelines.
J Laryngol Otol. 2016; 130(S2):S125-S132 [PubMed] Free Access to Full Article Related Publications
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. This paper provides consensus recommendations on the management of cutaneous basal cell carcinoma and squamous cell carcinoma in the head and neck region on the basis of current evidence. Recommendations • Royal College of Pathologists minimum datasets for NMSC should be adhered to in order to improve patient care and help work-force planning in pathology departments. (G) • Tumour depth is of critical importance in identifying high-risk cutaneous squamous cell carcinoma (cSCC), and should be reported in all cases. (R) • Appropriate imaging to determine the extent of primary NMSC is indicated when peri-neural involvement or bony invasion is suspected. (R) • In the clinically N0 neck, radiological imaging is not beneficial, and a policy of watchful waiting and patient education can be adopted. (R) • Patients with high-risk NMSC should be treated by members of a skin cancer multidisciplinary team (MDT) in secondary care. (G) • Non-infiltrative basal cell carcinoma (BCC) <2 cm in size should be excised with a margin of 4-5 mm. Smaller margins (2-3 mm) may be taken in sites where reconstructive options are limited, when reconstruction should be delayed. (R) • Where there is a high risk of recurrence, delayed reconstruction or Mohs micrographic surgery should be used. (R) • Surgical excision of low-risk cSCC with a margin of 4 mm or greater is the treatment of choice. (R) • High-risk cSCC should be excised with a margin of 6 mm or greater. (R). • Mohs micrographic surgery has a role in some high-risk cSCC cases following MDT discussion. (R) • Delayed reconstruction should be used in high-risk cSCC. (G) • Intra-operative conventional frozen section in cSCC is not recommended. (G) • Radiotherapy (RT) is an effective therapy for primary BCC and cSCC. (R) • Re-excision should be carried out for incompletely excised high-risk BCC or where there is deep margin involvement. (R) • Incompletely excised high-risk cSCC should be re-excised. (R) • Further surgery should involve confirmed marginal clearance before reconstruction. (R) • P+ N0 disease: Resection should include involved parotid tissue, combined with levels I-III neck dissection, to include the external jugular node. (R) • P+ N+ disease: Resection should include level V if that level is clinically or radiologically involved. (R) • Adjuvant RT should include level V if not dissected. (R) • P0 N+ disease: Anterior neck disease should be managed with levels I-IV neck dissection to include the external jugular node. (R) • P0 N+ posterior echelon nodal disease (i.e. occipital or post-auricular) should undergo dissection of levels II-V, with sparing of level I. (R) • Consider treatment of the ipsilateral parotid if the primary site is the anterior scalp, temple or forehead. (R) • All patients should receive education in self-examination and skin cancer prevention measures. (G) • Patients who have had a single completely excised BCC or low-risk cSCC can be discharged after a single post-operative visit. (G) • Patients with an excised high-risk cSCC should be reviewed three to six monthly for two years, with further annual review depending upon clinical risk. (G) • Those with recurrent or multiple BCCs should be offered annual review. (G).

Azimi A, Kaufman KL, Ali M, et al.
In Silico Analysis Validates Proteomic Findings of Formalin-fixed Paraffin Embedded Cutaneous Squamous Cell Carcinoma Tissue.
Cancer Genomics Proteomics. 2016 11-12; 13(6):453-465 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is a common type of skin cancer but there are no comprehensive proteomic studies on this entity.
MATERIALS AND METHODS: We employed liquid chromatography coupled with tandem mass spectrometry (MS/MS) using formalin-fixed paraffin-embedded (FFPE) cSCC material to study the tumor and normal skin tissue proteomes. Ingenuity Pathway Analysis (IPA) was used to interpret the role of altered proteins in cSCC pathophysiology. Results were validated using the Human Protein Atlas and Oncomine database in silico.
RESULTS: Of 1,310 unique proteins identified, expression of an average of 144 and 88 proteins were significantly (p<0.05) increased and decreased, respectively, in the tumor samples compared to their normal counterparts. IPA analysis revealed disruptions in proteins associated with cell proliferation, apoptosis, and migration. In silico analysis confirmed that proteins corresponding to 12 antibodies, and genes corresponding to 18 proteins were differentially expressed between the two categories, validating our proteomic measurements.
CONCLUSION: Label-free MS-based proteomics is useful for analyzing FFPE cSCC tissues.

Inayat F, Saif MW
New Drug and Possible New Toxicity - Squamous Cell Carcinoma Following Imatinib in Patients with Gastrointestinal Stromal Tumors.
Anticancer Res. 2016; 36(11):6201-6204 [PubMed] Related Publications
BACKGROUND: Molecularly targeted therapy has revolutionized the treatment of advanced gastrointestinal stromal tumors (GISTs). Specifically, the consistent dependence of GISTs on proto-oncogene c-KIT signaling led to the development and successful implementation of imatinib, a small-molecule c-KIT inhibitor. Imatinib induces, rapid and sustained clinical benefit by blocking the signaling via c-KIT. The most frequently reported adverse reactions (>30%) include edema, nausea, vomiting, muscle cramps, musculoskeletal pain, diarrhea, rash, fatigue and abdominal pain.
CASE SERIES: Herein, we report a case series of cutaneous squamous cell carcinoma (SCC) occurring secondary to imatinib in two patients treated for GISTs. Both patients were successfully managed with surgical resection of SCC and the discontinuation of the drug. Furthermore, we undertook a comprehensive literature review on this association. Few cases of cutaneous SCC secondary to imatinib therapy were reported in patients with chronic myeloid leukemia. However, there was no clinical evidence on causation of imatinib-associated SCC in patients with GIST.
CONCLUSION: To our knowledge, the present report is the first to describe imatinib-related SCC in patients undergoing treatment for GISTs. This implicates that safety and long-term tolerability of imatinib in patients with GISTs warrant rigorous testing and close monitoring.

Lim RS, Evans L, George AP, et al.
Do demographics and tumour-related factors affect nodal yield at neck dissection? A retrospective cohort study.
J Laryngol Otol. 2017; 131(S1):S36-S40 [PubMed] Related Publications
BACKGROUND: Nodal metastasis is an important prognostic factor in head and neck squamous cell carcinoma. This study aimed to determine the average nodal basin yield per level of neck dissection, and to investigate if age, gender, body mass index, tumour size, depth of tumour invasion and p16 status influence nodal yield.
METHOD: A retrospective review of 185 patients with head and neck squamous cell carcinoma generated 240 neck dissection specimens.
RESULTS: The respective mean nodal yields for levels I, II, III, IV and V were 5.27, 9.43, 8.49, 7.43 and 9.02 in non-cutaneous squamous cell carcinoma patients, and 4.2, 7.57, 9.65, 4.33 and 12.29 in cutaneous squamous cell carcinoma patients. Multiple regression analysis revealed that p16-positive patients with mucosal squamous cell carcinoma yielded, on average, 2.4 more nodes than their p16-negative peers (p = 0.04, 95 per cent confidence interval = 0.116 to 4.693). This figure was 3.84 (p = 0.008, 95 per cent confidence interval = 1.070 to 6.605) for p16-positive patients with oral cavity squamous cell carcinoma.
CONCLUSION: In mucosal squamous cell carcinoma, p16-positive status significantly influenced nodal yield, with the impact being more pronounced in oral cavity squamous cell carcinoma patients.

Praestegaard C, Kjaer SK, Andersson M, et al.
Risk of skin cancer following tamoxifen treatment in more than 16,000 breast cancer patients: a cohort study.
Breast Cancer. 2016; 23(6):908-916 [PubMed] Related Publications
BACKGROUND: Women with breast cancer are at increased risk of developing skin cancer. Little is known about how tamoxifen affects this risk. We aimed to investigate whether tamoxifen treatment following breast cancer is associated with skin cancer.
METHODS: A cohort consisting of 44,589 women diagnosed with breast cancer during 1977-2007 from the nationwide clinical database of the Danish Breast Cancer Cooperative Group, was followed for a primary skin cancer [basal cell carcinoma (BCC), squamous cell carcinoma (SCC) or melanoma] in the Danish Cancer Registry supplemented by data on BCC and SCC from the Danish Pathology Register. We investigated incidence of skin cancer among 16,214 women treated with tamoxifen compared to 28,375 women not treated with tamoxifen by calculating incidence rate ratios (IRRs) in Cox regression models.
RESULTS: Tamoxifen users were followed for a median of 2.9 years. The median duration of tamoxifen treatment increased from around 1 year among women diagnosed before 1999 to nearly 2.5 years among women diagnosed in 1999 or later. Women treated with tamoxifen had an IRR 1.06 (95 % CI 0.72-1.55) for SCC and an IRR 1.40 (95 % CI 0.95-2.08) for melanoma when compared to non-users. The observed number of these types of cancer (37 SCCs and 38 melanomas among users) did not allow stratification on calendar-period. The overall IRR for BCC was 0.96 (95 % CI 0.84-1.09), but the IRR differed by menopausal status and calendar-period at diagnosis of breast cancer.
CONCLUSIONS: Our overall results indicate that tamoxifen is not associated with skin cancer. However, the inconsistency of results from stratifications prevents a firm conclusion.

Zhao MJ, Abdul-Fattah B, Qu XY, et al.
Mycosis fungoides patient accompanied actinic keratosis, actinic keratosis with squamous cell carcinoma transformation, and porokeratosis after NBUVB therapy - 1st case report and review of the literature.
Medicine (Baltimore). 2016; 95(41):e5043 [PubMed] Free Access to Full Article Related Publications
INTRODUCTION: Mycosis fungoides (MF) is the most common form of primary cutaneous T cell lymphoma. Narrowband ultraviolet B light (NBUVB) is used increasingly in treating MF because of its good toleration and well-established management.
CONCERNS: To discuss the risk factors and underlying pathogenic factors in the patients with secondary skin diseases after NBUVB therapy.
METHODS: We report in details the first case of a patient with MF accompanied with actinic keratosis (AK), AK with squamous cell carcinoma (SCC) transformation and porokeratosis after NBUVB therapy. Meanwhile, Sequence variants in tumor suppressor p53 gene in the patient's specimens were detected. A literature search of the key word "narrowband ultraviolet B light "and "side effects" was performed on PubMed, 14 cases of this entity were found. A total of 15 patients including our case were reviewed in this study and meaningful conclusion could be drawn.
OUTCOMES: The mean age at diagnosis of secondary skin dermatoses after NBUVB therapy was 62.08 years with a male to female ratio of 2:1. The cases were reported more in Europeans than in Asians (2.75:1), and the Fitzpatrick skin type was mainly Ito III (12/15). The mean cumulative number and cumulative dose of UVB treatments were 43.71 and 42, 400 (mJ/cm), respectively. There was a positive relationship between Fitzpatrick skin type and cumulative dose of UVB treatments. Among the secondary skin diseases after NBUVB treatment, 12 were tumors, 2 were non-tumorous dermatoses. Only our patient presented with both. By polymerase chain reaction-single nucleotide polymorphism (PCR-SNP) analysis, C-G mutation of exon 4 of p53 was found in AK and MF specimens in our patient.
CONCLUSION: To our knowledge, our case is the first MF patient accompanied with AK, AK with SCC transformation and Porokeratosis after NBUVB treatment. Lower Fitzpatrick skin type may be the risk factor of secondary skin diseases after NBUVB treatment.

Naik MP, Mehta A, Abrol S, et al.
Topical 5% 5-fluorouracil in the treatment of multifocal basal cell carcinoma of the face: A novel chemotherapeutic approach.
Orbit. 2016; 35(6):352-354 [PubMed] Related Publications
To determine the safety and efficacy of topical 5-fluorouracil (5-FU) 5% ointment in treatment of non-syndromic multifocal basal cell carcinoma. A 55-year-old male patient, with 8 hours of daily sun exposure, having histologically proven and radiologically non-syndromic, multifocal basal cell carcinoma with involvement of 6 sites on the face, was treated with topical 5-FU 5% ointment twice daily over all sites except the site involving lid margin to prevent corneal toxicity. Left lid lesion underwent wide surgical excision with 5-mm clear margins and reconstruction with nasal septal mucoperichondrium and local skin mobilization. Pharmacologic effects first appeared at 4 weeks and by 8 weeks, the lesions had scabbed and had fallen off with no induration but residual mild perilesional erythema. Patient had post-op histopathological clear margins and recovered uneventfully. No recurrence in 6 months. A topical 5-FU 5% ointment represents a paradigm shift in the treatment of BCC from invasive and disfiguring options (surgery and chemoradiotherapy) to cheap, convenient, effective, non-invasive, non-disfiguring topical chemotherapy. Topical 5% 5-FU is a safe and effective modality of treatment of superficial spreading multifocal basal carcinoma, especially lesions larger than 10 mm, where margins cannot be identified clearly and recurrent lesions.

Cheo T, Ng I, Ooi KH, Ai Choo B
Long-term remission after low dose radiotherapy in patient with extensive squamous cell carcinoma of the hand: A case report.
Medicine (Baltimore). 2016; 95(39):e5013 [PubMed] Free Access to Full Article Related Publications
RATIONALE FOR CASE REPORT: Cutaneous Squamous Cell Carcinoma (cSCC) of the hand is uncommon and tends to have poorer outcomes. Surgical resection with wide margins around the tumor is recommended as the treatment of choice, and radiotherapy is considered second-line treatment. Nodal evaluation involves dissection necessitating some morbidity. The role of less invasive modalities of nodal evaluation is not well established.
CASE PRESENTATION: We report a case of locally advanced case of hand cSCC. Positron emission tomography-computed tomography (PET-CT) showed disease involving full thickness of the hand as well as the ipsilateral axillary node. To achieve adequate surgical margins would have necessitated amputation at the wrist, which the patient did not consent to. Instead, he was given a two-and-a-half week course radiotherapy to the hand without axillary radiation. With the radiotherapy treatment, he managed to achieve complete remission of disease while retaining full function of the hand, which was maintained at 22 months post-treatment.
MAIN LESSONS: CSCC of the hand is uncommon and challenging to treat. Radiotherapy is a highly effective treatment modality which is able to achieve functional preservation. Care should be taken when evaluating nodal status using PET-CT.

Lee CN, Pan SC, Lee JY, Wong TW
Successful treatment of cutaneous squamous cell carcinoma with intralesional cryosurgery: Case report.
Medicine (Baltimore). 2016; 95(39):e4991 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Wide excision or Mohs surgery is the standard treatment of skin squamous cell carcinoma (SCC). Superficial SCC or tumor smaller than 1 cm has been treated successfully with open spray cryosurgery. Larger tumor may not be as effective because tissue destruction is usually superficial. Intralesional cryosurgery (IC) may provide a deeper and better cell killing effect in larger tumors. We investigated the safety and efficacy of treating nodular SCC in 4 patients with IC.
METHODS: Four patients with nodular SCC/keratoacanthoma (tumor size, 1-2.5 cm, average 1.48 cm) on the face and extremity were treated with IC. An 18-ga needle was connected to a cryogun and inserted into the center of the tumor after local anesthesia. The tumors were treated with 2 freeze-thaw cycles with a 5- to 10-mm free margin. Additional IC or open spray cryosurgery was applied if residual tumor was noted during monthly follow-up.
RESULTS: No patient required analgesics or experienced wound infection after the procedures. After IC, all tumors reduced 40% to 75% in size within 1 week. Two patients received 1 additional spray cryosurgery. Complete remission was noted in all tumors (100%) in 2 months. No recurrence was noted during follow-up (average 5.1 years). All patients were satisfied with the results.
CONCLUSION: Our observation suggests that IC can be simple and effective alternative treatment for SCC patients whose condition is not suitable for or who refused operation.

Lin SH, Cheng YW, Yang YC, et al.
Treatment of Pigmented Basal Cell Carcinoma with 3 mm Surgical Margin in Asians.
Biomed Res Int. 2016; 2016:7682917 [PubMed] Free Access to Full Article Related Publications
Background. In Asians, most basal cell carcinomas (BCCs) are pigmented with clear borders. The consensus of 4 mm surgical margin for BCC largely depends on studies in nonpigmented BCCs in Caucasians. However, little is known about recurrences of pigmented BCCs with a narrower surgical margin. We aimed to investigate 5-year recurrence of BCCs, either pigmented or nonpigmented, in Taiwanese with 3 mm surgical margin. Materials and Methods. 143 patients with BCC (M/F = 66/77, average 64 years) were confirmed pathologically from 2002 to 2013. Based on the pathological margin (>1 mm, ≤1 mm, and involved), patients were categorized into the complete excision group (n = 77), histology with close proximity group (n = 43), and unclear surgical margin group (n = 23). Results. Among 143 cases, 105 were pigmented. With standard 3 mm excision, there were 7 recurrences, with 6 of them from nonpigmented BCC group. Logistic regression showed that pigmentation was associated with lower recurrence. Interestingly, 5-year recurrence of completely excised and histology with close proximity BCC (0/77 versus 1/43) was not different statistically. Conclusions. A 3 mm surgical margin is adequate for pigmented BCC. A "wait and see" approach rather than further wide excision is appropriate for BCC with <1 mm free margin.

Voiculescu V, Calenic B, Ghita M, et al.
From Normal Skin to Squamous Cell Carcinoma: A Quest for Novel Biomarkers.
Dis Markers. 2016; 2016:4517492 [PubMed] Free Access to Full Article Related Publications
Squamous cells carcinoma (SCC) is the second most frequent of the keratinocyte-derived malignancies after basal cell carcinoma and is associated with a significant psychosocial and economic burden for both the patient himself and society. Reported risk factors for the malignant transformation of keratinocytes and development of SCC include ultraviolet light exposure, followed by chronic scarring and inflammation, exposure to chemical compounds (arsenic, insecticides, and pesticides), and immune-suppression. Despite various available treatment methods and recent advances in noninvasive or minimal invasive diagnostic techniques, the risk recurrence and metastasis are far from being negligible, even in patients with negative histological margins and lymph nodes. Analyzing normal, dysplastic, and malignant keratinocyte proteome holds special promise for novel biomarker discovery in SCC that could be used in the future for early detection, risk assessment, tumor monitoring, and development of targeted therapeutic strategies.

Fife K, Herd R, Lalondrelle S, et al.
Managing adverse events associated with vismodegib in the treatment of basal cell carcinoma.
Future Oncol. 2017; 13(2):175-184 [PubMed] Related Publications
Basal cell carcinomas are the most common form of skin cancer. Some develop into advanced cases not suitable for standard therapy. Vismodegib is the first-in-class oral hedgehog pathway inhibitor (which is dysregulated in 90% of basal cell carcinomas), and has demonstrated efficacy for advanced disease in clinical trials. An UK expert panel met to discuss management strategies for adverse events associated with vismodegib (most commonly taste disturbances, muscle cramps and alopecia). Managing patient expectations and implementing treatment breaks were considered important strategies. Quinine was useful to alleviate muscle cramps. For taste disturbances, food swaps alongside dietician referral were suggested. The experts concluded that these common adverse events can be successfully managed to allow optimum treatment duration of vismodegib.

Karayannopoulou G, Euvrard S, Kanitakis J
Tumour Budding Correlates with Aggressiveness of Cutaneous Squamous-cell Carcinoma.
Anticancer Res. 2016; 36(9):4781-5 [PubMed] Related Publications
BACKGROUND/AIM: Tumour budding (TB) is a specific pathological feature that has been found to be associated with an aggressive outcome in several cancer types; however, to our knowledge, TB has not yet been assessed in squamous-cell carcinomas of the skin (SCC). The aim of the study was to study whether TB correlates with aggressiveness in cutaneous SCC.
MATERIALS AND METHODS: We examined 31 aggressive SCC (that later developed local recurrences or metastases) in comparison with 21 non-aggressive SCC (not complicated by recurrence or metastasis). TB was expressed as the mean number of tumour buds in five adjacent high-power fields of each SCC.
RESULTS: Aggressive SCC had a much higher TB score compared to control SCC (1.63±1.35 vs. 0.49±0.9, p<0.001).
CONCLUSION: As with other cancer types, TB seems to be a pathological marker of aggressiveness of cutaneous SCC, along with other features known to be associated with an aggressive outcome (tumour thickness, level of invasion and lymphovascular or perineural invasion). Further studies including a larger number of tumours will hopefully validate TB as a new pathological predictor of aggressiveness in cutaneous SCC and will allow its correlation with other pathological features of SCC aggressiveness to be defined.

DO Carmo NG, Sakamoto LH, Pogue R, et al.
Altered Expression of PRKX, WNT3 and WNT16 in Human Nodular Basal Cell Carcinoma.
Anticancer Res. 2016; 36(9):4545-51 [PubMed] Related Publications
BACKGROUND/AIM: Nodular and superficial are the most common subtypes of basal cell carcinoma (BCC). Signaling pathways such as Hedgehog (HH) and Wingless (WNT) signaling are associated with BCC phenotypic variation. The aim of the study was to evaluate of the expression profiles of 84 genes related to the WNT and HH signaling pathways in patients with nodular and superficial BCC.
MATERIALS AND METHODS: A total of 58 BCCs and 13 samples of normal skin were evaluated by quantitative real-time polymerase chain reaction (qPCR) to detect the gene-expression profile.
RESULTS: qPCR array showed segregation in BCC subtypes compared to healthy skin. PRKX, WNT3 and WNT16 were significantly (p<0.05) altered: PRKX was up-regulated, and WNT3 and WNT16 were down-regulated in nodular BCC.
CONCLUSION: PRKX, WNT3 and WNT16 genes, belonging to the WNT signaling pathway, are involved in the tumorigenic process of nodular BCC.

Xia S, Zhao Z, Xie F, et al.
Poly r(C) binding protein is post-transcriptionally repressed by MiR-490-3p to potentiate squamous cell carcinoma.
Tumour Biol. 2016; 37(11):14773-14778 [PubMed] Related Publications
Squamous cell skin carcinoma remains a leading cause of cancer-related mortality with a huge cost of treatment, necessitating discovery and validation of potent therapeutic targets. Poly r(C) binding protein 1 (PCBP1) has been previously shown to function as a tumor suppressor. Previous work has shown that PCBP1 expression is inversely correlated to maintenance of cancer stem cells in squamous cell skin carcinoma and prostate cancer, respectively. However, the precise mechanism that regulates PCBP1 expression has not been elucidated. Here, we show that loss of PCBP1 protein expression observed in CD34+ COLO-16 cells is orchestrated by translational silencing. Translational silencing is caused by targeting of PCBP1 mRNA by miR-490-3p. Exogenous manipulation of miR-490-3p levels can accordingly modulate PCBP1 protein expression, thus suggesting that miR-490-3p as a potential biomarker in squamous cell skin cancer with therapeutic benefits.

Sobhani M, Taheri AR, Jafarian AH, Hashemy SI
The activity and tissue distribution of thioredoxin reductase in basal cell carcinoma.
J Cancer Res Clin Oncol. 2016; 142(11):2303-7 [PubMed] Related Publications
PURPOSE: Basal cell carcinoma (BCC) is the most prevalent cancer worldwide. Different mechanisms are proposed to be involved in its pathogenesis such as oxidative stress. Oxidative stress, which is the consequence of the disruption of redox balance in favor of oxidants, is involved in the initiation or progression of many tumors. Thioredoxin reductase (TrxR) is a key enzyme of the thioredoxin (Trx) system, containing Trx and TrxR and NADPH, which is one of the main cellular oxidoreductases with an essential role in cellular health and survival through providing and maintaining redox balance. Therefore, we aimed to study and compare the activity and tissue distribution of TrxR in tumoral tissue and its healthy margin in patients with BCC.
METHODS: After biopsy and taking samples from 18 patients, TrxR activity was measured using a commercial kit and its tissue distribution was assessed immunohistochemically.
RESULTS: Both the activity and tissue distribution of TrxR in tumoral tissues were significantly higher compared to their healthy margins. Regarding the tissue distribution, this significant increase in TrxR in tumoral tissues was documented based on both staining intensity and abundance of positive cells in immunohistochemistry.
CONCLUSIONS: Based on these results, it is concluded that TrxR is involved in the pathogenesis of BCC; however, more investigations are required to clarify whether this increase is a consequence of BCC or it is an initiating mechanism.

von Schuckmann LA, Hughes MC, Green AC, van der Pols JC
Forearm hair density and risk of keratinocyte cancers in Australian adults.
Arch Dermatol Res. 2016; 308(9):617-624 [PubMed] Related Publications
Evidence suggests that progenitor cells of keratinocyte cancers (basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)) may originate from epidermal stem cells including hair follicle stem cells. We hypothesised that, therefore, a relatively higher density of hair follicles on human skin may increase keratinocyte cancer risk. To evaluate this, we assessed density of mid-forearm hair in Australian adults who were randomly selected participants in a community-based cohort study of skin cancer. Hair density was assessed clinically against a set of four standard photographs showing grades of hair density, and incidence data on histologically confirmed BCC and SCC across a 20-year period were collected. Incidence rate ratios were calculated for categories of forearm hair density using multivariable regression analysis with adjustment for age, sex, phenotypic characteristics and markers of chronic sun exposure. Among the 715 participants (43 % male, average age 61 years), 237 developed at least one BCC and 115 persons developed at least one SCC. Participants with dense forearm hair (n = 169, all male) had a higher incidence of BCC (IRR = 2.24, 95 % CI 1.20, 4.18, P = 0.01) and SCC (IRR = 2.80, 95 % CI 1.20, 6.57, P = 0.02) compared to individuals with sparse forearm hair after multivariable adjustment. Stratified analyses showed that among men, those with dense versus sparse hair developed SCC more commonly (IRR = 3.01, 95 % CI 1.03, 8.78, P = 0.04). Women with moderate versus sparse hair density were more likely affected by BCC (IRR = 2.29, 95 % CI 1.05, 5.00, P = 0.038). Thus, our study suggests that in both men and women, a higher density of body hair may be associated with increased BCC and SCC risk.

Lupu M, Caruntu C, Ghita MA, et al.
Gene Expression and Proteome Analysis as Sources of Biomarkers in Basal Cell Carcinoma.
Dis Markers. 2016; 2016:9831237 [PubMed] Free Access to Full Article Related Publications
Basal cell carcinoma (BCC) is the world's leading skin cancer in terms of frequency at the moment and its incidence continues to rise each year, leading to profound negative psychosocial and economic consequences. UV exposure is the most important environmental factor in the development of BCC in genetically predisposed individuals, this being reflected by the anatomical distribution of lesions mainly on sun-exposed skin areas. Early diagnosis and prompt management are of crucial importance in order to prevent local tissue destruction and subsequent disfigurement. Although various noninvasive or minimal invasive techniques have demonstrated their utility in increasing diagnostic accuracy of BCC and progress has been made in its treatment options, recurrent, aggressive, and metastatic variants of BCC still pose significant challenge for the healthcare system. Analysis of gene expression and proteomic profiling of tumor cells and of tumoral microenvironment in various tissues strongly suggests that certain molecules involved in skin cancer pathogenic pathways might represent novel predictive and prognostic biomarkers in BCC.

Zhang Z, Behshad S, Sethi-Patel P, Valenzuela AA
Glasses: Hiding or causing skin cancer?
Orbit. 2016; 35(5):262-6 [PubMed] Related Publications
This article evaluates malignant transformation of lesions presenting in the periocular skin under the eye spectacle nose pad. A non-comparative retrospective chart review of clinical features and pathological findings of patients presenting with periocular malignancies in the exact vicinity where the nose pads of their eye spectacles rested was completed. The study took place in one tertiary oculoplastic referral center between 2007-2013. Ten patients were included, six of whom were male. All subjects wore eye spectacles while awake for at least 15 years, and had an evident suspicious lesion in the exact area that coincided with the resting place of the nose pad. The mean age was 73.5 years (range 65-85 years) and all patients had the lesion present for at least one year. Most cases were squamous skin malignancies (five squamous cell carcinomas [SCC], 2 intra-epidermal carcinomas [IEC], while 3 basal cell carcinomas [BCC]). Treatment involved surgical excision of the lesion with frozen section for margin control and reconstruction with a myocutaneous flap. Periocular malignancies of the inferior medial canthal area, where the nose pad of eye spectacle places pressure, can be easily missed or misdiagnosed. Marjolin ulcers (MU) classically present as an aggressive SCC in area of chronic inflammation, which has been previously correlated to constant pressure, repetitive trauma, or non-healing wounds in other areas of the body. We propose that the traumatic chronic pressure in the infero-medial canthal region from long-term eye spectacle nose pad use, may induce poor lymphatic regeneration leading to an immune system deficiency that predisposes this skin to a malignant transformation. The presence of chronic eye spectacle nose pads also prevents proper and timely detection of such malignancies. Complete excision of these lesions with margin control, adequate follow-up for possible recurrence, and surveillance for new lesions on the patient's contralateral side, is crucial for adequate management.

Belaid A, Nasr C, Benna M, et al.
Radiation Therapy for Primary Eyelid Cancers in Tunisia.
Asian Pac J Cancer Prev. 2016; 17(7):3643-6 [PubMed] Related Publications
Management of eyelid cancers is based on surgery and/or radiotherapy (RT). The treatment objective is to control tumors with acceptable functional and esthetic outcomes. The aim of this study was to evaluate the results of radiation therapy in management of epithelial eyelid cancers, reviewing retrospectively the clinical records of patients treated in our institution from January 1989 to December 2013. We focused on clinical and histological features, treatment characteristics, tolerance and disease control. One hundred and eight patients (62 men and 46 women) were enrolled, with a mean age of 61 years [ranges 1587]. The most frequent tumor location was the inner canthus (42.6%). Median tumor size was 21 mm [ranges 470]. Histological type was basal cell carcinoma in 88 cases (81.5%), squamous cell carcinoma in 16 (14.8%) and sebaceous carcinoma in 4 (3.7%). Radiation therapy was exclusive in 67 cases (62%) and postoperative for positive or close margins in the remaining cases. Kilovoltage external beam radiotherapy (KVRT) was used in 63 patients (58.3%) and lowdoserate interstitial brachytherapy in 37 (34.3%). Eight (7.4%) were treated with cobalt or with a combination of KVRTcobalt, KVRTelectron beams, KVRTbrachytherapy or cobaltelectron beams. The total delivered radiation doses were 70 Gy (2 Gy/fraction) in 62 patients (57.4%), 66 Gy (2 Gy/fraction) in 37 (34.3%) and 61.2 Gy (3.4Gy/fraction) in 9 (8.3%). After a median followup of 64 months, we noted 10 cases of local recurrences(9.2%): 7 after exclusive and 3 after postoperative RT. No local recurrence occurred in patients treated with brachytherapy. Actuarial 5year local recurrencefree rate, diseasefree survival and overall survival were respectively 90%, 90% and 97%. Tstage was found to be a significant factor for recurrence (p=0.047). All acute radiationrelated reactions were scored grade I or II. Delayed effects were eye watering in 24 cases (22.2%), eye dryness in 19 (17.6%), unilateral cataract in 7 (6.4%) and ectropion in 4 (3.7%). Radiation therapy and especially brachytherapy is an efficient treatment of eyelid cancers, allowing eye conservation and functional preservation with good local control rates and acceptable toxicity.

AlZou AB, Thabit MA, AlSakkaf KA, Basaleem HO
Skin Cancer: ClinicoPathological Study of 204 Patients in Southern Governorates of Yemen.
Asian Pac J Cancer Prev. 2016; 17(7):3195-9 [PubMed] Related Publications
BACKGROUND: Skin cancer is a group of heterogeneous malignancies, in general classified into nonmelanoma skin cancer (NMSC) and melanoma skin cancer (MSC). Incidences are high in many parts in the world with considerable geographical and racial variation. In the Yemen, there has been scarce information about skin cancer. The aim of this study was to evaluate the demographic characteristics and histological trend of skin cancer in Southern Governorates of Yemen.
MATERIALS AND METHODS: This retrospective study covered 204 cases of skin cancer at the Modern Histopathology Laboratory and Aden Cancer Registry and Research Center, Faculty of Medicine and Health Sciences, University of Aden, for the period 20062013. Data were classified regarding different demographic and tumor related variables and analyzed using CanReg4 for cancer registry and SPSS (version 21).
RESULTS: The commonest encountered skin cancer was NMSC (93.1%). Generally, skin cancer appears slightly more frequently in females than males with a 1:1.06 male: female ratio, with a mean age of 62.9 years. Slightly higher than onethird (36.3%) were from Aden governorate. The head and neck proved to be the most common site in both males and females (58%). Basal cell carcinoma (BCC) is the most common histological type of skin cancer (50.5%).
CONCLUSIONS: Skin cancer is a common cancer in patients living in southern governorates of Yemen. The pattern appears nearly similar to the international figures with a low incidence of MSC.

Yu KK, Dasanu CA
Rapidly Fatal Dissemination of Merkel Cell Carcinoma in a Patient Treated with Alemtuzumab for Chronic Lymphocytic Leukemia.
Conn Med. 2016 Jun-Jul; 80(6):353-8 [PubMed] Related Publications
Alemtuzumab is FDA-approved for the treatment of chronic lymphocytic leukemia (CLL). Nonetheless, its use for this indication has fallen out of favor due to serious concerns for infectious complications and increased risks of second malignancies from the profound and lasting immunosuppression. We report here in a patient with a rapidly progressive metastatic Merkel cell carcinoma (MCC) who was previously treated with alemtuzumab and fludarabine for CLL. He developed profound lymphopenia and hypogammaglobulinemia. While the risk of MCC is increased in CLL, its rapid dissemination has not been previously reported with fludarabine alone. In light of the rapidly fatal outcome in our patient due to MCC, we advise caution with the use of alemtuzumab. In patients treated with alemtuzumab for nononcologic indications, aggressive surveillance for cutaneous malignancies should be implemented until its safety profile can be further characterized.

Strassen U, Hofauer B, Jacobi C, Knopf A
Management of locoregional recurrence in cutaneous squamous cell carcinoma of the head and neck.
Eur Arch Otorhinolaryngol. 2017; 274(1):501-506 [PubMed] Related Publications
Cutaneous squamous cell carcinomas often affect elderly patients. Follow-up monitoring is difficult in these patients due to their multi-morbidity and reduced compliance. Tumour recurrence is consequently diagnosed in advanced tumour stages. Surgical therapy with curative intention often requires extended resections. The study at hand should determine whether surgical concepts are warranted in this collective. Sixty-seven patients who underwent surgical procedure due to recurrent disease of cutaneous head and neck squamous cell carcinoma were included. The cohort was divided in patients with/without adjuvant therapeutic regimens. Data were assessed retrospectively. Complete tumour resection was achieved in 85 % of our patients. Patients with adjuvant treatment demonstrated a favorable 5-year-recurrence-free interval (78 vs 30 %) and overall survival (79 vs 46 %). Complete surgical resection of advanced recurrent head and neck cutaneous squamous cell carcinomas is possible and yields favorable results in terms of survival, especially if combined with adjuvant treatment.

Ruini C, Hartmann D, Saral S, et al.
The invisible basal cell carcinoma: how reflectance confocal microscopy improves the diagnostic accuracy of clinically unclear facial macules and papules.
Lasers Med Sci. 2016; 31(8):1727-1732 [PubMed] Related Publications
Difficult to diagnose and early non-melanoma skin cancer lesions are frequently seen in daily clinical practice. Besides precancerous lesions such as actinic keratosis, basal cell carcinomas (BCCs) score the highest frequency in skin tumors. While infiltrative and nodular BCCs require a surgical treatment with a significant impact on the patients' quality of life, early and superficial BCCs might benefit from numerous conservative treatments, such as topical immune-modulators or photodynamic therapy. Dermoscopy has shown a high sensitivity and specificity in the diagnosis of early BCCs, and non-invasive imaging techniques like reflectance confocal microscopy (RCM) have proven to be helpful. The aim of our study was to investigate the importance of RCM in the diagnosis of BCCs with indistinct clinical and dermoscopic features. We retrospectively examined 27 histologically proven BCCs in which diagnosis was not possible based on naked eye examination; we separately reviewed clinical, dermoscopic, and confocal microscopy features and evaluated the lesions meeting the common diagnostic criteria for BCCs, and our diagnostic confidence. All lesions were clinically unclear, with no characteristic features suggestive for BCC; dermoscopy showed in most cases unspecific teleangiectasias (74 %) and micro-erosions (52 %). Confocal microscopy revealed in most of the cases the presence of specific criteria: peripheral palisading of the nuclei (89 %), clefting (70 %), stromal reaction (70 %), dark silhouettes (70 %), inflammatory particles (70 %), and tumor islands (67 %). In the absence of significant diagnostic clinical signs and with unclear dermoscopic features, specific confocal patterns were present in most of the lesions and enabled a correct diagnosis. In the absence of significant clinical features of BCC and in the case of uncertain dermoscopy, striking confocal features are detectable and easy to recognize in most cases. Confocal microscopy can therefore be instrumentful in the diagnosis of the so-called invisible BCCs.

Wilson ME, Pointdujour-Lim R, Lally S, et al.
Acute Charles Bonnet Syndrome following Hughes procedure.
Orbit. 2016; 35(5):292-4 [PubMed] Related Publications
A 69-year-old male experienced monocular formed visual hallucinations after occlusion of the right eye following resection of eyelid basal cell carcinoma and reconstruction with a Hughes procedure (tarsoconjunctival flap). His symptoms included recurrent, well-defined, organized, complex, formed images of small children playing in the snow. These visual phenomena occurred only in the occluded eye, began several hours after surgery, and recurred intermittently several times daily for 4 days, lasting several minutes with each occurrence. The patient retained insight into the false nature of the images throughout the duration of his symptoms, and the hallucinations resolved spontaneously while the flap was still in place. To our knowledge, this is the first reported case of Charles Bonnet Syndrome (CBS) following a Hughes procedure in a patient with normal visual acuity in the non-occluded fellow eye. Unlike other reported cases of acute onset CBS following transient monocular occlusion, hallucinations in the occluded eye remitted prior to restoration of vision in the occluded eye. Ophthalmologists should be aware of the potential for CBS following even transient monocular occlusion and should consider warning patients about its potential to occur.

Wernli KJ, Henrikson NB, Morrison CC, et al.
Screening for Skin Cancer in Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.
JAMA. 2016; 316(4):436-47 [PubMed] Related Publications
IMPORTANCE: Skin cancer, primarily melanoma, is a leading cause of morbidity and mortality in the United States.
OBJECTIVE: To provide an updated systematic review for the US Preventive Services Task Force regarding clinical skin cancer screening among adults.
DATA SOURCES: MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials were searched for relevant studies published from January 1, 1995, through June 1, 2015, with surveillance through February 16, 2016.
STUDY SELECTION: English-language studies conducted in asymptomatic populations 15 years and older at general risk for skin cancer.
DATA EXTRACTION AND SYNTHESIS: Relevant data were abstracted, and study quality was rated.
MAIN OUTCOMES AND MEASURES: Melanoma incidence and mortality, harms from cancer screening, diagnostic accuracy, and stage distribution.
RESULTS: No randomized clinical trials were identified. There was limited evidence on the association between skin cancer screening and mortality. A German ecologic study (n = 360,288) found a decrease of 0.8 per 100,000 melanoma deaths in a region with population-based skin cancer screening compared with no change or slight increases in comparison regions. The number of excisions needed to detect 1 skin cancer from clinical visual skin examinations varied by age and sex; for example, 22 for women 65 years or older compared with 41 for women aged 20 to 34 years. In 2 studies of performing visual skin examination, sensitivity to detect melanoma was 40.2% and specificity was 86.1% when conducted by primary care physicians (n = 16,383). Sensitivity was 49.0% and specificity was 97.6% when skin examinations were performed by dermatologists (n = 7436). In a case-control study of melanoma (n = 7586), cases diagnosed with thicker lesions (>0.75 mm) had an odds ratio of 0.86 (95% CI, 0.75-0.98) for receipt of a physician skin examination in the prior 3 years compared with controls. Eight cohort studies (n = 236,485) demonstrated a statistically significant relationship between the degree of disease involvement at diagnosis and melanoma mortality, regardless of the characterization of the stage or lesion thickness. Tumor thickness greater than 4.0 mm was associated with increased melanoma mortality compared with thinner lesions, and late stage at diagnosis was associated with increased all-cause mortality.
CONCLUSIONS AND RELEVANCE: Only limited evidence was identified for skin cancer screening, particularly regarding potential benefit of skin cancer screening on melanoma mortality. Future research on skin cancer screening should focus on evaluating the effectiveness of targeted screening in those considered to be at higher risk for skin cancer.

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