Characterizing dermatologic findings among patients with PTEN hamartoma tumor syndrome: Results of a multicenter cohort study.

BACKGROUND: Dermatologic phenotypes in PTEN hamartoma tumor syndrome (PHTS) are heterogeneous and poorly documented. OBJECTIVE: To characterize dermatologic findings among PHTS and conduct an analysis of genotype-dermatologic phenotype associations. METHODS: Mucocutaneous findings were reviewed in a multicenter cohort study of PHTS. Genotype-dermatologic phenotype associations were tested using multivariable regression. RESULTS: A total of 201 patients were included. Children were significantly less likely than adults to have oral papillomas, vascular malformations, benign follicular neoplasms, and acral keratoses. There were no cases of skin cancer among children. Basal cell carcinoma, cutaneous squamous cell carcinoma, and melanoma developed in 5%, 2%, and 1% of White adults, respectively. After adjusting for age, missense mutations were associated with 60% lower odds of developing cutaneous papillomatous papules (odds ratio: 0.4; 95% confidence interval [0.2, 0.7]), oral papillomas (0.4; 95% confidence interval [0.2, 0.9]), and vascular malformations (0.4; 95% confidence interval [0.2, 0.8]). LIMITATIONS: Partly retrospective data. CONCLUSION: Children are less likely than adults to have certain dermatologic findings, likely due to age-related penetrance. The risk of pediatric melanoma and the lifetime risk of nonmelanoma skin cancer in PHTS may not be elevated. Missense variants may be associated with the development of fewer dermatologic findings but future validation is required.

Factors associated with matching into research-focused dermatology residency programs.

Although dermatology is one of the most competitive specialties to match into, there is limited transparency in the residency match process. In this retrospective cohort study of 2234 allopathic medical graduates, we identify applicant characteristics associated with matching into research oriented dermatology programs. Many of the statistically significant variables in our study, including PhD/MD status, graduating from a Top-25 NIH funded medical school, increasing total number of pre-residency publications (PRPs), and increasing number of high-impact PRPs, correlate with future academic employment. Although literature shows an association between an increasing number of first author PRPs and future academic employment, we did not find number of first or last author PRPs to be predictive of matching into a research oriented residency program. A more comprehensive evaluation of an applicant's research output, considering both the final products of an applicant's research endeavors and an applicant's role in various projects, may better approximate an applicant's commitment to academics.

Can the alcohol withdrawal scale be applied to post-operative patients?

BACKGROUNDS: Assessment scales are commonly used to diagnose and treat alcohol withdrawal syndrome (AWS) in acute hospitals, although they have only been validated for use in detoxification facilities. There is a significant overlap between the symptoms and signs of AWS and other clinical presentations, including systemic inflammatory response syndrome (SIRS) and the physiological response to surgery. This may lead to both over-diagnosis and inappropriate treatment of AWS. This study sought to determine the false-positive rate for the commonly used Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) among post-operative patients. METHODS: This was a prospective study of patients undergoing major abdominal surgery at University Hospital Geelong. Patients were recruited who were NOT at risk of alcohol dependency (using the World Health Organisation Alcohol Use Disorders Identification Test). Patients were assessed for AWS using the CIWA-Ar day one post-operatively with a false positive measured as a CIWA-Ar > 7. RESULTS: A total of 67 patients were included in the study. There were 31 (46%) men and 36 women. Their median age was 52 years (range 27-85). Thirty-six (52%) of patients underwent elective procedures, and 32 were emergencies. Twelve of the 67 patients (18%) had CIWA-Ar scores >seven. CONCLUSION: In the early post-operative period, the CIWA-Ar tool over-diagnoses AWS in 18% of patients. These false-positives could lead to delayed treatment of serious underlying conditions. We call for caution in the use of alcohol withdrawal scales in the acute hospital setting.

Trends of Research Output of Allopathic Medical Students Matching Into Dermatology, 2007-2018.

IMPORTANCE: According to the National Residency Matching Program's biennial Charting Outcomes in the Match (NRMP ChOM) reports, the mean number of research items of matched allopathic dermatology applicants has nearly tripled since 2007, rising from 5.7 to 14.7. Research items are self-reported by applicants and serve as an approximation of research output. Because the NRMP research items field is unverified and reported as an aggregate of several different research pursuits, it may not be an accurate representation of applicant research output. OBJECTIVE: To determine if the rise in NRMP-reported data is associated with a rise in verifiable, indexed publications from matched allopathic dermatology applicants from 2007 to 2018. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study including a bibliometric analysis on accepted applicant research output among 2234 matched allopathic dermatology applicants, with a total of 6229 publications, in dermatology residency programs for the years 2007, 2009, 2011, 2014, 2016, and 2018. MAIN OUTCOME AND MEASURES: The primary outcomes were the mean number of peer-reviewed indexed publications and mean number of NRMP ChOM research items. Secondary outcomes assessed the quality of indexed publications by analyzing article type and journal of publication. RESULTS: From 2007 to 2018, the mean number of indexed publications per matched dermatology applicant increased from 1.6 to 4.7 (203% increase). Indexed publications consistently compose a minority of NRMP ChOM research items (28.8% across the 6 years of the study). Nonindexed research items increased at more than double the rate of indexed publications. Bibliometric analysis showed that all other types of publications are increasing at a rate of 6 to 9 times that of basic science publications, dermatology-related publications increased at 5 times the rate of non-dermatology publications, and publications in lower-impact factor dermatology journals increased at 4 times the rate of publications in higher-impact factor dermatology journals. CONCLUSIONS AND RELEVANCE: This cross-sectional study provides data on the research output of matched dermatology applicants. Indexed publications compose a minority of NRMP research items. Medical student self-reports of research output may emphasize research quantity over quality.

Brigham and Women's Hospital tumor classification system for basal cell carcinoma identifies patients with risk of metastasis and death.

BACKGROUND: Despite approximately 4400 locally advanced US cases annually, high-stage basal cell carcinoma (BCC) is ill-defined. OBJECTIVE: To develop a tumor (T) staging system for BCC that will predict metastasis/death and compare its performance with that of the American Joint Committee on Cancer 8th edition (AJCC8) T-staging system. METHODS: Brigham and Women's Hospital (BWH) T staging was developed from a previously published nested cohort of 488 primary BCCs. Tumors were staged via BWH and AJCC8 T-staging systems, and predictions of metastasis and/or death were compared. RESULTS: The BWH and AJCC8 T-staging systems both captured all metastases/deaths in high T stages (BWH, T2; AJCC8, T3/T4). BWH T2 included 54% fewer cases ≥2 cm than AJCC8 T3/T4. BWH had a higher specificity (0.92 vs 0.80; P < .001) and positive predictive value (24% vs 11%, P < .001) for identifying cases at risk for metastasis/death, and the C-statistic was superior for BWH (P < .001). The BWH T2 10-year cumulative incidence of metastasis/death was 37% (95% confidence interval, 21%-60%). LIMITATIONS: Two-center cohort. CONCLUSIONS: BWH and AJCC 8 BCC staging both capture all metastases and deaths in the upper stages. However, BWH staging does so in half the number of cases, thus minimizing inappropriate up-staging. The risk of metastasis or death in BWH T2 BCC is sufficient to warrant surveillance for recurrence and clinical trials of adjuvant therapy.

Factors predictive of recurrence, metastasis, and death from primary basal cell carcinoma 2 cm or larger in diameter.

BACKGROUND: Basal cell carcinoma (BCC) recurrence and metastatic rates are known to be very low. The risk factors for these rare outcomes are subsequently not well studied. OBJECTIVE: To identify risk factors independently associated with local recurrence (LR) and metastasis and/or death (M/D) in large (≥2 cm) BCC. METHODS: BCCs histologically confirmed between 2000 and 2009 were retrospectively screened for tumor diameter at 2 academic centers. Medical records of all large BCCs and an equal number of randomly selected small BCCs were reviewed for LR and M/D. RESULTS: Included were 248 large BCC and 248 small BCC tumors. Large BCCs had a significantly higher risk of LR and M/D than small BCCs (LR: 8.9% vs 0.8%, P < .001; M/D: 6.5% vs. 0%, P < .001). Because the risks were so low in small BCCs, they were excluded from further analysis. On multivariable logistic regression, head/neck location (odds ratio [OR], 9.7; 95% confidence interval [CI], 3.0-31.3) and depth beyond fat (OR, 3.1; 95% CI, 1.0-9.6) were associated with LR in large BCCs. Risk of LR was lower with Mohs micrographic surgery (OR, 0.14; 95% CI, 0.04-0.5). Head/neck location (OR, 5.3; 95% CI, 1.2-23.2), tumor diameter ≥4 cm (OR, 11.9; 95% CI, 2.4-59.4), and depth beyond fat (OR, 28.6; 95% CI, 6.7-121) were significant predictors of M/D in large BCCs. LIMITATIONS: Retrospective cohort design. CONCLUSIONS: Large BCCs, particularly those with additional risk factors, have a high enough risk of recurrence and metastasis to warrant further investigation to optimize management.

A comparison of skin cancer screening and treatment costs at a Massachusetts cancer center, 2008 versus 2013.

BACKGROUND: Temporal analyses of skin cancer costs are needed to examine how expenditure differences between diagnoses are changing. OBJECTIVE: To tabulate the costs of skin cancer-related care (SCRC), including both screening and treatment, at an academic cancer center at 2 time points. METHODS: Cost data (insurance and patient payments) at an academic cancer center from 2008 and 2013 were queried for International Classification of Diseases, Ninth Revision, codes pertaining to skin cancer. Screening costs were separated from treatment costs through associated Current Procedural Terminology codes. RESULTS: The total annual cost of SCRC increased by 64%, the number of patients receiving SCRC increased by 45%, and the mean cost per patient treated increased by 13%. Screening accounted for 17% and 16% of total annual costs in 2008 and 2013, respectively. The mean cost per patient with melanoma increased by 84%, which was the largest increase among skin cancer diagnoses. In 2013, the few patients with melanoma who were treated with ipilimumab (n = 48 [4% of patients with melanoma]) accounted for 42% of melanoma treatment costs and 20% of SCRC costs. LIMITATIONS: Prescription costs were unavailable. CONCLUSIONS: Melanoma costs have increased as a result of the introduction of ipilimumab. Ongoing studies are needed to monitor the cost-effectiveness of SCRC at a national level.

Association of Nodal Metastasis and Mortality With Vermilion vs Cutaneous Lip Location in Cutaneous Squamous Cell Carcinoma of the Lip.

Importance: Although the lip is considered a high-risk location in cutaneous squamous cell carcinoma (cSCC), it has not been established whether this risk stems from vermilion or cutaneous locations or both. Objective: To compare differences in risks of recurrence, metastasis, and death from cSCCs on the vermilion vs cutaneous lip. Design, Setting, and Participants: Retrospective cohort study of 303 patients with 310 primary cSCCs of the lip (138 cutaneous, 172 vermilion) diagnosed between 2000 and 2015 at 2 academic tertiary care centers in Boston, Massachusetts. Main Outcomes and Measures: Development of local recurrence, nodal metastasis, distant metastasis, disease-specific death, and all-cause death. Results: Of the 303 study participants with 310 SCCs of the lip, 153 (50.5%) were men, and 150 (49.5%) were women; median age at diagnosis, 68 years (range, 27-93 years). Outcomes were as follows for vermilion vs cutaneous locations: local recurrence, 6.4% (11 of 172) vs 2.9% (4 of 138); nodal metastasis, 7.6% (13 of 172) vs 1.5% (2 of 138); distant metastasis, 0.6% (1 of 172) vs 0.7% (1 of 138); disease-specific death, 3.5% (6 of 172) vs 2.9% (4 of 138); and all-cause death, 26.7% (46 of 172) vs 29.0% (40 of 138). The difference was statistically significant for nodal metastasis (P = .01). In multivariable analysis, nodal metastasis was associated with vermilion lip location (subhazard ratio, 5.0; 95% CI, 1.1-23.8) and invasion beyond fat (fascia or beyond for vermilion lip) (subhazard ratio, 4.4; 95% CI, 1.3-14.9). Conclusions and Relevance: The risk of nodal metastasis is 5-fold greater for cSCCs on the vermilion lip compared with those on the cutaneous lip. Squamous cell carcinomas of the cutaneous lip have a nodal metastasis risk similar to cSCCs in general (1.5%). Thus, vermilion involvement appears responsible for the increased risk associated with cSCC of lip. Vermilion involvement may merit radiologic nodal staging and inclusion in future tumor staging, since it was independently associated with higher-risk cSCC of the lip region.

An ecological study of skin biopsies and skin cancer treatment procedures in the United States Medicare population, 2000 to 2015.

BACKGROUND: Analyses of skin cancer procedures adjusted for population changes are needed. OBJECTIVE: To describe trends in skin cancer-related biopsies and procedures in Medicare beneficiaries. METHODS: An ecological study of Medicare claims for skin biopsies and skin cancer procedures in 2000 to 2015. RESULTS: Biopsies increased 142%, and skin cancer procedures increased 56%. Mohs micrographic surgery (MMS) utilization increased on the head/neck, hands/feet, and genitalia (increasing from 11% to 27% of all treatment procedures) but was low on the trunk/extremities (increasing from 1% to 4%). Adjusted for increased Medicare enrollment (+36%) between 2000 and 2015, the number of biopsies and MMS procedures performed per 1000 beneficiaries increased (from 56 to 99 and from 5 to 15, respectively), whereas the number of excisions and destructions changed minimally (from 18 to 16 and from 19 to 18, respectively). Growth in biopsies and MMS procedures slowed between each time period studied: 4.3 additional biopsies per year and 0.9 additional MMS procedures per year per 1000 beneficiaries between 2000 and 2007, 2.2 and 0.5 more between 2008 and 2011, and 0.5 and 0.3 more between 2012 and 2015, respectively. LIMITATIONS: Medicare claims-level data do not provide patient-level or nonsurgical treatment information. CONCLUSIONS: The increased number of skin cancer procedures performed was largely the result of Medicare population growth over time. MMS utilization increased primarily on high- and medium-risk and functionally and cosmetically significant locations where tissue sparing and maximizing cure are critical.

Comparison of Tumor Classifications for Cutaneous Squamous Cell Carcinoma of the Head and Neck in the 7th vs 8th Edition of the AJCC Cancer Staging Manual.

Importance: Previous studies have shown that the AJCC Cancer Staging Manual, 7th edition (AJCC 7), tumor classification for cutaneous squamous cell carcinoma (CSCC) failed to accurately stratify disease-related outcomes. The recently released 8th edition (AJCC 8) features a revised tumor classification for only head and neck CSCC (HNCSCC). Objective: To compare AJCC 7 and AJCC 8 tumor classifications for HNCSCC and to validate AJCC 8. Design, Setting, and Participants: This was a 10-year retrospective cohort study (2000-2009) at an academic tertiary care center reviewing 680 primary HNCSCC tumors in 459 patients. Main Outcomes and Measures: Primary HNCSCC tumors were reviewed for disease-related outcomes (DROs): local recurrence (LR), nodal metastasis (NM), and disease-specific death (DSD). Tumors were stratified by AJCC 7 and AJCC 8 tumor classification. Distinctiveness (outcome differences between categories), homogeneity (outcome similarity within categories), and monotonicity (outcome worsening with increasing categories) were assessed for both classifications. Results: Most of the 459 patients were white (451 [98.3%]) and male (312 [68.0%]). AJCC 8 high tumor categories (T3/T4) accounted for 121 (17.8%) of total cases but 50 of 71 DROs (70.4%) (22 of 34 of LRs [64.7%], 17 of 24 NMs [70.8%], and 11 of 13 of DSDs [84.6%]). This was a significant improvement over AJCC 7, where only 12 of 71 DROs (16.9%) (4 of 34 LRs [11.8%], 3 of 24 NMs [12.5%], and 5 of 13 DSDs [38.5%]) occurred in T3/T4 categories. However, AJCC 8 T2 and T3 were indistinct, with overlapping 95% CIs for 10-year cumulative incidences of LR, NM, and DSD. The 10-year cumulative incidence of DROs in the 119 AJCC 8 T3 cases were 19.7% (95% CI, 13.0%-29.7%) for LR, 14.1% (95% CI, 9.7%-20.7%) for NM, and 9.3% (95% CI, 6.8%-14.0% for DSD). Conclusions and Relevance: AJCC 8 demonstrates superior homogeneity and monotonicity compared with AJCC 7. It now may be possible for AJCC 8 HNCSCC T2, T3, and T4 cases to be recorded and tracked by tumor registries because they represented a 23.1% subset in this study, which includes nearly all poor outcomes (85.9%). Further work is needed to validate AJCC 8 with population-level data and to compare AJCC 8 performance against alternative tumor classifications.

Clinical and Incidental Perineural Invasion of Cutaneous Squamous Cell Carcinoma: A Systematic Review and Pooled Analysis of Outcomes Data.

Importance: Perineural invasion (PNI) in cutaneous squamous cell carcinoma (CSCC) has been associated with an increased risk of poor outcomes. Patients with PNI may present with clinical symptoms and/or radiologic evidence of PNI (clinical PNI [CPNI]), yet most patients are asymptomatic and PNI is often found on histologic examination (incidental PNI [IPNI]). Evidence-based estimates of the risks of disease-related outcomes comparing IPNI and CPNI are limited in the dermatology literature. Objectives: To review and synthesize outcomes data for patients with CSCC and CPNI or IPNI. Data Sources: A systematic review was conducted in MEDLINE and EMBASE for English-language articles published since inception to November 11, 2016. Study Selection: All studies that reported a disease-related outcome (local recurrence, nodal metastasis, distant metastasis, or disease-specific death) of CSCCs with CPNI and IPNI were included. Data Extraction and Synthesis: Articles were screened for eligibility, and any possible discrepancies in this screening were resolved. Data extracted included study characteristics, tumor characteristics, treatments performed, and disease-related outcomes. Overall risks of disease-related outcomes were generated by pooling patients from eligible studies. χ2 Statistics and Fisher exact tests were used to evaluate differences in disease-related outcomes. Main Outcomes and Measures: Risks of disease-related outcomes and 5-year recurrence-free, disease-specific, and overall survival. Results: A total of 12 studies containing 241 patients with CPNI and 381 patients with IPNI were included in the systematic review and analysis. The overall risks of local recurrence and disease-specific death were significantly higher in patients with CSCC and CPNI compared with those with CSCC and IPNI (local recurrence, 37% vs 17%; P < .001; disease-specific death, 27% vs 6%; P < .001). The risks of nodal metastasis and distant metastasis did not differ significantly by PNI classification. Patients with CSCC and CPNI had poorer mean 5-year recurrence-free survival and disease-specific survival compared with patients with IPNI (recurrence-free survival, 61% vs 76%; P = .009; disease-specific survival, 70% vs 88%; P = .002). Conclusions and Relevance: Patients with CSCC and CPNI are at an increased risk of local recurrence and disease-specific death compared with patients with CSCC and IPNI and have a 30% risk of death. Patients with PNI may benefit from increased long-term surveillance. Further studies are needed to establish standardized guidelines on follow-up and dermatologic surveillance in this high-risk patient population.