Primary Cutaneous Atypical Spindle Cell Lipomatous Tumor

This report documents an exophytic, pedunculated nodule in a 74-year-old man that upon histopathological examination revealed an atypical spindle cell/pleomorphic lipomatous tumor (ASPLT) confined to the papillary and reticular dermis, representing the fourth documented case within the skin. Despite the overt pleomorphic changes present histologically, the patient is free of metastasis or recurrence five years after surgery.

Primary Anetoderma and Acquired Cutis Laxa Associated with Glomerulonephritis in a 37-year-old Filipino Male: A Case Report

A 37-year-old Filipino man presented with a 9-month history of sagging skin progressing cephalocaudally from the chin and neck to the axillae, side of the trunk, and pelvic area. This was followed by a 2-month history of increasing serum creatinine levels associated with periorbital and bipedal edema, generalized weakness, decreased appetite, vomiting, and headache. Subsequently, skin-colored, non-tender sac-like plaques appeared on the abdomen, inguinal, and intergluteal areas. Histopathology of the latter lesions showed increased spaces between collagen bundles in the dermis. Staining with Verhoeff-van Gieson revealed focal sparse elastic fibers in the papillary dermis compared to that of the reticular dermis consistent with anetoderma. Further work-up revealed normal ANA titer and low serum C3. Kidney biopsy showed IgG deposition in the tubular basement membrane and trace C3 deposition in the glomerular mesangium, giving a diagnosis of rapid progressive glomerulonephritis. On subsequent follow-up, the sac-like plaques became lax and presented as generalized wrinkling of the skin, raising the question whether cutis laxa and anetoderma are occurring in a spectrum instead as distinct entities. Based on the current review of literature, this is the first reported case of primary anetoderma co-occurring with cutis laxa in a patient with glomerulonephritis. Deposition of immunoglobulins along the elastic fibers could have activated the complement system, mediating the destruction of the elastic fibers, resulting to cutis laxa and anetoderma. This case also considers the possibility of anetoderma and type I acquired cutis laxa occurring either in a spectrum or as distinct diseases in a single patient. Further investigations may identify an ultrastructural pattern that can help differentiate the two entities.

Use of 816 consecutive burn wound biopsies to inform a histologic algorithm for burn depth categorization

Introduction Burn experts are only 77% accurate when subjectively assessing burn depth, leaving almost a quarter of patients to undergo unnecessary surgery or conversely suffer a delay in treatment. To aid clinicians in burn depth assessment (BDA), new technologies are being studied with machine learning algorithms calibrated to histologic standards. Our group has iteratively created a theoretical burn biopsy algorithm (BBA) based on histologic analysis, and subsequently informed it with the largest burn wound biopsy repository in the literature. Here, we sought to report that process. Methods The was an IRB-approved, prospective, multicenter study. A BBA was created a priori and refined in an iterative manner. Patients with burn wounds assessed by burn experts as requiring excision and autograft underwent 4mm biopsies procured every 25cm 2. Serial still photos were obtained at enrollment and at excision intraoperatively. Burn biopsies were histologically assessed for presence/absence of epidermis, papillary dermis, reticular dermis, and proportion of necrotic adnexal structures by a dermatopathologist using H&E with whole slide scanning. First degree and superficial 2 nd degree were considered to be burn wounds likely to have healed without surgery, while deep 2 nd and 3 rd degree burns were considered unlikely to heal by 21 days. Biopsy pathology results were correlated with still photos by five burn experts for consensus of final burn depth diagnosis. Results Sixty-six subjects were enrolled with 117 wounds and 816 biopsies. The BBA was used to categorize subjects’ wounds into 4 categories: 7% of burns were categorized as 1 st degree, 13% as superficial 2 nd degree, 43% as deep 2 nd degree, and 37% as 3 rd degree. Therefore 20% of burn wounds were incorrectly judged as needing excision and grafting by the clinical team as per the BBA. As H&E is unable to assess the viability of papillary and reticular dermis, with time our team came to appreciate the greater importance of adnexal structure necrosis over dermal appearance in assessing healing potential. Conclusions Our study demonstrates that a BBA with objective histologic criteria can be used to categorize BDA with clinical misclassification rates consistent with past literature. This study serves as the largest analysis of burn biopsies by modern day burn experts and the first to define histologic parameters for BDA.

Cutaneous mucinosis of infancy: a rare case of joint involvement

Background Primary cutaneous mucinosis are a heterogeneous group of diseases characterized by the deposition of glycosaminoglycans in the dermis and the follicles. These diseases are rare in children therefore their diagnosis and management are still challenging. Joint involvement has been reported in patients with secondary cutaneous mucinosis and, rarely, in primary mucinosis. We describe a case of Cutaneous Mucinosis of Infancy with joint involvement. Case presentation An healthy 5-year-old boy showed acute arthritis of the left knee and left elbow confirmed by ultrasound. Laboratory tests were within normal range. Symptoms disappeared after a course of nonsteroid anti-inflammatory drugs. One year later, the knee swelling reappeared; juvenile idiopathic arthritis was diagnosed and intra-articular steroid injection was performed. Due to persistence of arthritis of the knee he was admitted to our hospital. On physical examination variable skin-colored lesions were observed, which had been in existence for over 2 years. We performed a skin biopsy that showed an interstitial mucine deposition in the reticular dermis. Cutaneous Mucinosis of Infancy was diagnosed. Discussion and conclusions Cutaneous Mucinosis of Infancy is a persistent dermatosis with benign prognosis and no treatment is generally required. Our case report is particularly interesting because it is the first in which joint involvement has been reported in CMI, a disorder that has so far been described as limited to skin involvement. Further studies will be necessary in order to clarify the pathogenesis of joint involvement in primary mucinosis.

Three Cases of Lymphocytic Infiltration of the Eyelid

Lymphocytic infiltration of the skin (LIS), first reported by Jessner and Kanof in 1953, is a disease of unknown etiology characterized by erythematous papules and plaques on the head, neck, and upper back and histopathological findings of a normal epidermis with underlying lymphocytic infiltration of the reticular dermis without mucin deposition. A 69-year-old man and a 21-year-old woman presented with edematous indurative erythema of the left upper eyelid. Lymphocytic infiltration of the dermis with CD4+ T cell predominance was noted on biopsy. A 68-year-old man presented with a four-year history of recurrent edematous indurative erythema of the right upper eyelid that extended up to the right cheek. Predominantly dermal infiltration of CD8+ T lymphocytes was found on biopsy. We treated all three patients with 8–16 mg of methylprednisolone daily, and the erythema and induration improved. CD4+ T cells were predominant in the acute phase (patients 1 and 2), whereas CD8+ T cells were predominant in the chronic phase (patient 3). CD8+ T cells may be involved in LIS recurrence. Lymphocytic infiltration of the eyelid may be associated with isolated circumscribed, edematous, indurative, colorless lesions that are responsive to daily low-to-middle doses of oral methylprednisolone.

In vitro beneficial effects of a flax extract on papillary fibroblasts define it as an anti-aging candidate

Objective: During aging, skin undergoes structural, cellular and molecular changes, which not only alter skin mechanical properties but also biological and physiological functions. Structurally the epidermis becomes thinner, the dermal epidermal junction flattens and the extra-cellular matrix component of the dermis is disorganized and degraded. The dermis is composed of two compartments: The Reticular dermis is the deepest and thickest part while the upper layer, the papillary dermis, which is much thinner and is in close contact with epidermis, plays an important role in the structure and function of the skin. We have recently shown that the papillary dermis was preferentially affected by skin aging because the activity of fibroblasts in this region was especially altered as a function of age. The purpose of this study was to investigate the capacity of a flax extract as anti-aging component. Method: We investigated the capacity of a flax extract to stimulate or restore the activity of papillary fibroblasts from young and old donors in cultured monolayers and in reconstructed skin. Several biological markers of extracellular matrix homeostasis and mechanical properties were investigated. Results: The tested flax extract seemed to improve parameters known to change with age: I/ In monolayers after treatment the number of aged fibroblasts increased II/ In reconstructed skin the flax extract appears to positively regulate some biological activities; particularly in aged fibroblasts where the deposition of laminin 5, fibrillin 1, procollagen I were increased in the dermis and the secretion of specific soluble factors like MMP1, MMP3 and KGF were regulated to levels similar to those observed in young fibroblasts III/ Mechanical properties were improved particularly for elastics parameters (R5, R2 and R7). Conclusion: The flax extract is a promising anti-aging compound. The treatment of aged papillary fibroblasts resulted in a return to a younger-like profile for some of the studied parameters.

Classification and clinical evaluation of the types of angiokeratoma

Background: Angiokeratoma is a group of benign vascular telangiectasias in the superficial dermis associated with hyperkeratosis of the epidermis. There are different types of angiokeratoma and the color of the lesions—pink, red, dusky red, blue-red—depends on their age. Materials and Methods: Twenty-four patients with different varieties of angiokeratoma were collected from April 2013 through March 2020 and classified according to well-defined types. Each patient gave their formal consent after the nature of the disease was explained to them. Full medical history taking and clinical examination were performed on all patients. Skin biopsies were taken from 12 cases and processed for histopathology with H&E stain. As for therapy, diathermy was used for the treatment of selected localized cases, especially those on the scrotum. Results: Twenty-four cases with different types of angiokeratoma were evaluated, 19 (79.16%) males and 5 (20.83%) females, with ages ranging from 13 to 25 years and a mean age of 19 years. The age of onset was most commonly around adolescence and early adulthood. The lesions were classified into the following: 11 (45.83%) cases of Fordyce, 5 (20.83%) cases solitary, 4 (16.66%) cases circumscriptum, 3 (12.5%) cases oral (on the tongue), and one (4.16%) corporis diffusum (Fabry disease). All patients displayed warty red, blue, or black papules, nodules, or plaques, with the exception of isolated angiokeratoma. Their histopathology revealed hyperkeratosis of the epidermis, which could have been mild or marked acanthosis, as seen in the form of pseudoepithelial hyperplasia with marked elongation of rete ridges. As a dermal change, markedly dilated blood vessels occupied the papillary and reticular dermis. Diathermy was an effective mode of therapy in selected patients with satisfactory cosmetic and therapeutic results. Conclusion: All types of angiokeratoma were recognized but the most common were angiokeratoma of Fordyce, mainly affecting male genitalia, followed by solitary angiokeratoma, affecting mainly the limbs, and angiokeratoma circumscriptum linearly along the limbs. Oral angiokeratoma of the tongue appeared in three patients. All these types have a characteristic presentation that is easy to recognize: warty dusky-red lesions.

136 Use of 816 Consecutive Burn Wound Biopsies to Inform a Histologic Algorithm for Burn Depth Diagnosis

Introduction Burn experts are only 77% accurate when subjectively assessing burn depth, leaving almost a quarter of patients to undergo unnecessary surgery or conversely suffer a delay in treatment. To aid clinicians in burn depth assessment (BDA), new technologies are being studied with machine learning algorithms calibrated to histologic standards. Our group has iteratively created a theoretical burn biopsy algorithm (BBA) based on histologic analysis, and subsequently informed it with the largest burn wound biopsy repository in the literature. Here, we sought to report that process. Methods This was an IRB-approved, prospective, multicenter study. A BBA was created a priori and refined in an iterative manner, resulting in the current state of the algorithm seen in Figure 1. Patients with burn wounds assessed by burn experts as requiring excision and autograft underwent 4mm biopsies procured every 25cm2. Serial still photos were obtained at enrollment and at excision intraoperatively. Burn biopsies were histologically assessed for presence/absence of epidermis, papillary dermis, reticular dermis, and proportion of necrotic adnexal structures by a dermatopathologist using H&E with whole slide scanning. First degree and superficial 2nd degree were considered to be burn wounds likely to have healed without surgery, while deep 2nd and 3rd degree burns were considered unlikely to heal by 21 days. Biopsy histopathology results were correlated with still photos by 3 burn experts for consensus of final burn depth diagnosis. Results Sixty-six subjects were enrolled with 117 wounds and 816 biopsies. The BBA was used to categorize 100% of subjects into 4 categories: 7% of burns were categorized as 1st degree, 13% as superficial 2nd degree, 43% as deep 2nd degree, and 37% as 3rd degree. Therefore 20% of burn wounds were incorrectly judged as needing excision and grafting by the clinical team. As H&E is unable to assess the viability of papillary and reticular dermis, with time our team came to appreciate the greater importance of adnexal structure necrosis over dermal appearance in assessing healing potential. Conclusions Our study demonstrates that a BBA with objective histologic criteria can be used to categorize BDA with clinical misclassification rates consistent with past literature. This study serves as the largest analysis of burn biopsies by modern day burn experts and the first to define histologic parameters for BDA.

T cell infiltration on local CpG-B delivery in early-stage melanoma is predominantly related to CLEC9A+CD141+ cDC1 and CD14+ antigen-presenting cell recruitment

BackgroundWe previously reported CpG-B injection at the primary tumor excision site prior to re-excision and sentinel node biopsy to result in immune activation of the sentinel lymph node (SLN), increased melanoma-specific CD8+ T cell rates in peripheral blood, and prolonged recurrence-free survival. Here, we assessed recruitment and activation of antigen-presenting cell (APC) subsets in the SLN and at the injection site in relation to T cell infiltration.MethodsRe-excision skin specimens from patients with clinical stage I-II melanoma, collected 7 days after intradermal injection of either saline (n=10) or 8 mg CpG-B (CPG7909, n=12), were examined by immunohistochemistry, quantifying immune subsets in the epidermis, papillary, and reticular dermis. Counts were related to flow cytometric data from matched SLN samples. Additional in vitro cultures and transcriptional analyses on peripheral blood mononuclear cells (PBMCs) were performed to ascertain CpG-induced APC activation and chemokine profiles.ResultsSignificant increases in CD83+, CD14+, CD68+, and CD123+ APC were observed in the reticular dermis of CpG-B-injected skin samples. Fluorescent double/triple staining revealed recruitment of both CD123+BDCA2+ plasmacytoid dendritic cells (DCs) and BDCA3/CD141+CLEC9A+ type-1 conventional DC (cDC1), of which only the cDC1 showed considerable levels of CD83 expression. Simultaneous CpG-B-induced increases in T cell infiltration were strongly correlated with both cDC1 and CD14 counts. Moreover, cDC1 and CD14+ APC rates in the reticular dermis and matched SLN suspensions were positively correlated. Flow cytometric, transcriptional, and chemokine release analyses of PBMC, on in vitro or in vivo exposure to CpG-B, indicate a role for the activation and recruitment of both cDC1 and CD14+ monocyte-derived APCs in the release of CXCL10 and subsequent T cell infiltration.ConclusionThe CpG-B-induced concerted recruitment of cDC1 and CD14+ APC to the injection site and its draining lymph nodes may allow for both the (cross-)priming of T cells and their subsequent homing to effector sites.

From SARS-CoV-2 hematogenous spreading to endothelial dysfunction: clinical-histopathological study of cutaneous signs of COVID-19

Background To date, very few studies on clinical-histopathological correlations of cutaneous disorders associated with COVID-19 have been conducted. Case presentation The Case 1 was a 90-year-old man, who tested positive for SARS-CoV-2 from a nasopharyngeal swab. Two days later, he was hospitalized and after eleven days transferred to Intensive Care Unit. A chest CT showed bilateral ground-glass opacities. Just that day, an erythematous maculo-papular rash appeared on trunk, shoulders and neck, becoming purpuric after few days. Histological evaluations revealed a chronic superficial dermatitis with purpuric aspects. The superficial and papillary dermis appeared edematous, with a perivascular lympho-granulocytic infiltrate and erythrocytic extravasation. At intraepithelial level, spongiosis and a granulocyte infiltrate were detected. Arterioles, capillaries and post-capillary venules showed endothelial swelling and appeared ectatic. The patient was treated with hydroxychloroquine, azithromycin, lopinavir-ritonavir and tocilizumab. Regrettably, due to severe lung impairment, he died. The Case 2 was a 85-year-old man, admitted to Intensive Care Unit, where he was intubated. He had tested positive for SARS-CoV-2 from a nasopharyngeal swab two days before. A chest RX showed bilateral atypical pneumonia. After seven days, a cutaneous reddening involving trunk, upper limbs, neck and face developed, configuring a sub-erythroderma. Histological evaluations displayed edema in the papillary and superficial reticular dermis, and a perivascular lymphocytic infiltrate in the superficial dermis. The patient was treated with hydroxychloroquine, azithromycin, lopinavir-ritonavir and tocilizumab. Sub-erythroderma as well as respiratory symptoms gradually improved until healing. Conclusions The endothelial swelling detected in the Case 1 could be a morphological expression of SARS-CoV-2-induced endothelial dysfunction. We hypothesize that cutaneous damage could be initiated by endothelial dysfunction, caused by SARS-CoV-2 infection of endothelial cells or induced by immune system activation. The disruption of endothelial integrity could enhance microvascular permeability, extravasation of inflammatory cells and cytokines, with cutaneous injury. The Case 2 developed a sub-erythroderma associated with COVID-19, and a non-specific chronic dermatitis was detected at histological level. We speculate that a purpuric rash could represent the cutaneous sign of a more severe coagulopathy, as highlighted histologically by vascular abnormalities, while a sub-erythroderma could be expression of viral hematogenous spreading, inducing a non-specific chronic dermatitis.