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.

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.

[Common variable immunodeficiency disorders: Part 2. Updated clinical manifestations and therapeutic management]. / Les déficits immunitaires communs variables (DICV) : partie 2. Mise à jour clinique et thérapeutique.

Common variable immunodeficiency disorders (CVID) are the most common symptomatic primary antibody deficiency in adults with an estimated prevalence of 1/25,000. The most frequent clinical manifestations are upper respiratory tract infections (including pneumonia, bronchitis, and sinusitis) predominantly with Streptococcus pneumoniae or H. influenzae. However, CVID are complicated in 20 to 30 % of cases of non-infectious manifestations which have been well characterized in recent years. Several complications can be observed including autoimmune, lymphoproliferative, granulomatous or cancerous manifestations involving one or more organs. These complications, mostly antibody-mediated cytopenias, are correlated with a decrease in the number of circulating switched memory B cells. Replacement therapy with polyvalent gammaglobulins has greatly improved the prognosis of these patients but it remains poor in the presence of digestive complications (especially in the case of chronic enteropathy and/or porto-sinusoidal vascular disease), pulmonary complications (bronchiectasis and/or granulomatous lymphocytic interstitial lung disease) and when progression to lymphoma. Much progress is still to be made, in particular on the therapeutic management of non-infectious complications which should benefit in the future from targeted treatments based on knowledge of genetics and immunology.

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.

[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.

[Cryptococcal infection and sarcoidosis: a coincidence?]. / Cryptococcose disséminée et sarcoïdose pulmonaire : une association fortuite ?

INTRODUCTION: We report a case of cryptococcal infection that underwent in a patient with a medical history of asymptomatic sarcoidosis. This finding seems to be not incidental. CASE REPORT: A 35-years-old female was referred to hospital for a community-acquired pneumonia with pleural involvement. A physical examination showed a pleural syndrome. Chest imaging showed a parenchymal involvement with pleural effusion and numerous mediastinal nodes. Fiberoptic bronchoscopy revealed an obstruction of the right apical bronchus of the lower lobe. Biopsies and bronchoalveolar lavage confirmed a cryptococcal infection. The disease was considered as disseminated with a urinary and neurologic involvement. The outcome was fair under prolonged antifungal therapy. CONCLUSIONS: Cryptococcal infection is generally associated with immunosuppression. We suggest that sarcoidosis, although non symptomatic, may be a condition that promote the onset of cryptococcal infection. Even rare, cryptococcal infection is the most frequent opportunistic infection recorded with sarcoidosis patients. Histologic similarities between sarcoidosis and cryptococcal infection and the role of the macrophages which phagocyte the Cryptococcus neoformans are one of the hypothesis to assess these pathologic findings. A register is warranted to recover all opportunistic infection related to sarcoidosis in order to better understand the pathogeny.

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.

[Facial confluent and reticulate papillomatosis (Gougerot-Carteaud syndrome) or hyperkeratotic head and neck Malassezia dermatitis?]. / Papillomatose confluente et réticulée de Gougerot et Carteaud faciale ou hyperkeratotic head and neck Malassezia dermatosis?

BACKGROUND: We report three patients with brown hyperkeratotic lesions of the face. Two cases have been published [Boralevi et al. (2006)] under the title "Hyperkeratotic Head and Neck Malassezia Dermatosis (HHNMD)". A patient recently diagnosed with confluent and reticulated papillomatosis (CRP) (Gougerot-Carteaud) allowed us to link theses two entities. PATIENTS AND METHODS: A 56-year-old woman was followed for extensive CRP. Cultures for fungi and bacteria were negative. During the course of the disease, she developed brown hyperkeratotic dermatitis on both cheeks. DISCUSSION: CRP is a rare or probably under-diagnosed condition. Brown, scaly, hyperkeratotic macules and patches are observed with a confluent and reticulated disposition. The chest and neck are generally involved, but extensive forms are possible. Facial involvement is rare. HHNMD, the disorder we earlier described, could be a facial presentation of CRP with contingent yeast colonisation. A therapeutic test with tetracyclines may be considered in HHNMD.

Mast cell adhesion to bronchial smooth muscle in asthma specifically depends on CD51 and CD44 variant 6.

BACKGROUND: Mast cells infiltrate the bronchial smooth muscle (BSM) in asthmatic patients, but the mechanism of mast cell adhesion is still unknown. The adhesion molecules CD44 (i.e. hyaluronate receptor) and CD51 (i.e. vitronectin receptor) are widely expressed and bind to many extracellular matrix (ECM) proteins. The aims of the study are (i) to identify the role of ECM in mast cell adhesion to BSM and (ii) to examine the role of CD51 and CD44 in this adhesion. METHODS: Human lung mast cells, human mast cell line (HMC-1), and BSM cells from control donors or asthmatic patients were cultured in the presence/absence of various cytokines. Mast cell-BSM interaction was assessed using (3)H-thymidine-pulsed mast cells, confocal immunofluorescence, or electron microscopy. Adhesion molecules expression and collagen production on both cell types were evaluated by quantitative RT-PCR, western blot, and flow cytometry. RESULTS: Mast cell adhesion to BSM cells mostly involved type I collagen of the ECM. Such an adhesion was increased in normal BSM cells under inflammatory condition, whereas it was maximal in asthmatic BSM cells. Blockade of either CD51 or CD44 significantly decreased mast cell adhesion to BSM. At the molecular level, protein and the transcriptional expression of type I collagen, CD51 or CD44 remained unchanged in asthmatic BSM cells or in mast cells/BSM cells under inflammatory conditions, whereas that of CD44 variant isoform 6 (v6) was increased. CONCLUSIONS: Mast cell-BSM cell adhesion involved collagen, CD44, and CD51, particularly under inflammatory conditions. CD44v6 expression is increased in asthmatic BSM cells.

Bioenergetics of lung tumors: alteration of mitochondrial biogenesis and respiratory capacity.

Little is known on the metabolic profile of lung tumors and the reminiscence of embryonic features. Herein, we determined the bioenergetic profiles of human fibroblasts taken from lung epidermoid carcinoma (HLF-a) and fetal lung (MRC5). We also analysed human lung tumors and their surrounding healthy tissue from four patients with adenocarcinoma. On these different models, we measured functional parameters (cell growth rates in oxidative and glycolytic media, respiration, ATP synthesis and PDH activity) as well as compositional features (expression level of various energy proteins and upstream transcription factors). The results demonstrate that both the lung fetal and cancer cell lines produced their ATP predominantly by glycolysis, while oxidative phosphorylation was only capable of poor ATP delivery. This was explained by a decreased mitochondrial biogenesis caused by a lowered expression of PGC1alpha (as shown by RT-PCR and Western blot) and mtTFA. Consequently, the relative expression of glycolytic versus OXPHOS markers was high in these cells. Moreover, the re-activation of mitochondrial biogenesis with resveratrol induced cell death specifically in cancer cells. A consistent reduction of mitochondrial biogenesis and the subsequent alteration of respiratory capacity was also observed in lung tumors, associated with a lower expression level of bcl2. Our data give a better characterization of lung cancer cells' metabolic alterations which are essential for growth and survival. They designate mitochondrial biogenesis as a possible target for anti-cancer therapy.

[Lethal pulmonary involvement of neutrophilic dermatosis following erythropoietin therapy]. / Extension pulmonaire d'une dermatose neutrophilique rapidement létale dans les suites d'un traitement par érythropoïétine.

BACKGROUND: Neutrophilic disease is characterized by aseptic visceral infiltration by normal polymorphonuclear leukocytes that can occur in any organ. Association with an underlying systemic disease, particularly haematological malignancy or inflammatory bowel disease, is frequent. This may produce a multisystem disorder, but diagnosis is usually based on skin lesions because of their clinical and histological accessibility. Pulmonary manifestations are the most common extracutaneous symptoms but may be misdiagnosed, as in our case report. CASE REPORT: A 77-year-old woman with IgA myeloma presented with an inflammatory bullous plaque of the leg coupled with fever lasting one week. The clinical and histological examinations were evocative of a neutrophilic dermatosis such as Sweet's syndrome. Significant improvement was initially obtained with systemic corticosteroids and colchicine. The course became complicated by necrotic neutrophilic papulopustular lesions of the upper limbs and pulmonary manifestations, with fever and decline in overall condition occurring the day after administration of erythropoietin. A hypothesis of septic aetiology prompted antibiotic and antifungal therapy, which remained ineffective. The patient died the day after the second erythropoietin injection. DISCUSSION: This case involved late identification of the aseptic neutrophilic aetiology of pulmonary manifestations. Several factors favouring their appearance and the fatal outcome may be suggested: the existence of a myeloma, association with myelodysplastic syndrome and the possible iatrogenic action of erythropoietin. To the best of our knowledge, this is the first reported case of extracutaneous neutrophilic infiltrate occurring in a patient treated with this haematopoietic hormone.

[Cutaneous, pulmonary and bone aspergillosis in a patient presumed immunocompetent presenting subacute cutaneous lupus erythematosus]. / Aspergillose cutanée, pulmonaire et osseuse chez un malade ayant un lupus érythémateux cutané subaigu sans déficit immunitaire associé.

INTRODUCTION: We report a case of cutaneous, pulmonary and bone aspergillosis successfully treated after many years of progression in a patient presumed immunocompetent presenting subacute cutaneous lupus erythematosus. CASE-REPORT: A 43-year-old man, treated with thalidomide for subacute cutaneous lupus erythematosus, presented chest pain with haemoptysis and dyspnea. A pulmonary nodule was detected but the microbiological investigation was negative. The histological examination showed granuloma with round structures. No cause was found. Three years later, skin lesions appeared on the patient's face concomitantly with a pulmonary relapse. Histopathological examination of these lesions demonstrated septate hyphae. Aspergillus fumigatus was isolated in skin and lung. Disseminated aspergillosis was then diagnosed as spondylodiscitis developed. Treatment with combined voriconazole and caspofungin produced significant and rapid improvement of lesions. DISCUSSION: While aspergillosis is commonly seen in immunocompetent patients, angiotropic dissemination points to cellular immunodepression. Our patient, however, was not presenting immunodepression. We discuss the possible contributory role of thalidomide in dissemination of aspergillosis given that the literature to date contains only one reported case of cutaneous aspergillosis secondary to A. fumigatus in an immunocompetent patient. We would also point out the specific histopathological pattern of this disseminated aspergillosis with both septate hyphae and round structures. Invasive aspergillosis is highly lethal but the chances of recovery are now greater thanks to new antifungal agents.

[Cyclosporine-induced follicular eruption]. / Toxidermie folliculaire à la ciclosporine.

BACKGROUND: Cyclosporine is one of the immunosuppressant agents most widely used in the prevention and treatment of organ transplant rejection and also in autoimmune diseases. Many cutaneous side effects have been described with oral cyclosporine, mainly in transplant recipients, for example, hypertrichosis, gingival hyperplasia and viral skin infections. Here, we report an unusual follicular eruption induced by this drug. PATIENTS AND METHODS: A 22-year-old man presenting cystic fibrosis received a double-lung graft in January 2005. Six weeks later, he developed a subacute eruption of follicular papules, not highly pruritic, located mainly on the trunk, the extensor surfaces of the limbs and the face. Diagnosis of cyclosporine-induced follicular eruption was adopted on the basis of the histological and microbiological findings. Complete regression was obtained after switching to tacrolimus. DISCUSSION: Three similar cases were previously reported characterized by typical follicular changes different from those observed in hypertrichosis or pilar keratosis. This rare cutaneous side effect may be explained by the direct action of cyclosporine on the pilosebaceous unit: this drug is known to extend the anagen phase of the follicular cycle and to induce toxic follicular dystrophy at higher tissue concentrations. This particular toxicity is usually seen after many months of treatment. In our patient, the time to onset was shorter, probably due to occasionally excessive plasma concentrations.

Inflammation of bronchial smooth muscle in allergic asthma.

BACKGROUND: Recent observations in asthma suggest that bronchial smooth muscle is infiltrated by inflammatory cells including mast cells. Such an infiltration may contribute to airway remodelling that is partly due to an increase in smooth muscle mass. Whether muscle increase is the result of smooth muscle cell hypertrophy remains controversial and has not been studied by ultrastructural analysis. A morphometric analysis of airway smooth muscle (ASM) was undertaken in asthmatic patients using electron microscopy to examine the interactions between ASM cells and inflammatory cells. METHODS: ASM specimens were obtained from 14 asthmatic subjects and nine non-asthmatic controls undergoing fibreoptic endoscopy. Inflammatory cell counts were assessed by immunohistochemistry, and ultrastructural parameters were measured using electron microscopy in a blinded fashion on smooth muscle cells and inflammatory cells. RESULTS: ASM from asthmatic patients was infiltrated by an increased number of mast cells and lymphocytes. Smooth muscle cells and their basal lamina were thicker in asthmatic patients (9.5 (0.8) and 1.4 (0.2) microm) than in controls (6.7 (0.4) and 0.7 (0.1) microm). In asthmatics the extracellular matrix was frequently organised in large amounts between ASM cells. Myofibroblasts within smooth muscle bundles were only observed in asthmatics, some of them displaying a close contact with ASM cells. CONCLUSION: In asthma, airway myositis is characterised by a direct interaction between ASM cells and mast cells and lymphocytes. Smooth muscle remodelling was present, including cell hypertrophy and abnormal extracellular matrix deposition moulding ASM cells.

Liposarcoma of the pleural cavity. An exceptional tumour.

Primitive liposarcomas of the pleura are exceptional tumours. We report a new case of primitive liposarcoma of the pleura revealed by chest pains in a 50 year old man. Computed tomography showed a large fat density mass in the left pleural cavity. Surgical resection was performed, completed with adjuvant radiotherapy. Few reports are available in the literary world. We present our case, review previously reported cases and discuss treatment.

Detection of circulating cells expressing chromogranin A gene transcripts in patients with lung neuroendocrine carcinoma.

High grade lung neuroendocrine carcinomas, like small and large cell neuroendocrine carcinomas, pose therapeutic problems. Most initially respond to chemotherapeutic agents, but early relapses are frequent and are resistant to the presently available treatments. Our study reports for the first time the development and evaluation of a test for detecting the presence of circulating tumour cells by measuring chromogranin A gene transcripts with reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blotting. The test is specific and sensitive (detection of 10 cancer cells/ml blood), and only minimally invasive. Positivity is statistically correlated to high grade neuroendocrine carcinomas and to a poor prognosis with a 3-fold higher lethal risk. The test now needs to be assessed for its usefulness as a tool in the initial staging procedures and follow-up by comparison with the recent immunoradiometric assay (RIA) for detection of chromogranin A in the serum.

[Solitary fibrous thoracic tumor: a rare tumor with unpredictable course]. / Tumeur fibreuse solitaire de la plèvre.

A 68-year-old woman presented chest pain and exercise-induced dypnea for one year. Diagnosis was a thoracic solitary fibrous tumor. These tumors are very rare. Clinical outcome is generally good except in 13% of the cases with a malignant component. Complete surgical resection is required.

[Clear cell adenoma of the parathyroid gland: a rare and misleading lesion]. / Adénome parathyroïdien à cellules claires: une lésion rare et trompeuse.

Parathyroid adenomas are common lesions and are considered to be the cause of most of the primary hyperparathyroidism cases. We report the case of a 73 year-old man who presented with a primary hyperparathyroidism. Clinical and histological explorations revealed the presence of an isolated parathyroid tumor containing exclusively clear cells and devoid of malignancy. This is the second reported case of clear cell parathyroid adenoma. Thus, in spite of its low occurrence, this diagnosis must be considered after rejection of the most frequent parathyroid clear cell hyperplasia and parathyroid carcinoma, or depending of the location, clear cell thyroid tumor and clear cell renal carcinoma metastasis.