[Surgery for small-cell lung cancer]. / Chirurgie du cancer pulmonaire à petites cellules.

Small-cell lung cancer (SCLC) is a high-grade neuroendocrine carcinoma, metastatic at the time of initial diagnosis in 70% of cases. Within the 30% of localised tumours only 5% of patients are eligible for surgical treatment according to the recommendations of learned societies. These recommendations are mainly based on old phase II and III randomised prospective trials and more recent registry studies. Surgical care is only possible within a multimodal treatment and essentially concerns small-sized tumours without involvement of hilar or mediastinal lymph nodes. As with non-small cell lung cancer (NSCLC), lobectomy with radical lymph node removal is the recommended procedure to achieve complete tumour resection. Patient selection for surgery includes age, performance status and comorbidity factors. Adjuvant chemotherapy combining Platinum salts and Etoposide for resected stage I tumours is recommended by ASCO, ACCP and NCCN. The precise sequence of neo-adjuvant or adjuvant treatments remains controversial because of the large heterogeneity in clinical practice reported in the studies and the context at the time of SCLC discovery. The 5-year survival rate of patients with early stage disease (pT1-2N0M0) treated by lobectomy and adjuvant chemotherapy is between 30% and 58%, which validates the primary place that surgery must have in these early forms. There is certainly little or even no place for such a therapeutic sequence in locally advanced stages (T3-T4 or N2). However, the stage heterogeneity, as in NSCLC, makes final conclusions difficult. In fact, some registry studies with pairing scores reported a median survival of more than 20 months in N2 SCLC. So, all files of SCLC must be evaluated in a multidisciplinary meeting in order to find the optimal solution for patients with rare and heterogeneous tumours.

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.

Chemoradiotherapy efficacy is predicted by intra-tumour CD8+/FoxP3+ double positive T cell density in locally advanced N2 non-small-cell lung carcinoma.

BACKGROUND: Radiotherapy is a standard of care for locally advanced stage III N2 non-small-cell lung carcinoma (NSCLC) combined with surgery/chemotherapy. Radiotherapy is hypothesised to induce tumour immunogenic cell death, to release neoantigen resulting in intra-tumoural immune infiltration and abscopal effect. Conversely, it has not been demonstrated if immune cells are necessary to drive radiotherapy efficacy and predict patient's survival. PATIENTS AND METHODS: We retrospectively analysed tumour samples and clinical data from 113 patients, 89 resected (PORT) and 24 non-resected (DRC) N2-NSCLC treated with chemotherapy and radiotherapy (same radiotherapy department from 2002 to 2015). The immune environment was characterised with in situ multiplex staining (CD8, FoxP3, PD-L1 and cytokeratin) and correlated with clinical data and survival. RESULTS: High density of CD8+ T cells was associated with OS (p = 0.04, HR = 1.93 [0.99-3.78]) and DFS (p = 0.003, HR = 2.42 [1.31-4.47]) in the PORT. High density of CD8+/FoxP3+ double positive cells was associated with OS (p = 0.01, HR = 1.97 [1.11-3.48]) in the whole population, with OS (p = 0.05, HR = 1.92 [0.98-3.74]) and PFS (p = 0.03, HR = 1.83 [1.03-3.23]) in the PORT without reaching significance for the DRC. Intermediate PD-L1 expression in tumour cells (TPS = 1-49%) was associated with a higher survival in the PORT. CONCLUSIONS: Intra-tumoural CD8+ T cell and particularly CD8+/FoxP3+ double positive T cell densities predict survival in stage III N2-NSCLC suggesting the need for a pre-existing intra-tumour immunity to mediate the action of radiotherapy. Density of CD8+/FoxP3+ cells was the best predictor of patient's survival in multivariate analysis and could represent a biomarker of radiotherapy efficacy.

Banff Lung Report: Current knowledge and future research perspectives for diagnosis and treatment of pulmonary antibody-mediated rejection (AMR).

The Lung session of the 2017 14th Banff Foundation for Allograft Pathology Conference, Barcelona focused on the multiple aspects of antibody-mediated rejection (AMR) in lung transplantation. Multidimensional approaches for AMR diagnosis, including classification, histological and immunohistochemical analysis, and donor- specific antibody (DSA) characterization with their current strengths and limitations were reviewed in view of recent research. The group also discussed the role of tissue gene expression analysis in the context of unmet needs in lung transplantation. The current best practice for monitoring of AMR and the therapeutic approach are summarized and highlighted in this report. The working group reached consensus of the major gaps in current knowledge and focused on the unanswered questions regarding pulmonary AMR. An important outcome of the meeting was agreement on the need for future collaborative research projects to address these gaps in the field of lung transplantation.

[Mucoepidermoid tracheo-bronchial tumors in adulthood. A series of 22 cases]. / Tumeurs muco-épidermoïdes trachéo-bronchiques chez l'adulte. À propos d'une série de 22 cas.

INTRODUCTION: Mucoepidermoid tumours (TME) are rare tumours arising from the submucosal glands of the tracheobronchial tree. The majority of these tumours develop in a benign fashion but some of them are malignant. The latter can be easily mistaken for adenosquamous carcinomas. PATIENTS AND METHOD: We have reviewed 22 patients suffering from TME observed over a period of 25 years. Two arose from the trachea and 20 from the cartilaginous bronchi; 12 of these tumours had macroscopic and histological criteria of low-grade malignancy, 4 had macroscopic and 6 macroscopic and microscopic criteria of high grade malignancy. RESULTS: Prognosis of the latter was very poor and no survival observed after 6 years follow-up, a behavior similar to that observed in non-small cell lung carcinomas and adenosquamous carcinomas. CONCLUSION: The best treatment of these orphan tumours remains surgery.

[Diaphragmatic bronchogenic cyst: an exceptional location]. / Kyste bronchogénique diaphragmatique: une localisation exceptionnelle.

A 64-year-old man complained of persistent dyspnea and bilateral basi-thoracic pain with shoulder irradiation. Chest computed tomography revealed a heterogeneous left diaphragmatic mass, while magnetic resonance imaging showed hypo-T1 and hyper-T2 signal. Positron-emission tomography did not show any hypermetabolism. Video-assisted thoracic surgery was decided. At inspection, tumour appeared within the posterior costal part of the diaphragmatic muscle. Tumour resection was extended to a 8-cm-long portion of the lumbar part of diaphragm. Diaphragm was repaired with non-absorbable interrupted sutures. Postoperative course was uneventful. Final pathology revealed an intra-diaphragmatic bronchogenic cyst, which is an exceptional condition. Primary diaphragmatic tumours are very rare and preoperative diagnosis cannot be affirmed. Embryologic hypotheses (migration along the oesophagus or envelopment within diaphragmatic precursors of an abnormal supernumerary lung bud) including recent molecular findings of deregulated pathways (fibroblast growth factor-10 and NOTCH) are discussed.

[Typical pulmonary carcinoid tumor: evolution, related prognostic factors and lymphadenectomy indications]. / Tumeurs carcinoïdes typiques du poumon : évolution, critères de malignité et indications du curage ganglionnaire.

The bronchopulmonary typical carcinoid tumors are often considered as non-metastatic neoplasia. The appearance of metastases is observed in 10% of the cases. We detail here studies based on the identification of the risk factors of metastases occurrence to adapt the lung surgery and lymph node dissection to the individual patient risk.

[Impact of induction therapies on pathology and outcome after surgical resection of non-small lung cancer: a 30-year experience of 859 patients]. / Traitements néoadjuvants : évaluation d'une pratique couramment indiquée en RCP.

UNLABELLED: The management of localized non-small cell lung cancer (NSCLC) has been modified over the last decades, with induction therapies being increasingly recommended as a prerequisite to surgical resection. However, the relative impact of chemo- and chemoradiotherapy on tumours' pathology and patients' survival is still discussed. METHODS: We set a retrospective study including every patient who underwent surgical resection for NSCLC in 2 French centres from 1980 to 2009. We then compared the tumours' pathology and patients' survival according to the use of induction chemotherapy (group 1) or induction chemoradiotherapy (group 2). RESULTS: There were 733 patients in group 1 and 126 patients in group 2. In group 1, 669 patients (91%) had platinum-based chemotherapy, for 2 to 3 cycles in 564 cases (77%). In group 2, chemoradiotheray was concomitant in 68 patients (54%), and sequential in 58 patients (46%). As compared with group 1, group 2 was characterized by younger age (mean 59.8±9.5 vs 56.4±9.6, respectively, P<.001), a higher rate of tumours deemed unresectable before induction treatment (25% vs 44%, P<.001), and a higher proportion of T4 (25% vs 44%, P<.001) or N2 diseases (56% vs 69%, P=.005). The type of resection, postoperative complications, and postoperative mortality were not significantly different between groups. On final pathologic report, as compared with group 1, there were more N0 and N1 disease in group 2 (N0: 43% vs 58%, P=.002; N1: 22% vs 10%, P=.002) while the rate of N2 disease was comparable (34% vs 32%, P=ns). The median, 5-, and 10-year survivals were 28 months, 35%, and 21% for group 1, and 29 months, 36%, and 23% for group 2, respectively (P=ns). CONCLUSION: As compared with induction chemotherapy, induction chemoradiotherapy was performed in more advanced NSCLC, and resulted in better downstaging, similar postoperative course, and comparable long-term outcome after surgical resection.

[Lymphatic spread of lung cancer: anatomical lymph node chains unchained in zones]. / Extension lymphatique du cancer du poumon : une anatomie enchaînée dans des zones.

Lung cancer is characterized by its lymphophilia. Its metastatic spread mainly occurs by tumor cells lymphatic drainage into the blood circulation. Initially, the lymph node TNM classification was based on clinical and therapeutic considerations, particularly concerning N2 involvement. The goals were to avoid futile exploratory thoracotomies without lung resection, to provide more accurate data from mediastinoscopy, and to take into account the radiation therapy fields. Since 1997, the international lymph node classification was more used to analyse the disparities within N1 and N2 groups. However, this attempt did not succeed in clarifying the lymphatic metastazing process, and was not progressing any more. Anatomy not being considered, it did not permit to grasp the anatomical and physiological significances of N2 and N3 involvement. In effect, this classification is now confined in zones and is lacking the anatomical and physiological descriptions that characterise the lymphatic pathways draining the lungs and their tumoral pathology. The stations proposed in numbers in cartographies should have gained in accuracy and in prognostic value if they had been expressed in their anatomical counterparts.

[Molecular profiling of non-small cell lung cancer]. / Biologie moléculaire et prise en charge des patients atteints d'adénocarcinomes du poumon.

The management of locally advanced and metastatic non-small cell lung cancer has been revolutionized thanks to recent progress in pathology and molecular biology. The first molecular subgroup is defined by activating mutations of the epidermal growth factor receptor (EGFR), and a dramatic response to specific tyrosine kinase inhibitors. Since then, multiple genetic alterations (KRAS, HER2, BRAF, PIK3CA, ALK, ROS, RET…) have been identified as potential target of novel therapies, and molecular profiling has become common practice. This review focus on the molecular alterations associated with non-small cell lung cancer, including molecular profiling and response to targeted therapies.

[Lymphatic extension and lymphangiogenesis in non-small cell lung cancer]. / Extension lymphatique et lymphangiogenèse dans les cancers pulmonaires non à petites cellules.

Lymph node metastasis is a major adverse prognostic factor of malignant tumors, including non-small cell lung carcinoma (NSCLC). However the characterization of tumor associated lymphatic vessels and lymphangiogenic mediators in NSCLC are recent and their prognostic role is debated. Lymphatic vascular invasion (LVI) appears like a robust adverse prognostic factor when reported in NSCLC. This parameter should be better standardized and could be of use in adjuvant therapy indications. Moreover, anti-lymphangiogenesis therapies are currently under investigation and may become part of the anti-cancer strategy.

Within 1 h, HIV-1 uses viral synapses to enter efficiently the inner, but not outer, foreskin mucosa and engages Langerhans-T cell conjugates.

Although circumcision reduces male acquisition of human immunodeficiency virus type-1 (HIV-1) by 60%, the initial mechanisms of HIV-1 transmission at the foreskin remain elusive. We have established two novel and complementary models of the human adult foreskin epithelium, namely, ex vivo foreskin explants and in vitro reconstructed immunocompetent foreskins. In these models, efficient HIV-1 transmission occurs after 1 h of polarized exposure of the inner, but not outer, foreskin to mononuclear cells highly infected with HIV-1, but not to cell-free virus. HIV-1-infected cells form viral synapses with apical foreskin keratinocytes, leading to polarized budding of HIV-1, which is rapidly internalized by Langerhans cells (LCs) in the inner foreskin. In turn, LCs migrate toward the epidermis-dermis interface to form conjugates with T cells, thereby transferring HIV-1. Seminal plasma mixed with cervicovaginal secretions inhibits HIV-1 translocation. This set of results rationalizes at the cellular level the apparent protective outcome of circumcision against HIV-1 acquisition by men.

Diffuse EGFR staining is associated with reduced overall survival in locally advanced oesophageal squamous cell cancer.

Squamous cell carcinoma of the oesophagus (SCCO) is still a pathology of bad prognosis. Specific therapies are now developed against epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2, c-kit receptor (CD117), vascular endothelial growth factor (VEGF) and p53 protein. This study was aimed at assessing their expression in a large series of SCCO, as well as their potential therapeutic interest in this pathology. Immunohistochemical expression of these factors was assessed retrospectively in 107 cases of SCCO with primary surgery, as well as their relationships to recurrence, metastasis and overall survival on a long-term follow-up. Human epidermal growth factor receptor 2 and CD117 were expressed in less than 3% of the cases. Epidermal growth factor receptor and p53 were overexpressed in 68.2 and 66.4% of the cases, and VEGF in 38.3%. Epidermal growth factor receptor overexpression was significantly related to vascular invasion (P=0.023). Its diffuse positivity was significantly related in multivariate analysis to higher local recurrence (P=0.006) and lower overall survival (P=0.003), in a subgroup of patients of poor outcome who had received postoperative adjuvant treatment. These results highlight the great potential prognostic and therapeutic interest of evaluating EGFR diffuse positivity in locally advanced SCCO.