Cumulative risks and rates of subsequent basal cell carcinomas in the Netherlands

Background The incidence of multiple basal cell carcinomas (BCCs) is not well documented. Objectives To calculate the cumulative risks, rates and risk factors for the development of subsequent histologically confirmed BCCs. Methods For this cohort study the Dutch nationwide network and registry of histopathology and cytopathology (PALGA) was used. The first 2483 patients diagnosed with a first histologically confirmed BCC in the year 2004 were followed for 5 years. Multifailure survival models were used to study whether gender or age affected the risk of developing subsequent tumours. Results During our observational period, the 2483 patients developed a total of 3793 histologically confirmed BCCs. The 5‐year cumulative risk of developing one or more subsequent BCCs was 29·2%. Incidence rates were 25 318 per 100 000 person‐years in the first 6 months after first BCC diagnosis, decreasing to 6953 per 100 000 person‐years after 5 years of follow‐up. Males compared with females had a 30% [adjusted hazard ratio (HR) 1·30, 95% CI (confidence interval) 1·11–1·53] higher risk of developing multiple BCCs and those aged 65–79 years had more than 80% (adjusted HR 1·81, 95% CI 1·37–2·41) higher risk of having subsequent tumours compared with patients younger than 50 years. Conclusions The high incidence rate of subsequent BCCs among patients with a first BCC is highest in the first months after diagnosis of the first BCC but persists long term, indicating that patients with BCC should undergo full‐body skin examinations at first presentation and subsequent follow‐up visits. Special attention should be paid to males and persons of older age at index lesion.     

PTCH1 gene haplotype association with basal cell carcinoma after transplantation

Background Basal cell carcinoma (BCC) is 10 times more frequent in organ transplant recipients (OTRs) than in the general population. Factors in OTRs conferring increased susceptibility to BCC include ultraviolet radiation exposure, immunosuppression, viral infections such as human papillomavirus, phototype and genetic predisposition. The PTCH1 gene is a negative regulator of the hedgehog pathway, that provides mitogenic signals to basal cells in skin. PTCH1 gene mutations cause naevoid BCC syndrome, and contribute to the development of sporadic BCC and other types of cancers. Associations have been reported between PTCH1 polymorphisms and BCC susceptibility in nontransplanted individuals. Objectives To search for novel common polymorphisms in the proximal 5′ regulatory region upstream of PTCH1 gene exon 1B, and to investigate the possible association of PTCH1 polymorphisms and haplotypes with BCC risk after organ transplantation. Methods Three PTCH1 single nucleotide polymorphisms (rs2297086, rs2066836 and rs357564) were analysed by restriction fragment length polymorphism analysis in 161 northern Italian OTRs (56 BCC cases and 105 controls). Two regions of the PTCH1 gene promoter were screened by heteroduplex analysis in 30 cases and 30 controls. Results Single locus analysis showed no significant association. Haplotype T₁₆₈₆–T₃₉₄₄ appeared to confer a significantly higher risk for BCC development (odds ratio 2·98, 95% confidence interval 2·55–3·48; P = 0·001). Two novel rare polymorphisms were identified at positions 176 and 179 of the 5′UTR. Two novel alleles of the ‐4 (CGG)_n microsatellite were identified. No association of this microsatellite with BCC was observed. Conclusions Haplotypes containing T₁₆₈₆–T₃₉₄₄ alleles were shown to be associated with an increased BCC risk in our study population. These data appear to be of great interest for further investigations in a larger group of transplant individuals. Our results do not support the hypothesis that common polymorphisms in the proximal 5′ regulatory region of the PTCH1 gene could represent an important risk factor for BCC after organ transplantation.     

High discordance between punch biopsy and excision in establishing basal cell carcinoma subtype: analysis of 500 cases

Background Basal cell carcinoma (BCC) is the most frequently occurring cancer in humans. Worldwide incidences rise about 10% each year, increasing the burden on dermatologists, general practitioners and pathologists as well as increasing costs for the health care system. Increasingly non‐surgical treatment options are used in the treatment of BCC, without histological confirmation of BCC subtype, potentially resulting in under‐treatment. Objective We evaluated the diagnostic accuracy of a punch biopsy for the BCC histological subytpe in a primary BCC and the prevalence of biopsy‐based under‐diagnosis of aggressive subtypes. Accuracy of a punch biopsy was defined as concordance of the diagnosis of subtype of BCC at punch biopsy and excision. Methods A retrospective chart‐review was performed of primary BCC, which were proven by punch biopsy and subsequently treated by excision. The first 100 consecutive BCCs per year during the years 2004–2009 were included, yielding a total of 500 evaluated BCCs. Results The overall accuracy of punch biopsy for BCC subtype at excision was 69%, in single‐type BCC 83% (n = 343) and in mixed‐type BCC 37% (n = 157). Accuracy varied substantially according to BCC subtype, being highest in the superficial subtype (84%) and subsequently in infiltrative (69%), nodular (63%) and micronodular subtype (38%). In 11% of all cases, an unsuspected more aggressive subtype was present. Conclusion Punch biopsy has a high accuracy in single‐type BCCs and a considerably lower accuracy in mixed‐type BCCs for establishing BCC subtype compared to excision. The presence of an unsuspected aggressive subtype could explain therapy failure of non‐surgical treatments like imiquimod or photodynamic therapy.     

No association of vitamin D metabolism-related polymorphisms and melanoma risk as well as melanoma prognosis: a case–control study

Melanoma is one of the most aggressive human cancers. The vitamin D system contributes to the pathogenesis and prognosis of malignancies including cutaneous melanoma. An expression of the vitamin D receptor (VDR) and an anti-proliferative effect of vitamin D in melanocytes and melanoma cells have been shown in vitro. Studies examining associations of polymorphisms in genes coding for vitamin D metabolism-related proteins (1α-hydroxylase [CYP27B1], 1,25(OH)(2)D-24hydroxylase [CYP24A1], vitamin D-binding protein [VDBP]) and cancer risk are scarce, especially with respect to melanoma. Mainly VDR polymorphisms regarding melanoma risk and prognosis were examined although other vitamin D metabolism-related genes may also be crucial. In our hospital-based case-control study including 305 melanoma patients and 370 healthy controls single nucleotide polymorphisms in the genes CYP27B1 (rs4646536), CYP24A1 (rs927650), VDBP (rs1155563, rs7041), and VDR (rs757343, rs731236, rs2107301, rs7975232) were analyzed for their association with melanoma risk and prognosis. Except VDR rs731236 and VDR rs2107301, the other six polymorphisms have not been analyzed regarding melanoma before. To further improve the prevention as well as the treatment of melanoma, it is important to identify further genetic markers for melanoma risk as well as prognosis in addition to the crude phenotypic, demographic, and environmental markers used in the clinic today. A panel of genetic risk markers could help to better identify individuals at risk for melanoma development or worse prognosis. We, however, found that none of the polymorphisms tested was associated with melanoma risk as well as prognosis in logistic and linear regression models in our study population.     

Basal cell nevus syndrome: clinical and molecular review and case report

Basal cell nevus syndrome (BCNS), also referred to as nevoid basal cell carcinoma syndrome or Gorlin–Goltz syndrome, was first described by Gorlin and Goltz in 1960 as an autosomal dominant disorder characterized by the early appearance of multiple basal cell carcinomas (BCCs), keratocysts of the jaw, ectopic calcifications, palmar and plantar pits, and anomalies of the ocular, skeletal, and reproductive systems. The genesis of this cancer's etiology in relation to BCNS was unclear until a few years ago when molecular analysis studies suggested a relationship between BCC and the loss‐of‐function mutations of the patched gene (PTCH) found on chromosome arm 9q. PTCH inhibits signaling by the membrane protein Smoothened (Smo), and this inhibition is relieved by binding sonic hedgehog (SHH) to PTCH. We describe a patient with multiple BCCs associated with x‐ray anomalies of BCNS and review the basis of the SHH signaling pathway and clinical aspects of BCNS.     

Margin involvement and clinical pattern of basal cell carcinoma with mixed histology

Background Mixed basal cell carcinoma (BCC) has not been sufficiently and specifically studied. Objective The aim of this study was to estimate in adults the prevalence of mixed cases observed among primary BCCs and to compare clinical and anatomical features of mixed vs. single BCCs, with focus on the incomplete excision. Patients and methods A total of 3636 histologically confirmed primary BCCs were examined. Data on gender, age, histological subtype, anatomical location and margin involvement were collected. Mixed type was defined as a combination of two or more single subtypes. Results Prevalence of single and mixed BCCs was 82.2% and 17.8% respectively. Prevalence of BCCs on the upper limbs was higher in mixed than single cases (8.8% vs. 4.0%; P < 0.001) while prevalence on the back was lower (16.9% vs. 23.7%; P < 0.001). Tumour was aggressive in 59.1% of mixed vs. 16.0% of single BCCs (P < 0.001). Margin involvement was more prevalent in mixed than in single BCCs (16.7% vs. 9.6%; P < 0.0001). At multivariate analysis being mixed vs. single BCC was associated with aggressiveness of tumour (OR = 8.5, 95% CI, 6.9–10.4), lateral margin involvement (OR = 1.98, 95% CI, 1.42–2.76) and subject being man (OR = 1.31, 95% CI, 1.10–1.60) but not with deep involvement of margin or anatomical location. Conclusion Among BCCs, the mixed type may be observed in adults with relatively high rate and may represent a complex and individual subset of BCCs with potential aggressive behaviour.     

Preliminary evidence of an association of tumour necrosis factor microsatellites with increased risk of multiple basal cell carcinomas

Tumour necrosis factor alpha (TNF-alpha) appears important in ultraviolet-induced immunosuppression, suggesting that it is a susceptibility candidate for cutaneous basal cell carcinoma (BCC). We now describe data on the association between TNF microsatellite polymorphisms, first on susceptibility in 202 controls and 133 cases each having two to 30 BCCs, and secondly, within the cases, on BCC numbers. The data show that the proportions of individuals with TNF a1- and a7-containing genotypes were significantly different (P = 0. 0271, P = 0.0393, respectively) between cases and controls. Secondly, within the cases, TNF alleles d4 (P = 0.023) and d6 (P = 0.006) alone, and the TNF a2-b4-d5 haplotype (P = 0.007), were significantly associated with the number of BCC lesions. These preliminary data provide the first evidence that TNF microsatellite polymorphism may influence the pathogenesis of multiple BCC.     

Association of UVRAG polymorphisms with susceptibility to non‐segmental vitiligo in a Korean sample

Please cite this paper as: Association of UVRAG polymorphisms with susceptibility to non‐segmental vitiligo in a Korean sample. Experimental Dermatology 2010; 19 : e323–e325. Abstract: Autoimmune, self‐destructive, oxidative stress and genetic theories have been proposed for the pathogenesis of vitiligo. Autophagy is essential for cellular homeostasis and is implicated in many pathophysiological conditions such as cancer, response to oxidative stress and autoimmunity. The ultraviolet (UV) radiation resistance‐associated gene (UVRAG) activates the Beclin1‐PI(3)KC3 complex, promoting autophagy. To evaluate whether UVRAG polymorphisms are associated with non‐segmental vitiligo (NSV) patients in a Korean sample, we conducted a case–control association study of 225 NSV patients and 439 matched healthy controls. A total of five single nucleotide polymorphisms (SNPs) of UVRAG were selected for analysis. Among these, two SNPs (rs1458836, rs7933235) showed significant genotypic differences between the NSV patient group and the control group. These two SNPs were located within a strong linkage disequilibrium (LD) block. In addition, the haplotype of the UVRAG polymorphism was associated with NSV. This study suggests a possible association between UVRAG and NSV susceptibility.     

Frequency of non‐histologically diagnosed basal cell carcinomas in daily Dutch practice

Background Population‐based basal cell carcinoma (BCC) incidences are based on cancer registry data; however, these only include histologically diagnosed tumours. Objectives First, to investigate the number of subsequent non‐histologically diagnosed BCC(s) in patients with a first histologically diagnosed BCC in 2004. Secondly, to observe differences in tumour characteristics between subsequent histologically and subsequent non‐histologically diagnosed BCC(s). Methods All patients, from four hospitals located in the serving area of the Eindhoven Cancer Registry, with a first histologically diagnosed BCC in 2004 (n = 1290) were selected. A linkage was made with PALGA, the nationwide network and registry of histo‐ and cytopathology, to obtain pathology reports of subsequent histologically diagnosed BCC(s) up to 1 November 2010. Patient records were extracted from the participating dermatology departments and reviewed up to 1 November 2010 to identify non‐histologically diagnosed BCC(s). Results Overall, 33.2% of the 1089 followed up patients developed subsequent histologically and/or non‐histologically diagnosed BCCs. In total, 1974 BCCs were observed of which 1833 were histologically and 141 were non‐histologically diagnosed BCCs. The distribution of tumour site and subtype differed significantly between subsequent histologically and subsequent non‐histologically diagnosed BCCs. Conclusions The total burden of BCC is underestimated by the absence of data on the occurrence of non‐histologically diagnosed BCCs in daily dermatological practice. It is pivotal for Dutch healthcare policy makers to acknowledge this to make accurate BCC‐related cost estimates.     

PTCH promoter methylation at low level in sporadic basal cell carcinoma analysed by three different approaches

Please cite this paper as: PTCH promoter methylation at low level in sporadic basal cell carcinoma analysed by three different approaches. Experimental Dermatology 2010. Abstract: Basal cell carcinoma (BCC) is the most common form of skin cancer. Mutations of the PTCH hallmark gene are detected in about 50–60% of BCCs, which raises the question whether other mechanisms such as promoter methylation can inactivate PTCH. Therefore, we performed methylation analysis of the PTCH promoter in a total of 56 BCCs. The sensitivity of three different methods, including direct bisulphite sequencing PCR, MethyLight and high‐resolution melting (HRM), was applied and compared. We found that HRM analysis of DNA from fresh tissue [rather than formalin‐fixed and paraffin‐embedded tissue (FFPE)] was the most sensitive method to detect methylation. Low‐level methylation of the PTCH promoter was detected in five out of 16 analysed BCCs (31%) on DNA from fresh tissue but only in two (13%) samples on short‐time stored FFPE DNA from the very same tumors. In contrast, we were unable to detect methylation by HRM on long‐time stored DNA in any of the remaining 40 BCC samples. Our data suggest that (i) HRM on DNA extracted from fresh tissue is the most sensitive method to detect methylation and (ii) methylation of the PTCH promoter may only play a minor role in BCC carcinogenesis.     

Melanocytic naevi and basal cell carcinoma: is there an association?

Background Melanoma and basal cell carcinoma (BCC) affect similar body sites and share a complex relationship with sun exposure. Objective To establish the existence and magnitude of association between melanocytic naevi, the strongest predictors of melanoma, and BCC to give possible insights into shared pathways of solar ultraviolet tumourigenesis. Methods In a community‐based longitudinal Australian study, detailed information was collected about sun sensitivity, and dermatologists assessed skin colour and counted naevi on the forearms (1986) and back (1992). The BCC frequency and sites were prospectively monitored until 2007. Multivariate logistic regression was used to assess the association of naevi on the forearms or on the back with the development of BCC, adjusting for other risk factors. Results Of 1621 study participants in 1992, 1339 (average age 49) had complete follow‐up and 401 (30%) of these had 1202 histologically confirmed BCCs until 2007. After adjustment for age, gender, skin colour, naevi on the back and sun exposure, overall BCC risk increased significantly in those with forearm naevi (odds ratio: 1.5; 95% confidence intervals: 1.1–1.9). Risk of BCC specifically on the back was doubled in those with many (11 or more) forearm naevi compared with no forearm naevi (odds ratio: 2.4; 95% confidence interval: 1.1–4.8). Naevi on the back were not associated with subsequent basal cell carcinoma. Conclusions High naevus prevalence on the arms is associated with future BCC development.     

Association of ITGAM polymorphism with systemic lupus erythematosus: a meta‐analysis

Background ITGAM is one of the major non‐human leucocyte antigen that has been implicated in the pathogenesis of systemic lupus erythematosus (SLE). The association of ITGAM polymorphism with SLE has been reported in several studies, but with inconclusive results. Objectives The aim of this study was to assess whether combined evidence shows the association between ITGAM polymorphism and SLE. Methods A meta‐analysis was performed to survey studies on the ITGAM polymorphism and SLE using comprehensive Medline search and review of the references. A total of five published studies including 12 123 patients with SLE and 17 016 controls were involved. Meta‐odds ratios (ORs) and 95% confidence intervals (CIs) based on fixed effects models or random effects models were depended on Cochran’s Q‐statistic and I² values. Results The overall ORs for the minor A‐allele (OR 1.795; 95%CI 1.676–1.921), AA vs. GG (OR 3.540; 95%CI 2.771–4.522), AG vs. GG (OR 1.750; 95%CI 1.617–1.895), dominant model (OR 1.857;95%CI 1.719–2.005), recessive model (OR 3.041; 95%CI 2.384–3.878) of ITGAM rs1143679 were significantly increased in SLE and fixed effects models were conducted. All controls were in Hardy–Weinberg (HW) proportion. Although this meta‐analysis showed significant association of rs1143683 (A vs. G, OR 1.534;95%CI 1.312–1.792), rs9888739 (T vs. C,OR 1.627;95%CI 1.380–1.918), rs1143678 (T vs. C, OR 1.543; 95%CI 1.330–1.790), rs9937837 (A vs. G, OR 0.466; 95%CI 0.227–0.957) with SLE; all of these were conducted in random effects model as heterogeneity was detected. No significant association was detected in the analysis between rs11574637 and SLE. No publication bias was presented. Conclusions This meta‐analysis demonstrates a significant association between ITGAM gene polymorphism and SLE in multiple ethnic populations.     

Increased immunoreactivity of membrane type-1 matrix metalloproteinase (MT1-MMP) and β-catenin in high-risk basal cell carcinoma

Background Although various immunohistological markers have been investigated to assess the aggressive characteristics of basal cell carcinoma (BCC), the role of membrane type‐1 matrix metalloproteinase (MT1‐MMP) has not been well established. Objectives To clarify the precise role of MT1‐MMP in BCC, MT1‐MMP expression was studied in various histological subtypes of BCC. Materials and methods High‐risk subtypes of BCC were compared by assessing the expression of β‐catenin and MT1‐MMP. The tissue microarray technique was used for immunohistochemical staining. Fifty‐eight samples were divided into six subtypes (10 nodular, 12 mixed, nine infiltrative, eight morphoeiform, 10 micro‐nodular and nine basosquamous). Overall, the 10 nodular BCC samples were classified as low‐risk BCC and the remaining 48 samples were classified as high‐risk BCCs. Results β‐Catenin immunoreactivity was increased in the high‐risk BCCs compared with the low‐risk (nodular) BCC (P < 0·001). Nuclear β‐catenin immunoreactivity was increased at the invading front of mixed BCC tumour islands compared with the upper portion of the lesion (P < 0·01). For the mixed BCC (P < 0·01), infiltrative BCC (P < 0·001), morphoeiform BCC (P < 0·001), micronodular BCC (P < 0·001) and basosquamous (P < 0·001) carcinoma, β‐catenin immunoreactivity was increased at the invading front compared with nodular BCC. MT1‐MMP immunoreactivity was increased in the high‐risk BCCs compared with the low‐risk (nodular) BCC (P < 0·01). The membranous MT1‐MMP immunoreactivity was increased at the invading front of mixed BCC tumour islands compared with the upper portion of the lesions (P < 0·01). For the mixed (P < 0·01), infiltrative (P < 0·05), morphoeiform (P < 0·05), micronodular (P > 0·05) and basosquamous (P < 0·05) BCC, MT1‐MMP immunoreactivity was also increased at the invading front compared with nodular BCC. Conclusions The results of this study suggest that MT1‐MMP might be a novel marker for high‐risk BCC. In addition, expression of both β‐catenin and MT1‐MMP was increased in high‐risk BCC tumour cells, indicating that these two proteins may play an important role in locally invasive and highly destructive growth behaviour of high‐risk BCCs.     

Epidemiology of basal cell carcinoma: scholarly review

Basal cell carcinoma (BCC) is the most common cancer in white‐skinned individuals with increasing incidence rates worldwide. Patients with BCC place a large burden on healthcare systems, because of the high incidence and the increased risk of synchronous and metachronous BCCs and other ultraviolet radiation (UVR) related skin cancers (i.e. field cancerization). As a result, the disability‐adjusted life years and healthcare costs have risen significantly in recent decades. BCC is a complex disease, in which the interplay between UVR, phenotype (UVR‐sensitive) and genotype (somatic mutations and germline mutations/polymorphisms) fulfils a key role in the aetiopathogenesis. Prevention programmes with continual refinements and improvements could be of major importance in tackling the growing skin cancer problem. To provide the most appropriate BCC care, physicians should engage in shared decision‐making and choose their treatments wisely.     

Basal cell carcinoma in a series of renal transplant recipients: epidemiology and clinicopathologic features

Background Basal cell carcinoma (BCC) is the most common malignancy among Caucasians worldwide. The risk of BCC is 10–16 times higher among immunosuppressed transplant recipients compared with the general population. Objective To analyze the incidence, clinical presentation, histologic features, treatment and recurrence rate of BCC in a cohort of 69 renal transplant recipients (RTRs; 53 male). Methods Retrospective population‐based cohort study of immunosuppressed RTRs. Results Ten of 69 patients (14.5%, five male) developed a total of 17 BCCs, mostly on the head. Mean age at first diagnosis of BCC was 65.5 ± 8.5 years, and latency between kidney transplantation and diagnosis of the first BCC was 11.1 ± 6.3 years (mean ± SD). The risk of female RTRs to develop BCCs appeared to be three times higher than the risk of male RTRs, and female RTRs developed BCCs earlier after transplantation. Nodular BCC was the most common histologic subtype. Most BCCs in these RTRs were treated by complete surgical excision. Recurrence after surgical excision was observed in one of the 10 patients (10%). Conclusion Our results suggest female RTRs to be at higher risk to develop cutaneous BCCs than male RTRs. There are no differences in localization and clinicopathologic presentation of BCCs developing in RTRs compared with immunocompetent patients. Therefore, BCCs in RTRs do not require different treatment than in other patient groups. As patients tend to develop a second BCC, close follow‐up is mandatory.     

An enhanced risk of basal cell carcinoma is associated with particular polymorphisms in the VDR and MTHFR genes

Background: Vitamin D and folate are influenced by ultraviolet radiation (UVR), and both are implicated in skin carcinogenesis. Polymorphisms in the genes involved in the metabolism of these two compounds may alter the risk of basal cell carcinoma (BCC). Objective: To assess the frequency of four polymorphisms in the gene encoding the vitamin D receptor (VDR) (FokI, BsmI, TaqI and ApaI) and two in the gene encoding methylenetetrahydrofolate reductase (MTHFR) (677C/T and 1286A/C) in 142 patients of Polish origin with BCC and the same number of controls. The expression of VDR and MTHFR proteins in the skin, and the vitamin D status of a subset of patients and controls were also measured. Patients/Methods: The polymorphisms were assayed by PCR‐RFLP, the VDR and MTHFR proteins by immunoblotting and vitamin D status as 25‐hydroxyvitamin D (25(OH)D) level in the serum by RIA. Results: The presence of the TT genotype in the FokI VDR polymorphism resulted in a >10‐fold higher risk of BCC development. The CT genotype in 677C/T MTHFR polymorphism and CC genotype in 1286A/C MTHFR polymorphism also significantly increased the risk of BCC development. The expression of the VDR and MTHFR proteins was significantly higher in BCCs of the patients than in the healthy skin of the controls. The median serum level of 25(OH)D was significantly higher in the control group compared with the patients with BCC. Conclusions: Certain VDR and MTHFR gene polymorphisms increase the risk of BCC development in individuals of Polish origin.     

Segmental basal cell naevus syndrome caused by an activating mutation in smoothened

Aberrant sonic hedgehog signalling, mostly due to PTCH1 mutations, has been shown to play a central role in the pathogenesis of basal cell carcinoma (BCC), as well as in basal cell naevus syndrome (BCNS). Mutations in smoothened (SMO) encoding a receptor for sonic hedgehog have been reported in sporadic BCCs but not in BCNS. We report a case with multiple BCCs, pits and comedones in a segmental distribution over the upper part of the body, along with other findings compatible with BCNS. Histopathologically, there were different types of BCC. A heterozygous mutation (c.1234C>T, p.L412F) in SMO was detected in three BCCs but not in peripheral blood lymphocytes or the uninvolved skin. These were compatible with the type 1 mosaic form of BCNS. The p.L412F mutation was found experimentally to result in increased SMO transactivating activity, and the patient responded to vismodegib therapy. Activating mutations in SMO may cause BCNS. The identification of a gain‐of‐function mutation in SMO causing a type 1 mosaic form of BCNS further expands our understanding of the pathogenesis of BCC, with implications for the treatment of these tumours, whether sporadic or inherited.     

Reflectance confocal microscopy allows in vivo real‐time noninvasive assessment of the outcome of methyl aminolaevulinate photodynamic therapy of basal cell carcinoma

Background Photodynamic therapy (PDT) with methyl aminolaevulinate (MAL) is an approved noninvasive treatment option for basal cell carcinoma (BCC). In vivo reflectance confocal microscopy (RCM) is a noninvasive imaging technique that has proved useful for in vivo real‐time cytomorphological analysis of BCC cells infiltrating the epidermis. Objectives To investigate the use of in vivo RCM to assess the persistence of BCC cells surviving MAL‐PDT. Methods In vivo RCM images of 20 biopsy‐proven BCCs were taken before patients underwent a treatment cycle with MAL‐PDT. Follow‐up after 3 months was performed using clinical examination, RCM and conventional dermoscopy. Treated areas also underwent a targeted 3‐mm punch biopsy for standard haematoxylin and eosin histology stain to establish the clinical and instrumental correlation of the treatment outcome. Results Three months after PDT, clinical examination established that two out of 20 BCCs were persistent; dermoscopy found three out of 20 residual BCCs, but RCM showed that one of these lesions was a false positive, and showed persistent BCC foci in five out of 20 lesions. Histological analysis of targeted biopsies confirmed these results. Conclusions RCM provided noninvasive, early detection of incipient recurrences of BCC after MAL‐PDT. RCM findings steered targeted biopsies and surgical removal, or a new MAL‐PDT, of these subclinical recurrences with minimal invasiveness.