The diagnostic performance of micro-RNA and metabolites in lung cancer: A meta-analysis.

BACKGROUND: The diagnosis of lung cancer is based on the microscopic exam of tissue or liquid. During the recent decade, many biomarkers have been pointed to have a potential diagnostic role. These biomarkers may be assessed in blood, pleural effusion or sputum and they could avoid biopsies or other risky procedures. The authors aimed to assess the diagnostic performances of biomarkers focusing on micro-RNA and metabolites. METHODS: This meta-analysis was conducted under the PRISMA guidelines during a nine-year-period (2013-2022). the Meta-Disc software 5.4 (free version) was used. Q test and I2 statistics were carried out to explore the heterogeneity among studies. Meta-regression was performed in case of significant heterogeneity. Publication bias was assessed using the funnel plot test and the Egger's test (free version JASP). RESULTS: According to our inclusion criteria, 165 studies from 79 articles were included. The pooled SEN, SPE and dOR accounted, respectively, for 0.76, 0.79 and 13.927. The AUC was estimated to 0.859 suggesting a good diagnostic accuracy. The heterogeneity in the pooled SEN and SPE was statistically significant. The meta-regression analysis focusing on the technique used, the sample, the number of biomarkers, the biomarker subtype, the tumor stage and the ethnicity revealed the biomarker number (p = 0.009) and the tumor stage (p = 0.0241) as potential sources of heterogeneity. CONCLUSION: Even if this meta-analysis highlighted the potential diagnostic utility of biomarkers, more prospective studies should be performed, especially to assess the biomarkers' diagnostic potential in early-stage lung cancers.

Granular cell tumor of the lung and tracheobronchial tree: Two case-presentation with a review of the literature.

Pulmonary granular cells tumors (CGT) are rare tumors, that derive from Schwann cells. In the tracheobronchial and pulmonary tree, they remain a diagnostic challenge. There are no well-established criteria to differentiate between benign, atypical, and malignant GCT. Moreover, its real frequency in the respiratory tract is still unknown. Here, we represent 2 cases of bronchial and lung GCTs. We aim to highlight the frequency of all clinicopathological characteristics of this rare tumor in the tracheobronchial and pulmonary tree location based on our cases and the available literature in a large systematic review.

Utility of the cytological criteria in the diagnosis of malignant pleural mesothelioma: Making the bridge between theory and practice.

INTRODUCTION: The diagnosis of malignant pleural mesothelioma (MPM) depends on microscopic examination performed on pleural biopsies taken under thoracoscopy. However, it has recently been established that cytology presents a significant diagnostic contribution enabling an earlier diagnosis with a minimally invasive procedure. AIM: To assess the diagnostic value of consensual cytological features of MPM in the differentiation between adenocarcinoma, mesothelioma and reactive mesothelial cells in pleural liquid. METHODS: All available retrospective records from the computerized pathology database system and pathology reports were searched for malignant pleural effusion cytology specimens, over a 5-year period from January 2015 to February 2020. The cytological criteria based on the international Guidelines for cytopathologic diagnosis of epithelioid and mixed type of MPM were assessed. Malignant mesothelial cells, MNML and RL were considered as the gold standard. RESULTS: 189 pleural biopsies with their corresponding cytology specimens were available for review. Among the reviewed cytologies, the diagnoses of 21/189 pleural cytologies were modified. The highest sensitivities were attributed to cytoplasmic blebbing, hypercellularity and cell ball clusters. The most specific feature was the absence of extracellular granular hyaluronic acid cores in reactive cytology and the absence of intercellular openings in NMML cell clusters. Extracellular granular hyaluronic acid cores had the highest positive predictive value and the highest negative predictive value was attributed to the cytoplasmic blebbing in both reactive cytology and NMML. CONCLUSION: These results highlight the fact that no sign is pathognomonic of the diagnosis of MPM pointing out the necessity of immunocytochemical techniques in equivocal cases.

The use of biomarkers in the diagnosis of lung cancer.

Using a simple 10 to 20 milliliters of blood sample in order to make the diagnosis of lung cancer is the dream of every patient and practitioner. In fact, even if tissue samples or bronchial liquid represent the gold standard for microscopic diagnosis, using less invasive procedures represented the aim of many researches published in the literature. The utility of biomarkers has been widely reported in screening context, mainly in association to low dose CT-scan, or in therapeutic context in order to highlight therapeutic targets or to change treatment in a context of resistance to target therapies. The use of biomarkers in a diagnostic context has been recently highlighted in the literature. The authors aimed to present a general review of different biomarkers that could be used in the diagnosis of lung cancer.

Spindle cell hemangioma of the lung: An unusual presentation.

Spindle cell hemangioma (SCH) is a benign vascular tumour, first identified by Weiss and Enzinger in 1986. Habitually, the SCH affects almost exclusively the dermis and subcutaneous tissues of distal extremities. So far, only 2 cases have been described in the lung. We describe herein the third case of SCH occurring in the lung in a 47 year-old woman. The patient was successfully treated by right lower lobectomy. The histopathological and immunohistochemistry examination of the excised tumour leads to the definitive diagnosis. Our case is instructive by its different clinical and radiological presentation compared to the previous two cases.

Collision lung tumor associating typical carcinoid tumor to sclerosing hemangioma.

Collision tumors associating carcinoid tumor and sclerosing pneumocytoma have rarely been reported in the literature. The clinical presentation may be challenging especially in cases showing multiple and bilateral nodules. This case illustrates the association of both tumors diagnosed incidentally and illustrates a full spectrum of neuroendocrine lesions and sclerosing pneumocytoma. The authors present the case of a 52-year-old patient presenting an abdominal pain revealing a vesicular lithiasis and multiple pulmonary nodules. Radiologic follow-up of the asymptomatic lung lesions revealed the stabilization of a left lobe lesion with a disappearance of the other lesions. A lobectomy with a mediastinal lymph node curettage was performed. The microscopic examination revealed both tumor components associating a typical carcinoid tumor to a sclerosing pneumocytoma in association to lesions of diffuse neuroendocrine hyperplasia present in the peri-tumoral parenchyma. This case illustrates radiologic, gross, and microscopic features of a rare pulmonary tumor.

Mediastinal cysts : a 52-case retrospective study.

INTRODUCTION: mediastinal cysts are rare lesions developed from mediastinal structures. They may be acquired like thoracic duct cysts or lymphangiomas or congenital like the bronchogenic cysts, enteric cysts or celomic cysts. These cysts are rare and may cause diagnostic challenges. AIM: To assess the major characteristics of these cysts based on a single institution experience. METHODS: the authors performed a descriptive, retrospective study from January 2009 to March 2020 in a single institution. Cystic lesions taking birth from the mediastinum for which gross features, microscopic features were available were included. RESULTS: this study contained 52 mediastinal cysts that were completely resected and no patient presented complications after the surgical resection. The bronchogenic cysts were the most frequent and represented 57.69% of all lesions. Thymic cysts and pericardial cysts represented respectively 40.38% and 1.92% of the cases. The positive diagnosis was based on the microscopic exam. The final diagnosis was concordant with the radiologic findings in 15 cases reaching a rate of 28%. CONCLUSION: the diagnosis of mediastinal cysts is based on the microscopic analysis of the cystic wall. Pericardial cysts may be suspected based on their characteristic location in the cardiophrenic angle, thymic cyst may be evoked based on their location in the thymic region and bronchogenic cysts are mainly located in the middle mediastinum. Inspite of these most frequent locations, the cysts may be located in any part of the mediastinum and may be difficult to diagnose when the key diagnostic features are absent.

Prognostic impact of tumor-infiltrating lymphocytes in non-small cell lung carcinomas.

INTRODUCTION: Tumor-infiltrating lymphocytes represent a pivotal component of the host anti-tumor response. Thus, they considerably influence the evolution of cancers including non-small cell lung carcinomas. Even if, this important role is consensual, many discordant results are published in the literature about the prognostic role of the different populations of tumor-infiltrating lymphocytes. The aim of our work was to evaluate the prognostic impact of CD8+, CD4+, and forkhead box protein P3+ lymphocytes in the tumor microenvironment of non-small cell lung carcinomas. METHODS: We conducted a retrospective descriptive study, which included non-small cell lung carcinomas diagnosed in the department of pathology and followed in the medical oncology department of the same hospital between 2011 and 2015. Tumor-infiltrating lymphocytes were analyzed by the immunohistochemical method for forkhead box protein P3, CD4, and CD8. Intratumoral and stromal-labeled lymphocytes were quantified by manual counting at high magnification (×400). Forkhead box protein P3+/CD8+, forkhead box protein P3+/CD4+, and CD8+/CD4+ ratios were subsequently calculated. The prognostic value of tumor-infiltrating lymphocytes was assessed in respect of overall survival, recurrence-free survival, and relapse-free survival. RESULTS: Thirty-nine patients were included. The mean age of patients was 59.6 years. A complete surgical resection (p = 0.009), and a CD8/CD4 ratio (p = 0.008) were prognostic factors for overall survival. Complete surgical resection (p = 0.003), the forkhead box protein P3/CD8 (p = 0.005), and forkhead box protein P3/CD4 (p = 0.037) ratios were prognostic factors for recurrence-free survival. The CD8+ tumor-infiltrating lymphocytes rate (p = 0.037) was a prognostic factor for relapse-free survival with a threshold of 67.8/high power field. Microscopic subtype (p = 0.037) was a prognostic factor for relapse-free survival when only adenocarcinoma and squamous cell carcinoma were considered. In multivariate analysis, age (p = 0.004) and a CD8/CD4 ratio (p = 0.016) were independent predictors of overall survival. CONCLUSION: Despite the limitations of our study, our results confirm the prognostic value of tumor-infiltrating lymphocytes in non-small cell lung carcinomas and the importance of the combined quantification of their different subpopulations.

[Thymic hyperplasia: A study of 46 cases]. / Les hyperplasies thymiques.

BACKGROUND: Thymic hyperplasia presents as an anterior mediastinal mass and poses important diagnostic and therapeutic challenge. Two types of thymic hyperplasia are described: true hyperplasia and follicular hyperplasie. Literature data are peculiar concerning both entities. We aimed to describe the clinical and microscopic characteristics of thymic hyperplasia through a single institution experience during an 11-year-period. METHODS: Thymic hyperplasia diagnosed during the period between 2009 and 2020 were included. RESULTS: In all, 46 thymic hyperplasias were diagnosed. The 46 patients consisted in 33 women and 13 men with a mean age of 30 years. Microscopic diagnosis concluded to a follicular hyperplasia in 12 cases and a true thymic hyperplasia in 34 cases. The diagnosis of true thymic hyperplasia posed a diagnostic challenge with an involuted thymus in 1 case and a thymolipoma in 1 case. The confrontation with the clinical data allowed retaining the diagnosis. CONCLUSION: The diagnosis of thymic hyperplasia is based on microscopic features. The confrontation with clinical data and the measurements of the thymus according to the age allow to retain the diagnosis in most challenging cases.

An unusual clinical manifestation of a relapsed typical pulmonary carcinoϊd tumor.

Typical carcinoid tumors of the lungs carry an excellent prognosis after complete surgical excision. However, recurrence of these cancers remains poorly described in the literature and may occur many years after surgery. We report a case of carcinoid tumor of the lung. Clinical presentation and follow-up were uneventful. The 55 years old patient had got a surgical removal of a huge typical carcinoid tumor of the left lung. A left pneumonectomy with a mediastinal lymph node resection were performed. Thirteen years later, paraneoplastic acromegaly revealed a pulmonary and extrapulmonary recurrence of the tumor. We prescribed a chemotherapy regimen including Cisplatin and Etoposide. Endocrine paraneoplastic syndromes are related to mutations in specifically known genes. Several mutations may become a promising therapeutic target in the future. In the case of neuro-endocrine pulmonary tumors, authors described BCOR gene mutation as an oncogenic development inducer and an eventual generator of ectopic tumoral secretions. The more we get familiar with carcinoid tumor mutations, the closer we get to targeted therapy for non-resectable tumors.

Amenorrhea and elevated ßhuman chorionic gonadotropin of unknown origin: An unexpected location of choriocarcinoma.

Choriocarcinoma is a rare malignancy originating from trophoblastic cells that is known to arise from the placenta. In this report, we describe the case of a 28-year-old female who consulted for amenorrhea and elevated ßhCG mimicking a pregnancy of an unknown location, which ultimately turned out to be primary choriocarcinoma of the lung.

The place of the bronchoalveolar lavage in the diagnosis of interstitial lung disease: a descriptive and qualitative study.

BACKGROUND: Interstitial lung disease represents a challenge and consists in more than 200 entities. Their diagnoses are assessed through a multidisciplinary approach including pulmonologists, radiologists, pathologists and biologists. BAL analysis is useful mainly when clinical and radiological findings aren't suggestive of an etiology. Even if, the indication of BAL is consensual, its real place as a diagnostic mean remains non consensual. AIM: To describe the BAL findings and to analyse the perceptions of the pulmonologists, anaesthesiologists and pathologists implicated in the interpretation of the BAL data, that are related to the presentation and the validity of the results. METHODS: the authors performed a descriptive study about BAL results during an 8-year-period (2010-2018) and a qualitative study assessing the pulmonologists, anaesthesiologists and pathologists' opinions concerning the different results performed in the same institution. Two questionnaires were conceived with participation of different experts and satisfaction scores were calculated. RESULTS: 2508 BAL were recorded including 1320 women (53%) and 1188 men (47%) with a sex-ratio (H/F) of 0,9. The mean age of the patients was 51 years. The mean response delay was 3.25 days. An accurate diagnosis was retained in 24.3%. It consisted in infection evoked in 13.89% cases. Eosinophilic pneumonia was evoked in 0.35% cases. 15.01% cases presented erythrophagocytosis with a golde score>100 favouring active alveolar haemorrhage with occult alveolar haemorrhage. Lipoproteinosis was diagnosed in 2 cases. Adenocarcinoma was retained in 1.04% cases and lymphoma in 0.16% cases. Langerhans cell histiocytosis was confirmed in 1.51% cases. In the other cases, cellular profile was not specific evoking tuberculosis or sarcoidosis in 316 cases with a CD4/CD8 ratio superior to 1,6 and the diagnoses of tuberculosis or hypersensitivity pneumonia in 202 cases with a CD4/CD8 ratio inferior to 1,2. Concerning the questionnaire-based study, 50 pulmonologists and anaesthesiologists attributed a mean score of 7.96/10 (DS=0.55) concerning the presentation of the results and 9.28/15 (DS=0.77) concerning the quality and validity of the results. On the other hand, the mean satisfaction score rated by pathologists reached 24/40. CONCLUSION: BAL results could be helpful for the management of interstitial lung disease depending on the experience of pathologists and a good communication between pulmonologists, anaesthesiologists and pathologists.

Interobserver Agreement in Histopathological Subtyping of Malignant Pleural Mesotheliomas.

OBJECTIVE: Many recent studies are pointing out the heterogeneity between pathologists in the classification of malignant pleural mesotheliomas. Besides, they reported the prognostic impact of classifying epithelioid mesotheliomas according to the predominant architectural features and the nuclear grade. The authors assessed the interobserver and the intraobserver agreement of subtyping mesotheliomas between 2 pathologists used to thoracic pathology. MATERIAL AND METHOD: The observers reviewed all the slides of the malignant pleural mesotheliomas diagnosed during the period ranging from 2004 to 2017. The Cohen Kappa was performed in order to evaluate the agreement between both observers into classifying mesotheliomas, subtyping and grading epithelioid mesotheliomas. Two rounds of examination were planned with a delay period of one month. After the first round, the reviewers discussed the different difficulties and challenges they faced. All the statistic tests were performed using the SPSS software version 12.0. RESULTS: After the first round, a fair agreement between both observers was reported. After the second round, an improvement of the concordance rate with a good agreement in subtyping epithelioid mesotheliomas was noticed. Concerning the grading of mesotheliomas, the interobserver agreement was poor even after the second round examination. The intraobserver reproducibility of epithelioid mesothelioma subtyping was fair or moderate for both reviewers. The intraobserver agreement was poor concerning the grading of epithelioid mesothelioma. CONCLUSION: Integrating subtyping and grading of epithelioid mesotheliomas into a new classification necessitates an important training of the pathologists. The architectural features' definitions have to be clarified in order to avoid using own subjective opinions and habits by pathologists.

[Pulmonary blastomycosis]. / Blastomycose pulmonaire.

Blastomycosis is a rare fungal disease in Africa which is often due to inhalation of "Blastomyces dermatitidis". Pulmonary blastomycosis is the most common clinical manifestation which presents with a variety of clinical features, ranging from asymptomatic to rapidly fatal. We report the case of a Tunisian patient aged 35 years with no previous medical history, hospitalized with chronic cough, bilateral basithoracic pain, fever and weight loss. Clincal examination showed fever and left paravertebral subcutaneous swelling next to the tenth thoracic vertebra (T10). Chest imaging objectified bilateral alveolar and nodular opacities with excavations in some places. Sputum stain for Koch bacillus (BK) was negative (direct examination and culture). Bronchial fibroscopy was normal. Anatomopathological examination of dorsal mass biopsy revealed blastomycosis. The diagnosis was confirmed by cultures of the biopsic fragments of the mass. Antifungal therapy with itraconazole was started with clinical and radiological improvement. This case study highlights challenges in the diagnosis of blastomycosis in our country, in particular when lesions mimick tuberculosis; hence delayed therapy.

Classifying multiple lung cancers using morphological features: a meta-analysis.

Multiple lung cancers may be intrapulmonary metastases or multiple primaries. Management and prognosis of both entities are different and make the pathologist's role challenging. In fact, distinguishing both entities may be difficult especially when the tumors present the same microscopic subtype. The microscopic diagnoses of these tumors have been improved based on the 2015 WHO classification. The aim of the authors was to assess the diagnostic value of morphologic features in comparison to the gold standard test represented by molecular testing in the distinction between intrapulmonary metastases and multiple lung primaries. To retrieve all eligible articles, PubMed and Embase databases and Cochrane Library were comprehensively searched from 1999 to 2020 with limitation to French andEnglish language. The Meta-Disc software 5.1.32 was used to conduct this meta-analysis. The pSEN, pSPE, NLR, PLR, and DOR with the 95% confidence intervals were calculated. The area under the SROC was calculated based on the SEN and SPE of each study. Q test and I2 statistics were carried out to explore the heterogeneity among studies. P value <.1 for q test or I2 value >50% represented substantial between-study heterogeneity. Meta-regressions were performed to explore the sources of heterogeneity if necessary. Twelve eligible articles with 309 patients were included. pSEN was estimated to 65% with I-square estimated to 53%. pSPE reached 49% with I-square estimated to 56%. PLR was estimated to 1.23 with I-square estimated to 33%. NLR was estimated to 0.65 with I-square estimated to 23.1%. dOR was estimated to 2.13 [1.07-4.25] with I-square estimated to 26.5%. AUC was estimated to 0.63. The meta-regression analysis showed non-significant effect of the WHO classification, next-generation sequencing, or nucleotide-specific sequencing with p reaching respectively 0.38, 0.06, and 0.36. These results highlight that morphologic features may be useful in the diagnosis of multiple lung cancers especially when dealing with surgical specimen. The mild heterogeneity observed in this meta-analysis may be due to other covariates that were not described in the different articles including the sample nature.

Immunotherapy in lung cancer : point of view of the pathologist.

Immunotherapy in lung cancer has been playing a key role. This role can be explained by the gain in term of survival without progression. The place of the PD-L1 testing is important to know. Because of the multiple clones available and the differrent systems available in pathology labs, it was important to present the last recommendations concerning PD-L1 testing in order to make pathologists and treating doctors aware of the major principles and the different limits.

Evaluation and acceptability of concept maps as a learning tool in medical studies.

BACKGROUND: the use of concept maps (CM) in medical studies has been largely reported in the literature. In our context, we used to promote case-based-teaching methods but students aren't used to construct CM. AIM: To evaluate the acceptability of using CM by the students and the reproducibility of 2 methods of scoring, a holistic and an analytic one, associated to a master map in order to assess them. METHODS: the authors supervised a 2-session-case-based-learning performed in a department of pathology. One case dealing with a real story about a colon cancer diagnosed in the musician Debussy (http://fr.wikipedia.org/wiki/Debussy) was adapted and presented to the students. At the end of the first session, the students were encouraged to construct collectively a concept map. At the end of the second session, the students were asked to fulfill a questionnaire about their acceptability of the learning process. Besides, two raters scored all the concept maps using 2 different scoring methods associated to a master map. The reproducibility of both scoring systems was evaluated using the kappa coefficient. RESULTS: 31 students were enrolled in this study with a mean age of 21 years. The raters evaluated 8 CM. The kappa coefficient reached a value of 1 in the holistic scoring and a value of 0.46 in the hierarchical scoring indicating respectively a very strong and a moderate agreement between evaluators. 15 students reported their satisfaction about the use of CM collectively. 10 students expressed their will to use CM individually, 17 students felt that using the CM collectively made them feel to belong to a group but without expressing their own knowledge and reflecting their progress. CONCLUSIONS: our study highlighted the acceptability of using concept maps in medical studies and the possibility of reaching valid and reproducible scoring methods especially when associating a master map.

Impact on survival of nuclear atypia in epithelioid malignant mesothelioma.

INTRODUCTION: Malignant pleural mesothelioma is a rare tumour with a bad prognosis. The only consensual prognostic factors are represented by the stage and the histologic type. Concerning the histologic type, epithelioid mesothelioma is known to have better prognosis in comparison with the sarcomatoid and biphasic types. Epithelioid mesotheliomas have been reported to be a heterogeneous prognostic group. Our aim was to assess the impact on the survival of different characteristics of epithelioid mesothelioma, including nuclear atypia, mitotic count, MIB-1 index, inflammatory host response, stromal desmoplasia, necrosis, vascular emboli and invasion depth. MATERIAL AND METHODS: We performed a study of survival of 30 malignant pleural mesotheliomas according to the different parameters studied. RESULTS: The study included 26 women and 4 men. The mean age of the patients was 61 years. The microscopic exam concluded to an epithelioid mesothelioma in 17 cases, sarcomatoid mesothelioma in 4 cases and biphasic mesothelioma in 9 cases. The 17 cases of epithelioid mesothelioma developed severe nuclear atypia in 6 cases and mild nuclear atypia in 11 cases. The mitotic count and the MIB-1 score were respectively inferior to 5 mitoses/50 HPF and inferior to 10% in 11 cases and were superior to 5 mitoses/50 HPF and superior to 10% in 6 cases. No vascular emboli were recorded. Tumour necrosis was reported in 1 case. The inflammatory host response was severe in 4 cases and mild in 13 cases. The tumoral stroma was desmoplastic in 4 cases. The invasion depth was superior to 0.5mm in 16 cases. The median overall survival amounted to 180 days. Nuclear atypia was the only feature that had impact on survival in the group of epithelioid mesothelioma. CONCLUSION: Our results highlight the correlation of nuclear atypia with survival.