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.

Guidelines for May-Grünwald-Giemsa staining in haematology and non-gynaecological cytopathology: recommendations of the French Society of Clinical Cytology (SFCC) and of the French Association for Quality Assurance in Anatomic and Cytologic Pathology (AFAQAP).

OBJECTIVE: Since the guidelines of the International Committee for Standardisation in Haematology (ICSH) in 1984 and those of the European Committee for External Quality Assessment Programmes in Laboratory Medicine (EQALM) in 2004, no leading organisation has published technical recommendations for the preparation of air-dried cytological specimens using May-Grünwald-Giemsa (MGG) staining. DATA SOURCES: Literature data were retrieved using reference books, baseline-published studies, articles extracted from PubMed/Medline and Google Scholar, and online-available industry datasheets. RATIONALE: The present review addresses all pre-analytical issues concerning the use of Romanowsky's stains (including MGG) in haematology and non-gynaecological cytopathology. It aims at serving as actualised, best practice recommendations for the proper handling of air-dried cytological specimens. It, therefore, appears complementary to the staining criteria of the non-gynaecological diagnostic cytology handbook edited by the United Kingdom National External Quality Assessment Service (UK-NEQAS) in February 2015.

[Analysis of asbestos bodies and nude fibres in the lung parenchyma of operated lung cancers. A retrospective monocentric study of 73 cases]. / Analyse de corps asbestosiques et de fibres nues dans le parenchyme pulmonaire de cancers du poumon opérés. Étude monocentrique rétrospective de 73 cas.

We report on a study concerning a retrospective monocentric series of 73 lung cancers operated on between July 2004 and December 2009. All patients had a mineralogical analysis of a sample of lung tissue combined with an occupational questionnaire. This combination enables us to suggest a declaration of occupational exposure in almost one third of cases. We suggest that a healthy parenchymal fragment is to be obtained by biopsy routinely in cases of lung cancer surgery. The analysis should be carried out if the occupational survey does not demonstrate any evident exposure and if the patient is not known to be presenting a pleuropulmonary disease following asbestos exposure (pleural plaques and asbestosis).

Characterisation of severe obliterative bronchiolitis in rheumatoid arthritis.

The characteristics of patients with rheumatoid arthritis (RA) who develop obliterative bronchiolitis characterised by severe airflow obstruction have been hitherto poorly investigated. A retrospective study of 25 patients with RA and functional evidence of obliterative bronchiolitis (forced expiratory volume in one second (FEV(1))/forced vital capacity (FVC) <50% and/or residual volume (RV)/total lung capacity (TLC) >140% predicted) was conducted. Patients (mean+/-SD age 64+/-11 yrs) included 17 never-smokers and eight ex-smokers (10.5+/-5.4 pack-yrs). The diagnosis of RA preceded respiratory symptoms in 88% of cases. Dyspnoea on exertion was present in all patients and bronchorrhea in 44%. High-resolution computed tomography findings included: bronchial wall thickening (96%), bronchiectasis (40%), mosaic pattern (40%), centrilobular emphysema (56%), and reticular and/or ground-glass opacities (32%). Pulmonary function tests showed: FEV(1) 41+/-12% pred, FEV(1)/FVC 49+/-14%, FVC 70+/-20% pred, RV 148+/-68% pred and RV/TLC 142+/-34% pred. Lung biopsy, available in nine patients, demonstrated constrictive, follicular and mixed bronchiolitis. Patients were followed for 48.2+/-49 months. Treatment was poorly effective. Chronic respiratory failure occurred in 40% of patients, and four patients died. Obliterative bronchiolitis associated with rheumatoid arthritis is a severe and under-recognised condition leading to respiratory failure and death in a high proportion of patients.

[Use of talc and sarcoidosis - pathogenic role of cutaneous talc exposure in sarcoidosis]. / Application cutanée de talc et sarcoïdose. A propos de deux cas.

INTRODUCTION: We report on two patients with sarcoidosis with disseminated nodes, who used talc on irritated cutaneous areas. CASE REPORT: A histologic examination with intense polarised light showed up cristalline bi-refringent particles within vessels in contact with granulomatous areas. Microdissection followed by an electronic microscopy study and microanalysis was realised. In situ microanalysis allowed us to identify bi-refringent particles with a size of roughly 0.25microm as silica or silicate coming possibly from talc. We consequently studied a brand name talc. The diffraction spectrum showed that this product not only contained talc but also chlorite and quartz. Electron microscopy examination showed particles of all sizes even smaller than 0.25microm. These infra-microscopic particles, visible in a vessel only when agglomerated, could be invisible under optic microscopy (resolution: roughly 0.5microm) inside the granuloma even though they are responsible for it. Moreover, at this level of size of particles, they may escape mineralogic analyses which use methods involving the destruction of organic material, the mineral residue collecting on cellulose filter with a diameter generally of 0.45microm. CONCLUSION: Two recent epidemiologic studies confirm the possible role of mineral exposure in sarcoidosis. Some sarcoidosis could be caused by mineral overload on genetically predisposed patients. Some cases could be related to mineral powder application. Among different types of mineral exposure, applications of cosmetic products may induce disseminated granulomatous reaction on genetically predisposed patients. Such applications have to be considered in epidemiologic studies.

Circumstances of death and gross and microscopic observations in a series of 200 cases of sudden death associated with arrhythmogenic right ventricular cardiomyopathy and/or dysplasia.

BACKGROUND: Sudden death is a possible consequence of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D). Prevalence of ARVC/D in unexpected sudden cardiac death (USCD), however, remains imprecise, as do circumstances of death and ARVC/D-associated gross and microscopic findings, especially His bundle anomalies. METHODS AND RESULTS: We reviewed 14 000 forensic autopsies required by judicial authorities from January 1980 to January 1999 in a 2 000 000-resident area. Age, gender, and circumstances of death were recorded. Hearts were examined macroscopically and microscopically. In this series, the ARVC/D group accounted for 200 consecutive cases (10.4%) of USCD, including 108 males and 92 females (average age 32.5 and 34.5 years, respectively). Nearly one third of deaths occurred during the fourth decade of life. Circumstances of death were various, but 75.6% occurred during everyday life events (at home, 63.1%; in the street, 6.6%; or at work, 6.1%); only 7 cases (3.5%) occurred during sports activity. Nineteen cases (9.5%) happened during the perioperative period. Adipose infiltration of the right ventricle was either isolated (20%) or associated with fibrosis (74.5%) and lymphocytes (5.5%). A total of 14.5% of cases had cardiac hypertrophy, assessed by an increase in heart weight and/or left ventricular wall thickness. In most cases, the His bundle and its branches were abnormal either because of infiltration of adipose tissue (8.1%), fibrosis (54.3%), or both (5.6%). CONCLUSIONS: In ARVC/D, both sexes are equally affected, and there is a peak of risk during the fourth decade. Death most frequently occurs during sedentary activity. His abnormalities and left ventricular hypertrophy may be associated with ARVC/D.

Pathology of human bronchioloalveolar carcinoma and its relationship to the ovine disease.

Lung cancer is a leading cause of cancer with a poor prognosis. Bronchioloalveolar carcinoma (BAC) is a rare tumor that has always intrigued physicians. Since the last World Health Organization classification the pathology has been clarified; BAC per se is an adenocarcinoma with a pure bronchioloalveolar growth pattern and appears as an in situ alveolar adenocarcinoma. More usually BAC is a clinically recognizable entity presenting as multi-focal nodules evolving towards pneumonia associated with pulmonary shunting. Pathology is that of a multifocal mixed adenocarcinoma: bronchioloalveolar and papillar. Whatever the stage, survival is better than in other forms of non-small cell lung cancer (NSCLC). The true frequency of BAC is unknown, although it is a rare form of lung cancer; smoking cannot be excluded as a risk factor. It appears that p53 and ras genes are less often mutated than in other lung adenocarcinomas, suggesting that the cellular mechanisms involved are different. Ovine pulmonary adenocarcinoma (OPA) presents with the same symptoms as BAC in humans and is caused by a betaretrovirus Jaagsiekte sheep retrovirus. Very early on, clinical and histological similarities with human BAC were stressed. A recent series of OPA described, according to the third edition of the WHO classification for human lung cancer, mixed adenocarcinoma, BAC and papillary and/or acinar carcinoma. An immunohistochemical study suggested that some human pulmonary tumors (including BAC) may be associated with a Jaagsiekte sheep retrovirus-related retrovirus,but so far no molecular study has confirmed this observation. Thus, OPA is an exquisite model of carcinogenesis for human lung adenocarcinomas.

["Spontaneous" resolution of two severe methotrexate-induced pneumonias]. / Résolution spontanée de deux pneumopathies sévères au méthotrexate.

The beneficial role of corticosteroid therapy for the treatment of methotrexate-induced pneumonia remains controversial. We report two cases of acute severe interstitial pneumonia induced by methotrexate in patients with non-Hodgkin lymphoma given a polychemotherapy protocol (M'BACOD). The first signs appeared on the eleventh day of the first cycle in patient one and on the tenth day of the third cycle in patient two. The causal implication of methotrexate was based on the history, the clinical and radiological presentation, and the negative tests in both patients: lymphocyte alveolitis with granulomatous lesions on the transbronchial biopsy in patient one and positive leukocyte migration test in the presence of methotrexate in patient two. Early acute respiratory failure required high flow rate oxygen therapy with positive expiratory pressure ventilatory assistance. The course was rapidly favorable both for blood gases and radiographic presentation without corticosteroids. These two cases illustrate that pulmonary disease can be cured without corticosteroids despite severe respiratory failure at onset. This provides a further argument on reservations about using corticosteroids for suspected methotrexate-induced pneumonia.

[Nonspecific interstitial pneumonitis: a new anatomoclinical entity among idiopathic diffuse interstitial pneumonias]. / Pneumopathie interstitielle non spécifique: une nouvelle entité anatomoclinique au sein des pneumopathies interstitielles diffuses idiopathiques.

Nonspecific interstitial pneumonitis with fibrosis has been individualized within the group of idiopathic diffuse interstitial pneumonias by pathological criteria. It is differentiated from usual interstitial pneumonitis by the temporal uniformity of the lesions, a prominent inflammatory interstitial infiltration, and the absence of honeycombing. Clinical and functional symptoms are those of diffuse interstitial pneumonitis. An etiology may be found in about half the cases, including connective tissue disease, exposure to organic antigens, or recent acute lung injury. Computed tomography of the chest shows bilateral ground glass opacities, and alveolar opacities with a peribronchiolar or patchy distribution. Prognosis is rather good, since a majority of patients improve when treated with corticosteroids or with an association of corticosteroids and immunosuppressive drugs. These etiologic and prognostic features justify the individualization of nonspecific interstitial pneumonitis with fibrosis as a distinct clinicopathological entity.

[Rare etiology of multiple pulmonary lacunae]. / Une étiologie rare de lâcher de ballons pulmonaire.

Sarcoma of the common pulmonary artery are rare malignant tumors which can mimic pulmonary embolism. In the case presented here, the inaugural signs were particularly misleading: multiple pulmonary lacunae on computed tomography. The unusual aspect and asymmetric localizations at pulmonary angiography then suggested the doubtful nature of the embolism etiology. Magnetic resonance imaging findings suggested the diagnosis of sarcoma of the pulmonary artery. Certain diagnosis was obtained at pathology examination of the surgical specimen after thoracotomy. A malignant fibrous histiocytoma was identified. Curative resection was not possible and chemotherapy was performed. Unusual parenchymal lesions were then evidenced on the radiography. Better and better magnetic resonance imaging criteria are described in the literature and help distinguish between thromboembolism and sarcoma of the pulmonary artery. Follow-up of the clinical course is thus improved. It is nevertheless necessary to evaluate intravascular extension to determine whether curative surgery is possible.

Migratory organizing pneumonitis "primed" by radiation therapy.

We report on two women presenting with cough and fever, 4 and 7 months, respectively, after starting breast radiation therapy following surgery for breast carcinoma. Chest roentgenogram and computed tomographic (CT) scan demonstrated alveolar opacities, initially limited to the pulmonary area next to the irradiated breast, but later migrating within both lungs. Intra-alveolar granulation tissue was found in transbronchial lung biopsies. Corticosteroid treatment resulted in dramatic clinical improvement, together with complete clearing of the pulmonary opacities on chest imaging. However, clinical and imaging relapses occurred when corticosteroids were withdrawn too rapidly; with further improvement when they were reintroduced. The reported cases clearly differ from radiation pneumonitis. They were fairly typical of cryptogenic organizing pneumonitis, also called idiopathic bronchiolitis obliterans organizing pneumonia, with the exception of the radiation therapy, partially affecting the lung, which had been performed within the previous months. Since focal radiation therapy involving the lung may induce diffuse bilateral lymphocytic alveolitis, we hypothesize that this may "prime" the lung to further injury, leading to cryptogenic organizing pneumonitis.

[Diagnostic difficulties in angiosarcoma of the pulmonary artery with hemoptysis]. / Difficultés diagnostiques d'une forme hémoptoïque d'angiosarcome de l'artère pulmonaire.

Intimal sarcomas growing from the pulmonary trunk or branches of the pulmonary artery, are rare tumours in which the diagnosis is most often made at autopsy or during a thoracotomy. Usually the clinical pictures is non specific resembling a severe pulmonary embolus which is resistant of all treatment. With the help of new imaging techniques, a pre-operative diagnosis is made in more than half the cases. When there is a tumour which is relatively localised and without endoluminal invasion, as in the observation reported here, the diagnosis rests on the histology from the operative specimen.

[Value of cytological study by flow cytometry or analysis of image as a complement to macroscopic study by cytoscopy. Apropos of therapeutic follow-up of a case of tumor of the bladder]. / Intérêt de l'étude cytologique par cytométrie en flux ou analyse d'image en complément de l'examen macroscopique par cystoscopie. A propos du suivi thérapeutique d'un cas de tumeur de vessie.

The case described corresponds to a grade G2 urothelial tumor with stage pTa extension (according to the World Health Organisation classification). After transurethral resection of the tumor and treatment by Bacillus Calmette Guerin (BCG), the efficacy of treatment was evaluated by cystoscopy, standard cytology, flow cytometry or image analysis. According to these various methods it has been shown that a normal cystoscopy may or may not be associated with aneuploidy revealed by flow cytometry. Such a case clearly illustrates the value of combining macroscopic examination and a cytologic analysis in particular by flow cytometry in order to increase the accuracy of diagnosis and to evaluate without ambiguity the efficacy of treatment.

Expression of neuron-specific enolase immunoreactivity by cutaneous and extracutaneous Langerhans-cell histiocytoses ("X").

The immunohistochemical expression of Neuron-Specific Enolase (NSE) and of S100 protein was studied in 10 cases of cutaneous and 19 cases of extracutaneous Langerhans cell histiocytoses (LCH), including acute/proliferative forms (cutaneous Letterer-Siwe disease) and chronic/granulomatous forms (eosinophilic granuloma, Hand-Schüller-Christian disease). Of the LCH cases, 18 (62%) exhibited detectable NSE-immunoreactivity as compared to 82.8% for S100. NSE expression was found more frequently and intensely within acute (as compared to chronic) forms of LCH. This result lends further support to the cellular unicity of LCH, but also suggests some degree of heterogeneity among LCH cells. It can be speculated that NSE-expression is correlated with the proliferation/activation state of (abnormal) Langerhans cells.

[Malpighian epithelia and papillomavirus infections]. / Epithéliums malpighiens et infections à papillomavirus.

Human papillomaviruses (HPV) are a large group of DNA viruses, with over 60 types identified to date, which can cause the development of benign tumors in the skin and mucosal squamous epithelia. Most of these tumors regress spontaneously but some, especially in the mucosal membranes, become malignant. HPV types with a high risk for inducing malignancies (e.g. 16 and 18) are the subject of increasing interest. HPVs are both host-specific and tissue-specific: some types preferentially infect specific epithelia, giving rise to lesions with distinct topographic characteristics. HPVs are difficult to study because they do not replicate in available in vitro models. In vivo, HPVs replicate well in epithelial cells undergoing terminal differentiation, e.g. in keratinized cells. Some 40 different types have been reported in epidermal keratinocytes, the most common being types 1 and 2 which produce large amounts of viral antigens and viral particles. In contrast, HPVs replicate poorly in the weakly keratinized squamous epithelia which line the digestive, respiratory, and genital tracts. Junctional epithelia, e.g. on the uterine cervix, are especially prone to HPV infection. The most prevalent HPV types in benign genital lesions are types 6 and 11, whose characteristic features include extrachromosomal DNA and production of only small amounts of viral antigens. The profound nuclear and cytoplasmic changes induced by HPVs lead to the formation of koïlocytes which are found mainly in the granular layer of epithelia and have been especially well described in the uterine cervix and vagina. HPV epithelial tumors are squamous cell carcinomas that often harbor HPV types 16 and 18; this is especially true of cervical intraepithelial neoplasias.(ABSTRACT TRUNCATED AT 250 WORDS)

Human papillomavirus DNA in cervix. In-situ hybridization with biotinylated probes on Bouin's fixed paraffin embedded specimens.

We examined retrospectively a series of 65 Bouin's fixed, paraffin-embedded tissue specimens from 8 condylomatous lesions, 16 condylomas associated with cervical intraepithelial neoplasia (CIN), and 12 neoplasia without condylomatous signs, for histological characteristics, the detection of viral structural antigen, the presence and typing of HPV DNA by molecular in situ hybridization with biotinylated probes types 6, 11, 16 and 18 under stringent conditions (Tm - 12 degrees C). HPV DNA was present in 34/65 (52%) specimens. Detection of viral structural antigen was positive in only 14% (3/22) specimens. HPV DNA were identified in 9/9 (100%) condylomatous lesions (with HPV type 6, 11, 18). Three condylomas were coinfected with both HPV type 6 or 11 and type 18; viral antigen was found in two specimens. HPV DNA were detected in 18/31 (58%) low grade and advanced CIN associated with condylomatous changes (type 6 = 5 specimens, type 11 = 3 specimens, type 16 = 4 specimens, type 18 = 6 specimens). Four of these cases were coinfected with both HPV type 6/11 and HPV type 16/18. Viral antigen was negative in all specimens. HPV DNA were detected in 7/25 (28%) advanced intra-cervical neoplasia (CIN III) without anatomopathological condylomatous changes (type 6 = 1 specimen, type 16 = 3 specimens, type 18 = 3 specimens). One of these specimens contained both HPV types 6 and 18. Viral antigen was found in one case. Our data confirm the association of HPV types 6 and 11 with condyloma and low grade neoplasia; HPV types 16 and 18 were associated with advanced cervical neoplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

[Malpighian epithelia and papillomavirus infections]. / Epithéliums malpighiens et infections à papillomavirus.

Human papillomaviruses (HPV) are a large group of DNA viruses, with over 60 types identified to date, which can cause the development of benign tumors in the skin and mucosal squamous epithelia. Most of these tumors regress spontaneously but some, especially in the mucosal membranes, become malignant. HPV types with a high risk for inducing malignancies (e.g. 16 and 18) are the subject of increasing interest. HPVs are both host-specific and tissue-specific: some types preferentially infect specific epithelia, giving rise to lesions with distinct topographic characteristics. HPVs are difficult to study because they do not replicate in available in vitro models. In vivo, HPVs replicate well in epithelial cells undergoing terminal differentiation, e.g. in keratinized cells. Some 40 different types have been reported in epidermal keratinocytes, the most common being types 1 and 2 which produce large amounts of viral antigens and viral particles. In contrast, HPVs replicate poorly in the weakly keratinized squamous epithelia which line the digestive, respiratory, and genital tracts. Junctional epithelia, e.g. on the uterine cervix, are especially prone to HPV infection. The most prevalent HPV types in benign genital lesions are types 6 and 11, whose characteristic features include extrachromosomal DNA and production of only small amounts of viral antigens. The profound nuclear and cytoplasmic changes induced by HPVs lead to the formation of koïlocytes which are found mainly in the granular layer of epithelia and have been especially well described in the uterine cervix and vagina. HPV epithelial tumors are squamous cell carcinomas that often harbor HPV types 16 and 18; this is especially true of cervical intraepithelial neoplasias. These tumors contain the viral DNA, which may or may not be integrated into the cellular DNA, whereas viral antigens are lacking. The high incidence and broad spectrum of HPV types found in patients with acquired immunodeficiencies (e.g. under immunosuppressive therapy) suggest a key role for cellular immunity in the development of HPV-induced lesions. A number of cofactors, including UV radiations and smoking, as well as oncogene activation and anti-oncogene inactivation, may increase the risk of progression to malignancy.

[Cytologic examinations during bronchial endoscopy. Bronchial brushing and aspiration]. / Les examnes cytologiques lors de l'endoscopie bronchique. Brossage et aspiration bronchiques.

Bronchial cytology has become an essential diagnostic means in lung pathology for the diagnosis and typing of primary or secondary lung cancers. Bronchial cytology, initially consisting in the study of expectorations, has become increasingly interesting with the development of flexible fiberendoscopes, which allow the visual exploration of areas of the lungs as far down as the subsegmental bronchi. The effectiveness of this type of cytology applied to detected and located lesions accounts for the development of aspiration and brushing. However, the obtention of good cytological results primarily depends on the operator's and nurse's experience, as well as on the quality of the preparation of the slides and of their interpretation in the laboratory.