Real-world EGFR testing practices for non-small-cell lung cancer by thoracic pathology laboratories across Europe.

BACKGROUND: Testing for epidermal growth factor receptor (EGFR) mutations is an essential recommendation in guidelines for metastatic non-squamous non-small-cell lung cancer, and is considered mandatory in European countries. However, in practice, challenges are often faced when carrying out routine biomarker testing, including access to testing, inadequate tissue samples and long turnaround times (TATs). MATERIALS AND METHODS: To evaluate the real-world EGFR testing practices of European pathology laboratories, an online survey was set up and validated by the Pulmonary Pathology Working Group of the European Society of Pathology and distributed to 64 expert testing laboratories. The retrospective survey focussed on laboratory organisation and daily EGFR testing practice of pathologists and molecular biologists between 2018 and 2021. RESULTS: TATs varied greatly both between and within countries. These discrepancies may be partly due to reflex testing practices, as 20.8% of laboratories carried out EGFR testing only at the request of the clinician. Many laboratories across Europe still favour single-test sequencing as a primary method of EGFR mutation identification; 32.7% indicated that they only used targeted techniques and 45.1% used single-gene testing followed by next-generation sequencing (NGS), depending on the case. Reported testing rates were consistent over time with no significant decrease in the number of EGFR tests carried out in 2020, despite the increased pressure faced by testing facilities during the COVID-19 pandemic. ISO 15189 accreditation was reported by 42.0% of molecular biology laboratories for single-test sequencing, and by 42.3% for NGS. 92.5% of laboratories indicated they regularly participate in an external quality assessment scheme. CONCLUSIONS: These results highlight the strong heterogeneity of EGFR testing that still occurs within thoracic pathology and molecular biology laboratories across Europe. Even among expert testing facilities there is variability in testing capabilities, TAT, reflex testing practice and laboratory accreditation, stressing the need to harmonise reimbursement technologies and decision-making algorithms in Europe.

[Management of EGFR mutated non-small cell lung carcinoma patients]. / Analyse de la prise en charge des cancers bronchiques avec mutation du gène de l'EGFR.

INTRODUCTION: Mutations in the epidermal growth factor receptor (EGFR) gene are commonly observed in non-small-cell lung cancer (NSCLC). Over the past decade, the management of NSCLC-carrying EGFR mutation has evolved considerably with the use of tyrosine kinase inhibitors (TKIs). The main objective of this retrospective study was to analyze the evolution of therapeutic strategies in a cohort of patients with metastatic or locally advanced EGFR- mutated NSCLC. METHODS: Data on patients with EGFR-mutated NSCLC, eligible for TKIs, and treated between 2010 to 2019 were collected. The main therapeutic strategies adopted following progression under TKIs and the prognostic factors for survival were analyzed. RESULTS: The median age of the 177 patients was included in the cohort was 70years. The majority of patients (77.4%) received TKIs as first-line treatment, while 16.4% received chemotherapy. Osimertinib initiation as second-line treatment was a factor for better prognosis (OR=0.5). Finally, change of chemotherapy line was the main therapeutic strategy adopted for 41.3% of the patients having relapsed under TKIs. DISCUSSION: Therapeutic management of EGFR-mutated NSCLC patients was in accordance with regional, national and international recommendations. The characterization of progression under TKI therapy has become systematic, allowing better adaption of therapeutic strategies.

The likely extinction of hundreds of palm species threatens their contributions to people and ecosystems.

Protecting nature's contributions to people requires accelerating extinction risk assessment and better integrating evolutionary, functional and used diversity with conservation planning. Here, we report machine learning extinction risk predictions for 1,381 palm species (Arecaceae), a plant family of high socio-economic and ecological importance. We integrate these predictions with published assessments for 508 species (covering 75% of all palm species) and we identify top-priority regions for palm conservation on the basis of their proportion of threatened evolutionarily distinct, functionally distinct and used species. Finally, we explore palm use resilience to identify non-threatened species that could potentially serve as substitutes for threatened used species by providing similar products. We estimate that over a thousand palms (56%) are probably threatened, including 185 species with documented uses. Some regions (New Guinea, Vanuatu and Vietnam) emerge as top ten priorities for conservation only after incorporating machine learning extinction risk predictions. Potential substitutes are identified for 91% of the threatened used species and regional use resilience increases with total palm richness. However, 16 threatened used species lack potential substitutes and 30 regions lack substitutes for at least one of their threatened used palm species. Overall, we show that hundreds of species of this keystone family face extinction, some of them probably irreplaceable, at least locally. This highlights the need for urgent actions to avoid major repercussions on palm-associated ecosystem processes and human livelihoods in the coming decades.

Spinal Arachnoid Web: A didactic report of two cases with clinical, radiological, surgical and pathological correlations.

BACKGROUND: Arachnoid web (AW) is a rare but probably underestimated cause of spinal cord injury that is complex to diagnose due to subtle MRI findings and similarities to other better-known diseases such as arachnoid cyst (AC) or transdural spinal cord herniation (TSCH). Increased recognition of AW is mandatory since delay in diagnosis can lead to potentially serious neurological sequelae. CASE PRESENTATIONS: We report two additional cases of AW for didactic purposes, with special emphasis on the distinctive MRI and intraoperative findings. Both patients presented with progressively worsening neurological symptoms, including proprioceptive ataxia, motor weakness, numbness and neuropathic pain. The diagnosis of AW was suspected on the basis of specific MRI criteria, especially the so-called "scalpel sign". Formal confirmation of the diagnosis was obtained in two patients that were managed surgically. Postoperative follow-up demonstrated significant functional recovery. DISCUSSION: There is a need for better recognition of AW by the medical community. Careful analysis of MRI semiology is crucial for the distinction between AW, AC and TSCH. Prompt and accurate diagnosis is mandatory to conserve functional prognosis, since appropriate surgical treatment with AW resection is curative, halting or even resolving the neurological symptoms.

[Multiple synchronous lung adenocarcinoma: Interest of molecular biology for staging]. / Adénocarcinomes pulmonaires multifocaux synchrones : intérêt de la biologie moléculaire pour la stadification.

INTRODUCTION: The presence of multiple synchronous lung tumors is not a rare event. Distinguishing intra-pulmonary metastases from multiple synchronous lung adenocarcinoma is a challenge for pathologists and physicians. We present observation of a patient with three lung tumors corresponding to three adenocarcinomas for which molecular analysis had a significant impact on tumor staging. OBSERVATION: Three suspect lesions were discovered in a 61-year-old patient, a smoker, in each lobe of the right lung. Right pneumonectomy with lymph node dissection was performed. Pathological examination showed that each tumor was in fact an adenocarcinoma. In order to more precisely indicate tumor staging, molecular analysis was performed with next generation sequencing showing a different point mutation in a driver gene on each tumor. The final diagnosis is that the three tumors are distinct synchronous tumors, which must be staged separately. CONCLUSIONS: In modern-day practice of thoracic oncology and of surgical pathology, molecular biology represents a complement for tumor staging in the event of multiple lung tumors.

[Silica causes difficulties]. / La silice cause des difficultés.

Silicosis and sarcoidosis are two very distinct entities in the literature. All the additional non-invasive examinations, including the chest CT scan, often do not differentiate them. The history, including occupational exposure to identified silica particles, is a discriminating factor. However, due to the pathogenic power of silica, it would be possible to have the simultaneous development of these two pathologies in the same patient. To illustrate this situation, here is the case of a 62-year-old patient, who presented initially with a picture of dyspnea and productive cough. The chest CT showed micronodular peribronchovascular infiltrates and mediastinal lymphadenopathy. The other additional examinations did not find anything specific. In the diagnostic process, the patient had multiple endoscopic samples which did not make it possible to be conclusive on one or the other of these pathologies. He therefore underwent a surgical lung biopsy which revealed histological lesions compatible with the two pathologies. Recent studies suggest that inhaled particles, especially silica, could be responsible for the pattern of sarcoidosis. However, it is difficult to say whether, in this case, silica was responsible for the development of sarcoidosis.

Clinical and molecular practice of European thoracic pathology laboratories during the COVID-19 pandemic. The past and the near future.

BACKGROUND: This study evaluated the consequences in Europe of the COVID-19 outbreak on pathology laboratories orientated toward the diagnosis of thoracic diseases. MATERIALS AND METHODS: A survey was sent to 71 pathology laboratories from 21 European countries. The questionnaire requested information concerning the organization of biosafety, the clinical and molecular pathology, the biobanking, the workload, the associated research into COVID-19, and the organization of education and training during the COVID-19 crisis, from 15 March to 31 May 2020, compared with the same period in 2019. RESULTS: Questionnaires were returned from 53/71 (75%) laboratories from 18 European countries. The biosafety procedures were heterogeneous. The workload in clinical and molecular pathology decreased dramatically by 31% (range, 3%-55%) and 26% (range, 7%-62%), respectively. According to the professional category, between 28% and 41% of the staff members were not present in the laboratories but did teleworking. A total of 70% of the laboratories developed virtual meetings for the training of residents and junior pathologists. During the period of study, none of the staff members with confirmed COVID-19 became infected as a result of handling samples. CONCLUSIONS: The COVID-19 pandemic has had a strong impact on most of the European pathology laboratories included in this study. Urgent implementation of several changes to the organization of most of these laboratories, notably to better harmonize biosafety procedures, was noted at the onset of the pandemic and maintained in the event of a new wave of infection occurring in Europe.

Rare histologic types of rectal cancer: A monocentric cases series report.

PURPOSE: There is paucity of data on rectal cancer with uncommon histologic types. The objective was to describe managements of care and outcomes in patients with rectal cancer of histologic types other than adenocarcinoma. MATERIAL AND METHODS: This monoinstitutional retrospective study included all patients with rectal cancer undergoing rectal radiotherapy. RESULTS: From 2004 to 2015, 744 patients were treated for rectal cancer, and ten had a histologic type other than adenocarcinoma. The median age was 60.7 years (range: 34.6-80.4 years). Histologic types were neuroendocrine (four), adenosquamous (one), undifferentiated with large cell (one), clear cell (one), anaplastic with small cell (one), signet ring cell (one) and adenocarcinoma with choriocarcinomatous differentiation (one). Four patients were initially diagnosed with a stage IV rectal cancer, and two ultimately became metastatic. Six patients underwent surgery, with four neoadjuvant chemoradiotherapies. None experienced complete response and two had incomplete resections. First-line and concomitant chemotherapies were adapted to histology results, mainly with etoposide and platinum salts for neuroendocrine and small cells tumours. Four patients experienced progression before first line treatments were achieved. Median progression free survival and overall survival were 3.8 and 10.1 months respectively. Two patients were long survivors (22 and 54.7 months, both still alive). All other died of rectal cancer. CONCLUSION: The present study highlights the rarity and the specificities of uncommon histologic types of rectal cancer. We report the real-life management and outcome of rare histologic types of rectal cancers, with dismal prognosis of stage IV tumours. We also report that treatments were adapted to histology.

[A not so poorly-defined opacity]. / Un nodule pas si flou.

A 60-year-old patient was under follow-up for pulmonary hypertension consistent with pulmonary veno-occlusive disease. During his follow-up, a parenchymal opacity was discovered. We describe the management of the suspicion of lung cancer, highlighting the modification of the conventional diagnostic and therapeutic strategy on account of the pulmonary hypertension. Chest physicians should be able to adapt their diagnostic and therapeutic management in the case of neoplasia in patients with severe pulmonary hypertension.

[Rhabdomyosarcoma of adult genital tract: A short review]. / Rhabdomyosarcomes d'origine gynécologique chez l'adulte : revue générale et principes de prise en charge.

Rhabdomyosarcoma, most common soft tissue tumor in children, represent 8% of solid tumors in children. Conversely, in adults, this histology is very rare and no consensual recommendation is supported. If gynecological localization is one of the most frequent in children, it is a minority in adults. The management of this type of tumor is based on treatment multimodality combining surgery, chemotherapy, radiotherapy and brachytherapy. This pathological separate entity differs from other sarcomas by its greater sensitivity to chemotherapy and radiotherapy. The aim of this study is to conduct a general review of diagnostic and treatment of genital tract rhabdomyosarcoma in adults, and to report pathological characteristics of this type of tumor.

Isolated primary central nervous system lymphoma arising from the optic chiasm.

A 58-year-old previously healthy woman rapidly developed progressive bilateral visual loss. Magnetic resonance imaging revealed a bulging appearance of the optic chiasm, with homogeneous enhancement after gadolinium administration, which suggested an optic glioma or inflammatory disease. In the absence of (para)clinical clues for a specific diagnosis despite extensive investigation, a biopsy of one optic nerve was performed, resulting in a diagnosis of non-Hodgkin B-cell lymphoma. There was no evidence of any other ocular or systemic involvement, therefore the conclusion was that this immunocompetent patient had a primary central nervous system lymphoma isolated in the anterior visual pathway. Treatment included two cycles of polychemotherapy (rituximab, methotrexate, carmustine, etoposide, methylprednisolone), followed by autologous peripheral blood stem cell transplantation and rituximab plus cytarabine consolidation therapy. Subsequently, the patient exhibited significant improvement in vision, and was still disease-free at the 1-year follow-up examination. The aim of the present paper was to provide well-documented clinical, radiological, and intraoperative features of isolated primary malignant lymphoma arising from the anterior visual pathway. A better recognition of this rare pathological entity is necessary for clinicians who may encounter similar presentations, as prompt management is crucial for both a visual and vital prognosis.

Genomics of the divergence continuum in an African plant biodiversity hotspot, I: drivers of population divergence in Restio capensis (Restionaceae).

Understanding the drivers of population divergence, speciation and species persistence is of great interest to molecular ecology, especially for species-rich radiations inhabiting the world's biodiversity hotspots. The toolbox of population genomics holds great promise for addressing these key issues, especially if genomic data are analysed within a spatially and ecologically explicit context. We have studied the earliest stages of the divergence continuum in the Restionaceae, a species-rich and ecologically important plant family of the Cape Floristic Region (CFR) of South Africa, using the widespread CFR endemic Restio capensis (L.) H.P. Linder & C.R. Hardy as an example. We studied diverging populations of this morphotaxon for plastid DNA sequences and >14 400 nuclear DNA polymorphisms from Restriction site Associated DNA (RAD) sequencing and analysed the results jointly with spatial, climatic and phytogeographic data, using a Bayesian generalized linear mixed modelling (GLMM) approach. The results indicate that population divergence across the extreme environmental mosaic of the CFR is mostly driven by isolation by environment (IBE) rather than isolation by distance (IBD) for both neutral and non-neutral markers, consistent with genome hitchhiking or coupling effects during early stages of divergence. Mixed modelling of plastid DNA and single divergent outlier loci from a Bayesian genome scan confirmed the predominant role of climate and pointed to additional drivers of divergence, such as drift and ecological agents of selection captured by phytogeographic zones. Our study demonstrates the usefulness of population genomics for disentangling the effects of IBD and IBE along the divergence continuum often found in species radiations across heterogeneous ecological landscapes.

[N-methyl-d-aspartate receptor antibody encephalitis: a treatable disorder involving B-lymphocytes. A report of two patients]. / Encéphalite à anticorps anti-récepteur du NMDA : une entité traitable impliquant les lymphocytes B. Deux observations.

INTRODUCTION: N-methyl-D-aspartate receptor antibody (anti-NMDA-r AB) encephalitis has been recently identified. We report two cases illustrating the clinical features, response to immunomodulatory treatment and involvement of B-lymphocytes that characterizes this disorder. CASE REPORTS: These patients illustrated the classic clinical features of anti-NMDA-r AB encephalitis including occurrence in young female, presence of severe neurological and psychiatric manifestations with confusion, seizures, mutism, hypovigilence and involuntary movements, and inflammatory cerebrospinal fluid. Both patients improved after immunotherapy. In case 1, the encephalitis was associated with an ovarian teratoma containing neuronal elements. In case 2, there was no tumor identified. A brain biopsy showed prominent perivascular B-cells infiltrates with some T-cells distributed in the brain parenchyma. CONCLUSION: Anti-NMDA-r AB encephalitis is certainly not rare and needs to be promptly recognized and treated. An associated neoplasia is inconstant and the pathophysiology involves humoral immunity.