[A case of bronchial mucous gland adenoma: A rare diagnosis that should not be mistaken!] / Un cas d'adénome muqueux glandulaire bronchique : un diagnostic rare à ne pas méconnaître !

We report the case of a 32-year-old man, who was admitted for a recurrent pneumopathy. The thoracic computed tomography revealed a small well-circumscribed lesion of the lower right lobe of the lung. Microscopic examination from the biopsy material of the endoscopy concluded a mucoepidermoid carcinoma. A lobectomy was realized. Microscopic examination revealed the presence of a well-delineated lesion composed of glands and cysts containing mucous and limited by mucous and cylindric and ciliated cells without atypia. The proliferation index was very low. A diagnosis of mucous gland adenoma was made. It is an exceptional tumor and is very difficult to diagnose on biopsy material but should be known by pathologists. It is associated with a good prognosis. The aims of our observation are to present the macroscopic and microscopic features of this tumor and data from recent literature review to better diagnose it. This is also the second observation with molecular details for this entity.

Doege-Potter syndrome: hypoglycaemic coma in a 90-year old due to a solitary fibrous tumour.

Solitary fibrous tumour of the pleura (SFTP) is a rare primary tumour of the pleura associated with 4% of cases with a paraneoplastic hypoglycaemia, termed Doege-Potter syndrome (DPS). We report a case of DPS presenting with severe coma in a 90-year-old woman. The cause was a malignant SFTP treated with surgical resection, from which the patient made a full recovery with prevention of recurrent hypoglycaemia. Surgical resection of the SFTP presenting with symptomatic hypoglycaemia should be considered even in elderly patients.

Multiple tuberculous aneurysms of the aorta.

Tuberculous aneurysms of the aorta are quite rare, but are exceptional when found in multiple locations. We report the case of multiple tuberculous aortic aneurysms of the thoracic and abdominal aorta in a 19-year-old female discovered when she consulted for thrombocytopenic purpura. The treatment for both locations included prolonged antituberculous therapy and surgical resection with cryopreserved aortic allograft patch for the reconstruction.

Mutational Diversity of Lung Cancer and Associated Lymph Nodes. An Exploratory Prospective Study of 4 Resected cIIIA-N2.

Mutational heterogeneity could explain different metastatic patterns among IIIA-N2 lung cancer and influence prognosis. The identification of subclonal mutations using deep sequencing to evaluate the degree of molecular heterogeneity may improve IIIA-N2 classification. The aim of this prospective study was to assess mutational and immunohistochemical characteristics in primary tumours and involved lymph nodes (LN) in operated patients. Four patients operated for primary lung carcinoma and unisite N2 mediastinal involvement were consecutively selected. Samples (tumour and paired LN) were analysed for PD1, PD-L1 and CD8 immunostaining. Somatic mutation testing was performed by deep targeted next generation sequencing (NGS), with the AmpliSeq™ Colon and Lung Cancer Panel (LifeTechnology). A total of 9 primary lung cancer samples and 10 LN stations were analysed. For each cancer, we found 2 mutations, with allelic ratios from 3% to 72%. Mutational patterns were heterogeneous for 2 primary tumours. In 3 cases, mutations observed in the primary tumour were not found in LN metastases (ALK, FGFR3, MET). Inversely, in 1 case, a KRAS mutation was found in LN but not in the primary tumour. All primary tumours were found PD-L1 positive while CD8+ T cells infiltrate varied. In the different examined LN samples, PD-L1 expression, CD8+ and PD1+ T cells infiltrate were not similar to the primary tumour. This preliminary prospective study shows the diversity of intra-tumour and LN mutations using routinely-used targeted NGS, concerning both mutated gene and allelic ratio. Further studies are needed to evaluate its prognostic impact.

Pulmonary benign metastasizing leiomyoma presented as acute respiratory distress.

Benign metastasizing leiomyoma (BML) is a very rare condition and is characterized by the presence of benign smooth muscle tumours in organs distant from the uterus, most commonly the lung. It generally affects women of reproductive age and prognostic is usually excellent. However, the course of the disease is unpredictable. We report here the case of a 76-year-old woman with a previous medical history of uterine benign leiomyomas in whom BML was acutely revealed by a respiratory distress due to voluminous pulmonary and pleural leiomyomas requiring surgical extraction. Clinical evolution was remarkable by resistance to medical treatment and development of rare bone localization. BML is a contradictory entity characterized by benign histological features but with metastatic potential. Pulmonologists as well as oncologists in charge of patients with multiple pulmonary nodules and a history of uterine leiomyoma should be aware of this potential diagnosis in order to implement appropriate diagnostic procedures for this benign tumour.

Solitary fibrous tumors of the pleura: a poorly defined malignancy profile.

BACKGROUND: The aim of this study was to evaluate the clinical characteristics and factors that influence the long-term outcomes of solitary fibrous tumors of the pleura. METHODS: We conducted a retrospective study in 2 centers and reviewed 80 patients who underwent surgery between May 1984 and April 2011. RESULTS: Of the 80 patients (29 male; median age, 60 years [33 to 85 years]), 47 were symptomatic (59%). The tumors originated from the visceral pleura in 62 cases (79%) and from the parietal pleura in 18 cases (22%). The tumors were pedunculated in 66 cases (83%) and sessile in 20 cases (17%). Surgical resection with histologically free margins was accomplished in 76 of 79 patients (93%). The tumors were classified as benign in 51 cases (65%) and as malignant in 28 (35%). The factors that were significantly associated with malignant tumors were the presence of symptoms (p = 0.03), a mean diameter 10 cm or greater (p = 0.0004), fibrous adherences (p = 0.003), pleural effusion (p = 0.003), and a Ki67 10% or greater (p = 0.003). The median follow-up was 69 months (range, 1 to 315). Local recurrence occurred in 3 cases. The overall 5- and 10-year survival rates were 90% and 86%, respectively, and the mean survival time was 255 ± 15 months. There were no differences between the benign and malignant tumors. CONCLUSIONS: The recurrence rates are low after surgeries for both benign and malignant solitary fibrous tumors of the pleura. However, the factors that are predictive of recurrence have yet to be specified and require additional immunohistochemical and genetic investigations.

Adenosquamous carcinoma of the lung: surgical management, pathologic characteristics, and prognostic implications.

BACKGROUND: Adenosquamous carcinoma (ASC) is a mixed glandular and squamous cell carcinoma with a more aggressive behavior than the other histologic subtypes of lung cancer. We revisited the pathologic characteristics and surgical results associated with ASC. METHODS: Patients who underwent surgical resection of non-small cell lung cancer in two French centers were retrospectively reviewed. Patients presenting with ASC (n=141) were compared to those with adenocarcinomas (AC, n=2415) and squamous cell carcinomas (SCC, n=2662) regarding preoperative data, histologic characteristics, and outcome. RESULTS: The frequency of ASC and SCC decreased over time. ASC patients were similar to AC patients regarding age, sex, and smoking habits. The type of resections performed in ASC patients was intermediary between SCC (more pneumonectomy) and AC (more lobectomy) patients. ASC was associated with larger size, more frequent visceral pleura invasion, microinvasion of the lymphatic vessels, and ipsilateral second nodules, compared with SCC and AC. Among the 135 patients with documented ASC, 48% presented with a combination of AC and SCC tumor cells ranging between 40% and 60% of each component, and 55% of cases were associated with undifferentiated large cells. ASC was associated with a lower 5-year survival rate (37%) than SCC and AC (43.4% and 42.8%, respectively, p=0.017). For ASC patients, survival was better during the last decade or in cases of balanced AC/SCC components. CONCLUSIONS: ASC is characterized by both histologic aggressiveness and adverse prognosis. In this setting, the impact of adjuvant therapies needs to be reevaluated.

Unexpected extensions of non-small-cell lung cancer diagnosed during surgery: revisiting exploratory thoracotomies and incomplete resections.

OBJECTIVES: Only patients with a complete resection of non-small-cell lung cancer (NSCLC) may expect long-term survival. Despite the recent progress in imaging and induction therapy, a thoracotomy may remain exploratory or with incomplete resection (R2). Our purpose was to revisit these situations. METHODS: A total of 5305 patients who underwent surgery for NSCLC between 1980 and 2009 were reviewed. We compared the epidemiology, pathology, causes and prognosis characteristics of exploratory thoracotomy (ET) and R2 resections. RESULTS: ET and R2 resections were observed in 223 (4%) and 197 (4%) patients, respectively. The frequency of ET decreased with time, while the frequency of R2 resection remained almost stable. The indications for ET and R2 resections were not significantly different. In comparison with ET, R2 resections were characterized by a significantly higher frequency of induction therapy (22 vs 17%, P < 10(-3)), adenocarcinomas (49 vs 15%, P < 10(-6)), T1-T2 (53 vs 29%, P < 10(-6)) and N0-N1 extension (67 vs 42%, P = 10(-6)). R2 resections were also characterized by a higher rate of postoperative complications (19.1 vs 9.9%, P = 0.014), with no significant difference in postoperative mortality (6.9 vs 4.9%, P = non significant). R2 resections resulted in a higher 5-year survival compared with ET (11.1 vs 1.2%, P = 10(-3)). There was no long-term survivor after ET, except during the last decade. CONCLUSIONS: ET and R2 remain unavoidable. In comparison with ET, R2 resection is associated with a higher rate of postoperative complications, but a higher long-term survival.

History of multiple previous malignancies should not be a contraindication to the surgical resection of lung cancer.

BACKGROUND: Patients with a history of previous malignancy are often encountered in a discussion of surgical resection of non-small-cell lung cancer (NSCLC). The outcome of patients with 2 or more previous cancers remains unknown. METHODS: We performed a retrospective study including all patients undergoing resection for NSCLC from January 1980 to December 2009 at 2 French centers. We then compared the survival of patients without a history of another cancer (group 1), those with a history of a single malignancy (group 2), and those with a history of 2 or more previous malignancies (group 3). RESULTS: There were 5,846 patients: 4,603 (78%) in group 1, 1,147 (20%) in group 2, and 96 (2%) in group 3. The proportion of patients included in group 3 increased from 0.3% to 3% over 3 decades. Compared with groups 1 and 2, group 3 was associated with older age, a larger proportion of women, earlier tumor stage, less induction therapy, and fewer pneumonectomies. Despite this, postoperative complications and mortality were similar in groups 2 and 3, and higher than in group 1. Five-year survival rates were 44.6%, 35.1%, and 23.6% in groups 1, 2, and 3, respectively (p < 0.000001 for comparison between 3 groups; p = 0.18 for comparison between groups 2 and 3). In multivariate analysis, male sex, higher T stage, higher N stage, incomplete resection, and study group were significant predictors of adverse prognosis. CONCLUSIONS: Despite earlier diagnosis and acceptable long-term survival, patients operated on for NSCLC after 2 or 3 previous malignancies carried a worse prognosis than did those undergoing operation after 1 malignancy or if there was no previous diagnosis of cancer.

Prognosis of lung cancer resection in patients with previous extra-respiratory solid malignancies.

OBJECTIVES: Non-small-cell lung cancer (NSCLC) following pulmonary or pharyngolaryngeal malignancies has been widely studied, but only a few articles have focussed on lung cancers following other solid malignancies. Our purpose was to compare the characteristics and prognosis of patients with NSCLC according to the medical history of the extra-pulmonary and extra-pharyngolaryngeal solid malignancy. METHODS: Patients who underwent surgery for NSCLC from January 1980 to December 2009 in two French thoracic centres were reviewed. We compared patients with no history of cancer (Group 1) and patients with a history of extra-pulmonary and extra-pharyngolaryngeal solid malignancy (Group 2). RESULTS: There were 4992 patients: 4603 (92%) in Group 1 and 389 (8%) in Group 2. In comparison with Group 1, Group 2 showed an increasing incidence over the last 3 decades (2-8%), an older population (65.9 vs 61 years, P < 0.001), a higher proportion of women (34 vs 18%, P < 0.001), non-smokers (20 vs 10%, P < 0.001), adenocarcinomas (53 vs 40%, P < 0.001), T1 (16 vs 14%, P = 0.047) and second nodule in the same lobe (4 vs 2%, P < 0.001). The overall survival was not significantly different between the two groups (P = 0.09). In multivariate analysis, older age, male gender, pneumonectomy, higher T, higher N, incomplete resection and history of extra pulmonary-extra pharyngolaryngeal solid malignancy were significantly associated with a worse prognosis. CONCLUSIONS: Despite an earlier diagnosis, a history of extra-pulmonary and extra-pharyngolaryngeal solid malignancy is associated with a worse prognosis in patients with NSCLC undergoing surgical resection. Overall survival is particularly low after a history of bladder and upper gastrointestinal malignancies.

High grade neuroendocrine lung tumors: pathological characteristics, surgical management and prognostic implications.

Among non-small cell lung cancers (NSCLC), large cell carcinoma (LCC) is credited of significant adverse prognosis. Its neuroendocrine subtype has even a poorer diagnosis, with long-term survival similar to small cell lung cancer (SCLC). Our purpose was to review the surgical characteristics of those tumors. The clinical records of patients who underwent surgery for lung cancer in two French centers from 1980 to 2009 were retrospectively reviewed. We more particularly focused on patients with LCC or with high grade neuroendocrine lung tumors. High grade neuroendocrine tumors were classified as pure large cell neuroendocrine carcinoma (pure LCNEC), NSCLC combined with LCNEC (combined LCNEC), and SCLC combined with LCNEC (combined SCLC). There were 470 LCC and 155 high grade neuroendocrine lung tumors, with no difference concerning gender, mean age, smoking habits. There were significantly more exploratory thoracotomies in LCC, and more frequent postoperative complications in high grade neuroendocrine lung tumors. Pathologic TNM and 5-year survival rates were similar, with 5-year ranging from 34.3% to 37.6% for high grade neuroendocrine lung tumors and LCC, respectively. Induction and adjuvant therapy were not associated with an improved prognosis. The subgroups of LCNEC (pure NE, combined NE) and combined SCLC behaved similarly, except visceral pleura invasion, which proved more frequent in combined NE and less frequent in combined SCLC. Survival analysis showed a trend toward a lower 5-year survival in case of combined SCLC. Therefore, LCC, LCNEC and combined SCLC share the same poor prognosis, but surgical resection is associated with long-term survival in about one third of patients.

Bronchial carcinoid tumors causing Cushing's syndrome: more aggressive behavior and the need for early diagnosis.

BACKGROUND: The aim of this study was to revisit the characteristics and outcomes of adrenocorticotropin-secreting bronchial carcinoid tumor (BCT) responsible for Cushing's syndrome (CS). METHODS: We conducted a single-institution retrospective review of 14 patients who underwent pulmonary resection for BCT that presented as CS from October 1993 to November 2011. RESULTS: The group consisted of 8 male patients (57%) and 6 female patients. The mean age was 40 years (range, 16-63 years). Three patients (21%) underwent unnecessary adrenalectomy or hypophysectomy, or both, before diagnosis of the main cause. The mean interval between clinical presentation and the chest operation was 33 months (range, 3-136 months). Operations included 12 lobectomies (86%), 1 segmentectomy, and 1 wedge excision. All patients underwent radical lymph node dissection. Histologic examination showed 11 typical carcinoids (79%) and 3 atypical carcinoids. Twelve patients were classified pT1 (86%) and 2 patients were classified pT3 because of the presence of 2 tumors in the same lobe. Lymph node metastases were found in 7 patients (50%) (3 pN1 and 4 pN2). The mean follow-up was 59 months (range, 3-174 months). No recurrence was observed. CONCLUSIONS: Early detection of adrenocorticotropin-secreting BCTs is challenging. However, it avoids adrenalectomy and unnecessary hypophysectomy, limits the deleterious effects of chronic hypercortisolism, and reduces the risk of metastasis. The high prevalence of lymph node involvement confirms the aggressiveness of these tumors and justifies anatomic resection and radical lymph node dissection. Under these circumstances, the prognosis remains favorable, even in cases of N2 disease.

Lung cancer invading the pericardium: quantum of lymph nodes.

BACKGROUND: Lung cancer may invade the pericardium (T3) and the intrapericardial pulmonary veins and left atrium (T4). Our purpose was to analyze the characteristics of this invading process in search of the reasons explaining its poor prognosis. METHODS: The clinical records of 4,668 patients who underwent surgery for lung cancer between January 1983 and December 2006 in two thoracic surgery centers were retrospectively reviewed. The epidemiology, pathology, and prognostic characteristics of the tumors invading the pericardium alone (T3) or with pulmonary veins and atrium (T4) were analyzed and compared with all other tumors. RESULTS: There were 75 male and 16 female patients, with 85 pneumonectomies and 6 lobectomies that proved R0 in 59.3% of patients, and contained 69 squamous cell cancers, 11 adenocarcinomas, and 13 miscellaneous tumors; 12 were N0 (13.2%), 31 were N1 (34.1%), and 48 were N2 (52.8%). Pericardium alone was invaded in 32 patients (35.2%), and with pulmonary vein and atrium in 34 (37.3%) and 25 (27.5%), respectively. Patient characteristics were similar in each group. Five-year and 10-year survival rates were 15.1% and 10.4%, respectively. Frequency of pneumonectomy, R1-2 resection, and N1-2 involvement were significantly more important compared with noninvading tumors (p < 10(-6)). CONCLUSIONS: Reports on T3 and T4 cancer with pericardial involvement are few, but also stress that pulmonary vein and left atrium invasion does not worsen the prognosis more than pericardial invasion alone. The rich pericardial lymph drainage might enhance the spread of tumor cells, explaining excessively high N1-N2 rates and pericardial invasion-related poor prognosis.