Trends in the incidence of basal cell carcinoma by histopathological subtype

Background As a result of the high prevalence, basal cell carcinoma (BCC) causes a significant and expensive health care problem. Objective In this study, we evaluate the proportional increase in BCC by histological subtype over the last two decades. Methods We retrospectively reviewed all primary histological confirmed BCCs diagnosed in the Maastricht University Medical Centre in The Netherlands in the years 1991, 1999 and 2007. Results An annual increase of the number of BCCs of 7% for both genders was shown. The age‐standardized incidence rates for BCC increased between 1991 and 2007 from 54.2 to 162.1 per 100 000 men and from 61.7 to 189.8 per 100 000 women. The proportion of superficial BCC increased significantly from 17.6% to 30.7%. Conclusion The incidence of BCC is continuing to increase this century. The observed shift to the superficial histological subtype, which can be treated non‐surgically, might reduce the workload in the busy dermatologists practice.     

A prospective study of the incidence of skin cancer and its risk factors in a Spanish Mediterranean population of kidney transplant recipients

BACKGROUND: Skin cancer is the most common malignancy occurring in kidney transplant recipients (KTRs). OBJECTIVES: Our purpose was to investigate, prospectively, the cumulative incidence of cancerous and precancerous skin lesions as well as their risk factors in a close follow-up population of KTRs from a Mediterranean area of Spain. PATIENTS AND METHODS: One hundred and seventy-four consecutive KTRs were examined at the moment of transplant and then at 6-month intervals. The cumulative incidence of skin cancer was computed. To analyse the role of potential risk factors (age at transplantation, cause of renal failure, duration of pretransplant dialysis, type of immunosuppressive regimen, sun-reactive skin type and history of occupational sun exposure), the Cox regression method was used. RESULTS: After a median follow-up of 72 months (range, 12-140), 39 patients (25.3%) developed 142 tumours [84 basal cell carcinoma (BCC) and 58 squamous cell carcinoma (SCC)]. The BCC/SCC ratio was 1.4 : 1. The cumulative incidence for skin cancer was 13% after 3 years of graft survival, increasing to 27.5% at 6 years and 48% at 10 years. Only age at the time of transplantation and occupational sun exposure had statistical significance as risk factors (P < 0.001). CONCLUSIONS: Our study confirms the high incidence of non-melanoma skin cancer among KTRs in a Mediterranean population with occupational sun exposure and the patient's age at the time of transplantation being the main risk factors. We believe that all organ transplant programs should provide educational information about protecting oneself from the sun as well as include follow-up visits by dermatologists in order to facilitate early diagnosis and treatment of skin cancer.     

Cytokine mRNA expression in basal cell carcinoma

There is evidence that cytokines (CKs) play a significant role in the development and/or progression of skin cancer. The aim of the present study was to investigate the mRNA expression of tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-8 in biopsy specimens of basal cell carcinoma (BCC), and to compare the results with the mRNA levels of non-lesional skin of BCC patients and healthy subjects. Skin samples were obtained from 22 patients with BCC (lesional, non-lesional) and 25 healthy subjects (controls). Routine histology and real-time RT-PCR was performed. Histological examination revealed 12 nodular BCCs and 10 superficial BCCs. The mRNA levels of CKs observed in healthy controls did not significantly (P > 0.05) differ from non-lesional CK levels of BCCs patients. However, IL-6 and IL-8 levels of lesional skin were significantly (P < 0.05) higher than the CK levels observed in non-lesional skin and controls, respectively. mRNA expression of IL-6 and IL-8 showed a significant positive correlation (r = 0.51; P < 0.05). There was no significant (P > 0.05) difference between lesional mRNA levels of TNF-α and those levels observed in non-lesional skin and controls. The mRNA expression of CKs found in nodular and superficial BCCs did not significantly differ (P > 0.05). BCC is associated with a significant increase of IL-6 and IL-8 expression. We have shown for the first time that upregulation of IL-6 mRNA significantly correlates with IL-8 overexpresssion. In accordance with previous studies our data suggest a role for IL-6 and IL-8 in the development and/or progression of BCC, since mRNA expression of both CKs are significantly increased in tumour tissue.     

Basal cell carcinoma in a 17 year‐old organ transplant recipient

Skin cancer is among the most frequent cancers in pediatric organ transplant recipients. We report a 17‐year‐old Caucasian girl who had had a kidney transplant 6 years before and was referred to our outpatient clinic for a basal cell carcinoma of the scalp. This case emphasizes the importance of teaching sun‐protective behavior to transplant recipients and their parents and having a high index of suspicion and arrange for early referral for dermatologic care if skin changes are observed.     

CUSP/p63 expression in basal cell carcinoma

Chronic ulcerative stomatitis protein (CUSP), the most abundant cutaneous isoform of p63, is a p53-related gene essential for epithelial development. CUSP lacks the N-terminal transactivation domain found on other p53 family members and has been shown to inhibit p53 function in vitro. In this study, biopsies of normal skin (21 of 21), benign neoplasms [seborrheic keratosis (3 of 3), acrochordon (2 of 3), and verruca plana (3 of 3)], and squamous cell carcinomas (SCC) (4 of 4) displayed strong nuclear CUSP immuno-reactivity in epidermal cells. In contrast few basal cell carcinomas (BCC) (7 of 27) and sebaceous nevi (1 of 2) displayed this pattern of CUSP immunoreactivity. Thus, biopsies of cutaneous conditions characterized by sonic hedgehog (SHH) pathway dysregulation were more than 86 times as likely to lack CUSP/p63 immunofluorescence as were other cutaneous samples. Adjacent normal-appearing skin from patients with basal cell nevus syndrome (BCNS) (2 of 3) also lacked CUSP immuno-staining. Lastly, a BCC arising in a patched heterozygous mouse also lacked CUSP immuno-staining. Because CUSP mRNA and protein were detected via Northern and Western analysis in BCC samples lacking CUSP immuno-staining, we sequenced the coding region of CUSP from two non-staining BCCs but found no mutations. Therefore, CUSP appears to be present, unmutated, and yet frequently undetectable by immunofluorescence in cutaneous lesions in both humans and mice that are associated with SHH pathway dysregulation (BCCs, BCNS, and nevus sebaceous).     

High diversity of the T‐cell receptor repertoire of tumor‐infiltrating lymphocytes in basal cell carcinoma

Whether specific T‐cell clones are present in tumor infiltrating lymphocytes (TILs) in BCC is unknown. We employed deep sequencing of mRNA coding for the T‐cell receptor (TCR) chains α‐ and β to characterize the repertoire of TILs in BCC. V and J gene‐usage and CDR3 length were computed to determine the clonality of TCR and degree of overlap in TCR repertoires between skin resident T‐cells and TILs. We found high diversity of the TCR repertoire in BCC and control skin with random V‐J gene usage and similar CDR3‐length distribution. Lack of TCR repertoire restriction indicates absence of tumor‐specific TIL clones in BCC.     

Genetics of basal cell carcinoma

Basal cell carcinoma is the most common human malignancy in populations of European origin, and Australia has the highest incidence of basal cell carcinoma in the world. Great advances in the understanding of the genetics of this cancer have occurred in recent years. Mutations of the patched 1 gene (PTCH1) lead to basal cell carcinoma predisposition in Gorlin syndrome. PTCH1 is part of the hedgehog signalling pathway, and derangements within this pathway are now known to be important in the carcinogenesis of many different cancers including sporadic basal cell carcinoma. The molecular biology of the hedgehog pathway is discussed, and mouse models of basal cell carcinoma based on this pathway are explored. New developments in non‐surgical treatment of basal cell carcinoma are based on this knowledge. Other genes of importance to basal cell carcinoma development include the tumour suppressor gene P53 and the melanocortin‐1 receptor gene. In addition, we discuss molecules of possible importance such as the glutathione‐S‐transferases, DNA repair genes, cyclin‐dependent kinase inhibitor 2A, Brahma and connexins. Evidence of familial aggregation of this cancer is explored and supports the possibility of genetic predisposition to this common malignancy.     

Clinical and histopathological characteristics of extra‐facial basal cell carcinoma: Analysis of 35 patients at the Chonbuk National University Hospital in Korea

Basal cell carcinoma (BCC) primarily develops in the head and neck region, with 74–83 per cent of BCC occurring in this region. Unfortunately, most published studies on BCC were conducted in Caucasian populations, and analytic data on extra‐facial BCC in Asian and Korean patients, in particular, are not readily available. Here, we report on a retrospective analysis of extra‐facial BCC in Korean patients. Thirty‐five patients (16 men, 19 women) diagnosed with extra‐facial BCC at Chonbuk National University Hospital between January 1981 and December 2008 were evaluated. Their average age was 62.3 years and most of the patients (11 of 35, 31%) were in their fifties. The relative tumour density (RTD) was the highest in the genitalia (0.769), followed by the axilla (0.481). Other regions such as the trunk, buttocks and upper and lower extremities exhibited a much lower RTD (average: 0.1). Histopathological examinations showed that 16 tumours were nodular (46%), eight were superficial (23%) and seven were mixed (20%). Additionally, potential predisposing factors were identified in seven cases. In five patients the use of Asian medicine, including acupuncture and herbal medication, was ascertained. To the best of our knowledge, the present study is the first to analyse the clinical and histopathological characteristics of extra‐facial BCC in Korean patients. Our results indicate that the incidence of extra‐facial BCC is higher in the axilla and genitalia than at other locations, although these sites are frequently overlooked during routine skin examinations.     

Region growing by sector analysis for detection of blue‐gray ovoids in basal cell carcinoma

Blue‐gray ovoids (B‐GOs) are critical dermoscopic structures in basal cell carcinomas (BCCs) that pose a challenge for automatic detection. Due to variation in size and color, B‐GOs can be easily mistaken for similar structures in benign lesions. Analysis of these structures could help further accomplish the goal of automatic BCC detection. This study introduces an efficient sector‐based method for segmenting B‐GOs. Four modifications of conventional region‐growing techniques are presented: (i) employing a seed area rather than a seed point, (ii) utilizing fixed control limits determined from the seed area to eliminate re‐calculations of previously‐added regions, (iii) determining region growing criteria using logistic regression, and (iv) area analysis and expansion by sectors. Contact dermoscopy images of 68 confirmed BCCs having B‐GOs were obtained. A total of 24 color features were analyzed for all B‐GO seed areas. Logistic regression analysis determined blue chromaticity, followed by red variance, were the best features for discriminating B‐GO edges from surrounding areas. Segmentation of malignant structures obtained an average Pratt's figure of merit of 0.397. The techniques presented here provide a non‐recursive, sector‐based, region‐growing method applicable to any colored structure appearing in digital images. Further research using these techniques could lead to automatic detection of B‐GOs in BCCs.     

Water‐based correction fluid is a useful skin marker for determination of the tumor margin of basal cell carcinoma under high‐frequency ultrasound

We propose a new method to determine the appropriate preoperative surgical margin of basal cell carcinoma (BCC) by using water‐based correction fluid as a skin marker showing the tumor position on the skin under high‐frequency ultrasound (HFUS). After a provisional evaluation by dermoscopy, an approximately 2‐mm dot of water‐based correction fluid is applied to the tumor margin. The ultrasound waves are blocked by the dot of correction fluid, and a low‐signal column is observed under the dot of correction fluid. The dots of correction fluid are moved and located as near as possible to the tumor margin, which is shown as a solid hypoechoic area by the HFUS. After confirming that the dots of correction fluid are applied to the circumferential margin, we draw a line in the gaps between the dots. Before the operation, the dots of correction fluid are removed by forceps, and a line for the tumor margin is drawn where the dots were. The surgical margin is set just outside of this line with the use of a measuring device. Water‐based correction fluid is thus a useful skin marker under HFUS to determine the circumferential surgical margin of BCC.     

The density of epidermal p53 clones is higher adjacent to squamous cell carcinoma in comparison with basal cell carcinoma

BACKGROUND: It is well accepted that ultraviolet radiation from the sun can induce and promote growth of skin tumours. Skin cancer develops as a consequence of multiple genetic hits, where an initial, important step includes proliferation of cells susceptible to malignant transformation. Foci of morphologically normal epidermal keratinocytes overexpressing p53 protein are common in chronically sun-exposed skin. Such foci have previously been shown to represent expanding clones of p53-mutated keratinocytes. Although several characteristics concerning epidermal p53 clones remain to be resolved, an important role in skin carcinogenesis is anticipated. The density of epidermal p53 clones in human skin is largely unknown. OBJECTIVES: To compare the occurrence of epidermal p53 clones in skin surrounding cancers with that in skin surrounding benign melanocytic naevi. To assess the influence of age on frequency and size of epidermal p53 clones in human facial skin. METHODS: We have analysed the number and sizes of epidermal p53 clones in skin specimens from patients with squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and benign melanocytic naevi. Cases included normal facial skin from four different age groups. Tissue sections were immunohistochemically stained and the presence of p53 clones was recorded. Approximately 1.4 m of epidermis from a total of 112 biopsies was analysed. RESULTS: We found 128 epidermal p53 clones in biopsy specimens from 112 patients. The results showed that the number and size of p53 clones increase with age. In normal skin adjacent to SCC p53 clones were significantly more numerous and greater in size in comparison with those in normal skin both adjacent to benign naevi and adjacent to BCC. Interestingly, normal skin in the close vicinity of BCC and melanocytic naevi showed similar results regarding both number and size of epidermal p53 clones. CONCLUSIONS: Our findings suggest a connection between development of epidermal p53 clones and SCC.     

A new hypofractionated schedule of weekly irradiation for basal cell carcinoma of the head and neck skin area in elderly patients

The effectiveness of radiotherapy in patients with basal cell carcinoma (BCC) has been already reported in the literature. However, there is little information about the irradiation of BCC in elderly patients, especially due to the low conformity of them to daily irradiation. Thirty‐eight retrospectively selected elderly patients (78 years as median age) diagnosed with skin BCC of the head and neck area were treated with five weekly fractions of 600 cGy by three‐dimensional conformal radiotherapy (3DCRT) as an adjuvant treatment. The primary endpoint was the relapse free survival. Acute toxicity, as secondary endpoint, was assessed according to EORTC/RTOG criteria. Among our patients, there were only three local recurrences at 15, 32 and 38 months post‐3DCRT. There was no severe toxicity, while only 10 out of 38 patients presented grade II/III skin toxicity. Our proposed irradiation schedule seems effective in terms of local control and acute toxicity and could be an alternative scheme for elderly patients unfit for daily irradiation.     

A pilot study of fluorescence diagnosis of basal cell carcinoma using a digital flash light-based imaging system

Background/purpose: Fluorescence diagnosis (FD) is a promising method for the non‐invasive detection of tumor boundaries. We aimed to investigate the clinical utility of a flash light‐based fluorescence imaging system. Methods: Sixteen patients with basal cell carcinomas were included in this pilot study. FD was performed using a 20% 5‐aminolevulinic acid (ALA) cream. The FD tumor area was determined 3 h after the ALA application using a digital flash light‐based fluorescence imaging system and an image analysis system. The tumor area was also assessed by means of the clinical diagnosis (CD) based on the normal colored picture. The tumors were excised following the FD procedure, but according to the clinically diagnosed lesional area. Results: Though there was a very strong correlation between the tumor areas assessed by FD and CD, the mean tumor area that was visualized by FD was significantly smaller than the tumor area determined by CD. The mean±SD FD/CD ratio was 0.78±0.11 in total. In 81.3% of cases, complete tumor excision was achieved. Conclusion: This pilot study indicates that the FD technology may be less sensitive than CD, and refinements of the technique along with larger systematic trials on the sensitivity and specificity of FD are required.