Scleromyxedema and Breast-Implant Associated Lymphoma: Investigating an Unusual Clinical Association.

Scleromyxedema, a rare skin condition, is characterized by a waxy-appearing papular eruption that tends to impact middle-aged adults. Scleromyxedema is often linked to monoclonal gammopathies. However, some patients do not have a coinciding monoclonal gammopathy and experience an atypical presentation of the disease.

The Influence of Melanoma Extracellular Vesicles on Benign Melanocytes: A Role for PRAME in Modulation of the Tumor Microenvironment.

Melanoma is an aggressive skin cancer with a high tendency for metastasis and resistance to conventional therapies. This study explores the role of preferentially expressed antigen in melanoma (PRAME), a cancer-testis antigen, in melanoma progression, focusing on its function in melanoma-derived extracellular vesicles (EVs) and its impact on benign melanocytes. We show that PRAME is highly expressed in melanoma cell lines, tissues, and patient plasma and is present in EVs.

The Utilization of PRAME in the Diagnosis, Prognosis, and Treatment of Melanoma.

Melanoma, a deadly form of skin cancer, has seen improved survival rates due to advances in diagnosis and treatment, yet the need for further improvement remains critical. Tumor-associated antigens, such as PRAME (Preferentially Expressed Antigen in Melanoma), offer promising avenues for enhanced diagnostic precision, prognostic assessment, and targeted immunotherapy. PRAME, a cancer testis antigen, is selectively expressed in various cancers, including melanoma, and plays a key role in promoting tumorigenesis through inhibition of retinoic acid signaling, epithelial-to-mesenchymal transition, and immune evasion.

Perifollicular Melanocyte Regeneration in Bullous Pemphigoid.

Bullous pemphigoid (BP) is an autoimmune skin disorder that causes fluid-filled blisters to appear on various body parts, often preceded by urticaria and pruritis. This case report describes the perifollicular melanocyte regeneration within diseased areas in a skin of color patient with BP. By reviewing the various pathologies that can result in melanocyte destruction and the basic science of melanocyte regeneration, we can better identify and explain this phenomenon to patients and lead to earlier diagnoses.

Histiocytoid Sweet's Syndrome in the Setting of Myelodysplastic Syndrome.

Acute febrile neutrophilic dermatosis, or Sweet's syndrome, is characterized by tender, edematous papules and plaques, favoring the upper extremities and the head and neck regions. The classic variant of Sweet's syndrome involves a predominantly neutrophilic dermal infiltrate on histopathology. However, histiocytoid Sweet's syndrome has been noted to have a primary histiocytoid mononuclear infiltrate and is typically found in patients with malignancies such as myelodysplasia.

Role of human Kallistatin in glucose and energy homeostasis in mice.

Objective: Kallistatin (KST), also known as SERPIN A4, is a circulating, broadly acting human plasma protein with pleiotropic properties. Clinical studies in humans revealed reduced KST levels in obesity. The exact role of KST in glucose and energy homeostasis in the setting of insulin resistance and type 2 diabetes is currently unknown.

Case Report: Methotrexate and hydroxychloroquine in combination for the treatment of NOD2-mutation-associated Blau syndrome.

Mutations in nucleotide binding oligomerization domain containing 2 receptor (NOD2) are associated with Blau syndrome (also known as early-onset sarcoidosis)-a rare autosomal dominant, chronic granulomatous disease that typically presents before 5 years of age. Blau syndrome is characterized by the clinical triad of arthritis, granulomatous dermatitis, and recurrent uveitis. Here, we report a case of NOD2-mutation-associated early-onset sarcoidosis in which a combination of methotrexate and hydroxychloroquine was used to achieve improvement in arthritis, granulomatous dermatitis, and uveitis.

The effect of mesenchymal stem cells improves the healing of burn wounds: a phase 1 dose-escalation clinical trial.

Background: Stem cell therapy holds promise to improve healing and stimulate tissue regeneration after burn injury. Preclinical evidence has supported this; however, clinical studies are lacking. We examined the application of bone marrow-derived mesenchymal stem cells (BM-MSC) to deep second-degree burn injuries using a two-dose escalation protocol.

Preferentially expressed antigen in melanoma and p16 expression in acral melanocytic neoplasms.

Acral melanocytic neoplasms often pose diagnostic difficulty. Preferentially expressed antigen in melanoma (PRAME) expression and loss of p16 expression have diagnostic utility in melanocytic tumors. We examined PRAME and p16 expression in 30 acral melanocytic neoplasms (n = 11 nevi; n = 2 dysplastic nevi; n = 7 Spitz nevi; n = 10 acral melanomas).

Proteomic analysis of bone marrow-derived mesenchymal stem cell extracellular vesicles from healthy donors: implications for proliferation, angiogenesis, Wnt signaling, and the basement membrane.

Background: Bone marrow-derived mesenchymal stem cells (BM-MSCs) have shown therapeutic potential in various in vitro and in vivo studies in cutaneous wound healing. Furthermore, there are ubiquitous studies highlighting the pro-regenerative effects of BM-MSC extracellular vesicles (BM-MSC EVs). The similarities and differences in BM-MSC EV cargo among potential healthy donors are not well understood.

A rare case of syringocystadenocarcinoma papilliferum of the breast: An institutional retrospective case review and brief literature review.

Syringocystadenocarcinoma papilliferum (SCACP) is a rare cutaneous adnexal tumor thought to originate from its benign counterpart, syringocystadenoma papilliferum. These tumors are predominantly located on the head and neck with their location on the breast extraordinarily reported; mammary localization poses a great diagnostic dilemma to the practicing pathologist. Herein, we report an unusual case of an 85-year-old woman with an outside diagnosis on a core needle biopsy of metaplastic mammary carcinoma.

Development of sacral/buttock retiform purpura as an ominous presenting sign of COVID-19 and clinical and histopathologic evolution during severe disease course.

Retiform purpura has been described as a relatively frequent cutaneous finding in patients with coronavirus disease 2019 (COVID-19). The etiology is hypothesized to be related to thrombotic vasculopathy based on lesional biopsy specimen findings, but the pathogenesis of the vasculopathy is not completely understood. Here, we present a case of a retiform purpuric patch on the sacrum/buttocks in a hospitalized patient prior to subsequent diagnosis of COVID-19 and an eventual fatal disease course.

Dual mechanism of type VII collagen transfer by bone marrow mesenchymal stem cell extracellular vesicles to recessive dystrophic epidermolysis bullosa fibroblasts.

Recessive dystrophic epidermolysis bullosa (RDEB) is a severe blistering disease resulting from a lack of type VII collagen production. Recent clinical trials have shown efficacy of bone marrow-derived mesenchymal stem cells (BM-MSCs) in the treatment of epidermolysis bullosa, including improved basement membrane restructuring and cutaneous wound healing. The mechanism as to how type VII collagen is transferred from donor stem cell to recipient RDEB cells has not been defined.

Bone Marrow Mesenchymal Stem Cell-Derived CD63 Exosomes Transport Wnt3a Exteriorly and Enhance Dermal Fibroblast Proliferation, Migration, and Angiogenesis In Vitro.

Wnts are secreted glycoproteins that regulate stem cell self-renewal, differentiation, and cell-to-cell communication during embryonic development and in adult tissues. Bone marrow mesenchymal stem cells (BM-MSCs) have been shown to stimulate dermis repair and regeneration; however, it is unclear how BM-MSCs may modulate downstream Wnt signaling. While recent reports implicate that Wnt ligands and Wnt messenger RNAs (such as Wnt4) exist within the interior compartment of exosomes, it has been debated whether or not Wnts exist on the exterior surface of exosomes to travel in the extracellular space.

Extracellular Vesicles as Biomarkers and Therapeutics in Dermatology: A Focus on Exosomes.

Extracellular vesicles (exosomes, microvesicles, and apoptotic bodies) are ubiquitous in human tissues, circulation, and body fluids. Of these vesicles, exosomes are of growing interest among investigators across multiple fields, including dermatology. The characteristics of exosomes, their associated cargo (nucleic acids, proteins, and lipids), and downstream functions are vastly different, depending on the cell origin.

Transgenic expression of a canonical Wnt inhibitor, kallistatin, is associated with decreased circulating CD19 B lymphocytes in the peripheral blood.

Members of the family of serine proteinase inhibitors, such as kallistatin, have been shown to inhibit canonical Wnt-TCF/LEF-β-catenin signaling via their interactions with the Wnt co-receptor LRP6. Yet the effects of transgenic overexpression of anti-Wnt serpins on hematopoiesis and lymphopoiesis are not well known. We studied the effects of human kallistatin (SERPINA4) on Wnt reporter activity in various cell types throughout the hematopoietic system and associated impacts on circulating white blood cell profiles.

Proximal nailfold microhemorrhage events are manifested as distal cuticular (eponychial) hemosiderin-containing deposits (CEHD) (syn. Maricq sign) and can aid in the diagnosis of dermatomyositis and systemic sclerosis.

Importance: Many patients present with cutaneous signs and symptoms that suggest a diagnosis on the autoimmune disease spectrum. During the "acute phase" of disease activity, patients with systemic sclerosis (SSc) and dermatomyositis (DM) have characteristic nailfold findings, including dilated capillaries, microhemorrhages, and hemosiderin deposits.

Objective: To review the literature on the presentation of microhemorrhages and to highlight the differences (in terms of terminology, characterization, and clinical relevance) between proximal microhemorrhage events and the distal products, often thought of as "hemosiderin deposits" located in the cuticle (eponychium).

Elevated circulation levels of an antiangiogenic SERPIN in patients with diabetic microvascular complications impair wound healing through suppression of Wnt signaling.

Wound healing, angiogenesis, and hair follicle maintenance are often impaired in the skin of diabetic patients, but the pathogenesis has not been well understood. Here, we report that circulation levels of kallistatin, a member of the serine proteinase inhibitor (SERPIN) superfamily with antiangiogenic activities, were elevated in type 2 diabetic patients with diabetic vascular complications. To test the hypothesis that elevated kallistatin levels could contribute to a wound-healing deficiency via the inhibition of Wnt/β-catenin signaling, we generated kallistatin-transgenic (KS-TG) mice.

Antiangiogenic and antineuroinflammatory effects of kallistatin through interactions with the canonical Wnt pathway.

Kallistatin is a member of the serine proteinase inhibitor superfamily. Kallistatin levels have been shown to be decreased in the vitreous while increased in the circulation of patients with diabetic retinopathy (DR). Overactivation of the Wnt pathway is known to play pathogenic roles in DR.