Residual Basal Cell Carcinoma Research Articles

Diagnostic accuracy of autofluorescence-Raman spectroscopy for surgical margin assessment during Mohs micrographic surgery of basal cell carcinoma.

Autofluorescence (AF) - Raman spectroscopy is a technology that can detect residual basal cell carcinoma (BCC) on the resection margin of fresh surgically excised tissue specimens. The technology does not require tissue fixation, staining, labelling, or sectioning, and provides quantitative diagnosis maps of the surgical margins in 30 minutes. To determine the accuracy of the AF-Raman instrument to detect incomplete excisions of BCC during Mohs micrographic surgery, using histology as reference standard. Skin layers from 130 patients undergoing Mohs surgery at the Nottingham University Hospitals NHS Trust (September 2022 to July 2023) were investigated with the AF-Raman instrument. The layers were measured fresh, immediately after excision. The AF-Raman results and the intra-operative assessment by Mohs surgeons were compared to a post-operative consensus-derived reference produced by three dermatopathologists. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated. The AF-Raman analysis was successfully completed for 125 out of the 130 layers. The AF-Raman analysis covered 91% of the specimen surface area on average, with the lowest being 87% for eyelid and the highest being 94% for forehead specimens. The AF-Raman instrument identified positive margins in 24 out of 36 BCC-positive cases, resulting in a 67% sensitivity (95% confidence intervals (CI): 49%-82%) and negative margins in 65 out of 89 BCC-negative cases, resulting in a 73% specificity (95% CI 63%-82%). Only one out of the 12 false negative cases was caused by misclassification by the AF-Raman algorithm. The other 11 false negatives cases were produced because no valid Raman signal was recorded at the location of the residual BCC due to either occlusion by blood or poor contact between tissue and cassette window. The intra-operative diagnosis by Mohs surgeons identified positive margins in 31 out of 36 BCC-positive cases, 86% sensitivity (95% CI: 70%-95%), and negative margins in 79 out of 89 BCC-negative cases, 89% specificity (95% CI: 81%-95%). This study shows that the AF-Raman instrument has potential for intra-operative microscopic assessment of surgical margins in surgery of BCC. Further improvements are required for tissue processing to ensure complete coverage of the surgical specimens. ClinicalTrials.gov ID NCT03482622.

Using optical coherence tomography to optimize Mohs micrographic surgery

Mohs micrographic surgery (MMS) is considered the gold standard for treating high-risk cutaneous basal cell carcinoma (BCC), but is expensive, time-consuming, and can be unpredictable as to how many stages will be required or how large the final lesion and corresponding surgical defect will be. This study is meant to investigate whether optical coherence tomography (OCT), a highly researched modality in dermatology, can be used preoperatively to map out the borders of BCC, resulting in fewer stages of MMS or a smaller final defect. In this prospective study, 22 patients with BCC undergoing surgical excision were enrolled at a single institution. All patients had previously received a diagnostic biopsy providing confirmation of BCC and had been referred to our center for excision with MMS. Immediately prior to performing MMS, OCT was used to map the borders of the lesion. MMS then proceeded according to standard protocol. OCT images were compared to histopathology for agreement. Histopathologic analysis of 7 of 22 MMS specimens (32%) revealed a total absence of BCC, indicating resolution of BCC after previous diagnostic biopsy. This outcome was correctly predicted by OCT imaging in 6 of 7 cases (86%). Nine tumors (9/22, 41%) had true BCC and required a single MMS stage, which was successfully predicted by pre-operative OCT analysis in 7 of 9 cases (78%). The final six tumors (27%) had true BCC and required two MMS stages for complete excision; preoperative OCT successfully predicted the need for a second stage in five cases (5/6, 83.3%). Overall, OCT diagnosed BCC with 95.5% accuracy (Cohen’s kappa, κ = 0.89 (p-value = < 0.01) in the center of the lesion. Following a diagnostic biopsy, OCT can be used to verify the existence or absence of residual basal cell carcinoma. When residual tumor is present that requires excision with MMS, OCT can be used to predict tumor borders, optimize surgery and minimize the need for additional surgical stages.

Ex vivo assessment of basal cell carcinoma surgical margins in Mohs surgery by autofluorescence‐Raman spectroscopy: A pilot study

AbstractBackgroundAutofluorescence (AF)‐Raman spectroscopy is a technology that can detect tumour tissue in surgically excised skin specimens. The technique does not require tissue fixation, staining, labelling or sectioning, and provides quantitative diagnosis maps within 30 min.ObjectivesTo explore the clinical application of AF‐Raman microscopy to detect residual basal cell carcinoma (BCC) positive margins in ex vivo skin specimens excised during real‐time Mohs surgery. To investigate the ability to analyse skin specimens from different parts of the head‐and‐neck areas and detect nodular, infiltrative and superficial BCC.MethodsFifty Mohs tissue layers (50 patients) were investigated: 27 split samples (two halves) and 23 full‐face samples. The AF‐Raman results were compared to frozen section histology, carried out intraoperatively by the Mohs surgeon and postoperatively by dermatopathologists. The latter was used as the standard of reference.ResultsThe AF‐Raman analysis was completed within the target time of 30 min and was able to detect all subtypes of BCC. For the split specimens, the AF‐Raman analysis covered 97% of the specimen surface area and detected eight out of nine BCC positive layers (similar to Mohs surgeons). For the full‐face specimens, poorer contact between tissue and cassette coverslip led to lower coverage of the specimen surface area (92%), decreasing the detection rate (four out of six positives for BCC).ConclusionsThese preliminary results, in particular for the split specimens, demonstrate the feasibility of AF‐Raman microscopy for rapid assessment of Mohs layers for BCC presence. However, for full‐face specimens, further work is required to improve the contact between the tissue and the coverslip to increase sensitivity.

Optical coherence tomography for diagnosing recurrent or residual basal cell carcinoma after topical treatment: A diagnostic cohort study

Recurrent/residual basal cell carcinoma (BCC) after topical treatment may not be visible during clinical and dermatoscopic examination (CDE). Optical coherence tomography (OCT) may detect these subclinical recurrences or residues. To compare the diagnostic accuracy of CDE with that of CDE combined with OCT (CDE-OCT) for detecting recurrent/residual BCC after topical treatment of superficial BCC. In this diagnostic cohort study, the suspicion level for recurrence or residue was recorded on a 5-point confidence scale. All patients with high suspicion of recurrence or residue based on CDE and/or CDE-OCT were referred for punch biopsy. Patients with a low suspicion on CDE and CDE-OCT were asked to (voluntarily) undergo a control biopsy. Histopathologic results of the biopsy were used for verification of CDE and CDE-OCT diagnoses (gold standard). This study included 100 patients. A histopathologic recurrent/residual BCC was found in 20 patients. For recurrence or residue detection, sensitivity was 100% (20 of 20) for CDE-OCT and 60% (12 of 20) for CDE (P=.005) and specificity was 95% for CDE-OCT and 96.3% for CDE (P=.317). The area under the curve for CDE-OCT (0.98) was significantly higher than that for CDE (0.77) (P=.001). Results are based on 2 OCT assessors. Compared with CDE alone, CDE-OCT results in a significantly higher ability to detect recurrent/residual BCCs after topical treatment.

Intralesional Treatment of Basal Cell Carcinoma in a Genetically Inducible Mouse Model

Introduction: Patients with nevoid basal cell carcinoma syndrome (NBCCS), also termed Gorlin syndrome, develop numerous basal cell carcinomas (BCCs). Current treatment options include systemic hedgehog pathway inhibitors, with significant side effects when used long term, and multiple surgeries with the risk of scarring and sometimes even disfigurement over the long term. We have developed an intralesional treatment for BCC based on the intracellular delivery of an antisense oligonucleotide (ASO) targeting Gli1, the main protein active in the hedgehog pathway responsible for BCC. To test the efficacy of our treatment, we developed an inducible NBCCS-like mouse model, genetically modified at the level of the expression of the Ptch1 and p53 genes in the skin.&#x0D; Methods: The inducible mouse model uses Ptch1- and P53-knockdown mice irradiated with UVB three times a week until BCCs appear. These BCCs were treated once or twice a week with injections of an antisense oligonucleotide (ASO) targeting the production of the Gli1 protein, with and without the use of a peptide (the “Feldan shuttle") designed to introduce the ASO into the tumor cells. The evolution of the tumors was monitored several times a week with caliper measurements and photography. Following the treatments, the tumor site tissue was harvested and analyzed by both routine (H&amp;E) and specialized (IHC, IF) histologic methods .&#x0D; Results: Intralesional treatment of BCCs in the inducible mouse model using the ASO and peptide combination (FLD103) resulted in rapid and marked tumor regression, and sometimes complete eradication, over a few weeks. In addition, healthy perilesional skin appeared unaffected by the treatment, demonstrating targeted treatment specificity. The healed skin appeared grossly normal. Histologic examination of the treated sites after recovery showed no residual BCC as well as complete healing of the epidermis, dermis and subcutaneous tissue. We also observed that intralesional treatment with the ASO alone is not associated with tumor regression and in fact permits continued tumor growth.&#x0D; Conclusion: We have demonstrated the utility of a specific intralesional treatment for BCC in a genetically inducible mouse model. This alternative and novel treatment produces rapid results with normal healing of the treated site. This treatment could offer an attractive option for patients with multiple BCCs who wish to avoid systemic treatments or multiple surgeries.

34785 Epidermal reconstruction during ex vivo confocal microscopy for detection of superficial basal cell carcinoma with 3D-mosaicking and intensity projection

Background: Ex vivo confocal microscopy (EVCM) rapidly images fresh tissues to create digitally colorized H&E-images. It has a high sensitivity (79.8%-100%) and specificity (78%-100%) for the detection of residual basal cell carcinoma (BCC) during Mohs surgery. However, with current tissue mounting techniques, tissue flattening affects the visualization of the entire epidermis, impacting detection of superficial BCC (sBCC).

Superficial basal cell carcinoma, think deeper: Step sectioning of skin biopsy specimens yields 14% more aggressive subtypes.

IntroductionBecause of different therapeutic regimens for superficial and non-superficial basal cell carcinomas (BCCs), accurate histopathological examination of a punch biopsy to determine its subtype is essential. The aim of the current study was to evaluate the additional yield of a more extensive step-section method to that of a standard histologic examination at 4 levels.Material and methodsData for this prospective study was obtained from the Pathology department of a Dutch tertiary hospital. Biopsy specimens of subsequent patients from March 2019 to June 2020 were sectioned to 8-levels instead of the regular 4-levels. Only patients with a superficial BCC subtype in the first 4-levels of sectioning were included (n = 100). After 8-level sectioning, it was recorded in which level (5–8) a more aggressive BCC component was found (i.e. nodular, infiltrative, or micronodular). Patients were followed-up to evaluate further treatment, and in case of excision, the excision specimen was reviewed to determine the BCC subtype. A logistic regression was performed to assess characteristics associated with a more aggressive BCC component in levels 5–8.ResultsIn 14 patients (14%) a more aggressive component was found in levels 5–8, all with a nodular component. Thirteen of these patients underwent excision, confirming a more aggressive BCC subtype. Of the 86 patients that had no deeper BCC component in levels 5–8, 26 (30.2%) underwent excision; In 4 patients no residual BCC was found, in 15 patients superficial BCC, and in 7 a more aggressive BCC subtype (1 nodular and 6 a combination of superficial/nodular/infiltrative). In multivariable analysis, head&neck localization was associated with finding a more aggressive BCC subtype in levels 5–8 (OR 6.41 (95%CI 1.56–26.30), p = 0.01)).ConclusionsMore extensive sectioning of superficial BCC biopsy specimens, especially in the head&neck area, leads to a more accurate BCC subtype diagnosis requiring different clinical management strategies.

Line-Field Confocal Optical Coherence Tomography May Enhance Monitoring of Superficial Basal Cell Carcinoma Treated with Imiquimod 5% Cream: A Pilot Study.

Simple SummaryLine-field confocal optical coherence tomography (LC-OCT) is a new non-invasive technique that allows the visualization of the epidermis and dermis and their different structures and findings at the cellular level, providing a sort of “virtual biopsy”. The interest of using LC-OCT in the diagnosis of skin disorders is growing. The purpose of this study was to investigate if LC-OCT may be useful to enhance the monitoring of superficial basal cell carcinoma (BCC) in a series of patients treated with IQ 5% cream, an immune response modifier currently approved in Europe and the USA. In our experience, LC-OCT was able to show sub-clinical signs of BCC after treatment, leading to a further cycle of IQ 5% cream. Based on our preliminary results, LC-OCT may represent a promising tool able to enhance the evaluation of the treatment response of BCCs to non-surgical treatments.Line-field confocal optical coherence tomography (LC-OCT) is a novel, non-invasive technique for real-time skin imaging. Imiquimod (IQ) 5% cream is an immune response modifier currently approved for the treatment of small, superficial basal cell carcinoma (BCC). The aim of this study was to investigate if LC-OCT may be useful to enhance the treatment monitoring of BCC. Twenty superficial BCCs from 12 patients were treated with IQ 5% cream once daily, five days a week, for six weeks. Clinical and LC-OCT evaluations were performed at baseline and 4 weeks after the end of treatment. At the end of the study, 13 lesions showed a complete clinical and LC-OCT response, 4 lesions a partial clinical and LC-OCT response, and 3 lesions a complete clinical response but residual tumoral signs at LC-OCT. Our pilot study suggests that LC-OCT may represent a promising tool able to enhance the evaluation of the treatment response of BCCs to non-invasive treatments. In our case series, its use highlighted, through a detailed, fast, and complete examination of the treated area, three cases of residual BCC that otherwise would have gone undetected at clinical examination. Future studies on larger series of patients treated with different modalities and with a longer follow-up are advisable.

Characteristics of Superficial Basal Cell Carcinomas Containing More Aggressive Subtypes on Final Histopathologic Diagnosis.

The prognosis and treatment of basal cell carcinoma (BCC) are largely dependent on tumor subtype, which is typically determined by punch or shave biopsy. Data regarding concordance between BCC subtype on initial biopsy and final histopathology for Mohs micrographic surgery (MMS) or excision with frozen sections (EFS) are limited. To determine the concordance between initial biopsy and final MMS or EFS subtyping of BCC. We aim to investigate the incidence and clinical characteristics of lesions initially diagnosed as superficial BCC (sBCC) that are later found to have a nodular, micronodular, or infiltrative component. We conducted a retrospective review of all MMS or EFS cases performed at a single academic center from August 1, 2015 to August 31, 2017. Inclusion criteria were a biopsy-proven diagnosis of sBCC and presence of residual tumor following stage I of MMS or EFS. Fisher&rsquo;s exact test was used to evaluate significance of clinical characteristics and outcomes associated with the presence of a nodular, micronodular, or infiltrative BCC component. A total of 164 MMS or EFS cases had an initial biopsy showing sBCC. Of these, 117 had residual BCC on stage I, and 43 (37%) were found to have a nodular, micronodular, or infiltrative component. Significant predictors of reclassified BCC subtype included age over 60 years (P=0.006) and location on the head or neck (P=0.043). Reclassified lesions required significantly more stages of MMS to clear (P=0.036). Shave biopsy was used to diagnose 114 (98%) of the included cases. Over one third of shave biopsies that initially diagnosed sBCC failed to detect a nodular, micronodular, or infiltrative component. Management of biopsy-proven sBCC should take into account the possible presence of an undiagnosed deeper tumor component with appropriate margin-assessment treatment modalities when clinically indicated. J Drugs Dermatol. 2021;20(3):283-288. doi:10.36849/JDD.5383.

Photodynamic therapy as a treatment option for multiple pigmented basal cell carcinoma: Long-term follow-up results.

Photodynamic therapy (PDT) has been used worldwide as a non-surgical option for the treatment of basal cell carcinoma (BCC). PDT treatment for pigmented BCC is not frequently performed because of poorer results, which are explained by lower penetration of the light, possibly related to the melanin absorption in the visible range wavelengths. However, there is evidence for an increase in PDT cure rates with prior debulking of the lesion. In this study, we reported a complete clearance of 30 pigmented basal cell carcinomas in 2 patients. PDT was performed in a single visit protocol, which consists of two illumination sessions performed on the same day (125 mW/cm² of irradiance and 150 J/cm² of fluence). Imediately after the debulking of the BCC, a 20 % methyl aminolevulinate cream was applied and occluded for 3 h in the first session and 1.5 h in the second. After 30 days of the treatment, all regions were evaluated clinically and histologically, showing no residual BCC. Even with long-term follow-up (mean of 24 months), no recurrence was detected.. This PDT protocol achieved 100 % control for pigmented BCC. Therefore, it was demonstrated that PDT may be a successful treatment option for small and multiple pigmented BCC.

Neoadjuvant vismodegib in the management of locally advanced periocular basal cell carcinoma.

Vismodegib, a hedgehog pathway inhibitor, has been used in the management of locally advanced basal cell carcinoma (BCC) not suitable for surgery or radiation therapy. We report our experience using neoadjuvant vismodegib for locally advanced periocular BCC, followed by surgical excision. Our aim was to assess the effect on the extent of surgical excision and histological response. A retrospective case series of patients treated with neoadjuvant vismodegib, for the management of locally advanced periocular BCC prior to surgical excision, with intraoperative margin control. Patients were treated until a maximum clinical response was seen. The difference between the estimated surgical margins prior to vismodegib and the eventual margins used was compared. Fine (1 mm) vertical sections through the excised tumour were performed to assess the histological response and look for a multifocal tumour. Eight Caucasian patients had neoadjuvant treatment with vismodegib for a median duration of 6 months. Some clinical response was seen in all cases but was only partial in 6/8 patients. Histological evaluation of the excised specimen showed residual BCC in 6/8 cases and thus 2/8 showed complete histological regression. Two cases showed squamous differentiation. Side effects occurred in 7/8 patients all which resolved on cessation of therapy. The mean follow-up was 13.4 ± 5.2 months. Neoadjuvant treatment of periocular BCC showed a mixed clinical and histological response. Final surgical excision achieved clear margins in all patients with no recurrence at 13 months and a reduction in predicted defect size, but possible squamous differentiation in two cases.

Complete visualization of epidermal margin during ex vivo confocal microscopy of excised tissue with 3-dimensional mosaicking and intensity projection

Ex vivo confocal microscopy allows evaluation of margins of freshly excised tissue for residual basal cell carcinoma (BCC) during staged excision. This approach helps assess margins in the initial stages of excision, while histopathology provides final-stage confirmation for clearance. 1 Jain M. Rajadhyaksha M. Nehal K. Implementation of fluorescence confocal mosaicking microscopy by “early adopter” Mohs surgeons and dermatologists: recent progress. J Biomed Opt. 2017; 22: 24002-24078 Crossref PubMed Scopus (23) Google Scholar However, with the existing tissue mounting devices 1 Jain M. Rajadhyaksha M. Nehal K. Implementation of fluorescence confocal mosaicking microscopy by “early adopter” Mohs surgeons and dermatologists: recent progress. J Biomed Opt. 2017; 22: 24002-24078 Crossref PubMed Scopus (23) Google Scholar ,2 Pérez-Anker J. Puig S. Malvehy J. A fast and effective option for tissue flattening: optimizing time and efficacy in ex vivo confocal microscopy. J Am Acad Dermatol. 2020; 82: e157-e158 Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar flattening the peripheral edges of excised tissue on the cover glass window of the microscope, and imaging of the complete epidermis, which is crucial for the detection of underlying superficial BCCs (sBCC), remains challenging.

Topical Fluorouracil Therapy for Residual Superficial Basal Cell Carcinoma Following Mohs Micrographic Surgery

When treating invasive basal cell carcinoma (BCC) with Mohs micrographic surgery (MMS), including infiltrative and nodular subtypes, the goal is complete surgical removal of the tumor. In some cases, after several stages of MMS, residual foci of superficial BCC are noted with no dermal invasive components apparent. Some patients and surgeons have opted for halting surgery and treating residual superficial BCC with adjuvant topical fluorouracil. In this retrospective study, this treatment method is shown to be effective with a recurrence rate of BCC of 3.7% over a mean follow up of 28 months. This treatment method reduces the number of stages of MMS as the surgery is stopped was invasive BCC is removed. This can be beneficial when considering the morbidity of prolonged surgical procedures in frail, elderly patients experiencing surgical fatigue, the cost of additional stages, and the cost of advanced repairs due to enlarging defect size. J Drugs Dermatol. 2020;19(5): doi:10.36849/JDD.2020.4811.

Topical Fluorouracil Therapy for Residual Superficial Basal Cell Carcinoma Following Mohs Micrographic Surgery

Topical Fluorouracil Therapy for Residual Superficial Basal Cell Carcinoma Following Mohs Micrographic Surgery

Management of complex head-and-neck basal cell carcinomas using a combined reflectance confocal microscopy/optical coherence tomography: a descriptive study.

Recently, a combined reflectance confocal microscopy (RCM)-optical coherence tomography (OCT) has been tested for the diagnosis of basal cell carcinoma (BCC). Evaluating the role of RCM-OCT in management of complex BCCs has not been studied. The objective of the study was to investigate the utility of a new combined RCM-OCT device in the evaluation and management of complex BCCs in a descriptive study. Prospective study of consecutive cases (July 2018-June 2019) of biopsy-proven 'complex' BCC defined as BCC in the head-and-neck area with multiple high-risk criteria such as large size in the mask area, multiple recurrences, and high-risk subtype. All cases were evaluated with a combined RCM-OCT device that provided simultaneous image viewing on a screen. Lesions were evaluated bedside with RCM-OCT according to previously described criteria. Ten patients with complex head-and-neck BCCs had mean age of 73.1 ± 13.0years. Six (60%) patients were males. Mean BCC clinical size was 1.9 ± 1.2cm (range 0.6-4.0cm). RCM detected residual BCC in 8 out of 10 cases (80%) and OCT detected residual BCC in all 10 cases (100%). Six BCCs (60%) had a depth estimate of > 1000µm under OCT. In five cases, (50%) RCM-OCT imaging results led to a change/modification in BCC management. The use of a combined RCM-OCT device may help in the evaluation of complex head-and-neck BCCs by guiding treatment selection and defining the extent of surgery.

Reflectance confocal microscopy confirms residual basal cell carcinoma on clinically negative biopsy sites before Mohs micrographic surgery: A prospective study

Biopsy specimens from patients with basal cell carcinoma (BCC) can present to surgery with no clinically residual tumor, complicating treatment decisions. To evaluate reflectance confocal microscopy (RCM) for the assessment of residual BCC following biopsy. Consecutive patients with biopsy-proven BCC and no clinical evidence of residual tumor who had been referred for Mohs micrographic surgery were included. Biopsy sites were imaged with a handheld RCM device. On the basis of RCM evaluation, cases were labeled RCM positive or RCM negative. Mohs micrographic surgery was performed in all cases; margins and 15-μm serial vertical sectioning were evaluated. A total of 61 patients were included (mean age, 61.7years [standard deviation, 12.2years]; range, 37-87years); 60.7% were women. The mean lesion size was 5.1mm (range, 3-12mm); 73.8% of patients were positive on RCM, and 68.9% had residual BCC on histopathologic examination. The rates of RCM sensitivity, specificity, positive predictive value, and negative predictive value were 92.8%, 68.4%, 86.6%, and 81.2%, respectively. Three cases of BCC (high-risk, infiltrative, and basosquamous) were missed with use of RCM. When high-risk subtypes were excluded (n = 5), sensitivity and negative predictive value were both 100%. RCM can miss deep-seated residual tumor. RCM is a valuable tool for the evaluation of residual BCC following biopsy, with the potential to reduce unnecessary surgical procedures.

Highlights from Recent Cancer Literature

Highlights from Recent Cancer Literature

A cell identity switch allows residual BCC to survive Hedgehog pathway inhibition.

Despite the efficacy of Hedgehog pathway inhibitors in the treatment of basal cell carcinoma (BCC)1, residual disease persists in some patients and may contribute to relapse when treatment is discontinued2. Here, to study the effect of the Smoothened inhibitor vismodegib on tumour clearance, we have used a Ptch1-Trp53 mouse model of BCC3 and found that mice treated with vismodegib harbour quiescent residual tumours that regrow upon cessation of treatment. Profiling experiments revealed that residual BCCs initiate a transcriptional program that closely resembles that of stem cells of the interfollicular epidermis and isthmus, whereas untreated BCCs are more similar to the hair follicle bulge. This cell identity switch was enabled by a mostly permissive chromatin state accompanied by rapid Wnt pathway activation and reprogramming of super enhancers to drive activation of key transcription factors involved in cellular identity. Accordingly, treatment of BCC with both vismodegib and a Wnt pathway inhibitor reduced the residual tumour burden and enhanced differentiation. Our study identifies a resistance mechanism in which tumour cells evade treatment by adopting an alternative identity that does not rely on the original oncogenic driver for survival.

Low recurrence rate of head and neck basal cell carcinoma treated with Mohs micrographic surgery: A retrospective study of 1021 cases.

Mohs micrographic surgery (MMS) is the treatment of choice for high-risk primary basal cell carcinoma (BCC) and recurrent BCC of the head and neck, showing fewer recurrences compared with surgical excision (SE). The objectives of this study were to determine the recurrence rate of head and neck BCC after MMS and to develop a prediction model with significant risk factors for recurrence. A retrospective study of patient records. All BCCs treated with MMS between 1 January 1995 and 1 July 2013 at the University Medical Center Groningen (UMCG) were selected retrospectively. Recorded parameters were patient characteristics, tumour size, tumour location, histopathological subtype, previous treatment, the number of stages until microscopic clearance, defect size, adverse events, follow-up time and recurrence after MMS. The study covered 1021 MMS operations conducted on primary BCCs (57.4%), residual BCCs (25.6%) and recurrent BCCs (17.0%). The median follow-up time was 54.0months (ranging from 1 to 221months). The 5-year cumulative probability of recurrence was 3.3%: 2.6% for primary BCCs, 5.4% for residual BCCs and 2.9% for recurrent BCCs. An aggressive histopathological subtype, residual BCCs and recurrent BCCs were significant risk factors for predicting a higher risk of recurrence after MMS. This large-scale retrospective study showed low recurrence rates after MMS for primary and recurrent BCCs. Residual BCCs treated with MMS had relatively higher recurrence rates. The risk of recurrence for MMS-treated residual aggressive BCCs was more than four times higher than that for primary non-aggressive BCCs.

Ocular preservation with neoadjuvant vismodegib in patients with locally advanced periocular basal cell carcinoma

Locally advanced (T4 perAmerican Joint Committee on Cancer (AJCC) 8th edition) periocular basal cell carcinoma (BCC) can lead to loss of the eye. We report the neoadjuvant use of vismodegib followed by surgery in patients with such lesions with eye preservation as primary goal. This retrospective interventional study includes all patients with a T4 periocular BCC (per 8th edition AJCC for eyelid carcinoma) treated by the senior author between 2013and2017 with neoadjuvant vismodegib prior to definitive surgery. Eight patients had a T4 tumour. Six patients presented with recurrent disease. Indications for neoadjuvant treatment were an unresectable tumour in onepatient, an attempt to avoid an orbital exenteration in sixpatients and an attempt to avoid disfiguring facial surgery in onepatient. Patients were treated for a median of 14 months (range: 4-36 months). All patients underwent an eye-sparing surgery following neoadjuvant vismodegib and all final surgical margins were negative for tumour. Five patients had a complete response to vismodegib with no microscopic residual BCC found during surgery; threepatients had a significant partial response with residual tumour found on pathology. At last follow-up, a mean of 18 (range:6-43) months after surgery, all patients were off-vismodegib and alive without evidence of disease. Neoadjuvant vismodegib for locally advanced (T4) periocular BCC enabled an eye-sparing surgery in all patients in our cohort. Prolonged treatment was welltolerated by most patients. Over half of patients achieved a complete response with no residual microscopic disease. Careful long-term follow-up is needed to confirm long-term disease-free survival.