Multicenter Observational Study on Metastatic Non-Small Cell Lung Cancer Harboring BRAF Mutations: Focus on Clinical Characteristics and Treatment Outcome of V600E and Non-V600E Subgroups.

INTRODUCTION: BRAF mutation involved 2-4% of lung adenocarcinoma. Differences in clinicopathologic features and patient outcome exist between V600E and non-V600E BRAF mutated NSCLC. Thus, we sought to assess the frequency and clinical relevance of BRAF mutations in a real-life population of advanced-NSCLC, investigating the potential prognostic significance of distinct genetic alterations. MATERIALS AND METHODS: The present multicenter Italian retrospective study involved advanced BRAF mutant NSCLC. Complete clinicopathologic data were evaluated for BRAF V600E and non-V600E patients. RESULTS: A total of 44 BRAFmut NSCLC patients were included (V600E, n = 23; non-V600E, n = 21). No significant differences in survival outcome and treatment response were documented, according to V600E vs. non-V600E mutations, although a trend towards prolonged PFS was observed in the V600E subgroup (median PFS = 11.3 vs. 6.0 months in non-V600E). In the overall population, ECOG PS and age significantly impacted on OS, while bone lesions were associated with shorter PFS. Compared to immunotherapy, first-line chemotherapy was associated with longer OS in the overall population, and especially in the BRAF V600E subtype. CONCLUSIONS: Here, we report on real-life data from a retrospective cohort of advanced-NSCLC harboring BRAF alterations. Our study offers relevant clues on survival outcome, therapeutic response, and clinicopathologic correlations of BRAF-mutant NSCLC.

Monitoring cfDNA in Plasma and in Other Liquid Biopsies of Advanced EGFR Mutated NSCLC Patients: A Pilot Study and a Review of the Literature.

In order to study alternatives at the tissue biopsy to study EGFR status in NSCLC patients, we evaluated three different liquid biopsy platforms (plasma, urine and exhaled breath condensate, EBC). We also reviewed the literature of the cfDNA biological sources other than plasma and compared our results with it about the sensitivity to EGFR mutation determination. Twenty-two EGFR T790M-mutated NSCLC patients in progression to first-line treatment were enrolled and candidate to osimertinib. Plasma, urine and EBC samples were collected at baseline and every two months until progression. Molecular analysis of cfDNA was performed by ddPCR and compared to tissue results. At progression NGS analysis was performed. The EGFR activating mutation detection reached a sensitivity of 58 and 11% and for the T790M mutation of 45 and 10%, in plasma and urine samples, respectively. Any DNA content was recovered from EBC samples. Considering the plasma monitoring study, the worst survival was associated with positive shedding status; both plasma and urine molecular progression anticipated the radiological worsening. Our results confirmed the role of plasma liquid biopsy in testing EGFR mutational status, but unfortunately, did not evidence any improvement from the combination with alternative sources, as urine and EBC.

Pneumothorax and pulmonary hemorrhage after CT-guided lung biopsy: incidence, clinical significance and correlation.

OBJECTIVES: To evaluate the incidence and clinical significance of pneumothorax (PTX) and pulmonary hemorrhage (PH) after CT-guided lung biopsy (CT-LB). To test correlations of PTX and chest tube insertion (CTI) with PH and other imaging and procedural parameters. METHODS: Pre-procedural CT and CT-LB scans of 904 patients were examined. Incidence of PTX and PH and PH location (type-1 along needle track; type-2 perilesional) and severity according to its thickness (low grade < 6 mm; high grade > 6 mm) were recorded. PTX was considered clinically significant if treated with CTI, PH if treated with endoscopic/endovascular procedure. Binary logistic regression analyses were used to determine the effects of different imaging and procedural parameters on the likelihood to develop PTX, CTI and PH and to define their correlation. RESULTS: PTX occurred in 306/904 cases (33.8%); CTI was required in 18/306 (5.9%). PH occurred in 296/904 cases (32.7%), and no case required treatment. Nodule-to-pleura distance (ORPTX = 1.052; ORCTI = 1.046; ORPH 1.077), emphysema (ORPTX = 1.287; ORPH = 0.573), procedure time (ORPTX = 1.019; ORCTI = 1.039; ORPH = 1.019), target size (ORPTX = 0.982; ORPH = 0.968) and needle gauge (ORPTX = 0.487; ORCTI = 4.311; ORPH = 2.070) showed statistically significant correlation to PTX, CTI and PH. Type-1 PH showed a protective effect against PTX and CTI (ORPTX = 0.503; ORCTI = 0.416). CONCLUSION: PTX and PH have similar incidence after CT-guided lung biopsy. PH along needle track may represent a protective factor against development of PTX and against PTX requiring CTI.

Optimizing PD-L1 evaluation on cytological samples from advanced non-small-cell lung cancer.

Aim: Programmed cell death-ligand 1 (PD-L1) predicts response to immune checkpoint inhibitors in non-small-cell lung cancer (NSCLC) patients. Most NSCLCs are diagnosed at an advanced stage and using minimally invasive diagnostic procedures that yield small biopsies or cytological samples. Methods: Cytological smears and paired histological samples from 52 advanced NSCLC patients were tested for PD-L1 expression by immunocyto/histochemistry (ICC/IHC) and for PD-L1 gene status by FISH. Results:PD-L1 was overexpressed in 9/52 (17%) cytological samples and in seven (13.5%) matched biopsies. The concordance between immunocytochemistry and IHC was 92.3% (48/52; p < 0.001). The concordance between PD-L1 gene status on cytology and histology was 69.2% (18/26; p < 0.001). No correlation between IHC and fluorescence in situ hybridization results was found. Conclusion: Our data support the feasibility and reliability of PD-L1 protein and PD-L1 gene assessment on direct cytological smears from NSCLC patients whenever histological sample are inadequate.

Transthoracic computed tomography-guided lung biopsy in the new era of personalized medicine.

Computed tomography-guided lung biopsy is a valid and safe procedure for characterizing pulmonary nodules. In the past years, this technique has been mainly used to confirm the malignant nature of undetermined pulmonary lesions; however, today its role has been completely renewed. With the advent of target therapy and immunotherapy, it has arisen for lung cancer, in inoperable patients, the necessity to obtain adequate bioptical material to perform a correct molecular characterization of the lesion. Moreover, the possibility of acquired drug-resistance mechanisms makes it necessary in some cases to rebiopsy these lesions over time. For these reasons, it is likely that the request of computed tomography-guided lung biopsy will increase in the future, therefore every radiologist should be confident with its most important aspects.

Looking for Lepidic Component inside Invasive Adenocarcinomas Appearing as CT Solid Solitary Pulmonary Nodules (SPNs): CT Morpho-Densitometric Features and 18-FDG PET Findings.

OBJECTIVE: To investigate CT morphologic and densitometric features and 18-FDG PET findings of surgically excised lung adenocarcinomas "mixed subtype" with predominant lepidic component, appearing as solid solitary pulmonary nodules (SPNs) on CT scan. MATERIALS AND METHODS: Approval for this study was given from each local institutional review board according to its retrospective nature. Nodules pathologically classified as lung adenocarcinoma mixed subtype with bronchioloalveolar otherwise lepidic predominant component, in three different Italian institutions (Napoli; Varese; Parma), were retrospectively selected. RESULTS: 22 patients were identified. The number of SPNs with smooth margins was significantly lower with respect to the number of SPNs with spiculated margins (p: 0.033), radiating spiculations (p: 0.019), and notch sign (p: 0.011). Mean contrast enhancement (CE) was 53.34 HU (min 5.5 HU, max 112 HU); considering 15 HU as cut-off value, CE was positive in 20/22 cases. No significant correlation was found between size and CE. Mean SUVmax was 2.21, ranging from 0.2 up to 7.5 units; considering 2.5 units as cut-off, SUVmax was positive in 7/22 cases. The number of SPNs with positive CE was significantly higher than the number of SPNs with positive SUVmax (p: 0.0005). CONCLUSION: CT generally helps in identifying solid SPN suspicious for malignancy but 18-FDG PET may result in false-negative evaluation; when 18-FDG PET findings of a solid SPN are negative even though CT morphology and CE suggest malignancy, radiologist should consider that lepidic component may be present inside the invasive tumor, despite the absence of ground glass.

Extra-pleuric coaxial system for CT-guided percutaneous fine-needle aspiration biopsy (FNAB) of small (≤20 mm) lung nodules: a novel technique using multiplanar reconstruction (MPR) images.

The aim of the study is to present the diagnostic feasibility, usefulness, and safety of a novel technique for coaxial CT-guided fine-needle aspiration biopsy of small (≤20 mm in diameter) lung nodules. A 18-gauge (G) (1.2 × 40 mm) needle is inserted through the skin in the depth of the thoracic wall tissues remaining outside the pleura. Its positioning is planned and adjusted using multiplanar reconstruction (MPR) images along the 18-G guide needle axis tracing a reference outline extended from the needle tip to the target nodule. When the insertion of the 18-G extra-pleuric needle (EPN) proves to be precise, a 22-G Chiba needle is then passed through the outer 18-G EPN until it reaches the thoracic lesion for the sampling procedure. Patient population included 153 males and 94 females, with a mean age of 61.3 ± 21.6 years. Mean nodule diameter was 14.1 ± 2.2 mm. The lesion depth from pleural plane ranged from 0 mm to 127 mm. An average of 1.29 aspirates were performed per lesion. The most common complication was pneumothorax in 27 cases; there were no cases of PNX requiring chest tube insertion. Intrapulmonary bleeding along the needle track was observed in 32 patients. Exploiting the advantage of MPR images, our novel technique of extra-pleuric coaxial system with a 18-G EPN allows the operator to multiple samplings of small (≤20 mm) target lesions in various locations with a thinner (22-G Chiba) needle, thus reducing the degree of pleural, parenchymal, or adjacent organs damage.

CT-guided fine-needle aspiration of abdominal and retroperitoneal small lesions with the coaxial technique using MPR images.

PURPOSE: To demonstrate the advantages of CT-guided fine-needle aspiration (FNA) of abdominal and retroperitoneal small lesions with the coaxial technique using MPR images. MATERIALS AND METHODS: The study included retrospectively 50 patients who underwent CT-guided FNA of abdominal and/or retroperitoneal small lesion (<30 mm). Patients with suspected lymphomas or sarcomas were excluded. Cytology reports were the reference standard. RESULTS: The cytology was diagnostic in 48/50 biopsies (96%): out of 41 neoplastic lesions (85%), 37 were malignant (90.2%) and 4 were benign (9.8%); 7 out of 48 were non-neoplastic (14.6%). No procedural complications were observed (0%). CONCLUSION: By using MPR images there is an effective improvement in coaxial CT-guided FNA of abdominal and retroperitoneal small lesions.

Isolation and Characterization of Circulating Tumor Cells in Squamous Cell Carcinoma of the Lung Using a Non-EpCAM-Based Capture Method.

INTRODUCTION: The exclusion of circulating tumor cells (CTCs) that have lost epithelial antigens during the epithelial-to-mesenchymal transition (EMT) process by using Epithelial Cell Adhesion Molecule (EpCAM) based capture methods is still a matter of debate. In this study, cells obtained after depletion procedure from blood samples of squamous cell lung cancer (SQCLC) patients were identified based on morphology and characterized with the combination of FISH assessment and immunophenotypic profile. MATERIALS AND METHODS: Five mL blood samples, collected from 55 advanced SQCLC patients, were analyzed by a non-EpCAM-based capture method. After depletion of leukocytes and erythroid cells, the negative fraction was characterized by both FISH using a fibroblast growth factor receptor 1 (FGFR1) probe and by immunocytochemistry. Thirty healthy donors were also tested. RESULTS: Based on morphology (nuclear dimension ≥10 µm, shape and hypercromatic aspect) suspicious circulating cells clearly distinguishable from contaminant leukocytes were observed in 49/55 (89%) SQCLC patients. Thirty-four of the 44 (77%) samples evaluable for FGFR1 FISH showed ≥ 6 FGFR1 gene copy number on average per cell. Vimentin expression involved 43% (18/42) of pooled circulating SQCLC cells, whereas only 29% (14/48) were EpCAM positive. Confocal microscopy confirmed the localization of FGFR1 probe in suspicious circulating cells. Suspicious circulating elements were also observed in healthy donors and did not show any epithelial associated antigens. A significantly lower number of suspicious circulating cells in healthy donors compared to SQCLC patients was found. CONCLUSIONS: Among the heterogeneous cell population isolated by depletion procedure, the coexistence of cells with epithelial and/or mesenchymal phenotype suggests that EMT may participate to transendothelial invasion and migration of tumor cells in advanced SQCLC. The finding of cells with neither EpCAM or EMT phenotype, retrieved after non-EpCAM-based systems, underlines the presence of suspicious elements in the blood of both SQCLC patients and healthy donors. Further phenotyping and molecular analyses are necessary to fully characterize these circulating elements.

ALK and ROS1 rearrangements tested by fluorescence in situ hybridization in cytological smears from advanced non-small cell lung cancer patients.

BACKGROUND: The identification of ALK and ROS1 rearrangements and the availability of an effective target therapy, such as crizotinib, represent a new option in the treatment of advanced non-small cell lung cancer (NSCLC) patients. In light of recent advances in non-invasive diagnostic procedures, we aimed to demonstrate that direct cytological smears are suitable for assessing ALK and ROS1 rearrangements in patients with NSCLC. METHODS: Fifty-five patients with a cytological diagnosis of lung adenocarcinoma (ADC) were evaluated for ALK rearrangements by fluorescence in situ hybridization (FISH) and 12 patients for ROS1 FISH rearrangements. Seventeen of the 55 cytological samples tested for ALK were obtained from the primary tumor and 38 from metastatic lesions. Ten of 12 samples evaluated for ROS1 were obtained from metastatic sites and two from the primary tumor. RESULTS: ALK FISH was successful in 49/55 (89%) cytological ADC samples and ROS1 FISH in all 12 cytological samples. ALK rearrangements were found in 3/13 (23%) primary tumors and 7/36 (19%) metastatic sites. ROS1 rearrangements were found in one of the two primary tumors and in two of the 10 metastases. Two of the three rearranged cases were tested on cytology after knowing that they were rearranged on histology in order to increase representativeness of ROS1 rearranged cases in this study. CONCLUSION: Whenever cytology represents the only available material for diagnosis and biological characterization of NSCLC, minimally invasive procedures may provide an additional important source of cellular material for FISH assessment of ALK and ROS1 rearrangements.

Conventional transbronchial needle aspiration with 23 gauge needle: a preliminary study.

BACKGROUND: Conventional transbronchial needle aspiration (cTBNA) is a safe and minimally invasive procedure with a high yield for the diagnosis of large lymph nodes (LNs) in favourable locations (LNs >1.5 cm in stations #4R and/or #7). However, it is usually underutilized by pulmonologist. One of the main reasons given for not performing cTBNA is the risk of puncturing vascular structures of the mediastinum. Recently, with the twofold objective of minimize the risk of bleeding and reduce the cTBNA cost, a thinner and less expensive needle has been commercialized. It is a 23 gauge (G) needle that costs 34, 37 €. The aim of our study was to analyze the sample adequacy, diagnostic accuracy and safety of this needle in comparison with 21 and 22 G needles (average cost: 6,400 €). METHODS: We retrospectively analysed medical records from patients who underwent bronchoscopy with cTBNA for the diagnosis of LNs >1.5 cm in stations #4R and/or #7 at the Thoracic Endoscopy Unit of the University Hospital of Parma from January 1st, 2007 to October 31(st), 2011. Five hundred patients underwent cTBNA from January 1(st), 2007 to October 31(st), 2011. In order to reduce the technical and personal bias for sampling procedure we analyzed only cases sampled by a single well-trained bronchoscopist, particularly skilful at cTBNA. RESULTS: A total of 222 patients (186 men; mean age 63 years±12, range 6-89) with LNs >1.5 cm in stations #4R and/or #7 were identified. A 23 G needle was used in 84 patients (38%), a 21 G needle in 88 patients (40%) and a 22 G needle in 50 patients (22%). No statistically significant differences between the 23 G group and the 21 or 22 G group in sample adequacy (P=0.78 and P=0.12, respectively) and diagnostic accuracy (P=0.9 and P=0.4, respectively) were found. There were no intraprocedural or postprocedural complications irrespective of the size of needle used. CONCLUSIONS: Transbronchial 23 G needle is as safe and effective as the 21 and 22 G needle for the sampling of LNs >1.5 cm in stations #4R and/or #7. For this reason, to obtain cytology specimens from large LNs in favourable locations, the 23 G needle may represent an alternative and less expensive choice compared to 21 and 22 G needles, even if our observation needs to be confirmed in a larger prospective study.

Curved Needles in CT-Guided Fine Needle Biopsies of Abdominal and Retroperitoneal Small Lesions.

PURPOSE: To demonstrate the advantages of using curved needles in fine needle aspiration (FNA) with CT-guided, for analyzing abdominal and/or retroperitoneal small lesions which are impossible to reach with conventional non-surgical biopsy techniques, particularly in cases in which the cytology sample was not possible to obtain by means of US or CT guide with axial images. MATERIALS AND METHODS: An authorization for CT-guided FNA in patients with neoplasms is not required by the institutional review board of our Institute. From April 2012 to November 2014, the study included retrospectively 25 patients (16 M, 9 F) who underwent CT-guided FNA of abdominal and/or retroperitoneal small lesions (<30 mm), in which the ultrasound and axial CT scans were not reliable guides for the biopsy procedure because of the interposition of anatomical obstacles. Patients with suspected lymphomas or sarcomas, pediatric patients and patients with bleeding diathesis were excluded. Cytology reports were used for evaluating suitability. RESULTS: The biological material was considered to be suitable for cytological study, with a diagnostic value in all 25 cases, finding in particular: out of 23 neoplastic lesions (85%), 21 were malignant (90.2%) and 2 were benign (8%). 2 out 25 were non-neoplastic benign lesions (8%). No procedural complications arose in any of the cases (0%). CONCLUSION: Using curved needles, there is an effective improvement in CT-guided FNA of abdominal and retroperitoneal small lesions which are difficult to achieve with conventional CT or ultrasound guide.

CT-guided biopsy of pulmonary nodules: is pulmonary hemorrhage a complication or an advantage?

PURPOSE: We aimed to assess the correlation between pulmonary hemorrhage and pneumothorax in computed tomography (CT)-guided transthoracic fine needle aspiration (TTFNA), particularly its possible value as protection against the development of pneumotorax. MATERIALS AND METHODS: We reviewed the CT images of 538 patients (364 males and 174 females, mean age 70 years, range 36-90 years) who underwent CT-guided TTFNA of pulmonary nodules between January 2008 and September 2013. The following CT findings were assessed: pulmonary hemorrhage (type 1, along the needle track; type 2, perilesional; low-grade, ≤6 mm; high-grade, >6 mm), pneumothorax, distance between the target nodule and the pleural surface, and emphysema. RESULTS: Pneumothorax occurred in 154 cases (28.6%) and pulmonary hemorrhage occurred in 144 cases (26.8%). The incidence of pneumothorax was lower in patients showing type 1 and high-grade pulmonary hemorrhage pattern. The incidence of pneumothorax in biopsies ≥30 mm from pleural surface was 26% (12/46) in cases showing this pattern, while it was 71.4% (30/42) when this pattern was not seen. Similarly, the incidence of pneumothorax in biopsies <30 mm from the pleural surface was 0% (0/28) in cases showing this hemorrhage pattern, while it was 19% (76/394) when this pattern was not seen. CONCLUSION: Pulmonary hemorrhage during TTFNA is a frequent event that protects against pneumothorax. A bleeding greater than 6 mm along the needle track is associated with lower incidence of pneumothorax, especially in biopsies deeper than 3 cm.

Predictive factors of diagnostic accuracy of CT-guided transthoracic fine-needle aspiration for solid noncalcified, subsolid and mixed pulmonary nodules.

PURPOSE: The aim of this study was to analyse factors predicting the diagnostic accuracy of computed tomography (CT)-guided transthoracic fine-needle aspiration (TTFNA) for solid noncalcified, subsolid and mixed pulmonary nodules, with particular attention to those responsible for false negative results with a view to suggesting a method for their correction. MATERIALS AND METHODS: From January 2007 to March 2010, we retrospectively reviewed the CT images of 198 patients of both sexes (124 males and 74 females; mean age, 70 years; range age, 44-90) used for the guidance of TTFNA of pulmonary nodules. Aspects considered were: lesion size and density, distance from the pleura, and lesion site. Multiplanar reformatted images (MPR) were retrospectively obtained in the sagittal and axial oblique planes relative to needle orientation. RESULTS: The overall diagnostic accuracy of TTFNA CT-guided biopsy was 86% for nodules between 0.7 and 3 cm, 83.3% for those between 0.7 and 1.5 cm, and 92% for those between 2 and 3 cm. Accuracy was 95.1% for solid pulmonary nodules, 84.6% for mixed nodules, and 66.6% for subsolid nodules. The diagnostic accuracy of CT-guided TTFNA in relation to the distance between the nodule and the pleural plane was 95.6% for lesions adhering to the pleura and 83.5% for central ones. The diagnostic accuracy was 84.2% for the pulmonary upper lobe nodules, 85.3% for the lower lobe and 90.9% for those in the lingula and middle lobe. In 75% of false negative and inadequate/insufficient cases the needle was found to lie outside the lesion, after reconstruction of the needle path by MPR. CONCLUSIONS: The positive predictive factors of CT-guided TTFNA are related to the nodule size, density and distance from the pleural plane. The most common negative predictive factor of CT-guided TTFNA is the wrong position of the needle tip, as observed in the sagittal and axial oblique sections of the MPR reconstructions. The diagnostic accuracy of CT-guided TTFNA can therefore be improved by using the MPR technique to plan the needle path during the FNA procedure.

Reliability of EGFR and KRAS mutation analysis on fine-needle aspiration washing in non-small cell lung cancer.

INTRODUCTION: Molecular profiling of advanced non-small cell lung cancer (NSCLC) has become essential for predicting customized medical treatment decision. In light of recent advances in non-invasive diagnostic procedures in NSCLC, we aimed to demonstrate the reliability of assessing molecular tests for epidermal growth factor receptor (EGFR) and KRAS genes on cytological samples by comparing the molecular profile obtained on cells from scraped smears with that on paired needle washing in a series of NSCLC cases. METHODS: Thirty-two cytological specimens obtained by fine-needle aspiration biopsy procedures from primary or metastatic lesions of NSCLCs were Giemsa stained for a rapid on-site evaluation and, in case of an adequate sampling, the cellular material obtained from needle washing was collected into a saline solution. Scraped smears and needle washings were tested for EGFR and KRAS by polymerase chain reaction followed by direct sequencing. RESULTS: The concordance between EGFR and KRAS mutational status in 29 paired scraped smears and needle washing was 100%, with 7 paired samples showing the same EGFR mutation (4 L858R mutation, 2 E746_A750 deletion and 1 A767_V769 duplication) and 8 paired samples showing the same KRAS mutations (4 G12D, 1 G12A, 1 G12V and 2 G12C). Three scraped smears, uninformative for poor DNA quality, resulted EGFR mutated on paired needle washings. CONCLUSIONS: Needle washing obtained in the course of NSCLC non-invasive fine needle diagnostic procedures allows reliable mutation testing and can be regarded as an additional important source of biological material for molecular profiling of advanced NSCLC.

Epidermal growth factor receptor and Kras gene expression: reliability of mutational analysis on cytological samples.

Epidermal growth factor receptor (EGFR) and Kras gene mutations are crucial for discriminating patients responsive to anti-EGFR drugs in non-small cell lung cancer (NSCLC) and colorectal cancer (CRC), respectively. The majority of NSCLCs come to clinical attention at an advanced stage when surgery is no longer recommended and a considerable number of them are diagnosed by cytology only. A large number of metastatic CRCs are also diagnosed by imaging and minimally invasive techniques such as fine-needle aspiration biopsy. Here, we report our experience in the mutation analysis of EGFR and Kras on cytological material obtained from superficial and deep lesions of NSCLC and CRC. Our series included 63 cytological specimens from primary or metastatic lesions of 42 NSCLCs and 21 CRCs. The cytological material was adequate for the mutation analysis in 39/42 (93%) NSCLCs and in 20/21(95%) CRCs. EGFR and Kras mutations were found in 9 (23%) and 9 (23%) NSCLC cases, respectively. Kras mutations were found in 9/20 (45%) CRC specimens. Histological samples from the primary tumors were available in 9/42 NSCLCs and in 17/21 CRCs. The agreement of EGFR and Kras mutational status in cytological vs. histological samples was 100% for NSCLC and 88% for CRC. Our results suggest that standard cytology provides adequate material for the assessment of EGFR and Kras mutational status in NSCLC and CRC patients and could be specifically indicated in patients not eligible for surgery but candidate to anti-EGFR therapy.

Endometrial metastasis of lung adenocarcinoma: a case report.

The female genital tract is an infrequent site of metastasis, in particular from extragenital primary tumors such as non-small cell lung cancer. Ovarian metastases have been described as disseminations of lung adenocarcinoma; rare cases of secondary localizations in adnexa, cervix and vagina were also observed in the literature, but none of these had endometrial involvement. We report the first case, to our knowledge, of non-small cell lung cancer with metastatic spread to the endometrium.

Accuracy of fine needle aspiration cytology in the pathological typing of non-small cell lung cancer.

BACKGROUND: Histological typing of non-small cell lung cancer (NSCLC) has an increasing clinical relevance due to the emerging differences in medical treatment between squamous and nonsquamous tumors. However, most NSCLCs are diagnosed in an advanced stage, and the diagnosis is often obtained exclusively by cytology either exfoliative or following fine needle aspiration. We investigated the accuracy of fine needle aspiration cytology (FNAC) in NSCLC typing as compared with histology. METHODS: Over the period 2000-2009, 1182 transbronchial needle aspirate or transthoracic needle aspirate samples were obtained from patients with suspicious thoracic lesions. In 474 patients, a cytological diagnosis of primary NSCLC was obtained, and 186 (39%) of them (108 transbronchial needle aspirates and 78 transthoracic needle aspirates) received a parallel or subsequent histologic diagnosis on endoscopic biopsy (112) or surgery (74). RESULTS: At cytology, 158 (85%) NSCLC cases were typed (89 adenocarcinoma and 69 squamous cell carcinoma), while 28 (15%) were classified as NSCLC not otherwise specified. At histology, 183 (98%) cases were typed (109 adenocarcinoma, 69 squamous cell carcinoma, 3 adenosquamous carcinoma, and 2 large cell carcinoma), and only 3 (2%) were classified as NSCLC not otherwise specified. Cytological and histological typing was concordant in 137 of 156 (88%) cases (K = 0.755; p < 0.001). The positive predictive value of FNAC in typing NSCLC was 92% for adenocarcinoma and 82% for squamous cell carcinoma. CONCLUSION: FNAC in expert hands is fairly accurate for typing NSCLC and can be regarded as an acceptable procedure for diagnostic and medical treatment planning purposes in most NSCLC cases, especially when more invasive approaches are unfeasible. In poorly differentiated and doubtful cases, the use of ancillary techniques, such as immunocytochemistry, may be required to improve the diagnostic yield.

Accuracy and relative value of bone marrow aspiration in the detection of lymphoid infiltration in non-Hodgkin lymphoma.

AIMS AND BACKGROUND: In hematologic malignancies, bone marrow aspiration is considered complementary to bone marrow biopsy for the detection of tumor infiltration. The present study evaluated the accuracy of bone marrow aspiration and the relative contributions of bone marrow aspiration and bone marrow biopsy in detecting bone marrow involvement by non-Hodgkin lymphomas. METHODS AND STUDY DESIGN: We compared 51 simultaneous marrow aspirates and core biopsies from non-Hodgkin lymphoma patients for sensitivity, specificity, concordance, quality and clinical relevance. RESULTS: The agreement level of bone marrow biopsy and bone marrow aspiration was 80%, and the overall sensitivity and specificity for bone marrow aspiration were 69% and 86%, respectively. When considering only the indolent non-Hodgkin lymphoma samples, the sensitivity of bone marrow aspiration was 82% and the specificity was 85%, whereas the sensitivity and specificity were 40% and 86%, respectively, in the aggressive non-Hodgkin lymphoma specimens. Five cases (10%) were reported in which bone marrow biopsy did not detect lymphoid infiltration even though the bone marrow aspiration was positive. In one of these, lymphoid infiltration was documented by a second bone marrow biopsy performed thereafter. CONCLUSIONS: The data from the current study show that bone marrow aspiration is a useful procedure with which to detect bone marrow infiltration by lymphoma. Although it cannot be a substitute for examination of the marrow by core biopsy, the utility of adding an aspirate to bone marrow biopsy is supported by its earlier and easier availability for bone marrow examination, the larger amounts of marrow that can be examined with both procedures, and the percentage, although small, of potentially true-positive bone marrow aspirates with negative biopsies.

Is cytology reliable for epidermal growth factor receptor gene evaluation in non-small cell lung cancer?

BACKGROUND: Epidermal growth factor receptor (EGFR) gene copy number has been proposed as predictor of response to epidermal growth factor receptor tyrosine kinase inhibitors in advanced non-small cell lung cancer (NSCLC). METHODS: Cytologic and matched histologic samples from 33 primary non-small cell lung cancers were analyzed by fluorescence in situ hybridization (FISH) for epidermal growth factor receptor gene. RESULTS: FISH was positive in 52% and negative in 35% of the 31 matched evaluable samples. Four of 31 (13%) cases were discordant (K = 0.736; p < 0.001). CONCLUSION: Our data support the feasibility and reliability of epidermal growth factor receptor gene assessment by FISH on cytology.