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.

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.

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.

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.

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.

[Multicentric tubulopapillary carcinoma of the kidney associated with renal adenomatosis]. / Carcinome tubulopapillaire multicentrique du rein associé à une adénomatose rénale.

Tubulopapillary tumors of the kidney represent a particular group of the renal tumors. They cover a continuous spectrum of tumors ranging from the adenoma to the renal cells papillary carcinoma. The histological and immunohistochemical similarities, as well as the high recurrence of the association of these two entities suggest a continuity of the same biological process. Although rare, the association between adenoma and papillary carcinoma remains still subject to controversy and plead in favor of a narrow relation between them. We report the case of a multicentric tubulopapillary carcinoma of the kidney associated with multifocal adenomas, discovered by fortuity in a right nephrectomy at a 57-year-old patient operated for an obstructive chronic pyelonephritis.

Sub-cutaneous histiocytic sarcoma in a child: a case report.

BACKGROUND: Histiocytic sarcoma (HS) is a rare hematologic malignancy with morphologic and immunophenotypic evidence of histiocytic differentiation. This tumor follows an aggressive clinical course. CASE PRESENTATION: We report the case of a 14 year-old white girl who presented with a nodular lesion in the thigh, involving the skin and soft tissue. The histologic diagnosis retained was a HS. CONCLUSION: HS is a rare neoplasm that may cause a diagnostic pitfall. Unfortunately, incomplete clinical data and histopathologic disparities in addition to the overall rarity of the neoplasms induced difficulties of management and of full appreciation of their clinical behavior.

[Fatal pulmonary mycosis in a diabetic and cirrhotic patient]. / Une mycose pulmonaire d'issue fatale chez une patiente diabétique et cirrhotique.

Pulmonary mucormycosis is a rare, devastating, opportunistic fungal infection, caused by the ubiquitous filamentous fungi of the Mucorales order of the class of Zygomycetes. This infection occurs principally in some particular conditions, specially in diabetic patients and immunocompromised host, and rarely in cirrhotic patients. The diagnosis of mucormycosis can only be confirmed by pathological and mycological examination of biopsy specimens. We report a case of pulmonary mucormycosis in a 68-year-old woman with underlying liver cirrhosis and diabetes mellitus. Endoscopic and radiologic findings supported the diagnosis of hydatid cyst of the lung. The patient underwent surgical resection and was started on amphotericin B, after pathological examination. Unfortunately, she succumbed to the infection within one month of surgery.

[Sarcomatoid carcinoma of the lung: retrospective study of 28 cases]. / Carcinomes sarcomatoïdes du poumon: étude rétrospective de 28 cas.

INTRODUCTION: Sarcomatoid carcinoma (SC) of the lung is defined by the World Health Organization as poorly differentiated non-small cell carcinoma that contains a component of sarcoma or sarcoma-like elements. It represents an overall continuum of epithelial and mesenchymal differentiation. Five subtypes are recognized: pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma, and pulmonary blastoma. The diagnosis is pathological and requires a good sampling of the tumor. PATIENTS AND METHODS: Twenty-eight cases of primary sarcomatoid carcinoma, diagnosed between 1993 and 2010, were reviewed retrospectively, noting the clinicopathological characteristics. RESULTS: The patient population consisted of 25 males and 3 females with mean age of 62.9 years (48-75 years). The symptomatology was dominated by respiratory symptoms. Imaging features showed a pulmonary mass invading pleura or thoracic wall in 5 cases. The diagnosis was made in all cases on histological examination. These 28 tumors were divided as below: into 19 pleomorphic carcinomas, 4 giant cell carcinomas, 1 spindle cell carcinoma and 4 carcinosarcomas. Twenty-seven tumors were treated surgically. Associated treatments were neoadjuvant (3 cases) or adjuvant chemotherapy (1 case) and preoperative radiotherapy (5 cases). Deaths occurred in 7 patients. Twenty-two patients were lost to follow up. CONCLUSION: These tumors are frequently symptomatic, are locally advanced, and have higher rates of recurrence. Its prognosis is worse than that of other non-small cell lung cancer.

[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.

Is galectin-3 antibody a useful marker in the diagnosis of malignant pleural mesothelioma?

Malignant pleural mesothelioma (MPM) is a challenging diagnosis characterized by the absence of real specific diagnostic markers. Positivity with the galectin-3 antibody was assessed by a cytoplasmic expression in 17 MPM. Fourteen cases expressed the galectin-3 antibody. The three negative cases consisted of epithelioid, biphasic, and sarcomatoid MPM. The 14 positive cases consisted of epithelioid MPM in 12 cases, sarcomatoid MPM in one case, and biphasic MPM in one case. In spite of our inability to prove the real diagnostic value of the galectin-3 antibody, our findings make us wonder about the implication of this antibody in the carcinogenesis of MPM.

[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.

Is critical thinking potential correlated to critical appraisal skills of medical literature?

INTRODUCTION: Critical appraisal of medical literature is a mandatory skill to practice evidence-based medicine. The relation between the critical appraisal skills and the critical thinking potential has been rarely assessed in the literature. AIM: To assess the relation of critical thinking potential to critical appraisal of medical literature competencies. Besides, they tried to highlight the variation of the critical thinking potential according to the students' level. METHODS: The authors conducted a mixed study associating a quantitative and a qualitative approach. The study included second year (SYME), third year (TYME) and postgraduate medical students (CME) and family doctors (FD) from the same faculty of medicine. All the students received the same active training focused on critical appraisal of medical literature. They were asked to fulfil a pre-requisite test and a self-assessment questionnaire before the training session and a final test after the training. The self-assessment questionnaire was conceived by an expert committee and assessed the main characteristics of critical thinking consisting of sensitivity to context, self-correction and search for criteria. Three months after the training, the students were interviewed using a semi-structured interview. The SPSS software 16.0 was used. RESULTS: In our study, 58.9% of the students presented a high critical thinking potential profile. Their scores varied according to their levels with better scores in SYME and FD and intermediate scores in TYME and CME. The pre-requisite test scores varied according to the critical thinking profile and the level. On the other hand, final test scores didn't differ according to the critical thinking profile or the level. CONCLUSION: Our results put emphasis on the variation of the critical thinking potential according to the students' levels. The better results of the SYME students in comparison to those in the TYME put emphasis on the necessity of changing curriculum in order to enhance the sensitivity and the inclination of the students.

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.

[Primary malignant tumors of the sternum]. / Tumeurs malignes primitives du sternum.

BACKGROUND: Primary tumors of the sternum are rare and account only 0.5% of all primary bone tumors. They are often malignant, osteolytic and aggressive. They often present difficulties in management. AIM: to determine clinical, pathological and therapeutic characteristics for primary malignant tumors of the sternum. PATIENTS AND METHODS: We report a series of six cases of primary malignant tumors of the sternum, collected in our institution between 1993 and 2009. RESULTS: There were 4 men and 2 women with a mean age of 69, 5 years. Parietal swelling was the most frequent symptom. Imaging showed a sternal lytic lesion. Three tumors were treated surgically. Associated treatments were neoadjuvant chemotherapy (1 case) and postoperative radiotherapy (1 case). A medical treatment (radiotherapy alone or chemotherapy) was performed in 3 cases. These tumors were divided as below: 3 plasmacytoma, 1 chondrosarcoma, 1 osteosarcoma and 1 large B cell lymphoma. CONCLUSION: The management of primary malignant tumors of the sternum is multidisciplinary. It depends on the histological type, the possibility of surgical treatment and the distant and local aggressiveness.

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.

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.