Genetic landscape of indolent and aggressive Kaposi sarcomas.

BACKGROUND: Kaposi sarcoma (KS) is a rare skin tumour caused by herpesvirus 8 infection and characterized by either indolence or an aggressive course necessitating systemic therapies. The genetic basis of this difference remains unknown. OBJECTIVES: To explore the tumour mutational burden in indolent and aggressive KS. METHODS: We performed whole-exome sequencing on a cohort of 21 KS patients. We compared genetic landscape including tumor mutational burden between the two forms of indolent and agressive KS. RESULTS: Aggressive KS tumours had a significantly higher TMB and a larger cumulative number of deleterious mutations than indolent KS tumours. In addition, all aggressive tumours had at least three deleterious mutations, whereas most indolent tumours harboured only one or no predicted deleterious mutations. Deleterious mutations listed in the Cancer Gene Census were detected exclusively in patients with aggressive disease. An analysis of somatic copy-number alterations (SCNA) revealed a tendency towards higher number of alterations in aggressive KS. CONCLUSIONS: These data suggest that SCNA alterations and an increase in mutational burden promote aggressive KS and that it might be more appropriate to consider indolent KS as an opportunistic skin disease rather than a cancer.

High prevalence of syphilis in women, minors and precarious patients: a cross-sectional study in a Reunion Island sexually transmitted infection clinic, 2017-2020.

BACKGROUND: Syphilis is a sexually transmitted infection (STI) with a global prevalence estimated at 0.5% in 2012. Syphilis has been on the rise among men who have sex with men (MSM) in high-income countries and remains at endemic levels in low- and middle-income countries. This trend, however, has not been observed in Reunion Island. OBJECTIVES: To determine the prevalence, clinical characteristics and risk factors of syphilis in at-risk patients visiting the South Reunion STI clinic in Reunion Island. METHODS: This monocentric cross-sectional study included all patients who visited our STI clinic between 2017 and 2020. Syphilis serology was performed on all included patients, and data were collected using a standardized self-administered questionnaire. RESULTS: Over the 3-year study period, 2593 patients were enrolled. The prevalence of syphilis was 7.52% (n = 195, 95% CI, 6.50-8.65%) in the overall study population, 11.76% (n = 18, 95% CI, 6.97-18.59%) in minors (aged under 18 years) and 36.36% (n = 16, 95% CI, 21-59%) in pregnant women. The risk factors identified in multivariate analysis were being female [adjusted Prevalence Ratio (aPR) 1.85, 95% CI, 1.10-3.11], being MSM (aPR 2.87, 95% CI, 1.71-4.80), being aged under 18 years (aPR 3.54, 95% CI, 1.90-6.57), living in precarious conditions [aPR 3.12, 95% CI, 2.11-4.62] and being born in Reunion Island (aPR 2.43, 95% CI, 1.42-4.13). The clinical presentation was heterogeneous (plaques and papules, chancre, atypical ulcerations, multiple ulcerations, condyloma lata, etc.). CONCLUSIONS: These findings suggest a high prevalence of syphilis in at-risk patients visiting our STI clinic. Unlike the situation in other high-income countries, the people most at risk of syphilis in Reunion Island are local-born residents, minors, women and precarious patients. This is a source of concern, especially given the risk of resurgence of congenital syphilis on the island.

Benefits of simulation using standardized patients for training dermatology residents in breaking bad news.

INTRODUCTION: Simulation in healthcare is a rapidly developing teaching method in the training of technical procedures. It is also used to enable caregivers to learn how to inform patients of serious illness and complex health status. However, its use is not widespread in the field of dermatology. This study investigated the utility of simulation as regards disclosing melanoma diagnosis, taking resident physician satisfaction as a primary endpoint. MATERIALS AND METHODS: Fifteen dermatology residents were recruited as trainees. Four scenarios were allocated based on length of residency. An introductory briefing was held prior to the training sessions. Debriefing took place on completion of the diagnosis disclosure consultation. The participants completed questionnaires after the simulation session, after debriefing, and 3 months after the simulation session. The primary endpoint was usefulness of the session felt by trainees several months after the simulation. RESULTS: The majority of participants (93.3%) thought the session helped with stress management, improved their attitude and control over their reaction (86.6%), and improved their communication skills (100%). They rated the usefulness of the simulation at 7.79/10 on average (range: 5-10). DISCUSSION: According to our findings the resident physicians involved, particularly those with the least experience, were satisfied with this type of learning technique. Any difficulties encountered by these residents were brought to light and addressed during debriefing. CONCLUSION: There would appear to be real benefits to be reaped from simulation, whatever the stage of medical training at which it takes place. Simulation should become an increasingly important part of contemporary pregraduate specialty programs.

A fifth subtype of Kaposi's sarcoma, classic Kaposi's sarcoma in men who have sex with men: a cohort study in Paris.

BACKGROUND: Classic Kaposi's sarcoma (CKS) occurs predominantly among elderly men and is associated with Kaposi's sarcoma-associated herpesvirus (KSHV). In low-endemic countries, KSHV infects predominantly men having sex with men (MSM). OBJECTIVES: To describe a cohort of classic Kaposi sarcoma in a low-endemic area for KSHV, to highlight the features of CKS in MSM and identify prognostic factors. METHODS: Retrospective single-centre study of CKS cases. We compared MSM to heterosexual patients. Then, we divided the patients into two subgroups, those requiring a systemic treatment and the others, and we performed univariate and multivariate analyses to determine aggressiveness of CKS. RESULTS: Between 2006 and 2015, seventy-four patients were included. Mean age at diagnosis was 68.9 years; sex ratio (M/F) was 6.4, and 28% were MSM; MSM patients were younger (P = 0.02), less often originated from endemic areas (P < 0.0001). KS was less severe (P = 0.04), required more often a local treatment than a systemic one (P = 0.03). On multivariate analysis, CD4 T-cell count > 500/mm3 at baseline was associated with a reduced risk of severe evolution. CONCLUSION: First CKS cohort in low-endemic zone. We describe a fifth subtype of KS: KS in MSM. The CD4 T-cell count was found to correlate with prognosis.

Anaplastic Kaposi's sarcoma: 5 cases of a rare and aggressive type of Kaposi's sarcoma.

BACKGROUND: Anaplastic Kaposi's sarcoma (KS) is a rare form of KS characterized clinically by the development of a tumour mass with unusual local aggressiveness and histologically by a specific architecture and cytological morphology. A very small number of limited series in endemic countries have established characteristics common to these anaplastic forms of KS. We present five patients with an anaplastic form in a context of KS ongoing for several years in a non-endemic country. MATERIALS AND METHODS: We collected 5 cases of anaplastic KS followed in our department over a period of 20years. We describe the main developmental, clinical, virological and histological features. RESULTS: The cases involved 4 men and 1 woman whose mean age at diagnosis of anaplastic KD was 70years, with an average time of 25years between initial diagnosis of KD and anaplastic transformation. Our patients were all treated with chemotherapy and/or radiotherapy (RT) prior to diagnosis of anaplastic transformation. All patients had a tumour mass of the lower limbs developing in classically indolent KS with associated chronic lymphoedema. Progression was very aggressive locally with deep invasion of the soft tissues as well as osteoarticular involvement, without visceral dissemination. At present, three patients are dead, one patient is showing partial response, and one patient is in locoregional progression. Diagnosis of the disease was based on histopathological findings. The tumour cells were undifferentiated, pseudo-cohesive, and chiefly organized in sheets. The mitotic count was high (27 mitoses per 10 fields at high magnification). Necrosis was constant. DISCUSSION: To our knowledge, this is the first series describing anaplastic Kaposi's sarcoma in a non-endemic country. The severity of the prognosis, despite the absence of visceral dissemination, is related to the local aggressiveness of anaplastic KS and to its resistance to radiotherapy and chemotherapy, with amputation being required in certain cases.

[Dermatologic surgery, hemophilia and Von Willebrand disease]. / Risques en dermatologie interventionnelle chez les patients hémophiles ou atteints de la maladie de Willebrand.

BACKGROUND: Von Willebrand disease (VWD) and hemophilia A and B are the most common types of hereditary coagulation-factor deficiencies. The frequency and type of complications of skin surgery in these patients are unknown. The increasing incidence of skin cancer prompted us to reflect upon this issue. While the incidence of skin cancer is increasing, the complications of skin surgery or ablative laser treatment remain unknown in this population. AIM: The aim of this study was to determine the frequency of bleeding complications during and after skin surgery in patients with a hereditary coagulation-factor deficiency (hemophilia or VWD). PATIENTS AND METHODS: We conducted a retrospective study in patients with hemophilia A or B or VWD undergoing skin surgery or ablative laser treatment at the Dermatology Department of the Cochin Hospital in Paris, France. RESULTS: Fourteen procedures were performed in 8 patients. Three episodes of bleeding occurred (n=3/14, 21.4%): one hematoma, one delayed bleed and one immediate bleed. None of these complications required surgical revision or resuscitation. DISCUSSION: The rate of hemorrhagic complications was higher than in the general population. However, these complications can be considered non-serious and the risk-benefit ratio remains favorable. Multidisciplinary management and coordination with the reference hemophilia center are mandatory in this population to establish a coagulation-factor (CF) substitution protocol suited to the disease characteristics and the surgical procedure.

[CONDYDAV: A multicentre observational study of patients presenting external genital warts in France]. / CONDYDAV : étude observationnelle multicentrique des patients présentant des condylomes dans les dispensaires antivénériens en France.

BACKGROUND: Since 2007 in France, human papilloma virus (HPV) vaccination has been licensed for use as a vaccine against HPV 6, 11, 16 and 18. The impact on the epidemiology of external genital warts (EGWs) in a large population remains unclear. OBJECTIVES: To determine epidemiologic and clinical features of patients presenting EGWs in France in the era of HPV vaccination. PATIENTS AND METHODS: In this prospective, observational study, we analyzed clinical features and treatments between January 1st, 2012 and March 31, 2012 for patients consulting for EGWs at 15 STI clinics throughout France. RESULTS: A total of 372 men and 111 women were included; mean age 31.2 years. The women were younger than the men (31.7 and 28.9 years respectively P<0.05). Among the patients, 416 (85.7%) were heterosexual, 13 bisexual and 54 (11.2%) homosexual, including one female. Males reported more sexual partners in the last 12 months (more than 3 partners in 32.6% versus 11.9%, P<0.01). Among the men, 230 had involvement of the penis alone and 46 had involvement of the anus alone. Seventy-six patients had EGWs of the anus, and of these 26 were MSM. In females, 76 had an infection of the vulva alone and 22 co-infection of the vulva and anus. MSM and females were at higher risk than heterosexual males for anal involvement (P<0.0001 and P=0.004, respectively). Three women had been vaccinated: two with Gardasil® and one with Cervarix®. Cryotherapy was the preferred treatment. CONCLUSION: With the advent of HPV vaccination, a global strategy for the prevention and treatment of EGW should be implemented.

Expression pattern of the CXCL12/CXCR4-CXCR7 trio in Kaposi sarcoma skin lesions.

BACKGROUND: Recent studies have independently implicated the chemokine CXCL12 and its receptors, CXCR4 and CXCR7, in the pathophysiology of Kaposi sarcoma (KS). OBJECTIVES: We investigated whether the CXCL12/CXCR4-CXCR7 protein trio could constitute KS biomarkers. METHODS: Endothelial and spindle cells positive for CXCL12/CXCR4-CXCR7, human herpesvirus-8 latency-associated nuclear antigen (LANA), Ki67 antigen (proliferation) and vascular endothelial growth factor (VEGF) were quantitated in skin lesions from patients with AIDS-associated KS, patients with classic KS and patients with angiomas, using immunohistochemistry and quantitative image analysis (16, 21 and 20 skin lesions, respectively). Plasma CXCL12 concentrations were measured by enzyme-linked immunosorbent assay from 20 patients with AIDS-KS, 12 HIV-infected patients without KS and 13 healthy donors' samples. RESULTS: Cells positive for CXCL12, CXCR4, CXCR7, LANA, Ki67 and VEGF were significantly enriched in patients with AIDS-associated KS and classic KS vs. angiomas (P < 0·001), and in nodular vs. macular/papular KS lesions (P < 0·05). CXCL12, CXCR4 and CXCR7 detection correlated with LANA, Ki67 and VEGF detection (r > 0·4; P < 0·05). However, plasma CXCL12 concentrations did not differ between patients with AIDS-associated KS, HIV-infected patients without KS, and healthy donors. CONCLUSIONS: The CXCL12/CXCR4-CXCR7 trio is upregulated in KS and correlates with KS pathophysiological markers and the severity of skin lesions. Histological assessment of the CXCL12 axis could serve as a valuable biomarker for KS diagnosis and progression.

Prognostic value of antibodies to Merkel cell polyomavirus T antigens and VP1 protein in patients with Merkel cell carcinoma.

BACKGROUND: Merkel cell polyomavirus (MCPyV) is the main aetiological agent of Merkel cell carcinoma (MCC). Serum antibodies against the major MCPyV capsid protein (VP1) are detected in the general population, whereas antibodies against MCPyV oncoproteins (T antigens) have been reported specifically in patients with MCC. OBJECTIVES: The primary aim was to assess whether detection of serum antibodies against MCPyV proteins at baseline was associated with disease outcome in patients with MCC. The secondary aim was to establish whether evolution of these antibodies during follow-up was associated with the course of the disease. METHODS: Serum T-antigen and VP1 antibodies were assessed by enzyme-linked immunosorbent assay using recombinant proteins in a cohort of 143 patients with MCC, including 84 patients with serum samples available at baseline. RESULTS: Low titres of VP1 antibodies at baseline (< 10 000) were significantly and independently associated with increased risk of recurrence [hazard ratio (HR) 2·71, 95% confidence interval (CI) 1·13-6·53, P = 0·026] and death (HR 3·74, 95% CI 1·53-9·18, P = 0·004), whereas T-antigen antibodies were not found to be associated with outcome. VP1 antibodies did not differ between patients in remission and those with recurrence or progression during follow-up. However, T-antigen antibodies were more frequently detected in patients with recurrence or progression at 12 months (P = 0·020) and 24 months (P = 0·016) after diagnosis. CONCLUSIONS: VP1 antibodies constitute a prognostic marker at baseline, whereas T-antigen antibodies constitute a marker of disease recurrence or progression if detected > 12 months after diagnosis.