Changing trends in non-melanoma skin cancer in South Wales, 1988-98

BACKGROUND: In 1988 our department carried out a population-based epidemiological study of non-melanoma skin cancer (NMSC) incidence, over a 6-month period, in West Glamorgan, South Wales. Objectives To reassess the incidence of NMSC in this defined population over a similar 6-month period 10 years after the initial study. METHODS: All cases of basal cell carcinoma and squamous cell carcinoma diagnosed in West Glamorgan are recorded by the local skin cancer registry. All cases for the relevant 6-month period were analysed. RESULTS: Using these figures, we have identified a significant rise in the crude incidence of NMSC from 173.5 10 years ago to 265.4 per 100,000 population per annum. We also applied the world standard population for age to our crude figures, demonstrating a combined male and female world population-corrected rate of 129.9 per 100,000 population. CONCLUSIONS: In our population the crude incidence of NMSC has risen significantly over 10 years. Additionally, the combined male and female world population-corrected rate appears to be the highest published standardized incidence of NMSC to date from any European country.     

The role of radiotherapy in the management of non-melanoma skin cancer

The global incidence of non-melanoma skin cancer continues to increase as the global population ages with the highest incidence in the world occurring in Australian and New Zealand patients. There are numerous treatment options available for non-melanoma skin cancer patients of which radiotherapy is an efficacious and versatile tissue preserving non-surgical (or medical) option. In patients where excision may not be an option (medically/technically inoperable) or considered less ideal (e.g. cosmetic outcome), radiotherapy offers an excellent option. Following surgery, adjuvant radiotherapy in patients with unfavourable pathology can decrease the risk of recurrence and associated morbidity. Elderly and co-morbid patients with poor performance status can benefit from short-course hypofractionated radiotherapy in the setting where surgery is not an option. As with any modality, radiotherapy has advantages and disadvantages and it is therefore important for clinicians to appreciate these. We aim to present an update for clinicians that manage patients with non-melanoma skin cancer on the role of radiotherapy.     

Multiple aggressive squamous skin cancers in association with nonbullous congenital ichthyosiform erythroderma

Nonbullous congenital ichthyosiform erythroderma (NBCIE) is one of the autosomal recessive inherited non-syndromic ichthyoses and is currently diagnosed on clinical grounds alone. Skin cancer is not a recognized complication of NBCIE. We report here two NBCIE patients who have developed multiple aggressive nonmelanoma skin cancers, predominantly cutaneous squamous cell carcinoma. NBCIE may be a risk factor for skin cancer development.     

Diet and basal cell skin cancer: results from the EPIC-Norfolk cohort

BACKGROUND: The incidence of non-melanoma skin cancer (NMSC) in Britain has been increasing over the past 50 years. This has been attributed to increased sunlight exposure, but the increased exposure has not been quantified, and in any case, much of the increase in incidence has occurred in those parts of the body, mainly the head and neck, that have always been exposed to sunlight. There is evidence that increased dietary fat intake has increased the sensitivity of the skin to the carcinogenic potential of sunlight, particularly in causing squamous cell tumours. OBJECTIVES: To test the hypothesis that increased dietary fat is a risk factor for NMSC. METHODS: The hypothesis was tested in a nested case-control study. The cohort was that recruited for the EPIC-Norfolk study, the cases (n = 123) were subjects with NMSC diagnosed since recruitment, and the controls (n = 247) were randomly selected from the same cohort. The effect of diet on the incidence of NMSC was assessed using conditional logistic regression. RESULTS: As there were so few cases (14) with squamous cell tumours they were excluded from the statistical analyses. Fat intake was not found to be a risk factor: the unadjusted odds ratio (OR) of basal cell cases vs. controls was estimated as 0.860/(25.5 g total fat daily) with 95% confidence interval (CI) (0.663, 1.116), P = 0.25. Exploratory analyses of diet components and food groups found a protective effect of increased vitamin E consumption: unadjusted OR of basal cell cases vs. controls was 0.731/(3.06 mg vitamin E daily), 95% CI (0.564, 0.948), P = 0.015. Adjusted analyses gave broadly similar results. CONCLUSIONS: The potentiating factor remains unknown: if dietary fat has any effect on NMSC, it is not apparent when basal cell tumours are considered. There was no evidence of a generalized healthy eating effect. A substantial protective effect was found in exploratory analyses for the fat soluble antioxidant vitamin E.     

Cutaneous squamous cell carcinoma of the scalp extending to the skull: A case report and review of the literature

Squamous cell carcinoma (SCC) of the scalp has increased prevalence in older patients and often presents later in life. Mohs micrographic surgery remains the most effective treatment in most cases. Delayed presentation may result in localized bony invasion or distant metastases. We present a case of an elderly woman presenting with extension of SCC into the parietal bone of the skull.     

A broad spectrum of human papillomavirus types is present in the skin of Australian patients with non-melanoma skin cancers and solar keratosis

BACKGROUND: Human papillomavirus (HPV) may play a role in the pathogenesis of non-melanoma skin cancer (NMSC) in epidermodysplasia verruciformis (EV) patients, but in the general population no specific HPV types have been associated with these lesions. Objectives To examine the spectrum of HPV types present in the skin and tumours of Australian patients with NMSC or solar keratosis (SK). METHODS: Biopsies from tumours, and cotton swab samples of perilesional skin and buttock skin from each of 59 Australian patients with basal cell carcinoma (BCC), squamous cell carcinoma (SCC) or SK were tested for HPV DNA by polymerase chain reaction (PCR) using HPV consensus (FAP) primers and by type-specific primers for HPV 38 and candidate HPV 92. The identification of HPV type from consensus PCR was performed by sequencing and comparison with GenBank. RESULTS: In total, 49 of 59 (83%) patients harboured HPV DNA, which was detected in 28 of 64 (44%) biopsies, 48 of 64 (75%; P < 0.001) perilesional swabs and 36 of 59 (61%; P = 0.04) buttock swabs. Forty-five different HPV types/putative types were detected: 15 were previously characterized HPV types, 17 were earlier described putative types and 13 were new putative types. In addition, six subtypes and four variants of HPV sequences were identified. HPV types within the B1 group (EV HPV types) were found in 26 of 64 (40%) lesions, 44 of 64 (69%) perilesional swabs and 35 of 59 (59%) buttock swabs. HPV 38 was detected in 23 of 59 (39%) patients, and was found in seven of 16 (43%) SKs, but was less common in SCCs [three of 23 (13%); P = 0.037] and BCCs [four of 25 (16%); P = 0.056]. Candidate HPV 92 was found in seven of 59 (12%) patients. CONCLUSIONS: A broad spectrum of HPV types, the majority from the B1 group, was found in skin of Australian patients with skin tumours. HPV 38 was found significantly more often in SK than in SCC. However, the role of cutaneous HPV infection in the pathogenesis of NMSC remains elusive.     

Seborrhoeic keratosis and malignancy: Collision tumour or malignant transformation?

A retrospective study of 813 histological specimens reported as seborrhoeic keratoses included 43 (5.3%) associated with non-melanoma skin cancer. Intraepidermal carcinoma (squamous cell carcinoma in situ) was the most common of these (36). There were five basal cell carcinomas (one with intraepidermal carcinoma also) and two invasive squamous cell carcinomas. No melanomas were reported. Twenty-seven of the intraepidermal carcinomas appeared to arise within the seborrhoeic keratosis as did one of the invasive squamous cell carcinomas. Of these 28 lesions, the head was the most common site. Fourteen were clinically diagnosed as a non-melanoma skin cancer with only nine clinically felt to be a seborrhoeic keratosis. These lesions may represent malignant transformation within the seborrhoeic keratosis. Twelve specimens reported adjacent dual pathologies, with the trunk and limbs the most common sites. Seven were diagnosed clinically as a skin malignancy, whereas three were thought to be solar keratoses. Clinically, the remaining two were seborrhoeic keratoses. The origin of the malignancy in these cases is less obvious and may represent collision tumours. Three curette specimens could not be assessed for architecture.     

Invasive squamous cell carcinoma after treatment of carcinoma in situ with 5% imiquimod cream

Squamous cell carcinoma in situ has the potential to progress to invasive squamous cell carcinoma. This report presents two cases of punch biopsy-proven squamous cell carcinoma in situ, treated with once-daily application of 5% imiquimod cream for 6 weeks. Both patients developed moderate local inflammatory reactions during treatment. The first patient demonstrated clinical clearance of the scalp lesion after treatment. Two months later, he re-presented with a subcutaneous nodule at the same site. Histology was consistent with recurrent squamous cell carcinoma. Five months following excision of the recurrent tumour, he presented with metastatic squamous cell carcinoma to a cervical lymph node. The second patient had low-grade chronic lymphocytic leukaemia and presented with squamous cell carcinoma in situ of the leg that failed to clear clinically after treatment with imiquimod. He presented 4 months later with a focus of invasive squamous cell carcinoma within the lesion.     

Use of 5% imiquimod cream in the treatment of facial basal cell carcinoma: a 3-year retrospective follow-up study

There has been considerable research into the safety and efficacy of topical 5% imiquimod cream for the treatment of skin cancers in recent years, in particular superficial and nodular basal cell carcinomas. However, there are limited long-term follow-up studies. This retrospective study aims to determine the efficacy of 5% imiquimod cream in the treatment of facial basal cell carcinomas over 3 years. Medical records of 12 patients treated with 5% imiquimod cream at a private dermatology practice during 2001 and 2002 were retrospectively reviewed. Target tumours included superficial and nodular basal cell carcinomas, giving a total lesion number of 19. Patients were commenced on a once daily treatment regimen for up to 9 weeks, and given rest periods as required according to the severity of application site reactions. We found that 5% imiquimod cream is an effective treatment option for superficial and nodular basal cell carcinomas, giving a clearance rate of 89.5% at an average of 39 months of follow up.     

Distinctive distribution of human papillomavirus type 16 and type 20 DNA in the tonsillar and the skin carcinomas of a patient with epidermodysplasia verruciformis

BACKGROUND: Epidermodysplasia verruciformis (EV) is a rare skin disease characterized by disseminated pityriasis versicolor-like or flat wart-like lesions and by the development of skin carcinomas. It is well established that specific cutaneous human papillomaviruses (EV-HPVs) are associated with both benign and malignant skin lesions in EV patients. However, little is known of the relationship between HPV and the mucosal lesions of EV patients. OBJECTIVES: To detect and identify HPV types associated with skin and mucosal lesions of an EV patient. PATIENT/METHODS: We investigated the skin carcinoma and the coexisting tonsillar carcinoma of a 41-year-old man with EV. Histopathologically, both lesions were squamous cell carcinomas. We analysed these two lesions by immunohistochemistry, in situ hybridization, and by molecular virology. RESULTS: Neither skin nor tonsillar lesions exhibited positivity for HPV capsid antigen by immunohistochemistry. By Southern blot hybridization, however, the skin carcinoma harboured 'EV-specific' HPV20 DNA, while the tonsillar carcinoma harboured 'genital' HPV16 DNA. In addition, in situ hybridization localized the respective viral DNA in the corresponding lesion. CONCLUSIONS: The results indicate that EV-HPV could be responsible for the development of the skin carcinoma, but not the mucosal carcinoma in this patient.     

Oral S‐1 in advanced cutaneous squamous cell carcinoma

Squamous cell carcinoma (SCC) is the second most common type of skin cancer in Japan, and its incidence has been increasing in recent years. Early diagnosis and complete excision can provide a high cure rate. However, advanced cases of SCC showing local invasion, regional lymph node metastasis or distant metastasis are not curative and are difficult to treat with surgery alone. Some chemotherapy regimens have been used for treating advanced cutaneous SCC. However, almost all these regimens require intravenous administration and result in serious toxicities in elderly people. We gave S‐1, a novel oral chemotherapeutic agent, for six patients with advanced cutaneous SCC. Three patients achieved complete response and one achieved partial response. Two patients showed stable disease. The overall response rate was 66.7% (four of six patients), and the disease control rate was 100%. Two of six patients developed grade 3 anaemia. Oral S‐1 treatment is safe and effective for treating advanced cutaneous SCC. However, a prospective trial is necessary to confirm the effectiveness of oral S‐1 for advanced cutaneous SCC.     

Lichen sclerosus is frequently present in penile squamous cell carcinomas but is not always associated with oncogenic human papillomavirus

BACKGROUND: Penile squamous cell carcinoma (SCC) may occur on pre-existing lesions of lichen sclerosus (LS). However, the prevalence of histological changes of LS in penile SCC is not well established. Moreover, mucosal oncogenic human papillomaviruses (HPVs) are sometimes detected in penile SCC, but have not been systematically sought in LS-associated penile SCC. OBJECTIVES: To establish the prevalence of LS histological changes and of mucosal oncogenic HPV in a series of patients with penile SCC. METHODS: Consecutive cases of histologically proven penile SCC from a single university hospital over a 14-year period were retrospectively selected and reviewed. Histological signs of LS were systematically sought. HPV was detected by polymerase chain reaction (PCR) amplification of DNA from paraffin-embedded skin samples using general primers GP5+/GP6+ (allowing detection of mucosal HPV) and oncogenic type 16-, 18-, 31- and 33-specific primers. RESULTS: Eighteen cases of penile SCC were found. The mean +/- SD age of patients at diagnosis was 67.3 (14.5 years). In eight of 18 (44%) cases, SCC was associated with histological features of LS. Seventeen skin biopsy specimens of SCC (nine without and eight with LS histology) were subjected to PCR amplification for HPV. Mucosal HPV was detected in six of them (35%). Five of nine SCCs without histological features of LS were positive for mucosal HPV: three with HPV type 16 and two with only general primers. In contrast, all eight SCCs associated with LS were negative for oncogenic HPV types, although one was positive with general primers. CONCLUSIONS: Penile SCC seems to be frequently associated with LS histological changes. As with vulval SCC, we found that non-LS-associated penile SCC tended to be frequently associated with oncogenic HPV infection, whereas LS-associated penile SCC was not. Larger series are needed to confirm this association.     

Malignant transformation of leg ulcers: a retrospective study of 85 cases

Background  Malignant transformation remains a rare, under-recognized and ominous, complication of leg ulcers, although its exact prevalence is unknown.
Patients and methods  This retrospective French study included cases of chronic ulcers of vascular origin complicated by histologically proven carcinomas. For squamous cell carcinomas (SCC), the duration of the ulcer had to be longer than 3 years. For basal cell carcinomas (BCC), a negative previous biopsy of the ulcer was considered.
Results  Eighty patients, accounting for 85 tumours, were included, with a female : male ratio of 2.5 : 1 and a mean age of 75 years. Eighty-eight percent of the ulcers were of venous origin and their mean duration was 27.5 years. Five patients developed bilateral cancers. Clinical findings included abnormal granulation tissue in 76% of cases, absence of healing in 14% and unusual extension in 6%. Histologically, 83/85 (98%) of tumours were SCC, among which 82% were very well or well differentiated and 18% moderately or poorly differentiated. The two remaining cases were BCC. The overall death rate was 32%; it was higher when lymph-node (66%) or visceral metastases (83%) were present. Leg amputation was performed in 29/51 (57%) of patients, irrespective of the degree of histological differentiation. For well-differentiated (grade I) and localized (stage Ia) SCC, simple surgical excision was preferred to amputation.
Conclusion  Malignant transformation of chronic leg ulcers of vascular origin is mainly encountered in elderly patients and manifests as an abnormally vegetating lesion, which may be occasionally bilateral. Malignant transformation usually occurs towards well-differentiated SCC and only exceptionally towards BCC. The high death rate, especially in metastatic cases, is at least partly due to delay in diagnosis. Surgery remains the treatment of choice. Leg amputation should be considered in the most extensive cases.     

CD147 expression in advanced cutaneous squamous cell carcinoma

Background: CD147 is upregulated in multiple cancer types, but its expression in advanced cutaneous squamous cell carcinoma (SCC) is unknown. Our purpose was to evaluate the expression patterns of CD147 and related monocarboxylate transporters (MCT1, MCT4) to determine their correlation with survival. Methods: This is a retrospective cohort study of patients with advanced stage cutaneous SCC of the head and neck who presented to a tertiary care center between 1998 and 2006 (n=50). CD147, MCT1 and MCT4 expression levels were assessed using immunofluorescence analysis of archived tumor samples and correlated with survival and clinicopathologic characteristics. Results: The majority of patients (92%, n = 46) were diagnosed with stage III disease, with 46% (n = 23) having positive regional lymph node metastasis and 8% (n = 4) with distant metastasis. Primary malignancies had an overexpression of CD147 (78%; n = 35), MCT1 (23%; n = 10) and MCT4 (47%; n = 20). In addition, there was a significant relationship between the overexpression of CD147 and node positive disease (p = 0.048). Two‐ and five‐year survival rates were 69 and 61%, respectively. There was a trend toward decreased survival in patients with overexpression of CD147 (p = 0.17), MCT1 (p = 0.11) and MCT4 (p = 0.15). Conclusion: CD147 may represent a biomarker or potential therapeutic target in advanced cutaneous SCC. Sweeny L. Dean NR, Frederick JW, Scott Magnuson J, Carroll WR, Desmond RA, Rosenthal EL. CD147 expression in advanced cutaneous squamous cell carcinoma.     

An open-label, pilot study examining the efficacy of curettage followed by imiquimod 5% cream for the treatment of primary nodular basal cell carcinoma

SUMMARY The short-term efficacy of imiquimod 5% cream for the treatment of primary superficial basal cell carcinoma has been established. This study investigated its efficacy following curettage (without electrodesiccation) for the treatment of primary nodular basal cell carcinoma on the trunk and limbs. Seventeen patients with a total of 34 lesions were enrolled. Curettage was used to de-bulk the lesion and confirm suitable histology. Lesions displaying more aggressive subtypes (such as micronodular or morpheoic components) were excluded. Lesions were treated daily for 6 to 10 weeks with imiquimod 5% cream. Three months post treatment all lesions were excised, and 32 of 34 treated lesions (94%) were histologically clear of basal cell carcinoma. Fourteen of 17 patients rated the cosmetic outcome of treatment as excellent or good. Curettage followed by imiquimod 5% cream is effective for the treatment of primary nodular basal cell carcinoma on the trunk and limbs, and most patients are pleased with the cosmetic outcome.