Enriched sera protein profiling for detection of non-small cell lung cancer biomarkers.

BACKGROUND: Non Small Cell Lung Cancer (NSCLC) is the major cause of cancer related-death. Many patients receive diagnosis at advanced stage leading to a poor prognosis. At present, no satisfactory screening tests are available in clinical practice and the discovery and validation of new biomarkers is mandatory. Surface Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-ToF-MS) is a recent high-throughput technique used to detect new tumour markers. In this study we performed SELDI-ToF-MS analysis on serum samples treated with the ProteoMiner™ kit, a combinatorial library of hexapeptide ligands coupled to beads, to reduce the wide dynamic range of protein concentration in the sample. Serum from 44 NSCLC patients and 19 healthy controls were analyzed with IMAC30-Cu and H50 ProteinChip Arrays. RESULTS: Comparing SELDI-ToF-MS protein profiles of NSCLC patients and healthy controls, 28 protein peaks were found significantly different (p < 0.05), and were used as predictors to build decision classification trees. This statistical analysis selected 10 protein peaks in the low-mass range (2-24 kDa) and 6 in the high-mass range (40-80 kDa). The classification models for the low-mass range had a sensitivity and specificity of 70.45% (31/44) and 68.42% (13/19) for IMAC30-Cu, and 72.73% (32/44) and 73.68% (14/19) for H50 ProteinChip Arrays. CONCLUSIONS: These preliminary results suggest that SELDI-ToF-MS protein profiling of serum samples pretreated with ProteoMiner™ can improve the discovery of protein peaks differentially expressed between NSCLC patients and healthy subjects, useful to build classification algorithms with high sensitivity and specificity. However, identification of the significantly different protein peaks needs further study in order to provide a better understanding of the biological nature of these potential biomarkers and their role in the underlying disease process.

Double synchronous pulmonary lymphatic-related lesions.

A wide range of pathologies may primarily affect the lymphatic vessels in the lungs. In this article, a unique case of pulmonary silicosis associated with a subtle lymphangitic carcinomatosis from an unknown prostate cancer is reported and discussed.

Role of chemotherapy and the receptor tyrosine kinases KIT, PDGFRalpha, PDGFRbeta, and Met in large-cell neuroendocrine carcinoma of the lung.

PURPOSE: Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a relatively uncommon, high-grade neuroendocrine tumor sharing several features with small-cell lung carcinoma (SCLC) but currently considered as a variant of non-SCLC and accordingly treated with poor results. Little is known about the optimal therapy of LCNEC and the possible therapeutic molecular targets. PATIENTS AND METHODS: We reviewed 83 patients with pure pulmonary LCNEC to investigate their clinicopathologic features, therapeutic strategy, and immunohistochemical expression and the mutational status of the receptor tyrosine kinases (RTKs) KIT, PDGFRalpha, PDGFRbeta, and Met. RESULTS: LCNEC histology predicted a dismal outcome (overall median survival, 17 months) even in stage I patients (5-year survival rate, 33%). LCNEC strongly expressed RTKs (KIT in 62.7% of patients, PDGFRalpha in 60.2%, PDGFRbeta in 81.9%, and Met in 47%), but no mutations were detected in the exons encoding for the relevant juxtamembrane domains. Tumor stage and size (> or = 3 cm) and Met expression were significantly correlated with survival. At univariate and multivariate analysis, SCLC-based chemotherapy (platinum-etoposide) was the most important variable correlating with survival, both in the adjuvant and metastatic settings (P < .0001). CONCLUSION: Pulmonary LCNEC represents an aggressive tumor requiring multimodal treatment even for resectable stage I disease, and LCNEC seems to respond to adjuvant platinum-etoposide-based chemotherapy. Patients who received this therapy had the best survival rate. Despite our failure in finding mutational events in the tested RTKs, the strong expression of KIT, PDGFRalpha, PDGFRbeta, and Met in tumor cells suggests an important role of these RTKs in LCNEC, and these RTKs seem to be attractive therapeutic targets.

Large cell neuroendocrine carcinoma of the lung: a retrospective analysis of 144 surgical cases.

OBJECTIVE: Large cell neuroendocrine carcinoma of the lung are considered aggressive. However, reported prognoses are heterogeneous and the optimum treatment remains undefined. We retrospectively evaluated outcomes in a series of patients with a pathological diagnosis of large cell neuroendocrine lung carcinoma, who underwent lung resection. We also assessed the utility of chemotherapy in a small subgroup. PATIENTS AND METHODS: The clinical records of 144 consecutive patients were reviewed in a multicenter study. Survival times, assessed from the day of surgery until death or most recent follow-up, were estimated by the Kaplan-Meier method, and compared by the log rank test. RESULTS: There were 117 men and 27 women of median age 63 years. Twelve wedge resections, 3 segmentectomies, 95 lobectomies, 7 bilobectomies and 24 pneumonectomies were performed. Induction chemotherapy was given in 21 and postoperative chemotherapy in 24. Pathologically, 73 (50%) were stage I, 29 (20%) stage II, 40 (28%) stage III and 2 stage IV. Postoperative mortality was 2.8% and morbidity 26%. Overall 5-year survival was 42.5%: 52% for stage I, 59% for stage II and 20% for stage III (p=0.001 log-rank test on Kaplan-Meier curves). A trend to better outcome was associated with preoperative or postoperative chemotherapy in stage I disease (p=0.077) compared to no chemotherapy. The response rate to induction chemotherapy was 80% in the 15 patients with data available. CONCLUSION: large cell neuroendocrine carcinoma of the lung are confirmed as aggressive but are also chemosensitive. Our experience suggests that chemotherapy may improve prognosis in stage I disease.

Bronchial typical carcinoid tumors.

The current WHO classification of lung tumors recognizes bronchial typical carcinoid as low-grade neuroendocrine tumors. These tumors grow slowly but can metastasize to regional nodes (4 to 20%) and more rarely to extrathoracic sites. Symptoms are usually related to local compression and obstruction of the bronchial tree. Paraneoplastic syndrome can be present (carcinoid syndrome, Cushing's syndrome, acromegaly). Preoperative diagnosis is usually obtained with bronchoscopic biopsy. Computed tomography and somatostatin receptor scintigraphy are useful in the preoperative staging. Only selected cases can be treated endoscopically with laser resection. The complete surgical resection remains the only therapy with curative intent in the majority of patients. Parenchyma-sparing resections are indicated whenever possible. Overall survival after surgery is excellent (5-year rate, 87 to 100%) with low recurrence rate (2 to 11%). N-status and type of resection seem not to affect prognosis. Local relapse can be treated successfully with surgery, whereas distant metastases have a poor prognosis even after chemotherapy.

Talc poudrage versus talc slurry in the treatment of malignant pleural effusion. A prospective comparative study.

OBJECTIVE: The aim of this study was to investigate the effectiveness, safety and appropriate mode of administration of intrapleural talc for pleurodesis, in the treatment of malignant pleural effusion (MPE). METHODS: Prospective not randomized trial was conducted to compare thoracoscopic talc poudrage (TP) with tube thoracostomy and talc slurry (TS) for the local control of malignant pleural effusion. Both procedures were previously standardized; 6g of talc was administered for each procedure. Only the patients with lung re-expansion after drainage entered the study. Patients at high risk for general anaesthesia, poor general conditions and short life-expectancy received talc slurry through a chest tube, at the bedside. All the other patients underwent videothoracoscopic talc poudrage, with a pneumatic atomizer, under general anaesthesia. Morbidity, 30-day freedom from recurrence and long-term results were assessed and the two groups were compared. RESULTS: One hundred and nine patients entered the study (72 TP, 37 TS). Sixty-three patients in the TP group (87.5%) and 27 in the TS group (73%) had an immediate successful pleurodesis (p = 0.049); 53 patients (88.3%) and 16 patients (69.6%) had a successful pleurodesis 90 days after the procedure; 59 patients (81.9%) and 23 patients (62.2%), respectively, had a life-long pleural symphysis (p = 0.023). Adverse effects were generally mild: chest pain (36.1% in TP patients, 48.6% in TS patients) and fever (38.8% and 35.1%, respectively) were the more common but the difference was not significant between the two groups. We observed neither acute respiratory failure nor mortality due to the procedure. CONCLUSIONS: Our study confirms that intrapleural talc carries good results in the treatment of malignant pleural effusion. TP was significantly more effective than TS; both methods were safe but TS had a higher incidence of thoracic pain during the procedure. Talc pleurodesis should be offered to every patient with MPE, apart from terminally ill ones, provided that a satisfying lung re-expansion has been achieved. TP should be performed whenever possible; otherwise, a slurry bedside procedure will be worthwhile, even in patients with low performance status (PS), though poorer results have to be expected. A careful selection is essential to define the proper technique.

Exclusive intrapulmonary lepidic growth of a malignant pleural mesothelioma presenting with pneumothorax and involving the peritoneum.

We report a rare case of malignant pleural mesothelioma presenting clinically with pneumothorax and histologically with an exclusive intrapulmonary lepidic growth. Neither intrathoracic nodules nor pleural thickening were found. The patient subsequently experienced acute abdominal pain with peritonitis and intestinal occlusion by peritoneal mesothelioma. The morphologic clues leading to the correct diagnosis of mesothelioma with prominent intrapulmonary growth are briefly discussed.

Prediction of distant recurrence in resected stage I and II lung adenocarcinoma.

OBJECTIVES: Optimal procedures for adjuvant treatment and post-surgical surveillance of resected non-small-cell lung cancer remain under discussion. Pathological features are the main determinant of follow-up therapy but have limited ability to identify patients at risk of recurrence. Increasingly, molecular markers are incorporated into clinical decision-making, including measures of tumor growth. The CCP score is a quantitative, molecular measure of proliferation derived from the RNA expression of 31 cell cycle genes and a component of the molecular prognostic score (mPS). The mPS score is a linear combination of CCP score and pathological stage. CCP score and mPS are independent predictors of survival in resected lung adenocarcinoma. MATERIALS AND METHODS: CCP scores were determined by RT-qPCR for 318 patients diagnosed with stage I-II lung adenocarcinoma. Association of mPS and CCP score with distant recurrence and lung-cancer specific survival was assessed in Cox proportional hazards regression models adjusted for age, gender, tumor size, pathological stage and pleural invasion. Distant recurrence-free survival and lung-cancer specific survival by mPS risk group were calculated by Kaplan-Meier survival analysis. RESULTS: CCP scores were obtained for 205 stage I and 84 stage II patients. CCP score and mPS were independent markers of distant recurrence (CCP: HR 1.62, 95%CI 1.15-2.29, p=0.0055; mPS: HR 2.22, 95%CI 1.11-4.44, p=0.023). Patients with low mPS tumors were at significantly reduced risk of distant recurrence (log-rank p=4.2×10-5). Among stage I patients, stratification by mPS identified a patient group with increased risk of distant recurrence (36%, 95%CI 28-46%, log-rank p=0.0011) CONCLUSIONS: The molecular prognostic score stratifies early-stage, resected lung cancer patients for risk of distant recurrence and could be useful to inform treatment and surveillance decisions.

Prognostic factors in surgically resected N2 non-small cell lung cancer: the importance of patterns of mediastinal lymph nodes metastases.

OBJECTIVE: Patients with non-small cell lung cancer (NSCLC) with metastases to ipsilateral mediastinal lymph nodes (N2) are an heterogeneous group of patients as regard to prognosis and treatment. Indication and timing of surgery remain controversial. The present study investigates the prognostic factors, in order to identify homogenous subgroups of patients. METHODS: Histologically proven N2-NSCLC patients, who underwent a complete surgical resection were retrospectively reviewed. Clinical and pathological features were reported and analyzed, and survival study was performed. RESULTS: One hundred eighty-three patients were analyzed. Overall 1.3 and 5 years survival rates were, respectively, 70, 35 and 20%, with a median survival time of 24 months. Univariate analysis showed a significant better prognosis for: incidental N2 respect to clinical N2 (5-years 35.4 vs 17.4%); single level lymph node involvement respect to multiple levels (5-years 23.8 vs 14.7%); metastases to superior mediastinal or aortic nodes respect to lower mediastinal nodes (5-years 32 and 24.3 vs 16.3%); right upper lobe tumors with superior mediastinal nodes and left upper lobe tumors with aortic nodes respect to lower lobes tumors with lower mediastinal nodes (5-years 31.8 and 26.9 vs 15.7%). Skip metastases had not a significant survival advantage respect to continuous lymphatic spread. N2 clinical status, the number of levels involved and the two specific patterns of lymphatic spread resulted significant prognostic factors at multivariate analysis. CONCLUSIONS: Clinical N2 status, number of lymph nodes levels involved and specific patterns of lymphatic spread identify homogenous subgroups of patients that can be proposed for different therapeutic strategies.

The prognostic role of c-kit protein expression in resected large cell neuroendocrine carcinoma of the lung.

BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) is a high-grade neuroendocrine tumor of the lung that shares some clinicopathologic and molecular features with small cell lung carcinoma (SCLC). Optimal treatment has not yet been standardized and significant prognostic factors are lacking. Because c-kit protein overexpression has been recently reported as a negative prognostic factor in SCLC we investigated its expression and prognostic value in a series of LCNEC. METHODS: Resected LCNEC fulfilling the morphologic criteria of the 1999 World Health Organization classification of lung tumors and showing neuroendocrine differentiation by appropriate immunohistochemical markers were retrospectively reviewed. Immunostaining for c-kit protein expression was performed using the polyclonal antibody CD117. Clinical and pathologic characteristic were reported and analyzed and a survival study was performed. RESULTS: Thirty-three patients underwent radical resection. Thirty-one were male (94%) and 32 were smokers (97%). Ten (30.3%), 11 (33.3%), 5 (15.2%), and 7 (21.2%) were at stage IA, IB, IIB, and IIIA respectively. Overall 1-, 3-, and 5-year survival rates were respectively 79%, 58%, and 51%. Survival analysis showed no differences for any of the clinicopathological features except for CD117 immunostaining: 1-year and 3-year survival rates were respectively 91% and 82% for CD117-negative LCNEC, and 72% and 44% for CD117-positive ones (p = 0.046). Positivity of CD117 was significantly related to recurrence rate: 60% versus 23% for CD117 positive and negative LCNEC respectively (p = 0.037). CONCLUSIONS: Radical resection of large cell neuroendocrine carcinoma achieves poor outcomes. The c-kit protein is frequently expressed in this neoplasia and its expression represents a negative prognostic factor. This immunohistochemical marker may represent the basic rationale to select LCNEC for novel targeted therapy.

Prognostic factors in a multicentre study of 247 atypical pulmonary carcinoids.

OBJECTIVES: To analyse clinical and biomolecular prognostic factors associated with the surgical approach and the outcome of 247 patients affected by primary atypical carcinoids (ACs) of the lung in a multi-institutional experience. METHODS: We retrospectively evaluated clinical data and pathological tissue samples collected from 247 patients of 10 Thoracic Surgery Units from different geographical areas of our country. All patients were divided into four groups according to surgical procedure: sub-lobar resections (SURG1), lobar resections (SURG2), tracheobronchoplastic procedures (SURG3) and pneumonectomies (SURG4). Overall survival analysis was performed using the Kaplan-Meier method and log-rank test. Survival was calculated from the date of surgery to the last date of follow-up or death. The parameters evaluated included age, gender, smoking habits, laterality, type of surgery, 7th edition of TNM staging, mitosis Ki-67 (MIB1), multifocal forms, tumourlets, type of lymphadenectomy and neo/adjuvant therapy. For multivariate analysis, a Cox regression model was used with a forward stepwise selection of covariates. RESULTS: Two hundred and forty-seven patients (124 females and 123 males; range 10-84, median 60 years) underwent surgical resection for AC in the last 30 years as follows: n = 38 patients in SURG1, 181 in SURG2, 15 in SURG3 and 14 in SURG4. A smoking history was present in 136 of 247 (55%) patients. The median follow-up period was 98.7 (range 11.2-369.9) months. The overall survival probability analysis of the AC was 86.7% at 5 years, 72.4% at 10 years, 64.4% at 15 years and 58.1% at 20 years. Neuroendocrine multicentric forms were detected in 12 of 247 patients (4.8%; 1 of 12 pts) during the follow-up (range 11.2-200.4, median 98.7 months) and 33.4% had recurrence of disease. There were no significant differences between gender, tumour location and type of surgery at the multivariate analysis. Age [P < 0.001, hazard ratio (HR) 0.60; confidence interval (CI) 0.32-1.12], smoking habits (P = 0.002; HR 0.43, 95% CI 0.23-0.80) and lymph nodal metastatic involvement (P = 0.008; HR 0.46, 95% CI 0.26-0.82) were all significant at multivariate analysis. CONCLUSIONS: ACs of the lung are malignant neuroendocrine tumours with a worst outcome in patients over 70 years and in smokers. With the exception of pneumonectomy, the extent of resection does not seem to affect survival and should be accompanied preferably by lymphadenectomy. Pathological staging, along with a mitotic index more than Ki-67 (MIB1), appears to be the most significant prognostic factor at the univariate analysis.

Role of blebs and bullae detected by high-resolution computed tomography and recurrent spontaneous pneumothorax.

BACKGROUND: The prevention of recurrence after a first episode of primary spontaneous pneumothorax (PSP) remains a debated issue. The likelihood of recurrence based on the presence of blebs and bullae detected on high-resolution computed tomography (HRCT) imaging is controversial. METHODS: We evaluated patients conservatively treated for PSP who underwent chest HRCT scan in a single-institution retrospective longitudinal study. Absolute risk values and positive and negative predictive values of recurrence based on HRCT findings were the primary end points. RESULTS: We analyzed 176 patients. Ipsilateral and contralateral recurrence developed in 44.8% and 12% of patients, respectively. The risk of recurrence was significantly related to the presence of blebs or bullae, or both, at HRCT. The risk of ipsilateral recurrence for patients with or without blebs and bullae was 68.1% and 6.1%, respectively (positive predictive value, 68.1%; negative predictive value, 93.9%). The risk of contralateral pneumothorax for patients with or without blebs and bullae was 19% and 0%, respectively (positive predictive value, 19%; negative predictive value, 100%). The risk of ipsilateral recurrence was directly related to the dystrophic severity score: recurrence risk increased by up to 75% in patients with bilateral multiple lesions. Multivariate analysis showed that a positive HRCT was significantly related to ipsilateral recurrence. CONCLUSIONS: The presence of blebs and bullae at HRCT after a first episode of PSP is significantly related to the development of an ipsilateral recurrence or a contralateral episode of pneumothorax. Further studies are needed to validate the dystrophic severity score in the selection of patients for early surgical referral.

Preoperative predictors of successful surgical treatment in the management of parapneumonic empyema.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) and thoracotomy are the main surgical options for treating parapneumonic empyema. The choice of either operation depends on many preoperative features, including the patient's condition, clinical and radiologic findings, and pleural fluid characteristics. The identification of the combination of those preoperative findings that will allow surgeons to select the appropriate approach for a successful operation (VATS or thoracotomy) could be of great interest in clinical settings. METHODS: We retrospectively reviewed a series of 97 patients who had undergone successful VATS or thoracotomy for parapneumonic empyema; in all cases, the operation had begun through VATS and was changed to a thoracotomy if a complete decortication was needed. Preoperative clinical, radiologic, and laboratory features were compared between the two groups to search for differences that might serve as predictive factors for either operation. Perioperative findings were also analyzed. RESULTS: The operation was accomplished by VATS in 40 patients (41%), and conversion to thoracotomy was necessary in 57 (59%). Significant predictive factors for conversion were a prolonged delay from diagnosis to operation, the presence of fever and of pleural thickness on computed tomography (CT) images. The 25 patients who presented with these three features were cured by thoracotomy. The operative time and postoperative complication rate were significantly higher for the thoracotomy patients. CONCLUSIONS: Some preoperative features can help the surgeon to better select patients for the appropriate operation. Delayed operation, fever, and pleural thickness can be used to predict the likelihood of conversion to thoracotomy.

Integrated FDG-PET/CT imaging is useful in the approach to carcinoid tumors of the lung.

BACKGROUND: Carcinoids enter the differential diagnosis of the solitary pulmonary nodule. Bronchial carcinoids have been traditionally considered as FDG-PET negative but recent studies have found an higher sensitivity of integrated FDG-PET/CT for the detection of these neoplasms. The purpose of this study was to investigate the value of integrated FDG-PET/CT for the evaluation of SPN suspected to be carcinoids. METHODS: All patients with pathologically proven bronchial carcinoids who had FDG-PET/CT scans between 2006 and 2012 have been retrospectively reviewed. PET/CT was performed with the same scanner and the same technique for all patients. The following data were retrieved: age, sex CT findings (side, location, size, shape, margins), SUVmax, type of operation, pathological findings (size and number of mitoses). Regarding PET findings, only SUVmax was considered, whereas the visual assessment was not undertaken. Carcinoids were defined as typical and atypical and as central and peripheral. The long-term follow-up was also recorded. The SUVmax was compared with the other clinical, radiological and pathological variables to find any significant difference or correlation. RESULTS: Twenty-five patients were retrieved, 24 typical and one atypical carcinoid, 21 peripheral and 4 central lesions. The mean diameter on CT-scan was 25.3 mm and the clinical size correlated well with the pathological size. Sixty percent of the tumors were ovoid and 68% had smooth margins. The mean SUVmax was 3.6 (range 1.4-12.9). All the lesions were completely resected. The regression analysis showed a direct correlation between the SUVmax and the tumor size (p = 0.004). No further correlations were found between the SUVmax and the other variables. None of the patients had recurrent disease or died during the follow-up. CONCLUSIONS: Our study showed that FDG-PET/CT might be a useful tool in the evaluation of SPNs suspected to be bronchial carcinoids. When a solitary pulmonary nodule shows an ovoid/round shape and smooth margins on the CT scan and demonstrates an FDG uptake higher than that of the normal lung and with a SUVmax value >1-1.5, a carcinoid should be suspected. If benign lesions can be presumably excluded, surgical resection or at least a biopsy of the lesion is recommended.

Prognostic role of clusterin in resected adenocarcinomas of the lung.

RATIONALE: Clusterin expression may change in various human malignancies, including lung cancer. Patients with resectable non-small cell lung cancer (NSCLC), including adenocarcinoma, have a poor prognosis, with a relapse rate of 30-50% within 5 years. Nuclear factor kB (Nf-kB) is an intracellular protein involved in the initiation and progression of several human cancers, including the lung. OBJECTIVES: We investigate the role of clusterin and Nf-kB expression in predicting the prognosis of patients with early-stage surgically resected adenocarcinoma of the lung. FINDINGS: The level of clusterin gradually decreased from well-differentiated to poorly differentiated adenocarcinomas. Clusterin expression was significantly higher in patients with low-grade adenocarcinoma, in early-stage disease and in women. Clusterin expression was inversely related to relapse and survival in both univariate and multivariate analyses. Finally, we observed an inverse correlation between Nf-kB and clusterin. CONCLUSIONS: Clusterin expression represents an independent prognostic factor in surgically resected lung adenocarcinoma and was proven to be a useful biomarker for fewer relapses and longer survival in patients in the early stage of disease. The inverse correlation between Nf-kB and clusterin expression confirm the previously reported role of clusterin as potent down regulator of Nf-kB.

N1 non-small-cell lung cancer. A 20-year surgical experience.

N1 non-small-cell lung cancer has heterogeneous prognosis in relation to node descriptors. There is no agreement on the ideal type of resection. A new classification of N1 descriptors was proposed in the 7(th) edition of the TNM staging system. A retrospective study was conducted on 384 patients with T1-T3N1 non-small-cell lung cancer who underwent complete pulmonary resection. The prognostic role of N1 descriptors according to the current and new staging systems and type of resection was investigated. The 5-year survival rate was 46%. Involvement of hilar node stations, multiple stations, and multiple nodes were poor prognostic factors (5-year survival, 33%, 21%, and 30%, respectively), as well as involvement of the hilar zone and multiple zones (5-year survival, 27% and 23%, respectively). Pneumonectomy showed significantly better survival rates compared to lobectomy or bilobectomy (5-year survival, 60% vs. 29%). Multivariate analysis showed that the number of N1 zones and type of resection were independent prognostic factors. Patients with hilar nodal, multiple-level, or multiple-zone involvement had poor prognosis. Standard lobectomy remains the procedure of choice, but in cases of fixed nodes in the hilar zone, sleeve resection or even pneumonectomy should be considered.

Primary pulmonary cancer colliding with metastatic breast carcinoma: hitherto unreported cases of cancer-to-cancer metastasis focusing on clinical implications.

Lung is one of the main sites of metastatic tumors, but collision neoplasms consisting of a primary lung cancer and metastatic breast carcinoma have never been so far reported. We describe here 2 cases of primary non-small cell lung cancers (squamous cell and adenocarcinoma, respectively) colliding with metastatic breast carcinomas (ductal and lobular carcinomas, respectively). Clinico-pathologic features characterizing this challenging diagnosis and the important therapeutic implications are discussed.

The variation of prognostic significance of Maximum Standardized Uptake Value of [18F]-fluoro-2-deoxy-glucose positron emission tomography in different histological subtypes and pathological stages of surgically resected Non-Small Cell Lung Carcinoma.

Even if the prognostic role of SUVmax of 18-FDG-PET has been largely investigated, many issues regarding its relationship with pathologic staging and histological subtypes still remain controversial. This retrospective study investigated the prognostic significance of SUVmax in 119 completely resected, pathologically proven NSCLC. The SUVmax values resulted significantly related to histological subtypes (p<0.001), histological grading (p<0.001), and pathologic stage (p<0.001). The optimal cut-off value of SUVmax to predict prognosis in the whole series was 6.7 (p=0.029). 2-Year disease-specific survival (DSS) was 91% for SUVmax < or =6.7 and 55% for SUVmax >6.7 (p<0.001). SUVmax still remain a significant predictor of survival in Stage IB (2-year DSS of 100% for SUVmax < or =6.7; 51% for SUVmax >6.7, p=0.016). The optimal cut-off values of SUVmax to predict prognosis were 5 for adenocarcinoma (p=0.027) and 10.7 for other non-adenocarcinoma NSCLC subtypes (p=0.010). These histologic-specific cut-offs resulted significantly related to survival when stratified for stage: 2-year DSS for Stage IB adenocarcinoma were 100% for SUV< or =5 and 40% for SUVmax >5 (p=0.051); 2-year DSS for Stage IB non-adenocarcinoma were 83% for SUVmax < or =10.7 and 26% for SUVmax >10.7 (p=0.018). Adenocarcinomas showed significantly lower survival results respect to other NSCLC for intermediate SUVmax level (range 5.5-11.3) (p=0.021). High SUVmax resulted an independent negative prognostic factor at multivariate analysis (HR of 15.7, 95% CI of 2.50-98.44, p=0.003). In conclusion, SUVmax represents a significant prognostic factor in surgically resected NSCLC but a great variability between different histological subtypes, even when adjusted for stage, is present and could be considered when planning future trials on prognostic role of FDG uptake.