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Purpose: To investigate the early radiological features and survival of Large Cell Carcinoma (LCC) cases diagnosed in low-dose computed tomography (LDCT) screening trials., Methods: Two radiologists jointly reviewed the radiological features of screen-detected LCCs observed in NLST, ITALUNG, and LUSI trials between 2002 and 2016, comprising a total of 29,744 subjects who underwent 3-5 annual screening LDCT examinations. Survival or causes of death were established according to the mortality registries extending more than 12 years since randomization., Results: LCC was diagnosed in 30 (4 %) of 750 subjects with screen-detected lung cancer (LC), including 15 prevalent and 15 incident cases. Three additional LCCs occurred as interval cancers during the screening period. LDCT images were available for 29 cases of screen-detected LCCs, and 28 showed a single, peripheral, and well-defined solid nodule or mass with regularly smooth (39 %), lobulated (43 %), or spiculated (18 %) margins. One case presented as hilar mass. In 9 incident LCCs, smaller solid nodules were identified in prior LDCT examinations, allowing us to calculate a mean Volume Doubling Time (VDT) of 98.7 ± 47.8 days. The overall five-year survival rate was 50 %, with a significant (p = 0.0001) difference between stages I-II (75 % alive) and stages III-IV (10 % alive)., Conclusions: LCC is a fast-growing neoplasm that can escape detection by annual LDCT screening. LCC typically presents as a single solid peripheral nodule or mass, often with lobulated margins, and exhibits a short VDT. The 5-year survival reflects the stage at diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Diagnosing COVID-19 and treating its complications remains a challenge. This review reflects the perspective of some of the Dragon (IMI 2-call 21, #101005122) research consortium collaborators on the utility of bronchoalveolar lavage (BAL) in COVID-19. BAL has been proposed as a potentially useful diagnostic tool to increase COVID-19 diagnosis sensitivity. In both critically ill and non-critically ill COVID-19 patients, BAL has a relevant role in detecting other infections or supporting alternative diagnoses and can change management decisions in up to two-thirds of patients. BAL is used to guide steroid and immunosuppressive treatment and to narrow or discontinue antibiotic treatment, reducing the use of unnecessary broad antibiotics. Moreover, cellular analysis and novel multi-omics techniques on BAL are of critical importance for understanding the microenvironment and interaction between epithelial cells and immunity, revealing novel potential prognostic and therapeutic targets. The BAL technique has been described as safe for both patients and healthcare workers in more than a thousand procedures reported to date in the literature. Based on these preliminary studies, we recognize that BAL is a feasible procedure in COVID-19 known or suspected cases, useful to properly guide patient management, and has great potential for research., Competing Interests: ST declares consultancy and speaker’s fees from Roche and Boehringer Ingelheim. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tomassetti, Ciani, Luzzi, Gori, Trigiani, Giuntoli, Lavorini, Poletti, Ravaglia, Torrego, Maldonado, Lentz, Annunziato, Maggi, Rossolini, Pollini, Para, Ciurleo, Casini, Rasero, Bartoloni, Spinicci, Munavvar, Gasparini, Comin, Cerinic, Peired, Henket, Ernst, Louis, Corhay, Nardi and Guiot.)

Background: Emerging evidence identified sex as a variable regulating immune system functions and modulating response to immunotherapy in cancer patients., Objective: This retrospective study analysed sex-related differences in immunotherapy outcomes in a real-world population of non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs)., Methods: e retrospectively investigated clinical data of 99 patients with advanced NSCLC and treated with single-agent nivolumab and pembrolizumab at Medical Oncology Unit, Careggi University Hospital, Florence (Italy), between April 2014 to August 2019. Main clinical characteristics and clinical outcomes were analysed., Results: Our study showed that the efficacy of ICI treatment differed according to gender. A trend for better median progression-free survival (mPFS) was reported in males (mPFS 5.0 months, 95% Confidence Interval [CI] 4.0-11.0) than females (mPFS 4.5 months, 95% CI 2.0-9.0) (p=0.133), while no significant difference for overall survival (OS) between the two sex groups was observed (p=0.622). In the nivolumab cohort, we showed a statistically significant difference for a longer PFS in men compared to women (log-rank p=0.054), HR for PFS in females versus males was 1.81 (95% CI 0.97- 3.37, p=0.062). Disease control rate (DCR) was achieved in 55.7% and 45.7% of men and women, respectively, while disease progression was registered in 44.3% of males and 54.3% of females (p=0.386)., Conclusions: Gender is a variable that should be taken into account in the choice of immunotherapy. Future prospective randomized trials testing tailored sex-based immunotherapy strategies are required to validate our findings before integrating into clinical practice., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The incidental discovery of pre-clinical interstitial lung disease (ILD) has led to the designation of interstitial lung abnormalities (ILA), a radiological entity defined as the incidental finding of computed tomography (CT) abnormalities affecting more than 5% of any lung zone. Two recent documents have redefined the borders of this entity and made the recommendation to monitor patients with ILA at risk of progression. In this narrative review, we will focus on some of the limits of the current approach, underlying the potential for progression to full-blown ILD of some patients with ILA and the numerous links between subpleural fibrotic ILA and idiopathic pulmonary fibrosis (IPF). Considering the large prevalence of ILA in the general population (7%), restricting monitoring only to cases considered at risk of progression appears a reasonable approach. However, this suggestion should not prevent pulmonary physicians from pursuing an early diagnosis of ILD and timely treatment where appropriate. In cases of suspected ILD, whether found incidentally or not, the pulmonary physician is still required to make a correct ILD diagnosis according to current guidelines, and eventually treat the patient accordingly., Competing Interests: Conflict of interest: S. Tomassetti declares consultancy and speaker's fees from Roche and Boehringer Ingelheim, outside this project. Conflict of interest: V. Poletti has nothing to disclose. Conflict of interest: C. Ravaglia has nothing to disclose. Conflict of interest: N. Sverzellati has nothing to disclose. Conflict of interest: S. Piciucchi has nothing to disclose. Conflict of interest: D. Cozzi has nothing to disclose. Conflict of interest: V. Luzzi has nothing to disclose. Conflict of interest: C. Comin has nothing to disclose. Conflict of interest: A.U. Wells has nothing to disclose., (Copyright ©The authors 2022.)

Pulmonary hamartoma (PH) may show various combinations of mesenchymal tissues with entrapment of respiratory epithelium. An uncommon variant of PH prevalently consisting of smooth muscle with mucinous proliferation has been reported in literature under several definitions as sporadic reports. We collected a series of 6 leiomyomatous PH associated with mucinous growth from consultation files (3 cases) and multicentric revision of archival files among 128 consecutive surgically resected PH. The lesions have a prevalence for male gender (5:1) and lower lobes (5:1), with a mean age at diagnosis of 61 years. All cases were incidentally disclosed in asymptomatic patients and had an indolent behavior. At histology, 2 cases consisted uniquely of smooth muscle and 4 also showed mature adipose tissue. The mucinous proliferation consisted of a monotonous growth of columnar cells lacking p63-positive basal cells and expressing pan-CKs, MUC5A, and CK7, but negative with TTF-1, napsin, MUC1, MUC2, MUC6, CK20, and CDX2. Smooth muscle was negative with hormonal receptors. Molecular analysis using a multiplex gene panel did not reveal gene mutations, while ALK, BRAF, and ROS1 were negative. In conclusion, we describe a small series of uncommon PH with prevalent leiomyomatous mesenchymal component associated with a mucinous growth (mucinous adenomyomatous hamartoma). Despite the lack of basal cells coating mucinous proliferation and irregular architecture, the favorable outcome and lack of molecular alterations most likely lay for a benign/low-grade tumor. Pathologists should be aware of this unusual occurrence to prevent a diagnosis of overt malignancy, particularly in frozen section, small biopsy, and cytology.

Purpose: To report criticisms and barriers to the "real-life" application of international guidelines and recent developments in the management of locally advanced non-small cell lung cancer (NSCLC) in Italy., Methods: Three 2-day courses were organized. During the first day, experts in different fields of thoracic oncology gave their lecture on diagnosis and therapy for locally advanced NSCLC. During the second day, all participants were divided into four groups to discuss on a clinical case as a multidisciplinary team (MDT). The aim was to stimulate the discussion on practical issues in the management of NSCLC patients in the real-life practice., Results: A total of 196 physicians were involved in the courses as learners. Invasive diagnosis of nodal disease for staging purposes, a priori definition of "surgical resectability" and a regular MDT with all crucial participants available were the three main key points identified for a good management of these patients. The main barriers to the clinical application of a good diagnostic and therapeutic approach to the patient were the absence of a regular and complete MDT in the South and Centre of Italy, while in the North of Italy, time for discussion of clinical cases in the MDT and waiting lists for staging and therapeutic interventions were deemed as the major concerns., Conclusion: The meetings showed that diagnosis and treatment of locally advanced NSCLC are still extremely variable between different Italian regions. Logistic issues, waiting lists, paucity of well-trained staff and expertise seem to be the main barriers to international guidelines application.

Background: Stereotactic ablative body radiation therapy (SBRT) has evolved as the standard treatment for patients with inoperable stage I non-small-cell lung cancer (NSCLC). We report the results of a retrospective analysis conducted on a large, well-controlled cohort of patients with stage I to II NSCLC who underwent lobectomy (LOB) or SBRT., Materials and Methods: One hundred eighty-seven patients with clinical-stage T1a-T2bNoMO NSCLC were treated in 2 academic hospitals between August 2008 and May 2015. Patients underwent LOB or SBRT; those undergoing SBRT were sub-classified as surgical candidates and nonsurgical candidates, according to the presence of surgical contraindications or comorbidities., Results: In univariate analysis, no significant difference was found in local control between patients who underwent SBRT and LOB, with a trend in favor of surgery (hazard ratio [HR], 0.27; 95% confidence interval [CI], 0.07-1.01; P < .053). Univariate analysis showed that overall survival (OS) was significantly better in patients who underwent LOB (HR, 0.44; 95% CI, 0.23-0.85) with a 3-year OS of 73.4% versus 65.2% for surgery and radiation therapy patients, respectively (P < .01). However, no difference in OS was observed between operable patients undergoing SBRT and patients who underwent LOB (HR, 1.68; 95% CI, 0.72-3.90). Progression-free survival was comparable between patients who underwent LOB and SBRT (HR, 0.61; P = .09)., Conclusion: SBRT is a valid therapeutic approach in early-stage NSCLC. Furthermore, SBRT seems to be very well-tolerated and might lead to the same optimal locoregional control provided by surgery for patients with either operable or inoperable early-stage NSCLC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Despite the high rates of perinatal mortality in dogs, the study of canine perinatology did not receive strong scientific interests until recently, probably due to the difficulties in studying long term changes evaluations without incur with ethical issues. In the recent years, however, the usefulness of new matrices, such as the claws, collectable without invasiveness and providing information about a long-term, retrospective window of time were reported to be a suitable tool for the study of canine perinatology in spontaneously dead puppies. The present study was therefore aimed to assess the usefulness of claws as matrices collectable without invasiveness for the study of immunoreactive cortisol and dehydroepiandrosterone (sulfate) in alive puppies at birth, at 30 and at 60 days of age. Beside the effect played by the sampling time, the possible effect of type of birth, vaginal delivery (VD) or elective Cesarean section (CS), as well as of some other maternal or neonatal factors was assessed. The results showed a significant decrease of both hormones from birth to 30 and to 60 days of age (p < 0.001) and from 30 to 60 days of age (p < 0.05), and highlighted, for both hormones, the influence of the type of birth, with newborns born by VD having higher concentrations of immunoreactive cortisol (p < 0.01) and dehydroepiandrosterone (sulfate) (p < 0.001) than the newborns born by elective CS in collections made at birth. No other significant effect was detected. The study confirmed the usefulness of claws as matrix collectable without invasiveness for the retrospective, long-term assessment of hormonal changes in alive newborn puppies and that both hormones declined from birth to 60 days of age. The differences between puppies born by vaginal delivery or elective Caesarean section suggest a possible different HPA activation in puppies born by the two types of birth., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Lung cancer is the most frequent human malignancy and the principal cause of cancer-related death worldwide. Adenocarcinoma is now the main histologic type, accounting for almost half of all the cases. The 2015 World Health Organization has adopted the classification recently developed by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. This new adenocarcinoma classification has incorporated up-to-date advances in radiological, molecular and oncological knowledge, providing univocal diagnostic criteria and terminology. For resection specimens, new entities have been defined such as adenocarcinoma in situ and minimally invasive adenocarcinoma to designate adenocarcinomas, mostly nonmucinous and ≤ 3 cm in size, with either pure lepidic growth or predominant lepidic growth with ≤ 5 mm invasion, respectively. For invasive adenocarcinoma, the new classification has introduced histological subtyping according to the predominant pattern of growth of the neoplastic cells: lepidic (formerly non mucinous brochioloalveolar adenocarcinoma), acinar, papillary, micropapillary, and solid. Of note, micropapillary pattern is a brand new histologic subtype. In addition, four variants of invasive adenocarcinoma are recognized, namely invasive mucinous (formerly mucinous brochioloalveolar adenocarcinoma), colloid, fetal, and enteric. Importantly, three variants that were considered in the previous classification have been eliminated, specifically mucinous cystadenocarcinoma, signet ring cell, and clear cell adenocarcinoma. This review presents the changes introduced by the current histological classification of lung adenocarcinoma and its prognostic implications., (Copyright © 2018 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.)

Objectives: EGFR T790M mutation is the most common mechanism of resistance to first-/second-generation EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) and could be overcome by third-generation EGFR-TKIs, such as osimertinib. Liquid biopsy, a non-invasive technique used to test the presence of the resistant mutation, may help avoiding tissue re-biopsy. However, analysing only circulating-free DNA, information about other less frequent and coexisting resistance mechanisms may remain unrevealed., Materials and Methods: All patients reported in this series participated in the ASTRIS trial, a real world treatment study testing the efficacy of osimertinib (80mg os die) in advanced T790M-positive NSCLC progressed to prior EGFR-TKI. Patients were considered eligible to osimertinib if T790M positive on tissue or plasma samples. In our patients, EGFR molecular testing on blood sample was conducted with digital droplet PCR (ddPCR)., Results: We report our experience of five patients treated with osimertinib after T790M detection on liquid biopsy that presented a disease progression at first tumor assessment mediated by SCLC transformation, as evidenced at tissue re-biopsies. All patients showed low ratio T790M/activating mutation in the blood before osimertinib (lower than 0.03). For three patients, EGFR mutational analysis was T790M-negative when re-assessed by using a less sensitive method (therascreen ® ) on the same liquid biopsy sample analysed by ddPCR before osimertinib therapy., Conclusion: Although liquid biopsy is a relevant tool to diagnose T790M presence in NSCLC patients resistant to EGFR-TKI, in case of a low ratio T790M/activating mutation, tissue biopsy should be considered to exclude the presence of SCLC transformation and/or other concomitant resistance mechanisms., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: In 2008, the first transplantation of a tissue-engineered trachea in a human being was done to replace an end-staged left main bronchus with malacia in a 30-year-old woman. We report 5 year follow-up results., Methods: The patient was followed up approximately every 3 months with multidetector CT scan and bronchoscopic assessment. We obtained mucosal biopsy samples every 6 months for histological, immunohistochemical, and electron microscopy assessment. We also assessed quality of life, respiratory function, cough reflex test, and production and specificity of recipient antibodies against donor human leucocyte antigen., Findings: By 12 months after transplantation, a progressive cicatricial stenosis had developed in the native trachea close to the tissue-engineered trachea anastomosis, which needed repeated endoluminal stenting. However, the tissue-engineered trachea itself remained open over its entire length, well vascularised, completely re-cellularised with respiratory epithelium, and had normal ciliary function and mucus clearance. Lung function and cough reflex were normal. No stem-cell-related teratoma formed and no anti-donor antibodies developed. Aside from intermittent bronchoscopic interventions, the patient had a normal social and working life., Interpretation: These clinical results provide evidence that a tissue-engineering strategy including decellularisation of a human trachea, autologous epithelial and stem-cell culture and differentiation, and cell-scaffold seeding with a bioreactor is safe and promising., Funding: European Commission, Knut and Alice Wallenberg Foundation, Swedish Research Council, ALF Medicine., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Introduction: Recruitment and nodule management are critical issues of lung cancer screening with low-dose computed tomography (LDCT). We report subjects' compliance and results of LDCT screening and management protocol in the active arm of the ITALUNG trial., Methods: Three thousand two hundred six smokers or former smokers invited by mail were randomized to receive four annual LDCT (n = 1613) or usual care (n = 1593). Management protocol included follow-up LDCT, 2-[18F]fluoro-2-deoxy-D glucose positron emission tomography (FDG-PET), and CT-guided fine-needle aspiration biopsy (FNAB)., Results: One thousand four hundred six subjects (87%) underwent baseline LDCT, and 1263 (79%) completed four screening rounds. LDCT was positive in 30.3% of the subjects at baseline and 15.8% subsequently. Twenty-one lung tumors in 20 subjects (1.5% detection) were found at baseline, and 20 lung tumors in 18 subjects (0.5% detection) in subsequent screening rounds. Ten of 18 prevalent (55%) and 13 of 17 incident (76%) non-small-cell cancers were in stage I. Interval growth enabled diagnosis of lung cancer in 16 subjects (42%), but at least one follow-up LDCT was obtained in 741 subjects (52.7%) over the screening period. FDG-PET obtained in 6.5% of subjects had 84% sensitivity and 90% specificity for malignant lesions. FNAB obtained in 2.4% of subjects showed 90% sensitivity and 88% specificity. Positivity of both FDG-PET and FNAB invariably predicted malignancy. Surgery for benign lesions was performed on four subjects (10% of procedures) but followed protocol violations on three subjects., Conclusions: High-risk subjects recruited by mail who entered LDCT screening showed a high and stable compliance. Efficacy of screening is, however, weakened by low detection rate and specificity. Adhesion to management protocol might lessen surgery for benign lesions.

In this article, a series of tables (presented in alphabetic order) summarize the differential diagnosis of diffuse parenchymal lung diseases starting from the most frequent elementary lesions.

Primary bladder adenocarcinoma accounts for 0.5-2% of all malignant bladder tumours. Literature data indicate the bladder as the second most common site of metastatic genitourinary tumours, with the kidney as the most frequent location. Secondary tumours of the bladder account for about 2.3% of all bladder malignancies encountered in surgical specimens. Herein, we describe an adenocarcinoma deeply infiltrating the bladder wall, with no morphologic features of transitional cell carcinoma, in a patient with a previous diagnosis of primary lung adenocarcinoma, mixed subtype. In this case, the use of a limited immunohistochemical panel including napsin A, a recently described highly sensitive marker for lung adenocarcinoma, GATA3 and S100P, two novel markers of urothelial differentiation, was of crucial importance in differentiating between lung adenocarcinoma metastatic to the bladder and primary bladder adenocarcinoma.

Background: Recent studies have shown that the cyclooxygenase (COX) and the inducible nitric oxide synthase (iNOS) pathways are involved in the development of tumor angiogenesis in human cancers., Aims: To investigate whether a different pattern of COX-2 and iNOS expression/activity exists within different areas of colorectal tumors and to analyze the relationship between these two enzymes and tumor angiogenesis., Methods: Microvessel density (MVD) and COX-2, iNOS, vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) protein expression were evaluated at both the invasive front (IF) and the tumor center (TC) in 46 human colorectal cancer specimens. We also investigated the concentration of PGE2 and NO at the same sites., Results: COX-2 and iNOS protein expression and activity were significantly higher within the IF than the TC of the tumor specimens. Similarly, MVD and VEGF/VEGFR-2 expression significantly increased from the TC to the IF. Only COX-2 expression was significantly correlated with MVD and VEGF/VEGFR-2 expression at both the TC and the IF., Conclusion: Our study shows a heterogeneous expression of COX-2 and iNOS in colorectal cancer. The up-regulation of COX-2 at the IF parallels an increase in vessel density and VEGF/VEGFR-2 expression, thus supporting the hypothesis that the tumor periphery is the most aggressive portion of a colorectal tumor., (Copyright (c) 2009 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Aim: The aim of this study was to conduct a retrospective clinical and pathological analysis of the authors' 20-year experience on treatment of typical and atypical carcinoid tumours., Methods: A retrospective clinical and pathological analysis was conducted on 89 patients treated for bronchial carcinoid neoplasms at the Division of Thoracic Surgery, Hospital of Florence (Italy) between January 1986 and January 2006. They were 47 male (52.8%) and 42 female patients, age ranging from 22 to 77 years (average: 55.5 years). Diagnosis was made with radiological methods such as plain chest roentgenography, computed tomography (CT), and bronchoscopy. On the basis of bronchoscopic findings 63 carcinoids (70.8%) were centrally located and 26 (29.2%) were classified as peripheral. In 38 cases of central lesion the diagnosis was obtained by endobronchial biopsy. A correct pathological diagnosis was obtained before surgery in 58 patients; in the others resected cases the correct diagnosis was determined by intraoperative histology during surgery. All operation were performed through a thoracotomy, with sparing muscle in last ten years. Surgical procedures utilized were lobectomy, pneumonectomy, segmentectomy, wedge resections, sleeve resections and bronchoplastic procedures. A radical mediastinal lymphadenectomy was performed in every operation., Results: There were 63 (70.8%) typical carcinoid (TC) and 26 (29,2%) atypical carcinoid (AC). No operative or postoperative mortality was seen. Ten patients (11.7%) experienced complications: 4 prolonged air leaks, 2 bleeding requiring re-operation, 1 chylothorax, 1 pulmonary embolism, 2 late cicatricial bronchial stenosis after sleeve lobectomy treated successfully by laser therapy. Four patients (4.5%) were treated with endoscopy plus surgery. In all that patients a Laser Nd-YAG coagulation and excision of the lesion was performed. Four patients (4.5%) were treated only with endoscopy, overall because of bad general condition. On the basis of the hystopatological documentation of all patients operated before 1999 (60 patients) the authors observed that in 4 cases (6.6%) the diagnosis has changed from AC to TC while only 1 case (1.6%) of AC was classified as TC with new criterias. During median 122-month follow-up 7 relapses (8.2%) were diagnosed in operated patients; recurrent cancer developed preferentially in AC (N=4, 16.6%) than TC (N=3, 4.9%). The overall survival at 10 and 15 years was 92% and 82% respectively., Conclusions: Anatomical resection, including formal lobectomy (or pneumonectomy when indicated) and radical mediastinal lymphadenectomy, should be performed in carcinoid tumours.

Background: Results of randomized clinical trials (RCTs) are needed to assess the efficacy of lung cancer screening with low-dose chest computed tomography (CT) in reducing lung cancer mortality. We report design and results of enrolment and baseline screening test in the ITALUNG trial, a RCT., Methods: Invitation letters were sent to subjects of 55-69 years of age clients of 269 general practitioners. Smokers or former smokers of at least 20 pack/years were eligible and after written consent were randomized in an active arm undergoing a low-dose CT annually for 4 years and in a control arm receiving no screening. Management of positive screening test was carried out using follow-up low-dose CT, fluorodeoxyglucose positron emission tomography, fine needle aspiration cytology and fiber optic bronchoscopy., Results: A sample of 3206 eligible subjects was achieved by sending 71,232 letters (enrolment efficacy = 4.5%). Subjects in control (n = 1593) and active (n = 1613) arm were balanced for age, gender and smoking history. Two-hundred and seven (12.8%) subjects did not undergo CT after randomization. The baseline screening test was positive in 426 (30.3%) of 1406 subjects. Twenty-one lung cancers (prevalence = 1.5%) were found in 20 subjects: 18 non-small cell lung cancer (NSCLC), 2 small cell lung cancer (SCLC) and a case of typical carcinoid. Ten NSCLC (47.6%) were in Stage I. Sixteen fine needle aspirations were performed in 15 lung cancers, with a positive result in 12 (75%) cases. One biopsy only (6.3%) was performed on a benign lesion. Seventeen lung cancers (81%) were treated with surgical resection in 16 subjects. One subject underwent surgery for a benign lesion (5.5% of all surgical resections)., Conclusions: Recruitment by mail of high risk subjects for a lung cancer screening RCT is feasible but not efficient. Results of the baseline screening test in the active arm of the ITALUNG trial are substantially in line with those of RCT and observational studies.

Homozygous deletion of p16/CDKN2A is the most common genetic abnormality in malignant mesotheliomas. The aim of this study was to determine prognostic significance of p16/CDKN2A loss in malignant pleural mesotheliomas (MPM) as defined by immunohistochemistry and fluorescence in situ hybridization (FISH). High-density tissue microarrays were constructed from archival formalin-fixed paraffin-embedded samples of 48 MPM. Long survival (LS) was defined as survival greater than 3 years from the time of diagnosis, and short survival was defined as less than 3 years from the time of diagnosis. Both loss of p16 protein expression by immunohistochemistry and homozygous deletion of p16 by FISH were associated with adverse prognosis. Female gender, positive p16 immunoexpression, and lack of p16/CDKN2A deletion significantly predicted the survival for the LS group. Statistical analysis showed a very strong correlation of immunohistochemistry and FISH data. Cases positive for p16 immunoexpression and negative for 9p21 deletion showed the best survival time. Our study is the first to demonstrate decreased frequency of homozygous deletion of 9p21 and loss of p16 immunoreactivity in pleural mesotheliomas from patients with long-term survival of greater than 3 years in contrast to patients with rapidly fatal mesotheliomas. A possible implementation of these tests into preoperative prognostication of MPM and therapeutic decisions should be considered.

Background: A retrospective study including all patients with non-small cell lung cancer carcinoma in a population-based registry was performed to characterize gender differences in lung cancer and to analyze the factors influencing prognosis in women., Methods: We retrieved through the Tuscan Cancer Registry (RTT) archive 2,523 lung tumor cases diagnosed during the period 1996-1998 in the provinces of Florence and Prato, central Italy. We compared the prognosis within 464 non-small lung cancer women and 1,798 men in a population-based case series. The influence of the following variables on postoperative survival were analyzed: age, cell type, pathologic T and N status, site of tumor and type of surgical resection., Results: The age at diagnosis was similar in women and in men. Women were significantly more likely to have adenocarcinoma but less likely to have squamous cell carcinoma compared with men. Fewer pneumonectomies were performed in women than in men. Nevertheless, prognosis was similar in both sexes and type of surgical resection was significant prognostic factor., Conclusions: Lung cancer was more frequent in men than in women, but overall survival is similar. Differences in lung cancer histology and rate of pneumonectomies were found between men and women.

A case of primary pulmonary rhabdomyosarcoma occurring in a 62-year-old man is reported, and a review of the literature is presented. The tumor affected the left upper lobe and involved the mediastinal lymph nodes. Immunohistochemical and ultrastructural studies supported the myogenic phenotype of the neoplasm. A left pneumonectomy was performed with complete surgical removal of the tumor. Postoperative radiotherapy was carried out. The patient is currently alive and free of disease 9 months after operation. Despite the rarity of primary pulmonary rhabdomyosarcoma, this tumor should be differentiated from other poorly differentiated pulmonary neoplasms and from metastatic sarcomas.

The distinction between pleural epithelial mesothelioma and peripheral lung adenocarcinoma involving the pleura is still an important diagnostic problem for surgical pathologists. The aim of our study was to identify the most specific and sensitive markers for the positive identification of mesothelioma to select a limited, appropriate panel of antibodies to differentiate between mesothelioma and adenocarcinoma. Forty-two cases of epithelial mesotheliomas and 23 cases of pulmonary adenocarcinomas were stained with the following antibodies: anticalretinin, antithrombomodulin, anti-CD44H, and monoclonal antibody HBME-1. We also studied the value of other markers in current use: cytokeratins AE1/AE3 and CAM5.2, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), Ber-EP4, B72.3, and CD15. Of the mesotheliomas, 42 stained for calretinin, 39 (92.8%) for thrombomodulin, 42 stained for CD44H, and 41 (97.6%) stained for HBME-1. Among negative markers, 4 (9.5%) mesothelioma cases stained for CEA, 5 (11.9%) stained for Ber-EP4, 6 (14.2%) stained for B72.3, and 2 (4.7%) stained for CD15. Of the lung adenocarcinomas, 2 (8.7%) cases showed reactivity for calretinin, 5 (21.7%) for thrombomodulin, 13 (56.5%) for CD44H, all for HBME-1, 22 (95.6%) for CEA, 22 (95.6%) for Ber-EP4, 8 (34.7%) for B72.3, and all for CD15. In conclusion, calretinin and thrombomodulin were the most specific positive mesothelial markers, whereas CD44H and HBME-1 showed high sensitivity but very low specificity. Among negative markers, we advocate the use of CEA and CD15 which were the most specific in differentiating mesotheliomas from adenocarcinomas.

We report on a 14-year-old boy who presented with a 4-year history of acral pains and febrile episodes. On physical examination, numerous small reddish papules were present on his abdomen, located predominantly on the periumbelical region. Renal function was within normal limits. Ophthalmological examination revealed whorled opacities of the cornea (cornea verticillata) and dilated tortuous conjunctival vessels. Histopathological examination of one of the cutaneous papules showed several dilated blood vessels in the superficial dermis surrounded by collarettes of thickened rete ridges, consistent with a diagnosis of angiokeratoma. The electron-microscopic study of a skin specimen demonstrated the presence of dilated lysosomes with deposition of electron-dense bodies, some of which with laminated structure, in endothelial cells and fibroblasts. These findings were regarded as indicative of Fabry's disease. Subsequent biochemical analysis confirmed the presence of a alpha-galactosidase A deficiency in leukocytes. In conclusion, we described the clinical, histopathological and submicroscopic findings of a case of Fabry's disease, in which the combination of electron microscopic and biochemical approaches allowed the correct diagnosis.

While the analysis of the clinical, radiologic, and histopathologic features of surface osteosarcomas has been the subject of several papers, identification of the phenotypic features of these tumors has so far received little attention. The aim of the present study was to characterize the neoplastic cells of surface osteosarcomas using an ultrastructural and immunohistochemical approach. Glutaraldehyde-fixed, epoxy resin-embedded archival pieces of tissue from 8 surface osteosarcomas (4 parosteal low-grade osteosarcomas, 3 dedifferentiated parosteal osteosarcomas, 1 periosteal osteosarcoma) were investigated using transmission electron microscopy. Sections of formalin-fixed, paraffin-embedded tumor specimens were employed for the immunohistochemical analysis of osteonectin and osteocalcin, two markers of cells of osteoblastic lineage, and sigma-smooth muscle actin and muscle specific actin. By electron microscopy, the tumors were composed of a mixture of neoplastic cells with varied differentiation, i.e., osteoblast-like, fibroblast-like, myofibroblast-like, and chondroblast-like. The latter were particularly abundant in the periosteal osteosarcoma. Osteocalcin expression was detected in the cytoplasm of neoplastic cells in 6 cases (66.6%), while osteonectin was expressed at least focally in all cases. The expression of the noncollagenous bone proteins was higher in low-grade osteosarcomas than in dedifferentiated osteosarcomas. sigma-Smooth muscle actin and muscle-specific actin expression were detected in 4 (44.4%) and 5 (55.5%) cases respectively, and the distribution was similar in both low-grade and dedifferentiated lesions. The results do not confirm previous observations regarding the prevalence of a specific cellular phenotype in surface osteosarcomas. Further, the myofibroblast-like cells that are present in variable numbers in these tumors are probably modified osteoblasts, since they co-express actin, osteonectin, and osteocalcin.