Establishing Consensus for Mohs Micrographic Surgical Techniques in the Treatment of Melanoma in Situ for Future Clinical Trials: A Modified Delphi Study.

BACKGROUND: Mohs micrographic surgery (MMS) is a promising treatment modality for melanoma in situ (MIS). However, variations in surgical technique limit the generalizability of existing data and may impede future study of MMS in clinical trials. METHODS: A modified Delphi method was selected to establish consensus on optimal MMS techniques for treating MIS in future clinical trials. The Delphi method was selected due to the limited current data, the wide range of techniques used in the field, and the intention to establish a standardized technique for future clinical trials. A literature review and interviews with experienced MMS surgeons were performed to identify dimensions of the MMS technique for MIS that (1) likely impacted costs or outcomes of the procedure, and (2) showed significant variability between surgeons. A total of 8 dimensions of technical variation were selected. The Delphi process consisted of 2 rounds of voting and commentary, during which 44 expert Mohs surgeons across the United States rated their agreement with specific recommendations using a Likert scale. RESULTS: Five of eight recommendations achieved consensus in Round 1. All 3 of the remaining recommendations achieved consensus in Round 2. Techniques achieving consensus in Round 1 included the use of a starting peripheral margin of ≤5 mm, application of immunohistochemistry, frozen tissue processing, and resecting to the depth of subcutaneous fat. Consensus on the use of Wood's lamp, dermatoscope, and negative tissue controls was established in Round 2. CONCLUSIONS: This study generated 8 consensus recommendations intended to offer guidance for Mohs surgeons treating MIS. The adoption of these recommendations will promote standardization to facilitate comparisons of aggregate data in multicenter clinical trials.

Institutional Adherence to Current Mohs Surgery Appropriate Use Criteria With Reasons for Nonadherence and Recommendations for Future Versions.

BACKGROUND: The appropriate use criteria (AUC) were established to optimize the use of Mohs micrographic surgery (MMS) and confer the highest possible clinical benefit to the patient. OBJECTIVE: We documented our adherence to AUC and review reasons for nonadherence regarding lesions classified as inappropriate, in the hopes of informing future versions of the AUC. MATERIALS AND METHODS: A retrospective review of 1,000 consecutive patients who underwent MMS at a single institution. A total of 1,318 biopsy-proven nonmelanoma skin cancers were treated with MMS, and each skin cancer that underwent MMS was classified as appropriate, uncertain, or inappropriate based on the AUC. RESULTS: Data were collected on 1,318 lesions with 1,237 (93.9%) categorized as appropriate, 59 (4.5%) uncertain, and 22 (1.7%) not appropriate. The primary variables that determined appropriateness were type of cancer (p = .001), size (p < .001), and area of body (p < .001). CONCLUSION: Institutional adherence to AUC was high, with 93.9% of treated tumors classified as appropriate, 4.5% as uncertain and 1.7% as inappropriate. By far the most commonly reported reason for performing MMS on an inappropriate lesion in our review was the treatment of adjacent lesions in 1 session.

Assessing SPP1/Osteopontin (OPN) Splice Variants and Their Association to Nonmelanoma Skin Cancer by Absolute Quantification: Identification of OPN-5 Subvariants and Their Protein Coding Potential.

The study evaluated whether SPP1/osteopontin (OPN) splice variants are differentially expressed in nonmelanoma skin cancer compared to normal skin. The absolute number of mRNA molecules of OPN-a predominated in normal skin and nonmelanoma skin cancer compared to OPN-b, OPN-c, and OPN-5. However, mRNAs of OPN-a, OPN-b, and OPN-c were expressed in higher levels in cutaneous squamous cell carcinomas (cSCCs) and basal cell carcinomas relative to normal skin. Additionally, OPN-5 expression was higher than OPN-b and OPN-c, and OPN-c, in normal skin and nonmelanoma skin cancer, respectively. Furthermore, we identified four OPN-5 splice variants, which were cloned and analyzed for protein expression.

Sebaceous carcinoma: evidence-based clinical practice guidelines.

Sebaceous carcinoma usually occurs in adults older than 60 years, on the eyelid, head and neck, and trunk. In this Review, we present clinical care recommendations for sebaceous carcinoma, which were developed as a result of an expert panel evaluation of the findings of a systematic review. Key conclusions were drawn and recommendations made for diagnosis, first-line treatment, radiotherapy, and post-treatment care. For diagnosis, we concluded that deep biopsy is often required; furthermore, differential diagnoses that mimic the condition can be excluded with special histological stains. For treatment, the recommended first-line therapy is surgical removal, followed by margin assessment of the peripheral and deep tissue edges; conjunctival mapping biopsies can facilitate surgical planning. Radiotherapy can be considered for cases with nerve or lymph node involvement, and as the primary treatment in patients who are ineligible for surgery. Post-treatment clinical examination should occur every 6 months for at least 3 years. No specific systemic therapies for advanced disease can be recommended, but targeted therapies and immunotherapies are being developed.

Initial skin cancer screening for solid organ transplant recipients in the United States: Delphi method development of expert consensus guidelines.

Skin cancer is the most common malignancy affecting solid organ transplant recipients (SOTR), and SOTR experience increased skin cancer-associated morbidity and mortality. There are no formal multidisciplinary guidelines for skin cancer screening after transplant, and current practices are widely variable. We conducted three rounds of Delphi method surveys with a panel of 84 U.S. dermatologists and transplant physicians to establish skin cancer screening recommendations for SOTR. The transplant team should risk stratify SOTR for screening, and dermatologists should perform skin cancer screening by full-body skin examination. SOTR with a history of skin cancer should continue regular follow-up with dermatology for skin cancer surveillance. High-risk transplant patients include thoracic organ recipients, SOTR age 50 and above, and male SOTR. High-risk Caucasian patients should be screened within 2 years after transplant, all Caucasian, Asian, Hispanic, and high-risk African American patients should be screened within 5 years after transplant. No consensus was reached regarding screening for low-risk African American SOTR. We propose a standardized approach to skin cancer screening in SOTR based on multidisciplinary expert consensus. These guidelines prioritize and emphasize the need for screening for SOTR at greatest risk for skin cancer.

Randomized controlled pilot study of the preoperative use of brimonidine 0.33% topical gel for hemostasis in Mohs micrographic surgery.

BACKGROUND: Brimonidine topical gel may be useful in cutaneous surgical procedures because of its vasoconstricting properties. OBJECTIVE: Assess the hemostatic effect of topically applied brimonidine in patients being treated with anticoagulants and undergoing Mohs micrographic surgery (MMS). METHODS: Subjects undergoing MMS were randomly assigned to the control (n = 10) or study arm (n = 14). Controls received standard-of-care MMS, whereas the study arm received the same and preoperative application of brimonidine. Evaluations included rate of blood flow, percentage of wound bed surface area needing electrocautery, and changes in skin colorimeter readings. RESULTS: The treatment arm had 68% less blood loss over 30 seconds versus the control arm (P < .05). No patient in the brimonidine arm had more than 50% of the wound bed cauterized versus 80% in the controls. Erythema in the treatment arm was decreased by 3.89 times (P < .01) versus in the control arm. LIMITATIONS: Limitations were small sample size; sites limited to the face; the fact that measurement of bleeding did not account for anesthetic mixed with blood; visual estimation of percentage of wound surface area requiring cauterization; and no measurement of volume of anesthesia, wound depth, or postoperative complications. CONCLUSION: Preoperative application of brimonidine 0.33% gel may help decrease blood loss and the need for electrocautery during MMS for patients taking anticoagulants.

Observation of Dog-Ear Regression by Anatomical Location.

BACKGROUND: When an excision is performed by a method other than elliptical excision, direct primary wound closure can result in standing cones or "dog-ears." In 2008, Lee and colleagues noted that dog-ears of <8 mm in height have a statistically greater tendency to resolve without further surgical correction than larger dog-ears. OBJECTIVE: To stratify dog-ears by anatomic location and inform on the need for correction at the time of surgery. MATERIALS AND METHODS: After tumor extirpation, patients were counseled that primary closure of the surgical wound would result in dog-ears at the wound apices. Dog-ears were left uncorrected in participating patients. At 6 months, patients were assessed for resolution of the dog-ears and asked to rate the appearance of the scar. RESULTS: A total of 140 dog-ears were observed in the study period. Anatomical locations included the hand/foot, trunk, limb, and head/neck. Among these dog-ears, 114/140 (81%) showed complete resolution. Patient satisfaction with the scar appearance correlated well with the dog-ear resolution, with most patients rating the appearance of the scar as good to excellent. CONCLUSION: This study suggests that dog-ears on the hand and dog-ears ≤4 mm on the trunk may be observed without any final cosmetic penalty.

Utility of Wood's light in margin determination of melanoma in situ after excisional biopsy.

BACKGROUND: Margin evaluation of melanoma in situ (MIS) is difficult because of its ill-defined clinical borders. Wood's light examination is commonly used to help delineate MIS margin before excision. OBJECTIVE: To prospectively study the accuracy of preoperative Wood's light examination for margin assessment of MIS. MATERIALS AND METHODS: The authors evaluated 60 patients before excision of MIS under white light and Wood's light. Staged excision was performed using the square procedure technique. After achieving clear margins, they compared final wound size with expected wound size if surgical margins had been based on Wood's light examination. RESULTS: Seven patients (11.7%) had Wood's light enhancement beyond the visible margin of the biopsy site. In all 7, increased wounding would have occurred if the surgical margins had been based on Wood's light examination. In 1 of the 7, use of the Wood's light examination would have reduced the surgical stages needed by 1 stage but would have increased the wound size by 83.3%. CONCLUSION: Wood's light examination has limited utility if complete excisional biopsy of MIS is performed before treatment. In this study, surgical margin based on the Wood's light examination would have resulted in an increased average wound size and would not have reduced the number of stages needed when performing the square procedure.

Ablative fractionated CO2 resurfacing yields excellent result for severely atrophic traumatic scar on the face.

Ablative fractionated resurfacing has gained significant traction as an effective treatment for acne, burn, traumatic, and surgical scars over recent years. We report a case of a severely depressed, atrophic scar on the cheek of a middle aged woman treated with a 10,600 nm factionated CO2 laser. Serial treatments were performed, resulting in marked improvement in scar contour, texture, and overall cosmesis. Our report highlights the utility of ablative fractionated resurfacing for the treatment of post-traumatic, atrophic scars on the face.

Cyclosporine a mediates pathogenesis of aggressive cutaneous squamous cell carcinoma by augmenting epithelial-mesenchymal transition: role of TGFß signaling pathway.

Organ transplant recipients (OTRs) develop multiple aggressive and metastatic non-melanoma skin cancers (NMSCs). Yet, the underlying mechanism remains elusive. Employing a variety of immune-compromised murine models, immunoblotting, immunohistochemical and immunofluorescence techniques, we show that human squamous xenograft tumors in nude mice grow faster and become significantly larger in size following treatment with the immunosuppressive drug, cyclosporine A (CsA). Re-injected tumor cells isolated from CsA-treated xenografts continued to form larger tumors in nude mice than those from vehicle-controls and retained the CsA-signatures of calcineurin signaling inhibition. Similar results were obtained when these tumors were grown in SCID-beige mice or in immuno-competent mice inoculated with syngeinic tumor cells. Consistently, tumors in the CsA group manifested enhanced cellular proliferation and decreased apoptosis. Tumors in CsA-treated animals also showed an augmented epithelial-mesenchymal transition (EMT) characterized by an increased expression of fibronectin, α-SMA, vimentin, N-cadherin, MMP-9/-2, snail and twist with a concomitant decrease in E-cadherin. CsA-treated xenograft tumors manifested increased TGFß1 expression and TGFß-dependent signaling characterized by increased nuclear p-Smad 2/3. Our data demonstrate that CsA alters the phenotype of skin SCCs to an invasive and aggressive tumor-type by enhancing expression of proteins regulating EMT acting through the TGFß1 signaling pathway providing at least one unique mechanism by which multiple aggressive and metastatic NMSCs develop in OTRs.

Association between number of stages in Mohs micrographic surgery and surgeon-, patient-, and tumor-specific features: a cross-sectional study of practice patterns of 20 early- and mid-career Mohs surgeons.

OBJECTIVE: To determine the number of Mohs micrographic surgery (MMS) stages per tumor taken by early- to mid-career Mohs surgeons and to assess other factors affecting number of stages. METHODS: Statistical analysis of MMS logs of 20 representative early- to mid-career surgeons. RESULTS: There was no difference in stages when surgeons were divided into two categories based on whether they had more than 500 cases per year or more than 5 years of experience. Similarly, when surgeons were categorized according to geographic location, there was no difference in number of stages. Anatomic location was associated with the number of stages (analysis of variance, p<.001), with the greatest number of stages for nose (2.01) and ear (2.06) lesions and the fewest for neck (1.47), back and shoulder (1.47), and lower extremity (1.33) lesions. Basal cell carcinomas required 1.92 stages (median 2.00), compared with 1.66 (median 1.00) for squamous cell carcinoma (p<.001). CONCLUSIONS: Early- and mid-career Mohs surgeons appear to remove tumors with similar numbers of stages regardless of their experience, case volume, or geographic location. Number of stages varies with anatomic location and tumor type. The authors have indicated no significant interest with commercial supporters.

Solitary plaque on the scalp as a primary manifestation of Hodgkin lymphoma: a case report and review of the literature.

Cutaneous Hodgkin lymphoma is infrequent and typically occurs after extensive involvement of the lymph nodes. The condition decreased significantly in incidence in the past two decades, likely owing to the new treatment protocols composed of chemotherapy, radiotherapy and stem cell transplantation. Nevertheless, recognition of this uncommon but significant disease manifestation is important from a prognostic and therapeutic perspective. We are sharing a recent case of Hodgkin lymphoma where the primary presentation appeared as a solitary plaque on the left side of the occipital scalp, clinically suspected to represent a ruptured follicular cyst. The patient underwent excisional biopsy. Histological assessment revealed Hodgkin lymphoma affecting the skin. Radiological studies showed no regional lymphadenopathy. However, two enlarged lymph nodes were identified in the mediastinum and were positron emission tomography avid. The patient underwent systemic treatment without further histopathological examination of these two lymph nodes. Not being clear if these enlarged two lymph nodes were related to his cutaneous disease or not, we cannot be sure if the patient was afflicted either by primary cutaneous Hodgkin lymphoma or by secondary cutaneous involvement because of hematogenous spread. In either case, primary or secondary cutaneous Hodgkin disease is an extreme rarity. The literature is critically reviewed.

Evidence-Based Clinical Practice Guidelines for Microcystic Adnexal Carcinoma: Informed by a Systematic Review.

IMPORTANCE: Microcystic adnexal carcinoma (MAC) occurs primarily in older adults of white race/ethnicity on sun-exposed skin of the head and neck. There are no formal guiding principles based on expert review of the evidence to assist clinicians in providing the highest-quality care for patients. OBJECTIVE: To develop recommendations for the care of adults with MAC. EVIDENCE REVIEW: A systematic review of the literature (1990 to June 2018) was performed using MEDLINE, Embase, Web of Science, and the Cochrane Library. The keywords searched were microcystic adnexal carcinoma, sclerosing sweat gland carcinoma, sclerosing sweat duct carcinoma, syringomatous carcinoma, malignant syringoma, sweat gland carcinoma with syringomatous features, locally aggressive adnexal carcinoma, and combined adnexal tumor. A multidisciplinary expert committee critically evaluated the literature to create recommendations for clinical practice. Statistical analysis was used to estimate optimal surgical margins. FINDINGS: In total, 55 studies met our inclusion criteria. The mean age of 1968 patients across the studies was 61.8 years; 54.1% were women. Recommendations were generated for diagnosis, treatment, and follow-up of MAC. There are 5 key findings of the expert committee based on the available evidence: (1) A suspect skin lesion requires a deep biopsy that includes subcutis. (2) MAC confined to the skin is best treated by surgery that examines the surrounding and deep edges of the tissue removed (Mohs micrographic surgery or complete circumferential peripheral and deep margin assessment). (3) Radiotherapy can be considered as an adjuvant for MAC at high risk for recurrence, surgically unresectable tumors, or patients who cannot have surgery for medical reasons. (4) Patients should be seen by a physician familiar with MAC every 6 to 12 months for the first 5 years after treatment. Patient education on photoprotection, periodic skin self-examination, postoperative healing, and the possible normal changes in local sensation (eg, initial hyperalgesia) should be considered. (5) There is limited evidence to guide the treatment of metastasis in MAC due to its rarity. Limitations of our findings are that the medical literature on MAC comprises only retrospective reviews and descriptions of individual patients and there are no controlled studies to guide management. CONCLUSIONS AND RELEVANCE: The presented clinical practice guidelines provide an outline for the diagnosis and management of MAC. Future efforts using multi-institutional registries may improve our understanding of the natural history of the disease in patients with lymph node or nerve involvement, the role of radiotherapy, and the treatment of metastatic MAC with drug therapy.