Trends in Medicare Billing Among Mohs Surgeons in the United States During 2012: A Retrospective Cohort Study.

BACKGROUND: It is important to understand variability in practice patterns of Mohs surgeons. OBJECTIVE: To examine the practice patterns of physicians performing Mohs micrographic surgery (MMS) in the United States. METHODS AND MATERIALS: This retrospective cohort study of the 2012 Medicare Physician and Other Supplier Public Use Files includes all physicians who billed Medicare for MMS. RESULTS: The authors found 2,067 physicians who billed Medicare for MMS in 2012. American College of Mohs Surgery (ACMS) members took a significantly higher average number of head and neck (H&N) and trunk layers compared with American Society for Mohs Surgery (ASMS) members and those with no membership (p < .001). Male surgeons, surgeons with more experience (21+ years out), surgeons in private practice, and those practicing in rural populations closed a significantly greater proportion of cases with flaps or grafts, as compared to females (p < .001), those with less experience (<21 years out) (p < .001), surgeons in academic practice (p = .004), and those practicing in urban or cluster populations (p < .001), respectively. CONCLUSION: There is significant variability in practices of Mohs surgeons in the United States.

Decreased T-Cell Programmed Death Receptor-1 Expression in Pregnancy-Associated Melanoma.

INTRODUCTION: Pregnancy depends on tolerance of an immunologically foreign fetus through type 1 T-cell suppression. Worse melanoma outcomes have been described within 1 year of childbirth. We assessed immunopathologic factors that may account for the observed negative impact of pregnancy on outcome. MATERIALS AND METHODS: Women of child-bearing age with ≥24 months follow-up were identified from our Institutional Melanoma Registry. Women with available primary tumor blocks were compared [history of childbirth within 1 year of diagnosis (CB1Y) (n = 18) vs. nonpregnant age-matched controls (n = 13)]. Immunohistochemical staining with quantification of immune infiltrates: CD68 tumor-associated macrophages, CD3 tumor-infiltrating T cells, and PD-1 activated/exhausted T cells; and hematolymphangiogenesis: CD31/D2-40 blood vessels and D2-40 lymphatics was performed by 2 blinded dermatopathologists. RESULTS: CB1Y tumors showed decreased CD3 tumor-infiltrating T cells (P < 0.05) with significantly reduced PD1 expression (P ≤ 0.05). The CD3:PD1 ratio was higher in CB1Y (P < 0.05). Other tested parameters did not significantly differ between the 2 groups. DISCUSSION: As PD1 expression is induced during type 1 T-cell activation, these data suggest that immune ignorance or suppression may predominate in CB1Y. Further studies are required to identify interventions that may promote tumor-associated T-cell inflammation in such patients.

Determination of the impact of melanoma surgical timing on survival using the National Cancer Database.

BACKGROUND: The ideal timing for melanoma treatment, predominantly surgery, remains undetermined. Patient concern for receiving immediate treatment often exceeds surgeon or hospital availability, requiring establishment of a safe window for melanoma surgery. OBJECTIVE: To assess the impact of time to definitive melanoma surgery on overall survival. METHODS: Patients with stage I to III cutaneous melanoma and with available time to definitive surgery and overall survival were identified by using the National Cancer Database (N = 153,218). The t test and chi-square test were used to compare variables. Cox regression was used for multivariate analysis. RESULTS: In a multivariate analysis of patients in all stages who were treated between 90 and 119 days after biopsy (hazard ratio [HR], 1.09; 95% confidence interval [CI], 1.01-1.18) and more than 119 days (HR, 1.12; 95% CI, 1.02-1.22) had a higher risk for mortality compared with those treated within 30 days of biopsy. In a subgroup analysis of stage I, higher mortality risk was found in patients treated within 30 to 59 days (HR, 1.05; 95% CI, 1.01-1.1), 60 to 89 days (HR, 1.16; 95% CI, 1.07-1.25), 90 to 119 days (HR, 1.29; 95% CI, 1.12-1.48), and more than 119 days after biopsy (HR, 1.41; 95% CI, 1.21-1.65). Surgical timing did not affect survival in stages II and III. LIMITATIONS: Melanoma-specific survival was not available. CONCLUSION: Expeditious treatment of stage I melanoma is associated with improved outcomes.

Stage IV melanoma of unknown primary: A population-based study in the United States from 1973 to 2014.

BACKGROUND: Melanoma of unknown primary (MUP) is incompletely described on a population level. OBJECTIVE: We sought to characterize stage IV MUP in a population-based cancer registry. METHODS: We developed a novel search algorithm to identify cases of stage IV MUP in the Surveillance, Epidemiology, and End Results 18 registries from 1973 to 2014. Cases of stage IV melanoma of known primary (MKP) served as a comparison group. Age-standardized incidence rates, demographic characteristics, adjusted disease-specific survival, and Cox proportional hazard models were calculated for MUP and MKP. RESULTS: A total of 322 stage IV MUP cases and 12,796 stage IV MKP cases were identified in Surveillance, Epidemiology, and End Results 18 registries from 1973 to 2014. The incidence of stage IV MUP is increasing, particularly for patients younger than 30 years of age. In multivariate analyses, age older than 50 and a lack of surgical treatment were negative prognostic factors for stage IV MUP. Relative survival, but not 5-year adjusted disease-specific survival, was higher for stage IV MUP than for MKP. LIMITATIONS: Limitations include the retrospective study design and possible misclassification of MUP. CONCLUSIONS: The incidence of stage IV MUP is increasing, and stage IV MUP shares similar prognostic factors with stage IV MKP, including age and surgical treatment.

Mixed Versus Pure Variants of Desmoplastic Melanoma: The Cleveland Clinic Experience.

BACKGROUND: Desmoplastic melanoma (DM) is a subvariant of spindle cell melanoma, accounting for less than 4% of all cutaneous melanomas. It occurs later in life and is associated with chronic sun exposure. Desmoplastic melanoma prognosis is considered more favorable than other variants, with lower rates of metastasis and higher survival. Recently, DM has been further subclassified into pure and mixed, calling into question surgical management and patient outcomes as well as viability of current nationwide databases without this distinction. METHODS: We identified all patients with a histopathologic diagnosis of DM from the Cleveland Clinic electronic melanoma database (n = 58) from 1997 to 2013. Clinical and histopathologic data were collected. Comparison in clinical variables was performed between patients who had pure (n = 15) and mixed (n = 43) variants of DM. RESULTS: There were no differences in age, sex, location of lesion, Breslow depth, ulceration, or regression. Patients with mixed DM were more likely to have lymphovascular invasion (P = 0.03) compared with pure DM. There was no difference in performance of sentinel lymph node biopsy (P = 0.25) or sentinel lymph node positivity (P = 0.31) between the 2 groups. Recurrence was present in 13.3% of pure and 30.2% of mixed patients. Overall, Kaplan-Meier 3-year survival was 75% for pure and 80% for mixed DM (P = 0.53). CONCLUSIONS: Pure and mixed DMs seem to have similar clinical characteristics and outcomes. This indicates that analysis of national datasets without this subclassification remains viable.

Beck Depression Inventory-II: Factor Analyses with Three Groups of Midlife Women of African Descent in the Midwest, the South, and the U.S. Virgin Islands.

This research encompasses a factor analysis of the Beck Depression Inventory-II (BDI-II), which involves three groups of midlife women of African descent who reside in the Midwest, the South, and the U.S. Virgin Islands. The purpose of the study was to determine the factor structure of the BDI-II when administered to a sample of women aged 40-65 of African descent who reside in the three distinct geographical regions of the United States. A correlational, descriptive design was used, and 536 women of African descent were invited to participate in face-to-face interviews that transpired in community settings. Results of the factor analysis revealed a two-factor explanation. Factor one included symptoms such as punishment feelings and pessimism (cognitive), and the second factor included symptoms such as tiredness and loss of energy (somatic-affective). The application of the Beck Depression Inventory-II among the three groups of women generated specific information about each group and common findings across the groups. Knowledge gained from the research could help to guide specific intervention programs for the three groups of women, and explicate the common approaches that could be used for the three groups.

The role of immunosuppression in squamous cell carcinomas arising in seborrheic keratosis.

BACKGROUND: Seborrheic keratoses (SK) are common skin neoplasms considered to be benign. Reports of associated squamous cell carcinoma arising within seborrheic keratosis (SCC-SK) have been described. OBJECTIVE: To describe the histopathologic characteristics of SCC-SK and identify predisposing factors in formation of these rare lesions. METHODS: There were 162 cases of SCC-SK in a span of a decade (2003-2014). All of the histopathologic specimens and medical records were reviewed. Data from these patients were compared to a control group with seborrheic keratosis who were matched by age, sex, and location of lesion from the same time period (n = 162). RESULTS: SCC-SK has the classic histopathologic features of SK, such as hyperkeratosis, parakeratosis, papillomatosis, and pseudohorn cysts. The areas of squamous cell carcinoma were characterized by areas of squamous dysplasia (100%), hypogranulosis (79.6%), squamous eddies (79.6%), solar elastosis (80.9%), and brown pigmentation (59.9%). Patients with a history of immunosuppression had an increased risk for developing SCC-SK (19% vs 3%; P < .01), particularly when inhibition was transplant-associated (10% vs 0%; P < .01). LIMITATIONS: This was a single center, retrospective study. CONCLUSION: SCC-SK occurs more often in elderly men with a history of immunosuppression associated with organ transplants.

Risk factors and outcomes of cutaneous melanoma in women less than 50 years of age.

BACKGROUND: Melanoma is the fifth most common cancer in the United States, with recent reports indicating increasing incidence among young women. OBJECTIVE: This study sought to investigate histopathology, staging, risk factors, and outcomes of cutaneous melanoma in women younger than 50 years. METHODS: All female patients aged up to 49 years with biopsy-proven diagnosis of melanoma between 1988 and 2012 were included. Patients with a follow-up of less than 2 years were excluded. RESULTS: A total of 462 patients were identified, with mean age of 34.7 years. Invasive melanoma was less common in women 19 years of age or younger (P < .0008). Positive sentinel node status (P < .008), recurrence rates, metastatic disease (P < .001), and death rates (P < .008) were higher for women ages 40 to 49 years. The 41 patients with a pregnancy-associated melanoma had a significantly worse prognosis in comparison with a control group of nonpregnant patients, with a 9-fold increase in recurrence (P < .001), 7-fold increase in metastasis (P = .03) and 5-fold increase in mortality (P = .06). LIMITATIONS: This was a retrospective study. CONCLUSION: The increasing incidence of melanoma for women younger than 50 years suggests that regular skin checks and self-examinations are warranted. In addition, in women given the diagnosis of melanoma during or within 1 year after childbirth, regular follow-up and monitoring for recurrence are recommended.

Prevalence of Comorbid Conditions and Sun-Induced Skin Cancers in Patients with Alopecia Areata.

Alopecia areata is a multifactorial autoimmune disease causing non-scarring hair loss. Recent genome-wide association studies have pointed to connections between alopecia areata and other autoimmune disorders. Research of clinical conditions positively and negatively associated with alopecia areata is crucial for discovering the pathological mechanisms of disease and further treatment options.

Combining mechanism-based prediction with patient-based profiling for psoriasis metabolomics biomarker discovery.

Psoriasis is a chronic, debilitating skin condition that affects approximately 125 million individuals worldwide. The cause of psoriasis appears multifactorial, and no unified mitigating signal or single antigenic target has been identified to date. Metabolomic studies hold great potential for explaining disease mechanism, facilitating early diagnosis, and identifying potential therapeutic areas. Here, we present an integrated disease metabolomic biomarker discovery strategy that combines mechanism-based biomarker discovery with clinical sample-based metabolomic profiling. We applied this strategy in identifying and understanding metabolite biomarkers for psoriasis. The key innovation of our strategy is a novel mechanism-based metabolite prediction system, mmPredict, which assimilates vast amounts of existing knowledge of diseases and metabolites. mmPredict first constructed a psoriasis-specific mouse mutational phenotype profile. It then constructed phenotype profiles for a total of 259,170 chemicals/metabolites using known chemical genetics and human metabolomic data. Metabolites were then prioritized based on the phenotypic similarities between disease- and metabolites. We evaluated mmPredict using 150 metabolites identified using our in-house metabolome profiling study of psoriasis patient samples. mmPredict found 96 of the 150 metabolites and ranked them highly (recall: 0.64, mean ranking: 8.73%, median ranking: 2.33%, p-value: 4.75E-44). These results show that mmPredict is consistent with, as well as a complement to, traditional human metabolomic profiling studies. We then developed a strategy to combine outputs from both systems and found that the oxidative product of linoleic acid, 13(S)-hydroxy-9Z,11E-octadecadienoic acid (13- HODE), ranked highly by both mmPredict and our in-house experiments. Our integrated analysis indicates that 13- HODE may be a mechanistic link between psoriasis and cardiovascular comorbidities associated with psoriasis. In summary, we developed an integrated metabolomic prediction system that combines both human metabolomic studies and mechanism-based prediction and demonstrated its application in the skin disease psoriasis. Our system is highly general and can be applied to other diseases when patient-based metabolomic profiling data becomes more increasingly available. Data is publicly available at: http://nlp. CASE: edu/public/data/mmPredict_PSO.