Basal cell carcinomas showing histological features generally associated with cutaneous adnexal neoplasms

Basal cell carcinoma (BCC) is the commonest malignant neoplasm in humans. Although a histopathological diagnosis of BCC is straightforward in the vast majority of cases, unusual histological variants can present a diagnostic challenge. A small proportion of BCCs show features which are generally associated with cutaneous adnexal neoplasms. Such changes may involve either the epithelium or the stroma and can mislead the pathologist particularly in small biopsies. Despite the growing evidence which speculate that BCC is a primitive follicular tumor, it is unusual to encounter tumors which actually show definitive signs of adnexal differentiation. This review aims to address this somewhat overlooked aspect of a very common tumor and offers practical guidance to distinguish them from adnexal neoplasms which they might mimic.     

Treatment of multiple scalp basal cell carcinomas by photodynamic therapy

The use of surface protoporphyrin IX fluorescence detection to delineate multiple superficial basal cell carcinomas on a patient's scalp is described. Photodynamic therapy (PDT) was subsequently performed with clearance of six and partial clearance of the remaining two tumours. The treated lesions have not recurred during 12 months of follow-up. The opportunity to combine diagnostic fluorescence detection with subsequent treatment by PDT offers an effective and practical management option. PDT is a tissue-sparing modality with low morbidity and good cosmesis, leading us to propose 5-aminolaevulinic acid-PDT for multiple superficial basal cell carcinomas of the scalp.     

HLA-G expression in basal cell carcinomas of the skin recurring after radiotherapy

Basal cell carcinoma (BCC) of the skin represents the most common malignancy in the fair-skinned population worldwide. HLA-G is one of the molecules implicated in immunotolerance. To investigate the role of HLA-G in recurring BCCs, we constructed a tissue microarray containing 38 primary BCCs that underwent radiotherapy and 14 secondary BCCs recurring on the primary site after radiotherapy, and evaluated the HLA-G protein expression by immunohistochemistry. The HLA-G protein was most frequently expressed in aggressive sclerosing BCCs. Nodular BCC demonstrated the strongest HLA-G expression. Interestingly, tumor infiltrating mononuclear cells (TIMC) expressed the HLA-G molecule in BCCs that showed no recurrence. After comparing primary BCCs and BCCs relapsed after radiotherapy, we observed decreased HLA-G expression on tumor cells and the loss of HLA-G expression on TIMC in relapsed BCCs. After radiotherapy, immunobiology of BCC may change resulting in the down-regulation of HLA-G expression on tumor and on tumor-infiltrating cells.     

Mitochondrial D310 D-Loop instability and histological subtypes in radiation-induced cutaneous basal cell carcinomas

BackgroundBasal cell carcinoma (BCC) is the most frequent skin cancer. An elevated prevalence of BCC has been associated with radiation, namely after the Tinea capitis epilation treatment, being these tumors described as more aggressive. Mitochondrial DNA (mtDNA) mutations have been reported in many human tumors, but their occurrence in BCC is poorly documented.ObjectiveThe purpose of this work was to evaluate BCC histological subtypes in individuals subjected to X-ray epilation for Tinea capitis treatment when compared to non-irradiated patients. Moreover we also wanted to evaluate mitochondrial D-Loop instability in both groups of BCCs in order to compare the frequency of D-Loop mutations in post-irradiation BCC versus sporadic BCC.Methods228 histological specimens corresponding to BCCs from 75 irradiated patients and 60 non-irradiated patients were re-evaluated for histological subtype. Subsequently, we sequenced the D-Loop 310 repeat in blood, oral mucosa, tumor lesions and, whenever available, non-tumoral adjacent tissue from these patients.ResultsThe infiltrative subtype of BCC, considered to be more aggressive, was significantly more frequent in irradiated patients. BCC D-Loop D310 mutation rate was significantly higher in irradiated BCCs than in the non-irradiated ones. Moreover, it was associated with a higher irradiation dose. The presence of mtDNA heteroplasmy in patients’ blood was associated with a higher mutation rate in the BCCs suggesting that a more unstable genotype could predispose to mtDNA somatic mutation.ConclusionsOur results suggest that radiation-induced BCCs may be considered to be more aggressive tumors. Further studies are needed to clarify the role of mtDNA D-Loop mutations in tumors from irradiated patients.     

Evaluation of recurrence after photodynamic therapy with topical methylaminolaevulinate for 157 basal cell carcinomas in 90 patients

The aim of this study was to evaluate the effect of photodynamic therapy with topical methylaminolevulinate for the treatment of basal cell carcinomas in a single dermatological department. Ninety patients (34.4% men and 65.6% women) with a total of 157 basal cell carcinomas (111 superficial, 40 nodular, 6 unknown) were treated. Primary endpoint was clinically observed recurrence verified by biopsy 3, 6 and 12 months after treatment, then once a year. Estimated patient recurrence rates were 7% at 3 months, 19% at 6 months, 27% at 12 months and 31% at 24 months. Patients aged over 60 years had significantly higher estimated recurrence rates compared with patients aged 60 years or under (at 12 months, 35% vs. 19%, p?=?0.01). Estimated recurrence rates for tumours was 4% at 3 months, 11% at 6 months, 16% at 12 months and 19% at 24 months. There were significantly higher estimated recurrence rates for nodular basal cell carcinomas compared with superficial basal cell carcinomas (at 12 months, 28% vs. 13%, p?=?0.008). In conclusion, photodynamic therapy is only appropriate for treatment of superficial basal cell carcinoma, and, age above 60 years and histology showing nodular basal cell carcinoma are independent risk factors for developing a recurrent basal cell carcinoma.     

Comparative study of the clinical,histological, and biological characteristics of squamous cell carcinomas in areas previously treated with photodynamic therapy

Background

Although photodynamic therapy (PDT) is an effective treatment option for non-melanoma skin cancer, the development of aggressive tumours in PDT-treated areas has been described.

Objectives

To evaluate the clinical, histological, and biological characteristics of squamous cell carcinomas (SCCs) in areas previously treated with PDT vs those arising in areas never treated with this therapeutic modality.

Materials & methods

Aretrospective observational studywas designed. We collected all cases of invasive SCCs in areas previously treated with PDT. The control group consisted of an equivalent number of SCCs randomly selected from the database of our pathology department. Expression of specific markers implicated in SCC progression, including p53, Ki67, COX-2, cyclin D1, E-cadherin, EGFR, survivin, and pERK, was analysed.

Results

A total of 699 patients were treated with PDT for non-melanoma skin cancer during the course of the study. Ten invasive SCCs arising in areas previously treated with methylaminolevulinate-PDT were diagnosed in six patients. The control group consisted of 10 invasive SCCs from 10 patients never treated with PDT. In the PDT group, the mean tumour size was significantly lower and the absence of ulceration was more frequent than in the control group (p<0.024 and p = 0.035, respectively). Adiffuse survivin staining pattern was observed in 90% of tumours in the PDT group versus 50% in the comparative group (p = 0.141).

Conclusion

The number of SCCs arising in areas previously treated with PDT was very low and did not differ significantly from that of SCCs developing in non-PDT-treated areas.

     

Topical treatment of Basal cell carcinomas in nevoid Basal cell carcinoma syndrome with a smoothened inhibitor

Basal cell carcinoma (BCC) is a distinctive manifestation in nevoid basal cell carcinoma syndrome (NBCCS) patients. Both inherited and acquired mutations of patched 1 (PTCH1), a tumor-suppressor gene controlling the activity of Smoothened (SMO), are the primary cause of the constitutive activation of the Hedgehog (HH) pathway, leading to the emergence of BCCs in NBCCS. LDE225, a distinct, selective antagonist of SMO, showed potent inhibition of basaloid tumor nest formation and mediated regression of preformed basaloid tumors in organ cultures of skin derived from Ptch1 heterozygous knockout mice. In a double-blind, randomized, vehicle-controlled, intraindividual study, a total of 8 NBCCS patients presenting 27 BCCs were treated twice daily with 0.75% LDE225 cream or vehicle for 4 weeks. Application of 0.75% LDE225 cream was well tolerated and showed no skin irritation. Of 13 LDE225-treated BCCs, 3 showed a complete, 9 a partial, and only 1 no clinical response. Except for one partial response, the vehicle produced no clinical response in any of the 14 treated BCCs. Treatment with 0.75% LDE225 cream in NBCCS patients was very well tolerated and caused BCC regression, thus potentially offering an attractive therapeutic alternative to currently available therapies for this indication.JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article, please go to http://www.nature.com/jid/journalclub.     

Basal cell carcinoma: histological classification and body-site distribution

BACKGROUND: Basal cell carcinoma (BCC) is the most common cancer worldwide in white-skinned populations. Recent studies suggest that BCC is not a single entity and that different histological subtypes show different clinical behaviour and might have different aetiology. OBJECTIVES: To provide information on the incidence of BCC by histopathological subtype and body site. METHODS: A case series of BCC from a prospective population-based register study collecting information on all excised and histologically confirmed skin cancers in Townsville, north Australia between 1997 and 1999. RESULTS: Age-standardized incidence rates for nodular BCC were 727.1 per 100 000 inhabitants per year for males and 411.8 for females, while rates for superficial BCC were 336.5 for males and 251.4 for females. Incidence rates for 'high risk' BCC were 261.3 for males, 146.5 for females with infiltrative, and 156.7 for males and 100.2 for females with micronodular types. Superficial BCC occurred at a younger age, particularly in female patients. For all histological subtypes and both genders relative tumour density was highest for the face, followed by the neck. An exception was superficial BCC in males, where the posterior trunk was second, followed by the neck. CONCLUSIONS: The study found a higher rate of superficial BCC than previous studies from less sun-exposed countries, and a more equal distribution of superficial BCC on face, trunk and limbs. These results seem to blur the difference between intermittent and continuous sun exposure as the causative environmental agents. The clinical implications of 'high risk' BCC rates are discussed.     

Routine double treatments of superficial basal cell carcinomas using aminolaevulinic acid-based photodynamic therapy

BACKGROUND: Superficial basal cell carcinomas of the skin (sBCC) often respond poorly to single-treatment aminolaevulinic acid-based photodynamic therapy (ALA-PDT), with a number of reports indicating a relapse rate of 50% or more. OBJECTIVES: To determine whether a second treatment at seven days can improve the response. METHODS: Twenty-six lesions were treated twice with ALA-PDT, with an interval of 7 days between the two treatment sessions. RESULTS: We observed a complete response rate of 100% 1 month after treatment. Only one lesion relapsed (16 months post-PDT), a relapse rate of 4% (median follow up 27 months; range 15-45 months). Cosmetic results were excellent. CONCLUSIONS: We consider routine double treatments with ALA-PDT to be an effective approach to the management of sBCC, particularly those located in anatomically difficult, or cosmetically sensitive, sites.     

Comparison of risk factors of single Basal cell carcinoma with multiple Basal cell carcinomas

Background:

Basal cell carcinoma (BCC) is the most common malignant skin tumor. Although mortality attributable to BCC is not high, the disease is responsible for considerable morbidity. There is evidence that the number of patients who develop more than one BCC is increasing.

Aims:

The aim of this study was to elucidate possible risk factors for developing Multiple BCC.

Patients and Methods:

Patients with histologically proven BCC (n = 218) were divided into two groups (single BCC and Multiple BCC) according to the number of their tumors and their profile were reviewed. Probable risk factors were compared between these two groups.

Results:

Among 33 evaluated risk factors, mountainous area of birth, past history of BCC, history of radiotherapy (in childhood due to tinea capitis), abnormal underlying skin at the site of tumor, and pigmented pathologic type showed significant differences between the two groups.

Conclusions:

The high rate of additional occurrences of skin cancers among patients with previously diagnosed BCC emphasizes the need of continued follow-up of these individuals. Those with higher risk require closest screening.