[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.

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.

About the association of a lecture-based learning and team-based learning in a pathology course.

BACKGROUND: Team-based learning (TBL) is an active method of learning aiming to the promotion of the teamwork and improvement of critical thinking. Students of our university weren't used to TBL. We tried to implement a learning session combining TBL and lectures. METHODS: The study included residents in pathology. The learning scenario consisted in lectures followed by a TBL. Four steps characterized the learning scenario: an individual preparation based on resources made available in the internet by the tutors, an individual readiness assurance test (iRAT) performed during the first 15minutes of the session, a team readiness assurance test (tRAT) and a peer evaluation step. The final students' score was calculated by summing score A (iRAT weighted to 70%) and score C (derived by multiplying the score B [tRAT weighted to 30%] with percentage of peer evaluation). Anova test and Pearson coefficient were used to perform the statistical analyses. RESULTS: Forty-one residents were included. We assessed an improvement of the tRAT in comparison to iRAT. The only correlations established were between the iRAT and the tRAT and the tRAT and the students' scores. CONCLUSION: Implementing TBL in medical universities may induce an improvement of the individual knowledge and a change in behaviourism.

About the diagnostic value of BAP-1 antibody in malignant pleural mesothelioma: a meta-analysis.

BACKGROUND: The positive diagnosis of MPM is based on morphologic features coupled with immunohistochemical findings. Many antibodies have been published especially in order to differentiate between malignant tumors and atypical mesothelial hyperplasia. BAP-1 is a BRCA1-binding protein whose loss of expression was frequently reported in MPM. Our aim was to assess the diagnostic value of this antibody in comparison to the most sensitive diagnostic antibody represented by the calretinin antibody. METHODS: We performed a meta-analysis using the Meta-Disc software 5.1.32. RESULTS: According to our inclusion criteria, 19 studies with 11 studies dealing with BAP1 antibody and 8 studies dealing with calretinin antibody were included. The SEN of BAP 1 and calretinin antibodies was respectively estimated to 54.6% and 86.5%. The SPE reached respectively 95.7% and 76.6%. The dOR was estimated respectively to 23.664 and 38.8. The I-square revealed a heterogeneity of the parameters studied. The metaregression analysis revealed as covariates the amplification system and the histologic subtype as causing effects of heterogeneity for BAP1 antibodies and histologic subtype and chromogene as causing effects of heterogeneity for calretinin antibody. CONCLUSION: This meta-analysis revealed that BAP1 antibody should be associated with more sensitive antibodies in order to assess the diagnosis.

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 utility of bronchoalveolar lavage in the evaluation of interstitial lung diseases: A clinicopathological perspective.

Bronchoalveolar lavage (BAL) is a noninvasive and well-tolerated procedure that is performed with a fiberoptic bronchoscope in the wedged position within a selected bronchopulmonary segment. After it was introduced to clinical practice, BAL rapidly gained acceptance in a large number of centers as a procedure that could be applied to the clinical evaluation of patients with various pulmonary disorders, especially the group of interstitial lung diseases (ILD). Cytological and flow cytometric analysis of BAL fluid in ILD is done with knowledge of the clinical presentation and radiological findings. BAL typically reveals variations in the types and numbers of nucleated immune cells and acellular components in patients with ILD, which differ from those seen in normal control subjects. Many clinicians currently use this technique as a guide in the differential diagnoses of ILD; it can also be used to monitor the course of disease and possible response to therapeutic interventions. This article summarizes current clinicopathological information concerning the use of BAL by pulmonologists and pathologists.

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.

About molecular profile of lung cancer in Tunisian patients.

BACKGROUND: Molecular profile of lung cancer is well known in developed countries. These countries reached the era of liquid biopsies, immunotherapy, and urine circulating tumor DNA. The discrepancies between developed countries and developing ones are becoming deeper. Because of a lack of data in Tunisia, we tried to analyze the molecular profile of non-small-cell carcinomas and to assess the morphologic subtype of adenocarcinomas according to their mutational profile. METHODS: We performed molecular analyses in Tunisia and in France of 84 patients who were able to afford the cost of the diagnostic techniques carcinomas diagnosed between 2012 and 2015. The diagnosis was established in our Department of Pathology and the percentage of the tumor cells was estimated by the pathologists. The paraffin-embedded blocks were sent to France, in 41 cases and were analyzed in Tunisia in 43 cases. A next-generation sequencing was performed in France and a real-time polymerase chain reaction (PCR) was performed in our country. RESULTS: During the period of study, 1122 lung cancers were diagnosed and 87 patients were able to afford the molecular analyses cost. The mean age of these patients was 53 years. The sex ratio reached 1.9. The molecular analyses were not performed in three cases because of a low tumor cell rate. EGFR mutations were present in 16 cases: 3 men and 13 women. The adenocarcinomas were classified as acinar in 11 cases and solid in 5 cases. ALK-EML4 translocation was present in six cases. Mutations of BRAF, KRAS, P53, and ERBB4 genes were, respectively, detected in two cases, five cases (3 codon 12), three cases, and one case. CONCLUSION: This study made us wonder about the possibility of implementing molecular techniques in low-income countries and about the necessity of optimizing the financial resources.

Prognostic impact of the 2015 world health organisation classification of lung adenocarcinoma : a study in departement specialized in thoracic pathology.

BACKGROUND: The 2015 WHO classification of primary lung adenocarcinomas idendified not only new subtypes but also new prognostic groups. Solid and micropapillary adenocarcinomas are considered of bad prognosis, lepidici adenocarcinomas are considered of good prognosis and acinary and papillary ones are considered of intermediate prognosis. We aimed to assess the prognostic relevance of this classification through the experience of a specialized Department in Thoracic Oncology. METHODS: We described a survival study about 101 patients presenting primary adenocarcinomas diagnosed between 2008 and 2011. Survival curves were compared using the Log-Rank test. In order to assess the prognostic impact of the classification, 3 groups were formes: group 1 included lepidic adenocarcinomas, le group 2 included acinary and papillary subtypes and group 3 included solid subtype. A univariate analysis was performed to assess the age, sex, size, vascular emboli, lymph nodes, pTNM, histologic subtypes, neoadjuvant treatment and adjuvant treatment. Multivariate analysis using COX model was performed. RESULTS: There was no significant difference between the different subtypes. Besides, the multivariate analysis revealed the pTNM (p=0,02)  stage and the adjuvant treatment (p=0,007) as relevant prognostic factors. CONCLUSION: Our results are discordant with those reported in the literature. It seems that including large series is necessary in order to assess this prognostic classification.

About a lymphoepithelioma-like carcinoma of the lung with an endotracheal localization.

INTRODUCTION: Lympho-epithelioma like carcinoma is a rare lung tumour that acounts for less than 1% of non small cell lung carcinomas. It is defined as a special entity among the 2015 World Health Organization. AIM: Our aim was to describe a completely illustrated new case of lymhpo-epithelioma like carcinoma. We describe a new case diagnosed in our Department of Pathology. CASE PRESENTATION: The authors describe a case of a 22-year-old woman without a particular past medical history who presented non specific respiratory symptoms. Radiologic investigations revealed a tracheal tumor with enlarged mediastinal lumph nodes. A first biopsy was performed revealing a malignant tumor with a squamous differentiation highlighted by immunohischemistry. A surgical biopsy was performed and the final microscopic diagnosis revealed a lymphoepithelioma-like carcinoma of the lung. This diagnosis was retained after ruling out a possible metastasis of a nasopharyngeal carcinoma whose microscopic features are similar to this subtype of lung tumor. CONCLUSION: This case points out the rarity of this diagnosis, especially in a young and caucasian patient and highlights the diagnostic dilemma caused by this kind of tumor.

Unicentric Castleman's disease: an uncommon cause of chronic cough.

Castleman disease (CD) or angiofollicular lymph node hyperplasia is a rare lymphoproliferative disorder characterized by lymph node hyperplasia of uncertain etiology. CD is divided clinically into unicentric (localized to one region of the body) considered as a benign disease and multicentric with less favourable prognosis. We describe a case of intrathoracic unicentric CD revealed by a chronic non-productive cough in a 50-year-old non-smoker female. Chest computed tomography revealed a bulky right hilar mass with intense homogenous contrast enhancement. The patient underwent a right upper lobectomy and mediastinal lymphadenectomy. Histopathology was consistent with hyaline-vascular (HV) type CD. The patient remained asymptomatic throughout the subsequent 6-months of follow-up.

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.

[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 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.

Legal responsibility of the pathologist in Tunisia.

The role of the pathologist has been highlighted by the medias since the recent years and the Tunisian law system suffers from a huge and there are no rules or jury verdicts concerning the e responsability  of the doctors in general with emphasis on pathologists. One might think that the lack of laws benefits to the pathologist, on the other hand, we can consider this as dangerous either for the patients or the pathologists. This lack of laws makes the judge dependant on the expert view. Other countries like European ones and the United States, has available data furnished by the insurance bodies that enrich the jury verdicts and the different laws that are available. Our aim was to help the pathologists understand their legal responsibilities and the law system. The latter may seem as complex for the pathologist as a pathologic report for a judge.

Liquid biopsy in lung cancer.

In the era of the personalized medicine, we need not only to an accurate diagnosis of lung cancer but also to assess the molecular pathways involved in order to target them. The most relevant targets in lung cancer are the genes EGFR, ALK-EML4, ROS1, Her2Neu, BRAF. Mutations or translocations of these genes are performed on biopsies in 80% of the cases and 30% of the patients cannot have their molecular tests done. This may be due to the lack of tumor samples secondary to the morphologic and immunohistochemical techniques, contraindication to biopsy or difficulties to biopsy. Besides, tumor cells tend to activate other pathways that weren't activated at the onset in order to escape to therapeutic drugs. This phenomenon of resistance is observed 3 to 6 months after the onset of the treatment. In order to escape all these limitations, liquid biopsy was developed. It consists in a simple blood sample of 5 to 10 ml in which circulating tumor cells, circulating tumor DNA, tumor RNA, exosomes and secretomes are explored. In this paper, we tried to define liquid biopsy, to highlight the means of diagnosis, its limits, its advantages and its perspectives in Tunisia.

The role of the pathologic exam in the acute exacerbations of the interstitial pneumonia.

Acute exacerbation of interstitial pneumonia is a new terminology with recent debated criteria. Its prognosis is bad and its management remains non consensual. This lack of consensus seems to be due to the lack of knowledge concerning the physiopathologic phenomenon. This lack of knowledge results in few efficient therapeutics. The diagnosis of acute exacerbation is challenging for clinicians and the real place of the pathologic exam remains unknown. Our aim was to assess the different situations faced by the pathologists by emphasizing their real role.

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.

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.

CD56 antibody: old-fashioned or still trendy in endocrine lung tumors.

BACKGROUND: In 2010, the World Health Organization published a new classification of the endocrine tumors based on the mitotic rate and index. Concerning lung endocrine tumors, the classification of 2004 remains acceptable and widely approved. We noticed in many publications that the most used antibodies in these tumors are chromogranin and synaptophysin. This finding let us wonder about the diagnostic utility of the CD56 antibody which is widely used in our department. MATERIAL AND METHODS: Sixty-nine endocrine lung cancers were diagnosed over a 12-month period in our Department of Pathology. Immunohistochemical technique using the three antibodies: chromogranin, synaptophysin, and CD56 was performed. The sensitivity of the three antibodies was performed using the ratio: true negative cases/true negative cases + false positive cases. The specificity wasn't performed because the antibodies were used only in endocrine tumors. The comparison of the different percentages of expression of the three antibodies was made by the SPSS software 22.0. RESULTS: The sensitivity of the chromogranin, synpatophysin, and CD56 accounted for 69%, 77%, and 98%, respectively. The mean percentage of immunoreactive cells with CD56 was 70% towards 15% and 20% with chromogranin and synaptophysin antibodies, respectively. The comparison of the percentages of expression showed a significant statistical difference between the expression of CD56 versus synaptophysin and CD56 versus chromogranin with P<0.001. CONCLUSION: CD56 antibody seems to be of diagnostic value in endocrine lung tumors with the highest sensitivity. This fact highlights the necessity of using it as a first-line neuroendocrine marker in association to chromogranin which is considered as the most specific endocrine antibody.