How to assess the best immunohistochemical panel in the diagnosis of malignant pleural mesothelioma in a pathology lab.

BACKGROUND: malignant pleural mesothelioma (MPM) is a rare tumor with a challenging diagnosis. Even if, clinical data are mandatory to suspect the diagnosis, the positive diagnosis is based on microscopic features. Morphologic features are still the port of call of the diagnosis but their non specific character and the multiplicity of differential diagnoses made the immunohistochemical markers mandatory for the diagnosis. Many antibodies with a positive diagnostic value including claretinin, mesothelin, WT1 and antibodies with a negative diagnostic value including TTF1, EMA, CD15 are recommended by the scientific societies. This is due to the diagnostic limits of every antibody which necessitate the association of multiple antibodies. In the diagnostic demarch, pathologists deal with different antibodies and clones. Even if many recommendations are available, every pathology lab has to experiment its own antibodies in order to optimize the routine diagnostic demarch especially in low-income country. Our aim was to assess the diagnostic value of different antibodies available in our lab and to recommend a decisional flowchart. PATIENTS AND METHODS: we conducted a retrospective study about 30 MPM diagnosed over a 20-year-period. The different techniques were realized manually. The different antibodies used were anti-calretinin, anti-Epithelial Membrane Antigen (EMA), anti-mesothelin, anti-Thyroid Transcription Factor 1 (TTF1), anti-ACE, anti-cytokeratin, anti-vimentin, anti-CD15, anti-cytokeratin 5/6, anti-bcl2, and anti-CD99 and anti-CD34 antibodies. The sensitivity and specificity of these antibodies were assessed. RESULTS: the microscopic exam concluded to an epithelioid mesothelioma (EM) in 17 cases, sarcomatoid mesothelioma (SM) in four cases and biphasic mesothelioma (BM) in nine cases. The immunohistochemical study was performed in all cases. A mean of eight antibodies was used in every case, average 4 to 20 antibodies. The immunohistochemical study was repeated from 2 to 5 times in 15 cases and concerned a mean of 3 antibodies per case. In EM and BM, the antibodies with positive predictive value and highest sensitivity were calretinin, EMA, cytokeratin, and vimentin reaching respectively a sensitivity of 86.2%, 89.7%, 92.9% and 89.3%. The most valuable antibodies with negative predictive value were TTF1, CD15 and ACE that presented a specificity reaching respectively 100%. In sarcomatoid mesothelima, the most sensitive antibody was the cytokeratin antibody. CONCLUSION: these results yielded to a diagnostic flowchart that we can use in routine practice and that is in accordance with the literature findings. Many diagnostic and technical pitfalls have to be known by pathologists when dealing with MPM.

Is CD10 antibody useful in the diagnosis of angioimmunoblastic T-cell lymphoma?

Angioimmunoblastic T-cell lymphoma (AITL) is a rare lymphoma accounting for less than 1% of non Hodgkin lymphomas. The lack of specific clinical and histologic features in addition to the multiplicity of morphologic mimickers makes the diagnosis challenging. Some authors reported the utility of CD10 antibody as a diagnostic marker. Our aim is to explore the value of this marker through a presentation of a study about four cases diagnosed over a six-year-period and a mini-review of the literature. We present a study of 4 cases of AITL diagnosed in lymph node biopsies. Microscopic findings showed in all cases early AITL characterized by a pattern I. The diagnosis of AITL was made in all cases based on the morphologic and immunohistochemical features. The CD3 antibody was expressed in all cases but CD10 antibody was negative in all cases. All the patients died and the initiation of a conventional chemotherapy wasn't possible in all cases because of the rapid course of the disease. Because of the small number of our cases, we can't rule out a possible diagnostic value of CD10 but its negativity in all our cases makes us doubt its sensitivity.

Genomic classification of lung cancer: toward a personalized treatment.

Lung cancer is the first cause of death by cancer worldwide. In Tunisia, its incidence has increased from 17.6 cases per 100.000 persons in 1997 to 27.6 cases per 100.000 persons in 2003. Its prognosis has been improving thanks to the emergence of molecular targets. The first one is represented by EGFR (Epidermal growth factor receptor), which marks this (2014) its tenth anniversary. many other targets have been identified. the most famous and useful of them the fusion gene ALK-EML4 but other oncogenic pathways have been implicated and under investigations including HER2, BRAF, MET, RET... The relevant challenges encountered are represented by the difficulty to achieve a consensual decisional and therapeutic algorithm, the absence of standardized diagnostic techniques and unavoidable occurrence of secondary resistance due to the activation of other oncogenic pathways that must be explored and targeted. In this update, we tried to present the major pathways implicated and the most relevant practice routine strategies.

[Carcinogenesis of non small cell lung cancer and therapeutic implications]. / Carcinogénèse des carcinomes bronchiques non a petites cellules et implications thérapeutiques.

The occurrence of a lung cancer is a consequence of a long-lasting process dealing with a transformation of a normal cell to a malignant one. The four steps of transformation reflect the genetic modifications of the cells. The molecular studies of pre-invasive lesions have already established a correlation between the lesion continuum and the multi-step carcinogenesis. Gradual genetic alterations are correlated with the increase of the cell's malignant potential. We tried to present the carcinogenesis of the lung non microcellular carcinomas and to highlight the main therapeutic targets.

[The new classification of lung adenocarcinomas according to the American Thoracic Society and the European Respiratory Society: new recommendations to improve management]. / La nouvelle classification des adénocarcinomes pulmonaires proposée par la Société Thoracique Américaine et la Société Respiratoire Européenne: De nouvelles recommandations pour une meilleure prise en charge.

BACKGROUND: Lung cancer represents a major public health problem.It represents the first cause of mortality by cancer in Tunisia. Its incidence reaches 40% of lung cancers. Its clinical, radiologic and molecular aspects have been improved inducing the necessity of a new classification which will consider the necessity of a multidisciplinary management. AIM: To highlight the new classification of lung adenocarcinomas and to present the major recommendations. METHODS: We tried to present the main recommendations of the American Thoracic Society and the European Respiratory Society of lung adenocarcinoma. RESULTS: This new classification identifies pre-invasive lesions represented by in-situ adenocarcinoma (the ancient bronchioloalveolar), the micro-invasive adenocarcinoma and invasive adenocarcinoma. The latter have been divided in sub-types according to the predominant architectural features. Thus, three groups of invasive adenocarcinoma with presumed different prognoses have been identified: the lepidic predominant adenocarcinoma which has a good prognosis, the micro-papillary and solid predominant adenocarcinomas which have a bad prognosis and the papillary and acinar adenocarcinomas which have an intermediate prognosis. All these entities have specific diagnostic features and criteria. These recommendations are available for biopsies and surgical resected specimen. CONCLUSION: The new classification of lung adenocarcinoma puts emphasis on the necessity of a multi-disciplinary management of these tumors in order to improve their prognosis. It identifies new entities with different prognoses that could justify specific modalities of treatment and follow up.