[Vulvar oedema revealing systemic mastocytosis]. / Œdème vulvaire révélant une mastocytose systémique.

BACKGROUND: Systemic mastocytosis is characterised by abnormal proliferation of mast cells in various organs. We report an original case of systemic mastocytosis revealed by vulvar oedema. PATIENTS AND METHODS: A 24-year-old patient was examined in the dermatology department for vulvar oedema appearing during sexual intercourse. She presented vasomotor dysfunction of the lower limbs, urticaria on the trunk on exertion, diarrhoea and bone pains. Laboratory tests showed serum tryptase of 29.7µg and plasma histamine at twice the normal value. Myelogram results showed infiltration by dysmorphic mast cells. Screening for c-kit D816V mutation was positive. Duodenal biopsies revealed mast-cell clusters with aggregation involving over 15 mast cells. CD2 staining was inconclusive and CD25 staining could not be done. Trabecular osteopenia was found, and we thus made a diagnosis of indolent systemic mastocytosis (ISM variant Ia) as per the WHO 2008 criteria. Symptomatic treatment was initiated (antiH1, H2, antileukotrienes) and clinical and laboratory follow-up was instituted. DISCUSSION: The cutaneous signs leading to diagnosis in this patient of systemic mastocytosis involving several organs were seemingly minimal signs associated with mastocyte degranulation. This is the third recorded case of mastocytosis revealed by vulvar oedema and the first case revealing systemic involvement. The two previously reported cases of vulvar oedema revealed cutaneous mastocytosis alone. Mastocytosis, whether systemic or cutaneous, must be included among the differential diagnoses considered in the presence of vulvar oedema.

Update on gene fusions and the emerging clinicopathological landscape of peritoneal and pleural mesotheliomas and other neoplasms.

BACKGROUND: Mesothelioma is a rare and aggressive malignant neoplasm arising from mesothelial cells, which occasionally manifests recurrent fusions. EWSR1/FUS-CREB, YY1, MAP3K8, NR4A3, and ALK-rearranged proliferations have been reported in limited series with no clear histological or clinical correlations, limiting clinicians' ability to assess prognosis and integrate these new entities into therapeutic decisions. The aim of this study was to better characterize these rearranged proliferations histologically, molecularly, and clinically. METHODS: Clinical, pathological, and comprehensive transcriptome and mutation data were collected for each case. RESULTS: A total of 41 tumors were included, encompassing 7 ALK, 10 MAP3K8, 4 NR4A3, 8 ESWR1/FUS::ATF1, 8 EWSR1::YY1, and 4 SUFU-fused cases. We found a female predominance, except for cases harboring NR4A3 and SUFU; and most patients were around 60 years of age, but those harboring ALK or EWSR1/FUS::ATF1 gene fusions were younger. Each group exhibited distinct histological, immunohistochemical, molecular features, and oncological courses. Specifically, MAP3K8 and ALK presented PAX8+ papillary proliferations, ESWR1/FUS::ATF1 and EWSR1::YY1 displayed angiomatoid fibrous histiocytoma-like patterns, while SUFU showcased 'tissue culture'-like spindle cell proliferation. Poor prognosis factors were the pleural site, male sex, Ki67 ≥10%, and ESWR1/FUS::ATF1 or SUFU gene fusions. CONCLUSIONS: This study significantly broadens the spectrum of mesothelial tumors associated with fusions, offering insight into novel epithelioid (mesothelial) proliferations with distinctive histological appearances, molecular profiles, and prognoses to guide adapted treatments for patients.

DCF (docetaxel, cisplatin and 5-fluorouracil) chemotherapy is a promising treatment for recurrent advanced squamous cell anal carcinoma.

BACKGROUND: Squamous cell carcinoma of the anal canal (SCCA) is a rare disease, mostly diagnosed at early stage. After concurrent chemoradiation (CRT) with mitomycin C and 5-fluorouracil (5FU), local or metastatic recurrences occur in >20% of the patients. After treatment failure, cisplatin (CDDP)-based chemotherapy is the standard option, but complete response (CR) is a rare event and the prognosis remains poor. PATIENTS AND METHODS: Eight consecutive patients with advanced recurrent SCCA after CRT were treated with DCF regimen (docetaxel 75 mg/m(2) day 1, CDDP 75 mg/m(2) day 1 and 5FU at 750 mg/m(2)/day for 5 days every 3 weeks). Tumour samples were analysed for human papillomavirus (HPV) genotyping, as well as p16 and p53 expression. RESULTS: After a median follow-up of 41 months, the overall survival rate at 12 months was 62.5% (95% CI 22.9-86.1 months). Four patients achieved a complete remission and remain relapse-free at the time of analysis with a progression-free survival of 19, 33, 43 and 88 months. Three of these patients underwent surgery for all involved metastatic sites. For all of them, pathological CR was confirmed. DCF regimen appeared feasible in these patients previously exposed to pelvic CRT, and no grade IV toxicity occurred. All patients in complete remission had HPV-16-positive SCCA, while HPV could only be detected among 50% of the non-responding patients. Of interest, immunohistochemical study revealed a p16(+)/p53(-) phenotype in these patients, while none of non-responders expressed p16. CONCLUSION: The high level of complete and long-lasting remission among SCCA patients treated with DCF regimen supports the assessment of this strategy in prospective cohorts.

[Giant condyloma acuminatum in pregnancy]. / La tumeur de Buschke Lowenstein chez la femme enceinte.

Buschke Lownestein's tumour is a giant acuminate condyloma characterised by its degenerative potential, its invasive nature and its recurrence after treatment. It is a rare condition, transmitted mainly by sexual transmission and induced by to the human papillomavirus (HPV). The discussion will be illustrated by a clinical case The treatment is still under discussion but surgery seems to be the best option. Management during pregnancy is more complex since it must take into account the mother and her fetus. The delivery route is still debated. The post-treatment evolution was satisfactory and without recurrence until the delivery which, due to the antecedent of 3 caesarean sections, was carried out by cesarean section. HPV vaccination, sex education and early treatment of condyloma lesions should prevent and in any case improve the prognosis of this disease.

T1 Vertebra Pedicular Osteoid Osteoma: Minimally Invasive Surgical Resection Aided by New Integrated Navigation to 3D Imaging Device.

We hereby describe a minimally invasive resection of a T1 pedicular osteoid osteoma next to the vertebral canal. The patient had an 18-month report of painful radiculopathy. We performed the surgery under 3D imaging guidance using navigation with an all-in-one device. Full procedure irradiation was 1.17 mSv for a 181-picture acquisition. Complete operative time incision to closure was 58 minutes. Despite sparing the vertebral stability without any fixation, the tumor resection was well-margined, thanks to the focused guidance. After surgery, the patient had complete relief of his symptoms at the 6-month follow-up. 3D imaging system coupled to navigation made the procedure safe without consuming time. The single Surgivisio® device allows comfortable 3D minimally invasive spine navigation surgery with the ergonomics of a C-arm.

Prevalence and distribution of HPV genotypes and cervical-associated lesions in sexually active young French women following HPV vaccine.

BACKGROUND: Despite the availability of safe and effective HPV vaccines in France, more than 80% of girls remain unvaccinated. SETTING: A regional university hospital referral center in France. OBJECTIVE: To estimate the overall prevalence and distribution of HPV in vaccinated, sexually active young French women who were screened for cervical cancer by cytology and HPV testing. METHODS: High-risk HPV (HR-HPV) prevalence, genotype-specific prevalence and extent of multiple infections were assessed in 125 cervical samples from females with available vaccine data using hc2 assay and INNO-LiPA assay. HPV status was analyzed in accordance with cytological data. RESULTS: In our series, mean age was 23 years, overall prevalence of HR-HPV was 52% and was correlated with the lesion grade. The diversity of HPV genotypes was broad. Single HR-HPV infections were identified in 11%, 21% and 47% of women with NILM, ASC-US/-H and LSIL respectively. Multiple infections with HR-HPV were detected in 28% of the specimens. Only 24.5% of women with NILM presented infections with 2 genotypes or more, vs 28% of women with ASC-US/-H and 35% of women with LSIL. The overall prevalence of genotypes covered by the quadrivalent vaccine was low (5.9%); with 4.2%, 0%, 0.8% and 0.8% for HPV 16, HPV 18, HPV 6 and HPV 11 respectively. CONCLUSION: Among HPV-vaccinated young women, HR-HPV are detected at a high rate, and an association with the grade of cytological abnormalities was observed. However, HPV 16 and 18, both targeted by the vaccines, are remarkably rare among young French women since program implementation.

In situ delivery of allogeneic natural killer cell (NK) combined with Cetuximab in liver metastases of gastrointestinal carcinoma: A phase I clinical trial.

Despite successful introduction of NK-based cellular therapy in the treatment of myeloid leukemia, the potential use of NK alloreactivity in solid malignancies is still elusive. We performed a phase I clinical trial to assess the safety and efficacy of in situ delivery of allogeneic NK cells combined with cetuximab in liver metastasis of gastrointestinal origin. The conditioning chemotherapy was administrated before the allogeneic NK cells injection via hepatic artery. Three escalating doses were tested (3.106, 8.106 and 12.106 NK cells/kg) following by a high-dose interleukin-2 (IL-2). Cetuximab was administered intravenously every week for 7 weeks. Nine patients with liver metastases of colorectal or pancreatic cancers were included, three per dose level. Hepatic artery injection was successfully performed in all patients with no report of dose-limiting toxicity. Two patients had febrile aplasia requiring a short-term antibiotherapy. Grade 3/4 anemia and thrombopenia were also observed related to the chemotherapy. Objective clinical responses were documented in 3 patients and among them 2 occurred in patients injected with cell products harboring two KIR ligand mismatches and one in a patient with one KIR ligand mismatch. Immune monitoring revealed that most patients presented an increase but transient of IL-15 and IL-7 cytokines levels one week after chemotherapy. Furthermore, a high expansion of FoxP3+regulatory T cells and PD-1+ T cells was observed in all patients, related to IL-2 administration. Our results demonstrated that combining allogeneic NK cells transfer via intra-hepatic artery, cetuximab and a high-dose IL-2 is feasible, well tolerated and may result in clinical responses.

Polymyalgia rheumatica and vagal paraganglioma.

INTRODUCTION: Vagal paraganglioma are rare tumors that are mostly asymptomatic. We report a case of vagal paraganglioma associated with paraneoplastic polymyalgia rheumatica and review the literature on benign paragangliomas of the head and neck associated with paraneoplastic syndrome. CASE REPORT: A 53-year-old man presented with atypical polymyalgia rheumatica. MRI revealed a tumor that was then surgically excised. Histological examination confirmed the diagnosis of benign vagal paraganglioma. Rapid, complete and permanent resolution of all rheumatological symptoms were observed postoperatively, confirming the diagnosis of paraneoplastic polymyalgia rheumatica. CONCLUSION: Paraganglioma of the neck associated with paraneoplastic syndrome remains exceptional. A predisposing gene mutation must be systematically investigated. Long-term surveillance must be ensured due to the risk of local recurrence, second tumors or metastasis.

Transfer of the lateral antebrachial cutaneous nerve to the dorsal branch of the ulnar nerve without nerve graft in case of lower brachial plexus injuries: Anatomical and feasibility study.

In the context of lower (C8-T1) brachial plexus injury, transfer of the lateral antebrachial cutaneous nerve (LABCN) to the dorsal branch of the ulnar nerve (DBUN) with an interposed sural nerve graft has been proposed to restore sensitivity on the ulnar side of the hand. The purpose of this study was to assess the feasibility of performing this transfer directly - without interposition of a nerve graft - by intraneural dissection of the DBUN. An anatomical study was performed with 20 upper limbs from adult human cadavers. The LABCN and the DBUN were dissected. The LABCN emerged from the lateral side of the biceps brachii muscle at an average of 2.6±0.4cm from the interepicondylar line and was 13.5±2.6cm long, on average. The DBUN arose from the ulnar nerve 8.2±1.6cm from the styloid process of the ulna. The maximum length of DBUN intraneural dissection relative to the ulnar nerve was 7.5±2.1cm, on average. The LABCN could be transferred to the DBUN in a tension-free manner with end-to-end suturing. Intraneural dissection of the DBUN allows LABCN nerve transfer without interposition of a graft.

Immunohistochemical evaluation of two antibodies against PD-L1 and prognostic significance of PD-L1 expression in epithelioid peritoneal malignant mesothelioma: A RENAPE study.

BACKGROUND: Epithelioid peritoneal malignant mesothelioma (EPMM) is the most common subtype of this aggressive tumor. We compared two antibodies against PD-L1, a recent theranostic biomarker, and evaluated the prognostic value of PD-L1 expression by mesothelial and immune cells in EPMM. METHODS: Immunohistochemistry was performed on 45 EPMM. Clinical and pathological data were extracted from the RENAPE database. Using E1L3N and SP142 clones, inter-observer agreement, PD-L1 expression by mesothelial and immune cells and inter-antibody agreement were evaluated. The prognostic relevance of PD-L1 expression was evaluated in 39 EPMM by univariate and multivariate analysis of overall survival (OS) and progression-free survival (PFS). RESULTS: Inter-observer agreement on E1L3N immunostaining was moderate for mesothelial and immune cells, and fair for mesothelial and poor for immune cells using SP142. Using E1L3N, 31.1% of mesothelial and 15.6% of immune cells expressed PD-L1, and 22.2% of mesothelial and 26.7% of immune cells using SP142. Inter-antibody agreement was moderate. In most positive cases, 1-5% of tumor cells were positive. Using E1L3N, PD-L1 expression by lymphocytes was associated with better OS and PFS by both univariate and multivariate analysis. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy predicted better prognosis than other treatments. Solid subtype was an independent prognostic factor for worse OS. CONCLUSION: E1L3N appeared easier to use than SP142 to evaluate PD-L1 expression. A minority of EPMM expressed PD-L1, and only a few cells were positive. PD-L1 expression by immune cells evaluated with E1L3N was an independent prognostic factor in EPMM.