The Lone Lump: Cutaneous Rosai-Dorfman Disease as an Isolated Upper Arm Lesion.

Rosai-Dorfman disease (RDD) is a rare disorder characterized by excessive growth of histiocytes. We present a case of a 14-year-old female with cutaneous RDD who had a subcutaneous lump on her left arm for three years. The lump became tender and progressively larger over the past year. She had no systemic symptoms, and her physical examination revealed a mobile, tender lump. Laboratory tests were normal. Surgical excision of the lump was performed, and histopathological examination confirmed RDD with the presence of epithelioid histiocytes with eosinophilic and clear cytoplasm, along with emperipolesis and positive staining for CD68, CD163, S100, and OCT2. The patient was referred for follow-up and required no further treatment. RDD can present with subcutaneous masses without systemic symptoms, and it is important to consider RDD in the differential diagnosis of such cases. Surgical excision is the main treatment, and long-term monitoring is necessary due to the potential for disease recurrence. Awareness of cutaneous RDD presentations is crucial for accurate diagnosis and management.

Novel UROD mutation for porphyria cutanea tarda, type 2: a case report.

Background: Porphyria cutanea tarda (PCT) is usually caused by acquired defects in uroporphyrinogen decarboxylase (UROD) activity in the liver. This more common form of PCT is called type 1 PCT. Major known risk factors for PCT include iron overload, such as occurs due to mutations in HFE, associated with classical hereditary hemochromatosis, chronic hepatitis C infection, heavy alcohol use, tobacco use, and estrogen therapy. In addition, in about 25% of patients with PCT, namely, those with PCT type 2, an inherited partial defect in UROD activity is found. In such persons, this partial defect, which is found in all cells, including hepatocytes, red blood cells, and others, contributes to the development of biochemically and clinically active disease. Case Description: Herein we describe salient features of a man in his eighth decade of life with onset of clinical PCT. Among risk factors were heavy alcohol and tobacco use. Genetic testing revealed a novel mutation in one of his alleles of the UROD gene, namely, c.224 G>C; p. Arg 75 Pro, and enzymatic testing revealed that red blood cell UROD activity was decreased by 50%. This mutation in the UROD gene is predicted to have a major effect on protein structure and function, confirmed by the 50% decrease in activity of the enzyme. Conclusions: The previously undescribed mutation in UROD, found in this man, namely, c.224 G>C; p. Arg 75 Pro is pathogenic.

Atypical presentation of γ/δ mycosis fungoides with an unusual phenotype and SOCS1 mutation.

Mycosis fungoides is the most frequent subtype of primary cutaneous T-cell lymphomas. The diagnosis is based on a thorough clinic-pathologic correlation, which can, especially in early-stage disease, be challenging due to similarities with several benign skin disorders such as psoriasis and atopic dermatitis. Here, we present a case of an 81-year-old man with a 20-year-long medical history of skin problems treated as psoriasis with limited effect. Since December 2021, the patient experienced worsening of his skin symptoms with rapidly growing tumors and widespread patches and plaques. Positron emission tomography/computed tomography evaluation revealed markedly metabolic activity related to the skin tumors and increased FDG uptake in several retroperitoneal lymph nodes. Histological assessment of skin biopsies demonstrated a highly proliferative T-cell lymphoma with a γ/δ+ and CD8+ cytotoxic phenotype. The morphology of the tumor cells appeared blastic with an abnormal immunephenotype CD3+, CD2-, CD5dim, CD4-, CD8+, CD56-, and CD30-. Next-generation sequencing detected a likely pathogenic SOCS1 mutation with an allele frequency of 72% as well as a STAT3 variant of unknown significance. This case highlights the diagnostic complexity of an indolent skin lymphoma evolving into an aggressive cytotoxic lymphoma.

Successful Treatment of Refractory Cutaneous Protothecosis With MAT2203, an Oral Lipid Nanocrystal Formulation of Amphotericin B.

Prototheca wickerhamii is a rare cause of cutaneous and systemic infection that requires long treatment courses with potentially toxic medications. We describe a patient with cutaneous protothecosis refractory to triazole monotherapy who experienced clinical and radiographic improvement with the novel oral lipid nanocrystal formulation of amphotericin B without experiencing toxicity.

Serosurvey of canine leishmaniasis in five departments near an identified human clinical case in Marseille (France).

Leishmania infantum is a protozoan parasite of the family Trypanosomatidae, transmitted by the bite of phlebotomine sand flies (Diptera: Psychodidae). It is responsible for human and canine leishmaniasis in countries bordering the Mediterranean basin. Here we describe a clinical case of human cutaneous leishmaniasis in a 76-year-old female patient living in Marseille. Upon interrogation, the patient had no history of recent travel or contact with animals. The study involved clinical, serological, and molecular investigation of the occurrence of Leishmania infection in 718 dogs from five departments within a 130 km radius perimeter around Marseille. Five dogs showed signs of moderate leishmaniasis. Additionally, the serological survey of dogs revealed a global seroprevalence of 5.1%, with a significantly different prevalence in the Vaucluse department. Molecular analysis and phylogenetic studies highlighted the close relatedness of Leishmania strains between human and canine hosts with 99.6% of identity, indicating local transmission. The findings underscore the importance of serological surveillance in dogs and human. In a One Health approach, it is necessary to continue investigating Leishmania infection in all potential reservoirs, especially for zoonotic L. infantum in wildlife (red foxes, leporids, rodents, etc.) but also in dogs, cats, and equids.

Impact of the COVID pandemic on melanoma thickness and ulceration: a meta-analysis.

The global healthcare sector faced immense challenges due to the COVID-19 pandemic. Oncologists noted reduced cancer screening, which impacted melanoma diagnosis and treatment, leading to concerns about delayed care and poorer outcomes. This review analyzes how the pandemic influenced melanoma ulceration risk and Breslow thickness index through a meta-analysis of published studies. Following PRISMA guidelines, we conducted a systematic review of literature from January 2021 to December 2022 on cutaneous melanoma before and during the COVID-19 pandemic. Upon screening 1854 manuscripts, the review led to 13 studies meeting inclusion standards. The quality assessment followed MINORS and Newcastle-Ottawa Scale criteria. Regarding ulceration, post-COVID ulceration surpassed pre-COVID levels significantly, with a risk ratio of 1.31 and an estimated odds ratio of 1.41, indicating a 44% rise post-COVID. As for Breslow thickness, studies show a rising trend in the Breslow index post-COVID, but less significantly, with an effect size of 0.08 regarding the meta-analysis model (P = 0.02) with a pre-COVID mean Breslow of 1.56 mm and post-COVID of 1.84 mm. This meta-analysis concluded that post-COVID ulceration rates significantly surpassed pre-COVID levels. Considering that ulcerated melanomas usually undergo sentinel lymph node biopsy and are more likely to benefit from adjuvant therapies, this indicates important implications, as many patients might have missed the opportunity to start therapy appropriately, regardless of their Breslow thickness status.

Variations of the extrapsoas course of the lumbar plexus with implications for the lateral transpsoas approach to the lumbar spine: a cadaveric study.

BACKGROUND: Together with an increased interest in minimally invasive lateral transpsoas approach to the lumbar spine goes a demand for detailed anatomical descriptions of the lumbar plexus. Although definitions of safe zones and essential descriptions of topographical anatomy have been presented in several studies, the existing literature expects standard appearance of the neural structures. Therefore, the aim of this study was to investigate the variability of the extrapsoas portion of the lumbar plexus in regard to the lateral transpsoas approach. METHODS: A total of 260 lumbar regions from embalmed cadavers were utilized in this study. The specimens were dissected as per protocol and all nerves from the lumbar plexus were morphologically evaluated. RESULTS: The most common variation of the iliohypogastric and ilioinguinal nerves was fusion of these two nerves (9.6%). Nearly in the half of the cases (48.1%) the genitofemoral nerve left the psoas major muscle already divided into the femoral and genital branches. The lateral femoral cutaneous nerve was the least variable one as it resembled its normal morphology in 95.0% of cases. Regarding the variant origins of the femoral nerve, there was a low formation outside the psoas major muscle in 3.8% of cases. The obturator nerve was not variable at its emergence point but frequently branched (40.4%) before entering the obturator canal. In addition to the proper femoral and obturator nerves, accessory nerves were present in 12.3% and 9.2% of cases, respectively. CONCLUSION: Nerves of the lumbar plexus frequently show atypical anatomy outside the psoas major muscle. The presented study provides a compendious information source of the possibly encountered neural variations during retroperitoneal access to different segments of the lumbar spine.

Microemulsions strongly promoted the activity of α-bisabolol against different Leishmania species and its skin permeation.

This study aimed to develop microemulsions (MEs) containing α-bisabolol for the topical treatment of cutaneous leishmaniasis (CL). Initially, pseudoternary phase diagrams were developed using α-bisabolol as the oil phase, Eumulgin® CO 40 as the surfactant, Polymol® HE as the co-surfactant, and distilled water as the aqueous phase. Two transparent liquid systems (TLS) containing 5% of α-bisabolol were selected and characterized (F5E25 and F5EP25). Next, skin permeation and retention assays were performed using Franz cells. The interaction of the formulation with the stratum corneum (SC) was evaluated using the FTIR technique. The cytotoxicity was evaluated in murine peritoneal macrophages. Finally, the antileishmanial activity of microemulsions was determined in promastigotes and amastigotes of L. amazonensis (strain MHOM/BR/77/LTB 0016). As a result, the selected formulations showed isotropy, nanometric size (below 25 nm), Newtonian behavior and pH ranging from 6.5 to 6.9. The MEs achieved a 2.5-fold increase in the flux and skin-permeated amount of α-bisabolol. ATR-FTIR results showed that microemulsions promoted fluidization and extraction of lipids and proteins of the stratum corneum, increasing the diffusion coefficient and partition coefficient of the drug in the skin. Additionally, F5E25 and F5EP25 showed higher activity against promastigotes (IC50 13.27 and 18.29, respectively) compared to unencapsulated α-bisabolol (IC50 53.8). Furthermore, F5E25 and F5EP25 also showed antileishmanial activity against intracellular amastigotes of L. amazonensis, with IC50 50 times lower than free α-bisabolol and high selectivity index (up to 15). Therefore, the systems obtained are favorable to topical administration, with significant antileishmanial activity against L. amazonensis promastigotes and amastigotes, being a promising system for future in vivo trials.

Anifrolumab for systemic lupus erythematosus with multi-refractory skin disease: A case series of 18 patients.

OBJECTIVE: Skin involvement is common in systemic lupus erythematosus (SLE), but may be resistant to conventional treatment. We sought to evaluate the efficacy of anifrolumab (ANI) in refractory cutaneous manifestations of SLE. METHODS: Case series of patients with refractory cutaneous SLE from three Rheumatology Departments in Greece. Outcome measures were improvement in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), physician global assessment (PGA) and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). Clinically relevant improvement in skin was defined as decrease ≥50% (CLASI50) from baseline values. RESULTS: Eighteen patients received ANI; all had active skin involvement at baseline. Mean (SD) SLEDAI and PGA at ANI initiation were 7.4 (2.7) and 1.4 (0.5), respectively, with a mean prednisone dose 4.9 (4.5) mg/day. Mean CLASI (Activity/Damage) at baseline was 13.9 (9.7)/2.9 (4.6). Patients were refractory to a mean 6.3 (1.5) immunomodulatory agents (including hydroxychloroquine and glucocorticoids) before the initiation of ANI. After a mean 8.5 (4.6) months, 89% (n = 16/18) of patients demonstrated significant improvement in general lupus and cutaneous disease activity, and glucocorticoid tapering. Mean SLEDAI and mean CLASI at last visit were 3.4 (1.9) and 2.1 (2.4)/1.4 (2.2), respectively, and mean daily prednisone dose decreased to 2.4 (2.2). Of note, in this group of highly refractory patients CLASI50 was achieved in 16/18 (89%) patients. One patient discontinued ANI after 4 infusions due to a varicella-zoster virus infection and one patient, who initially responded to treatment with ANI, experienced a skin flare due to temporary discontinuation due to Covid 19 infection. DORIS remission and LLDAS were attained in two (11.1%) and eleven (61.1%) patients, respectively. CONCLUSION: Anifrolumab is highly effective in various skin manifestations of SLE, even after prior failure to multiple treatments.

Direct immunofluorescence demystified: Essential insights and recent advances for dermatologists.

Direct immunofluorescence (DIF) is widely used in dermatopathology for the diagnosis of autoimmune blistering diseases (AIBDs), cutaneous vasculitis, and connective tissue disorders. Although it is easy and useful to perform, it needs technical expertise and experience for proper interpretation. The yield of DIF depends on multiple factors including the adequacy, transportation, storage, processing, and interpretation of the biopsy specimen. Effective collaboration between the dermatologist and dermatopathologist along with meticulous clinico-pathological correlation is crucial for accurately interpreting DIF in the appropriate clinical context. In this narrative review of DIF in dermatology, we discuss the indications of DIF, recent updates on the selection of optimum biopsy sites, basic techniques of DIF including the classical transport medium and its alternatives, processing and staining technique, patterns in various diseases, advancements such as serration pattern analysis, and latest recommendations on the use of DIF in cutaneous disorders.

Prognostic and immune infiltration implications of SIGLEC9 in SKCM.

The occurrence and progression of skin cutaneous melanoma (SKCM) is strongly associated with immune cells infiltrating the tumor microenvironment (TME). This study examined the expression, prognosis, and immune relevance of SIGLEC9 in SKCM using multiple online databases. Analysis of the GEPIA2 and Ualcan databases revealed that SIGLEC9 is highly expressed in SKCM, and patients with high SIGLEC9 expression had improved overall survival (OS). Furthermore, the mutation rate of SIGLEC9 in SKCM patients was found to be 5.41%, the highest observed. The expression of SIGLEC9 was positively correlated with macrophages, neutrophils and B cells, CD8 + T cells, CD4 + T cells, and dendritic cells, according to TIMER. Based on TCGA-SKCM data, we verified that high SIGLEC9 expression is closely associated with a good prognosis for SKCM patients, including overall survival, progression-free interval, and disease-specific survival. This positive prognosis could be due to the infiltration of immune cells into the TME. Additionally, our analysis of single-cell transcriptome data revealed that SIGLEC9 not only played a role in the normal skin immune microenvironment, but is also highly expressed in immune cell subpopulations of SKCM patients, regulating the immune response to tumors. Our findings suggest that the close association between SIGLEC9 and SKCM prognosis is primarily mediated by its effect on the tumor immune microenvironment.

Sister Mary Joseph Syndrome: A Report of a Rare Case.

The Sister Mary Joseph syndrome is characterized by cutaneous metastases localized at the umbilical level. It is a rare clinical sign estimated to occur in 1%-3% of patients with abdominopelvic cancer. The most common histology is adenocarcinoma (75% of cases). The presence of this nodule is often indicative of a poor prognosis, with average survival estimated at two to 11 months without treatment. We report the clinical case of Sister Mary Joseph syndrome in a 50-year-old woman who had been followed for three years for endometrioid adenocarcinoma of the endometrium. The diagnosis was established via umbilical biopsy after a computed tomography scan revealed the presence of an umbilical nodule. The patient is currently undergoing a palliative chemotherapy regimen.

Cutaneous Squamous Cell Carcinoma of the Head and Neck: A Retrospective Analysis of Loco-Regional Recurrences and Survival Rates Over a Consecutive 10-Year Period.

INTRODUCTION: Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin cancers worldwide. Due to the ever-increasing sun exposure and life expectancy, cSCCs are increasing worldwide. The aim of our study was to identify specific risk factors leading to local and regional recurrences, determine patients' survival rates, and identify best practices for the management of cSCC. METHODOLOGY: This study retrospectively analyzed 1197 head and neck cSCCs in 945 patients who consecutively presented to the clinics from January 2007 to December 2016. Patients were followed up for a minimum of 18 months. RESULTS: A total of 29 patients (3%) developed loco-regional recurrences (26 local, one regional, and two both local and regional) with a median time to recurrence of 25 (range, 1-81) months. The mean follow-up was 32 (range, 5-90) months. Treatment modality (p=0.027), depth of invasion (p<0.001), diameter > 20 mm (p<0.001), gender (p=0.022), histological differentiation (p<0.001), site of the lesion (p<0.001), perineural and intravascular invasion (p<0.001), positive lymphadenopathy (p=0.021), immunosuppression (p<0.001), and history of treatment (p=0.008) proved to be strong predictors for loco-regional recurrences. At one and five years after diagnosis, 95.6% and 59.9% of all patients were recurrence-free, respectively. The median survival time from recurrence was 2.6 years. CONCLUSION: Our study identifies prognostic indicators for reoccurrence by analyzing data from a large continuous cohort in the management of cSCCs.

Cutaneous Metastasis of Oral Carcinoma Tongue: A Rare Case.

Cutaneous metastasis from head and neck cancers is rare, typically presenting as single or multiple nodules. This report presents a truly unique and intriguing case of squamous carcinoma of the tongue, in which the patient developed numerous metastatic nodules in the face and neck, a phenomenon rarely seen in clinical practice. The patient, a known case of carcinoma tongue, was treated radically with concurrent chemoradiation. He presented with small cutaneous lesions in his neck and upper chest, which were confirmed as cutaneous malignancies. Despite receiving one cycle of palliative chemotherapy, the management of this case posed significant and complex challenges, requiring a deep understanding of the nature of the spread and metastatic pathway for choosing the appropriate management.

A Rare Presentation of Malignant Melanoma of the Face: A Case Report.

Melanoma is a malignant neoplasm of melanoblasts, which are the precursors of the melanocytes arising from the neural crest cells. Melanomas can occur at various sites like the skin, eyes, upper esophagus, and meninges due to the migration of neural crest cells. Usually, the prognostic factors are decided based on the Breslow index. This case report describes a 61-year-old female who presented with the complaint of pinkish irregular swelling over the left side of her face for six months. The patient had a surgical resection, and the condition was determined to be invasive melanoma following confirmation by magnetic resonance imaging (MRI) and histological examination. Through our case report, we aim to shed light on the existing protocol for managing malignant melanoma while also exploring new aspects of presentation and multidisciplinary action.

Semen Cannabis and Oleum Hyperici: Antileishmanial activity against Leishmania tropica promastigotes and intracellular amastigotes.

The exploration of alternative agents and novel drug candidates for the effective treatment of cutaneous leishmaniasis has garnered significant attention, driven by the high cost, toxic effects, and the emergence of drug resistance associated with current therapeutic options. Plant extracts derived from Semen Cannabis, the seeds of the Cannabis sativa L. (hemp) plant, and Oleum Hyperici, the oily macerate of Hypericum perforatum L. (St. John's Wort) plant, were prepared by using solvents of varying polarity (n-hexane, chloroform, ethanol, and 60% aqueous ethanol). The primary objective of this study was to research in vitro and ex vivo antileishmanial efficacy of Semen Cannabis and Oleum Hyperici plant extracts against Leishmania tropica promastigotes and intracellular amastigotes. The efficacy of plant extracts against promastigotes were assessed using the cell counting by hemocytometer and the CellTiter-Glo assay. Additionally, their impact on infected THP-1 macrophages and the quantity of intracelluler amastigotes were investigated. Cytotoxicity was evaluated in THP-1 macrophages. Among the tested plant extracts, chloroform extract of Oleum Hyperici demonstrated significant antileishmanial activity against promastigotes (SI: 12.6) and intracellular amastigotes (SI: 16.8) of L. tropica without inducing cytotoxic effects and hold promise for further investigation as potential antileishmanial agents.