[Fusion genes in salivary gland tumors]. / Les tumeurs des glandes salivaires associées à des transcrits de fusion.

Salivary gland tumors represent a diagnostic challenge for pathologists due to their rarity, their very wide histopathological and immuno-phenotypic spectrum, and the recent identification of new entities. This article presents the main molecular characteristics of these tumors in order to allow any pathologist to perceive the diagnostic tracks of these ENT tumors and to better guide the molecular approach to establish the diagnosis and guide therapy.

Paraneoplastic pemphigus uncovers distinct clinical and biological phenotypes of western unicentric Castleman disease.

Unicentric Castleman disease (UCD) is a lymphoproliferative disease of unknown cause. Paraneoplastic pemphigus (PNP) is a major complication shown to be associated with a poor prognosis, with particular severity in patients with bronchiolitis obliterans (BO). This study describes the clinical and biological characteristics of UCD-PNP patients in a large Western cohort. A total of 148 patients diagnosed with UCD were identified, including 14 patients with a defined PNP. PNP was significantly associated with myasthenia gravis (MG) and FDC sarcoma during follow-up (FDCS). PNP was also significantly associated with reduced survival. These data, together with a multivariate analysis by principal components, led to the identification of UCD-PNP as a group at risk of MG, FDCS and death. PDGFRB sequencing performed on UCD lesions from six patients found the gain-of-function p.N666S variant in two. Interestingly, both patients had hyaline-vascular UCD subtype, were in the UCD-PNP subgroup and had FDCS. Sera from 25 UCD-PNP patients and 6 PNP patients without UCD were tested for PNP-associated autoantibodies. Sera from UCD-PNP patients had a strong reactivity against the N-terminal domain of recombinant periplakin (rPPL, 82%) and showed reactivity against at least two domains of rPPL. These features were not found in patients with UCD alone or in the PNP group without UCD. These data indicate that UCD-PNP patients belong to a subgroup sharing strong clinical and biological identity that might help to decipher the different dynamics of UCD natural history.

No Long-Term Mucosal Lesions in the Esophagus but More Gastric Mucosal Lesions after Sleeve Gastrectomy in Obese Rats.

Sleeve gastrectomy (SG) often induces gastroesophageal reflux, with few and discordant long-term data on the risk of Barrett's esophagus (BE) in operated patients. The aim of this study was to analyze the impact of SG on esogastric mucosa in a rat model at 24 weeks postoperatively, which corresponds to approximately 18 years in humans. After 3 months of a high-fat diet, obese male Wistar rats were subjected to SG (n = 7) or sham surgery (n = 9). Esophageal and gastric bile acid (BA) concentrations were measured at sacrifice, at 24 weeks postoperatively. Esophageal and gastric tissues were analyzed by routine histology. The esophageal mucosa of the SG rats (n = 6) was not significantly different in comparison to that of the sham rats (n = 8), with no esophagitis or BE. However, there was more antral and fundic foveolar hyperplasia in the mucosa of the residual stomach 24 weeks after SG than in the sham group (p < 0.001). Luminal esogastric BA concentrations did not differ between the two groups. In our study, SG induced gastric foveolar hyperplasia but no esophageal lesions at 24 weeks postoperatively in obese rats. Therefore, long-term endoscopic esophageal follow-up that is recommended in humans after SG to detect BE may also be useful for detecting gastric lesions.

[Histiocytosis of Rosai-Dorfman-Destombes extranodal of the jawbone: Report of a case and review of the literature]. / Histiocytose de Rosai-Dorfman-Destombes extra-ganglionnaire du maxillaire : à propos d'un cas et revue de la littérature.

Rosai-Dorfman-Destombes histiocytosis is a rare histiocytosis characterized by an accumulation of histiocytes within the tissues. It is a heterogeneous entity with various clinical phenotypes: isolated lymph nodes, in association with extranodal involvement, autoimmune disease or neoplasm. These extra nodal lesions mainly affect the skin, the nasal cavity, orofacial sinuses, or are lytic bone lesions or even damage to the central nervous system. The diagnosis is histopathological. We present here the case of a histiocytosis of Rosai-Dorfman-Destombes in a 46-year-old patient with a lesion of the left palate. Our observation discuss the diagnostic hypotheses in front of a lytic lesion of the ENT sphere predominantly histiocytic.

A 29-Year-Old Man With an Osteolytic Rib Lesion.

CASE PRESENTATION: A 29-year-old man with no significant medical history presented to the ED with a 4-week history of chest pain. The pain was insidious, located on the right side of the chest, increased by deep breathing, and incompletely alleviated by acetaminophen. The patient had never smoked tobacco. He denied any recent fevers, chills, dyspnea, cough, night sweats, hemoptysis, or history of trauma but had lost at least 8 kg in the past 6 months. The patient was from Morocco and had lived in France for 1 year.

Bariatric surgery induces a new gastric mucosa phenotype with increased functional glucagon-like peptide-1 expressing cells.

Glucagon-Like Peptide-1 (GLP-1) undergoes rapid inactivation by dipeptidyl peptidase-4 (DPP4) suggesting that target receptors may be activated by locally produced GLP-1. Here we describe GLP-1 positive cells in the rat and human stomach and found these cells co-expressing ghrelin or somatostatin and able to secrete active GLP-1 in the rats. In lean rats, a gastric load of glucose induces a rapid and parallel rise in GLP-1 levels in both the gastric and the portal veins. This rise in portal GLP-1 levels was abrogated in HFD obese rats but restored after vertical sleeve gastrectomy (VSG) surgery. Finally, obese rats and individuals operated on Roux-en-Y gastric bypass and SG display a new gastric mucosa phenotype with hyperplasia of the mucus neck cells concomitant with increased density of GLP-1 positive cells. This report brings to light the contribution of gastric GLP-1 expressing cells that undergo plasticity changes after bariatric surgeries, to circulating GLP-1 levels.

Long-term consequences of one anastomosis gastric bypass on esogastric mucosa in a preclinical rat model.

Although bariatric surgery is proven to sustain weight loss in morbidly obese patients, long-term adverse effects have yet to be fully characterized. This study compared the long-term consequences of two common forms of bariatric surgery: one-anastomosis gastric bypass (OAGB) and Roux-en-Y Gastric Bypass (RYGB) in a preclinical rat model. We evaluated the influence of biliopancreatic limb (BPL) length, malabsorption, and bile acid (BA) reflux on esogastric mucosa. After 30 weeks of follow-up, Wistar rats operated on RYGB, OAGB with a short BPL (15 cm, OAGB-15), or a long BPL (35 cm, OAGB-35), and unoperated rats exhibit no cases of esogastric cancer, metaplasia, dysplasia, or Barrett's esophagus. Compared to RYGB, OAGB-35 rats presented higher rate of esophagitis, fundic gastritis and perianastomotic foveolar hyperplasia. OAGB-35 rats also revealed the greatest weight loss and malabsorption. On the contrary, BA concentrations were the highest in the residual gastric pouch of OAGB-15 rats. Yet, no association could be established between the esogastric lesions and malabsorption, weight loss, or gastric bile acid concentrations. In conclusion, RYGB results in a better long-term outcome than OAGB, as chronic signs of biliary reflux or reactional gastritis were reported post-OAGB even after reducing the BPL length in a preclinical rat model.

A prospective multicentre REFCOR study of 470 cases of head and neck Adenoid cystic carcinoma: epidemiology and prognostic factors.

BACKGROUND: Adenoid cystic carcinoma (ACC) accounts for 1% of malignant head and neck tumours [1] and 10% of salivary glands malignant tumours. The main objective of our study is to investigate the prognostic factors influencing the event-free survival (EFS) of patients with ACC. PATIENTS AND METHODS: A multicentre prospective study was conducted from 2009 to 2018. All 470 patients with ACC whose survival data appear in the REFCOR database were included in the study. The main judgement criterion was EFS. Both a bivariate survival analysis using log-rank test and a multivariate using Cox model were performed using the R software. RESULTS: Average age was 55 years. Females accounted for 59.4% of the cohort. The body mass index (BMI) was normal in 86% of cases. Tumours were located in minor salivary glands in 60% of cases. T3/T4 stages represented 58%; 89% of patients were cN0. histological grade III was observed on 21% of patients. The EFS and overall 5-year survival rates were 50% and 85%, respectively. After adjustment, the most significant pejorative prognostic factors were age ≥65 years (hazard ratio [HR] = 1.67), BMI<16.5 (HR = 2.62), and lymph node invasion cN (HR = 2.08). CONCLUSION: Age, BMI and N stage are the three main clinical prognostic factors determining EFS identified in this prospective series of patients with ACC. Such findings open new research perspectives on the influence of these components on initial patient care.

[Acinic cell carcinoma: an unsuspected malignancy of the nasal cavity]. / Une présentation inhabituelle d'un carcinome à cellules acineuses.

Acinic cell carcinoma (ACC) is a low grade malignant tumor of the salivary glands. Primary ACC affects most frequently the parotid gland and can rarely arise in the minor salivary glands of the oral cavity, pharynx and larynx. It is extremely rare in the nasal cavity; to our knowledge only 18 cases of primary ACC of the nasal cavity are reported in the English-written literature. Herein we report a case of acinic cell carcinoma of the nasal cavity, describe the clinical, radiological and microscopic features of this uncommon presentation and finally provide a discussion in the light of relevant literature.

Astonishing Evolution in Oropharyngeal Cancer with Immunotherapy: A Case Report.

Background: Head and neck cancer is particular due to its infiltrative nature and lymphatic extension, with multidisciplinary treatment. Immunotherapy may be a brand-new therapeutic approach.Case Presentation: We report a case of patient with advanced head and neck cancer resistant to cytotoxic treatment, with astonishing response to antibodies anti Programmed Death 1 (PD1).Conclusion: Further studies are needed in order to obtained predictive index of immunotherapy responding, aiming to select appropriately patients for this treatment.

A 22-Year-Old Woman With Fever, Palpitations, and a Cardiac Mass.

CASE PRESENTATION: A 22-year-old woman was admitted to our department for fever of unknown origin. The patient reported intermittent fever and nonspecific abdominal pain for several years. Six months before admission she started complaining of palpitations and exertional dyspnea. She had no weight loss, chest pain, headache, or joint complaints. Medical history was unremarkable. She did not consume tobacco, alcohol, or illicit drugs. The patient was from Malia. She had lived in France for 4 years and did not report recent travel.

[Diagnostic and treatment pitfalls and guidelines for variants of squamous cell carcinomas of the head and neck: on behalf of the REFCOR]. / Variants des carcinomes épidermoïdes dans les voies aérodigestives supérieures (VADS), implications pour le diagnostic et la prise en charge, selon les référentiels du REFCOR.

Among the 20,000 new cases of head and neck neoplasms in France each year, squamous cell carcinomas (HNSCC) represent about 90 % of the cases. Among these, variants of conventional squamous cell carcinomas represent between 5% and 10% of cases. Patient history and risk factors are often similar from those of conventional HSNCC. Variants may, however, be misdiagnosed, which can lead to therapeutic mismanagement due to confusion with sarcomas, glandular tumors or even benign tumors. Diagnostic workup needs to be more cautionary or to include additional exams not to omit their most aggressive component in the case of composite tumors or to under stage the tumor. Immunohistochemistry and specific molecular analyses may be required for proper diagnosis. Central pathological review may also be essential for some of these variants. In addition, some variants are radioresistant and, conversely, others are radiosensitive. An update of the REFCOR 2008 standards was carried out in the light of the international literature and the 2017 WHO/IARC classification for the seven main variants of HNSCC, verrucous, acantholytic (to be named adenoid carcinomas), basaloid, papillary, spindle cell (incorrectly named sarcomatoid), adenosquamous and lymphoepithelial carcinomas.

[A rare endolaryngeal tumor]. / Une tumeur rare endolaryngée.

We report the case of a 65-year-old woman who presented with a dysphonia. ENT tomography and laryngoscopy showed an endolaryngeal tumoral lesion extended to the right supraglottis. Biopsy of the lesion revealed dense lymphoid infiltrate in the lamina propria, without necrosis or ulceration of the mucosa. The infiltrate showed many CD3+, CD5+, CD4+, CD8+ lymphocytes and plasmocytes. Larger lymphoid cells with cytologic atypia expressed CD56 and cytotoxicity markers such as TIA1 and granzyme B. In situ hybridization for EBV revealed numerous positive cells. The diagnosis of extranodal NK/T cell lymphoma was proposed. The primary laryngeal localization of this disease is exceptionally rare. Heavy admixture of inflammatory cells may mimic inflammatory process and delay the diagnosis.

Uterine intravascular lymphoma as a cause of fever of unknown origin.

Primary intravascular large B cell lymphoma (IVL) remains a diagnostic challenge because of non-specific clinical, laboratory and imaging findings. The aim of the study was to analyse the major characteristics of IVL with uterine involvement. We retrospectively collected features of IVL with uterine involvement that was proven histologically or demonstrated by significant 18FDG uptake on 18FDG-PET/CT. Findings were compared to a comprehensive literature review. Five patients were identified. All of them were admitted for fever of unknown origin (FUO), with haemophagocytic lymphohistiocytosis in three cases. None had gynaecological symptom, contrasting with the literature data. Structural imaging (including whole-body CT scan and pelvic RMI) failed to yield any diagnosis. 18FDG-PET/CT showed intense uterine uptake in all cases. Endometrial biopsy was performed in three cases and was positive in one. Diagnosis was obtained from coelioscopic iliac adenopathy biopsy in one case and from total hysterectomy in another. Punch biopsy of skin lesions led to diagnosis in the two remaining cases. Bone marrow biopsy was normal in all cases. Clinicians should be aware of potential isolated uterine involvement in IVL, especially in elderly women with FUO. Normal structural imaging does not rule out the diagnosis and 18FDG-TEP/CT should be performed to guide high-yielding biopsy.

Cystic lung disease in Sjögren's syndrome: An observational study.

OBJECTIVES: To analyze the prevalence, characteristics and outcome of cystic lung disease associated with Sjögren's syndrome (SS). METHODS: From June 2010 to February 2015, 90 consecutive SS patients [60.1±14.8years; 88 (97.8%) female, 75 (83.3%) primary SS] had a systematic chest CT-scan. The presence of thin-walled cysts was analyzed by one experienced radiologist. Demographic data, clinical history, laboratory findings, and pulmonary function tests were extracted retrospectively from medical records. RESULTS: Twenty-one (23.3%) patients had cysts on CT scan performed 40.5±54.5months after SS diagnosis. Cysts number ranged from 1 to 25 were often bilateral (52.4%) and mostly located in the middle lung zone (76.2%). Cysts were isolated (n=6, 28.6%) or associated with other lesions, including bronchiectasis (n=5, 23.8%), micronodules (n=5, 23.8%), ground-glass opacity (n=4, 19%) and/or air trapping (n=3, 14.3%). Most patients with cysts (57.1%) had no respiratory symptoms. When comparing SS patients with and without cysts, patients with cysts tended to be older (65.3±15.3 versus 58.5±14.4years, P=0.06). Smoking habits were similar in both groups. Anti-SSB antibodies were more frequently detected in patients with cysts (57.1% vs. 26.1%, P=0.02). Pulmonary function tests were normal or displayed only mild small airways obstruction and reduced diffusion capacity to carbon monoxide. Four (19%) patients with cysts had a past history of associated pulmonary disease, including interstitial lung disease. During follow-up (25.1±17.7months), no patient developed specific lung disease or lymphoproliferative disorders. CONCLUSIONS: Cystic lung disease is frequent, benign, associated with anti-SSB/La antibodies and has no impact on outcome in SS.

Human papilloma virus prevalence in HIV patients with head and neck squamous cell carcinoma.

OBJECTIVE: The implication of human papilloma virus (HPV) in head and neck squamous cell carcinoma (HNSCC) is well established, especially in oropharyngeal SCC. HIV patients have a higher risk of persistent HPV infection. We investigated the role of HPV in HNSCC carcinogenesis in HIV population. DESIGN: Retrospective monocentric study. METHODS: We studied HIV patients who presented with HNSCC between 1994 and 2014. For each patient, tumor characteristics, HIV disease, and survival information were collected. Tumor HPV testing was performed using p16 immunohistochemistry (IHC), in-situ hybridization and PCR. We assessed the percentage of HPV in this population of HIV patients with HNSCC and compared HIV disease characteristics based on HPV status. RESULTS: Forty-seven patients were included: 11 women/36 men, the median age was 50 years. Tumor HPV testing was performed in 40 patients. Tumors were located in oropharynx (32%), oral cavity (32%), larynx (21%), and hypopharynx (11%). At the time of diagnosis, median CD4 level was 385 cells/µl, 31% of the patients were stage (Centers for Disease Control, stage C). The percentage of HPV linked to HNSCC for all locations in HIV patients was 30% (n = 12). HPV16 accounted for 50% of all HPV genotypes. HPV positive status was associated with a CD4 nadir of less than 200 (P = 0.026), but not with CD4 level at time of diagnosis (P = 0.414). HPV-negative tumors tend to be associated with poorer 5-year overall survival (hazard ratio = 2.9, P = 0.0711). CONCLUSION: HPV plays a critical role in HNSCC development in HIV population. HIV immunodeficiency may increase HPV persistence and progression of HNSCC.