Trichodysplasia Spinulosa.

Trichodysplasia spinulosa (TS) is a unique, rare clinical and histological dermatologic entity described mainly in a setting of immunosuppression. It is caused by a novel human polymoavirus, TS-associated polyomavirus. Reduction of immunosuppression and/or anti-viral therapy is the main therapeutic strategies used to treat such cases. We report a biopsy-proven case of TS in a male renal transplant patient who presented to a dermatology outpatient clinic in Montreal, Canada, in 2015. He was managed with valgancyclovir with no obvious response. Subsequently, a trial of topical imiquimod was commenced. Awareness of TS can prompt early diagnosis and management to prevent possible complications.

An unusually indolent well-differentiated Wilson-Jones angiosarcoma: A case report.

Cutaneous angiosarcomas are rare soft tissue tumours originating from hematogenous vasculature that are aggressive and carry a poor prognosis. We describe the case of a 73-year-old man with a low-grade well-differentiated angiosarcoma. Our case distinguishes itself from those previously reported in the slow progression and important delay to the presentation of 30 months and survival time of 5.5 years. Additionally, its severe clinical appearance (T2 stage) but milder pathological picture (T1 stage) is very uncommon. A repeat biopsy is warranted when results are inconclusive and there is a high clinical suspicion of angiosarcoma.

Spatially mapping the immune landscape of melanoma using imaging mass cytometry.

Melanoma is an immunogenic cancer with a high response rate to immune checkpoint inhibitors (ICIs). It harbors a high mutation burden compared with other cancers and, as a result, has abundant tumor-infiltrating lymphocytes (TILs) within its microenvironment. However, understanding the complex interplay between the stroma, tumor cells, and distinct TIL subsets remains a substantial challenge in immune oncology. To properly study this interplay, quantifying spatial relationships of multiple cell types within the tumor microenvironment is crucial. To address this, we used cytometry time-of-flight (CyTOF) imaging mass cytometry (IMC) to simultaneously quantify the expression of 35 protein markers, characterizing the microenvironment of 5 benign nevi and 67 melanomas. We profiled more than 220,000 individual cells to identify melanoma, lymphocyte subsets, macrophage/monocyte, and stromal cell populations, allowing for in-depth spatial quantification of the melanoma microenvironment. We found that within pretreatment melanomas, the abundance of proliferating antigen-experienced cytotoxic T cells (CD8+CD45RO+Ki67+) and the proximity of antigen-experienced cytotoxic T cells to melanoma cells were associated with positive response to ICIs. Our study highlights the potential of multiplexed single-cell technology to quantify spatial cell-cell interactions within the tumor microenvironment to understand immune therapy responses.

Rare case of primary cutaneous adenoid cystic carcinoma of the abdomen: A case report.

Adenoid cystic carcinoma is predominantly a tumor of the parotid glands and can sometimes be found in other glands. In most cases, skin location is usually a metastatic presentation and rarely a primary tumor. We describe the case of a 59-year-old female patient presenting with a 5-mm skin-colored nodule on the abdomen histologically compatible with a primary cutaneous adenoid cystic carcinoma. Extensive workup revealed no other primary source, nor evidence of metastatic disease; therefore, wide local excision was the preferred treatment given the low potential of recurrence. As this adnexal carcinoma is rare and its morphology non-specific clinically, we wanted to raise awareness of this entity and its management.

Verrucous plane xanthomas secondary to lipoprotein X dyslipidemia in the context of cholestatic fulminant hepatitis: A case report.

Cutaneous xanthomas are the result of dermal deposition of lipid, mostly caused by disorders of lipid metabolism. Less commonly, they occur in the setting of cholestatic liver disease, leading to accumulation of lipoprotein X, a rare form of dyslipidemia that does not respond well to conventional treatments. We describe an atypical presentation of sudden diffuse xanthomas secondary to lipoprotein X dyslipidemia in the context of cholestatic fulminant hepatitis caused by trimethoprim-sulfamethoxazole hypersensitivity. Histopathology was also atypical and showed an unusual verrucous appearance consisting of overlying epidermal hyperplasia with hyperkeratosis. Our patient had significant improvement, after normalization of her lipid panel under cholestyramine and 13 sessions of apheresis, with topical corticosteroids offering some relief. This rare case shows the importance of recognizing atypical presentations of xanthomas, particularly when they do not respond to conventional dyslipidemia treatments.

Multi-omic analysis reveals significantly mutated genes and DDX3X as a sex-specific tumor suppressor in cutaneous melanoma.

The high background tumor mutation burden in cutaneous melanoma limits the ability to identify significantly mutated genes (SMGs) that drive this cancer. To address this, we performed a mutation significance study of over 1,000 melanoma exomes, combined with a multi-omic analysis of 470 cases from The Cancer Genome Atlas. We discovered several SMGs with co-occurring loss-of-heterozygosity and loss-of-function mutations, including PBRM1, PLXNC1 and PRKAR1A, which encodes a protein kinase A holoenzyme subunit. Deconvolution of bulk tumor transcriptomes into cancer, immune and stromal components revealed a melanoma-intrinsic oxidative phosphorylation signature associated with protein kinase A pathway alterations. We also identified SMGs on the X chromosome, including the RNA helicase DDX3X, whose loss-of-function mutations were exclusively observed in males. Finally, we found that tumor mutation burden and immune infiltration contain complementary information on survival of patients with melanoma. In summary, our multi-omic analysis provides insights into melanoma etiology and supports contribution of specific mutations to the sex bias observed in this cancer.

Linear discoid lupus erythematosus mimicking en coup de sabre morphea: A case report.

Discoid or chronic lupus erythematosus is an autoimmune disease that produces skin lesions on the face and scalp. Rarely do lesions present with linear configuration, but when they do, the lesions often follow the lines of embryologic migration. A 24-year-old man presented with a slowly progressing asymptomatic violaceous linear patch running from the root of his frontal scalp to the nasal tip. A Doppler ultrasound and skin biopsy were performed and the histological findings demonstrated characteristic findings of discoid lupus erythematosus. A full physical examination, review of systems and laboratory investigations showed no indication of systemic lupus. High potency topical steroids and calcineurin inhibitors were prescribed along with photoprotection. At 4-month follow-up, all his lesions had mostly cleared. We report here the first case, to our knowledge, of discoid lupus erythematosus with en coup de saber presentation mimicking morphea.

Severe xanthomatosis in heterozygous familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia is a genetic lipoprotein disorder characterized by elevated plasma low-density lipoprotein cholesterol level, (tendinous xanthomas, xanthelasmas, and premature arcus corneus) and early onset atherosclerotic cardiovascular disease. Familial hypercholesterolemia is caused by mutations in the low-density lipoprotein receptor, apolipoprotein B or proprotein convertase subtilisin/kexin type 9 genes. Rare mutations in low-density lipoprotein receptor adapter protein 1, APOE p.Leu167del or lysosomal acid lipase genes can mimic FH. The prevalence of heterozygous familial hypercholesterolemia is estimated to be 1/250 worldwide, although some populations with founder effects show a higher prevalence. The rare homozygous form has an estimated prevalence of 0.000004 or 1/250,000 and is characterized by markedly elevated low-density lipoprotein cholesterol, skin manifestations (planar xanthomas, tendinous xanthomas) in childhood and extremely premature atherosclerotic cardiovascular disease. While tendinous xanthomas are considered pathognomonic for familial hypercholesterolemia, they can also be found in rare diseases, including sitosterolemia. Here, we report a case of severe tendinous xanthomatosis with heterozygous familial hypercholesterolemia due to the low-density lipoprotein receptor del >15 kb mutation. The phenotypic expression of the disease is out of proportion with the genetic diagnosis or biochemical measurements. CASE REPORT: We report the case of 51-year-old woman of French-Canadian origin diagnosed with heterozygous familial hypercholesterolemia since age 12. She presented with hypercholesterolemia with total cholesterol 7.6 mmol/L, with an imputed low-density lipoprotein cholesterol level of 6.5 mmol/L. She had extensive tendinous xanthomas of the Achilles tendons, knees, elbows and metacarpophalangeal joints. Because of cosmetic disfigurement, she had multiple excisions of Achilles, knee and elbow xanthomas, albeit with rapid recurrence. Our patient has a significant family history of lung cancer and other autoimmune diseases associated with familial hypercholesterolemia and xanthoma. Lipid-lowering therapy was started, at age 12; which included initially cholestyramine, then changed to statin and ezetimibe. Eventually, evolocumab was added. Despite trying different lipid-lowering therapy, there has been no noticeable decrease in the size of the xanthomas. CONCLUSION: Our patient has severe xanthomatosis out of proportion with the genetic diagnosis or biochemical measurements. Her xanthomatosis did not improve by pharmacological therapy consisting of statins and evolocumab despite a 50% reduction in low-density lipoprotein cholesterol. It is likely that the patient presented here has a second genetic disorder that leads to extensive xanthomatosis.

Complements c3 and c5 individually and in combination increase early wound strength in a rat model of experimental wound healing.

Background. Complements C3 and C5 have independently been shown to augment and increase wound healing and strength. Our goal was to investigate the combinatorial effect of complements C3 and C5 on wound healing. Methods. Each rat served as its own control where topical collagen was applied to one incision and 100 nM of C3 and C5 in collagen vehicle was applied to the other incision (n = 6). To compare between systemic effects, a sham group of rats (n = 6) was treated with collagen alone on one wound and saline on the other. At day 3, the tissue was examined for maximal breaking strength (MBS) and sectioned for histological examination. Results. There was a statistically significant 88% increase in MBS with the topical application of C3C5 when compared to sham wounds (n < 0.05). This was correlated with increased fibroblast and collagen deposition in the treated wounds. Furthermore, there appeared to be an additive hemostatic effect with the C3C5 combination. Conclusions. The combination of complements C3 and C5 as a topical application drug to skin wounds significantly increased wound healing maximum breaking strength as early as 3 days.

Accelerated wound healing with topical application of complement C5.

BACKGROUND: Delayed-healing traumatic, surgical, and chronic wounds can be detrimental to patients and the health care system. The authors set out to investigate the effects of complement C5, a naturally occurring chemotactic cytokine, on wounds. METHODS: The authors examined the effects of complement C5 on the rat paired skin incision model. Each rat served as its own control where topical collagen was applied to one incision and 100 nM of C5 in collagen vehicle was applied to the other incision. Rats were killed on days 3 (n = 6), 7 (n = 6), and 28 (n = 5) after wounding. RESULTS: There was a statistically significant, 65 percent increase in maximum wound breaking strength with the topical application of C5 at day 3 (p < 0.01). The increase persisted to 14 percent at 7 days after wounding (p < 0.05). When compared with the sham group, the C5-treated wound strength increased by 83 percent at day 3 and 64 percent at day 7. There was no change in breaking strength at 28 days. Western blot analysis demonstrated a significant increase in collagen and fibronectin content in the C5-treated wounds. CONCLUSIONS: Topical application of C5 to skin wounds significantly increases wound healing maximum breaking strength as early as 3 days and up to 7 days after wounding. C5 accelerated wound healing by at least 4 days in the first week of wounding. This was correlated with an increase in vascular permeability, increased inflammatory cell recruitment, subsequent fibroblast migration, and increased collagen deposition.

Diagnosis and management of eosinophilic cellulitis (Wells' syndrome): A case series and literature review.

INTRODUCTION: Eosinophilic cellulitis (Wells' syndrome) is an inflammatory dermatitis that is often misdiagnosed as infectious cellulitis due to its similarity in presentation. Misdiagnosis leads to delay of correct treatment and inappropriate use of antibiotics. METHODS: A case series of eosinophilic cellulitis and a literature review are presented. RESULTS: Patients with Wells' syndrome may present with a variety of nonspecific symptoms, such as fever, arthralgia and malaise, as well as myriad cutaneous lesions with associated erythema, presenting as blisters, bullae, papules and/or nodules. Several treatment modalities have been used to treat eosinophilic cellulitis and have been met with variable success rates; these include systemic corticosteroids, topical corticosteroids and antihistamines, with success rates of 91.7%, 50% and 25%, respectively. CONCLUSIONS: A high degree of clinical suspicion must be exercised to diagnose this rare condition. Cellulitis with an atypical presentation or not responding to appropriate antibiotic treatment should trigger suspicion of Wells' syndrome. To date, the most successful treatment method is a short course of systemic corticosteroids.

INTRODUCTION: La cellulite à éosinophiles (syndrome de Wells) est une dermatite inflammatoire souvent diagnostiquée à tort comme une cellulite infectieuse en raison de sa présentation similaire. Le mauvais diagnostic retarde le traitement pertinent et suscite une utilisation inadéquate des antibiotiques. MÉTHODOLOGIE: Les auteurs présentent une série de cas de cellulite à éosinophiles et une analyse bibliographique. RÉSULTATS: Les patients ayant le syndrome de Wells peuvent présenter divers symptômes non spécifiques, tels que la fièvre, l'arthralgie et les malaises, de même qu'une myriade de lésions cutanées associées à un érythème, sous forme de vésicules, de cloques, de papules ou de nodules. Plusieurs modalités thérapeutiques ont été utilisées pour traiter la cellulite à éosinophiles et ont obtenu des taux de succès variés. Ainsi, les corticoïdes systémiques, les corticoïdes topiques et les antihistaminiques ont obtenu des taux de succès de 91,7 %, de 50 % et de 25 %, respectivement. CONCLUSIONS: Il faut un fort degré de présomption clinique pour diagnostiquer cette maladie rare. La cellulite ayant une présentation atypique ou qui ne répond pas à une antibiothérapie convenable devrait soulever la possibilité de syndrome de Wells. Jusqu'à présent, la méthode thérapeutique la plus réussie consiste à administrer un court traitement aux corticoïdes systémiques.

The effects of topical collagen treatment on wound breaking strength and scar cosmesis in rats.

BACKGROUND: Topical application of collagen has been suggested to enhance wound healing; however, its long-term effect on wounds has not been studied in a rat model. HYPOTHESIS: Topical application of collagen type I will not facilitate incision healing or cosmesis in rats up to 28 days postwounding. METHODS: The effects of bovine collagen type I (6 mg/mL) on the rat surgical paired skin incision model were examined. Each rat served as its own control in which topical collagen was applied to one incision while normal saline (0.9%) was applied to the other incision. Rats were euthanized three (n=6), seven (n=6) and 28 (n=5) days after wounding. Tissue harvested from each time point was examined for maximal breaking strength, and for biochemical and histological analysis. RESULTS: There were no statistically significant differences (ie, P<0.05) in maximum wound breaking strength between the collagen- and saline-treated wounds at all time points. Histological analysis revealed a similar infiltration of inflammatory cells and fibroblasts in the wound edges of all incisions when matched with time of wounding. Western blot analysis revealed no differences in fibronectin or collagen I content in all wounds in each rat. CONCLUSIONS: The topical application of collagen did not facilitate wound healing from three to 28 days in the rat wound model.

HISTORIQUE: L'application topique de collagène améliorerait la guérison des plaies. Cependant, on n'a pas étudié son effet à long terme sur les plaies d'un modèle de rat. HYPOTHÈSE: L'application topique de collagène de type I ne facilitera pas la cicatrisation ou l'esthétique d'une incision chez les rats jusqu'à 28 jours après la formation de plaies. MÉTHODOLOGIE: Les auteurs ont examiné les effets du collagène bovin de type I (6 mg/mL) sur un modèle de double incision cutanée chez des rats. Chaque rat était son propre sujet témoin, car du collagène topique était appliqué sur une incision, et une solution physiologique normale (0,9 %), sur l'autre. Les rats étaient euthanasiés trois (n=6), sept (n=6) et 28 (n=5) jours après la création des plaies. Les auteurs ont prélevé des tissus à chacun de ces moments et les ont examinés pour établir leur résistance maximale à la rupture et pour procéder à une analyse biochimique et histologique. RÉSULTATS: Il n'y a pas de différence statistiquement significative (c'est-à-dire P<0,05) quant à la résistance maximale à la rupture des plaies traitées au collagène et de celles traitées au moyen d'une solution physiologique à l'un de ces trois moments. L'analyse histologique a révélé une infiltration similaire des cellules inflammatoires et des fibroblastes dans les lèvres de la plaie de chacune des incisions par rapport au moment de création de la plaie. Le transfert de Western n'a révélé aucune différence dans le contenu en fibronectine ou en collagène I des plaies de chaque rat. CONCLUSIONS: L'application topique de collagène ne facilite pas la cicatrisation des plaies au bout de trois à 28 jours dans un modèle de plaies chez les rats.