Incompletely excised lentigo maligna melanoma is associated with unpredictable residual disease: clinical features and the emerging role of reflectance confocal microscopy.

BACKGROUND: Lentigo maligna/lentigo maligna melanoma (LM/LMM) poses a treatment and surgical challenge given unpredictable subclinical extension resulting in incomplete excision. OBJECTIVES: To describe the demographic, clinical and pathologic characteristics of incompletely excised LM/LMM. To evaluate the potential role of reflectance confocal microscopy (RCM). PATIENTS AND METHODS: A retrospective review of a melanoma database at a tertiary cancer centre for patients referred with 'incompletely excised LM/LMM' or 'incompletely excised melanoma' between October 2006 and July 2017. We recorded clinical and pathological data and surgical margins needed to clear the residual LM/LMM. The second part consisted of a prospective cohort of patients in which RCM was performed when presenting with incompletely excised LM/LMM. RESULTS: We included a total of 67 patients (retrospective + prospective cohort); mean age was 64.9 (standard deviation: 11.3) years and 52.2% were males. For the retrospective cohort (n = 53), the mean scar size was 3.4 cm. The average initial margins excised prior to presentation were 4.8 mm (range 3-7 mm). The average additional margin needed to clear the residual, incompletely excised LM/LMM was 7.8 mm. For the prospective cohort (n = 14), there were no differences in age, gender or size when compared to the retrospective cohort. RCM had a diagnostic accuracy of 78.6%, a sensitivity of 90.9%, a specificity of 33.3% and a positive predictive value of 83.3% for the detection of incompletely excised LM/LMM. CONCLUSIONS: Incompletely excised LM/LMM is a poorly characterized clinical-pathological scenario that may require considerable extra margins for microscopic clearance. RCM may emerge as a valuable tool for the evaluation of patients with incompletely excised LM/LMM.

Reflectance confocal microscopy and dermoscopy aid in evaluating repigmentation within or adjacent to lentigo maligna melanoma surgical scars.

BACKGROUND: Determining whether repigmentation within or adjacent to lentigo maligna or lentigo maligna melanoma (LM/LMM) scars represents recurrence of melanoma is challenging. The use of reflectance confocal microscopy (RCM) and dermoscopy may aid in differentiating true melanoma recurrence from other causes of repigmentation. OBJECTIVES: To describe the characteristics of repigmentation within or adjacent to LM/LMM scars observable on RCM and dermoscopy. METHODS: We retrospectively analysed patients who presented with new pigmentation within or adjacent to scars from surgically treated LM/LMM between January 2014 and December 2018. Clinical and demographic characteristics and time to recurrence were recorded. RCM was used to evaluate areas of pigmentation before biopsy. If available, dermoscopic images were also evaluated. RESULTS: In total, 30 confocal studies in 29 patients were included in the study cohort. Twenty-one patients had biopsy-confirmed recurrent LM/LMM; the remainder had pigmented actinic keratosis (n = 4) or hyperpigmentation/solar lentigo (n = 5). RCM had sensitivity of 95.24% (95% CI, 76.18-99.88%), specificity of 77.7% (95% CI, 39.99-97.19%), positive predictive value of 90.91% (95% CI, 74.58-97.15%) and negative predictive value of 87.5% (95% CI, 50.04-98.0%). The most common dermoscopic feature observed among patients with recurrent LM/LMM was focal homogeneous or structureless areas of light-brown pigmentation (92.8% vs. 37.5% in patients with other diagnoses; P = 0.009). LM-specific dermoscopic criteria were present in only 28.5% of patients with recurrent LM/LMM. CONCLUSIONS: Reflectance confocal microscopy and dermoscopy are valuable tools for the comprehensive evaluation of repigmentation within or adjacent to LM scars.

FACE-Q Skin Cancer Module for measuring patient-reported outcomes following facial skin cancer surgery.

BACKGROUND: The patient's perspective of their facial scar after skin cancer surgery influences perception of care and quality of life (QoL). Appearance satisfaction after surgery is also an important but often overlooked treatment outcome. OBJECTIVES: To report the psychometric validation of the FACE-Q Skin Cancer Module consisting of five scales, measuring appearance satisfaction (Satisfaction with Facial Appearance, Appraisal of Scars), QoL (Cancer Worry, Appearance-related Psychosocial Distress) and the patient experience (Satisfaction with Information: Appearance). METHODS: Participants underwent Mohs surgery for facial basal or squamous cell carcinoma or excision of early facial melanoma. Cohort 1 received a set of scales before and after surgery. Cohort 2 received the scales on two occasions in the postoperative period for test-retest reliability. Rasch measurement theory was used to select (item-reduce) the most clinically meaningful items for the scales. Reliability, validity, floor and ceiling effects and responsiveness were also analysed. RESULTS: Of 334 patients, 209 (response rate 62·6%) were included. Rasch analysis reduced the total scale items from 77 to 41. All items had ordered thresholds and good psychometric fit. Reliability was high (Person separation index and Cronbach's α ≥ 0·90) and scales measuring similar constructs were correlated. High floor and ceiling effects were seen for the scales. The Cancer Worry scale demonstrated responsiveness (P = 0·004). CONCLUSIONS: The FACE-Q Skin Cancer Module meet the requirements of the Rasch model providing linearized measurement. Discriminating between patients with minimal appearance or worry impairment may be a limitation. The scales can be used for larger validation studies, clinical practice and research.

Carbon dioxide laser ablation of basal cell carcinoma with visual guidance by reflectance confocal microscopy: a proof-of-principle pilot study.

BACKGROUND: Laser ablation is an alternative, nonsurgical treatment modality for low-risk basal cell carcinoma (BCC). However, lack of confirmative tumour destruction or residual tumour presence has been a limiting factor to its adoption. Reflectance confocal microscopy (RCM) provides noninvasive, cellular-level resolution imaging of the skin and is capable of identifying tumour. OBJECTIVES: To evaluate the use of RCM to guide carbon dioxide (CO2 ) laser ablation of BCC, confirm destruction and correlate findings with histology. METHODS: RCM was used preablation to evaluate for features of BCC. Ablation was performed with a CO2 laser, and the response rapidly assessed using handheld RCM to evaluate for residual tumour. Confirmative pathology was used to verify confocal imaging. RESULTS: Preablation RCM imaging identified tumour with features not identified on normal, surrounding skin. Postablation, RCM documented complete removal of tumour in six cases and residual tumour in two. Histological examination identified the ablated area and confirmed clearance of tumour in the six aforementioned cases and corroborated confocal findings for residual tumour in the other two cases. CONCLUSIONS: We report successful treatment of superficial and nodular BCC using CO2 laser ablation augmented by RCM imaging for preablation guidance and verification of tumour removal postablation. Akin to complete circumferential and deep margin control techniques, using RCM helps to map peripheral and deep BCC margins to hone in on areas exhibiting persistent tumour after ablation. CO2 laser ablation visually guided by RCM can help circumvent previously cited limiting factors of laser ablation for tumour destruction by providing cellular-level resolution imaging of tumour and margin assessment in between each laser pass and postablation.

In vivo reflectance confocal microscopy of shave biopsy wounds: feasibility of intraoperative mapping of cancer margins.

BACKGROUND: Reflectance confocal microscopy (RCM) images skin at cellular resolution and has shown utility for the diagnosis of nonmelanoma skin cancer in vivo. Topical application of aluminium chloride (AlCl(3)) enhances contrast in RCM images by brightening nuclei. OBJECTIVES: To investigate feasibility of RCM imaging of shave biopsy wounds using AlCl(3) as a contrast agent. METHODS: AlCl(3) staining was optimized, in terms of concentration vs. immersion time, on excised tissue ex vivo. RCM imaging protocol was tested in patients undergoing shave biopsies. The RCM images were retrospectively analysed and compared with the corresponding histopathology. RESULTS: For 35% AlCl(3) , routinely used for haemostasis in clinic, minimum immersion time was determined to be 1 min. We identified three consistent patterns of margins on RCM mosaic images by varying depth: epidermal margins, peripheral dermal margins, and deep dermal margins. Tumour islands of basal cell carcinoma were identified at peripheral or deep dermal margins, correlating on histopathology with aggregates of neoplastic basaloid cells. Atypical cobblestone or honeycomb patterns were identified at the epidermal margins in squamous cell carcinomas, correlating with a proliferation of atypical keratinocytes extending to biopsy margins. CONCLUSIONS: RCM imaging of shave biopsy wounds is feasible and demonstrates the future possibility of intraoperative mapping in surgical wounds.

Detection of basal cell carcinomas in Mohs excisions with fluorescence confocal mosaicing microscopy.

BACKGROUND: High-resolution real-time imaging of human skin is possible with a confocal microscope either in vivo or in freshly excised tissue ex vivo. Nuclear and cellular morphology is observed in thin optical sections, similar to that in conventional histology. Contrast agents such as acridine orange in fluorescence and acetic acid in reflectance have been used in ex vivo imaging to enhance nuclear contrast. OBJECTIVES: To evaluate the sensitivity and specificity of ex vivo real-time imaging with fluorescence confocal mosaicing microscopy, using acridine orange, for the detection of residual basal cell carcinoma (BCC) in Mohs fresh tissue excisions. METHODS: Forty-eight discarded skin excisions were collected following completion of Mohs surgery, consisting of excisions with and without residual BCC of all major subtypes. The tissue was stained with acridine orange and imaged with a fluorescent confocal mosaicing microscope. Confocal mosaics were matched to the corresponding haematoxylin and eosin-stained Mohs frozen sections. Each mosaic was divided into subsections, resulting in 149 submosaics for study. Two Mohs surgeons, who were blinded to the cases, independently assessed confocal submosaics and recorded the presence or absence of BCC, location, and histological subtype(s). Assessment of confocal mosaics was by comparison with corresponding Mohs surgery maps. RESULTS: The overall sensitivity and specificity of detecting residual BCC was 96.6% and 89.2%, respectively. The positive predictive value was 92.3% and the negative predictive value 94.7%. Very good correlation was observed between confocal mosaics and matched Mohs frozen sections for benign and malignant skin structures, overall tumour burden and location, and identification of all major histological subtypes of BCC. CONCLUSIONS: Fluorescent confocal mosaicing microscopy using acridine orange enables detection of residual BCC of all subtypes in Mohs fresh tissue excisions with high accuracy. This observation is an important step towards the long-term clinical goal of using a noninvasive imaging modality for potential real-time surgical pathology-at-the-bedside for skin and other tissues.

Confocal mosaicing microscopy in skin excisions: a demonstration of rapid surgical pathology.

Precise micro-surgical removal of tumour with minimal damage to the surrounding normal tissue requires a series of excisions, each guided by an examination of frozen histology of the previous. An example is Mohs surgery for the removal of basal cell carcinomas (BCCs) in skin. The preparation of frozen histology is labour-intensive and slow. Confocal microscopy may enable rapid detection of tumours directly in surgical excisions with minimal need for frozen histology. Mosaicing of images enables observation of nuclear and cellular morphology in large areas of surgically excised tissue. In skin, the use of 10-1% acetic acid as a reflectance contrast agent brightens nuclei in 0.5-5 min and enhances nuclear-to-dermis contrast and detectability of BCCs. A tissue fixture was engineered for precisely mounting surgical excisions to enable mosaicing of 36 x 36 images to create a field of view of 12 x 12 mm. This large field of view displays the excision at 2x magnification, similar to that routinely used by Mohs surgeons when examining frozen histology. Comparison of mosaics to histology demonstrates detectability of BCCs. Confocal mosaicing presently requires 9 min, instead of 20-45 min per excision for preparing frozen histology, and thus may provide a means for rapid pathology-at-the-bedside to expedite and guide surgery.

Use of and beliefs about dermoscopy in the management of patients with pigmented lesions: a survey of dermatology residency programmes in the United States.

Dermoscopy is a non-invasive technique that can be utilized for the clinical diagnosis of pigmented lesions. The aim of this study was to assess the utilization and beliefs about the usefulness of dermoscopy in the evaluation of pigmented lesions by physicians in dermatology residency programmes, and to determine the extent of dermoscopy training received by residents in these programmes. Questionnaires were sent to the directors of all the accredited dermatology residency programmes in the United States (n = 105). A follow-up postcard questionnaire was sent to the chief resident of all the responding programmes. Eighty-three physicians responded to the questionnaire (79%). Fifty-one per cent of the respondents (n = 42) reported utilizing dermoscopy. Reported reasons for using dermoscopy by respondents included the fact that it helps detect melanoma early (74%), leads to fewer biopsies (74%) and reduces patient anxiety (64%). Lack of training (51%) and lack of usefulness (42%) were amongst the reported reasons for not utilizing dermoscopy. Sixty-seven per cent of respondents reported an increase of approximately 50% in the use of dermoscopy over the past 5 years, and 45% anticipated an increase in use over the next 5 years. Thirty-eight per cent of chief residents from the responding programmes reported receiving training in dermoscopy during residency. In conclusion, half of the dermatology residency programmes currently use dermoscopy in the evaluation of pigmented lesions. The main reason for not using dermoscopy was a lack of training. Respondents anticipated a future increase in the use of dermoscopy.

Use of and beliefs about baseline photography in the management of patients with pigmented lesions: a survey of dermatology residency programmes in the United States.

Medical photography is often used in dermatology to aid in the clinical surveillance of patients with pigmented lesions. This study aimed to assess the utilization, logistics, rationale and beliefs about the usefulness of baseline photography in patients with pigmented lesions by physicians in dermatology residency programmes, and to compare current utilization to that reported in the last decade. Questionnaires were mailed to directors of all accredited dermatology residency programmes in the United States (n = 105). Eighty-three physicians responded to the questionnaire (79%). Utilization of total body and individual lesion photography was reported by 63% and 75% of the respondents, respectively; 16% of the respondents did not use any method of photography. Reasons for using photography included the following beliefs: that it helps detect early melanoma, it results in fewer biopsies, and it reduces patient anxiety. Financial and logistical constraints were reasons why some programmes were not utilizing photography. Thus baseline photography is currently used in a majority of academic dermatology programmes as an aid in the early detection of melanoma.

Using nurse practitioners for skin cancer screening: a pilot study.

BACKGROUND: Skin cancer screening has the potential to detect early precancerous lesions and may ultimately be important in reducing melanoma mortality. The purpose of this study was to evaluate the ability of trained nurse practitioners to accurately identify suspicious lesions in a clinical setting. METHODS: We identified five nurse practitioners who had no previous experience in evaluating skin lesions. Each nurse practitioner participated in a training program for skin cancer detection consisting of a workshop, clinical apprenticeship, and didactic lectures. RESULTS: Evaluation of nurse practitioner competency involved three assessments. First, the nurse practitioner's ability to distinguish benign and malignant lesions was assessed using clinical color slides. The sensitivity of all five nurse practitioners to refer benign and malignant lesions for dermatologic follow-up based on the slides was 100%, whereas the specificity ranged from 53% to 100%. Second, each nurse practitioner evaluated approximately 25 different patients along with a single dermatologist. The nurse practitioner's ability to correctly refer patients with suspicious lesions for dermatologic follow-up was determined based on the dermatologist's assessment of need for referral. Results suggested a referral sensitivity and specificity ranging from 67% to 100% and 62% to 100%, respectively. In the final clinical assessment, 30 patients were independently examined by two dermatologists and four nurse practitioners. Using the consensus clinical diagnosis of the dermatologists as the gold standard, the nurse practitioner's sensitivity for detecting significant skin cancer lesions ranged from 50% to 100% and the detection specificity was 99% to 100%. CONCLUSIONS: These preliminary results have important implications for skin cancer screening efforts and suggest that nurse practitioners can be trained to accurately identify and triage suspicious lesions.

Histologic classification of tumor-infiltrating lymphocytes in primary cutaneous malignant melanoma. A study of interobserver agreement.

The density and distribution of lymphocytes infiltrating the vertical growth phase of primary cutaneous melanomas has been suggested by several studies to be of prognostic significance. However, few pathologists comment on tumor-infiltrating lymphocytes (TILs), and there is the perception that the assessment of TILs is subject to great interobserver variability. We studied interobserver agreement on the categorization of TILs; 20 cases of primary cutaneous malignant melanoma with a vertical growth phase component were circulated among 3 pathologists and 3 dermatologists. For each case, TILs were classified as brisk, nonbrisk, or absent according to Clark. Only 1 pathologist (a dermatopathologist) was familiar with the classification of TILs. Observers were given written guidelines and a brief tutorial before their examination of the slides. Our results show that with little instruction, overall agreement among observers was good (kappa values, 0.6 or more), especially among pathologists (kappa values, > 0.7). Three observers had excellent agreement among each other (kappa values, > 0.75). These findings suggest that the categorization of TILs can be easily taught and can be applied with an acceptable level of reproducibility in routine diagnostic practice.

Treatment of primary miliary osteoma cutis with incision, curettage, and primary closure.

BACKGROUND: Primary miliary osteoma cutis is characterized by de novo bone formation in skin without a known associated or pre-existing cutaneous disorder. These lesions often develop on the face and cause cosmetic concern. OBJECTIVE: Multiple treatments have been attempted, including topical and systemic agents and surgical techniques. The ideal treatment modality should be simple and effective with minimal side effects. METHODS: The technique of scalpel incision over visible lesions, curette extraction of bony fragments, and primary suture repair was used to remove multiple lesions of primary miliary osteoma cutis on the cheeks of an affected patient. RESULTS: This surgical technique resulted in a significant reduction of visible and palpable lesions and a smoother surface contour with minimal scarring. CONCLUSION: This surgical technique offers a simple but effective method for removal of multiple bony fragments in primary miliary osteoma cutis with minimal side effects.

Er:YAG laser for the treatment of actinic keratoses.

BACKGROUND: There is no single optimal treatment for multiple facial actinic keratoses. The existing therapies such as topical 5-fluorouracil, chemical peels, cryotherapy, dermabrasion, and CO2 laser resurfacing can produce prolonged recovery time or are often operator dependent. OBJECTIVE: The purpose of this study was to investigate another therapeutic modality which provides a shorter recovery time with uniform results. We performed a prospective pilot study investigating the use of the Er:YAG laser for the treatment of multiple facial actinic keratoses. METHODS: Five patients with multiple facial actinic keratoses were treated with two to three passes of Er:YAG laser. Anesthesia was achieved in all cases by topical application and local infiltration when indicated. All patients were treated with 2.0 J, 5 mm spot size, and a fluence of 10 J/cm2. Clinical and histologic evaluations were performed both pre- and postoperatively. RESULTS: All patients showed a decrease in the total number of clinical actinic keratoses on the face ranging from 86 to 96%. In addition to the reversal of actinic damage in the epidermis, histologic evidence revealed increased fibroplasia and decreased superficial solar elastosis 3 months after the laser resurfacing. Reepithelialization occurred in 5-8 days, and erythema lasted for about 3-6 weeks after the procedure. There was no evidence of scarring or pigmentary changes in any of the patients during the follow-up period. CONCLUSION: Er:YAG laser skin resurfacing is a safe and effective treatment for multiple facial actinic keratoses. Histologic data suggest a new zone of collagen deposition occurs in the superficial papillary dermis. Under our current parameters, Er:YAG laser skin resurfacing has a relatively short recovery period and a low risk of scarring. Unlike the CO2 laser, Er:YAG laser skin resurfacing can be performed with topical anesthesia alone.

Dog-ears: a review.

BACKGROUND: The closure of any circular or asymmetric wound results in puckering or excess of tissue known as dog-ears. OBJECTIVE: Facility in managing dog-ears is an invaluable tool in cutaneous surgery due to its common presentation. METHODS: Methods for correcting dog-ears are extensively detailed in both the plastic and dermatologic surgery literature. This review provides a practical outline of nine methods of dog-ear correction along with pertinent schematic and clinical illustration. RESULTS: A comprehensive approach to dog-ears requires knowledge of tissue dynamics, adherence to proper surgical technique, and strategies for the management of dog-ears. CONCLUSIONS: A thorough understanding of dog-ear formation and correction allows the surgeon to choose the most appropriate management for dog-ears in any clinical setting.

Treatment of mature striae with the pulsed dye laser.

INTRODUCTION: Striae are a common cosmetic problem with no effective treatment options. A recent study has shown improvement in the appearance of mature striae following a single 585-nm pulsed dye laser (PDL) treatment at low fluence. OBJECTIVE: To evaluate the effectiveness of treating mature striae with the 585-nm PDL. METHODS: Five patients with mature striae on the abdomen were prospectively treated with the 585-nm PDL at 2-month intervals for 1-2 years. The response of the striae to laser treatment was evaluated in each patient through sequential clinical, photographic, textural, and histologic assessment. RESULTS: All five patients reported a slight overall improvement in the appearance of the striae following multiple PDL treatments. Comparison of pre- and post-treatment photographs, however, failed to reveal improvement in any patients. Optical profilometry performed on striae impressions showed mild improvement in the surface texture of striae in three patients. Histologic comparison of pre- and post-treatment biopsy specimens failed to reveal normalization of skin architecture. CONCLUSIONS: Serial treatment of mature striae with the PDL results in mild, subjective, clinical improvement but no significant photographic, textural or histologic improvement.

Basal cell carcinoma of the genitalia.

BACKGROUND: Basal cell carcinomas (BCC) arising on the genitalia are exceedingly rare with an unclear pathogenesis. OBJECTIVE: To better understand risk factors, tumor characteristics, and the possible role of human papillomavirus (HPV) in the development of BCC of the genitalia. METHODS: 1543 records of Mohs micrographic surgery performed during a 6-year period were reviewed to identify cases of BCC arising on the genitalia. Tumor tissue was analyzed for HPV DNA by in situ hybridization. RESULTS: Four patients with BCC of the genitalia were treated with Mohs micrographic surgery. The malignancies were located on the scrotum, perineum, and perianal areas in the three male patients and on the vulva in the female patient. The mean age was 67 years. None of the patients had prior history of skin cancers. Histologic evaluation of the tumors revealed two nodular subtypes, one superficial subtype, and one with follicular differentiation. In situ hybridization failed to reveal DNA of HPV types 6, 11, 16, 18, 30, 31, 33, 35, 45, 51, and 52. CONCLUSION: In this small series, genital BCC occurred in an older age group with no identifiable predisposing risk factors and did not show evidence of HPV infection.