Imagerie protéomique des neurinomes de l'acoustique et des nerfs normaux. Corrélations anatomopathologiques

Objectives: Proteomic analysis of acoustic neuroma (AN), non-acoustic neuroma (NAN), and healthy nerve (hn) using the mass spectrometry and imaging of the MALDI-TOF (Matrix Assisted Laser Desorption Ionization-Time Of Flight).Materials and Methods: Prospective and qualitative study on AN, NAN, and hn. Samples were provided by the Bank of Tumor of the Pathology department of our institution, after signed consent from donor patients. Frozen samples were sectioned, analyzed histologically, then glued on a conductive slide and sprayed by an acid matrix. Thereafter, the laser beam of the MALDI performed desorption and then ionization of the sample. A mass spectrogram was drawn as a function of the time of flight of ionized protein biomolecules. Results has been transferred to a software to obtain a MALDI imaging with a color spectrum which depends on the protein content of the sample. The slide has been reexamined histologically and the results compared to those of the imaging.Results: Fifty neuromas have been sampled, of which 27 were exploitable. Eleven normal nerves were analyzed. Among the 22 analyzed AN, an almost total imaging-pathology correlation was seen in only 2 cases (9.1%), a partial correlation in 4 (18.2%), and no correlation in 16 (72.7%). The mass spectrogram showed a peptide spike at 2000 m/z in 7 cases (31.8%) and at 5000 m/z in all cases (100%). Among the 5 NAN, an almost total correlation was seen in 3 cases (60%), a partial correlation in 1 (20%), and no correlation in 1 (20%). The mass spectrogram showed a peptide spike at 2000 m/z in 2 cases (40%) and at 5000 m/z in 21 cases (95.5%). Among the 11 hn, an almost total correlation was seen in 9 cases (81.8%), a partial correlation in 1 (9.1%), and no correlation in 1 (9.1%).The mass spectrogram showed in no case a peptide spike at 2000 or at 5000 m/z. Behind homogeneous areas on histology, there was a great heterogeneity in MALDI imaging and on mass spectrometry, regarding AN and NAN, but not hn.Conclusions: the lack of correlation in acoustic neuroma could be due to its lack of growth and evolution compared to other neuromas and healthy nerves which presented a better correlation. The presence of two peptide spikes detected only in neuroma and not in healthy nerve opens up the prospect of tumor biomarkers and pathophysiological actors that should be purified and identified by sequencing. In the case of presence of an imaging-pathology correlation, histological areas of interest showed morphological aspects that were reproducible in the whole analyzed samples. This is the first work on proteomic imaging using the MALDI in acoustic neuroma and in neuromas in general. This is also a first comparison between proteomic imaging of the neuroma and that of normal nerve. Besides, and also for the first time, we found a proteomic polymorphism in acoustic neuroma and non-acoustic neuroma which were absent in normal nerve tissue thereby suggesting the presence de proteic biomarkers for the neuroma.Objectifs : Analyse protéomique du neurinome de l’acoustique (NA), du neurinome non acoustique (NNA) et du nerf sain (nf s), à l’aide de la spectrométrie de masse et de l’imagerie MALDI-TOF (Matrix Assisted Laser Desorption Ionization-Time Of Flight)Matériels et Méthodes : Nous avons mené une étude prospective et qualitative sur des NA, des NNA et des nf s. Les prélèvements provenaient de la Tumorothèque du service d’Anatomopathologie de notre établissement, après consentement signé des patients donneurs. Les échantillons congelés ont été découpés, analysés histologiquement, puis collés sur une lame conductrice et recouverts de matrice acide. Par la suite, le faisceau laser du MALDI a fait subir à l’échantillon une désorption puis une ionisation. Un spectrogramme de masse a été tracé en fonction du temps de vol des biomolécules protéiques ionisées. Les résultats ont été traités par un logiciel afin d’obtenir une imagerie MALDI avec un spectre de couleur dont l’intensité dépendait du contenu protéique de l’échantillon. La lame a été ré-analysée histologiquement et les résultats comparés à ceux de l’imagerie.Résultats : Cinquante neurinomes ont été prélevés, parmi lesquels 27 étaient exploitables : 22 NA et 5 NNA. Onze nerfs normaux ont été analysés. Sur les 22 NA analysés, une corrélation imagerie-anatomopathologie quasi totale était présente dans seulement 2 cas (9,1%), une corrélation partielle dans 4 (18,2%) et pas de corrélation dans 16 (72,7%). Le spectrogramme de masse montrait un pic peptidique à 2000 m/z dans 7 cas (31,8%) et à 5000 m/z dans 21 cas (95,5%). Sur les 5 NNA, une corrélation quasi totale était présente dans 3 cas (60%), une corrélation partielle dans 1 (20%) et pas de corrélation dans 1 (20%). Le spectrogramme de masse montrait un pic peptidique à 2000 m/z dans 2 cas (40%) et à 5000 m/z dans tous les cas (100%). Sur les 11 nf s, une corrélation quasi totale était présente dans 9 cas (81,8%), une corrélation partielle dans 1 (9,1%) et pas de corrélation dans 1 (9,1%). Le spectrogramme de masse ne montrait en aucun cas de pic peptidique à 2000 ou à 5000 m/z. Derrière des zones homogènes en histologie, il existait une grande hétérogénéité en imagerie MALDI et en spectrométrie de masse pour les NA et NNA mais non pour les nf s.Conclusions : Le manque de corrélation dans le neurinome de l’acoustique proviendrait du manque de croissance relativement aux autres neurinomes et aux nerfs sains qui présentaient une meilleure corrélation. La présence de deux pics peptidiques détectés uniquement dans le neurinome et non dans le nerf sain ouvre la perspective de possibles biomarqueurs tumoraux et acteurs physiopathologiques qu’il faudra purifier et identifier par séquençage. En cas de présence d’une corrélation imagerie-anatomopathologie, les zones d’intérêt histologique montraient des aspects morphologiques reproductibles sur l’ensemble des échantillons analysés. Il s’agit d’un premier travail sur l’imagerie protéomique MALDI dans le neurinome de l’acoustique et le neurinome en général et d’une première comparaison entre l’imagerie protéomique du neurinome et celle du nerf normal. Par ailleurs, et pour la première fois aussi, il a été constaté un polymorphisme protéomique dans le neurinome de l’acoustique et le neurinome non acoustique, qui était absent dans le tissu nerveux normal, suggérant ainsi la présence de biomarqueurs protéiques pour le neurinome

Imaging of proteomics of acoustic neuromas and normal nerves. Histopathological correlations

Objectifs : Analyse protéomique du neurinome de l’acoustique (NA), du neurinome non acoustique (NNA) et du nerf sain (nf s), à l’aide de la spectrométrie de masse et de l’imagerie MALDI-TOF (Matrix Assisted Laser Desorption Ionization-Time Of Flight)Matériels et Méthodes : Nous avons mené une étude prospective et qualitative sur des NA, des NNA et des nf s. Les prélèvements provenaient de la Tumorothèque du service d’Anatomopathologie de notre établissement, après consentement signé des patients donneurs. Les échantillons congelés ont été découpés, analysés histologiquement, puis collés sur une lame conductrice et recouverts de matrice acide. Par la suite, le faisceau laser du MALDI a fait subir à l’échantillon une désorption puis une ionisation. Un spectrogramme de masse a été tracé en fonction du temps de vol des biomolécules protéiques ionisées. Les résultats ont été traités par un logiciel afin d’obtenir une imagerie MALDI avec un spectre de couleur dont l’intensité dépendait du contenu protéique de l’échantillon. La lame a été ré-analysée histologiquement et les résultats comparés à ceux de l’imagerie.Résultats : Cinquante neurinomes ont été prélevés, parmi lesquels 27 étaient exploitables : 22 NA et 5 NNA. Onze nerfs normaux ont été analysés. Sur les 22 NA analysés, une corrélation imagerie-anatomopathologie quasi totale était présente dans seulement 2 cas (9,1%), une corrélation partielle dans 4 (18,2%) et pas de corrélation dans 16 (72,7%). Le spectrogramme de masse montrait un pic peptidique à 2000 m/z dans 7 cas (31,8%) et à 5000 m/z dans 21 cas (95,5%). Sur les 5 NNA, une corrélation quasi totale était présente dans 3 cas (60%), une corrélation partielle dans 1 (20%) et pas de corrélation dans 1 (20%). Le spectrogramme de masse montrait un pic peptidique à 2000 m/z dans 2 cas (40%) et à 5000 m/z dans tous les cas (100%). Sur les 11 nf s, une corrélation quasi totale était présente dans 9 cas (81,8%), une corrélation partielle dans 1 (9,1%) et pas de corrélation dans 1 (9,1%). Le spectrogramme de masse ne montrait en aucun cas de pic peptidique à 2000 ou à 5000 m/z. Derrière des zones homogènes en histologie, il existait une grande hétérogénéité en imagerie MALDI et en spectrométrie de masse pour les NA et NNA mais non pour les nf s.Conclusions : Le manque de corrélation dans le neurinome de l’acoustique proviendrait du manque de croissance relativement aux autres neurinomes et aux nerfs sains qui présentaient une meilleure corrélation. La présence de deux pics peptidiques détectés uniquement dans le neurinome et non dans le nerf sain ouvre la perspective de possibles biomarqueurs tumoraux et acteurs physiopathologiques qu’il faudra purifier et identifier par séquençage. En cas de présence d’une corrélation imagerie-anatomopathologie, les zones d’intérêt histologique montraient des aspects morphologiques reproductibles sur l’ensemble des échantillons analysés. Il s’agit d’un premier travail sur l’imagerie protéomique MALDI dans le neurinome de l’acoustique et le neurinome en général et d’une première comparaison entre l’imagerie protéomique du neurinome et celle du nerf normal. Par ailleurs, et pour la première fois aussi, il a été constaté un polymorphisme protéomique dans le neurinome de l’acoustique et le neurinome non acoustique, qui était absent dans le tissu nerveux normal, suggérant ainsi la présence de biomarqueurs protéiques pour le neurinome.Objectives: Proteomic analysis of acoustic neuroma (AN), non-acoustic neuroma (NAN), and healthy nerve (hn) using the mass spectrometry and imaging of the MALDI-TOF (Matrix Assisted Laser Desorption Ionization-Time Of Flight).Materials and Methods: Prospective and qualitative study on AN, NAN, and hn. Samples were provided by the Bank of Tumor of the Pathology department of our institution, after signed consent from donor patients. Frozen samples were sectioned, analyzed histologically, then glued on a conductive slide and sprayed by an acid matrix. Thereafter, the laser beam of the MALDI performed desorption and then ionization of the sample. A mass spectrogram was drawn as a function of the time of flight of ionized protein biomolecules. Results has been transferred to a software to obtain a MALDI imaging with a color spectrum which depends on the protein content of the sample. The slide has been reexamined histologically and the results compared to those of the imaging.Results: Fifty neuromas have been sampled, of which 27 were exploitable. Eleven normal nerves were analyzed. Among the 22 analyzed AN, an almost total imaging-pathology correlation was seen in only 2 cases (9.1%), a partial correlation in 4 (18.2%), and no correlation in 16 (72.7%). The mass spectrogram showed a peptide spike at 2000 m/z in 7 cases (31.8%) and at 5000 m/z in all cases (100%). Among the 5 NAN, an almost total correlation was seen in 3 cases (60%), a partial correlation in 1 (20%), and no correlation in 1 (20%). The mass spectrogram showed a peptide spike at 2000 m/z in 2 cases (40%) and at 5000 m/z in 21 cases (95.5%). Among the 11 hn, an almost total correlation was seen in 9 cases (81.8%), a partial correlation in 1 (9.1%), and no correlation in 1 (9.1%).The mass spectrogram showed in no case a peptide spike at 2000 or at 5000 m/z. Behind homogeneous areas on histology, there was a great heterogeneity in MALDI imaging and on mass spectrometry, regarding AN and NAN, but not hn.Conclusions: the lack of correlation in acoustic neuroma could be due to its lack of growth and evolution compared to other neuromas and healthy nerves which presented a better correlation. The presence of two peptide spikes detected only in neuroma and not in healthy nerve opens up the prospect of tumor biomarkers and pathophysiological actors that should be purified and identified by sequencing. In the case of presence of an imaging-pathology correlation, histological areas of interest showed morphological aspects that were reproducible in the whole analyzed samples. This is the first work on proteomic imaging using the MALDI in acoustic neuroma and in neuromas in general. This is also a first comparison between proteomic imaging of the neuroma and that of normal nerve. Besides, and also for the first time, we found a proteomic polymorphism in acoustic neuroma and non-acoustic neuroma which were absent in normal nerve tissue thereby suggesting the presence de proteic biomarkers for the neuroma

[A radiological case of sinusology: a schwannoma localized in the sinuses]

International audienceINTRODUCTION: In daily practice, the otorhinolaryngologist may face cases of facial tumors of sinonasal origin. Their diagnosis remains difficult based on clinical findings alone. Therefore, imaging techniques can guide the surgeon toward the correct diagnosis. METHODS: A 14-year-old male presented with a history of headaches and nasal obstruction. Physical examination revealed a mass in the right nasal fossa. RESULTS: A computed tomography scan showed an isodense lesion in the posterior half of the right nasal fossa, extending into the maxillary sinus, orbital floor, pterygopalatine fossa, and infratemporal fossa. Magnetic resonance imaging showed great enhancement upon gadolinium administration. The diagnosis of schwannoma was suggested after angiography was performed. The tumor was then resected via a transfacial approach with maxillozygomatic osteotomy. Pathologic examination confirmed the diagnosis of schwannoma. CONCLUSION: The definite diagnosis of a sinonasal tumor can be confirmed only histologically. However, preoperative radiological data can direct the surgeon toward the correct diagnosis and above all the most appropriate surgical approach

The quartile benefit plot: a middle ear surgery benefit assessment scheme.

International audienceOBJECTIVE: The purpose of this study is to present a new method for the assessment of hearing improvement following stapes surgery, taking into account additional, previously omitted evaluation criteria. STUDY DESIGN: Retrospective. METHODS: A quartile plot, based on the currently used Glasgow benefit plot, is structured to include two additional criteria of hearing assessment, namely the absence of postoperative sensorineural hearing loss and the closure of the air-bone gap to <10 dB. Pre- and postoperative hearing results of 132 patients diagnosed with bilateral otosclerosis and treated with bilateral stapes surgery were plotted on both the classical Glasgow benefit plot and the new quartile benefit plot. The difference in success assessment due to stricter assessment criteria is demonstrated. RESULTS: Functional success rate following bilateral stapes surgery as plotted on the traditional Glasgow benefit plot was 51.5%. Success rate for bilateral stapes surgery assessed on the new quartile plot with the addition of the two new criteria was 38.64%. The difference in success rates was found to be statistically significant. CONCLUSION: The basis of benefit assessment in stapes surgery solely on the mean deficit in air conduction results in overestimation of success rate. This study demonstrates that results that appear satisfactory when judged by the Glasgow benefit plot are of modest success when assessed by the new quartile plot. The quartile benefit plot presented in this paper provides a strict measure of presentation and evaluation of stapes surgery results

Respiratory distress and vocal cord immobilization caused by Forestier's disease.

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Spontaneous perforation in the upper oesophagus resulting from ulcer in heterotopic gastric mucosa.

International audienceHeterotopic gastric mucosa (HGM) can be found throughout the entire gastrointestinal tract, more frequently in the cervical oesophagus. Macroscopic HGM is named inlet patch (IP). The great majority of IPs are asymptomatic and discovered incidently during oesophageal endoscopy performed for another pathology. However, complications can occur. Among these, perforation is extremely rare. We report a case of a 27-year old man who presented with a perforation of an upper oesophageal ulcer arising from an IP. The diagnosis was made during endoscopy and confirmed with biopsy of the tissue surrounding the perforation, showing histologic modifications consistent with heterotopic gastric mucosa. Medical treatment using a proton pump inhibitor and antibiotics delivered with a gastric tube was advocated. The perforation was closed at day 7 and plasma Argon coagulation of the inlet patch was performed two months later. Annual endoscopy has been normal for three years

Osteoplastic maxillotomy approach for infraorbital nerve schwannoma, a case report.

International audienceBACKGROUND: Extracranial schwannomas can readily occur in the head and neck region and rarely involve the trigeminal nerve. As a rule, their treatment is surgical and dictated by the location of the tumor and nerve of origin. METHODS: We describe a case of a 14-year-old boy with a mass invading right nasal fossa, maxillary sinus, orbital floor, pterygopalatine fossa, and infratemporal fossa. The diagnosis of a nerve sheath tumor was evoked after angiography showed no vascular blush. RESULTS: The tumor was removed through a Weber-Fergusson incision with subciliary extension followed by maxillozygomatic osteotomy. This approach showed the tumor to be coming from the infraorbital nerve and allowed complete tumor exposure and removal. Pathology confirmed the diagnosis of a schwannoma. CONCLUSION: We describe the osteoplastic maxillotomy approach which we felt most appropriate for removal of the infraorbital schwannoma and discuss other possible surgical options for this type of tumor

[Outcome of surgical and adjuvant radiotherapy treatment of T3-T4 squamous cell carcinoma of the floor of the mouth: evaluation of oncological control and treatment related morbidity]

International audienceOBJECTIVE: The aims of this study were to evaluate the therapeutic outcome and morbidity associated with management of squamous cell carcinoma (SCC) T3-T4 of the floor of the mouth. PATIENTS AND METHODS: This was a retrospective study (1993 and 2005). Inclusion criteria were: 1) Presence of a locally advanced (T3-T4) lesion of the floor of the mouth; 2) Pathological confirmation of SCC; 3) No previous treatment of the floor of the mouth; 4) Absence of any synchronous lesions at the primary endoscopic work-up; 5) Absence of distant metastasis outside the aero-digestive tract; 6) Karnofsky performance index > 70. All patients were treated by surgery and adjuvant radiotherapy. The statistical analysis was conducted using the stat-view software; categorical variables were compared using the Fisher's exact test; analysis of recurrence-free survival rate was done following the Kaplan-Meier method, and the log-rank test was used for the comparison of survival graphs. RESULTS: Fourty-seven patients were included in this study (42 men), of a mean age of 53.3 years. The majority of patients (93.6%) presented with a stage IVa tumour and no clinical evidence of cervical lymphadenopathy in 60% of cases. All patients underwent bilateral neck dissection adapted to the cervical lymph node status. Forty-one (87%) patients underwent partial mandibulectomy with fibula free-flap reconstruction in 32 cases (78%). Early local complication rate was of 32%. The mean duration of hospitalization was 34 days. Late local complication rate was of 17%. The immediate post-operative death rate was 2%. The rate of survival and recurrence free survival was of 47.5% and 47% respectively. The 3 survival-influencing factors were age (p = 0.02), margins of surgical resection (p = 0.002), and histologic cervical lymph node status (p = 0.03). CONCLUSION: T3-T4 tumours of the floor of the mouth are managed by surgical resection and adjuvant radiotherapy. There is a high rate of treatment-associated complications. The prognosis of locally advanced tumours of the floor of the mouth remains humble

[Schwannomas of the neck. About 3 cases, and literature review]

International audienceINTRODUCTION: Schwannomas of the neck are rare. Their diagnosis remains difficult despite the evolution of imaging techniques. The goals of our study were to review the diagnostic and therapeutic approach for these tumors. MATERIALS AND METHODS: Retrospective study (1998-2005) concerning 3 cases of schwannoma in rare localizations: superior laryngeal nerve, ansa cervicalis and deep cervical plexus. These 3 patients were operated on in our ENT head and neck department. We made a review of the literature using the Medline database. RESULTS: The mean delay between symptomatology and treatment was 5 years. In all cases, the schwannoma presented with a slowly-growing cervical mass. In only one case, the diagnosis of schwannoma was maded preoperatively. All 3 patients were treated surgically and the involved nerve was sacrificied. There were no postoperative complications. The mean follow-up duration was 3.5 years, with no recurrence. DISCUSSION-CONCLUSION: To establish a diagnosis of neck schwannoma, ultrasound is the least sensitive imaging tool. Fine needle aspiration is especially useful to rule out other conditions. The most relevant diagnostic tools are CT-scan and especially MRI. Treatment is surgical; it should include sacrifice of the involved nerve. Surgical exploration of the neck and tumor resection could be performed at the same operation in the informed patient aware of the sequelae of nerve sacrifice, or otherwise be performed in two steps in the uninformed patient