Non-malignant Cytology Research Articles

Sensitive molecular testing methods can demonstrate NSCLC driver mutations in malignant pleural effusion despite non-malignant cytology.

Malignant pleural effusion (MPE) may be diagnosed by cytologic evaluation of pleural fluid, though false negative results can occur. Pleural effusions may provide a source of tumour material for genotyping in lung cancer patients. Detection of MPE may be improved through use of highly sensitive molecular techniques. We identified five patients with non-small cell lung cancer (NSCLC) with initial pleural fluid samples that were non-malignant on cytology, but were subsequently clinically confirmed to have MPE. Tumour mutation status was confirmed via routine testing of diagnostic clinical specimens. Cytologically negative pleural fluid cell-block specimens were analysed by amplicon-based parallel sequencing (APS) for somatic mutations commonly detected in NSCLC, and selected cases by improved and complete enrichment CO-amplification at lower denaturation temperature PCR (ICECOLD PCR) for known mutations. Mutations were detected in three out of three (sensitivity 100%) cytologically non-malignant pleural fluids from patients with a known mutation: two patients with known Kirsten rat sarcoma (KRAS) mutation demonstrated the same KRAS mutation in their pleural fluids by APS, both at approximately 2% mutant allele frequency. In one patient with a known KRAS mutation, ICECOLD PCR detected the same KRAS variant at 0.7% frequency. No mutations were detected in patients with wild-type findings from reference samples (specificity 100%). Sensitive DNA sequencing methods can detect cancer-driver mutations in cytologically non-malignant pleural fluid specimens from NSCLC patients with MPE. Our findings demonstrate the feasibility of sensitive molecular diagnostic techniques for improvement of diagnostic assessment of pleural effusions in patients with lung cancer.

Meningeal enhancement depicted by magnetic resonance imaging in tumor patients: neoplastic meningitis or therapy-related enhancement?

To assess the prevalence of false-positive meningeal contrast enhancement in patients with solid tumors who were undergoing chemotherapy. A total of 2572 magnetic resonance imaging (MRI) examinations of the brain were retrospectively evaluated by two readers for the presence of pathological meningeal contrast enhancement conspicuous for neoplastic meningitis. These patients either had malignant melanoma, breast or lung cancer, or lymphoma. The reference standards were cerebrospinal fluid cytology results and follow-up MRI. In cases with pathological contrast enhancement that decreased upon follow-up and non-malignant cytology, the enhancement pattern was further described as pial or dural, local or diffuse, or supra- or infra-tentorial. Moreover, the underlying therapy regimes were assessed. The final study cohort included 78 patients (51 females, median age 57years), of which 11 patients (14.1%) had a repeated non-malignant cytology ('pseudomeningeosis'). In one case, this finding, a granular pleocytosis, was attributed to previous radiotherapy. Of the remaining patients, seven were receiving multimodal, immunotherapy-based therapy regimens. Patients with unsuspicious cytology had a predominantly supratentorial distribution pattern in comparison to patients with neoplastic meningitis. The overall prevalence of the presence of false-positive meningeal contrast enhancement is low (< 1%) and not associated with specific imaging patterns. We hypothesize that there is a possible relationship between immunotherapy and 'pseudomeningeosis'. Therefore, in all cases with suspected neoplastic meningitis, the cerebrospinal fluid should be analyzed to confirm the diagnosis, especially in patients undergoing immunotherapy.

Utility of Intraoperative Frozen Section in Large Thyroid Nodules.

To determine if the routine use of intraoperative frozen section (iFS) results in cost savings among patients with nodules >4 cm with nonmalignant cytology undergoing a thyroid lobectomy. Case series with chart review; cost minimization analysis. Single academic center. Records were reviewed on a consecutive sample of 48 patients with thyroid nodules >4 cm and nonmalignant cytology who were undergoing thyroid lobectomy in which iFS was performed between 2010 and 2015. A decision tree model of thyroid lobectomy with iFS was created. Comparative parameters were obtained from the literature. A cost minimization analysis was performed comparing lobectomy with and without iFS and the need for completion thyroidectomy with costs estimated according to 2014 data from Medicare, the Bureau of Labor Statistics, and the Nationwide Inpatient Sample. The overall malignancy rate was 25%, and 33% of these malignancies were identified intraoperatively. When the malignancy rates obtained from our cohort were applied, performing routine iFS was the less costly scenario, resulting in a savings of $486 per case. When the rate of malignancy identified on iFS was adjusted, obtaining iFS remained the less costly scenario as long as the rate of malignancies identified on iFS exceeded 12%. If patients with follicular lesions on cytology were excluded, 50% of malignancies were identified intraoperatively, resulting in a savings of $768 per case. For patients with nodules >4 cm who are undergoing a diagnostic lobectomy, the routine use of iFS may result in decreased health care utilization. Additional cost savings could be obtained if iFS is avoided among patients with follicular lesions.

Pancreatic Resection for Side-Branch Intraductal Papillary Mucinous Neoplasm (SB-IPMN): a Contemporary Single-Institution Experience

BackgroundGiven the malignant potential of main duct intraductal papillary mucinous neoplasm (M-IPMN), surgical resection is generally indicated. With regard to side-branch intraductal papillary mucinous neoplasm (SB-IPMN), resection vs. observation is a topic of debate. Further review of SB-IPMN is necessary to clarify appropriate management. The primary focus of this project is to determine the incidence of malignant final pathology for patients undergoing surgery for isolated SB-IPMN with non-malignant fine-needle aspiration (FNA) cytology. We also sought to describe the relationship between factors considered in the international consensus guidelines and final pathologic outcome. MethodsThe study is a retrospective review of all patients who underwent surgical resection for intraductal papillary mucinous neoplasm (IPMN) from 2002 to 2013 at our institution. Patients with a preoperative diagnosis of isolated SB-IPMN and FNA results for non-malignant cytology were selected among this surgical cohort for further analysis of preoperative clinical characteristics and outcomes. ResultsA total of 137 patients undergoing resection for IPMN were identified. Of these, 81 patients (59 %) had a component of M-IPMN or invasive disease on FNA, leaving 66 (46 %) patients with SB-IPMN and non-malignant cytology. Invasive adenocarcinoma was found in 8/66 (12 %) patients and high-grade dysplasia (HGD) in 4/66 (8 %) patients. The mean [SD] diameter of benign SB-IPMN was 2.0 cm [1.1] (range 0.3–5.7) vs. that of HGD/invasive disease which was 3.1 cm [1.3] (range 1.5–6.0; P = 0.014). Of the 12 patients found to have HGD or invasive disease, symptoms, mural nodules, and septations were found in 7 (58 %), 5 (42 %), and 6 (50 %), respectively. Tumor staging were as follows: IA (2), IB (2), 2A (4), and 2B (1). ConclusionWith proper selection criteria, SB-IPMN is associated with a low rate of invasive pancreatic ductal adenocarcinoma at the time of resection. Nevertheless, given the demonstrated incidence of malignancy, appropriate operative candidates should undergo resection.

A clinical algorithm for fine-needle aspiration molecular testing effectively guides the appropriate extent of initial thyroidectomy.

To test whether a clinical algorithm using routine cytological molecular testing (MT) promotes initial total thyroidectomy (TT) for clinically significant thyroid cancer (sTC) and/or correctly limits surgery to lobectomy when appropriate. Either TT or lobectomy is often needed to diagnose differentiated thyroid cancer. Determining the correct extent of initial thyroidectomy is challenging. After implementing an algorithm for prospective MT of in-house fine-needle aspiration biopsy specimens, we conducted a single-institution cohort study of all patients (N = 671) with nonmalignant cytology who had thyroidectomy between October 2010 and March 2012, cytological diagnosis using 2008 Bethesda criteria, and 1 or more indications for thyroidectomy by 2009 American Thyroid Association guidelines. sTC was defined by histological differentiated thyroid cancer of 1 cm or more and/or lymph node metastasis. Cohort 2 patients did not have MT or had unevaluable results. In cohort 1, MT for a multigene mutation panel was performed for nonbenign cytology, and positive MT results indicated initial TT. MT guidance was associated with a higher incidence of sTC after TT (P = 0.006) and a lower rate of sTC after lobectomy (P = 0.03). Without MT results, patients with indeterminate (follicular lesion of undetermined significance/follicular or oncocytic neoplasm) cytology who received initial lobectomy were 2.5 times more likely to require 2-stage surgery for histological sTC (P < 0.001). In the 501 patients with non-sTC for whom lobectomy was the appropriate extent of surgery, lobectomy was correctly performed more often with routine preoperative MT (P = 0.001). Fine-needle aspiration biopsy MT for BRAF, RAS, PAX8-PPARγ, and RET-PTC expedites optimal initial surgery for differentiated thyroid cancer, facilitating succinct definitive management for patients with thyroid nodules.

Representativeness of Nodal Sampling With Endobronchial Ultrasonography in Non–Small-Cell Lung Cancer Staging

The objective of our study was to determine the procedure-related requirements of mediastinal node sampling with endobronchial ultrasonography with real-time transbronchial needle aspiration (EBUS-TBNA) that would provide negative predictive value (NPV) for the identification of stage III disease in non–small-cell lung cancer (NSCLC) high enough to consider the technique equivalent to cervical mediastinoscopy. Representative EBUS-TBNA was defined as a sampling procedure obtaining satisfactory samples from normal nodes in regions 4R, 4L and 7 or diagnosing malignancy in mediastinal nodes. NPV was estimated using the results of postsurgical staging in patients who underwent surgery as a reference. Two-hundred ninety-six patients staged with EBUS-TBNA were included. Representative samples from regions 4R, 4L and 7 showing nonmalignant cytology were obtained from 98 patients (33.1%) and EBUS-TBNA detected N2/N3 disease in 150 (50.7%). Accordingly, an EBUS-TBNA procedure accomplishing the representativeness criteria required for sampling was attained in 248 of the participating patients (83.8%). The NPV of the procedure in this setting was 93.6%, with false-negative results only found in 5 patients, four of them with nodal metastasis out of the reach of EBUS-TBNA (regions 5, 8 and 9). In conclusion, representative sampling of regions 4R, 4L and 7 is achieved in more than 80% of patients staged using EBUS-TBNA, and in the procedures that attain this requirement a NPV >90% for mediastinal malignancy is reached, a figure equivalent to cervical mediastinoscopy.

REVERSIBLE TRAPPED LUNG PHYSIOLOGY: POTENTIAL BENEFIT OF INTERVENTIONAL BRONCHOSCOPY ON PLEURAL PRESSURE

INTRODUCTION: Pleural effusions can develop with airway obstruction due to atelectasis, postobstructive pneumonia, and/ or malignant pleural studding. Even in the presence of an endobronchial malignancy a significant percentage of these effusions have nonmalignant cytology. This poses a staging dilemma due to the poor sensitivity of thoracentesis. This dilemma leads to lack of confidence in staging, need for further procedures and delays in therapy.Thoracentesis with pleural manometry is used to diagnose trapped lung, safely relieve symptoms, and predict outcome of pleurodesis for malignant effusions.(1,2) The effect of endobronchial intervention on pleural pressures has not been studied.

The desmoplastic melanocytic naevus: a distinct histological entity.

Fifteen cases of desmoplastic melanocytic naevi are described in 12 female and three male patients, ranging in age from 8 to 83 years. The commonest site for the lesions was the upper limb. The lesions were characterized by a dense sclerotic or desmoplastic appearance of the dermal collagen surrounding a population of predominantly epithelioid naevus cells, some of which had a bizarre but non-malignant cytology. The cause of the stromal change is not established. We suggest that these lesions constitute a discrete entity which should be described in standard textbooks of dermatopathology.

ROLE OF FINE NEEDLE ASPIRATION CYTOLOGY IN THE MANAGEMENT OF THORACIC LESIONS

Fine needle aspiration cytology was performed on 121 occasions in 100 patients with various thoracic lesions. The investigation was performed chiefly with the help of straight and lateral chest skiagrams regardless of the size or depth of the lesion. The cellular yield was 87.6%. Positive diagnosis of malignancy could be made in 50 cases. The histopathological correlation in malignant cases was 80%. Non-malignant cytology including neoplastic and inflammatory pathology was also found useful in patient management. This report highlights the versatile role of this procedure in arriving at a diagnosis and planning the treatment for malignant as well as non-malignant thoracic diseases.