Maurice PD, Fenton T, Cross N, et al.
A dedicated dermatology clinic for renal transplant recipients: first 5 years of a New Zealand experience.
N Z Med J. 2013; 126(1369):27-33 [PubMed]

AIM: Cancer following organ transplantation is a growing public health concern. We describe the first 5 years' experience of a dedicated dermatology clinic for renal transplant recipients, the first of its type in New Zealand.
METHODS: Data from patients seen in the clinic were collected on a nephrology/dermatology database.
RESULTS: 86 of 99 transplant recipients had a baseline dermatology assessment. Seventy-one skin cancers (45 squamous, 25 basal cell carcinomas, 1 melanoma) were found in 17 patients. Eighteen of these were an incidental finding at the baseline post-transplant examination of 7 patients: they had not been noted either by the patient or by their nephrologist. A further 44 cancers were found in 13 patients at follow-up examinations in the dedicated clinic. Squamous and basal cell carcinomas received definitive treatment after 26 and 38 days (median) respectively. A brief analysis showed this to be a cost-effective way of diagnosing and treating skin cancer in this cohort of patients.
CONCLUSION: The clinic is enabling prompt diagnosis and cost-effective treatment of skin cancers developing in renal transplant recipients and is also identifying significant numbers of pre-existing skin cancers in these patients.

Kostović K, Pastar Z, Ceović R, et al.
Photodynamic therapy in dermatology: current treatments and implications.
Coll Antropol. 2012; 36(4):1477-81 [PubMed]

This article provides an update on photodynamic therapy by discussing each of the essential components in sequence: mechanisms of action, common photosensitizers, typical light sources, and indications. In dermatology, photodynamic therapy (PDT) is mainly used in the treatment of superficial skin cancers: actinic keratoses, Bowen's disease and superficial basal cell carcinomas. However the range of indications has been expanding continuously. PDT is also used for the treatment of other oncological indications and non-malignant conditions such as acne vulgaris and photoaged skin. The 5-aminolevulinic acid (ALA) or its methyl ester (MAL) is applied topically as photosensitizer before activation with visible light. The advantages of topical PDT are: ability to treat multiple lesions simultaneously, low invasiveness, good tolerance and excellent cosmetic results.

Husein-Elahmed H, Gutierrez-Salmeron MT, Naranjo-Sintes R, Aneiros-Cachaza J
Factors related to delay in the diagnosis of basal cell carcinoma.
J Cutan Med Surg. 2013 Jan-Feb; 17(1):27-32 [PubMed]

BACKGROUND: There is often a delay between the clinical emergence of a basal cell carcinoma (BCC) and the point in time at which the patient presents for definitive diagnosis and treatment. Previously published studies on delays regarding skin cancer have focused on melanoma rather than BCC. We conducted a study aimed at identifying factors associated with the detection of BCC and reasons for the delay in diagnosis.
METHOD: A monocentric study was performed. Patients with a primary BCC diagnosed in 2010 were included in the study. They were asked about factors concerning BCC awareness and detection, tumor characteristics, previous history of nonmelanoma cutaneous cancer, family history of nonmelanoma cutaneous cancer, and the presence of comorbidities. Data were analyzed using SPSS software.
RESULTS: The mean diagnostic delay for BCC in our hospital setting was estimated at 19.79 ± 14.71 months. Delayed diagnosis was significantly associated with patients over 65 years, those without a previous history of BCC, those without a family history of BCC, those with BCC located elsewhere than the head or neck, and those with lesions not associated with itching or bleeding.
CONCLUSION: This study revealed considerable delay in the diagnosis of BCC. The main reason for delay in the diagnosis seems to be the initial decision of the patient to seek medical advice. These data suggest a need for greater information for the general public on the symptoms and signs that should prompt suspicion of a BCC.

Colmont CS, Benketah A, Reed SH, et al.
CD200-expressing human basal cell carcinoma cells initiate tumor growth.
Proc Natl Acad Sci U S A. 2013; 110(4):1434-9 [PubMed] Free Access to Full Article

Smoothened antagonists directly target the genetic basis of human basal cell carcinoma (BCC), the most common of all cancers. These drugs inhibit BCC growth, but they are not curative. Although BCC cells are monomorphic, immunofluorescence microscopy reveals a complex hierarchical pattern of growth with inward differentiation along hair follicle lineages. Most BCC cells express the transcription factor KLF4 and are committed to terminal differentiation. A small CD200(+) CD45(-) BCC subpopulation that represents 1.63 ± 1.11% of all BCC cells resides in small clusters at the tumor periphery. By using reproducible in vivo xenograft growth assays, we determined that tumor initiating cell frequencies approximate one per 1.5 million unsorted BCC cells. The CD200(+) CD45(-) BCC subpopulation recreated BCC tumor growth in vivo with typical histological architecture and expression of sonic hedgehog-regulated genes. Reproducible in vivo BCC growth was achieved with as few as 10,000 CD200(+) CD45(-) cells, representing ~1,500-fold enrichment. CD200(-) CD45(-) BCC cells were unable to form tumors. These findings establish a platform to study the effects of Smoothened antagonists on BCC tumor initiating cell and also suggest that currently available anti-CD200 therapy be considered, either as monotherapy or an adjunct to Smoothened antagonists, in the treatment of inoperable BCC.

Silverberg MJ, Leyden W, Warton EM, et al.
HIV infection status, immunodeficiency, and the incidence of non-melanoma skin cancer.
J Natl Cancer Inst. 2013; 105(5):350-60 [PubMed] Article available free on PMC after 06/03/2014

Background The incidence of non-melanoma skin cancers (NMSCs), including basal cell (BCC) or squamous cell carcinoma (SCC), is not well documented among HIV-positive (HIV(+)) individuals. Methods We identified 6560 HIV(+) and 36 821 HIV-negative (HIV(-)) non-Hispanic white adults who were enrolled and followed up in Kaiser Permanente Northern California from 1996 to 2008. The first biopsy-proven NMSCs diagnosed during follow-up were identified from pathology records. Poisson models estimated rate ratios that compared HIV(+) (overall and stratified by recent CD4 T-cell counts and serum HIV RNA levels) with HIV(-) subjects and were adjusted for age, sex, smoking history, obesity diagnosis history, and census-based household income. Sensitivity analyses were adjusted for outpatient visits (ie, a proxy for screening). All statistical tests were two-sided. Results The NMSC incidence rate was 1426 and 766 per 100 000 person-years for HIV(+) and HIV(-) individuals, respectively, which corresponds with an adjusted rate ratio of 2.1 (95% confidence interval [CI] = 1.9 to 2.3). Similarly, the adjusted rate ratio for HIV(+) vs HIV(-) subjects was 2.6 (95% CI = 2.1 to 3.2) for SCCs, and it was 2.1 (95% CI = 1.8 to 2.3) for BCCs. There was a statistically significant trend of higher rate ratios with lower recent CD4 counts among HIV(+) subjects compared with HIV(-) subjects for SCCs (P trend < .001). Adjustment for number of outpatient visits did not affect the results. Conclusion HIV(+) subjects had a twofold higher incidence rate of NMSCs compared with HIV(-) subjects. SCCs but not BCCs were associated with immunodeficiency.

Grelck K, Sukal S, Rosen L, Suciu GP
Incidence of residual nonmelanoma skin cancer in excisions after shave biopsy.
Dermatol Surg. 2013; 39(3 Pt 1):374-80 [PubMed]

BACKGROUND: Nonmelanoma skin cancer is an increasingly common disease that is typically treated surgically. After histopathologic confirmation by biopsy, the carcinoma is typically removed by excision, but not all excisional specimens contain residual carcinoma.
OBJECTIVES: To define the rate of residual basal and squamous cell carcinomas within excisional specimens after shave biopsy in a general dermatology office.
METHODS: We retrospectively reviewed 439 consecutive cases sent to a single dermatopathology lab from a practitioner's general dermatology office who also performs Mohs micrographic surgery. One hundred cases had a histopathologically proven carcinoma on biopsy with subsequent excision. Histopathologic type, location, age, sex, and time from biopsy to excision were all analyzed for statistical association.
RESULTS: Of 57 cases of basal cell carcinoma, 34 (59.6%) had positive residuals. Of 43 cases of squamous cell carcinoma, 12 (27.9%) had positive residuals. Histologic type was significantly associated (p = .002) with residual carcinoma in excisional specimens, with basal cells 2.13 times as likely to have residual carcinoma present.
CONCLUSION: The rate of residual nonmelanoma carcinoma in excision specimens after shave biopsy was found to be different from previously reported in the literature. These data may have therapeutic ramifications if further substantiated.

Abramson AK, Krasny MJ, Goldman GD
Tangential shave removal of basal cell carcinoma.
Dermatol Surg. 2013; 39(3 Pt 1):387-92 [PubMed]

OBJECTIVE: To determine the outcome of tangential shave removal (TS) of basal cell carcinoma (BCC) on the trunk and extremities.
DESIGN: Cohort study of patients with multiple truncal BCC treated using TS in an academic dermatologic surgery practice.
SETTING: Academic institution referral practice.
PATIENTS: Individuals with BCC referred to the dermatologic surgery unit for ongoing therapy of multiple lesions.
INTERVENTIONS: TS of amenable superficial and nodular BCCs with twice-annual follow-up. Lesions were removed using a scalpel as a uniform-depth mid-to-upper dermal shave and sent for routine pathology. Basic wound care was applied.
PRIMARY OUTCOME MEASURES: Apparent cure rate and outcome of scars.
RESULTS: One hundred eighty-two BCCs were treated in 19 individuals. Patients were followed for an average of 5.2 years. One lesion recurred. Three specimens had positive margins requiring further surgery. Scarring was acceptable and similar to what is observed with curettage and electrocoagulation.
CONCLUSIONS: TS is a reasonable treatment for primary superficial and nodular BCC on the trunk and extremities.

Moutran R, Maatouk I, Stephan F, Tomb R
Treatment of nodular basal cell carcinoma with cryotherapy and reduced protocol of imiquimod.
Cutis. 2012; 90(5):256-7 [PubMed]

Various treatment options are available for basal cell carcinoma (BCC). We report a case of a patient with a nodular BCC on the nose who was treated with combination therapy consisting of cryotherapy with liquid nitrogen followed by imiquimod cream 5% 5 times weekly for 6 weeks. Clearance of the lesion was histologically confirmed.

Iwasaki T, Kodama H, Matsushita M, et al.
Merkel cell polyomavirus infection in both components of a combined Merkel cell carcinoma and basal cell carcinoma with ductal differentiation; each component had a similar but different novel Merkel cell polyomavirus large T antigen truncating mutation.
Hum Pathol. 2013; 44(3):442-7 [PubMed]

Merkel cell polyomavirus infects up to 80% of patients with Merkel cell carcinoma. Combined Merkel cell carcinoma and cutaneous tumors occur occasionally. Previous reports have suggested that Merkel cell polyomavirus is absent from combined Merkel cell carcinoma and squamous cell carcinomas. This is the first report that Merkel cell polyomavirus infected in both lesions of a combined Merkel cell carcinoma and basal cell carcinoma. A 92-year-old Japanese man presented with a right thigh small subcutaneous mass. Histologic examination revealed a combined tumor with Merkel cell carcinoma and basal cell carcinoma with ductal differentiation. Both tumors and intermingled Merkel cells in basal cell carcinoma expressed Merkel cell polyomavirus large T antigen, and 17 and 240 copies of Merkel cell polyomavirus/cell were detected in the microdissected Merkel cell carcinoma and basal cell carcinoma specimens, respectively. Mutation analysis of Merkel cell polyomavirus large T antigen revealed a novel truncating mutation in Merkel cell carcinoma and a similar but different mutation in the basal cell carcinoma. These results suggest that each was infected by a different Merkel cell polyomavirus subclone derived from a single Merkel cell polyomavirus.

Cigna E, Tarallo M, Sorvillo V, et al.
Metatypical carcinoma of the head: a review of 312 cases.
Eur Rev Med Pharmacol Sci. 2012; 16(14):1915-8 [PubMed]

BACKGROUND: Metatypical cell carcinoma (MTC) is a quite rare malignancy accounting for 5% of all non melanoma skin cancers, with features of basal cell carcinoma and squamous cell carcinoma. It can be described as coexistence of basal cell carcinoma and squamous cell carcinoma with no transition zone between them.
AIM: Our review identified a correlation between gender and MTC affected region.
MATERIALS AND METHODS: We performed a retrospective study of 312 consecutive patients, diagnosed for MTC localized on face and scalp. Statistical analysis was made to determinate most affected areas, gender prevalence, average age, presence of ulceration and infiltration and peripheral clearance rate.
RESULTS: A relevant difference came out between two genders. χ2 test emphasized a relation between males and the presence of carcinoma on the scalp. In addition a strong correlation between mixed subtype and ulceration was evident. A strong relation between intermediate subtype and positive surgical margin was found; this data could identify a more aggressive behavior of intermediate type.
CONCLUSIONS: In our findings an important correlation between sun exposition and this tumor was found. Moreover, due to the difficulties that can occur in preserving the aesthetic subunits in the surgical treatment of these regions, the prevention of this pathology has an important role.

Kannan RY, Mathur BS
Perforator flaps of the facial artery angiosome.
J Plast Reconstr Aesthet Surg. 2013; 66(4):483-8 [PubMed]

For small to moderate-sized defects in the head and neck region, local flaps have been the mainstay of reconstruction for years. However, in certain instances, additional flap translation is required be it advancement, transposition or rotation. In such cases, the local flap concept is combined with perforator flap know-how, allowing larger loco-regional flaps to be raised to reconstruct relatively larger defects, even in cosmetically-expensive areas. In our cohort of fifteen patients', we have utilised detailed microanatomy of the facial artery perforators to reconstruct such defects with good results.

Alam M, Helenowksi IB, Cohen JL, et al.
Association between type of reconstruction after Mohs micrographic surgery and surgeon-, patient-, and tumor-specific features: a cross-sectional study.
Dermatol Surg. 2013; 39(1 Pt 1):51-5 [PubMed]

BACKGROUND: There are few data to indicate whether the type of final wound defect is associated with the type of post-Mohs repair.
OBJECTIVE: To determine the methods of reconstruction that Mohs surgeons typically select and, secondarily, to assess the association between the method and the number of stages, tumor type, anatomic location, and patient and surgeon characteristics.
METHODS: Statistical analysis of procedure logs of 20 representative young to mid-career Mohs surgeons.
RESULTS: The number of stages associated with various repairs were different (analysis of variance, p < .001.). Linear repairs, associated with the fewest stages (1.5), were used most commonly (43-55% of defects). Primary repairs were used for 20.2% to 35.3% of defects of the nose, eyelids, ears, and lips. Local flaps were performed typically after two stages of Mohs surgery (range 1.98-2.06). Referral for repair and skin grafts were associated with cases with more stages (2.16 and 2.17 stages, respectively). Experienced surgeons were nominally more likely perform flaps than grafts. Regression analyses did not indicate any association between patient sex and closure type (p = .99) or practice location and closure type (p = .99).
CONCLUSIONS: Most post-Mohs closures are linear repairs, with more bilayered linear repairs more likely at certain anatomic sites and after a larger number of stages.

Flohil SC, Seubring I, van Rossum MM, et al.
Trends in Basal cell carcinoma incidence rates: a 37-year Dutch observational study.
J Invest Dermatol. 2013; 133(4):913-8 [PubMed]

Basal cell carcinoma (BCC) incidence rates are increasing. From 1973 to 2009, data on all first histologically confirmed BCCs were gained from the Eindhoven Cancer Registry to estimate trends in patient-based BCC incidence rates by sex, age group, and site in the southeast Netherlands. Trends in European age-standardized rates and age- and site-specific incidence rates were assessed by calculating the estimated annual percentage change (EAPC). Between 1973 and 2009, the European standardized rate quadrupled from 40 to 165 per 100,000 person-years for men and from 34 to 157 for women, significantly increasing since 1973 in both sexes, but accelerating from 2002 until 2009 with an EAPC of 6.8% (95% confidence interval (CI), 5.3-8.3) for men and 7.9% (95% CI, 6.2-9.7) for women. Women below the age of 40 years exhibited a constant linear increase of 6.3% since 1973. The head and neck region was most often affected in both sexes, but the steepest increase was seen for the trunk (EAPC men 13%, women 15%). In the absence of reliable tumor-based rates, these alarming patient-based rates are probably an interesting indicator for the impact of more intensive UV exposure in a prosperous European population.

de Carvalho AV, Bonamigo RR, da Silva CM, Pinto AC
Positivity for HLA DR1 is associated with basal cell carcinoma in renal transplant patients in southern Brazil.
Int J Dermatol. 2012; 51(12):1448-53 [PubMed]

BACKGROUND: Renal transplant patients have a higher incidence of non-melanoma skin cancer (NMSC). Previous studies hypothesized that human leukocyte antigen (HLA), especially types DR1, DR4, and DR7, may influence the incidence of these tumors. This study investigates the association between NMSC and the presence of HLA DR1, DR4, and DR7 in renal transplant patients in southern Brazil.
METHODS: In a historical cohort study, 1032 patients who underwent renal transplantation during the period from January 1993 to December 2006 were examined to identify occurrences of NMSC and HLA status prior to transplant.
RESULTS: Of the 1032 patients examined, 59 (5.71%) developed NMSC (squamous cell carcinoma [SCC]: 2.42%; basal cell carcinoma [BCC]: 1.74%; both: 1.55%). The presence of HLA DR1 was associated with a higher probability of developing any NMSC and particularly with developing BCC (P < 0.05). There was no statistically significant association between the presence of HLA DR4 or DR7 and the occurrence of NMSC in this sample.
CONCLUSIONS: HLA DR1 appears to be associated with the development of BCC, as well as with the higher number of NMSC lesions in renal transplant patients. This study supports the trend to associate the DR1 allele with BCC and not with SCC.

Nolan K, Henry M, Shohet M, et al.
Use of a perimeter technique with Mohs micrographic surgery in the resection of a giant basal cell carcinoma.
J Cutan Med Surg. 2012 Nov-Dec; 16(6):465-8 [PubMed]

BACKGROUND: Giant basal cell carcinomas (GBCC) can demonstrate very malignant behavior and pose a surgical challenge.
OBJECTIVE: To present a surgical technique utilizing Mohs and the resection of narrow bands of tissue to excise a GBCC that created a large facial defect of 5 cm × 2 cm.
METHODS: A unique combination of Mohs micrographic surgery and the recently described perimeter techniques used for lentigo maligna were used to resect the tumor.
RESULTS: This hybrid technique was tissue sparing and therefore helped prevent the complications associated with a larger resection and allowed for an easier reconstruction. At 2 months post resection the patient had no known metastasis or tumor recurrence.
CONCLUSION: This case highlights the importance of early recognition of basal cell carcinoma and the complications that can arise when lesions are left untreated for a long duration. Also, we describe a surgical technique that could help reduce the complications associated with these large tumors.

Tecimer RS, Yildiz KD, Aktürk AS, Bilen N
Unusual localization of a common cutaneous neoplasm: basal cell carcinoma.
Cutan Ocul Toxicol. 2013; 32(2):179-81 [PubMed]

Basal cell carcinoma (BCC) is the most common form of the skin carcinomas and ultraviolet radiation is the major risk factor in the etiopathogenesis. However, reports of unusual sites for BCC are increased in the literature. Authors draw attention to possibility of other etiological agents for BCC like local trauma, ageing, ionizing radiation, arsenic, chronic inflammation, and immune deficiency. Here, we reported a 74-year-old male patient with nodular BCC on groin. We thought that ageing or local trauma may have a role in its formation.

Bartos V, Pokorny D, Zacharova O, et al.
Fibroepithelioma of Pinkus.
Bratisl Lek Listy. 2012; 113(10):624-7 [PubMed]

Basal cell carcinoma (BCC) is recently the most common cancer in humans characterized by several histopathological subtypes. Fibroepithelioma of Pinkus (FEP) is traditionally classified as a very rare variant of BCC, however, it manifests clinical and morphological differences that distinguish it from most other types BCCs. This study was performed to evaluate the incidence of FEP and clinical-pathological characteristics of patients diagnosed with this tumor. Four cases of primary FEP (3 females, 1 male, mean age 53.4 y) were analyzed retrospectively. The prevalence of FEP was 0.7 % of all diagnosed BCCs. Topographically, tumors were localized on the right brachium, right gluteal region, left mesogastrium, and right side of the abdomen. Histological examination showed typical anastomosing cords of basaloid cells extending from the overlying epidermis into the loose fibrous stroma in the dermis. Mitotic activity or significant cellular atypia, as well as sign of solar dermatosis were absent. Mean horizontal and vertical diameter of the lesions were 7.7 and 2.8 mm, retrospectively. We did not observe infiltration of deeper skin structures. All lesions were removed completely and classified as pathological stage pT1. Three cases manifested typical picture of a "pure" FEP, one lesion had partially a feature of nodular type BCC, too. Although FEP is conventionally considered as indolent BCC variant with a favorable clinical outcome, recent evidences also favors its classification as a form of trichoblastoma. This is appropriate example how some types of cutaneous tumors can overlap in terms of dignity and clinical-morphological characteristics. This should be taken into account in differential diagnosis and in predicting of biological behaviour of the individual tumors of the skin (Tab. 2, Fig. 3, Ref. 26).

Akcam TM, Gubisch W, Unlu H
Nonmelanoma skin cancer of the head and neck: surgical treatment.
Facial Plast Surg Clin North Am. 2012; 20(4):455-71 [PubMed]

This article focuses on the surgical treatment of nonmelanoma skin cancers of the head and neck. The risk factors of nonmelanoma skin cancers for recurrence and metastases that are important for choosing the best treatment option are summarized. Surgical treatment options including surgical excision with standard margins, frozen section, staged surgery, and Mohs micrographic surgery are described. Indications, techniques, outcomes, and advantages and disadvantages of each approach are reviewed. Finally, management of incomplete excisions is discussed.

Ermertcan AT, Hellings PW, Cingi C
Nonmelanoma skin cancer of the head and neck: nonsurgical treatment.
Facial Plast Surg Clin North Am. 2012; 20(4):445-54 [PubMed]

Nonmelanoma skin cancer (NMSC) is one of the most prevalent types of cancer worldwide, with basal cell carcinoma and squamous cell carcinoma being the most frequent histologic types. Surgical excision remains the mainstay of treatment, but nonsurgical treatment options may be indicated in specific cases. Nonsurgical treatment options for NMSC may be preferred as good alternatives under certain circumstances. This review provides a comprehensive overview of the nonsurgical treatment modalities for NMSCs, such as curettage and electrodesiccation, cryotherapy, radiotherapy, laser, photodynamic therapy, immunotherapy, and retinoid therapy.

Cobanoglu HB, Constantinides M, Ural A
Nonmelanoma skin cancer of the head and neck: molecular mechanisms.
Facial Plast Surg Clin North Am. 2012; 20(4):437-43 [PubMed]

Histopathologic examination is the gold standard for the diagnosis of skin cancer. Because analysis of molecular parameters such as nucleic acids and DNA are also gaining importance in diagnosis, prognosis, and therapy, an understanding of the molecular mechanisms underlying the pathogenesis of nonmelanoma skin cancer of the head and neck is of growing importance for the diagnostician and surgeon alike. This article presents a description of the effect on cells and impact on DNA of ultraviolet radiation, with a discussion of squamous cell and basal cell carcinoma in terms of the effects of genetic pathways and apoptosis.

Gencoglan G, Ozdemir F
Nonmelanoma skin cancer of the head and neck: clinical evaluation and histopathology.
Facial Plast Surg Clin North Am. 2012; 20(4):423-35 [PubMed]

Clinical and histopathologic features of nonmelanoma skin cancer, physical examination, and diagnostic methods (biopsy, dermoscopy, confocal microscopy) are summarized. A diagnostic algorithm provides a useful summarization of differential diagnosis of basal cell carcinoma, actinic keratosis, Bowen's disease, and squamous cell carcinoma.

Cakir BÖ, Adamson P, Cingi C
Epidemiology and economic burden of nonmelanoma skin cancer.
Facial Plast Surg Clin North Am. 2012; 20(4):419-22 [PubMed]

The authors present a succinct summary of the incidence and costs of nonmelanoma skin cancers. They present incidence and health care costs for this disease from Australia, United States, and Europe, noting that NMSC care cost stands in fifth place after prostate, lung, colon, and breast carcinomas.

Eskiizmir G, Cingi C
Nonmelanoma skin cancer of the head and neck: current diagnosis and treatment.
Facial Plast Surg Clin North Am. 2012; 20(4):415-7 [PubMed]

An overview of where nonmelanoma cancers appear in the hierarchy of cancers is succinctly presented, as well as their incidence, etiology, and costs. The examination and treatment of these cancers are summarized.

Atwood SX, Chang AL, Oro AE
Hedgehog pathway inhibition and the race against tumor evolution.
J Cell Biol. 2012; 199(2):193-7 [PubMed] Article available free on PMC after 06/03/2014

Dependence of basal cell carcinomas and medulloblastomas on the Hedgehog pathway provides an opportunity for targeted or "personalized" therapy. The recent effectiveness and FDA approval of the first Smoothened inhibitors validates this class of agents, but has revealed drug-resistant tumor variants that bypass Smoothened inhibition. Here, we summarize the effectiveness of Hedgehog pathway inhibitors and highlight promising areas for the development of next generation drug antagonists for Hedgehog-dependent cancers.

Gamba CA, Tang JY
Does a history of eczema predict a future basal cell carcinoma?
J Invest Dermatol. 2012; 132(11):2497-9 [PubMed]

Dyer et al. (this issue) assess the risk of new basal cell carcinoma (BCC) in the Veterans Affairs topical tretinoin chemoprevention trial, which included individuals with a history of at least two prior keratinocyte carcinomas. In addition to known risk factors for a future BCC, such as number of prior BCCs, a history of eczema and lower education levels were also associated with greater risk.

Tessone A, Amariglio N, Weissman O, et al.
Radiotherapy-induced basal cell carcinomas of the scalp: are they genetically different?
Aesthetic Plast Surg. 2012; 36(6):1387-92 [PubMed]

BACKGROUND: The treatment of tinea capitis using radiotherapy was introduced at the beginning of the twentieth century. In Israel, between 1949 and 1960, approximately 17,000 children underwent radiotherapy treatments for tinea capitis (actual numbers are probably higher due to irradiation in countries of origin as a prerequisite for immigration). Skin cancer presents a major problem for patients who underwent irradiation for the treatment of tinea capitis [aggressive biological behavior, multiple basal cell carcinomas (BCCs), up to 40 lesions in a single patient, with no predisposing condition such as Gorlin's or Bazex's syndromes]. There are ample data in the literature concerning the molecular changes in ultraviolet (UV) radiation-induced BCCs. However, similar data regarding ionizing radiation-induced BCCs are scarce. One work found higher rates of p53 and PTCH (both are tumor suppressor genes whose alterations are associated with BCC formation and frequency, but not biological behavior) abnormalities in post ionizing radiation BCCs. The absence of documented differences in gene expression that would account for a different biological behavior of radiotherapy-related BCCs, coupled with the aggressive and recurrent nature of these lesions, has propelled us to examine these differences by comparing gene expression in BCCs of the scalps of patients who were previously irradiated for tinea capitis in their childhood and of the scalps of patients who were not.
METHODS: Tissue samples of excised scalp BCCs from seven previously irradiated patients (five male, two female) and seven not previously irradiated patients (six male, one female) were frozen upon excision and genetically analyzed using DNA microarray chips.
RESULTS: No correlation was found between previous ionizing irradiation and gene expression.
CONCLUSIONS: The negative results of this study, coupled with the observation of aggressive biological behavior of BCCs in previously irradiated patients merit further attention. Other explanations for the aggressive biological behavior of radiotherapy-induced BCCs come to mind. One such explanation could be that the difference between the groups lies not in the tumor itself, but in the host, who is more susceptible to the local destruction caused by the tumor due to changes in the surrounding tissue (e.g., impaired blood supply due to radiation, structural damage in seemingly healthy skin). This hypothesis will be the focus of further research. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Diepgen TL, Fartasch M, Drexler H, Schmitt J
Occupational skin cancer induced by ultraviolet radiation and its prevention.
Br J Dermatol. 2012; 167 Suppl 2:76-84 [PubMed]

Skin cancer is by far the most common kind of cancer diagnosed in many western countries and ultraviolet radiation is the most important risk factor for cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). Although employees at several workplaces are exposed to increased levels of UV radiation, skin cancer due to long-term intense occupational exposure to UV radiation is often not considered as occupational disease. The actually available evidence in the epidemiological literature clearly indicates that occupational UV radiation exposure is a substantial and robust risk factor for the development of cutaneous SCC and also clearly shows a significant risk for developing BCC. There is enough scientific evidence that outdoor workers have an increased risk of developing work-related occupational skin cancer due to natural UV radiation exposure and adequate prevention strategies must be implemented. The three measures which are successful and of particular importance in the prevention of nonmelanoma skin cancer in outdoor workers are changes in behaviour regarding awareness of health and disease resulting from exposure to natural UV radiation, protection from direct UV radiation by wearing suitable clothing, and regular and correct use of appropriate sunscreens.

de Vries E, Arnold M, Altsitsiadis E, et al.
Potential impact of interventions resulting in reduced exposure to ultraviolet (UV) radiation (UVA and UVB) on skin cancer incidence in four European countries, 2010-2050.
Br J Dermatol. 2012; 167 Suppl 2:53-62 [PubMed]

BACKGROUND: Behavioural interventions to reduce exposure to ultraviolet radiation (UVR) can reduce risk of skin cancer.
OBJECTIVES: To integrate the data and to evaluate the impact of interventions to limit exposure to UVR on skin cancer incidence in four selected countries.
METHODS: Using PREVENT, a dynamic simulation model, we modelled the potential for skin cancer prevention in four European countries under various scenarios to avoid damage by UVR.
RESULTS: In general, the most effective interventions were those aimed at protecting people during outdoor work and outdoor hobbies against the harmful effects of UVR, and combinations of several interventions. These could in theory lead to reductions of up to 45% in skin cancer cases projected for the year 2050.
CONCLUSIONS: The scope for prevention depends on the prevalence of the risk factors in the different countries, as well as the associated risk factors and time lags modelled.

Flohil SC, Proby CM, Forrest AD, et al.
Basal cell carcinomas without histological confirmation and their treatment: an audit in four European regions.
Br J Dermatol. 2012; 167 Suppl 2:22-8 [PubMed]

BACKGROUND: Limited data are available on how often basal cell carcinomas (BCCs) are clinically diagnosed without histological confirmation and how they are treated.
OBJECTIVES: Within the framework of the EPIDERM project, an audit was conducted in four European countries to study the occurrence of clinically diagnosed BCCs without histological confirmation and to investigate how these are treated.
METHODS: In the Netherlands, Scotland, Finland and Malta studies were performed within different timeframes. Patients with one or more BCC(s) were selected and the number of clinically diagnosed BCCs without histological confirmation and their treatment was investigated by (manually) reviewing the (electronic) patient records and checking the (hospital) pathology databases to find evidence of histological confirmation.
RESULTS: In the Netherlands, 1089 patients with a first histologically confirmed BCC developed 1974 BCCs of which 1833 (92·9%) were histologically confirmed and 141 (7·1%) were not. A 4-month retrospective study conducted in Scotland selected 294 patients with 344 BCCs; 306 (89·0%) were histologically confirmed and 38 (11·0%) were not. A 3-month prospective study performed at the same centre in Scotland identified 44 patients who developed 58 BCCs; 44 (75·9%) of these were histologically confirmed and 14 (24·1%) were not. In Finland, there were 701 patients who developed 977 BCCs, of which 807 (82·6%) were histologically and 170 (17·4%) nonhistologically confirmed. In Malta, there were 420 patients with 477 BCCs. Only three (0·7%) of them were clinically diagnosed without histological confirmation. In the Netherlands and Finland, clinically diagnosed BCCs without histological confirmation were most often treated with cryotherapy, whereas in Scotland 5% imiquimod cream was the preferred treatment modality.
CONCLUSIONS: Although the frequency of clinically diagnosed BCCs without histological confirmation differed between the four European regions (range 0·7-24·1%), this confirms that the burden of BCC in Europe is underestimated when based on data from pathology and/or cancer registries.

de Vries E, Trakatelli M, Kalabalikis D, et al.
Known and potential new risk factors for skin cancer in European populations: a multicentre case-control study.
Br J Dermatol. 2012; 167 Suppl 2:1-13 [PubMed]

BACKGROUND: During recent years numerous studies have suggested that personal and environmental factors might influence cancer development.
OBJECTIVES: To investigate environmental and personal characteristics associated with skin cancer risk.
METHODS: A multicentre hospital-based case-control study was performed in Finland, Germany, Greece, Italy, Malta, Poland, Scotland and Spain, including 409 patients with squamous cell carcinoma (SCC), 602 with basal cell carcinoma (BCC) and 360 with cutaneous malignant melanoma (CMM) and 1550 control persons. Exposures were assessed by questionnaires that were partly self-administered, partly completed by dermatologists. Unconditional logistic regression modelling was used to assess associations including the influence of certain drugs and food items on skin cancer risk.
RESULTS: The usual associations were observed for sun exposure and pigmentation characteristics, with chronic sun exposure being most strongly associated with SCC risk, and naevi and atypical naevi with CMM risk. Use of ciprofloxacin was associated with a decreased risk of BCC [odds ratio (OR) 0·33] and use of thiazide diuretics was associated with an increased risk of SCC (OR 1·66). Ciprofloxacin was also associated with SCC (OR 0·34) and thiazines with BCC (OR 2·04), but these associations lost significance after correction for multiple testing. Consumption of pomegranate, rich in antioxidants, was associated with decreased BCC and SCC risk, also after correcting for multiple testing. Recent experience of stressful events was associated with increased risk, particularly of CMM.
CONCLUSIONS: In this large case-control study from across Europe the expected associations were observed for known risk factors. Some new potential protective factors and potential risk factors were identified for consumption of certain food items, medication use and stress, which deserve further investigation in future studies.