Probe-based confocal laser endomicroscopy for pleural malignancies diagnosis.

peer reviewedBACKGROUND AND OBJECTIVE: Probe based confocal laser endomicroscopy (pCLE) is an optical imaging technique allowing live tissue imaging at a cellular level. Currently, this tool remains experimental. Two studies regarding pleural disease have been published and suggest that pCLE could be valuable for pleural disease investigations. However, normal and malignant pleural pCLE features remain unknown. Therefore, we conducted a prospective trial of pCLE during medical thoracoscopy to study and describe the malignant and benign pleural pCLE features. METHODS: Every patient >18 years referred to our department for medical thoracoscopy was eligible. Medical thoracoscopy was performed under sedation, allowing spontaneous breathing. Five millilitres of fluorescein (10%) was intravenously administrated 5 min before image acquisition. The pCLE was introduced through the working channel of the thoracoscope and gently placed on the parietal pleura to record videos. Afterwards, biopsies were performed on the corresponding sites. Malignant and benign pleural pCLE features were precisely described and compared using 11 preselected criteria. RESULTS: A total of 62 patients were included in the analysis including 36 benign and 26 malignant pleura. Among our preselected criteria, 'abnormal tissue architecture' and 'dysplastic vessels' were strongly associated with malignancies (100% and 85% ss, 721% and 74% sp, respectively) whereas, the 'full chia seeds sign' and 'cell shape homogeneity' were associated with benignity (36% and 56% ss, 100% and 70% sp, respectively). No study-related adverse events occurred. CONCLUSION: Benign and malignant pleural involvement have clearly distinct pCLE features

The Role of MCM9 in the Etiology of Sertoli Cell-Only Syndrome and Premature Ovarian Insufficiency

peer reviewedInfertility in couples is a common problem, with both female and male factors contributing to similar extents. Severe, congenital disorders affecting fertility are, however, rare. While folliculogenesis and spermatogenesis are generally orchestrated via different mechanisms, some genetic anomalies can impair both female and male gametogenesis. Minichromosome maintenance complex component 9 (MCM9) is involved in DNA repair and mutations of the MCM9 gene have been previously reported in females with premature ovarian insufficiency (POI). MCM9 is also an emerging cancer risk gene. We performed next-generation and Sanger sequencing of fertility and related genes and hormonal and imaging studies in a kindred whose members had POI and disordered spermatogenesis. We identified a homozygous pathogenic MCM9 variant, c.394C>T (p.Arg132*) in three sisters affected by POI due to ovarian dysgenesis and their brother who had normal pubertal development but suffered from non-obstructive azoospermia. Testicular biopsy revealed Sertoli cell-only testicular histopathology. No evidence of early onset cancer was found in the homozygotic family members, but they were all young (<30 years) at the time of the study. In the male patient the homozygous MCM9 variant led to normal pubertal development and hormonal levels but caused a Sertoli-cell-only syndrome with non-obstructive azoospermia. In the homozygous females studied, the clinical, hormonal, and gonadal phenotypes revealed ovarian dysgenesis consistent with previous reports. Active screening for potential colorectal and other cancer risks in the homozygotic MCM9 subjects has been instigated

Clinical Case of the Month. Constipation and Abdominal Mass Syndrome in a 51-Year-Old Patient

peer reviewedA 51-year old patient consults for abdominal swelling and persistent constipation. Clinical exploration shows the presence of a left iliac fossa tumor corresponding to a papillary serous adenocarcinoma of the fallopian tube after macroscopic and microscopic examination. The diagnostic and therapeutic problems caused by this rare gynecologic tumor are discussed

First report of probe based confocal laser endomicroscopy during medical thoracoscopy.

Probe based confocal laser endomicroscopy (pCLE) is a new optical endoscopic technique, generating fluorescent light emission from the tissue of interest and allowing in vivo live imaging at a cellular level ("optical biopsies"). To the best of our knowledge, this article is the first to present pCLE images during medical thoracoscopy. We present here 3 different patients referred for various health problems. A precise description of pleural cavity pCLE images after intravenous fluorescein injection (a fluorophore) together with corresponding macroscopical and histological studies is performed. This led to the diagnosis of normal pleura in one case, carcinomatous pleuritis in another case and a malignant mesothelioma in the third case. We believe that optical biopsies could help clinicians to make an early diagnosis, thereby allowing rapid therapeutic intervention (talc pleurodesis for example). Furthermore, it could help to guide biopsies when affected zones are not obvious to macroscopic examination. In a near future, new fluorophores could be developed to stain some pathophysiological processes, therapeutic targets, or enzymes activities bringing new insights in endoscopic pleural disease work-up

Granulomatosis With Polyangiitis in a Patient on Programmed Death-1 Inhibitor for Advanced Non-small-cell Lung Cancer.

Objectives: To contribute to a precise and thorough knowledge of immune-related adverse events (irAE) induced by immune checkpoint inhibitors (ICI) and to emphasize the importance of this specific form of toxicity in terms of potential predictive value and long-term effects. Materials and Methods: We report the first case of granulomatosis with polyangiitis (GPA) in a patient treated with an anti-Programmed Death protein-1 (PD-1) antibody for advanced non-small-cell lung cancer (NSCLC). Results: After a single dose of this drug the patient showed severe myositis associated with a high anti-PR3 anti-neutrophil cytoplasmic antibody titer. Discontinuation of the anti-PD-1 and introduction of corticoids led to a remission of the irAE. Regarding tumor a partial response was noted. A year later a neutrophilic, sterile pleural exudate and cutaneous lesions appeared with the pathological findings of neutrophilic vasculitis. Retreatment with corticoids induced a new remission of symptoms. It remains unclear whether GPA was preexisting and clinically silent but revealed by the use of ICI or primarily induced by this treatment. Conclusions: irAE are rare when anti-PD-1 antibodies are used in monotherapy. They present with a distinct clinical picture and temporal course and require specific treatment. Patients with irAE usually have a favorable oncological outcome

Adrenal ganglioneuroma

Background: A 20-year-old man was referred after having been discovered a left adrenal incidentaloma. Characteristics on magnetic resonance imaging (MRI) suggested the diagnosis of adrenal ganglioneuroma or carcinoma. Pathological examination after adrenalectomy concluded it was an adrenal ganglioneuroma. We studied the characteristics of adrenal ganglioneuroma. Methods: We retrospectively reviewed hormonal status, computed tomography and MRI features, and histological findings of our series of 8 adrenal ganglioneuromas. Results: Specific features were: (1) no hormonal hypersecretion; (2) presence of calcifications, no vessel involvement; and a non-enhanced attenuation of less than 40 Hounsfield units on computed tomography; and (3) low non-enhanced T1-weighted signal, a slightly high and heterogeneous T2-weighted signal, and a late and gradual enhancement on dynamic MRI, especially if associated with a whorled pattern. Conclusions: Even if many aggressive tumors share some of those radiological features, the presence of all or most of them must lead the clinician to consider the diagnosis of adrenal ganglioneuroma. (C) 2007 Excerpta Medica Inc. All rights reserved.Peer reviewe

Adrenal Ganglioneuroma. A Neoplasia to Exclude in Patients with Adrenal Incidentaloma

OBJECTIVE: To determinate the MRI and CT scanning appearance of adrenal ganglioneuroma and correlate the imaging with histological features. SUMMARY BACKGROUND DATA: In the last 10 years, eight patients with a pathologically proven adrenal ganglioneuroma were operated on in our department of endocrine surgery. To our knowledge, these patients represent one the largest reported cohorts of adrenal ganglioneuroma treated in a single institution. METHODS: All these eight patients had a comprehensive hormonal work up and underwent CT and/or MRI. Biological data, radiological features and histological findings were thoroughly reviewed in order to further characterize these tumours. RESULTS: The most relevant characteristics of adrenal GN resected in our patients were: No hormonal hypersecretion, Presence of calcifications; no vessel involvement; and a non-enhanced attenuation of less than 40 HU on CT, A low non-enhanced T1W signal, a slightly high and heterogeneous T2W signal, a late and gradual enhancement on dynamic MRI, especially if associated with a whorled pattern. CONCLUSIONS: Even if many aggressive tumours, mainly adrenal carcinoma, may share some of these radiological features, the presence of all or most of them must made the clinician evoke the diagnosis of GN.Peer reviewe

Un cas de cirrhose néonatale sans surcharge en fer : hépatite alloimmune congénitale

Background. Fetal liver disease is a rare antenatal disorder for which etiology is frequently unknown. Recently, congenital alloimmune hepatitis emerged as a major cause of antenatal liver disease. Its typical presentation can be as a severe neonatal liver failure with hepatic and extrahepatic iron overload, a clinical state called neonatal hemochromatosis. Methods. A pregnant woman was investigated for heterogeneous fetal hepatomegaly. Pregnancy was also complicated by fetal alloimmune thrombocytopenia. The newborn presented at birth with liver cirrhosis and mild liver dysfunction. Follow-up until 36 months showed progressive normalization of all liver parameters. All metabolic and infectious analyses were negative. Liver biopsy showed severe hepatitis with post-necrotic fibrosis and regenerative nodules. There was no iron overload. To search for immune injury, paraffine sections of the liver biopsy were stained with an antibody against the membrane attack complex (MAC, anti human c5b-9, Peter Whitington’s Lab, Children’s Memorial Hospital, Chicago, IL), the terminal complement cascade neoantigen occurring specifically in complement activation by the IgG-mediated classical pathway, and which is responsible for cell death. Results. Strong immunostaining against MAC-antigen was found in the liver of the patient, with 90% of target hepatocytes whereas in a control group of patients with other neonatal liver diseases, it was 10.8±12.5%. Because IgG in neonates originate only from the mother, it signs the alloimmune nature of the disease. Conclusion. For a long time, pathophysiology of neonatal hemochromatosis remained unsolved. Recently, it was elucidated as congenital alloimmune hepatitis. With this case, we expend the recognized clinical spectrum by showing that congenital alloimmune hepatitis can present as milder cases, without iron overload. It should be considered as a cause of unexplained neonatal liver disease, even in the absence of siderosis. Such diagnosis is of great importance regarding the necessity of immunotherapy in further pregnancies in order to avoid recurrence of alloimmune injur

Breast carcinoma: the interest of pathological classification

peer reviewedThe breast pathology includes a large array of entities for which macroscopic and microscopic analysis remains fundamental. Tissue and cell morphology allows in most cases the distinction between benign or malignant tumours and therefore provides the clinicians with essential information for the therapeutic strategy. In the Pathology laboratory, immunohistochemistry and molecular biology have improved the specificity of the diagnosis and have introduced new prognostic and predictive markers for tumour management. The last edition of the WHO classification, released in 2003, distinguishes 21 varieties of invasive carcinoma and 2 categories of intraepithelial neoplasia based on the morphology and immunohistochemical profile. Other diseases can affect the breast, although much less frequently, such as Paget’s disease of the nipple, phyllode tumours, sarcomas, lymphomas... These diseases will not be reviewed here