Surgical margins of excision for basal cell carcinoma and squamous cell carcinoma

In excising basal and squamous cell carcinomata, the surgical margin that is wide enough to completely remove the tumor an acceptable percentage of the time and narrow enough to minimize removal of excessive normal tissue must be selected. This task can be reliably accomplished with comprehensive knowledge of factors that affect subclinical tumor extension such as tumor appearance, diameter, histology, location, treatment status, and, in the case of squamous cell carcinoma, vertical invasion depth and involvement of subcutaneous fat. Information regarding these factors along with specific recommendations about excisional margins for basal cell and squamous cell carcinomata is presented.     

Treatment of basal cell carcinomas in patients with nevoid basal cell carcinoma syndrome

Background  Nevoid basal cell carcinoma syndrome (NBCCS) is characterized by the development of multiple basal cell carcinomas (BCCs). A major problem for these patients is the enormous amount of BCCs which can invade in the deep underlying structures, especially in the face. Different treatment modalities are used in these patients; surgical excision, Mohs micrographic surgery, cryotherapy, photodynamic therapy, ablative laser therapy and topical 5% imiquimod. There is no evidence based advice how to treat a NBCCS patient.
Objective  To give a review of the literature about the possible treatment modalities for the multiple BCCs in NBCCS patients.
Results  Literature consists mainly of case reports; no evidence based advice how to treat a NBCCS patient exists. Multiple treatments are available (surgical and non-surgical), and a lot of them can be combined. Treatment in a megasession is an option to diminish the medical and social inconvenience for the patient.

Conflicts of interest

None declared     

An overview of Mohs micrographic surgery for the treatment of basal cell carcinoma

This article reviews Mohs micrographic surgery for basal cell carcinoma. Its evolution to the present day technique, indications, and limitations are discussed, along with future expectations for the procedure.     

Treatment of 208 extensive basal cell carcinomas with Mohs micrographic surgery

Aim With the rapidly increasing number of basal cell carcinomas in Europe, a close look at Mohs Micrographic Surgery (MMS) is timely. Subject We report the results of MMS in the Netherlands, as treatment for extensive basal cell carcinomas. Methods Patients (n= 198) with extensive basal cell carcinoma (n= 208) were treated with MMS. The mean follow up period was 6.4 years. Results Four of 208 BCCs recurred. Conclusions Considering a recurrence rate of only 2% for the treatment of extensive and mainly recurrent basal cell carcinomas, we suggest that MMS provides the best prospect for total tumour removal.     

Effect of inflammation on positive margins of basal cell carcinomas

Background/Objectives: The use of preparations such as imiquimod in the treatment of basal cell carcinoma is well accepted. Imiquimod induces interferon‐α, other cytokines, antigen‐presenting cells and innate immunity, against tumour cells. The current study investigated whether the inflammation induced from a surgical procedure could have a similar effect on removing residual tumour after an excision. Method: A retrospective audit was carried out on basal cell carcinoma removed in the Dermatology Clinic of the Royal Newcastle Centre in 2007. The end‐point focussed on the features of those tumours which initially had a positive margin, but were found to have no remaining tumour on subsequent excision. Result: A linear regression was carried out, revealing two significant predictors of outcome. These were the location of the basal cell carcinoma excision and the excision type. Punch biopsies and excisional biopsy had a greater number of histopathologically negative wider excisions despite initial positive margins. Facial lesions had a greater number of negative wider excisions. Conclusion: The study has shown the majority of negative re‐excisions were from lesions on the head which had had an initial surgical procedure. However, the evidence is not strong enough to advocate a protocol for dealing with positive margins. A larger sample size that encompassed all three factors that affect outcome, that is, the location of lesion, type of lesion and type of excision carried out, would be required in order to make a more definitive statement on protocol change for treatment of basal cell carcinoma.     

Histological evaluation of residual basal cell carcinoma after shave biopsy prior to Mohs micrographic surgery

Background Patients who are referred for Mohs surgery after pre‐operative biopsy has been performed show in some cases no clinical or pathological evidence of tumour persistence. We have previously shown that 25% of these patients show no residual skin cancer either basal cell carcinoma or squamous cell carcinoma. The reasons for ‘disappearance’ of the tumour may be true non‐persistence or false non‐persistence because of wrong‐site Mohs surgery. Objective To determine the incidence of residual basal cell carcinoma after shave biopsy of primary nodular basal cell carcinoma prior to Mohs micrographic surgery. Methods A prospective unblinded study was performed on patients undergoing Mohs surgery for primary nodular basal cell carcinoma. The tumour was removed as a shaved excision using a No. 15 blade at the clinical borders like a shave biopsy (Mohs shave). The bases of the tumors were excised and then sectioned vertically at the middle and cut to the periphery at 10–15 μm intervals till the edge. Results Fifty‐one patients were evaluated. In 40 patients, residual basal cell carcinoma was found at the base of the shave excision site (78.4%). Conclusions Pre‐operative shave biopsy performed during Mohs surgery for primary nodular basal cell carcinoma is ‘curative’ in 22% of the patients.     

A case of basal cell carcinoma treated with photodynamic therapy – changes in histological features and bcl-2 expression

Photodynamic therapy (PDT) is based on the phototoxicity of photosensitizers, mostly porphyrins. Since systemic photodynamic therapy with δ-aminolevulinic acid (δ-ALA) causes prolonged whole-skin photosensitivity, topical photodynamic therapy was developed. We describe the histological findings and the results of immunohistochemical staining for bcl-2 protein in the basal cell carcinoma of a 71-year-old patient treated by photodynamic therapy with δ-ALA. After histological confirmation of the diagnosis, 20%δ-ALA in an aqueous cream base was applied to one lesion for 3 h. After 3 h the tumor was exposed to light emitted by a Kodak carousel light projector. Biopsies were taken before exposure and at days 3 and 21 after exposure. The specimens were stained with hematoxylin-eosin and with monoclonal antibody to bcl-2 protein. The intermediate histological response 3 days after exposure was characterized by "squamoid" transformation of the tumor cells along with signs of necrosis, loss of bcl-2 expression and an inflammatory cell reaction. Clinical and histological examinations 3 weeks after treatment showed no sign of residual tumor.     

Treatment of basal cell carcinoma

Basal cell carcinoma is the most common tumor in Central Europe, the U.S. and Australia. The increasing incidence of basal cell carcinoma presents the health care system, especially dermatology, with great challenges. In recent years new options for treating basal cell carcinoma have become available, enriching our therapeutic options. We review the current status of each of these treatment approaches.     

Clinical factors predictive for histological aggressiveness of basal cell carcinoma: A prospective study of 2274 cases

IntroductionSince surgery is the first-line treatment for basal cell carcinomas (BCC), the histological aggressiveness of the disease must be clinically predicted in order to apply optimal safety margins that ensure a high rate of complete resection while minimising the risk of recurrence.ObjectivesTo evaluate clinical predictive factors of histological aggressiveness of BCC, we conducted a national prospective multi-centre study.MethodsAll consecutive patients presenting for BCC surgery were included, and standardised clinical data collected, and slides were submitted for review. Trabecular, micronodular and morpheaform BCCs were classified as aggressive.ResultsOf the 2710 cases included, 2274 were histologically confirmed. Clinical subtyping was correct in 49.9% of superficial BCCs, 86.2% of nodular BCCs and only 22% of aggressive BCCs. By multivariate analysis, aggressive BCCs were more frequently ulcerated (45%), indurated (70%), showed adherence (8.6%), and were associated with high-risk anatomical zones (50.3%, P < 0.0001). These predictive clinical features may be helpful for decision making.     

Image analysis for quantification of nucleolar organizer regions in basal cell carcinoma and seborrheic keratosis

Background/aims: Nucleolar organizer regions (NORs) have recently attracted much attention because of claims that their frequency within nuclei is significantly higher in malignant cells than in normal, reactive, or benign neoplastic cells. The purpose of this paper is to analyze a method allowing selection of the best morphometric criterion for quantifying AgNORs (Silver stained Nucleolar organizer Regions) under conventional observation conditions, by light microscopy.
Methods: The various parameters including NORs counting in cutaneous tumors using image analysis system were studied.
Results: There were significant differences in mean numbers of AgNORs per nucleus, mean ratio of AgNORs area per nucleus area, mean ratio of greatest AgNORs area per nucleus area, mean nucleus area per a AgNOR, and CV (Coefficient of Variation) of AgNORs area between basal cell carcinoma and seborrheic keratosis.
Conclusion: Study of AgNORs using the image analysis system is a useful tool for diagnosis of cutaneous tumors.     

Blue-white variant of pigmented basal cell carcinoma

Background

Basal cell carcinoma (BCC) is the most frequent of all skin cancers in the white population. The typical dermoscopic features of pigmented BCCs have been well known. In the literature a new dermoscopic pattern of BCC has been reported as “blue-white variant”.

Lack of selectivity of protoporphyrin IX fluorescence for basal cell carcinoma after topical application of 5-aminolevulinic acid: implications for photodynamic treatment

Clinical trials of topical ALA in photodynamic therapy (PDT) of basal cell carcinoma (BCC) show significant recurrence rates. Exogenous 5-aminolevulinic acid (ALA) is converted by intracellular enzymes to photoactive protoporphyrin IX (PpIX) in human tissues. PpIX generates cytotoxic singlet oxygen when irradiated with visible light in the 400–640 nm range. To evaluate variability and heterogeneity in PpIX production by tumors in such trials, and to assess the usefulness of PpIX for marking skin tumors, we measured PpIX fluorescence distribution in BCC after topical application of 20% ALA cream. ALA cream was applied under occlusion for periods ranging from 3 to 18 h (average 6.9 h, SD 4 h) to 16 BCCs. ALA conversion to PpIX in the BCCs was assessed by in vivo photography, ex vivo video fluorescence imaging, and fluorescence microscopy. External macroscopic PpIX fluorescence, as assessed by in vivo and ex vivo imaging, correlated with the clinical presence of BCC. Examination by a digital imaging fluorescence microscope revealed inter- and intratumor fluorescence variability and heterogeneity. PpIX fluorescence corresponding to full tomor thickness was found in six superficial and four nodular tumors, and partial-thickness fluorescence was observed in five nodular tumors, but no PpIX fluorescence was observed in some areas of superficial, nodular and infiltrating tumors. In a significant number of nodular and infiltrating BCCs, topical ALA appeared to provide little or no PpIX in deep tumor lobules. In addition, no selectivity for tumor tissue versus normal epidermis was seen. The grossly brighter external PpIX fluorescence over tumors may be due, therefore, to enhanced penetration through tumor-reactive stratum corneum and to the tumor thickness. The absence of reproducible fluorescence marking of nodular and infiltrating BCC suggests that topical ALA, at least under the present delivery protocols, may not be a reliable regimen for photodynamic treatment of these BCCs.     

Topical application of a first porphycene dye for photodynamic therapy – penetration studies in human perilesional skin and basal cell carcinoma

Photodynamic therapy (PDT) in dermatology has been proven to be a successful noninvasive therapeutic modality for treating skin cancer. To facilitate its clinical introduction, the development of topical photosensitizers is necessary to avoid generalized, cutaneous photosensitivity. Therefore the penetration of synthetic chemically pure 9-acetoxy-2,7,12,17-tetrakis-(β-methoxyethyl)-porphycene (ATMPn) into human skin was studied. Single specimens of freshly excised perilesional skin ( n = 70) and basal cell carcinomas ( n = 28) were evaluated after topical application of ethanolic ATMPn solutions (0.1% and 0.05%) for various times (2, 6, 16, 20 h). The penetration depth of ATMPn, recognized as red fluorescence in cryostat sections, was determined qualitatively by fluorescence imaging using a system of scoring related to the morphological structure of human skin (0 no fluorescence, 5 fluorescence deeper than basement membrane). Perilesional skin incubated for 2 or 6 h revealed fluorescence restricted to the upper parts of the epidermis, while after 16 or 20 h of incubation fluorescence was detected down to the basement membrane resulting in a significantly higher score (mean sum of scores : 2 h 2.6 ± 0.4; 6 h 3.2 ± 0.1; 16 h 3.8 ± 0.1; 20 h 3.6 ± 0.1). Quantitative evaluation by digital image analysis confirmed the qualitative results. Fluorescence was limited to the epidermis and the fluorescence intensity of the epidermis was higher after 16 h (4.9% of the fluorescence standard) than after 6 h (4.1%) incubation. Basal cell carcinomas showed fluorescence in the deep dermis as early as after 6 h incubation, but restricted to tumour cell nests. These results suggest that penetration of ATMPn into tumour tissue after topical application might be sufficient for topical PDT and that poor penetration into surrounding tissue might prevent scar formation following irradiation for PDT. The penetration characteristics of ATMPn now have to be proven in an in vivo setting. Received: 30 May 1996     

Photodynamic therapy of eyelid basal cell carcinoma

Background  Photodynamic therapy (PDT; i.e. selective destroying of malignant cells by exposing them to red light after photosensitization) has been increasingly used for non-melanoma skin cancers. Due to excellent cosmetic and functional results, especially in difficult-to-treat areas, it may offer a comprehensive alternative to previous treatment modalities.
Objective  A series of six patient cases was used to evaluate the efficacy of PDT in the treatment of lower eyelid basal cell carcinoma (BCC).
Methods  Histological confirmation of BCC, a detailed demonstration of the technique with an illustrative series of cases and a review of related literature.
Results  Six patients with lower eyelid BCC were treated with two treatment sessions of PDT within a week. Five patients had a nodular type and one patient had a superficial type of BCC. The follow-up after treatment continued for 20–36 (mean 26.5) months. No recurrences were observed during the follow-up. All the patients were satisfied with the good results and tolerated the treatment well without any harm to the eyeball or surrounding skin.
Conclusion  PDT, although experimental in the eyelid area because of the small amount of data and the lack of a long-term follow-up, may be considered a promising comprehensive alternative when treating BCC in the eyelid area.

Conflicts of interest

None declared     

Molecular aetiology and pathogenesis of basal cell carcinoma

Recent insights into the cell biology of the epidermis and its appendages are transforming our understanding of the pathogenesis of basal cell carcinoma (BCC). The significant progress that has been made warrants a comprehensive review of the molecular and cellular pathology of BCC. The items addressed include environmental and genetic risk factors, the biology of the putative precursor cell(s), and the contribution of aberrations in processes such as apoptosis, cell proliferation, differentiation and signalling to carcinogenesis. Furthermore, established and novel treatment modalities are discussed with particular attention to future biological approaches.