CD4 T Cells Occupy Perivascular and Perifollicular Niches in Healthy Human Skin.

Regulatory T cells (Tregs) are specialised T lymphocytes that sit at the nexus of immune regulation and tissue repair. While it is appreciated that a substantial number of Tregs are present in healthy human skin, less is known about their microanatomic spatial localisation. Knowledge about the specialised niches that Tregs occupy may aid in rational drug development to treat dermatologic diseases.

Cytokine Profiling of Erythroderma Biopsies Reveals Types 2 and 17 Immune Activation Status.

Background: Erythroderma is a dermatologic condition characterized by widespread red and scaly skin. The causes include, but are not limited to, psoriasis, eczema, drug eruptions, pityriasis rubra pilaris (PRP), and cutaneous T-cell lymphoma. Most of these are typified by Type 2 (e.

The Association of Interleukin-36 Staining Intensity and Response to Biologic Therapy in Patients With Psoriasis: A Retrospective Immunohistochemical and Chart Review Pilot Study.

Background: There are limited surrogate biomarkers to identify the active inflammatory pathway in psoriasis to direct treatment with targeted biologic therapies. We investigated the association of interleukin (IL)-36 epidermal expression, a diagnostic marker of psoriasis, with response to biologic therapy in patients with psoriasis.

Methods: Retrospective immunohistochemical and chart review pilot study.

Interleukin-36 Is Highly Expressed in Skin Biopsies from Two Patients with Netherton Syndrome.

Netherton syndrome (NS) is a rare autosomal recessive disorder that occurs due to a loss-of-function mutation in SPINK5; this loss results in significant inflammation, as well as perturbations of the skin barrier's integrity and functionality. While it is unclear which inflammatory pathways contribute to the development of NS, recent studies have demonstrated the expression of interleukin (IL)-17/IL-36, as well as several Th2 cytokines. Consequently, immunohistochemistry (IHC) with IL-36 may serve as a potential tool for aiding the histopathological diagnosis of this condition.

Recurrent inverse necrotizing infundibular crystalline folliculitis.

Necrotizing infundibular crystalline folliculitis (NICF) is a rare type of necrotizing folliculitis. The disease typically manifests as folliculocentric papules arising in a seborrheic distribution. Only 23 cases exist in the literature.

Primary Cutaneous Malignant Perivascular Epithelioid Cell Tumor Mimicking Undifferentiated Pleomorphic Sarcoma: A Report of a Rare Entity.

Primary cutaneous malignant perivascular epithelioid cell tumor (PEComa) is a rare and potentially aggressive neoplasm. In this article, we report the case of a 34-year-old man who initially presented with a 3-cm mass involving the skin and soft tissue of the right shoulder that, over 3 months, enlarged to 12 cm. Histologic examination of the mass revealed an infiltrative neoplasm with features resembling an undifferentiated pleomorphic sarcoma, including sheets of pleomorphic cells with abundant atypical mitoses and necrosis.

Defining Patient-Level Molecular Heterogeneity in Psoriasis Vulgaris Based on Single-Cell Transcriptomics.

Identifying genetic variation underlying human diseases establishes targets for therapeutic development and helps tailor treatments to individual patients. Large-scale transcriptomic profiling has extended the study of such molecular heterogeneity between patients to somatic tissues. However, the lower resolution of bulk RNA profiling, especially in a complex, composite tissue such as the skin, has limited its success.

Classification of human chronic inflammatory skin disease based on single-cell immune profiling.

Inflammatory conditions represent the largest class of chronic skin disease, but the molecular dysregulation underlying many individual cases remains unclear. Single-cell RNA sequencing (scRNA-seq) has increased precision in dissecting the complex mixture of immune and stromal cell perturbations in inflammatory skin disease states. We single-cell-profiled CD45 immune cell transcriptomes from skin samples of 31 patients (7 atopic dermatitis, 8 psoriasis vulgaris, 2 lichen planus (LP), 1 bullous pemphigoid (BP), 6 clinical/histopathologically indeterminate rashes, and 7 healthy controls).

Histopathologic and genetic findings in atypical spindle cell/pleomorphic lipomatous tumors and atypical pleomorphic fibromas.

Background: Spindle cell lipomas, pleomorphic lipomas (SCL/PLs), and pleomorphic fibromas (PF) are tumors with loss of retinoblastoma (RB). The latest World Health Organization classification includes a category of atypical spindle cell/pleomorphic lipomatous tumors (ASPLT), which encompasses tumors in this spectrum that show atypical histopathologic features. We have observed PFs that show similar atypical features.

Interleukin 36 expression in psoriasis variants and other dermatologic diseases with psoriasis-like histopathologic features.

Background: Elevated epidermal interleukin (IL)-36 expression distinguishes psoriasis from eczematous dermatitis, but other psoriasiform dermatitides (PDs) have not been thoroughly investigated for IL-36 expression. In this study, we assess the IL-36 staining pattern (IL36-SP) in psoriasis variants and other PDs including lichen simplex chronicus (LSC), prurigo nodularis (PN), lichen planus (LP), tinea, pityriasis rubra pilaris (PRP), mycosis fungoides (MF), pemphigus foliaceus (PF), acute generalized exanthematous pustulosis (AGEP), impetigo (IMP), and syphilis (SY).

Methods: IL-36 immunostaining was performed on 307 cases of psoriasis and various PDs.

Primary Cilia Are Preserved in Cellular Blue and Atypical Blue Nevi and Lost in Blue Nevus-like Melanoma.

Distinguishing cellular blue nevi (CBNs) and atypical CBNs from blue nevus-like melanoma (BNLM) can be diagnostically challenging. Immunohistochemistry may inform the diagnosis in a subset of cases but is not always diagnostic. Further, ancillary molecular testing is expensive and often requires significant tissue to complete.

Molecular Genetics of Sebaceous Neoplasia.

Sebaceous neoplasia primarily includes sebaceous adenoma, sebaceoma, and sebaceous carcinoma (SC). Sebaceous adenoma, sebaceoma, and a subset of cutaneous SC are frequently associated with defective DNA mismatch repair resulting from mutations in MLH1, MSH2, or MSH6. These tumors can be sporadic or associated with Muir-Torre syndrome.

The utility of PRAME staining in identifying malignant transformation of melanocytic nevi.

Background: PReferentially expressed Antigen in MElanoma (PRAME) immunohistochemical (IHC) staining is used to aid melanoma diagnosis. PRAME expression in nevus-associated melanoma (NAM) has not been evaluated.

Methods: PRAME IHC was applied to cases of NAM; staining for each population of melanocytes (benign and malignant) was graded based on the percentage of labeled cells.