Difficult to Diagnose Cutaneous Melanoma in a Patient with BAP1 Tumor Predisposition Syndrome.

BRCA1-associated protein 1 (BAP1)-inactivated melanomas can occur sporadically or in germline contexts, particularly in recently recognized BAP1-tumor predisposition syndrome. Diagnosis represents a clinical and histopathological challenge, requiring comprehensive analysis of morphology and sometimes molecular analysis in addition to immunohistochemistry. We report a BAP1-inactivated cutaneous melanoma initially diagnosed as an atypical Spitz tumor on the auricle in a patient with BAP1-tumor predisposition syndrome. Immunohistochemistry, fluorescence in situ hybridization, and comparative genomic hybridization allowed diagnosis. Cutaneous BAP1-inactivated melanocytic tumors, previously classified as atypical Spitz Nevi, may have a dermal mitotic activity that can resemble melanoma and on the other hand, atypical Spitz tumors are sometimes difficult to differentiate from BAP1-inactivated melanoma. Specific criteria, requiring molecular diagnosis have been proposed in order to support melanoma diagnosis.

Surgery for Cutaneous Squamous Cell Carcinoma and its Limits in Advanced Disease.

Surgery remains the first-line therapeutic option for most patients with cutaneous squamous cell carcinoma (cSCC). However, in the current therapeutic landscape, surgery must attempt to the complete tumor resection (R0 resection) with the lowest risk of surgical complications. This double aim is usually accomplished through standard excision with clinical margins in patients with low-risk tumors or by some of the micrographically controlled surgery procedures for patients with tumors at high-risk of local recurrence and metastasis. Surgery is also a first-line treatment for nodal metastases of cSCC as well as an option to consider in patients who develop recurrences while receiving immunotherapy, or as a palliation procedure in patients with advanced tumors. Neoadjuvant immunotherapy, that is the use of a medical treatment before surgery, is under investigation in patients with cSCC. The decision-making process and guidelines recommendations regarding cSCC surgery are reviewed in this manuscript.

Feasibility and cost of a telemedicine-based short-term plan for initial access in general dermatology in Andalusia, Spain.

BACKGROUND: In developed countries, health care delivery in dermatology is hampered by the low availability of dermatologists. OBJECTIVE: To analyze the feasibility of a teledermatology-based action plan to provide initial dermatologic care in areas with low availability of dermatologists. METHODS: A cross-sectional study describing the feasibility and cost of a 12-month action plan based on a store-and-forward teledermatology (TD) connecting primary care centers and a TD center. Teleconsultations from patients complaining of any cutaneous condition were included. The primary outcome measure was the percentage of patients not referred to the local dermatologist. RESULTS: Among the total of 15,523 teleconsultations attended in the TD-based action plan, 3360 (21.65%) required a face-to-face visit with a local dermatologist. In 32.32% (n = 5017) of the cases, a therapeutic and follow-up plan report was issued. The most common conditions managed were melanocytic nevi (15.63%, n = 2426), followed by seborrheic keratosis (14.89%, n = 2312), and actinic keratosis (8.65%, n = 1342). The average response time was 14.52 days (95% CI 14.35-15.23). The additional total investment in this action plan was $142,681.01, with a unit cost of 9.20$/patient. LIMITATIONS: Noncontrolled study. CONCLUSIONS: Experienced dermatologists working with store-and-forward TD can deliver a fast and effective response in health care areas with access limitations.

Factors associated with sentinel lymph node status and prognostic role of completion lymph node dissection for thick melanoma.

INTRODUCTION: Sentinel lymph node (SLN) biopsy is useful for the prognostic stratification of patients with thick melanoma. Identifying which variables are associated with SLN involvement and establishing risk in different subgroups of patients could be useful for guiding the indication of SLN biopsy. The value of complete lymph node dissection (CLND) in patients with a positive SLN biopsy is currently under debate. MATERIALS AND METHODS: To identify factors associated with SLN involvement in thick melanoma we performed a multicentric retrospective cohort study involving 660 patients with thick melanoma who had undergone SLN biopsy. To analyze the role of CLND in thick melanoma patients with a positive SLN biopsy, we built a multivariate Cox proportional hazards model for melanoma-specific survival (MSS) and disease-free survival (DFS) and compared 217 patients who had undergone CLND with 44 who had not. RESULTS: The logistic regression analysis showed that age, histologic subtype, ulceration, microscopic satellitosis, and lymphovascular invasion were associated with nodal disease. The CHAID (Chi-squared Automatic Interaction Detection) decision tree showed ulceration to be the most important predictor of lymphatic involvement. For nonulcerated melanomas, the histologic subtype lentigo maligna melanoma was associated with a low rate of SLN involvement (4.3%). No significant differences were observed for DFS and MSS between the CLND performed and not-performed groups. Nodal status on CLND was associated with differences in DFS and MSS rates. CONCLUSION: We identified subgroups of thick melanoma patients with a low likelihood of SLN involvement. CLND does not offer survival benefit, but provides prognostic information.

Survival analysis and sentinel lymph node status in thin cutaneous melanoma: A multicenter observational study.

Mitotic rate is no longer considered a staging criterion for thin melanoma in the 8th edition of the American Joint Committee on Cancer Staging Manual. The aim of this observational study was to identify prognostic factors for thin melanoma and predictors and prognostic significance of sentinel lymph node (SLN) involvement in a large multicenter cohort of patients with melanoma from nine tertiary care hospitals. A total of 4249 consecutive patients with thin melanoma diagnosed from January 1, 1998 to December 31, 2016 were included. The main outcomes were disease-free interval and melanoma-specific survival for the overall population and predictors of SLN metastasis (n = 1083). Associations between survival and SLN status and different clinical and pathologic variables (sex, age, tumor location, mitosis, ulceration, regression, lymphovascular invasion, histologic subtype, Clark level, and Breslow thickness) were analyzed by Cox proportional hazards regression and logistic regression. SLN status was the most important prognostic factor for melanoma-specific survival (hazard ratio, 13.8; 95% CI, 6.1-31.2; P < 0.001), followed by sex, ulceration, and Clark level for patients who underwent SLNB. A mitotic rate of >2 mitoses/mm2 was the only factor associated with a positive SLN biopsy (odds ratio, 2.9; 95% CI, 1.22-7; P = 0.01. SLN status is the most important prognostic factor in thin melanoma. A high mitotic rate is associated with metastatic SLN involvement. SLN biopsy should be discussed and recommended in patients with thin melanoma and a high mitotic rate.

Sentinel lymph node biopsy versus observation in thick melanoma: A multicenter propensity score matching study.

The clinical value of sentinel lymph node (SLN) biopsy in thick melanoma patients (Breslow >4 mm) has not been sufficiently studied. The aim of the study is to evaluate whether SLN biopsy increases survival in patients with thick cutaneous melanoma, and, as a secondary objective, to investigate correlations between survival and lymph node status. We included 1,211 consecutive patients with thick melanomas (>4 mm) registered in the participating hospitals' melanoma databases between 1997 and 2015. Median follow-up was 40 months. Of these patients, 752 were matched into pairs by propensity scores based on sex, age, tumor location, histologic features of melanoma, year of diagnosis, hospital and adjuvant interferon therapy. The SLN biopsy vs. observation was associated with better DFS [adjusted hazard ratio (AHR), 0.74; 95% confidence interval (CI) 0.61-0.90); p = 0.002] and OS (AHR, 0.75; 95% CI, 0.60-0.94; p = 0.013) but not MSS (AHR, 0.84; 95% CI, 0.65-1.08; p = 0.165). SLN-negative patients had better 5- and 10-year MSS compared with SLN-positive patients (65.4 vs. 51.9% and 48.3 vs. 38.8%; p = 0.01, respectively). As a conclusion, SLN biopsy was associated with better DFS but not MSS in thick melanoma patients after adjustment for classic prognostic factors. SLN biopsy is useful for stratifying these patients into different prognostic groups.

Increasing Frequency of Seborrheic Keratosis Diagnoses as a Favorable Consequence of Teledermatology-Based Skin Cancer Screening: A Cross-sectional Study of 34,553 Patients.

BACKGROUND: Screening of skin cancer by teledermatology (TD) has improved the early detection of skin cancer by enhancing access to skin cancer clinics. OBJECTIVE: We sought to analyze how TD-based skin cancer screening has changed the frequency of consultations for benign lesions. PATIENTS AND METHODS: A cross-sectional study including teleconsultations received during a 7-year period was conducted to analyze and compare the trendlines of each lesion type over the study period. Trendlines were analyzed using a linear regression model with the R-squared (R 2) test for goodness of fit. RESULTS: A total of 34,553 teleconsultations were included in the study. Seborrheic keratoses, followed by benign melanocytic lesions, were the most frequent lesions diagnosed. The pick-up rate for malignant lesions was 1:8.6 teleconsultations. Seborrheic keratoses and precancerous lesions showed a positive trendline with good fit to the linear model (R 2 = 0.8 and R 2 = 0.8, respectively). Tis-T1 malignant melanoma (in situ melanoma or melanoma with a Breslow thickness <1 mm) showed an increasing trendline with moderate-to-low fit to the model (R 2 = 0.4). CONCLUSIONS: TD-based screening of skin cancer is associated with an increasing rate of consultations involving seborrheic keratoses, which can be considered a consequence of improved access to dermatologists resulting from TD implementation.

Internet-based skin cancer screening using clinical images alone or in conjunction with dermoscopic images: A randomized teledermoscopy trial.

BACKGROUND: Teledermoscopy involves the use of dermoscopic images for remote consultation and decision-making in skin cancer screening. OBJECTIVE: We sought to analyze the potential benefits gained from the addition of dermoscopic images to an internet-based skin cancer screening system. METHODS: A randomized clinical trial assessed the diagnostic performance and cost-effectiveness of clinical teleconsultations (CTC) and clinical with dermoscopic teleconsultations. RESULTS: A total of 454 patients were enrolled in the trial (nCTC = 226, nclinical with dermoscopic teleconsultation = 228). Teledermoscopy improved sensitivity and specificity (92.86% and 96.24%, respectively) compared with CTC (86.57% and 72.33%, respectively). Correct decisions were made in 94.30% of patients through clinical with dermoscopic teleconsultations and in 79.20% in CTC (P < .001). The only variable associated with an increased likelihood of correct diagnosis was management using teledermoscopy (odds ratio 4.04; 95% confidence interval 2.02-8.09; P < .0001). The cost-effectiveness analysis showed teledermoscopy as the dominant strategy, with a lower cost-effectiveness ratio (65.13 vs 80.84). LIMITATIONS: Potentially, a limitation is the establishment of an experienced dermatologist as the gold standard for the in-person evaluation. CONCLUSIONS: The addition of dermoscopic images significantly improves the results of an internet-based skin cancer screening system, compared with screening systems based on clinical images alone.

Association between tumor size and Breslow's thickness in malignant melanoma: a cross-sectional, multicenter study.

The aim of this study was to assess the potential role of tumor diameter in explaining variations in tumoral invasion and in the initial prognosis for patients with malignant melanoma (MM). This was a multicenter, cross-sectional study that recruited between 2000 and 2009 patients with primary in-situ MM (Tis) and invasive cutaneous MM. Tis and MMs with a Breslow's thickness less than 1 mm (T1) were grouped (Tis-T1) and tumors with a Breslow's thickness 1 mm or more were also analyzed in combination (T2-T4). The tumor size was measured after routine formalin tissue fixation. Primary outcomes were the correlation between Breslow's thickness and tumor size, and the role of tumor size in explaining variations in Breslow's thickness, as assessed by the Pearson correlation test and logistic binary regression with calculation of the odds ratios. A total of 1610 MM patients were included and analyzed. The Pearson correlation between tumor size and Breslow's thickness was 0.42, with a determination coefficient of R2=0.18 (P>0.01). Correlations between tumor size and thickness were stronger in patients aged 30-60 years (r=0.42, R2=0.1764, P<0.001) and in tumors arising on the upper limbs (r=0.55, R2=0.3025). The odds ratio of identifying a T2-T4 stage MM in patients with tumors larger than 1 cm in size was 2.76 (95% confidence interval 2.25-3.39, P<0.001). Even though a direct, positive, and strong association between tumoral size and Breslow's thickness might be expected in melanoma cases, the strength of this association has been moderate. Tumor size explains a low burden of the variation observed in the Breslow's thickness.

Role of age and sex in the diagnosis of early-stage malignant melanoma: a cross-sectional study.

Age and sex have been identified as predictors of outcome in malignant melanoma (MM). This aim of this multicentre, cross-sectional study was to analyse the role of age and sex as explanatory variables for the diagnosis of thin MM. A total of 2430 patients with MM were recruited. Cases of in situ-T1 MM were more frequent than T2-T4 MM (56.26% vs. 43.74%). Breslow thickness increased throughout decades of life (analysis of variance (ANOVA) p < 0.001), with a weak correlation between Breslow thickness and patient's age (r = 0.202, p < 0.001). Breslow thickness was significantly less in women (1.79 vs. 2.38 mm, p = 0.0001). Binary logistic regression showed a significant (p < 0.001) odds ratio for age 0-29 years (1.18), and 30-59 years (1.16), and for women (1.09). Age and sex explained 3.64% of the variation observed in Tis-T1 frequency (R2 = 0.0364). Age and sex appear to explain a low percentage of the variation in the early detection of MM.

Disease control for patients with psoriasis receiving continuous versus interrupted therapy with adalimumab or etanercept: a clinical practice study.

BACKGROUND: Studies analyzing the efficacy and safety of interrupted psoriasis therapy with biologic drugs have not reported clear benefits in routine clinical practice. OBJECTIVES: To identify differences in the disease control of psoriasis patients undergoing continuous or interrupted therapy with adalimumab or etanercept. METHODS: This retrospective 3-year cohort study (interrupted vs. continuous therapy) involved 77 patients (47 adalimumab, 30 etanercept) who were managed under clinical practice conditions. The proportion of episodes with a Physician Global Assessment (PGA) ≥ 3 during the follow-up in each study cohort was the primary effectiveness endpoint. The relative risk of PGA ≥ 3 episodes in the interrupted therapy cohort was analyzed. RESULTS: Twenty-one patients receiving adalimumab were included in the interrupted therapy cohort (44.7 %), and 26 were included in the continuous therapy cohort (55.3 %). In the group of etanercept, 21 patients received continuous treatment (70.0 %), and nine patients started at least one interruption period (30.0 %). The proportion of PGA ≥ 3 episodes in continuous and interrupted groups were 19.2 % vs. 33.3 % for adalimumab patients (p = 0.27), and 42.9 % vs. 55.6 % in patients treated with etanercept (p = 0.52). The relative risk of PGA ≥ 3 episodes with interrupted therapy was 1.73 (95 % confidence interval 0.64-4.68; p = 0.27), and 1.30 (95 % confidence interval 0.60-2.79; p = 0.52) in the adalimumab and etanercept groups, respectively. CONCLUSION: In routine clinical practice, interrupted therapy with adalimumab or etanercept can provide adequate disease control for a subgroup of patients with excellent response to biologic drugs.

The role of accessibility policies and other determinants of health care provision in the initial prognosis of malignant melanoma: a cross-sectional study.

BACKGROUND: The prognostic benefit of health care service provision and delivery policies for patients with malignant melanoma (MM) is not yet clear. OBJECTIVE: To analyze the role of health care provision determinants in the initial prognosis of MM. METHODS: A multicenter cross-sectional study was conducted at 14 public hospitals and recruited 3550 patients with MM between 2000 and 2009. The study variables were analyzed using univariate and multivariate models to identify their role in the variations observed. RESULTS: In a 10-year period, the number of patients with MM increased by 78.54%, with primary in situ MM (Tis) or MMs with a Breslow thickness <1 mm (T1) representing 51.72% of the total number of MMs in 2000, increasing to 62.23% by the end of the study period (P = .005). Among the variables that explained the variation in MM frequency the year of diagnosis after 2004 (univariate odds ratio [OR], 1.43 [P < .001]; multivariate OR, 1.36 [P = .005]) and diagnosis in centers with specific fast-track referral systems (univariate OR, 1.24 [P = .01]; multivariate OR, 1.59 [P = .025]) were shown to explain the increasing frequency of Tis-T1 MM. LIMITATIONS: The primary potential limitation of this study is its retrospective nature. CONCLUSION: Health care provision policies and interventions aimed at improving accessibility to specialized care appear to explain the increasing frequency of Tis-T1 MM.