Development of the Melanoma Concerns Questionnaire (MCQ-28); refinement of the EORTC QLQ-MEL38 module.

OBJECTIVE: Few patient-reported outcome measures (PROMs) have been developed that adequately measure the patient-experience following diagnosis and treatment of melanoma. Building on previous research, which developed the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Module (QLQ-MEL38), the aim of this study was to further test the hypothesised domain structure and psychometric properties of the phase 3 module, in a new larger sample of melanoma patients. METHODS: Melanoma patients (n = 270) were recruited from four countries (Australia, England, Serbia, and Spain). Patients completed the EORTC core questionnaire (QLQ-C30), the QLQ-MEL38, and a sociodemographic survey. Using this new larger dataset, comparisons were made with the hypothesised domain structure of the EORTC phase 3 module using principal component analysis. Items which formed subscales in a revised domain structure were then tested for goodness of fit (GoF) to the Rasch model. RESULTS: The original hypothesised and final domain structures were similar but not identical. Twenty-four items (83%) loaded onto the same distinct subscales previously generated by phase 3, and item-by-item comparison of the two pattern matrices indicated an extremely close match. Ten items were removed from the QLQ-MEL38 phase 3 module, and rescoring of some items was required. Four subscales, together with five individual items, comprised the final instrument. CONCLUSION: The newly developed measure (named the Melanoma Concerns Questionnaire; MCQ-28) was found to tap into several important psychosocial domains of concern to melanoma patients, particularly those being managed in "usual" clinic settings.

Incidence rate and clinicopathological features of 62 atypical fibroxanthomas in a North-Western Spanish population.

BACKGROUND/OBJECTIVES: Atypical fibroxanthoma (AFX) is a mesenchymal neoplasm of unknown incidence. It has been determined that AFX is a tumour with low aggressiveness as long as it is properly diagnosed. Our objectives were to exclude pleomorphic dermal sarcomas or other skin tumours incorrectly diagnosed as AFX in our centre after applying strict diagnostic criteria and to assess the behaviour of appropriately diagnosed AFX. METHODS: We conducted an observational retrospective analysis of 73 patients diagnosed with AFX in our centre between 1998 and 2018. After selecting cases fulfilling AFX criteria, we made an analysis of predictive factors for local recurrence. Crude and sex-adjusted incidence rates were calculated. RESULTS: Out of 73 cases, 62 were eventually diagnosed as AFX. We examined for absence of tumour necrosis, lymphovascular or perineural invasion and infiltration of deep structures. Cytokeratin AE1-AE3, desmin and CD34 were negative in all cases. The remaining tumours were reclassified. The incidence of AFX in our health-care area was estimated at 0.59 cases every 100 000 inhabitants per year. In our series, 72.6% of the patients were men with mean age at diagnosis of 81 years. Average tumour diameter was 12 mm. The most common location was head and neck (96.8%). Only four local recurrences were detected over a mean of 47-month follow-up. CONCLUSIONS: We report a series of AFX in our health-care area. We verify its indolent course when it is properly diagnosed.

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.

The presence of Merkel cell carcinoma polyomavirus is associated with a distinct phenotype in neoplastic Merkel cell carcinoma cells and their tissue microenvironment.

AIMS: Merkel cell carcinoma (MCC) is an aggressive primary neuroendocrine tumor of the skin, associated with Merkel cell polyomavirus (MCPyV) in 49-89% of cases, depending on the country of origin and the techniques of detection. The presence of MCPyV defines heterogeneity in MCC; MCPyV-negative cases bear a much higher mutational load, with a distinct ultraviolet signature pattern featuring C > T transitions, as a consequence of exposure to ultraviolet light radiation. MCC stroma has not been thoroughly studied, although MCC patients benefit from therapy targeting PD1/PDL1. METHODS AND RESULTS: In this study, using Tissue Microarrays and immunohistochemistry, we have analyzed a series of 219 MCC cases in relation to the presence of MCPyV, and confirmed that the presence of MCPyV is associated with changes not only in the neoplastic cells, but also in the composition of the tumor stroma. Thus, MCPyV, found in 101/176 (57,4%) analyzable cases, exhibits changes in its tumor morphology, the density of the inflammatory infiltrate, the phenotype of the neoplastic cells, and the cell composition of the tumor stroma. MCPyV presence is negatively correlated with a higher level of p53 expression, and associated with a very high frequency (86%) of HLA-I expression loss, a higher apoptotic index, and a stroma richer in T-cells, cytotoxic T-cells, macrophages, PDL1-positive macrophages, and B-cells. CONCLUSIONS: Our findings provide evidence of the basic heterogeneity of MCC, supporting the hypothesis that the presence of MCPyV may induce a rich inflammatory response, which is at least partially avoided through loss of HLA-I antigen expression. On the other hand, MCPyV-negative cases show a much higher frequency of stronger p53 expression and, probably, p53 alterations.

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.