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.

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.

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.

[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.

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.

Interstitial lung disease: Elementary lesions and diagnosis.

An effective approach to the diagnosis of interstitial lung diseases requires a standardized method of evaluation with a structured analysis, beginning with scanning microscopy and proceeding to a more detailed assessment. This article is structured around the histologic patterns defined by Leslie that facilitate this process. They include acute injury, fibrosis, cellular infiltrates, airspace filling, formation of nodules, and minimal changes. Illustrations of all of these patterns are provided, together with a discussion of the disease entities that manifest them.

[The 2015 classification of lung adenocarcinomas: Reproducibility in a Tunisian department specialised in thoracic pathology]. / La nouvelle classification 2015 des adénocarcinomes pulmonaires : reproductibilité au sein d'un service Tunisien spécialisé en pathologie thoracique.

INTRODUCTION: The new classification of lung cancer contains modifications of terminology and a new subdivision of the tumors with the most relevant modifications concerning the group of adenocarcinomas. The latter has been increasing and represents nowadays the most frequent type. Our aim was to assess the reproducibility of the new classification through the experience of a Department of Pathology specialized in thoracic pathology. METHODS: Our study included initially 106 cases diagnosed as adenocarcinomas and reviewed by 2 pathologists and 1 referee. Five cases were ruled out because they corresponded to squamous carcinoma according to the immunohistochemical findings. The same number of slides was reviewed without a limit of time. Statistical analysis was performed using the SPSS software. The Kappa index was estimated and a second coefficient: rho was analyzed. RESULTS: A total concordance was noticed in 82 cases (81.2%) and a discordance was noticed in 19 cases (18.8%). The agreement degree was good with an index Kappa estimated to 0.743 and a rho index reaching 0.763. CONCLUSION: Our study highlights the good reproducibility of the 2015 WHO classification of lung cancer among a trained team. Whereas, in order to improve the reproducibility of such a classification, even in non specialised departments, a training of the pathologists is necessary in order to highlight the prognostic impact of this classification.

[Which technique should be used in the phenotyping of lymphocytic alveolitis: Immunocytochemistry or flow cytometry]. / Quelle technique adopter pour le phénotypage des alvéolites lymphocytaires : immunocytochimie ou cytométrie en flux ?

BACKGROUND: Diffuse interstitial pneumonias are considered as a group of multiple affections characterized by challenging diagnoses because of the lack of specific clinical signs. Radiologic investigations highlight the diagnoses in most of the cases but bronchoalveolar lavage plays a key role in the diagnostic diagram. We aim to compare the immunocytochemical technique and the flow cytometry in the phenotyping of lymphocytic alveolitis. METHODS: We described a series of 32 lymphocytic alveolitis, which were analyzed using immunocytochemistry and flow cytometry. RESULTS: We found a good reproducibility between the immunocytochemistry performed on smears and cytoblocks (kappa=0.7) and a poor reproducibility between immunocytochemistry and flow cytometry (kappa=0.35). CONCLUSION: Our study emphasized on the poor reproducibility between immunocytochemistry and flow cytometry. Further studies about the reliability of both techniques are needed especially in discordant cases.

The diagnostic importance of the bronchoalveolar lavage in lymphocytic alveolitis.

Multidisciplinary concertation is mandatory in order to assess interstitial pneumonias. The study of the bronchoalveolar lavage helps evoking a diagnosis according to the lavage profile. In lymphocytic alveolitis, immunocytochemistry, or in flux cytometry are necessary in order to identify the different clusters of lymphocytes implicated. Our objective was to evaluate the profile of 31 lymphocytic alveolitis using 2 different techniques which are the immunocytochemistry and the in flow cytometry in order to evaluate the efficacy of each technique and to compare the different results to the final diagnoses. We describe a retrospective study about 31 patients admitted to our hospital in order to explore an interstitial pneumonia between January and July 2014. Bronchial endoscopy and bronchoalveolar lavage were performed in all cases. The sensitivity of the in flow cytometry was estimated to 53% and its specificity reached 33%. On the other hand, the immunocytochemistry presented a specificity of 42.8% and a sensitivity of 42.8%. The final diagnoses retained consisted in sarcoidosis in 12 cases, infectious pneumonia in 10 cases, hypersensitivity pneumonia in 3 cases, cryptogenic pneumonia in 3 cases, idiopathic fibrosis in 2 cases, and adenocarcinoma in 1 case. The relevance of both techniques depends on many factors. They necessitate an available material, well-trained technicians, and experimented pathologists.

Synchronous mantle cell lymph node lymphoma and pulmonary adenocarcinoma: a case report with literature review.

BACKGROUND AND AIMS: Coexistence of mantle cell lymphoma and lung adenocarcinoma is extremely rare. The aim of this study is to present the first case of incidental discovery of primary lung adenocarcinoma associated to lymph node mantle cell lymphoma. METHODS: A 45 year-old man, admitted for inguinal mass appeared since three months. Physical examination showed a 1 cm axillary and 3 cm inguinal adenopathies which were hard and fixed. A biopsy of inguinal mass revealed mantle cell lymphoma. Assessment of disease extension found a right superior lobe tumor with mediastinal lymphadenopathies. Fibreoptic bronchoscopy was normal. A fine needle biopsy of lung tumor was performed to determinate the nature of the pulmonary lesion. Histopathological findings were consistent with primary poor differentiated pulmonary adenocarcinoma with TTF-1 expression. A first mediastinoscopy was realized to verify mediastinal lymphadenopathies; frozen section showed a mantle cell lymphoma. A right lobectomy was then performed confirming the diagnosis of lung adenocarcinoma. Then, the patient was treated for the mantle cell lymphoma by 6 cures of alternating RCHOP and RDHAP (dexamethasone, high-dose Ara-Cytarabine and cisplatin) regimens followed by autologous stem cell transplantation. RESULTS: The patient died because of treatment complications 3 years after diagnosis. CONCLUSION: Progresses are necessary to understand the pathogenesis of of synchronous occurrence of both diseases.

[Acquired hypogammaglobulinemia associated with thymoma: Good syndrome]. / Hypogammaglobulinémie acquise associée au thymome: le syndrome de Good.

Good syndrome (GS) is defined as the association between thymoma and immune deficiency. It is often complicated by broncho-pulmonary bacterial infections and rhinosinusitis. This disease accounts for only 5% of all parathymic syndromes. These recurrent respiratory infections can cause bronchiectasis associated with Good syndrome. We report the case of a 52-year old woman hospitalized for non resolutive infectious pneumonitis. Chest CT scan showed bronchiectasis associated with thymoma confirmed by biopsy. The discovery of hypogammaglobulinemia allowed the diagnosis of Good syndrome.

Diagnostic value of the bronchoalveolar lavage in interstitial lung disease.

Background The bronchoalveolar lavage (BAL) cellular analysis is an invasive method of exploration of the lung. Its diagnostic value in interstitial lung disease (ILD) is integrated to a multi-disciplianry approach implicating clinicians, radiologists and pathologists. Aim We targeted to evaluate the diagnostic value of the BAL. Methods We reported a retrospective study about patients hospitalized for an ILD since the 1st January 2011 to the 31th December 2013. Thirty three patients were admitted in the Department of Pulmonology and the BAL analyses were studied in the Department of Pathology of the same hospital. The different cell patterns were compared to the final diagnostics. Results our study contained 4 non specific interstitial pneumonia (NSIP), 10 usual interstitial pneumoniae (UIP), 4 organizing pneumoniae (COP), 8 sarcoidosis, 2 hypersensitivity pneumonitis, 3 infectious pneumonitis, 1 lymphoma and a pulmonary adenocarcinoma. We considered positive results those that were compatible with the final diagnosis. The profile lavage was typical in 1 NSIP, 3 UIP, 3 COP, 1 hypersensitivity pneumonitis, 6 sarcoidosis, 3 infectious pneumonitis and 1 adenocarcinoma. Among the 17 cases with an atypical profile lavage, radiological features were diagnostic in 10 cases. This finding highlights the fact that 7 cases/ 33 presented simultaneously an atypical profile lavage and non specific radiological findings Conclusion Our results put emphasis on the diagnostic value of BAL especially when it is integrated to a multi-disciplinary approach. Its value in the follow up, the evaluation of the activity of the disease and the prognosis is being more and more reported.

Clinicopathologic and prognostic factors of thymoma in Tunisia.

BACKGROUND: although rare, thymomas are the most common tumors of the thymus in adults. They represent about 20% of all mediastinal tumors. AIM: the aim of this study is to present clinicopathological features of thymomas in Tunisia and analyse the prognostic factors. METHODS: From 1993 to 2004, clinical data of 40 cases of thymomas were compiled retrospectively. Microscopic slides were reviewed and reclassified according to the WHO classification of thymic tumors 2004. Clinical staging adopted was Masaoka system. Analysis of survival was determined by Kaplan-Meier method and log-rank test was used to compare survival curves. These statistical analyses were performed by SPSS. RESULTS: they were 23 women and 17 males of ages ranging from 14 to 76 years (mean age 51 years). The distribution of histological WHO types was: 1 type A, 7 type AB, 6 type B1, 17 type B2, 6 type B3, 2 cases of micronodular thymoma with lymphoid stroma and 1 case of metaplastic thymoma. According to Masaoka stage, 10 patients were in stage I, 11 stage II, 9 stage IIIa, 4 stage IIIb, 5 stage Iva and 1 stage IVb. The average overall survival was 56 months. Univariate analyses showed that Masaoka stage, completeness surgical resection and age were prognostic factors whereas in multivariate analysis, age was the only prognostic factor. Neither myasthenia gravis nor histological WHO subtypes had effect in survival. CONCLUSION: masaoka stage, completeness surgical resection and age are the prognostic factors predicting survival in our series.

The inter-connection between fibrosis and microvascular remodeling in idiopathic pulmonary fibrosis: Reality or just a phenomenon.

BACKGROUND: Idiopathic pulmonary fibrosis is the most frequent interstitial disease with the worst prognosis. It is characterized by an uncontrolled fibrosis which is difficult to manage. The pathogenesis of this disease remains unclear with many theories resulting in multiple target therapies. The relation between fibrosis and vascular remodeling has been debated in the literature with different results that may seem contradictory. AIM: We target to evaluate the connection between fibrosis and vascular remodeling in usual interstitial pneumonia. MATERIAL AND METHODS: 26 cases of idiopathic pulmonary fibrosis were reviewed by 2 pathologists and the diagnosis of UIP was retained according to the American Thoracic Society's criteria. Fibrotic changes and vascular remodeling were evaluated blindly. The fibrotic changes were classified as severe, intermediate and mild. Vascular occlusion was graded in 4 grades extending from medial hypertrophy (grade 1) to plexiform lesions of the vascular wall (grade 4). RESULTS: We noticed that severe degrees of fibrosis were correlated with severe grades of vascular obstruction. In fact, our 26 cases were classified as severe fibrosis in 11 cases with grade IV vascular lesions in 6 cases, intermediate fibrosis in 12 cases with grade II vascular lesions in 8 cases and mild fibrosis in 3 cases with grade I vascular lesions in all cases. CONCLUSION: Many theories have been reported concerning the UIP's pathogenesis. Recently, many authors reported that the primum movens of these lesions was an epithelial/endothelial injury which induces uncontrolled fibrosis and microvascular remodeling using different pathways. This puts emphasis on the necessity of multi-target therapies in order to improve the management of this fatal disease.

About thymic carcinomas: challenges in diagnosis and management.

BACKGROUND: Thymic carcinomas are rare tumors with a challenging diagnosis. Our aim was to report our 17-year experience of these tumors and to highlight the challenges encountered and the main differential diagnoses ruled out. METHODS: We studied 12 (92%) men and 1 (7.7%) woman with a mean age of 37 years (range 15-60 years). All patients were symptomatic, with chest pain representing the most frequent symptom. Radiology revealed anterior mediastinal masses in all cases, with either infiltration of the adjacent organs or pulmonary parenchymal metastases. RESULTS: The diagnosis was made on surgical biopsies in 12 cases and a lymph node biopsy in one. Microscopic examination revealed squamous carcinoma in 3 cases, synovial sarcoma in 1, mucinous adenocarcinoma in 1, undifferentiated carcinoma in 2, clear cell carcinoma in 1, lymphoepithelioma-like carcinoma in 2, atypical carcinoid tumor in 2, and sarcomatoid carcinoma in 1. Total surgical resection was possible in one patient after neoadjuvant chemotherapy and radiotherapy. Follow-up was possible in only 6 patients, and the mean survival reached 13 months. CONCLUSION: In spite of the lack of follow-up information, this study demonstrates the poor outcome associated with these tumors and the need for standardized treatment.

Malignant glomus tumor of trachea: a case report with literature review.

Glomus tumors of the trachea are extremely rare and generally benign, with very few cases of malignant transformation reported in literature. We present the case of a 74-year-old man explored for cough and dyspnea. Bronchoscopy showed a polypoid mass arising from the posterolateral tracheal wall. Computed tomography demonstrated a mid-tracheal tissular mass obliterating the tracheal lumen. Resection and anastomosis of the trachea were performed. The histological and immunohistochemical findings were consistent with malignant glomus tumor.