Assessment of the current and emerging criteria for the histopathological classification of lung neuroendocrine tumours in the lungNENomics project.

BACKGROUND: Six thoracic pathologists reviewed 259 lung neuroendocrine tumours (LNETs) from the lungNENomics project, with 171 of them having associated survival data. This cohort presents a unique opportunity to assess the strengths and limitations of current World Health Organization (WHO) classification criteria and to evaluate the utility of emerging markers. PATIENTS AND METHODS: Patients were diagnosed based on the 2021 WHO criteria, with atypical carcinoids (ACs) defined by the presence of focal necrosis and/or 2-10 mitoses per 2 mm2. We investigated two markers of tumour proliferation: the Ki-67 index and phospho-histone H3 (PHH3) protein expression, quantified by pathologists and automatically via deep learning. Additionally, an unsupervised deep learning algorithm was trained to uncover previously unnoticed morphological features with diagnostic value. RESULTS: The accuracy in distinguishing typical from ACs is hampered by interobserver variability in mitotic counting and the limitations of morphological criteria in identifying aggressive cases. Our study reveals that different Ki-67 cut-offs can categorise LNETs similarly to current WHO criteria. Counting mitoses in PHH3+ areas does not improve diagnosis, while providing a similar prognostic value to the current criteria. With the advantage of being time efficient, automated assessment of these markers leads to similar conclusions. Lastly, state-of-the-art deep learning modelling does not uncover undisclosed morphological features with diagnostic value. CONCLUSIONS: This study suggests that the mitotic criteria can be complemented by manual or automated assessment of Ki-67 or PHH3 protein expression, but these markers do not significantly improve the prognostic value of the current classification, as the AC group remains highly unspecific for aggressive cases. Therefore, we may have exhausted the potential of morphological features in classifying and prognosticating LNETs. Our study suggests that it might be time to shift the research focus towards investigating molecular markers that could contribute to a more clinically relevant morpho-molecular classification.

Integrative and comparative genomic analyses identify clinically relevant pulmonary carcinoid groups and unveil the supra-carcinoids.

The worldwide incidence of pulmonary carcinoids is increasing, but little is known about their molecular characteristics. Through machine learning and multi-omics factor analysis, we compare and contrast the genomic profiles of 116 pulmonary carcinoids (including 35 atypical), 75 large-cell neuroendocrine carcinomas (LCNEC), and 66 small-cell lung cancers. Here we report that the integrative analyses on 257 lung neuroendocrine neoplasms stratify atypical carcinoids into two prognostic groups with a 10-year overall survival of 88% and 27%, respectively. We identify therapeutically relevant molecular groups of pulmonary carcinoids, suggesting DLL3 and the immune system as candidate therapeutic targets; we confirm the value of OTP expression levels for the prognosis and diagnosis of these diseases, and we unveil the group of supra-carcinoids. This group comprises samples with carcinoid-like morphology yet the molecular and clinical features of the deadly LCNEC, further supporting the previously proposed molecular link between the low- and high-grade lung neuroendocrine neoplasms.

New Insights on Diagnostic Reproducibility of Biphasic Mesotheliomas: A Multi-Institutional Evaluation by the International Mesothelioma Panel From the MESOPATH Reference Center.

INTRODUCTION: The 2015 WHO classification of tumors categorized malignant mesothelioma into epithelioid, biphasic (BMM), and sarcomatoid (SMM) for prognostic relevance and treatment decisions. The survival of BMM is suspected to correlate with the amount of the sarcomatoid component. The criteria for a sarcomatoid component and the interobserver variability between pathologists for identifying this component are not well described. In ambiguous cases, a "transitional" (TMM) subtype has been proposed but was not accepted as a specific subtype in the 2015 WHO classification. The aims of this study were to evaluate the interobserver agreement in the diagnosis of BMM, to determine the nature and the significance of TMM subtype, and to relate the percentage of sarcomatoid component with survival. The value of staining for BRCA-1-associated protein (BAP1) and CDKN2A(p16) fluorescence in situ hybridization (FISH) were also assessed with respect to each of the tumoral components. METHODS: The study was conducted by the International Mesothelioma Panel supported by the French National Cancer Institute, the network of rare cancer (EURACAN) and in collaboration with the International Association for the Study of Lung Cancer (IASLC). The patient cases include a random group of 42 surgical biopsy samples diagnosed as BMM with evaluation of SMM component by the French Panel of MESOPATH experts was selected from the total series of 971 BMM cases collected from 1998 to 2016. Fourteen international pathologists with expertise in mesothelioma reviewed digitally scanned slides (hematoxylin and eosin - stained and pan-cytokeratin) without knowledge of prior diagnosis or outcome. Cases with at least 7 of 14 pathologists recognizing TMM features were selected as a TMM group. Demographic, clinical, histopathologic, treatment, and follow-up data were retrieved from the MESOBANK database. BAP1 (clone C-4) loss and CDKN2A(p16) homozygous deletion (HD) were assessed by immunohistochemistry (IHC) and FISH, respectively. Kappa statistics were applied for interobserver agreement and multivariate analysis with Cox regression adjusted for age and gender was performed for survival analysis. RESULTS: The 14 panelists recorded a total of 544 diagnoses. The interobserver correlation was moderate (weighted Kappa = 0.45). Of the cases originally classified as BMM by MESOPATH, the reviewers agreed in 71% of cases (385 of 544 opinions), with cases classified as pure epithelioid in 17% (93 of 544), and pure sarcomatoid in 12% (66 of 544 opinions). Diagnosis of BMM was made on morphology or IHC alone in 23% of the cases and with additional assessment of IHC in 77% (402 of 544). The median overall survival (OS) of the 42 BMM cases was 8 months. The OS for BMM was significantly different from SMM and epithelioid malignant mesothelioma (p < 0.0001). In BMM, a sarcomatoid component of less than 80% correlated with a better survival (p = 0.02). There was a significant difference in survival between BMM with TMM showing a median survival at 6 months compared to 12 months for those without TMM (p < 0.0001). BAP1 loss was observed in 50% (21 of 42) of the total cases and in both components in 26%. We also compared the TMM group to that of more aggressive patterns of epithelioid subtypes of mesothelioma (solid and pleomorphic of our large MESOPATH cohort). The curve of transitional type was persistently close to the OS curve of the sarcomatoid component. The group of sarcomatoid, transitional, and pleomorphic mesothelioma were very close to each other. We then considered the contribution of BAP1 immunostaining and loss of CDKN2A(p16) by FISH. BAP1 loss was observed in 50% (21 of 41) of the total cases and in both component in 27% of the cases (11 of 41). There was no significant difference in BAP1 loss between the TMM and non-TMM groups. HD CDKN2A(p16) was detected in 74% of the total cases with no significant difference between the TMM and non-TMM groups. In multivariate analysis, TMM morphology was an indicator of poor prognosis with a hazard ratio = 3.2; 95% confidence interval: 1.6 - 8.0; and p = 0.003 even when compared to the presence of HD CDKN2A(p16) on sarcomatoid component (hazard ratio = 4.5; 95% confidence interval: 1.2 - 16.3, p = 0.02). CONCLUSIONS: The interobserver concordance among the international mesothelioma and French mesothelioma panel suggests clinical utility for an updated definition of biphasic mesothelioma that allows better stratification of patients into risk groups for treatment decisions, systemic anticancer therapy, or selection for surgery or palliation. We also have shown the usefulness of FISH detection of CDKN2A(p16) HD compared to BAP1 loss on the spindle cell component for the separation in ambiguous cases between benign florid stromal reaction from true sarcomatoid component of biphasic mesothelioma. Taken together our results further validate the concept of transitional pattern as a poor prognostic indicator.

[Prophylactic radiotherapy in a single fraction of 10Gy at intervention pleural site in patient with malignant pleural mesothelioma: A retrospective monocentric cohort study]. / Irradiation préventive en une séance de 10Gy des sites d'intervention pleurale des patients atteints de mésothéliome pleural malin : étude de cohorte rétrospective monocentrique.

PURPOSE: Prophylactic radiotherapy to prevent procedure-tracts metastases from malignant pleural mesothelioma remains controversial and clinical practice varies. The purpose was to assess the efficacy of local radiotherapy in a single fraction of 10Gy in preventing malignant seeding at intervention pleural site in patients with malignant pleural mesothelioma. MATERIAL AND METHODS: This is a retrospective cohort study, including patients with histological confirmed malignant pleural mesothelioma treated by prophylactic irradiation to prevent interventional site metastases with a unique fraction of 10Gy with 6 to 18MeV, from January 1990 to December 2013 in the institut de cancérologie de Lorraine (Nancy, France). RESULTS: Ninety-one patients were treated by irradiation in intervention site, involving 120 intervention pleural sites, 91 thoracoscopies, 17 thoracotomies with chest drain and 12 CT or ultrasound guided needle biopsies. The median follow-up was 7 months (interquartile between 3 and 15 months). The overall survival was 43.5% at 12 months. The local progression free survival was 43.7% at 12 month. The incidence of local recurrence was 8% at 12 months. The median interval from radiotherapy to local recurrence was 4 months (2; 32). No grade II or higher toxicity was observed. CONCLUSION: Irradiation of pleural intervention sites with a single fraction of 10Gy is effective, well tolerated, simple, fast and cost effective.

[Paraneoplastic hypoglycemia: The hopes of pathophysiological documentation]. / Hypoglycémie paranéoplasique : les espoirs d'une documentation physiopathologique.

Doege-Potter syndrome is a paraneoplastic syndrome characterized by non-islet cell tumor hypoglycemia secondary to a solitary fibrous tumor. These tumors are rare and usually asymptomatic. The syndrome of hypoglycemia is seen in less than 5% of the cases, and the associated tumors are large with a high mitotic rate. The cause of hypoglycemia is related to insulin-like growth factors produced by these tumors called "big" IGF-2. Several biological tests can demonstrate the increase of "big" IGF-2 plasma levels confirming the diagnosis of non-islet cell tumor induced hypoglycemia. The diagnosis is suggested by imaging but diagnostic confirmation is provided by the surgery, which remains the treatment of choice. Resection in many cases is the cure leading to hypoglycemia resolution. Recurrences and malignant transformations are possible which imposes a long-term monitoring. We report a case with relapsed malignant pleural fibrous tumor for which the pathophysiological mechanism of hypoglycemia could be documented as a paraneoplastic syndrome.

Zosteriform configuration of multiple eccrine spiradenomas of the scalp.

BACKGROUND: Eccrine spiradenoma (ES) is a benign adnexal tumor predominantly located in the head and neck regions. Multiple neoplasms located on the scalp have been reported but never with a zosteriform configuration on the first trigeminal area. CASE REPORT: We describe an original case report of a 75-year-old Caucasian man presenting multiple subcutaneous blue and purple nodules disseminated on the first left trigeminal dermatome. All the nodules appeared gradually on a one-year period. Biopsy revealed a nodular adnexal tumor in the dermis without malignant eccrine spiradenoma (MES) transformation. The surgical procedure was performed in a manner to protect the galea aponeurotica in the upper half on the first left trigeminal area. The frontalis muscle was raised with the surgical specimen in the lower half of the first trigeminal area. A split-thickness skin graft was applied on the surgical defect. Histological examination revealed multilobular well-defined tumors located in the dermis. CONCLUSION: The presence of multiple subcutaneous nodules in a trigeminal pattern should suggest a multiple localized zosteriform ES. The diagnosis is focused on clinical findings and the treatment is based on a large surgical excision. The histological examination is essential for not to fail a MES transformation.

[Bronchioloalveolar carcinoma: an exceptional cause of diffuse lung disease in a patient with acute myeloid leukemia]. / Le carcinome bronchiolo-alvéolaire, une cause exceptionnelle de pneumopathie infiltrante diffuse au cours d'une leucémie aiguë myéloïde.

INTRODUCTION: Bronchiolo-alveolar carcinoma is a primary pulmonary adenocarcinoma developing in the terminal respiratory unit. CASE REPORT: An 84-year-old non-smoker woman with a history of untreated acute myeloid leukaemia was referred to the intensive care unit for pneumonia and acute respiratory failure. The patient reported dyspnoea and a productive cough for 3 months, treated by antibiotics and steroids without improvement. Thoracic CT-scan showed alveolar condensations and multiple nodular lesions. All microbiological samples were negative and the evolution was fatal within 72 hours despite empirical antibiotic therapy and noninvasive ventilation. Post-mortem lung biopsies gave a diagnosis of mucinous and non-mucinous bronchiolo-alveolar carcinoma with typical lepidic growth pattern of tumor cells and discrete septal thickening but no fibrosis, inflammation or local invasion. CONCLUSION: Bronchiolo-alveolar carcinoma is an alternative diagnosis in alveolar condensations associated with pulmonary nodules even in a patient with immunosupression. Early diagnosis allows effective treatment in some cases.

[The French mesothelioma network from 1998 to 2013]. / Mésothéliome: les dispositifs en place en France « le réseau mésothéliome ¼ 1998-2013.

Mesothelioma is a rare disease less than 0.3% of cancers in France, very aggressive and resistant to the majority of conventional therapies. Asbestos exposure is nearly the only recognized cause of mesothelioma in men observed in 80% of case. In 1990, the projections based on mortality predicted a raise of incidence in mesothelioma for the next three decades. Nowadays, the diagnosis of this cancer is based on pathology, but the histological presentation frequently heterogeneous, is responsible for numerous pitfalls and major problems of early detection toward effective therapy. Facing such a diagnostic, epidemiological and medico-legal context, a national and international multidisciplinary network has been progressively set up in order to answer to epidemiological survey, translational or academic research questions. Moreover, in response to the action of the French Cancer Program (action 23.1) a network of pathologists was organized for expert pathological second opinion using a standardized procedure of certification for mesothelioma diagnosis. We describe the network organization and show the results during this last 15years period of time from 1998-2013. These results show the major impact on patient's management, and confirm the interest of this second opinion to provide accuracy of epidemiological data, quality of medico-legal acknowledgement and accuracy of clinical diagnostic for the benefit of patients. We also show the impact of these collaborative efforts for creating a high quality clinicobiological, epidemiological and therapeutic data collection for improvement of the knowledge of this dramatic disease.

Diagnostic value of immunohistochemistry for the detection of the BRAFV600E mutation in primary lung adenocarcinoma Caucasian patients.

BACKGROUND: Non-small-cell lung carcinoma (NSCLC) patients with a BRAF(V600E) mutation benefit from targeted therapy. The usefulness of immunohistochemistry (IHC) as an alternative approach for the detection of BRAF(V600E) in NSCLC patients has not been evaluated until now. This study compared the specificity and sensitivity of IHC with other methods for the detection of BRAF(V600E) in primary lung adenocarcinoma. PATIENTS AND METHODS: BRAF mutations were analysed by DNA sequencing of a Caucasian subpopulation of selected 450 of 1509 (30%) EGFR, KRAS, PI3KA, Her2 and EML4-ALK wild-type (wt) primary lung adenocarcinomas. Detection of the BRAF(V600E) mutation was carried out by IHC using the VE1 clone antibody and compared with the results of other molecular methodologies. RESULTS: Of 450 (9%) of tumours, 40 harboured a BRAF mutation, which corresponded to either a BRAF(V600E) or a non-BRAF(V600E) mutation in 21 of 450 (5%) and 19 of 450 (4%) cases, respectively. The IHC VE1 assay was positive in 19 of 21 (90%) BRAF(V600E)-mutated tumours and negative in all BRAF(nonV600E)-mutated tumours. CONCLUSION: IHC using the VE1 clone is a specific and sensitive method for the detection of BRAF(V600E) and may be an alternative to molecular biology for the detection of mutations in NSCLC.

Morphological analysis of circulating tumour cells in patients undergoing surgery for non-small cell lung carcinoma using the isolation by size of epithelial tumour cell (ISET) method.

BACKGROUND AND OBJECTIVE: Recurrence rates after surgery for non-small cell lung cancer (NSCLC) range from 25 to 50% and 5-year survival is only 60-70%. Because no biomarkers are predictive of recurrence or the onset of metastasis, pathological TNM (pTNM) staging is currently the best prognostic factor. Consequently, the preoperative detection of circulating tumour cells (CTCs) might be useful in tailoring therapy. The aim of this study was to characterize morphologically any circulating non-haematological cells (CNHCs) in patients undergoing surgery for NSCLC using the isolation by size of epithelial tumour cell (ISET) method. METHODS: Of 299 blood samples tested, 250 were from patients with resectable NSCLC and 59 from healthy controls. The presence of CNHCs was assessed blindly and independently by 10 cytopathologists on May-Grünwald-Giemsa stained filters and the cells classified into three groups: (i) malignant cells, (ii) uncertain malignant cells, and (iii) benign cells. We assessed interobserver agreement using Kappa (κ) analysis as the measure of agreement. RESULTS: A total of 123 out of 250 (49%) patients showed CNHCs corresponding to malignant, uncertain malignant and benign cells, in 102/250 (41%), 15/250 (6%) and 6/250 (2%) cases, respectively. No CNHCs were detected in the blood of healthy subjects. Interobserver diagnostic variability was absent for CNHCs, low for malignant cells and limited for uncertain malignant and benign cells. CONCLUSION: Identification of CTCs in resectable NSCLC patients, using ISET technology and according to cytopathological criteria of malignancy, appears to be a new and promising field of cytopathology with potential relevance to lung oncology.

Relationships between lung adenocarcinoma and gender, age, smoking and occupational risk factors: A case-case study.

BACKGROUND: The hypothesis that some risk factors for lung cancer may have more specific associations with particular histologic types remains controversial. The aim of this study was to investigate possible associations between adenocarcinoma and gender, age, smoking characteristics and selected occupational carcinogens in relation to other histologic types. METHODS: This study included all histologically confirmed lung cancer cases diagnosed consecutively in two French University hospitals from 1997 to 2006. All medical data were obtained by face-to-face patient interviews. Occupational carcinogen exposures of each patient were assessed by an industrial hygienist. Relationships between risk factors and adenocarcinoma were analyzed by case-case comparisons using unconditional logistic regressions (ULRs). RESULTS: A total of 1493 subjects were enrolled in this study, comprising 1303 men (87.3%), 67 nonsmokers (4.5%) and 489 adenocarcinomas (32.7%). Using ULR, no associations were observed between adenocarcinoma and age, gender or smoking characteristics except for a negative relationship with smoking duration (p<0.0001). Significant associations were observed between ADC and exposure to welding fumes and silica in the whole population and with polycyclic aromatic hydrocarbons in ever smokers. CONCLUSION: This study demonstrated that some risk factors, such as duration of smoking and certain occupational exposures but not gender or age, have a more important influence on the incidence of lung ADC than on other histologic types. As the distribution of histologic types may reflect underlying biological mechanisms, these findings also suggest that lung carcinogenesis pathways should be studied in relation to smoking duration and other lung cancer risk factors.

EUELC project: a multi-centre, multipurpose study to investigate early stage NSCLC, and to establish a biobank for ongoing collaboration.

The European Early Lung Cancer (EUELC) project aims to determine if specific genetic alterations occurring in lung carcinogenesis are detectable in the respiratory epithelium. In order to pursue this objective, nonsmall cell lung cancer (NSCLC) patients with a very high risk of developing progressive lung cancer were recruited from 12 centres in eight European countries: France, Germany, southern Ireland, Italy, the Netherlands, Poland, Spain and the UK. In addition, NSCLC patients were followed up every 6 months for 36 months. A European Bronchial Tissue Bank was set up at the University of Liverpool (Liverpool, UK) to optimise the use of biological specimens. The molecular-pathological investigations were subdivided into specific work packages that were delivered by EUELC Partners. The work packages encompassed mutational analysis, genetic instability, methylation profiling, expression profiling utilising immunohistochemistry and chip-based technologies, as well as in-depth analysis of FHIT and RARbeta genes, the telomerase catalytic subunit hTERT and genotyping of susceptibility genes in specific pathways. The EUELC project engendered a tremendous collaborative effort, and it enabled the EUELC Partners to establish protocols for assessing molecular biomarkers in early lung cancer with the view to using such biomarkers for early diagnosis and as intermediate end-points in future chemopreventive programmes.

CT assessment of woodworkers' nasal adenocarcinomas confirms the origin in the olfactory cleft.

BACKGROUND AND PURPOSE: Endoscopic endonasal surgery let us observe that woodworkers' nasal adenocarcinomas originate in the olfactory cleft. Our aim was the identification of CT imaging features that corroborate the olfactory cleft as the site of origin for woodworkers' adenocarcinoma. MATERIALS AND METHODS: We designed a retrospective study to compare CT scans of 27 unilateral olfactory cleft adenocarcinomas with 30 cases of nasosinusal polyposis (NSP) and 33 healthy sinus controls. Enlargement of the olfactory cleft, lateralization of the ethmoidal turbinate wall, and contralateral bulging of the nasal septum were measured on coronal scans passing through crista galli and posterior half of both ocular globes. Comparisons have been performed by using analysis of variance and the Bonferroni procedure. RESULTS: The nasal septum was significantly bulging across the midline in adenocarcinoma (4.6 +/- 3 mm; range, -0.1-13.7 mm) compared with NSP (0.7 +/- 1 mm; range, -2.1-2.3 mm) or healthy sinus controls (0.5 +/- 1 mm; range, -1.2-2 mm) (P < .001). The olfactory cleft was significantly wider in adenocarcinoma (15.1 +/- 4.5 mm; range, 8.6-25.7 mm) than in NSP (3.6 +/- 0.4 mm; range, 2.8-4.6 mm) or healthy sinus controls (3.3 +/- 0.7 mm; range, 1.4-4.6 mm). The ethmoidal labyrinth width was significantly smaller on the pathologic side in adenocarcinoma (7.2 +/- 2.7 mm; range, 3.2-14.2 mm) than in the control groups (P < .001). Whereas the angle between the conchal lamina and vertical midline was close to zero degrees in NSP (0.03 +/- 2.25 degrees ; range, -5 degrees -3 degrees ) and healthy sinus controls (0.45 +/- 2.13 degrees , range, -5 degrees -5 degrees ), it reached 39.76 +/- 13.83 degrees (P < .001) in adenocarcinoma. CONCLUSIONS: Radiologists should suspect nasal adenocarcinoma on sinus CT scans showing a unilateral expanding opacity of the olfactory cavity.

Alteration of the immunological synapse in lung cancer: a microenvironmental approach.

This study was designed to investigate the immunological properties of stroma reaction T cells and tumoral cells by comparison with non-tumoral lung tissue and local lymph nodes in order to explore interactions between tumour cells and the immune system. Immunodetection of major histocompatibility complex (MHC) molecules, CD3/T cell receptor (TCR) complex and T cell subsets markers was carried out in situ on frozen sections, and the semi-quantitative expression of CD3, CD4 and CD8 was examined in flow cytometry on lymphocytes of nodal, tumoral and healthy lung tissue from 62 patients with non-small cell lung cancer. This study showed alterations on lymphocytes and tumour cells in lung cancer, consistent with an impairment of T cell activation. CD3, TCR alpha beta and accessory molecules expression is down-modulated on peri- or intra-tumoral lymphocytes. MHC class I and class II molecules are down-modulated significantly on tumour cells. Other differences were noted, such as the reversed CD4/CD8 ratio of tumour infiltrating cells, compared to healthy lung tissues, consistent with the development of cytotoxic anti-tumoral responses. This study reports on the presence of a strong in vivo immunomodulating effect of tumour cells in human non-small cell lung cancer, likely to impair proper formation of the immunological synapse.

[Germ-cell tumors of the central nervous system in childhood: retrospective study of 13 patients]. / Les tumeurs germinales du système nerveux central de l'enfant : étude rétrospective de 13 patients.

BACKGROUND AND PURPOSE: Germ cell tumors (GCT) of the central nervous system are rare (2% of all brain tumors in children). Although originating from germ cells, GCT cover a spectrum of different tumors with different management and prognosis, depending on whether they secrete tumor markers or not. The aim of this study is to present a series of children with GCT and comment on overall management practices. METHODS: We retrospectively reviewed 13 children under the age of 18 years (nine boys and four girls), treated in the same institution between 1986 and 2006 for one or more primitive GCT of the central nervous system. RESULTS: Median age at diagnosis is 12.9 years (7-17 years). Tumor markers (alpha foetoprotein [alphaFP], human chorionic gonadotrophin [betaHCG]) were assessed 11 times in blood as well as cerebrospinal fluid (CSF). Tumors were located as follows: pineal region (10 cases), hypothalamus (eight cases), basal ganglia (one case) and corpus callosum (one case). Six were bifocal (pineal region and hypothalamus). Clinical signs were mostly dominated by diabetes insipidus and intracranial hypertension. Seven children required surgery for hydrocephalus. Tumor markers were positive in three cases and these children subsequently received chemotherapy followed by radiotherapy, except one child. Eventually, the three patients with positive markers required surgery because of a residual lesion. The eight other patients had a stereotactic biopsy for diagnosis. At the end of follow-up, treatment morbidity appears to be low and neither death nor recurrence was observed. Mean follow-up is 8.85 years (2-20 years). CONCLUSIONS: The prognosis of cerebral GCTs in children is excellent because of their pronounced chemo- and radiosensitivity. Surgery is crucial for diagnosis in the event of negative markers, or if there is evidence of residual tumor with normalization of tumor markers at the end of chemotherapy. Tumor markers must be monitored to check the diagnosis and for follow-up. The place of tumor biopsy during endoscopic third ventriculostomy (performed if hydrocephalus is present) is still debated.

[Aneurysmal bone cyst of the ethmoid: paralateronasal or endoscopic surgery? Case report]. / Kyste anévrysmal osseux de l'ethmoïde: abord paralatéronasal ou endoscopique? A propos d'un cas.

AIM: To report a typical case operated on under endonasal endoscopic surgery. CASE REPORT: A 20 year old girl came to the clinic with a left eye exophtalmus. Nasal endoscopy revealed a tumour developped into the left nasal fossa. Imaging allowed to suspect an ethmoidal aneurysmal cyst. CT showed a large tumour involving the left ethmoid, extending into the frontal and maxillary sinuses, with a fluid level in the middle of the tumour. MRI eliminated intracranial extension, showed a cystic component in the middle of the tumour and the presence of hemosiderin signals on T2. Complete resection of the tumour was performed under endoscopic endonasal surgery thanks to a cleavage plane between tumour periorbit and dura. Follow-up was simple with no recurrence at 2 years. CONCLUSION: Despite its rarity, this tumour needs to be known by ENT surgeons, and our surgical experience demonstrates that it can be resected endoscopically.

Endoscopic surgery reveals that woodworkers' adenocarcinomas originate in the olfactory cleft.

The olfactory cleft is a narrow chamber located under the cribriform plate and between the turbinate wall of the ethmoidal labyrinth and the corresponding nasal septum. Nasal adenocarcinomas are mostly described as originating in the ethmoid sinus and operated via external approaches. We designed a prospective study on twenty consecutive woodworkers' adenocarcinomas without intracranial extension to determine the precise site of origin of the tumour. All patients were operated under endoscopic endonasal control according to a methodical surgical procedure as follows: 1) debulking of the tumour and identification of the middle turbinate or conchal lamina, 2) exenteration of the ethmoidal labyrinth according to the nasalisation procedure, and 3) exenteration of the olfactory cleft. Endoscopic endonasal surgery showed that woodworkers' adenocarcinomas constantly originated in the olfactory cleft, appearing as polyp-like neoplasms with well-defined bodies. Over a long period of time, they do not invade, but just displace and push out the surrounding structures, i.e. the nasal septum and the turbinate wall. More than the volume of the tumour, the precise location of the pedicle and especially its connection to the cribriform plate could be of major prognosis value.