The effects of myosteatosis on skeletal muscle function in older adults.

Myosteatosis, or the infiltration of fatty deposits into skeletal muscle, occurs with advancing age and contributes to the health and functional decline of older adults. Myosteatosis and its inflammatory milieu play a larger role in adipose tissue dysfunction, muscle tissue dysfunction, and increased passive muscle stiffness. Combined with the age-related decline of sex hormones and development of anabolic resistance, myosteatosis also contributes to insulin resistance, impaired muscle mechanics, loss of force production from the muscle, and increased risk of chronic disease. Due to its highly inflammatory secretome and the downstream negative effects on muscle metabolism and mechanics, myosteatosis has become an area of interest for aging researchers and clinicians. Thus far, myosteatosis treatments have had limited success, as many lack the potency to completely rescue the metabolic and physical consequences of myosteatosis. Future research is encouraged for the development of reliable assessment methods for myosteatosis, as well as the continued exploration of pharmacological, nutritional, and exercise-related interventions that may lead to the success in attenuating myosteatosis and its clinical consequences within the aging population.

Unresectable infantile myofibroma discovered in utero.

The authors present a case of a proliferative nodule located beneath an infant's lower lip that was initially discovered on prenatal ultrasound and fetal magnetic resonance imaging (MRI). Biopsy revealed a smooth muscle actin-positive spindled cell proliferation with hemangiopericytoma-like vessels consistent with infantile myofibromatosis (IM). Since the location prevented surgical management, the clinicians opted to observe the lesion. Ultimately, the lesion fully regressed on its own confirming conservative management is an option for isolated IM.

Evaluation of the protection of sunscreen products against long wavelength ultraviolet A1 and visible light-induced biological effects.

BACKGROUND: Long wavelength ultraviolet-A1 in combination with visible light induces hyperpigmentation, particularly in dark-skin phototypes. This study evaluated the efficacy of four sunscreen formulations in protecting against VL + UVA1 (370-700 nm). METHODS: The test products (A-D) were applied to the back of 12 volunteers, then irradiated with 320 J/cm2 VL + UVA1 (3.5% UVA1 [370-400 nm]). Immediately after irradiation, and at Days 1, 7, and 14, erythema and pigmentation were assessed by investigator global assessment (IGA), colorimetry (Δa* and ΔITA) and diffuse reflectance spectroscopy (DRS)-measured relative dyschromia (area under the curve AUC). Control areas were irradiated without sunscreen. RESULTS: Product D, containing titanium dioxide 11%, iron oxides 1%, and antioxidants, provided the highest and most consistent protection. Compared with unprotected irradiated control, it had statistically significantly less erythema on IGA, DRS (Δoxyhemoglobin), and colorimetry (Δa*) at Day 0; less pigmentation on IGA at all time points, on DRS (relative dyschromia) at Days 7 and 14, and on colorimetry (ΔITA) at Day 0. Product B, containing zinc oxide 12% plus organic UV filters, iron oxides 4%, and antioxidants, also showed some efficacy. CONCLUSION: Of the sunscreens tested, the tinted products provided better protection against VL + UVA1 than the non-tinted products. Since the product with 1% iron oxides was superior to the product with 4% iron oxides, further studies are needed to evaluate whether iron oxide content correlates with better protection.

Distinguishing Keratoacanthoma from Well-Differentiated Cutaneous Squamous Cell Carcinoma Using Single-Cell Spatial Pathology.

Keratoacanthoma (KA) is a common keratinocyte neoplasm that is regularly classified as a type of cutaneous squamous cell carcinoma (cSCC) despite demonstrating benign behavior. Differentiating KA from well-differentiated cSCC is difficult in many cases due to the substantial overlap of clinical and histological features. Currently, no reliable discriminating markers have been defined, and consequently, KAs are often treated similarly to cSCC, creating unnecessary surgical morbidity and healthcare costs. In this study, we used RNA sequencing to identify key differences in transcriptomes between KA and cSCC, which suggested divergent keratinocyte populations between each tumor. Imaging mass cytometry was then used to identify single-cell tissue characteristics, including cellular phenotype, frequency, topography, functional status, and interactions between KA and well-differentiated cSCC. We found that cSCC had significantly increased proportions of Ki67+ keratinocytes among tumor keratinocytes, which were dispersed significantly throughout non-basal keratinocyte communities. In cSCC, regulatory T-cells were more prevalent and held greater suppressive capacity. Furthermore, cSCC regulatory T-cells, tumor-associated macrophages, and fibroblasts had significant associations with Ki67+ keratinocytes as opposed to avoidances with KA, indicating a more immunosuppressive environment. Our data suggest that multicellular spatial features can serve as a foundation to enhance the histological discrimination of ambiguous KA and cSCC lesions.

Real world validation of an adjunctive gene expression-profiling assay for melanoma diagnosis and correlation with clinical outcomes at an academic center.

A commercially available diagnostic gene expression profiling (GEP) assay (MyPath™) reportedly has high sensitivity and specificity in distinguishing nevi from melanoma based on manufacturer-conducted studies. However, data regarding the performance of this GEP assay in routine clinical practice are lacking. The purpose of this study was to better assess the real-world performance of GEP in a large academic practice. Retrospective review of GEP scores were compared with final histomorphologic interpretation on a wide spectrum of melanocytic lesions demonstrating some degree of atypia. In a sample of 369 lesions, the sensitivity (76.1%) and specificity (83.9%) of the GEP test as compared with final dermatopathologist-rendered diagnosis in our dataset was appreciably lower than that reported in the prior manufacturer-conducted validation studies. Limitations of this study were that it was a single-center study, its retrospective nature, nonblinded nature of GEP test result, concordance of only two pathologists, and limited follow-up time.The sensitivity and specificity of a commercially available GEP diagnostic assay for melanoma may be lower in routine clinical practice, where melanocytic lesions typically exhibit some degree of histomorphologic atypia. Reported cost effectiveness of GEP testing is questionable if all ambiguous lesions that undergo such testing are re-excised in clinical practice.

Single-Fraction Radiation Therapy for Localized Cutaneous T-Cell Lymphoma.

PURPOSE: Mycosis fungoides is the most common type of cutaneous T-cell lymphoma (CTCL). Single-fraction radiation therapy has been used as a skin-targeted therapy to treat localized CTCL lesions. The objective of this study was to investigate the treatment outcomes associated with single-fraction radiation therapy for CTCL. METHODS AND MATERIALS: We retrospectively studied the outcomes among patients with CTCL treated with single-fraction radiation therapy at our institution between October 2013 and August 2022. Clinical response (complete response [CR], partial response [PR], or no response [NR]) and retreatment response were evaluated. RESULTS: A total of 242 lesions from 46 patients were analyzed, for an average of 5.3 lesions treated per patient. The majority of lesions presented with a plaque morphology (n = 145, 60.0%). All lesions were treated to a dose of 8 Gy in 1 fraction. Median follow-up was 24.6 months (range, 1-88 months). Of the 242 lesions, 36 (14.8%) had an initial PR or NR; all were retreated with the same regimen to the same site at a median interval of 8 weeks. Eighteen of the retreated lesions (50.0%) went on to have a CR. Thus, the overall CR rate for CTCL lesions was 92.6%. No recurrences were noted in the treated areas after achieving CR. CONCLUSIONS: Single-fraction radiation therapy to a dose of 8 Gy in 1 fraction to localized areas provided a high rate of complete and durable responses in the affected sites.

Disorders of hyperpigmentation. Part I. Pathogenesis and clinical features of common pigmentary disorders.

Disorders of hyperpigmentation are common and, depending on the extent and location of involvement, can affect the quality of life and pose a significant psychologic burden for patients. Given the similarities in presentation of the various causes of hyperpigmentation, it is often difficult to elucidate the etiology of these conditions, which is important to guide management. Furthermore, certain disorders, such as lichen planus pigmentosus and ashy dermatosis, have similar clinical and/or histologic presentations, and their classification as distinct entities has been debated upon, leading to additional confusion. In this review, the authors selected commonly encountered disorders of hyperpigmentation of the skin, subdivided into epidermal, dermal, or mixed epidermal-dermal disorders based on the location of pigment deposition, along with disorders of hyperpigmentation of the mucosa and nails. Melanocytic nevi, genetic disorders, and systemic causes of hyperpigmentation were largely excluded and considered to be outside the scope of this review. We discussed the pathogenesis of hyperpigmentation as well as the clinical and histologic features of these conditions, along with challenges encountered in their diagnosis and classification. The second article in this 2-part continuing medical education series focuses on the medical and procedural treatments of hyperpigmentation.

Microcystic lymphatic malformation presenting as firm, skin-colored papules of the lips.

Microcystic lymphatic malformation (MiLM), also known as lymphangioma circumscriptum, is a superficial collection of lymphatic vessels measuring <1 cm in the largest diameter, often with a more extensive deeper malformation. It commonly presents as discrete or grouped plaques of clear or hemorrhagic vesicles classically described as "frogspawn"; however, here we describe a case of its unique presentation as firm papules on the lips of a healthy six-year-old child. These skin-colored papules in the absence of vesicles with lymphatic and/or hemorrhagic fluid may not be clinically indicative of MiLM. This case represents a diagnostic challenge due to the unique morphology of pink, fleshy papules as opposed to the clear or hemorrhagic vesicles typically observed in MiLM.

ETS-related Gene (ERG) is Differentially Expressed in Dermatofibroma (Fibrous Histiocytoma) as Compared With Dermatofibrosarcoma Protuberans and Hypertrophic Scars: A Pilot Immunohistochemical Study.

Immunohistochemical staining can be of great utility in differentiating various cutaneous spindle cell neoplasms, particularly when the histomorphologic appearance of the lesions is inconclusive. Nuclear staining for ETS-related gene (ERG), a highly sensitive endothelial cell marker, has seldom been studied in the context of cutaneous spindle cell neoplasms. Little is known about its specificity for vascular differentiation. In this pilot study, immunohistochemical analysis for ERG was performed on 15 dermatofibromas (DF), 10 keloids, and 9 dermatofibrosarcoma protuberans (DFSP) tumors. Consistent nuclear expression of ERG was found in DF [100% (15/15) of the lesions demonstrated >50% labeling of tumor cells with moderate to strong intensity]. However, ERG expression was largely absent in DFSP [89% (8/9) of the lesions demonstrating <50% labeling staining, generally of mild intensity] and hypertrophic scars-keloids [80% (8/10) without expression]. On the basis of the results of this pilot study, immunohistochemical staining for ERG may prove useful in helping to differentiate DF from DFSP and hypertrophic scars in the context of partial biopsy sampling. If replicated in a larger number of samples, this finding could mitigate the use of costly sequencing panels and potentially avoid unnecessary reexcisions in certain contexts.

Delayed drug hypersensitivity reaction to secukinumab in a patient with hidradenitis suppurativa.

A woman in her 30s presented to the dermatology clinic with widespread, pruritic, red papules and plaques involving the ears, trunk and extremities. The rash developed a few days after receiving her second injection of secukinumab, which was initiated for recalcitrant Hurley stage III hidradenitis suppurativa. Investigations revealed a psoriasiform drug hypersensitivity reaction secondary to secukinumab. In this report, we describe the clinical course, histopathological correlation and treatment of this rarely documented reaction.

A Rare Case of Primary Cutaneous Signet-Ring Cell Melanoma With Discrepant Findings on Gene Expression Profiling and Chromosomal Microarray Analysis.

ABSTRACT: Melanoma with signet ring cell features is an exceptionally rare variant of primary cutaneous and metastatic melanoma. The molecular mechanisms underlying this unusual cytologic phenotype in malignant melanocytes are largely unknown. In this report, we aim to add to the literature by describing the histomorphological, immunophenotypic, gene expression, and cytogenetic findings in 1 recently encountered case.

Unique Recognizable Histopathologic Variant of Palisaded Neutrophilic and Granulomatous Dermatitis that Is Associated With SRSF2-Mutated Chronic Myelomonocytic Leukemia: Case Report and Review of the Literature.

ABSTRACT: Palisaded neutrophilic and granulomatous dermatitis (PNGD) represents a cutaneous histopathologic reaction spectrum associated with several underlying disorders. Few cases of PNGD have been associated with chronic myelomonocytic leukemia (CMML), a malignant hematopoietic disorder with features in between those of a myeloproliferative neoplasm and myelodysplastic syndrome. We present a patient with a generalized papular skin reaction involving the neck, chest, and shoulders with histomorphological features on the spectrum of PNGD. Subsequent laboratory workup demonstrated a persistent mild monocytosis, raising concern for CMML. The diagnosis was ultimately confirmed with a bone marrow biopsy and associated mutational analysis through next-generation sequencing which identified deleterious variants in SRSF2, IDH2, and ASXL1. The findings in this case strengthen the previously made association between PNGD and SRSF2-mutated CMML and may help better define a unique recognizable clinical-histopathological-molecular subtype for dermatopathologists.