[Aid of artificial intelligence for the anatomo-pathological diagnosis of tumours]. / Intérêt de l'intelligence artificielle pour le diagnostic anatomo-pathologique des tumeurs.

The anatomo-pathological diagnosis of tumors is based on many criteria related mainly to image analysis. Currently, in most pathology laboratories, tissues or cells are placed on glass slides and directly analyzed with an optical microscope. Because of technological evolutions, it is currently possible to digitize slides (digital pathology). The digitization of whole slides has allowed the development of computer programs of artificial intelligence (AI) for image analysis. Applied to tumour pathology, this technology allows the detection, diagnosis or evaluation of the prognosis of neoplastic lesions. There are many challenges associated with the use of AI in routine pathology. These are mainly related to the amount of data to be analyzed and to the development of reliable algorithms. Nevertheless, this technology is promising and could become a valuable aid in the field of precision medicine for which the amount of data related to a patient is constantly increasing.

Le diagnostic anatomo-pathologique des tumeurs repose sur de nombreux éléments en relation principalement avec l'analyse d'images. Actuellement, dans la plupart des laboratoires d'anatomie pathologique, les tissus ou les cellules sont placés sur des lames en verre et directement analysés avec un microscope optique. Grâce aux évolutions technologiques, il est actuellement possible de numériser des lames (pathologie digitale). La digitalisation de lames entières a permis le développement de programmes informatiques d'intelligence artificielle (IA) d'analyse d'images. Appliquée à la pathologie tumorale, cette technologie permet, entre autres, la détection, le diagnostic ou l'évaluation du pronostic de lésions tumorales. Il existe de nombreux défis à l'utilisation de l'IA en anatomie pathologique de routine. Ceux-ci sont essentiellement liés à la quantité de données à analyser pour obtenir des résultats et au développement d'algorithmes fiables. Néanmoins, cette technologie est prometteuse et pourrait devenir une aide précieuse dans le cadre de la médecine de précision où la quantité de données liées à un patient s'accroît sans cesse.

[Melanoma : the patient's care pathway. From diagnosis to therapy]. / Le mélanome : le trajet de soins du patient. Le mélanome : le trajet de soins du patient Du diagnostic au traitement Du diagnostic au traitement.

The management of melanoma is a typical example of a pluridisciplinary approach, in order to provide the patient with a rapid and adequate treatment plan after the initial diagnosis. Both in the domains of dermatology, pathology and oncology, enormous progress has been made. Recent advances permit a rapid access to diagnostic techniques using teledermoscopy, an improved diagnostic accuracy using dermoscopy, pre-interventional high-frequency ultrasound and optical coherence tomography, a determination of risk factors using immunohistochemistry and genetic analyses on the pathology samples. Furthermore, the development of immunotherapies, in particular the anti-PD1 antibodies, and the directed therapies, therapies permitting an increased number of patients to experience an increased survival with an acceptable tolerance profile in the event of metastatic lesions. This article describes the patient's care pathway, from the initial diagnosis, staging, to an eventual treatment and follow-up.

Le traitement du mélanome est un exemple type de collaboration multidisciplinaire, afin de pouvoir garantir au patient une prise en charge rapide dès le moment de la détection de la lésion. Tant au niveau dermatologique, anatomopathologique et oncologique, d'énormes progrès ont eu lieu ces dernières années. Ils permettent un accès au diagnostic de plus en rapide par la télédermoscopie, une précision diagnostique accrue par la dermoscopie, l'ultrason à haute fréquence et la tomographie par cohérence optique, une détermination des facteurs de risque immunohistochimiques et génétiques sur les analyses anatomo-pathologiques ainsi que le recours à des immunothérapies, notamment les anti-PD1, et à des traitements ciblés. Ces nouveaux traitements permettent souvent une plus longue survie du patient, avec un profil de tolérance acceptable en cas de lésions métastatiques. Cet article reprend le trajet de soins du patient, du diagnostic initial et du staging au traitement éventuel avec son suivi.

Tandem inversion duplication within F8 Intron 1 associated with mild haemophilia A.

In approximately 90% of mild haemophilia A (HA) patients, a missense mutation can be identified using complete gene sequencing. In this study, multiplex ligation-dependent probe amplification analysis was performed as a second step in 10 French-speaking Belgian with mild HA presenting no detectable causal mutation by complete sequencing of the factor VIII (FVIII) (F8) gene's 26 exons and its 1.2 kb of contiguous promoter sequence. This gene dosage technique enabled the detection of exon 1 duplications of F8 in three apparently unrelated subjects. Using array-comparative genomic hybridization, breakpoint analysis delimited the duplication extent to 210 kb in the F8 intron 1 and VBP1 gene intragenic position. We postulated that the rearrangement responsible for this duplication, never before reported, could be attributed to a symmetrical tandem inversion duplication, resulting in a large 233 kb rearrangement of F8 intron 1. This rearranged intron should lead to the production of a small number of normal mRNA transcripts in relation to the mild HA phenotype. Our analysis of the entire F8 mRNA from index case 1, particularly the segment containing exons 1-9, revealed normal amplification and sequencing. Reduced plasma FVIII antigen levels caused by cross-reacting material is associated with a quantitative deficiency of plasma FVIII. Male patients were unresponsive to desmopressin (1-deamino-8-D-arginine vasopressin). All patients displayed identical F8 haplotypes, despite not being related, which suggests a possible founder effect caused by a 210 kb duplication involving F8 exon 1.

[Finding the drug in cutaneous drug eruptions]. / Imputabilité médicamenteuse dans les iatrogénies cutanées.

Drug eruptions are frequently encountered. Their putative diagnosis is based on a set of imputability arguments. The histopathological aspect is often evocative of the nature of the dermatosis. It varies according to the type of drug reaction. Some drug eruptions follow a benign course, but others are life-threatening.

[Mammary Paget's disease]. / La maladie de Paget mammaire indicatrice d'un adénocarcinome sous-jacent.

Mammary Paget's disease is an intraepithelial carcinoma present on the nipple and its areola. The tumor typically develops in middle aged women. It is frequently associated or contiguous to an underlying galactophoric adenocarcinoma. The histopathologic and immunopathologic aspects are typical and linked to the presence of Paget's cells. Early diagnosis is required searching for a possible underlying carcinoma. The surgical treatment is directed by the characteristics of the deep mammary carcinoma.

[Unraveling the ichthyosis types]. / Comment j'explore...le méli-mélo des ichtyoses.

Ichthyoses are hereditary and sometimes acquired diseases of keratinisation. They are heterogeneous according to their clinical and histopathological presentations, as well as to the nature of their molecular and genetic alterations. We present the most frequent types of hereditary ichthyoses.

[How I explore...a skin tumor in a transplant patient]. / Comment j'explore...une tumeur cutanée chez un transplanté.

Immunosuppressive therapy associated with organ transplant leads to an increased risk to develop skin cancers. In such circumstances, squamous cell carcinomas and basal cell carcinomas represent the most frequent tumors. Other neoplasms include malignant melanoma, Merkel cell carcinoma and Kaposi disease. Histopathology is primordial in the establishment of the diagnosis. In addition, bioengineering devices and skin imaging methods are useful in establishing the risk of cancers and for detecting incipient tumoral lesions.

[Clinical case of the month: clostridium difficile colitis]. / Le cas clinique du mois. Colite à clostridium difficile.

A 55-year-old patient with mant e cels underwent a cytotoxic chemotherapy (D.H.A.P. + Rituximab). During the medullar aplasia related to the third cycle, diarrhoea due to Clostridium difficile arised and relapsed 15 days later despite normal blood counts. This colitis was very severe with pluribacterial peritonitis, but resolved with intensive medical treatment. The incidence, the patient's risk factors, the iatrogenic and nosocomial characters of cl. difficile colitis are discussed.

[Multifocal germ cell tumors]. / Tumeurs germinales multicentriques.

A 16-year old male presented with a mediastinal germ cell tumor (seminoma) treated by combined surgery, radiotherapy and chemotherapy. Nine years later, he presented with an intracerebral germ cell tumor affecting both the suprasellar ventricles and the pineal area. After partial removal of the intraventricular tumor, the patient received radiotherapy and chemotherapy. No metastases could be found. He died 8 months later, probably from secondary cardiovascular disturbances. This case seems to be the first one to illustrate the possibility of multifocal extragonadal seminoma.

[Hibernal respiratory disorders]. / Les affections respiratoires hivernales.

A long term serological surveillance of the acute respiratory illnesses was conducted, looking for infections by adenoviruses, influenza A.B.C. parainfluenza 1,2,3 and respiratory syncytial viruses as well as Mycoplasma pneumoniae, Coxiella burneti and Chlamydia psittaci. The analysis of the results accumulated for the past 20 years was carried out. Influenza C. Coxiella burneti and Chlamydia psittaci infections were rare and could not account for any epidemic prevalence. The other agents produced mostly winter infections, but their contribution to the annual peak varied from year to year. One or several infections were associated with 21% of our total number of acute respiratory illnesses. Beside their close association with winter disease, the respiratory agents could be found all over the year, both amongst patients with or without respiratory tract involvement. To identify the above mentioned viruses we have been using monoclonal antibodies for 30 months including three epidemic seasons. From december 1987 on, we examined nearly 600 cell specimens collected by pharyngeal washing amongst young children admitted to local hospitals for respiratory tract involvement. The results were in agreement with those given by the serological surveillance. We still lack convenient methods to identify the agents which could account for most of the common acute respiratory diseases.

Detection by enzyme-linked immunosorbent assay of specific immunoglobulin G isotypes in primary and established cytomegalovirus infections.

An enzyme-linked immunosorbent assay using monoclonal antibodies was developed to study the subclass distribution of immunoglobulin G (IgG) to cytomegalovirus (CMV) in individuals from a number of clinical groups. Most CMV-seropositive individuals had IgG1 and IgG3. IgG2 and IgG4 were detected less frequently at very low levels of activity, mostly among mothers at delivery and renal patients. Most seroconversions were accompanied by an important increase of the IgG1 activity, whereas IgG3 appeared at lower levels; neither IgG2 nor IgG4 occurred. This suggests that these isotypes play a secondary role in the response to the CMV infection and that they may be considered markers of past infections. Anti-CMV IgG1 is the most efficiently transmitted through the placenta. Whether infected or not, newborns had the same subclass distribution and activity levels as their mothers. Isotype determination did not offer a decisive explanation of a number of discrepancies observed between CMV IgG enzyme-linked immunosorbent assay and complement fixation test results.

Phase II trial with high-dose ifosfamide and mesna given in a 24-h infusion for advanced GI tract cancer.

In all, 26 patients with advanced GI tract cancer (among whom 23 had liver metastases) were treated in a phase II trial with a 24-h infusion of high-dose ifosfamide and mesna (5 g/m2). Two PR, 1 CR and 4 NC were evidenced among 23 patients evaluable for response. The toxicity was significant and mainly expressed in the hair, digestive tract, granulocytes and CNS. One patient died from CNS and kidney toxicities. Only patients with good clinical indices, normal serum albumin and creatinine levels and without pelvic involvement seemed to be candidates to benefit from the treatment.

Monoclonal antibodies detect M-protein epitopes on the surface of influenza virions.

Various data obtained with activable hydrophobic probes, proteolytic treatments and anti M-protein polyclonal antibodies strongly suggest that M-protein of influenza A is an integral part of the lipid bilayer of native virions and somehow spans at the surface of the virions. Therefore we have looked for the presence of M-protein epitopes on the surface of influenza A virion by using four type A M-protein monoclonal antibodies. We developed a specific and sensitive competition ELISA where intact virions, dodecyl-sulfate disrupted virions and spikeless particles obtained after proteolytic treatment with caseinase C were used to test their ability to inhibit the reaction between these monoclonal antibodies and pure M-protein. Intact virions or SDS disrupted virions prevented three monoclonal antibodies from reacting with the M-protein. Spikeless particles also inhibited the specific binding of two of these antibodies, whereas the other fourth antibody was inhibited by contact with SDS disrupted particles only. Data presented show that at least three distinct M-protein epitopes were detected, of which at least two are exposed on the surface of intact virions. Of these two epitopes, one is inactivated by the proteolytic treatment. The third epitope could only react with its monoclonal antibody when the virus particles were solubilized with SDS. This work provides a clear demonstration that a substantial part of the M-protein spans the lipid bilayer and that the rest, protected by lipids, resists proteolytic enzymes and is prevented from binding with anti M-protein monoclonal antibodies.

Elimination of nonspecific cytomegalovirus immunoglobulin M activities in the enzyme-linked immunosorbent assay by using anti-human immunoglobulin G.

Direct enzyme-linked immunosorbent assay methods offer several advantages in assessing past or recent exposure to cytomegalovirus (CMV) infection, but there persist many pitfalls in the use of these methods for determining specific immunoglobulin M (IgM). The efficiency of absorption of sera by IgG-coated latex beads, aggregated human IgG, or Staphylococcus aureus, i.e., for removing nonspecific CMV IgM activities, was evaluated in comparison with the effect of an anti-human IgG hyperimmune serum. Large routine series comprising serum samples from patients of various clinical groups and healthy individuals were examined. The CMV IgM-positive samples were at first treated with latex or aggregated IgG, but these absorptions left too many CMV IgM-positive individuals. S. aureus increased the nonspecific activity of some sera and, in other cases, removed or impaired specific IgM activities. The anti-IgG treatment caused the disappearance of nonspecific CMV IgM activities that had resisted the other treatments, whereas specific activities remained intact. Utilizing this method, only 1.03% of the routine series patients remained CMV IgM positive by the enzyme-linked immunosorbent assay, a figure in good agreement with a mean probability of CMV antibody acquisition of 0.33% for the population living in Belgium. On the other hand, in a series of patients who were investigated for serological response to several viruses, eight individuals displayed multiple IgM activities after anti-IgG treatment. In these cases, most IgM activities were found in patients who had IgG toward the related antigen for a long time before transient IgM was detected. This result implies that to assess a diagnosis of primary infection, it is necessary to examine serial specimens for IgG acquisition accompanying specific IgM.