Brentuximab vedotin in the treatment of cutaneous T-cell lymphomas: Data from the Spanish Primary Cutaneous Lymphoma Registry.

BACKGROUND: Brentuximab vedotin (BV) has been approved for CD30-expressing cutaneous T-cell lymphoma (CTCL) after at least one previous systemic treatment. However, real clinical practice is still limited. OBJECTIVES: To evaluate the response and tolerance of BV in a cohort of patients with CTCL. METHODS: We analysed CTCL patients treated with BV from the Spanish Primary Cutaneous Lymphoma Registry (RELCP). RESULTS: Sixty-seven patients were included. There were 26 females and the mean age at diagnosis was 59 years. Forty-eight were mycosis fungoides (MF), 7 Sézary syndrome (SS) and 12 CD30+ lymphoproliferative disorders (CD30 LPD). Mean follow-up was 18 months. Thirty patients (45%) showed at least 10% of CD30+ cells among the total lymphocytic infiltrate. The median number of BV infusions received was 7. The overall response rate (ORR) was 67% (63% in MF, 71% in SS and 84% in CD30 LPD). Ten of 14 patients with folliculotropic MF (FMF) achieved complete or partial response (ORR 71%). The median time to response was 2.8 months. During follow-up, 36 cases (54%) experienced cutaneous relapse or progression. The median progression free survival (PFS) was 10.3 months. The most frequent adverse event was peripheral neuropathy (PN) (57%), in most patients (85%), grades 1 or 2. CONCLUSIONS: These results confirm the efficacy and safety of BV in patients with advanced-stage MF, and CD30 LPD. In addition, patients with FMF and SS also showed a favourable response. Our data suggest that BV retreatment is effective in a proportion of cases.

A Novel Approach for the Shape Characterisation of Non-Melanoma Skin Lesions Using Elliptic Fourier Analyses and Clinical Images.

The early detection of Non-Melanoma Skin Cancer (NMSC) is crucial to achieve the best treatment outcomes. Shape is considered one of the main parameters taken for the detection of some types of skin cancer such as melanoma. For NMSC, the importance of shape as a visual detection parameter is not well-studied. A dataset of 993 standard camera images containing different types of NMSC and benign skin lesions was analysed. For each image, the lesion boundaries were extracted. After an alignment and scaling, Elliptic Fourier Analysis (EFA) coefficients were calculated for the boundary of each lesion. The asymmetry of lesions was also calculated. Then, multivariate statistics were employed for dimensionality reduction and finally computational learning classification was employed to evaluate the separability of the classes. The separation between malignant and benign samples was successful in most cases. The best-performing approach was the combination of EFA coefficients and asymmetry. The combination of EFA and asymmetry resulted in a balanced accuracy of 0.786 and an Area Under Curve of 0.735. The combination of EFA and asymmetry for lesion classification resulted in notable success rates when distinguishing between benign and malignant lesions. In light of these results, skin lesions' shape should be integrated as a fundamental part of future detection techniques in clinical screening.

Graft versus host disease-related eosinophilic fasciitis: cohort description and literature review.

BACKGROUND: Chronic graft versus host disease (cGVHD) simulating eosinophilic fasciitis (EF) is an underdiagnosed and challenging complication due to the lack of knowledge about its pathogenesis, refractoriness to traditional immunosuppressive agents and their negative impact on the physical function and quality of life. The aim of this study is to describe the clinical-biological characteristics and response to treatment of a case series and to provide a comprehensive literature review on cGVHD related EF involvement. METHODS: Prospective observational study to describe the clinical and diagnostic evaluation characteristics of patients with EF-like follow-up as part of our multidisciplinary cGVHD consultations. In addition, the literature on joint and/or fascial musculoskeletal manifestations due to cGVHD was comprehensively reviewed. RESULTS: 118 patients were evaluated in multidisciplinary cGVHD consultations, 39 of whom (33%) developed fasciitis. Notably, 11 patients had isolated joint contractures without sclerotic skin. After a median of three lines of treatment, the vast majority of patients achieved some degree of response. 94 potentially eligible articles were identified by the search strategy, with 17 of them, the majority isolated case reports, making the final selection. The validated staging scales used for the assessment were the Joint and Fascial Score and the Photographic Range of Motion. CONCLUSION: Fascial/articular involvement needs to be recognized and evaluated early. To our knowledge, our cohort is the second largest series to have been reported. Literature addressing fascial/joints complications related to cGVHD is scarce. The search for new biomarkers, the use of advanced imaging techniques and multidisciplinary approach may help improve the prognosis of patients with cGVHD.

Deep Convolutional Neural Support Vector Machines for the Classification of Basal Cell Carcinoma Hyperspectral Signatures.

Non-melanoma skin cancer, and basal cell carcinoma in particular, is one of the most common types of cancer. Although this type of malignancy has lower metastatic rates than other types of skin cancer, its locally destructive nature and the advantages of its timely treatment make early detection vital. The combination of multispectral imaging and artificial intelligence has arisen as a powerful tool for the detection and classification of skin cancer in a non-invasive manner. The present study uses hyperspectral images to discern between healthy and basal cell carcinoma hyperspectral signatures. Upon the combined use of convolutional neural networks, with a final support vector machine activation layer, the present study reaches up to 90% accuracy, with an area under the receiver operating characteristic curve being calculated at 0.9 as well. While the results are promising, future research should build upon a dataset with a larger number of patients.

Clinical and histopathological evaluation of 50 acantholytic cutaneous squamous cell carcinomas: Analysis outcome in a retrospective case-control study.

BACKGROUND: Acantholytic cutaneous squamous cell carcinomas (aCSCCs) have been classically considered as a high-risk variant of CSCC. However, more recent studies show that aCSCC does not confer more aggressiveness. This study aims to establish whether the prognosis of the aCSCC is worse than that of the non-acantholytic (naCSCC) or not. METHODS: Retrospective case-control study with 50 aCSCCs and 50 naCSCCs. For each aCSCC, an naCSCC with similar high-risk features to the aCSCC but with no acantholysis was selected. Prognosis between both groups was compared. RESULTS: The mean age was 86 years (SD 9.61). Sixty-one patients were men. Thirty-nine CSCCs were located in high-risk head and neck areas. Twenty CSCCs exhibited a poor degree of differentiation, and 36 showed an infiltrative growth pattern. The tumor diameter was 18.71 mm (interquartile range, IQR 35), and the tumor thickness was 6.72 mm (IQR 15.50). Twelve CSCCs exhibited perineural infiltration, and eight CSCCs exhibited invasion beyond the subcutaneous fat. Positive margins after excision of the tumor in 22 aCSCCs vs eight naCSCCs (P < 0.02). Nineteen poor-prognosis events were observed (local recurrence, lymph node metastasis, and death from CSCC). However, no differences were observed between both groups when comparing poor-prognosis events. CONCLUSION: The proportion of unfavorable events is similar in aCSCC and naCSCC. The acantholytic histopathological subtype is not associated with a poorer prognosis than the non-acantholytic CSCC in our cohort.

Sentinel Lymph Node Biopsy vs. Observation in Thin Melanoma: A Multicenter Propensity Score Matching Study.

The therapeutic value of sentinel lymph node biopsy (SLNB) in thin melanoma remains controversial. The aim of this study is to determine the role of SLNB in the survival of thin melanomas (≤1 mm). A multicenter retrospective observational study was designed. A propensity score matching was performed to compare patients who underwent SLNB vs. observation. A multivariate Cox regression was used. A total of 1438 patients were matched by propensity score. There were no significant differences in melanoma-specific survival (MSS) between the SLNB and observation groups. Predictors of MSS in the multivariate model were age, tumor thickness, ulceration, and interferon treatment. Results were similar for disease-free survival and overall survival. The 5- and 10-year MSS rates for SLN-negative and -positive patients were 98.5% vs. 77.3% (p < 0.001) and 97.3% vs. 68.7% (p < 0.001), respectively. SLNB does not improve MSS in patients with thin melanoma. It also had no impact on DSF or OS. However, a considerable difference in MSS, DFS, and OS between SLN-positive and -negative patients exists, confirming its value as a prognostic procedure and therefore we recommend discussing the option of SLNB with patients.

Overcoming Resistance to Immunotherapy in Advanced Cutaneous Squamous Cell Carcinoma.

Cutaneous squamous cell carcinoma (CSCC) is the second most frequent cancer in humans, and is now responsible for as many deaths as melanoma. Immunotherapy has changed the therapeutic landscape of advanced CSCC after the FDA approval of anti-PD1 molecules for the treatment of locally advanced and metastatic CSCC. However, roughly 50% of patients will not respond to this systemic treatment and even those who do respond can develop resistance over time. The etiologies of primary and secondary resistance to immunotherapy involve changes in the neoplastic cells and the tumor microenvironment. Indirect modulation of immune system activation with new therapies, such as vaccines, oncolytic viruses, and new immunotherapeutic agents, and direct modulation of tumor immunogenicity using other systemic treatments or radiotherapy are now under evaluation in combined regimens. The identification of predictors of response is an important area of research. In this review, we focus on the features associated with the response to immunotherapy, and the evaluation of combination treatments and new molecules, a more thorough knowledge of which is likely to improve the survival of patients with advanced CSCC.

Hyperspectral imaging and robust statistics in non-melanoma skin cancer analysis.

Non-Melanoma skin cancer is one of the most frequent types of cancer. Early detection is encouraged so as to ensure the best treatment, Hyperspectral imaging is a promising technique for non-invasive inspection of skin lesions, however, the optimal wavelengths for these purposes are yet to be conclusively determined. A visible-near infrared hyperspectral camera with an ad-hoc built platform was used for image acquisition in the present study. Robust statistical techniques were used to conclude an optimal range between 573.45 and 779.88 nm to distinguish between healthy and non-healthy skin. Wavelengths between 429.16 and 520.17 nm were additionally found to be optimal for the differentiation between cancer types.

Viruses and Skin Cancer.

Advances in virology and skin cancer over recent decades have produced achievements that have been recognized not only in the field of dermatology, but also in other areas of medicine. They have modified the therapeutic and preventive solutions that can be offered to some patients and represent a significant step forward in our knowledge of the biology of skin cancer. In this paper, we review the viral agents responsible for different types of skin cancer, especially for solid skin tumors. We focus on human papillomavirus and squamous cell cancers, Merkel cell polyomavirus and Merkel cell carcinoma, and human herpesvirus 8 and Kaposi's sarcoma.

Definition of prognostic subgroups in the T3 stage of the eighth edition of the American Joint Committee on Cancer staging system for cutaneous squamous cell carcinoma: Tentative T3 stage subclassification.

BACKGROUND: Although the eighth edition of the American Joint Committee on Cancer staging system (AJCC8) provides improved prognosis stratification of cutaneous squamous cell carcinoma (CSCC) over AJCC7, T3 has a variable prognosis. OBJECTIVE: To define prognostic subgroups in T3-AJCC8 CSCC. METHODS: Retrospective cohort study of 196 primary T3-AJCC8 CSCCs. We conducted multidimensional scaling analysis using the 6 risk factors that define T3 CSCCs. The prognoses of the groups obtained were analyzed by means of competing risk analysis. RESULTS: Group 1 was characterized by a tumor thickness greater than 6 mm (without invasion beyond the subcutaneous fat), alone or in combination with a tumor width of at least 4 cm. Group 2 was characterized by the presence of either invasion beyond the subcutaneous fat or by the involvement of nerves (≥0.1 mm, or deeper than the dermis). Group 3 was characterized by the combination of both T3b risk factors, or of 3 or more risk factors. Group 3 (tentatively named T3c) patients had the worst prognosis for disease-specific poor outcome events and major events, Group 2 (T3b) had intermediate risk, and Group 1 (T3a) had the best prognosis (disease-specific poor outcome events: hazard ratio [HR], 1.94; P = .00009; major events: HR, 2.55; P = .00001; disease-specific death: HR, 10.25; P = .0009). LIMITATIONS: Retrospective study. CONCLUSIONS: There is statistically significant evidence that T3-AJCC8 may be classified into distinct prognostic subgroups.

Performance of Salamanca refinement of the T3-AJCC8 versus the Brigham and Women's Hospital and Tübingen alternative staging systems for high-risk cutaneous squamous cell carcinoma.

INTRODUCTION: The Brigham and Women's Hospital and the Tübingen cutaneous squamous cell carcinoma (SCC) stratification systems propose different criteria from the American Joint Committee on Cancer, eighth edition. Our group identified prognostic subgroups within T3 stage according to the American Joint Committee on Cancer eighth edition's classification, the most common classification for high-risk cutaneous SCCs. OBJECTIVE: To compare the performance and prognostic accuracy of these staging systems in a subset of high-risk cutaneous SCCs. METHODS: Homogeneity, monotonicity, and McNemar tests for pairwise comparisons were assessed. Distinctiveness and relative risk of poor outcome were calculated by stage. Prognostic accuracy was compared with respect to quality (Akaike and Bayesian information criteria), concordance (Harrell C-index and Gönen and Heller concordance probability estimate), and predictive accuracy (sensitivity, specificity, negative predictive value, positive predictive value, and global accuracy). RESULTS: The Brigham and Women's Hospital and Salamanca systems were more distinctive, homogeneous, and monotonic than the Tübingen system. The Tübingen system was the most specific, whereas the Salamanca and Brigham and Women's Hospital systems were more sensitive. Negative predictive value was high in all 3 systems, but positive predictive value and accuracy were low overall. CONCLUSIONS: Alternative staging systems may partially overcome the heterogeneity and low prognostic accuracy of the American Joint Committee on Cancer, eighth edition and enable high-risk cutaneous SCCs to be stratified more reliably, but their prognostic accuracy is still low. Considering the accumulation of risk factors may improve high-risk cutaneous SCC risk stratification.

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.

Comparing the eighth and the seventh editions of the American Joint Committee on Cancer staging system and the Brigham and Women's Hospital alternative staging system for cutaneous squamous cell carcinoma: Implications for clinical practice.

BACKGROUND: The new eighth edition of the American Joint Committee on Cancer staging system (AJCC-8) incorporates changes regarding cutaneous squamous cell carcinoma (CSCC). OBJECTIVES: We aimed to compare the AJCC-8 staging system with the previous seventh edition of the AJCC staging system (AJCC-7) and the Brigham and Women's Hospital (BWH) alternative staging system to identify their usefulness and the utility of their risk factors in defining prognostic groups in CSCC. METHODS: A series of 186 CSCCs of the head and neck were retrospectively collected. All 3 staging systems were compared from the standpoint of their ability to predict poor prognosis. Binary logistic regression models were built to determine which risk factors were most relevant. RESULTS: Poor prognosis was mainly associated with stage T2 of the AJCC-7, with stages T2b/T3 of the BWH system, and with stage T3 of the AJCC-8. The AJCC-8 and the BWH staging systems displayed overlap with each another in predicting poor prognosis, and both were superior to the AJCC-7. The new risk factors incorporated into the AJCC-8 and the poor degree of differentiation were independently associated with poor outcome. LIMITATIONS: Retrospective study and few cases with bone invasion. CONCLUSIONS: The AJCC-8 is more distinctive, monotonous, and homogeneous than the AJCC-7 and shows some overlap with the BWH system in stratification of tumors.

Familial papular epidermal nevus with "skyline" basal cell layer.

Papular epidermal nevus with "skyline" basal cell layer is a variant of keratinocytic nevus that usually occurs sporadically but may affect different family members. We report on the fourth family with papular epidermal nevus with "skyline" basal cell layer affecting a 3-month-old girl and her father.

Spontaneous Regression of a Plaque-Type Striated Muscle Hamartoma.

Striated muscle hamartoma (SMH) is a rare, congenital or acquired, benign tumor that predominantly affects children. Therapeutic management has classically been surgical intervention. We present a pediatric case of a facial plaque-type SMH with spontaneous regression that highlights the importance of clinical observation for a conservative approach.