Skin Cancer
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Skin cancer is the most common type of cancer and accounts for half of all new cancers in Western populations. It occurs more often in people with light coloured skin who have had a high exposure to sunlight. The two most frequent types of skin cancer are Basal Cell Carcinomas and Squamous Cell Carcinoma (often grouped under "non-melanoma skin cancer"). The third most frequent skin cancer is Melanoma, this is a malignancy of the cells which give the skin it's colour (melanocytes). In addition there are a number of other, less common cancers starting in the skin including Merkel cell tumours, cutaneous lymphomas, and sarcomas (see the pages on sarcoma and lymphoma in this guide).

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

Information Patients and the Public (10 links)

Information for Health Professionals / Researchers (6 links)

Latest Research Publications

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

Holm RP
Skin cancer prevention and screening.
S D Med. 2015; Spec No:75-7, 79-81 [PubMed] Related Publications
Skin cancer is the most common and recognizable of all cancers. The human dermis can turn malignant due to excessive solar exposure and chronic injury, with the influence of genetic risk and inherited pigmentation. Basal cell carcinoma, the most common skin cancer in lighter pigmented individuals, spreads locally, and usually appears pearly and often ulcerative. Squamous cell carcinoma, the most common skin cancer in darker pigmented people, metastasizes to lymph nodes 2-5 percent of the time, appears often scaly, smooth, nodular, ulcerative, or even pigmented. Malignant melanoma accounts for 2 percent of skin cancers, but for the vast majority of skin cancer deaths. All three can mimic each other. Solar or ultraviolet (UV) light exposure is the most common carcinogen; however, any chronic irritant can increase the risk, and efforts to avoid such exposure is apropos. Though not yet absolutely proven, skin cancer research strongly supports the following statements: sunscreen is protective, tanning devices are causative, and the routine screening of high-risk individuals is preventative. Authorities strongly recommend avoiding excess sun and UV light, using sunscreen, and keeping a watchful eye for unusual skin lesions.

Vemurafenib (Zelboraf) with longer follow-up. Metastatic melanoma: a few extra months of life, but many adverse effects.
Prescrire Int. 2015; 24(159):89-90 [PubMed] Related Publications
Further analysis of the unblinded trial described in the initial clinical evaluation suggests that vemurafenib prolongs survival by a median of about 4 months compared with dacarbazine. The adverse effects of vemurafenib are frequent and sometimes serious. More data are needed on renal and pancreatic toxicity and the risk of extracutaneous cancers.

Related: Vemurafenib (Zelboraf)

Gilani S, Al-Khafaji B
Dermatofibrosarcoma protuberans of the vulva: a mesenchymal tumour with a broad differential diagnosis and review of literature.
Pathologica. 2014; 106(4):338-41 [PubMed] Related Publications
Dermatofibrosarcoma protuberans (DFSP) is a malignant cutaneous soft tissue tumour, which rarely presents in the vulva. We report an unusual case of this tumour involving the vulva. A 61-year-old female presented with a mass in the left mons pubis. Subsequent excisional biopsy of the mass was performed. Histologic evaluation of the specimen showed a spindle cell lesion consisting of fibroblast-like cells arranged in a storiform pattern. On average, there were 2 to 3 mitotic figures per 10 high power field (hpf). The neoplastic cells showed extension into the surrounding fibroadipose tissue. A panel of immunohistochemical stains including CD34, S-100, melan-A, HMB-45, vimentin and smooth muscle actin (SMA) were tested. The neoplastic cells showed diffuse staining with CD34 and vimentin, while the rest were negative. Based on the morphologic and immunohistochemical staining pattern, a diagnosis of DFSP was rendered. The patient underwent two subsequent resections before she had clear resection margins. The postoperative course was unremarkable. The patient is disease free without recurrence after a follow-up of 12 months. DFSP infrequently involves the vulva and should be considered in the differential diagnosis of other spindle cell lesions presenting in this unusual site. The role of immunohistochemical staining with CD34 is imperative in establishing the diagnosis. The rate of local reoccurrence is high, but it rarely shows metastasis. Treatment of choice is wide local surgical excision with close follow-up to detect reoccur- rence.

Related: Dermatofibrosarcoma Protuberans Vulva Cancer

Filotico M, Damuri A, Filotico R
A peculiar fibroma-like lesion of superficial soft tissue: morphologic and immunophenotypic evaluation.
Pathologica. 2014; 106(4):327-9 [PubMed] Related Publications
Apeculiar lesion of superficial soft tissue characterised by fibroma-like morphology and an immunohistochemical profile consisting of CK+, VIM+, CD34+, CD31+/-, FLI1+ and INI-1 retained is described. The lesion entered into differential diagnosis with the so-called fibroma-like variant of epithelioid sarcoma, with the entities defined as ES-like/pseudomyogenic haemangioendothelioma and the recently identified entity defined as superficial CD34+ fibroblastic tumour. All of these entities share a common morphological structure, but differ in their immunophenotypic profile.

Related: Soft Tissue Sarcomas

Zhang RZ, Zhu WY, Zhou L
Centrally located acquired bilateral nevus of ota-like macules: a bizarre pattern.
Skinmed. 2014 Nov-Dec; 12(6):385-7 [PubMed] Related Publications
A 22-year-old woman was referred to our hospital for pigmented lesions located on her face. These had gradually increased during the past 4 years. Computed tomography (CT) of her head revealed no significant parenchymal abnormalities of temporal, maxillary and sphenoid bones or of either parietal bone. Further screening, including neurologic, ophthalmologic, orthopedic, and visceral investigations, did not reveal any abnormalities. There was no family history of abnormal cutaneous pigmentation.

Agar NJ, Kirton C, Patel RS, et al.
Predicting lymph node metastases in cutaneous squamous cell carcinoma: use of a morphological scoring system.
N Z Med J. 2015; 128(1411):59-67 [PubMed] Related Publications
BACKGROUND: Predicting which patients will develop nodal metastasis from cutaneous squamous cell carcinoma (cSCC) remains difficult. This study evaluates a recently described histological risk model validated for mucosal head and neck SCC (HNSCC) when applied to cutaneous tumours. In this model, morphologic variables including worst pattern of invasion, lymphocytic host response and perineural invasion were shown to predict disease recurrence, loco regional recurrence and overall survival in mucosal HNSCC.
METHODS: Patients with cSCC and known metastatic spread were identified from the author's database over a 5-year period between July 2007 and July 2012. Histology specimens from the original primary tumour were separately analysed by 2 histopathologists. Scores were compared against T-Stage matched control specimens without metastatic spread.
RESULTS: 27 patients with metastatic cSCC were identified. Scores for worst pattern of invasion (WPOI) were significantly higher in individuals with lymph node metastases (p=0.02).
CONCLUSIONS: Adverse pattern of invasion, defined as presence of small tumour islands or tumour satellites may be an independent risk factor for developing nodal metastases in cSCC. These tumours are difficult to investigate histopathologically as it is difficult to be confident the correct primary is chosen for study.

Audrain H, Bray A, De Berker D
Full-thickness skin grafts for lower leg defects: an effective repair option.
Dermatol Surg. 2015; 41(4):493-8 [PubMed] Related Publications
BACKGROUND: Repair of lower leg defects after excision of skin lesions that are not amenable to primary closure can be challenging.
OBJECTIVE: To evaluate the outcome of full-thickness skin grafts (FTSG) to repair lower leg defects after excision of cutaneous lesions. To assess graft take at Days 7 and 30 and the number of visits to secondary care after procedure.
MATERIALS AND METHODS: Retrospective review of 50 consecutive patients who underwent FTSG to cover defects below the knee between January 2009 and February 2014. Graft take was defined as good (90% healing and pink/purple), moderate (50% healing and pink/purple and >50% graft take), or poor (>50% graft failure).
RESULTS: Mean age was 75 years (range, 49-96 years). The mean area of the defect was 52.4 cm. The mean maximum and minimum diameters of the defect were 2.8 and 2.3 cm. Graft take was good in 44 patients (88%), moderate in 5 patients (10%), and poor in 1 patient (2%) at Day 30. Complications were infrequent and included infection and ulceration. There was no significant association between the graft size and graft take.
CONCLUSION: Full-thickness skin graft is an effective method of repairing defects on the lower leg after removal of cutaneous lesions. The aftercare of FTSG was acceptable with 86% of patients requiring 5 or fewer visits to secondary care.

Johnson AS, Crandall H, Dahlman K, Kelley MC
Preliminary results from a prospective trial of preoperative combined BRAF and MEK-targeted therapy in advanced BRAF mutation-positive melanoma.
J Am Coll Surg. 2015; 220(4):581-93.e1 [PubMed] Related Publications
BACKGROUND: We conducted a prospective trial of BRAF and mitogen-activated protein kinase kinase (MEK) targeted therapy in advanced, operable BRAF mutation-positive melanoma to determine feasibility, tumor response rates, and biomarkers of response and resistance.
STUDY DESIGN: Thirteen patients with locally or regionally advanced BRAF mutation-positive melanoma received dabrafenib 150 mg po bid for 14 days, followed by dabrafenib plus trametinib 2 mg po daily for 14 days before operation. Biopsies and tumor measurements were obtained at baseline and days 14 and 28. Formalin-fixed paraffin embedded specimens were analyzed with hematoxylin and eosin, Ki-67, cleaved caspase-3, CD8, phosphorylated extracellular signal-regulated kinase (ERK), and phosphorylated MEK immunostains.
RESULTS: Therapy was tolerated well, with toxicity ≥ grade 3 in 2 of 13 (15%) patients. All 12 patients receiving >14 days of therapy had substantial reduction in tumor volume (65% at day 14 and 78% at day 28) and underwent resection. After 14 days of dabrafenib therapy, there was a marked reduction in viable melanoma cells and a CD8 T-cell--rich infiltrate. Proliferation of the residual melanoma cells was reduced and apoptosis was increased. The cells continued to express phosphorylated ERK and phosphorylated MEK consistent with incomplete mitogen-activated protein kinase pathway inhibition.
CONCLUSIONS: Preoperative targeted therapy of advanced BRAF-mutant melanoma is feasible, well tolerated, induces brisk tumor responses, and facilitates correlative science. A CD8 T-cell-rich infiltrate indicates a potential immune-mediated mechanism of action. Both proliferation and apoptosis were inhibited, but the mitogen-activated protein kinase pathway remained activated, suggesting intrinsic resistance in a subset of tumor cells. Additional investigation of the anti-tumor immune response during targeted therapy and the mechanisms of intrinsic resistance can yield novel therapeutic strategies.

Related: MAP2K1 Melanoma BRAF

Geller AC, Swetter SM, Weinstock MA
Focus on early detection to reduce melanoma deaths.
J Invest Dermatol. 2015; 135(4):947-9 [PubMed] Related Publications
Thin fatal melanomas are a relatively new clinical and public health concern, representing an estimated 20% of melanoma deaths. Understanding this phenomenon will require a multi-pronged approach, including in-depth investigation of its behavioral and biological underpinnings. As we proceed with relevant studies, the benefits in lives saved will grow via early detection.

Related: Melanoma

Katiyar SK
Hsp90 inhibitor can inhibit UV carcinogenesis.
J Invest Dermatol. 2015; 135(4):945-7 [PubMed] Article available free on PMC after 01/10/2015 Related Publications
Extensive exposure to solar UVR is a well-recognized etiologic factor for cutaneous non-melanoma skin cancer. In this issue of the Journal, Singh et al. show that topical treatment of the skin with 17-[allylamino]-17-demethoxygeldanamycin (17AAG), a heat-shock protein 90 (Hsp90) inhibitor, prevents UVR-induced squamous cell carcinomas (SCCs) in mice. The inhibitory effect of 17AAG on SCC was associated with the inhibition of the UVR-induced (i) hyperplastic response, (ii) Hsp90β-PKCɛ interaction, and (iii) pStat3 and pAkt expression in mouse skin.

Related: Melanoma

Huang HP, Tsai MC, Hong KT, et al.
Outcome of microscopic excision of a subungual glomus tumor: a 12-year evaluation.
Dermatol Surg. 2015; 41(4):487-92 [PubMed] Related Publications
BACKGROUND: Glomus tumors are rare benign neurovascular tumors, up to 75% of which occur in the hand, mainly the subungual area. Local recurrence and nail deformity are commonly seen if tumor excision is not performed completely or properly.
OBJECTIVE: This study was designed to assess the long-term efficacy of microscopic excision of subungual glomus tumors.
MATERIALS AND METHODS: This retrospective analysis reviewed a total of 22 patients diagnosed with glomus tumors who underwent microscopic surgical excision at a single medical center over a 12-year period (2002-2014). Outcomes were analyzed based on symptom relief, recurrence rate, finger function, nail esthetics, and patient satisfaction.
RESULTS: With a mean follow-up period of 48.4 months, neither recurrence nor postexcision nail deformity developed in any patient. Patient satisfaction was rated as "good" in 86.3% of patients (19/22).
CONCLUSION: Microscopic surgical excision enables the surgeon to completely remove a glomus tumor while minimizing damage to the nail unit, thereby resulting in significantly decreased recurrence and nail deformity. In this study, an incision made according to the anatomic location provided an easy approach and the best visualization. Patients' finger function was successfully restored, nail esthetic outcome was good, and patient satisfaction was high.

Porcel Chacón R, del Boz González J, Navarro Morón J
Delayed-onset of multiple cutaneous infantile hemangiomas due to propranolol: a case report.
Pediatrics. 2015; 135(4):e1064-6 [PubMed] Related Publications
Infantile hemangiomas are the most common vascular tumors in childhood. In view of its proven effectiveness in such cases, propranolol is the drug of choice. We present the case of a male infant who started treatment with propranolol shortly after birth due to heart disease. After 7 months, when the patient had suffered various respiratory exacerbations, this treatment was suspended. One week later, multiple skin lesions (ie, multifocal infantile hemangiomas) began to appear, with no extracutaneous involvement. It was decided to resume treatment with propranolol, although at lower doses than before, and the skin lesions improved rapidly, with some disappearing completely. Treatment was definitively withdrawn at age 16 months, with only slight recurrence of the lesions. The case described is of multifocal infantile hemangiomas without extracutaneous involvement appearing beyond the neonatal period after treatment with propranolol beginning in the first days of life. The details of the case support the hypothesis that this drug is not only therapeutic but also plays a prophylactic role against infantile hemangiomas. In turn, this supports the recent proposal that this drug may be useful in preventing the growth and spread of tumors with high angiogenic potential. It is postulated that the inhibition of β-adrenergic receptors is associated with multiple intracellular processes related to the progression and metastasis of different tumors.

Burke MT, Morais C, Oliver KA, et al.
Expression of Bcl-xL and Mcl-1 in the nonmelanoma skin cancers of renal transplant recipients.
Am J Clin Pathol. 2015; 143(4):514-26 [PubMed] Related Publications
OBJECTIVES: This study aims to investigate how immunosuppression influences the protein expression of antiapoptotic members of the Bcl-2 family-namely, Bcl-xL and Mcl-1-in nonmelanoma skin cancer (NMSC) and the peritumoral epidermis of renal transplant recipients.
METHODS: NMSC and peritumoral epidermis protein expression of Bcl-xL and Mcl-1 were assessed by immunohistochemistry in renal transplant recipients receiving tacrolimus or sirolimus and the general population not receiving immunosuppression.
RESULTS: NMSC from renal transplant recipients compared with patients not receiving immunosuppressant medications had a reduced Bcl-xL expression intensity (P = .042). Mcl-1 expression intensity in NMSC was decreased in tacrolimus-treated patients compared with sirolimus-treated patients and the nonimmunosuppressed population (P = .024). Bcl-xL expression intensity was increased in peritumoral epidermis compared with NMSC (P = .002).
CONCLUSIONS: It was shown for the first time that Bcl-xL and Mcl-1 expression are widespread in the peritumoral epidermis and NMSC of renal transplant recipients. Importantly in NMSC, Bcl-xL expression was reduced with immunosuppression exposure, and Mcl-1 expression was reduced in tacrolimus-treated compared with sirolimus-treated patients.

Related: Apoptosis Basal Cell Carcinoma MCL1

Karamanou M, Stratigos AJ, Saridaki Z, et al.
René-Théophile-Hyacinthe Laennec (1781-1826) and the description of metastatic pulmonary melanoma.
J BUON. 2015 Jan-Feb; 20(1):354-6 [PubMed] Related Publications
In 19th century, the anatomo-clinical school of Paris linked clinical signs with anatomical lesions establishing clinical medicine. One of the most enlightened promoters of this method was the French physician René-Théophile-Hyacinthe Laennec, known as the inventor of stethoscope. In our article, we reveal his work on pulmonary melanoma.

Lee YH, Gyu Song G
Vitamin D receptor FokI, BsmI, TaqI, ApaI, and EcoRV polymorphisms and susceptibility to melanoma: a meta-analysis.
J BUON. 2015 Jan-Feb; 20(1):235-43 [PubMed] Related Publications
PURPOSE: The purpose of this study was to examine whether vitamin D receptor (lVDR) polymorphisms are associated with susceptibility to melanoma.
METHODS: A meta-analysis was carried out to investigate the association between the VDR FokI, BsmI, TaqI, ApaI, and EcoRV polymorphisms and susceptibility to melanoma.
RESULTS: A total of 11 studies were evaluated, which included 4,413 patients and 4,072 controls (all European). The meta-analysis revealed no association between melanoma and the BsmI B allele (odds ratio/OR=0.901, 95% confidence interval/CI=0.783-1.036, p=0.144). However, an association was shown between melanoma and the Bb+bb genotype (OR=0.868, 95% CI=0.767-0.982, p=0.025). No association was noticed between melanoma and FokI polymorphism (OR for the F allele=1.016, 95% CI=0.869-1.189, p=0.839). Moreover, melanoma risk was not associated with the TaqI, ApaI, and EcoRV polymorphisms (OR for the T allele=0.986, 95% CI=0.842-1.156, p=0.864; OR for the A allele=0.949, 95% CI=0.842-1.069, p=0.388; OR for the E allele=0.993, 95% CI=0.875-1.126, p=0.911, respectively).
CONCLUSIONS: This meta-analysis demonstrated that the VDR BsmI polymorphism is associated with susceptibility to melanoma in Europeans, suggesting that carrying the VDR BsmI B allele may be a protective factor against melanoma development.

Related: Melanoma Polymorphisms

Faries MB, Cochran AJ, Elashoff RM, Thompson JF
Multicenter Selective Lymphadenectomy Trial-I confirms the central role of sentinel node biopsy in contemporary melanoma management: response to 'No survival benefit for patients with melanoma undergoing sentinel lymph node biopsy: critical appraisal of the Multicenter Selective Lymphadenectomy Trial-I final report'.
Br J Dermatol. 2015; 172(3):571-3 [PubMed] Article available free on PMC after 01/03/2016 Related Publications
Sentinel lymph node (SLN) biopsy has become a standard procedure for many patients with melanoma and is recommended in numerous national and professional melanoma guidelines. The Multicenter Selective Lymphadenectomy Trial (MSLT-1) confirms earlier large database studies and prospective clinical trials in demonstrating the independent and unequalled prognostic value of the SLN. It also demonstrates the ability of biopsy-directed management to provide effective regional disease control with the least possible morbidity. These benefits are not in question and provide ample justification for the procedure, even without evidence of a survival benefit. However, MSLT-1 also provides strong evidence of a substantial reduction in the risk of melanoma death for patients with intermediate thickness melanomas who harbour occult nodal metastases at the time of presentation. Denying appropriately selected patients with melanoma the opportunity to undergo SLN biopsy is no longer reasonable or acceptable.

Related: Melanoma

Sladden M, Zagarella S, Popescu C, Bigby M
No survival benefit for patients with melanoma undergoing sentinel lymph node biopsy: critical appraisal of the Multicenter Selective Lymphadenectomy Trial-I final report.
Br J Dermatol. 2015; 172(3):566-71 [PubMed] Related Publications
BACKGROUND: Sentinel lymph node biopsy (SLNB) was developed in the hope that it would improve outcomes for patients with melanoma. SLNB is an area of discussion and controversy in melanoma medicine. The final trial results of the Multicenter Selective Lymphadenectomy Trial (MSLT-I) have now been published and the authors suggest their long-term results 'clearly validate the use of sentinel-node biopsy in patients with intermediate-thickness or thick primary melanomas'. An accompanying editorial states that MSLT-I is a practice-changing trial.
CONCLUSIONS: However, critical appraisal of MSLT-I data does not support the claims of the final report. On the contrary, MSLT-I failed to demonstrate that there is a significant treatment-related difference in the 10-year melanoma-specific survival rate in the overall study population. Furthermore, there was no improvement in overall or melanoma-specific survival of the intermediate-thickness group (1·2-3·5 mm). Completion lymphadenectomy can result in complications in about a third of patients, with a rate of clinically significant lymphoedema following axillary or groin dissection of 5-10%. Unnecessary lymphadenectomy can therefore have a major effect on patient quality of life. The evidence provided by Morton et al. does not support the claim that sentinel lymph node biopsy followed by lymphadenectomy in patients with positive sentinel nodes should be the standard of care in patients with melanoma. Readers are encouraged to check with registration sites to make sure declared primary outcomes are fairly reported. Post-hoc analyses are at best exploratory and cannot be used to form the principal conclusions of a trial.

Related: Melanoma

Hessam S, Georgas D, Sand M, et al.
Comparison of lipidocolloid and chlorhexidine-impregnated tulle gras dressings following microscopically controlled surgery.
J Wound Care. 2015; 24(3):135; 138-9 [PubMed] Related Publications
OBJECTIVE: Modified microscopically controlled surgery (MCS) is a staged and margin-controlled excision; after MCS, the selection of an appropriate initial wound dressing plays an important role in wound healing. A wide range of dressings is available for temporary wound coverage; however, data comparing different types of wound dressings after MCS are lacking. The aim of this study was to compare two commonly used and commercially available types of wound dressings.
METHOD: We assessed pain levels, wound adherence, bleeding upon dressing removal and signs of infection, with chlorhexidine-impregnated tulle gras and a lipidocolloid dressing used for primary wound dressing following MCS.
RESULTS: A total of 42 patients were included. Adherence of the dressing to the wound (p<0.001) and bleeding after removal (p=0.001) were significantly higher in the chlorhexidine-impregnated tulle gras dressing group. Pain during removal of wound dressing had a higher visual analogue scale score (1.9 ± 2.2) in the chlorhexidine-impregnated tulle gras dressing group compared to 0.7 ± 1.0 in the lipidocolloid dressing group (p=0.022).
CONCLUSION: The results indicate that the lipidocolloid dressing, when compared with the chlorhexidine-impregnated tulle gras dressing, offers a significant benefit during removal in terms of less pain, less wound adherence and less wound bleeding.
DECLARATION OF INTEREST: The authors have no conflict of interest to declare.

Nijhawan RI, Lee EH, Nehal KS
Biopsy site selfies--a quality improvement pilot study to assist with correct surgical site identification.
Dermatol Surg. 2015; 41(4):499-504 [PubMed] Related Publications
BACKGROUND: Determining the biopsy site location of a skin cancer before treatment is often challenging.
OBJECTIVE: To study the implementation and effectiveness of biopsy site selfies as a quality improvement measure for correct surgical site identification.
MATERIALS AND METHODS: In the first phase, the ability of dermatologic surgeon and patient to definitively identify the biopsy site and whether photography was needed to ensure site agreement were recorded. In the second phase, patients were requested to take biopsy site selfies, and after implementation, similar data were collected including whether a biopsy site selfie was helpful for definitive site identification.
RESULTS: In the first phase, the physician and patient were unable to identify the biopsy site 17.6% (49/278) and 25.5% (71/278) of cases, respectively. A photograph was needed in 22.7% of cases (63/278). After implementation of biopsy site selfies, the physician and patient were unable to identify the biopsy site 17.4% (23/132) and 15.2% (20/132) of cases, respectively. Biopsy site selfies were available for 64.1% of cases for which no internal image was available and critical for site identification in 21.4% of these cases.
CONCLUSION: Biopsy site selfies has proven to be helpful for correct surgical site identification by both the physician and the patient and may also provide further reassurance and confidence for patients.

Asgari MM, Warton EM, Whittemore AS
Family history of skin cancer is associated with increased risk of cutaneous squamous cell carcinoma.
Dermatol Surg. 2015; 41(4):481-6 [PubMed] Related Publications
BACKGROUND: The contribution of family history to cutaneous squamous cell carcinoma (SCC) risk has not been systematically quantified.
OBJECTIVE: To examine the association between self-reported family history of skin cancer and SCC risk.
METHODS AND MATERIALS: Cases (n = 415) with a pathology-verified SCC and 415 age-, gender-, and race-matched controls were identified within a large integrated health care delivery system. Family history and skin cancer risk factors were ascertained by survey. Odds ratios (ORs) for associations of SCC with family history of skin cancer were estimated using conditional logistic regression adjusted for environmental and innate SCC risk factors.
RESULTS: Any known family history of skin cancer was associated with a four-fold higher risk of SCC, adjusting for known environmental and innate SCC risk factors (OR, 4.0; confidence interval [CI]: 2.5-6.5). An unknown family history of skin cancer showed similar risk for SCC (OR, 3.9; CI: 2.4-6.5). In models including skin cancer type, the strongest association was for family history of basal cell carcinoma (OR, 9.8; CI: 2.6-36.8) and for multiple skin cancer types (OR, 10.5; CI: 3.7-29.6).
CONCLUSION: Family history of skin cancer is an important independent risk factor for cutaneous SCCs.

Lee SE, Choi JY, Hong KT, Lee KR
Treatment of acquired and small congenital melanocytic nevi with combined Er: YAG laser and long-pulsed alexandrite laser in Asian skin.
Dermatol Surg. 2015; 41(4):473-80 [PubMed] Related Publications
BACKGROUND: There is no gold standard for the treatment of benign melanocytic nevi for cosmetic purposes.
OBJECTIVE: To investigate the efficacy and safety of combined treatment with the short-pulsed erbium:yttrium-aluminum-garnet (Er:YAG) and long-pulsed alexandrite laser for acquired melanocytic nevi (AMN) and small congenital melanocytic nevi (CMN).
METHODS: Fifty-eight AMN and 7 small CMN in 24 Korean patients were treated with Er:YAG laser followed by long-pulsed alexandrite laser at 1-month intervals.
RESULTS: At 8 weeks after the final treatment, all treated nevi showed complete removal of pigmentation, and the mean overall improvement score assessed by physicians, with a quartile grading scale, was 3.6 ± 0.7. The mean number of treatment sessions required to treat CMN (1.5 ± 0.3) was significantly greater than that for junctional (1.1 ± 0.2) or compound (1.2 ± 0.5) AMN. Postinflammatory hyperpigmentation (4.6%), erythema (9.2%), hypertrophic scars (1.5%), and mild atrophic scars (10.8%) were observed, but all resolved within 6 months, except for hypertrophic scars and 1 atrophic scar. Recurrence of pigmentation was observed in 1 CMN (1.5%) during 6 months of follow-up.
CONCLUSION: Combined treatment with Er:YAG laser and long-pulsed alexandrite laser is effective for the removal of small benign melanocytic nevi with minimal adverse effects and low recurrence rates.

Atwood SX, Sarin KY, Whitson RJ, et al.
Smoothened variants explain the majority of drug resistance in basal cell carcinoma.
Cancer Cell. 2015; 27(3):342-53 [PubMed] Article available free on PMC after 09/03/2016 Related Publications
Advanced basal cell carcinomas (BCCs) frequently acquire resistance to Smoothened (SMO) inhibitors through unknown mechanisms. Here we identify SMO mutations in 50% (22 of 44) of resistant BCCs and show that these mutations maintain Hedgehog signaling in the presence of SMO inhibitors. Alterations include four ligand binding pocket mutations defining sites of inhibitor binding and four variants conferring constitutive activity and inhibitor resistance, illuminating pivotal residues that ensure receptor autoinhibition. In the presence of a SMO inhibitor, tumor cells containing either class of SMO mutants effectively outcompete cells containing the wild-type SMO. Finally, we show that both classes of SMO variants respond to aPKC-ι/λ or GLI2 inhibitors that operate downstream of SMO, setting the stage for the clinical use of GLI antagonists.

Related: Basal Cell Carcinoma Signal Transduction

Sharpe HJ, Pau G, Dijkgraaf GJ, et al.
Genomic analysis of smoothened inhibitor resistance in basal cell carcinoma.
Cancer Cell. 2015; 27(3):327-41 [PubMed] Related Publications
Smoothened (SMO) inhibitors are under clinical investigation for the treatment of several cancers. Vismodegib is approved for the treatment of locally advanced and metastatic basal cell carcinoma (BCC). Most BCC patients experience significant clinical benefit on vismodegib, but some develop resistance. Genomic analysis of tumor biopsies revealed that vismodegib resistance is associated with Hedgehog (Hh) pathway reactivation, predominantly through mutation of the drug target SMO and to a lesser extent through concurrent copy number changes in SUFU and GLI2. SMO mutations either directly impaired drug binding or activated SMO to varying levels. Furthermore, we found evidence for intra-tumor heterogeneity, suggesting that a combination of therapies targeting components at multiple levels of the Hh pathway is required to overcome resistance.

Related: Basal Cell Carcinoma SUFU

Ridky TW, Cotsarelis G
Vismodegib resistance in basal cell carcinoma: not a smooth fit.
Cancer Cell. 2015; 27(3):315-6 [PubMed] Related Publications
In this issue of Cancer Cell, two complementary papers by Atwood and colleagues and Sharpe and colleagues show that basal cell carcinomas resistant to the Smoothened (SMO) inhibitor vismodegib frequently harbor SMO mutations that limit drug binding, with mutations at some sites also increasing basal SMO activity.

Related: Basal Cell Carcinoma

Song SS, Wu Lee W, Hamman MS, Jiang SI
Mohs micrographic surgery for eccrine porocarcinoma: an update and review of the literature.
Dermatol Surg. 2015; 41(3):301-6 [PubMed] Related Publications
BACKGROUND: Eccrine porocarcinoma (EPC) is a rare malignancy of the eccrine sweat glands that is locally aggressive with a high propensity to metastasize. Most cases have been treated by wide local excision (WLE) with 20% local recurrence rate. There have been 20 cases of EPC treated with Mohs micrographic surgery (MMS) in the literature.
OBJECTIVE: To review the literature regarding the management of this aggressive tumor using MMS.
METHODS: A comprehensive literature review was conducted by searching the PubMed database using the keywords Mohs, porocarcinoma, malignant eccrine poroma, and eccrine neoplasms.
RESULTS: Most of the reported cases of EPC were treated by WLE, and only 20 cases were treated with MMS. Of the 20 EPC cases treated with MMS, there was only 1 nodal recurrence and no local recurrence. Other reported treatment modalities include radiation and excision with frozen sections. The authors report the second case of EPC on the temple, and the 21st case successfully treated with MMS.
CONCLUSION: Eccrine porocarcinoma is a rare neoplasm with potentially aggressive clinical behavior. In cases where tissue conservation is important, MMS should be considered.

Christensen KN, Henderson GP, Hocker TL, et al.
Outcomes of basal cell carcinomas directly invading the parotid gland.
Dermatol Surg. 2015; 41(3):390-6 [PubMed] Related Publications
BACKGROUND: Parotid involvement by basal cell carcinoma (BCC) is rare, and therefore management is controversial.
OBJECTIVE: To review the treatment and outcomes of patients with BCC involving the parotid by direct infiltration.
METHODS AND MATERIALS: The authors performed a retrospective chart review of BCC cases involving the parotid.
RESULTS: From 1994 to 2007, there were 19 cases of BCC involving the parotid gland by direct extension. Nine were primary tumors, and 10 recurrent (nonprimary). Eight tumors were treated with Mohs micrographic surgery (MMS), and 11 with wide local excision (WLE). One patient died of unrelated causes 5 months after treatment, and 2 did not follow up. The remaining 16 cases had an average follow-up of 55.2 months (range, 18-112 months). No primary BCC recurred after treatment. Six of 10 nonprimary BCC (60%) recurred, 2 of 10 metastasized, and 1 of 10 died of metastatic BCC. Two recurrences occurred after MMS, and 4 occurred after WLE with or without parotidectomy.
CONCLUSION: Mohs micrographic surgery or WLE with intra-operative margin control seems to be an acceptable first-line treatment for primary BCC involving the parotid. Recurrent BCC involving the parotid gland through direct infiltration has high rates of future recurrence, and adjuvant treatment may be required.

Related: Basal Cell Carcinoma

Rutherford MJ, Ironmonger L, Ormiston-Smith N, et al.
Estimating the potential survival gains by eliminating socioeconomic and sex inequalities in stage at diagnosis of melanoma.
Br J Cancer. 2015; 112 Suppl 1:S116-23 [PubMed] Article available free on PMC after 09/03/2016 Related Publications
BACKGROUND: Although inequalities in cancer survival are thought to reflect inequalities in stage at diagnosis, little evidence exists about the size of potential survival gains from eliminating inequalities in stage at diagnosis.
METHODS: We used data on patients diagnosed with malignant melanoma in the East of England (2006-2010) to estimate the number of deaths that could be postponed by completely eliminating socioeconomic and sex differences in stage at diagnosis after fitting a flexible parametric excess mortality model.
RESULTS: Stage was a strong predictor of survival. There were pronounced socioeconomic and sex inequalities in the proportion of patients diagnosed at stages III-IV (12 and 8% for least deprived men and women and 25 and 18% for most deprived men and women, respectively). For an annual cohort of 1025 incident cases in the East of England, eliminating sex and deprivation differences in stage at diagnosis would postpone approximately 24 deaths to beyond 5 years from diagnosis. Using appropriate weighting, the equivalent estimate for England would be around 215 deaths, representing 11% of all deaths observed within 5 years from diagnosis in this population.
CONCLUSIONS: Reducing socioeconomic and sex inequalities in stage at diagnosis would result in substantial reductions in deaths within 5 years of a melanoma diagnosis.

Related: Melanoma

Vismodegib (ERIVEDGE°) In basal cell carcinoma: too many unknowns.
Prescrire Int. 2015; 24(156):11-4 [PubMed] Related Publications
Basal cell carcinomas are the most common skin cancers. They are usually localised and carry a good prognosis. There is no standard treatment for the rare patients with metastatic basal cell carcinoma or very extensive basal cell carcinoma for whom surgery or radiotherapy is inappropriate. Vismodegib, a cytotoxic drug, is claimed to prevent tumour growth by inhibiting a pathway involved in tissue repair and embryogenesis. It has been authorised in the European Union for patients with metastatic or locally advanced and extensive basal cell carcinoma. Clinical evaluation of vismodegib is based on a non-comparative clinical trial involving 104 patients, providing only weak evidence. Twenty-one months after the start of the trial, 7 patients with metastases (21%) and 6 patients with advanced basal cell carcinoma (10%) had died. Given the lack of a placebo group, there is no way of knowing whether vismodegib had any effect, positive or negative, on survival. There were no complete responses among patients with metastases, but about one-third of them had partial responses. Among the 63 patients with locally advanced basal cell carcinoma, there were 14 complete responses and 16 partial responses. The recurrence rate in patients with complete responses was not reported. Similar results were reported in two other uncontrolled trials available in mid-2014. Vismodegib has frequent and sometimes serious adverse effects, including muscle spasms, fatigue and severe hyponatraemia. Cases of severe weight loss, alopecia, ocular disorders, other cancers (including squamous cell carcinoma) and anaemia have also been reported. More data are needed on possible hepatic and cardiovascular adverse effects. A potent teratogenic effect was seen in experimental animals. As vismodegib enters semen, contraception is mandatory for both men (condoms) and women. In practice, vismodegib has frequent and varied adverse effects, some of which are serious, while its benefits are poorly documented. Vismodegib should only be proposed to patients in whom basal cell cancer markedly undermines quality of life, and only in the context of clinical research.

Couto JA, Vivero MP, Kozakewich HP, et al.
A somatic MAP3K3 mutation is associated with verrucous venous malformation.
Am J Hum Genet. 2015; 96(3):480-6 [PubMed] Article available free on PMC after 05/09/2015 Related Publications
Verrucous venous malformation (VVM), also called "verrucous hemangioma," is a non-hereditary, congenital, vascular anomaly comprised of aberrant clusters of malformed dermal venule-like channels underlying hyperkeratotic skin. We tested the hypothesis that VVM lesions arise as a consequence of a somatic mutation. We performed whole-exome sequencing (WES) on VVM tissue from six unrelated individuals and looked for somatic mutations affecting the same gene in specimens from multiple persons. We observed mosaicism for a missense mutation (NM_002401.3, c.1323C>G; NP_002392, p.Iso441Met) in mitogen-activated protein kinase kinase kinase 3 (MAP3K3) in three of six individuals. We confirmed the presence of this mutation via droplet digital PCR (ddPCR) in the three subjects and found the mutation in three additional specimens from another four participants. Mutant allele frequencies ranged from 6% to 19% in affected tissue. We did not observe this mutant allele in unaffected tissue or in affected tissue from individuals with other types of vascular anomalies. Studies using global and conditional Map3k3 knockout mice have previously implicated MAP3K3 in vascular development. MAP3K3 dysfunction probably causes VVM in humans.

Socoliuc C, Zurac S, Andrei R, Stăniceanu F
A review of morphological aspects in dermatofibrosarcoma protuberans with clinicopathological correlations.
Rom J Intern Med. 2014 Oct-Dec; 52(4):239-50 [PubMed] Related Publications
Dermatofibrosarcoma protuberans represents a rare malignant neoplasm involving the skin affecting all ages, frequently young adults. It is characterized by high rates of local recurrences after surgery and rare distant metastasis. Clinically it may present as a non-protuberant or a protuberant lesion, having a relative non-specific aspect mimicking a scar, morphea, a benign cyst or other skin tumor. Several clinicopathologic subtypes of dermatofibrosarcoma protuberans have been described: fibrosarcomatous, pigmented, juvenile, myxoid, atrophic, sclerosing and myoid. Among these, the fibrosarcomatous variant stands out as the most aggressive subtype with higher risk of local recurrences and metastasis. All clinicopathologic variants have in common a characteristic microscopic pattern of infiltration into subcutaneous fat. However, this may be present on small areas or unavailable for examination on biopsy fragments. For this reason, the awareness of this variable morphology is essential for establishing a correct diagnosis and performing an optimal treatment.

Related: Dermatofibrosarcoma Protuberans

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