Multiomics Profiling Distinguishes Sebaceous Carcinoma from Benign Sebaceous Neoplasms and Provides Insight into the Genetic Evolution of Sebaceous Carcinogenesis.

PURPOSE: Sebaceous carcinoma is the third most common nonkeratinocyte skin cancer in the United States with 1,000 cases per year. The clinicopathologic features of sebaceous carcinoma and benign sebaceous neoplasms (adenomas, sebaceomas) can overlap, highlighting the need for molecular biomarkers to improve classification. This study describes the genomic and transcriptomic landscape of sebaceous neoplasms in order to understand tumor etiology and biomarkers relevant for diagnosis and treatment. EXPERIMENTAL DESIGN: We performed whole-genome sequencing (WGS) and whole-transcriptome sequencing (WTS) of sebaceous neoplasms from six academic and two federal healthcare facilities in the United States diagnosed between January 1, 1999, and December 31, 2021. RESULTS: We evaluated 98 sebaceous neoplasms: 64 tumors (32 adenomas, 2 sebaceomas, 5 atypical sebaceous neoplasms, 25 carcinomas) had sufficient material for WGS, 96 tumors (42 adenomas, 11 sebaceomas, 8 atypical sebaceous neoplasms, 35 carcinomas) had sufficient material for WTS, and 62 tumors (31 adenomas, 2 sebaceomas, 5 atypical sebaceous neoplasms, 24 carcinomas) had sufficient material for combined WGS and WTS. Overall, we found decreased cholesterol biosynthesis and increased TP53 mutations, copy number gains (chromosome 6, 8q, and/or 18), and tumor mutation burden-high (>10 mutations/MB) in carcinomas compared to adenomas. Although diminished compared to adenomas, most carcinomas still had higher cholesterol biosynthesis than nonmalignant skin. Multiomics profiling also supported a precancerous model of tumor evolution with sebaceomas and atypical sebaceous neoplasms being likely intermediate lesions. CONCLUSIONS: The study findings highlight key diagnostic biomarkers for sebaceous carcinoma and suggest that immunotherapy and modulation of cholesterol biosynthesis could be effective treatment strategies.

Serving up FLAN. a food literacy and nutrition intervention to fend off food insecurity.

BACKGROUND: Food insecurity, an ongoing and accelerating problem in the U.S., is an economic and social condition involving limited or uncertain access to adequate food. Some of the highest rates of food insecurity in 2022 were found among individuals who were Hispanic/Latinx (20.8%), a population that already faces disproportionate health and socioeconomic disadvantages. There remains an urgent health-related need to identify sustainable strategies to prevent food insecurity in the Latinx population. METHODS: A first-generation pilot investigation was conducted using data derived from a sub-study connected to the Computerized Physical Activity Support for Seniors (COMPASS) Trial, a 12-month cluster-randomized controlled trial among older Latinx adults. The sub-study focused on two nutrition interventions that included (1) the Food Literacy and Nutrition (FLAN) curriculum, and (2) a nutrition information-only control. Research hypotheses aimed to determine whether the FLAN intervention reduced food insecurity and increased daily fruit and vegetable servings. RESULTS: On average, participants (n = 39) were 61.5 years of age (SD = 6.7), mostly female (69%), and reported Spanish as their primary language (69%). The FLAN intervention was associated with decreased odds of food insecurity at 12 months (AOR = 0.71, 95% CI = 0.54, 0.95; p = 0.03) when compared to the nutrition-information only control intervention. Although no between-group differences in daily fruit and vegetable servings were found, there was a significant correlation between changes in daily fruit and vegetable servings from baseline to six months and changes in food insecurity from baseline to 12 months (r = -0.51, p = 0.01). CONCLUSIONS: The FLAN intervention, a bilingual and culturally tailored educational curriculum, yielded 12-month improvements in food security among a small sample of older Latinx adults. Evidence from this investigation highlights the potential utility of implementing the FLAN curriculum among individuals who are at an increased risk of food insecurity. Further investigation in a larger sample is merited to determine whether the 12-month decreases in food insecurity that were produced by the FLAN intervention can be replicated. TRIAL REGISTRATION: ClinicalTrials gov Identifier: NCT02111213. Registered on 04/02/2014.

Multiple Onychopapillomas and BAP1 Tumor Predisposition Syndrome.

Importance: BRCA1-associated protein (BAP1) tumor predisposition syndrome (TPDS) is a cancer genodermatosis associated with high risk of uveal and cutaneous melanoma, basal cell carcinoma, and multiple internal malignant neoplasms, including mesothelioma and renal cell carcinoma. Early detection of the syndrome is important for cancer surveillance and genetic counseling of family members who are at risk. Objective: To determine the prevalence of nail abnormalities in individuals with pathogenic germline variants in BAP1. Design, Setting, and Participants: In this prospective cohort study, individuals who were known carriers of pathogenic BAP1 germline variants were consecutively enrolled between October 10, 2023, and March 15, 2024. Dermatologic evaluation for nail abnormalities was performed, including a history of nail abnormalities and associated symptoms, physical examination, medical photography, and nail biopsy for histopathology. This was a single-center study conducted at the National Institutes of Health Clinical Center. Main Outcomes and Measures: Primary outcomes were the prevalence and spectrum of nail changes and histopathologic characterization. Results: Among 47 participants (30 female [63.8%]; mean [SD] age, 46.4 [15.1] years) ranging in age from 13 to 72 years from 35 families, nail abnormalities were detected in 41 patients (87.2%) and included leukonychia, splinter hemorrhage, onychoschizia, and distal nail hyperkeratosis. Clinical findings consistent with onychopapilloma were detected in 39 patients (83.0%), including 35 of 40 individuals aged 30 years or older (87.5%). Nail bed biopsy was performed in 5 patients and was consistent with onychopapilloma. Polydactylous involvement with onychopapillomas was detected in nearly all patients who had nail involvement (38 of 39 patients [97.4%]). Conclusions and Relevance: This study found that BAP1 TPDS was associated with a high rate of nail abnormalities consistent with onychopapillomas in adult carriers of the disease. Findings suggest that this novel cutaneous sign may facilitate detection of the syndrome in family members who are at risk and patients with cancers associated with BAP1 given that multiple onychopapillomas are uncommon in the general population and may be a distinct clue to the presence of a pathogenic germline variant in the BAP1 gene.

Serving Up FLAN. A Food Literacy and Nutrition Intervention to Fend Off Food Insecurity.

Background: Food insecurity, an ongoing and accelerating problem in the U.S., is an economic and social condition involving limited or uncertain access to adequate food. Some of the highest rates of food insecurity in 2022 were found among individuals who were Hispanic-Latinx (20.8%), a population that already faces disproportionate health and socioeconomic disadvantages. There remains an urgent health-related need to identify sustainable strategies to prevent food insecurity in the Latinx population. Methods: A first-generation pilot investigation was conducted using data derived from a sub-study connected to the Computerized Physical Activity Support for Seniors (COMPASS) Trial, a 12-month cluster-randomized controlled trial among older Latinx adults. The sub-study focused on two nutrition interventions that included 1) the Food Literacy and Nutrition (FLAN) curriculum, and 2) a nutrition information-only control. Research hypotheses aimed to determine whether the FLAN intervention reduced food insecurity and increased daily fruit and vegetable servings. Results: On average, participants (n = 39) were 61.5 years of age (SD = 6.7), mostly female (69%), and reported Spanish as their primary language (69%). The FLAN intervention was associated with decreased odds of food insecurity at 12 months (AOR = 0.71, 95% CI = 0.54, 0.95; p = 0.03) when compared to the nutrition-information only control intervention. Although no between-group differences in daily fruit and vegetable servings were found, there was a significant correlation between changes in daily fruit and vegetable servings from baseline to six months and changes in food insecurity from baseline to 12 months (r = -0.51, p = 0.01). Conclusions: The FLAN intervention, a bilingual and culturally tailored educational curriculum, yielded 12-month improvements in food security among a small sample of older Latinx adults. Evidence from this investigation suggests the potential utility of implementing the FLAN curriculum among individuals who are at an increased risk of food insecurity. Further investigation in a larger sample is merited to determine whether the 12-month decreases in food insecurity that were produced by the FLAN intervention can be replicated. Trial Registration: ClinicalTrials.gov Identifier: NCT02111213.

Type 2 Leprosy Reaction Mimicking Leukocytoclastic Vasculitis in a Postpartum Patient.

ABSTRACT: Leprosy is a disease caused by Mycobacterium leprae that, depending on a patient's baseline susceptibility and immune system function, can present in a wide variety of ways. The host's immune system response to the infection can be cell-mediated or humoral and can be further altered by changes in immune function or treatment. Depending on the time at which a skin biopsy is taken from affected areas, different inflammatory cell types are present, and the histopathology can mimic that of other infectious, autoimmune, or malignant entities, especially when the clinical information provided is vague. We present a case of a 24-year-old Micronesian woman who initially presented immediately postpartum with clinical and histopathological findings suggestive of urticarial vasculitis, but a subsequent biopsy resulted in a diagnosis of erythema nodosum leprosum reaction and borderline multibacillary leprosy. This case illustrates an unusual clinical and histological presentation of M. leprae and highlights the importance of clinical history.

A rapidly growing cutaneous malignant glomus tumor with a CCND3 mutation.

Glomus tumors are rare mesenchymal neoplasms composed of cells resembling the glomus body. They are most frequently seen in subungual regions but have been reported to arise in almost every anatomic location. Malignant glomus tumors, also called glomangiosarcomas, of cutaneous origin are exceedingly rare with only 47 reported cases. The genetic alterations that lead to the development of cutaneous malignant glomus tumors are not well understood. Small studies report glomus tumors with mutations in glomulin (GLMN), NF1, BRAF, NOTCH, PDGFRB, KRAS, and SMARCB1. These mutations have mostly been studied in deep or visceral glomus tumors. We report a case of a cutaneous malignant glomus tumor with a CCND3 point mutation identified on next generation sequencing, without any of the previously described genetic mutations. CCND3 mutations that cause cyclin D3 amplification may prove to be targets for CDK4/6 inhibitors in the treatment of malignant glomus tumors.

Physical activity mitigates the link between adverse childhood experiences and depression among U.S. adults.

BACKGROUND: Adverse Childhood Experiences (ACEs) include potentially traumatic exposures to neglect, abuse, and household problems involving substance abuse, mental illness, divorce, incarceration, and death. Past study findings suggest ACEs contribute to depression, while physical activity alleviates depression. Little is known about the link between ACEs and physical activity as it relates to depression among U.S. adults. This research had a primary objective of determining the role of physical activity within the link between ACEs and depression. The significance of this study involves examining physical activity as a form of behavioral medicine. METHODS: Data from the 2020 Behavioral Risk Factor Surveillance System were fit to Pearson chi-square and multivariable logistic regression models to examine the links between ACEs and depression, ACEs and physical activity, and physical activity and depression among U.S. adults ages 18-and-older (n = 117,204) from 21 states and the District of Columbia, while also determining whether physical activity attenuates the association between ACEs and depression. RESULTS: Findings from chi-square analyses indicated that ACEs are related to physical activity (χ2 = 19.4, df = 1; p<0.01) and depression (χ2 = 6,841.6, df = 1; p<0.0001). Regression findings suggest ACEs were linked to depression (AOR = 1.050; 95% CI = 1.049, 1.051). ACEs and physical activity (AOR = 0.994; 95% CI = 0.992, 0.995) and physical activity and depression (AOR = 0.927; 95% CI = 0.922, 0.932) were both inversely related. Physical activity mitigated the link between ACEs and depression (AOR = 0.995; 95% CI = 0.993, 0.996). CONCLUSIONS: This research addressed a critical knowledge gap concerning how ACEs and physical activity contribute to depression outcomes among U.S. adults. Findings suggest physical activity mitigates the effect of ACEs on depression. Future studies should apply physical activity interventions to alleviate depression among U.S. adults with high ACEs.

Food insecurity and adverse childhood experiences: a systematic review.

CONTEXT: Food insecurity (FI) and adverse childhood experiences (ACEs) disproportionally affect vulnerable populations and are key social determinants of health that predict nutrition-related outcomes. It is critical to understand how FI and ACEs are interrelated so prevention studies can be designed to better promote health equity. OBJECTIVE: A systematic literature review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses to determine the association between FI and ACEs. DATA SOURCES: Google Scholar, PubMed, and Scopus databases were used to find articles relevant to the study. Inclusion criteria included quantitative, qualitative, or mixed-methods studies of humans, using an experimental or observational research design to examine the relationship between FI and ACEs using the validated ACEs measure in its entirety. DATA EXTRACTION: Studies were assessed for study design, data set, population descriptions, and results of the association between FI and ACEs. Additionally, all included studies were assessed for bias and validity. DATA ANALYSIS: A total of 10 articles were included in the systematic review. Of those articles, 9 were reports on cross-sectional studies, and 1 reported on a longitudinal study; however, all 10 studies used a retrospective approach. Six studies were conducted using secondary data. Results reported in all 10 articles indicated a significant positive association between FI and ACEs. Evidence indicated greater odds of FI among individuals with high ACE scores, with most studies indicating a dose-response or a threshold effect of higher ACEs being associated with more severe FI. CONCLUSIONS: FI and ACEs are consistently related. Prevention study interventions should be designed to address FI and problems stemming from ACEs. Filling knowledge gaps regarding the relationship between ACEs and FI is critical for designing nutrition interventions that promote food security, prevent the occurrence of ACEs, and improve health outcomes among vulnerable populations with high ACEs. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no.: CRD42020210106.

Measures of an illuminant-induced metameric mismatch: theory, comparative analysis, and implications for application.

Illuminant-induced metameric mismatch is an important consideration in the specification of light sources for some architectural environments, yet there is currently no standardized performance measure. The goal of this work was to evaluate two recent research proposals: the metameric uncertainty index (Rt) and the metamer mismatching color rendering index (MMCRI). To compare the relative performance of these two measures, 100,000 spectral power distributions were generated with 3, 4, 5, 6, and 7 Gaussian spectral components and spectral widths varying from 1 nm (monochromatic) to 100 nm. Both measures generally agree with the theory that broadband radiation should cause less metameric mismatch than narrowband radiation. The two measures have relatively better agreement for broadband SPDs and relatively worse agreement for narrower spectra. Despite some similarities, non-parametric statistical tests suggest that Rt and MMCRI are significantly different quantifications of illuminant-induced metameric mismatch (p < 0.0001 for all comparisons). Characteristics of the MMCRI computation that are potentially problematic for applied lighting were observed.

Cutaneous Gamna-Gandy bodies: An unusual case of dystrophic calcification.

Dystrophic calcification is a common histopathologic finding that can be concomitant with a plethora of diseases, ranging from self-limited infections to insidious malignancies. Gamna-Gandy bodies (GGBs) are a form of dystrophic calcification associated with chronic hemolysis and are typically observed in the spleen. In this report, we present the case of a 92-year-old man who presented with a 4-mm blue papule that was biopsied given the concern for a blue nevus. The subsequent histopathologic examination of the biopsy specimen showed a dermal organizing hematoma adjacent to pale-yellow to brown, refractile material within fibrotic collagen consistent with GGBs. Scanning electron microscopy with energy-dispersive x-ray analysis (SEM/EDXA) revealed that the structures were composed of carbon (39%), oxygen (32%), iron (16%), phosphorus (7%), calcium (5%), and sodium (1%). Fourier transform infrared spectroscopy identified amorphous calcium phosphate. GGBs have not been previously described in the skin and have been rarely characterized with SEM/EDXA in other sites.

Food Insecurity is Related to Disordered Eating Behaviors Among College Students.

OBJECTIVE: To determine the association between food insecurity and disordered eating behaviors (DEBs) in undergraduate college students. METHODS: Cross-sectional data of college students (n = 533) were collected from February to April 2020. Food security was measured with the US Department of Agriculture's Adult Food Security Survey Module. Disordered eating behaviors were measured with the Eating Disorder Examination Questionnaire. Associations were examined statistically with Pearson chi-square tests of independence and general linear regression models. RESULTS: Across all food security ranges, linear trends detailed significant associations between food insecurity and global DEBs (ß = 0.17; P < 0.001), eating concern (ß = 0.27; P < 0.001), shape concern (ß = 0.17; P = 0.001), and weight concern (ß = 0.21; P < 0.001), but not restraint (ß = 0.10; P = 0.08). CONCLUSIONS AND IMPLICATIONS: Food insecurity was consistently related to DEBs. Future research may consider longitudinally examining this relationship, as food insecurity and DEBs may be associated with worse health outcomes among vulnerable college students.

Availability, variety and distribution of healthy and unhealthy foods and beverages sold at street food stands in Mexico City.

OBJECTIVE: To examine differences in the availability, variety and distribution of foods and beverages sold at street food stands (SFS) across neighbourhood income levels in Mexico City. DESIGN: Cross-sectional. SETTING: Twenty neighbourhoods representing low-, middle- and high-income levels in Mexico City. PARTICIPANTS: Direct observations of SFS (n 391). RESULTS: The availability of healthy foods such as fruits/vegetables was high in middle- and high-income neighbourhoods, whereas the availability of unhealthy foods such as processed snacks was higher in low-income neighbourhoods. However, statistically significant differences in food availability across neighbourhoods were only observed for dairy and processed snack items (P < 0·05). Similarly, differences in variety were only observed for cereal and processed snacks (P < 0·05). No statistically significant differences were seen for variety of fruits/vegetable across neighbourhood income levels (P > 0·05). No statistically significant differences across neighbourhood income levels were observed for beverage availability and variety (P > 0·05). Although street foods and beverages were often distributed near homes, public transportation centres and worksites, no differences were observed across neighbourhood income levels (P > 0·05). CONCLUSIONS: Findings suggest that SFS can be a source of both unhealthy foods and healthy foods for communities across neighbourhoods in Mexico City. Additional studies are needed to assess the relationship between street food and beverage availability, and consumption.

Acute Rheumatic Fever: A Review of Essential Cutaneous and Histological Findings.

Acute rheumatic fever (ARF) is an autoimmune response that may occur after infection with group A Streptococcus. Clinical manifestations are protean, making the syndrome difficult to recognize in the 21st century. Secondary prophylaxis with benzathine penicillin is given for 10 years after an episode of ARF to prevent recurrence and reduce the risk of rheumatic heart disease. This case highlights the importance of providing a detailed clinical history to the dermatopathologist when considering ARF in the differential diagnosis.

NRAS Mutation Detected in a Melanoma With Chondroid Stroma: A Case Report With Molecular Evaluation and Literature Review of a Rare Form of Melanoma.

Melanoma with cartilaginous differentiation is a rare histologic subtype that has been reported in the literature. It often presents clinically different than conventional melanomas and can be diagnostically challenging. Molecular alterations in previously reported cases have not been published. We present a case of melanoma with chondroid stroma from a 70-year-old man that was found to contain an NRAS mutation (c.182A>G (p.Q61R)) via Illumina TruSight Tumor 15 (TST15) next generation sequencing assay.

Squamous cell carcinoma with perineural involvement in nevus sebaceus.

Nevus sebaceus (NS), also known as an organoid nevus, is a congenital skin hamartoma involving the pilosebaceous unit, epidermis, and adnexa, frequently occurring in the scalp area. During childhood, the lesion remains unchanged but may subsequently increase in size during puberty in response to hormonal release, with possible tumor development. We report a case of squamous cell carcinoma (SCC) development in an NS with histologic evidence of perineural involvement on the anterior central scalp of a 13-year-old adolescent girl. We also review the management and prognosis.

Pseudomyogenic Hemangioendothelioma: Case Report and Review of the Literature.

Pseudomyogenic hemangioendothelioma (PHE; epithelioid sarcoma-like hemangioendothelioma) is a rare entity, with 129 reported cases. It is a rarely metastasizing, low-grade vascular tumor that can histologically mimic epithelioid sarcoma and often presents as multiple discontinuous nodules in the extremities. PHEs characteristically and consistently show immunoreactivity for cytokeratins and endothelial markers. We present a case in the thigh of a 65-year-old-man with a 3-month history of painful lesions in the dermis and review the published literature. In our case, the lesion exhibited the characteristic histologic findings and immunoprofile of a PHE: a solid proliferation of spindled to epithelioid cells with abundant eosinophilic cytoplasm and frequent rhabdoid cells. Cytologic atypia and mitotic figures were inconspicuous. The tumor cells were immunoreactive for CD31, ERG, AE1/3, and CK7 and negative for D2-40, P53, HMB45, desmin, CD34, SMA, EMA, and S100 protein. A balanced reciprocal translation between chromosomes 7 and 19 was present; this translocation seems unique to PHE. PHE is a unique and commonly misdiagnosed entity; therefore, we review the literature to describe the characteristics of this tumor.

Atypical Histiocyte-Rich Sweet's Syndrome.

Sweet's Syndrome is a rare neutrophilic dermatosis thought to be a result of immune dysregulation occurring in the setting of drug exposure, recent infection, pregnancy, and underlying malignancy or idiopathic with specific and widely accepted diagnostic criteria established in the literature. Other organ systems can be involved with varying degrees of severity. An unusual case of Sweet's Syndrome associated with myopericarditis, acral involvement, and atypical histological findings with predominance of histiocytes is described here.

Sweet's Syndrome Arising in a Scar.

Acute febrile neutrophilic dermatosis (Sweet's syndrome) is an uncommon inflammatory cutaneous disorder. It presents with lesions which are tender, erythematous, edematous papules and under histologic examination show dense neutrophilic infiltration of the dermis. These lesions are often accompanied by leukocytosis and fever. This paper reports a unique case of acute febrile neutrophilic dermatosis presenting as a Koebner response to a linear scar.