Acquired perforating dermatosis: A clinicopathologic study, and the features of dermoscopy and reflective confocal microscopy of 37 cases.

BACKGROUND: Acquired perforating dermatosis (APD) is a rare skin condition characterized by degenerated materials eliminated from the dermis. Several retrospective studies on APD have been reported; however, few data are available on Chinese APD and their features on dermoscopy and reflective confocal microscope (RCM) assays. OBJECTIVE: The aim of this study was to retrospectively evaluate the clinical and histopathologic data of 37 acquired perforating dermatosis cases, and assess their features on dermoscopy and RCM. METHODS: Thirty-seven APD patients were retrospectively enrolled in our study. We characterized the clinical histopathological features, concomitant diseases, treatment responses, and the dermoscopy and RCM findings. RESULTS: Pruritus was the most common symptom, with the lower extremities as the most predilection sites (86.5%, n = 32; 91.9%, n = 34, respectively). Concomitant diseases were found in 34 patients (92.6%), among which diabetes mellitus was the most common, followed by thyroid nodules, allergic dermatosis, and chronic renal insufficiency. Dermoscopy and RCM assays were performed in 11 patients. The typical RCM images were hyperreflective cord-like structures from the epidermis to dermis. Dermoscopy features of fully developed lesions showed central ulceration with peripheral hairpin-like or loop-like capillaries with characteristic garland arrangements. CONCLUSION: APD is an uncommon skin disorder associated with various systemic conditions in Chinese individuals. Thyroid disorders are an overlooked complication and may play an important role in the development of APD. The results of this study indicate that noninvasive dermoscopy and RCM examination are helpful in the rapid diagnosis and early intervention of APD.

Acquired Perforating Dermatosis Induced by PD-1 Inhibitor: A Case Report.

ABSTRACT: Acquired perforating dermatoses (APDs) are a group of diverse skin disorders in patients with systemic disease, most commonly chronic renal failure and diabetes mellitus. APD induced by medication has seldom been reported. Anti-PD-1 monoclonal antibody has recently been used as a broad-spectrum, effective, durable, and relatively safe antitumor therapy for various malignancies. Thus far, known side effects involving skin have included rash, pruritus, and vitiligo. Here, we present a rare case of a unilateral linear eruption with histopathologic features of APD in a 36-year-old man during treatment with Terepril monoclonal antibody. To the best of our knowledge, APD induced by the PD-1 inhibitor has not been described in the medical literature.

The Msi1-mTOR pathway drives the pathogenesis of mammary and extramammary Paget's disease.

Mammary and extramammary Paget's Diseases (PD) are a malignant skin cancer characterized by the appearance of Paget cells. Although easily diagnosed, its pathogenesis remains unknown. Here, single-cell RNA-sequencing identified distinct cellular states, novel biomarkers, and signaling pathways - including mTOR, associated with extramammary PD. Interestingly, we identified MSI1 ectopic overexpression in basal epithelial cells of human PD skin, and show that Msi1 overexpression in the epidermal basal layer of mice phenocopies human PD at histopathological, single-cell and molecular levels. Using this mouse model, we identified novel biomarkers of Paget-like cells that translated to human Paget cells. Furthermore, single-cell trajectory, RNA velocity and lineage-tracing analyses revealed a putative keratinocyte-to-Paget-like cell conversion, supporting the in situ transformation theory of disease pathogenesis. Mechanistically, the Msi1-mTOR pathway drives keratinocyte-Paget-like cell conversion, and suppression of mTOR signaling with Rapamycin significantly rescued the Paget-like phenotype in Msi1-overexpressing transgenic mice. Topical Rapamycin treatment improved extramammary PD-associated symptoms in humans, suggesting mTOR inhibition as a novel therapeutic treatment in PD.

Congenital Blaschkoid Angiolymphoid Hyperplasia With Eosinophilia of the Anogenital Region.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon, idiopathic vascular disorder. It manifests as dermal or subcutaneous red to brown papules or nodules, most commonly on the head and neck; other less common sites include the trunk, extremities, genitalia, lips, and oral mucosa. Although ALHE is a benign disease, lesions are often persistent and difficult to eradicate. ALHE occurs more frequently in Asian young and middle-aged women. Histologically, it is characterized by a florid vascular proliferation with hobnail epithelioid endothelial cells surrounding by lymphocytic and eosinophilic infiltrate. Here, we reported congenital ALHE in a 2-year-old girl. Unilateral lesions had a blaschkoid segmental distribution in the anogenital region and were successfully treated with the Nd:YAG laser.

Reduced Expression of RECK Protein May Help Differentiate Cutaneous Malignant Melanoma from Melanocytic Nevus.

BACKGROUND: Differentiating between vertical growth cutaneous malignant melanoma (CMM) and predominantly intradermal benign melanocytic nevus (BMN) can be extremely challenging. Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) is an endogenous inhibitor of many proteins that promote tumor invasion and progression. We investigated the difference in expression of RECK between CMM and BMN to determine whether RECK could assist in their differentiation. MATERIALS AND METHODS: The expression of RECK in skin biopsies of 39 cases, including 20 cases of CMM and 19 cases of BMN, was evaluated by immunohistochemistry. RESULTS: Two out of 20 cases (10%) of CMM were positive for RECK, and all (100%) 19 cases of BMN exhibited positivity at different levels. In 7/8 cases of CMM adjacent to benign nevus cells, malignant melanoma cells did not express RECK, but benign nevus cells stained positively. CONCLUSION: These findings suggest that immunohistochemical staining for RECK could be useful in the differential diagnosis between CMM and BMN.

Primary Cutaneous Interdigitating Dendritic Cell Sarcoma: A Case Report and Review of the Literature.

Interdigitating dendritic cell sarcoma (IDCS) is defined as a neoplastic proliferation of spindle to ovoid cells with phenotypic features similar to those of interdigitating dendritic cells, which are present in the T cell-rich areas of lymphoid organs and participate as antigen-presenting cells responsible for initiating primary T lymphocyte immune response. IDCS usually presents with lymphadenopathy. Solitary lymph node involvement is often seen. Extra nodal presentation has been described as well. Cutaneous lesions are extremely rare, and less than 10 cases have been previously documented in medical literature. Here, the authors describe another primary cutaneous IDCS in a 42-year-old patient and review the literature.

Panfolliculoma and histopathologic variants: a study of 19 cases.

Panfolliculoma (PF) is an uncommon benign follicular neoplasm exhibiting differentiation toward all components of a hair follicle. Several pathologic manifestations have been described in a limited number of cases. We studied 19 cases of PF to summarize the clinical parameters and to classify this unique neoplasm histopathologically. A study of the largest sample series of PF has been performed here. The lesions affect both genders after age 20. The head is the most common site of PF of all types. On microscopic examination, all cases demonstrated advanced follicular differentiation by showing cell components of infundibulum, isthmus, stem, bulb, and mesenchymal papilla. Based on the findings and various patterns in histopathology, we classified PF into 3 subtypes: nodular, superficial, and cystic. The superficial and cystic variants account for most of the cases in our study. The histopathologic differential diagnosis is also discussed for each subtype.

Exenatide-induced eosinophilic sclerosing lipogranuloma at the injection site.

Sclerosing lipogranuloma is a granulomatous reaction to the injection of a high-viscosity fluid in the tissues for the cosmetic purpose of improving body contour; lesions on the extremities and buttocks are commonly the results of injections of therapeutic agents in oily vehicles. Exenatide, once-weekly injection, is a therapeutic method for patients with type 2 diabetes. Here, we describe a case of exenatide once weekly induced eosinophilic sclerosing lipogranuloma at the injection site of a 62-year-old patient. To the best of our knowledge, the histopathologic features of this adverse event have not been reported in the medical literature.

Expression of glycoprotein non-metastatic melanoma protein B in cutaneous malignant and benign lesions: a tissue microarray study.

BACKGROUND: Glycoprotein non-metastatic melanoma protein B (GPNMB) plays an important role in the pathogenesis of inflammatory and malignant diseases. We investigated the expression of GPNMB in benign and malignant skin diseases. METHODS: Tissue microarray was performed in the skin tissues of 102 cases including malignant melanoma (MM), squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and benign dermatosis. The expression of GPNMB in the tissues was detected by immunohistochemistry. Twenty cases of normal skin and adjacent neoplastic normal skin tissues were selected as controls. RESULTS: GPNMB was positively stained in skin malignancies (38/50, 76%), which was significantly higher than that in the control and the benign skin tissues (P = 0.001 and < 0.001 respectively). GPNMB was positively stained in MM (13/15, 87%) and SCC (16/20, 80%) (P < 0.001). Significant higher expression of GPNMB was observed in patients aged ≥ 65 years than those less than 65 years (n = 11 and n = 9 respectively, P = 0.027). No significant difference of the expression rates was observed between normal control and BCC; however, stronger intensity was detected in the latter. Negative or weak expression was observed in the controls. CONCLUSION: Over-expression of GPNMB correlated strongly and might play an important role in the pathogenesis of MM and SCC.

Kanglaite attenuates UVB-induced down-regulation of aquaporin-3 in cultured human skin keratinocytes.

Ultraviolet (UV) radiation plays an important role in the pathogenesis of skin photoaging. Depending on the wavelength of UV, the epidermis is affected primarily by UVB. One major characteristic of photoaging is the dehydration of the skin. Membrane-inserted water channels (aquaporins) are involved in this process. In this study we demonstrated that UVB radiation induced aquaporin-3 (AQP3) down-regulation in cultured human skin keratinocytes. Kanglaite is a mixture consisting of extractions of Coix Seed, which is an effective anti-neoplastic agent and can inhibit the activities of protein kinase C and NF-κB. We demonstrated that Kanglaite inhibited UVB-induced AQP3 down-regulation of cultured human skin keratinocytes. Our findings provide a potential new agent for anti-photoaging. The related molecular mechanisms remain to be further elucidated.

Expression of survivin and human telomerase reverse transcriptase in extramammary Paget's disease.

BACKGROUND: Extramammary Paget's disease (EMPD) is a rare neoplasm of apocrine gland-bearing skin. It is known that over-expression of survivin and human telomerase reverse transcriptase (hTERT) correlates with malignancies. We investigated the expression of hTERT and survivin by Paget's cells and their role in the tissue invasion and recurrence of EMPD. METHOD: Forty-two patients were enrolled into the study. Expression of survivin and hTERT were analyzed by immunohistochemistry and in situ hybridization techniques. The variables including the expression level of survivin and hTERT, gender, age, lesion location, invasion level and number of surgeries were statistically analyzed using Fisher's exact test. RESULTS: Survivin was positively stained in 18 of 22 cases (81.8%), and hTERT in 18 of 29 cases (62.1%). Significantly higher level of survivin expression was detected in patients with multiple surgeries than those with single one (p = 0.0458). Expression of hTERT was significantly higher in the patients with micro-invasive and invasive lesions than those with non-invasive lesions (p = 0.0478). CONCLUSIONS: Over-expression of survivin and hTERT correlated strongly with recurrence and local invasion of EMPD lesions. EMPD has male gender predominance in Oriental population.