Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of mediastinal lymphadenopathy has been shown to be a valuable diagnostic tool in high-volume EUS centers (≥50 mediastinal EUS-FNA/endoscopist/year). Our goal was to assess the diagnostic accuracy of EUS-FNA and its impact on clinical management and costs in low-volume EUS centers (<50 mediastinal EUS-FNA/endoscopist/year).
Consecutive patients referred to two Dutch endoscopy centers in the period 2002–2008 for EUS-FNA of mediastinal lymphadenopathy were reviewed. The gold standard for a cytological diagnosis was histological confirmation or clinical follow-up of more than 6 months with repeat imaging. The impact of EUS-FNA on clinical management was subdivided into a positive impact by providing (1) adequate cytology that influenced the decision to perform surgery or (2) a diagnosis of a benign inflammatory disorder, and a negative impact which was subdivided into (1) false-negative or inconclusive cytology or (2) an adequate cytological diagnosis that did not influence patient management. Costs of an alternative diagnostic work-up without EUS-FNA, as established by an expert panel, were compared to costs of the actual work-up.
In total, 213 patients (71% male, median age = 61 years, range = 23–88 years) underwent EUS-FNA. Sensitivity, specificity, and negative and positive predictive values were 89%, 100%, 80%, and 100%, respectively. EUS-FNA had a positive impact on clinical management in 84% of cases by either influencing the decision to perform surgery (49%) or excluding malignant lymphadenopathy (35%), and a negative impact in 7% of cases because of inadequate (3%) or false-negative (4%) cytology. In 9% of cases, EUS-FNA was performed without an established indication. Two nonfatal perforations occurred (0.9%). Total cost reduction was €100,593, with a mean cost reduction of €472 (SD = €607) per patient.
Mediastinal EUS-FNA can be performed in low-volume EUS centers without compromising diagnostic accuracy. Moreover, EUS-FNA plays an important role in the management of patients with mediastinal lymphadenopathy and reduces total diagnostic costs.
EUS-FNA; Costs; Accuracy; Mediastinal lymphadenopathy
One of the novel techniques utilizing fine needle aspiration (FNA) in the diagnosis of mediastinal and lung lesions is the endobronchial ultrasound (EBUS)-guided FNA. In this study, we describe five cases which had a discrepancy between on-site evaluation and final diagnosis, or a diagnostic dilemma when rendering the preliminary diagnosis, in order to illustrate some of the diagnostic difficulties and pitfalls that can occur in EBUS FNA.
A total of five EBUS FNA cases from five patients were identified in our records with a discrepancy between the rapid on-site evaluation (ROSE) and final diagnosis, or that addressed a diagnostic dilemma. All of the cases had histological confirmation or follow-up. The cytomorphology in the direct smears, cell block, and immunohistochemical stains were reviewed, along with the clinical history and other available information.
Two cases were identified with a nondefinitive diagnosis at ROSE that were later diagnosed as malignant (metastatic signet-ring cell adenocarcinoma and metastatic renal cell carcinoma (RCC)) on the final cytological diagnosis. Three additional cases were identified with a ROSE and final diagnosis of malignant (large cell neuroendocrine carcinoma (LCNEC) and two squamous cell carcinomas), but raised important diagnostic dilemmas. These cases highlight the importance of recognizing discohesive malignant cells and bland neoplasms on EBUS FNA, which may lead to a negative or a nondefinitive preliminary diagnosis. Neuroendocrine tumors can also be difficult due to the wide range of entities in the differential diagnosis, including benign lymphocytes, lymphomas, small and nonsmall cell carcinomas, and the lack of immunohistochemical stains at the time of ROSE. Finally, the background material in EBUS FNAs may be misleading and unrelated to the cells of interest.
This study illustrates the cytomorphology of five EBUS FNA cases that address some of the diagnostic challenges witnessed while examining these specimens during ROSE. Many of the difficulties faced can be attributed to the baseline cellularity of the aspirates, the bronchial contamination, the difficulty identifying neoplasms with bland cytology, the wide spectrum of diseases that can occur in the mediastinum with overlapping cytomorphologic features, the mismatch between the background material and the cell populations present, and the overall unfamiliarity with these types of specimens.
Cytopathology; EBUS; endobronchial ultrasound; fine needle aspiration
In the recent years, the advances in digital methods in pathology have resulted in the use of telecytology in the immediate assessment of fine needle aspiration (FNA) specimens. However, there is a need for organ-based and body site-specific studies on the use of telecytology for the immediate assessment of FNA to evaluate its pitfalls and limitations. We present our experience with the use of telecytology for on-site evaluation of ultrasound-guided FNA (USG-FNA) of axillary lymph nodes in a remote breast care center.
Materials and Methods:
Real-time images of Diff-Quik-stained cytology smears were obtained with an Olympus digital camera attached to an Olympus CX41 microscope and transmitted via ethernet by a cytotechnologist to a pathologist who rendered preliminary diagnosis while communicating with the on-site cytotechnologist over the Vocera system. The accuracy of the preliminary diagnosis was compared with the final diagnosis, retrospectively.
A total of 39 female patients (mean age: 50.5 years) seen at the breast care center underwent USG-FNA of 44 axillary nodes. Preliminary diagnoses of benign, suspicious/malignant, and unsatisfactory were 41, 52, and 7%, respectively. Only one of the 23 cases that were initially interpreted as benign was reclassified as suspicious on final cytologic diagnosis. Seventeen of 18 suspicious/malignant cases on initial cytology corresponded with a malignant diagnosis on final cytology. One suspicious case was reclassified as benign on final cytologic diagnosis. All unsatisfactory cases remained inadequate for final cytologic interpretation. The presence of additional material in the cell block and interpretative error were the main reasons for discrepancy, accounting for the two discrepant cases.
This retrospective study demonstrates that the on-site telecytology evaluation of USG-FNA of axillary lymph nodes in patients at a remote breast care center was highly accurate compared with the final cytologic evaluation. It allows pathologists to use their time more efficiently and makes on-site evaluation at a remote site possible.
Axillary lymph nodes; FNA; telecytopathology; ultrasound-guided FNA
Lung cancer diagnosis is usually achieved through a set of bronchoscopic techniques or computed tomography guided-transthoracic needle aspiration (CT-TTNA). However these procedures have a variable diagnostic yield and some patients remain without a definite diagnosis despite being submitted to an extensive workup. The aim of this study was to evaluate the efficacy and cost of linear endobronchial (EBUS) and endoscopic ultrasound (EUS) guided fine needle aspiration (FNA), performed with one echoendoscope, for the diagnosis of suspicious lung cancer lesions after failure of conventional procedures.
One hundred and twenty three patients with an undiagnosed but suspected malignant lung lesion (paratracheal, parabronchial, paraesophageal) or with a peripheral lesion and positron emission tomography positive mediastinal lymph nodes who had undergone at least one diagnostic flexible bronchoscopy or CT-TTNA attempt were submitted to EBUS and EUS-FNA. Patients with endobronchial lesions were excluded.
Of the 123 patients, 88 had a pulmonary nodule/mass and 35 were selected based on mediastinal PET positive lymph nodes. Two patients were excluded because an endobronchial mass was detected at the time of the procedure. The target lesion could be visualized in 121 cases and FNA was performed in 118 cases. A definitive diagnosis was obtained in 106 cases (87.6%). Eighty-eight patients (72.7%) had non-small cell lung cancer, 15 (12.4%) had small cell lung cancer and metastatic disease was found in 3 patients (2.5%). The remaining 15 negative cases were subsequently diagnosed by surgical procedures. Twelve patients (9.9%) had a malignant tumor and in 3 (2.5%) a benign lesion was found. The overall sensitivity, specificity, positive and negative predictive values of EBUS and EUS-FNA to diagnose malignancy were 89.8%, 100%, 100% and 20.0% respectively. The diagnostic accuracy was 90.1% in a population with 97.5% prevalence of cancer. The ultrasonographic approach avoided expensive surgical procedures and significantly reduced costs (p < 0.001).
Linear EBUS and EUS-FNA are able to improve the diagnostic yield of suspicious lung cancer lesions after non-diagnostic conventional techniques. These techniques, performed with one scope, can be offered to patients with accessible lesions as an intermediate step for diagnosis since they may avoid more invasive procedures and hence reduce costs.
Lung cancer; Endobronchial ultrasound; Endoscopic ultrasound; Fine needle aspiration; Diagnosis
Background: A study was undertaken to evaluate the clinical impact of endoscopic ultrasound guided fine needle aspiration biopsy (EUS-FNA) in patients with mediastinal masses suspected of malignancy.
Methods: From April 1993 to December 1999, 84 patients were referred for EUS-FNA. In all patients CT scanning had shown a lesion of the mediastinum suspected of malignancy located adjacent to the oesophagus. In order to evaluate the clinical impact of EUS-FNA, the history of each patient up to referral for EUS-FNA was reviewed. A board of thoracic specialists was asked to decide the further course of the patient if EUS-FNA had not been available, and this diagnostic strategy was compared with the actual clinical course after EUS-FNA.
Results: For the 79 patients in whom sufficient verification was obtained, EUS-FNA had a sensitivity of 92%, specificity of 100%, PPV of 100%, NPV of 80%, and an accuracy of 94% for cancer of the mediastinum. In 18 of 37 patients (49%) a thoracotomy/thoracoscopy was avoided as a result of EUS-FNA, and in 28 of 41 patients (68%) a mediastinoscopy was avoided. The direct result of the cytological diagnosis obtained by EUS-FNA was that a final diagnosis of small cell lung cancer was made in eight patients resulting in referral for chemotherapy, and in another three patients with benign disease specific treatment could be initiated (sarcoidosis, mediastinal abscess, and leiomyoma of the oesophagus).
Conclusions: EUS-FNA is a safe and sensitive minimally invasive method for evaluating patients with a solid lesion of the mediastinum suspected by CT scanning. EUS-FNA has a significant impact on patient management and should be considered for diagnosing the spread of cancer to the mediastinum in patients with lung cancer considered for surgery, as well as for the primary diagnosis of solid lesions located in the mediastinum adjacent to the oesophagus.
The aim of this study is to perform a cost-effectiveness comparison between palpation-guided thyroid fine-needle aspiration biopsies (P-FNA) and ultrasound-guided thyroid FNA biopsies (USG-FNA).
Each nodule was considered as a case. Diagnostic steps were history and physical examination, TSH measurement, Tc99m thyroid scintigraphy for nodules with a low TSH level, initial P-FNA versus initial USG-FNA, repeat USG-FNA for nodules with initial inadequate P-FNA or USG-FNA, hemithyroidectomy for inadequate repeat USG-FNA. American Thyroid Association thyroid nodule management guidelines were simulated in estimating the cost of P-FNA strategy. American Association of Clinical Endocrinologists guidelines were simulated for USG-FNA strategy. Total costs were estimated by adding the cost of each diagnostic step to reach a diagnosis for 100 nodules. Strategy cost was found by dividing the total cost to 100. Incremental cost-effectiveness ratio (ICER) was calculated by dividing the difference between strategy cost of USG-FNA and P-FNA to the difference between accuracy of USG-FNA and P-FNA. A positive ICER indicates more and a negative ICER indicates less expense to achieve one more additional accurate diagnosis of thyroid cancer for USG-FNA.
Seventy-eight P-FNAs and 190 USG-FNAs were performed between April 2003 and May 2008. There were no differences in age, gender, thyroid function, frequency of multinodular goiter, nodule location and diameter (median nodule diameter: 18.4 mm in P-FNA and 17.0 mm in USG-FNA) between groups. Cytology results in P-FNA versus USG-FNA groups were as follows: benign 49% versus 62% (p = 0.04), inadequate 42% versus 29% (p = 0.03), malignant 3% (p = 1.00) and indeterminate 6% (p = 0.78) for both. Eleven nodules from P-FNA and 18 from USG-FNA group underwent surgery. The accuracy of P-FNA was 0.64 and USG-FNA 0.72. Unit cost of P-FNA was 148 Euros and USG-FNA 226 Euros. The cost of P-FNA strategy was 534 Euros and USG-FNA strategy 523 Euros. Strategy cost includes the expense of repeat USG-FNA for initial inadequate FNAs and surgery for repeat inadequate USG-FNAs. ICER was -138 Euros.
Universal application of USG-FNA for all thyroid nodules is cost-effective and saves 138 Euros per additional accurate diagnosis of benign versus malignant thyroid nodular disease.
Background and Aims
The diagnosis of intra-abdominal lymphadenopathy of is difficult, especially when no primary lesion has been identified. We aimed to evaluate the diagnostic yield of EUS-FNA cytology in patients with enlarged intra-abdominal lymph nodes of unknown etiology.
Patient and Methods
147 patients with abdominal lymphadenopathy on imaging in whom EUS-FNA was performed with a 22-gauge needle. Performance characteristics of EUS-FNA including the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were compared between the 2 groups.
AThe location of the enlarged lymph nodes was the celiac axis (8.2%), peri-gastric (34%), peri-pancreatic (25.2%), peri-portal (27.9%), and other intra-abdominal locations (4.8%). The median number of EUS-FNA passes was 5. The final diagnosis were lymphoma in (n=27), metastatic adenocarcinoma (n=44) patients, other miscellaneous malignancies (n=22) and benign disease (n=54). The sensitivity, specificity, and accuracy of EUS-FNA were 89.7, 98.3, and 93.5% respectively. A false positive FNA result was present in only 1 case (0.7%); false negative FNA results were present in eight cases (5.8%). Lymph node morphologic features of roundness, echogenicity, and homogeneity on EUS were not a predictor of lymph node malignancy.
In a retrospective cohort trial, EUS-FNA was found to be highly accurate and safe in diagnosing patients with intra-abdominal lymphadenopathy of unknown etiology.
lymphadenopathy; endosonography; fine needle aspiration
Small cell lung carcinoma represents a group of highly malignant tumors giving rise to early and widespread metastasis at the time of diagnosis. However, the pancreas is a relatively infrequent site of metastasis by this neoplasm, and there are only occasional reports on its fine needle aspiration (FNA) cytology diagnosis. A 66-year-old man presented with extensive mediastinal lymphadenopathy and a mass in the pancreatic tail. Ultrasound-guided FNA smears from the pancreatic mass contained small, round tumor cells with extensive nuclear molding. The cytodiagnosis was metastatic small cell carcinoma. Immunocytochemical staining showed that a variable number of neoplastic cell were positive for cytokeratin, chromogranin A, neurone-specific enolase and synaptophysin but negative for leukocyte common antigen. The trans-bronchial needle aspiration was non-diagnostic, but biopsy was suspicious of a small cell carcinoma. This case represents a rare metastatic lesion in the pancreas from small cell lung carcinoma, diagnosed by FNA cytology.
Fine needle aspiration cytology; metastasis; pancreas; small cell lung carcinoma; trans-bronchial biopsy
Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and Trucut biopsy (TCB) are sensitive techniques for diagnosing mediastinal lesions, but it is unclear how either one or both should be used to obtain a pathologic diagnosis. The objective of our study was to evaluate whether EUS-TCB impacts the diagnosis of mediastinal lesions after the initial on-site review of EUS-FNA specimen suggests a suboptimal result.
We enrolled consecutive
patients with mediastinal lesions who underwent EUS-TCB during the same procedure if the initial EUS-FNA demonstrated an inadequate FNA sample or suggested that histopathology was required for diagnosis. Diagnostic accuracies between procedures were compared as the main outcome.
Twenty-seven patients (14 men; median age, 56 years; range, 19 to 82 years) underwent EUS-FNA and EUS-TCB to evaluate a mediastinal lymphadenopathy or mass (n=17), to determine the cancer stage (n=3) or to exclude tumor recurrence or metastasis (n=7). The overall diagnostic accuracies of EUS-FNA and EUS-TCB were 78% and 67%, respectively (p=0.375). The combined diagnostic accuracy of EUS-FNA plus EUS-TCB was 82%. In six patients with nondiagnostic EUS-FNA, EUS-TCB provided a final diagnosis in one patient (17%).
In the current series of patients with mediastinal masses or adenopathy, the administration of EUS-TCB following suboptimal results for the on-site cytology review did not increase the diagnostic yield.
Endoscopic ultrasound; Endoscopic ultrasound-guided fine needle aspiration; Endoscopic ultrasound-guided Trucut biopsy; Mediastinum
Fine needle aspiration (FNA) biopsy has been rarely used in oral and oropharyngeal lesions. The goal of this study was to assess the value and accuracy of FNA biopsy in the diagnosis of oral and oropharyngeal lesions particularly in regards to discriminating benign from malignant tumors.
Sixteen cases of FNA biopsies obtained of various intraoral and oropharyngeal masses or lesions performed at our institution during the eight-year period from 1998 to 2006 were retrospectively reviewed. The aspiration cytologic diagnoses were correlated with the histologic examination of the corresponding resected lesions.
Sixteen cases of intraoral lesions evaluated by FNA biopsies during the period of 1998–2006 were reviewed. The sites of involvement were: lip , maxillary sinus , pharynx/oropharynx , floor of mouth , buccal mucosa  and peritonsillar area . Patients' age ranged from 30 to 87 with an average of 54 years. Male to female ratio was 1:3. Cytologically, 7 cases were diagnosed as suspicious/malignant, and 9 cases as benign (including 6 benign neoplasm, 1 atypical, and 2 reactive or "descriptive"). Fifteen cases had corresponding surgical resection for histologic examination, of these, 9 cases were interpreted as malignant, and 6 as benign. There were no false positive diagnoses of malignancy on FNA. Two cases were interpreted as benign or atypical cytologically, but were found to be malignant on histologic examination.
FNA biopsy of intraoral and oropharyngeal masses is a valuable procedure for the initial evaluation of various lesions. It provides helpful information about these lesions and avoids hasty or unnecessary surgical biopsy. It is a rapid and relatively noninvasive procedure. Furthermore, aspiration biopsy is an important tool in the diagnosis and management of these lesions, both neoplastic and non-neoplastic, and can be sometimes complemented by ancillary studies for more accurate interpretation. However, its sensitivity in the diagnosis of malignancy is lower than that of histologic samples. This is probably due to the superficial nature and small size of these lesions, the limited space for maneuvering the needle and difficulty in immobilizing the lesion to obtain adequate samples, rather than to interpretation or inherent limitations of the technique itself.
Endoscopic ultrasound (EUS) with fine-needle aspiration (FNA) is often used to assist in the evaluation of pancreatic lesions and may help to diagnose benign versus malignant neoplasms. However, there is a paucity of literature regarding comparative EUS characteristics of various malignant pancreatic neoplasms (primary and metastatic).
To compare and characterize primary pancreatic adenocarcinoma versus other malignant neoplasms, hereafter referred to as nonprimary pancreatic adenocarcinoma (NPPA), diagnosed by EUS-guided FNA.
The present study was a retrospective analysis of a prospectively maintained database. The setting was a tertiary care, academic medical centre. Patients referred for suspected pancreatic neoplasms were evaluated. Based on EUS-FNA characteristics, primary pancreatic adenocarcinoma was differentiated from other malignant neoplasms. The subset of other neoplasms was defined as malignant lesions that were ‘NPPAs’ (ie, predominantly solid or solid/cystic based on EUS appearance and primary malignant lesions or metastatic lesions to the pancreas). Pancreatic masses that were benign cystic lesions (pseudocyst, simple cyst, serous cystadenoma) and focal inflammatory lesions (acute, chronic and autoimmune pancreatitis) were excluded.
A total of 230 patients were evaluated using EUS-FNA for suspected pancreatic mass lesions. Thirty-eight patients were excluded because they were diagnosed with inflammatory lesions or had purely benign cysts. One hundred ninety-two patients had confirmed malignant pancreatic neoplasms (ie, pancreatic adenocarcinoma [n=144], NPPA [n=48]). When comparing adenocarcinoma with NPPA lesions, there was no significant difference in mean age (P=0.0675), sex (P=0.3595) or average lesion size (P=0.3801). On average, four FNA passes were necessary to establish a cytological diagnosis in both lesion subtypes (P=0.396). Adenocarcinomas were more likely to be located in the pancreatic head (P=0.0198), whereas masses in the tail were more likely to be NPPAs (P=0.0006). Adenocarcinomas were also more likely to exhibit vascular invasion (OR 4.37; P=0.0011), malignant lymphadenopathy (P=0.0006), pancreatic duct dilation (OR 2.4; P=0.022) and common bile duct dilation (OR 2.87; P=0.039).
Adenocarcinoma was more likely to be present in the head of the pancreas, have lymph node and vascular involvement, as well as evidence of pancreatic duct and common bile duct obstruction. Of all malignant pancreatic lesions analyzed by EUS-FNA, 25% were NPPA, suggesting that FNA is crucial in establishing a diagnosis and may be helpful in preoperative planning.
Adenocarcinoma; Endoscopic ultrasound; Fine-needle aspiration; Malignant neoplasm; Nonprimary pancreatic adenocarcinoma; Pancreas
AIMS: To evaluate the correlation of fine needle aspiration (FNA) cytology and frozen section biopsy in the diagnosis of thyroid nodules. METHODS: The medical records of 662 patients who underwent FNA cytology of the thyroid and thyroid surgery were analysed. Frozen section biopsies were taken from 586 of the 662 patients. The diagnostic correlations of FNA cytology, frozen section, and both FNA cytology and frozen section with definitive histological assessment were evaluated. RESULTS: Among the 662 patients who received FNA cytology, there were 356 cases (53.8%) diagnosed as benign, 114 cases (17.2%) as malignant, 148 cases (22.4%) as indeterminate, and 44 cases (6.6%) as unsatisfactory. The positive predictive value for the detection of malignancy by FNA cytology was 92.1% and the negative predictive value was 95.2%. The incidence of malignancy in the indeterminate cytological diagnosis was 23%. The diagnosis from frozen sections was benign in 445 cases (75.9%), malignant in 134 cases (22.9%), and deferred in 7 cases (1.2%). By frozen section, the positive and negative predictive values were 97% and 95.5%, respectively. Diagnostic accuracy up to 98% was achieved when FNA cytology and frozen section diagnoses were in agreement. No false positives were observed when FNA cytology and frozen sections were both positive for malignancy. When FNA cytology and frozen section diagnoses were discordant, frozen section showed a higher accuracy (78.9%) than FNA cytology (21.1%). In the face of an indeterminate or unsatisfactory cytological diagnosis, the diagnostic accuracy of frozen sections reached 92.6%. CONCLUSIONS: The results confirm that FNA cytology is a useful tool in the initial evaluation of thyroid nodules. Intraoperative frozen section is a valuable procedure to confirm the cytological diagnosis and identify malignancy in patients with indeterminate or unsatisfactory cytological diagnosis. With reliance on frozen sections as an intraoperative guide of thyroid surgery, the possibility of unnecessary extensive surgery and the need for the second operation are considerably lower.
The purpose of this study was to assess the usefulness of HER2 levels in ultrasonographically guided fine-needle aspiration biopsy (US-FNA) aspirates of axillary lymph nodes (ALNs) in the determination of lymph node metastasis or the characterization of primary breast cancer, and to correlate the HER2 levels in US-FNA aspirates (FNA-HER2s) of metastatic ALNs with the HER2 statuses of corresponding primary breast cancers. An institutional review board approved the study. Between January and October 2010, 164 patients with 167 ALNs examined by US-FNA were included. FNA-HER2s of ALNs were measured by chemiluminescence immunoassay, and they were correlated with cytologic/final diagnoses. Receiver operating characteristics (ROC) curve analysis was performed to evaluate the diagnostic ability to differentiate benign and metastatic ALNs. Additionally, FNA-HER2s of metastatic ALNs were correlated with HER2 status and other clinicopathologic variables of the primary breast cancers. Among the 167 ALNs, 138 were metastatic and 29 were benign. The mean FNA-HER2 (6.3 ng/ml) of metastatic ALNs was higher than that of benign ALNs. All 29 benign ALNs showed no measurable value of FNA-HER2 (0.0 ng/ml). The area under the ROC curves of FNA-HER2 of ALNs was 0.679 for the diagnosis of ALN metastasis. The FNA-HER2 statuses of 108 metastatic ALNs (79.4%) were concordant with the HER2 statuses of the corresponding primary breast cancers. In a subgroup analysis of HER2-positive cancers with ALN metastasis, distant metastasis was significantly associated with FNA-HER2-negativity of metastatic ALNs (P = 0.04). Although FNA-HER2 of ALNs did not improve the diagnostic performance of FNA cytology in preoperative diagnosis of ALN metastasis of overall patients, FNA-HER2-positive metastatic ALNs were significantly associated with HER2-positivity of primary breast cancers. Additionally, FNA-HER2 analysis of ALN may help to develop more personalized treatment protocol for breast cancer patients by determining the concordance or discordance of HER2 status between primary cancers and metastatic ALNs.
Fine-needle aspirations (FNAs) and core biopsies (CBs), with or without touch preparations (TPs), are performed to characterize pulmonary lesions. Although a positive (P) or suspicious report is sufficient for further management, the significance of unsatisfactory (U), negative (N) and atypical (A) cytological diagnoses remains uncertain. The aims of the study were to correlate U, N and A cytological diagnoses with histological and/or clinical/radiological follow-up and evaluate the utility of FNAs, TPs and CBs.
Materials and Methods:
We performed a retrospective search and examined 30 consecutive computed tomography-guided transthoracic U, N and A lung FNAs (n = 23) and TPs (n = 7) with surgical pathology (SP) (n = 17) and/or clinical/radiological follow-up (n = 13) and compared them to 10 SP-confirmed P FNAs, which served as controls.
The 30 FNAs and TPs were from 29 patients. All 6 U specimens were scantly cellular. Granulomas, the most common specific benign cytological diagnosis, were evident in 8 (of 13) and 7 (of 11) N and A cytology cases, respectively. Histology corroborated the presence of granulomas identified on cytology. Organizing pneumonia was the second leading benign specific diagnosis (5/17), but it was rendered on histology (n = 5) and not FNAs or TPs. Evaluation of the A cases revealed that type II pneumocytes were the source of “atypical”, diagnoses often associated with granulomas or organizing pneumonia and lacked 3-D clusters evident in all P cases.
U, N and A FNAs and TPs lacked 3-D clusters seen in carcinomas and were negative on follow-up. Granulomas and organizing pneumonia were the most common specific benign diagnoses, but the latter was recognized on histology only. In the absence of a definitive FNA result at the time of on-site assessment, a CB with a TP containing type II pneumocytes increases the likelihood of a specific benign diagnosis.
Benign; core biopsy; fine-needle aspiration; lung; pulmonary; touch preparations and imprints
AIM: To report the clinical impact of adrenal endoscopic ultrasound fine-needle aspiration (EUS-FNA) in the evaluation of patients with adrenal gland enlargement or mass.
METHODS: In a retrospective single-center case-series, patients undergoing EUS-FNA of either adrenal gland from 1997-2011 in our tertiary care center were included. Medical records were reviewed and results of EUS, cytology, adrenal size change on follow-up imaging ≥ 6 mo after EUS and any repeat EUS or surgery were abstracted. A lesion was considered benign if: (1) EUS-FNA cytology was benign and the lesion remained < 1 cm from its original size on follow-up computed tomography (CT), magnetic resonance imaging or repeat EUS ≥ 6 mo after EUS-FNA; or (2) subsequent adrenalectomy and surgical pathology was benign.
RESULTS: Ninety-four patients had left (n = 90) and/or right (n = 5) adrenal EUS-FNA without adverse events. EUS indications included: cancer staging or suspected recurrence (n = 31), pancreatic (n = 20), mediastinal (n = 10), adrenal (n = 7), lung (n = 7) mass or other indication (n = 19). Diagnoses after adrenal EUS-FNA included metastatic lung (n = 10), esophageal (n= 5), colon (n = 2), or other cancer (n = 8); benign primary adrenal mass or benign tissue (n = 60); or was non-diagnostic (n = 9). Available follow-up confirmed a benign lesion in 5/9 non-diagnostic aspirates and 32/60 benign aspirates. Four of the 60 benign aspirates were later confirmed as malignant by repeat biopsy, follow-up CT, or adrenalectomy. Adrenal EUS-FNA diagnosed metastatic cancer in 24, and ruled out metastasis in 10 patients. For the diagnosis of malignancy, EUS-FNA of either adrenal had sensitivity, specificity, positive predictive value and negative predictive value of 86%, 97%, 96% and 89%, respectively.
CONCLUSION: Adrenal gland EUS-FNA is safe, minimally invasive and a sensitive technique with significant impact in the management of adrenal gland mass or enlargement.
Adrenal gland neoplasms/diagnosis; Adrenal glands/pathology; Adrenal gland/ultrasonography; Adrenal gland neoplasms/secondary; Endosonography; Biopsy; Fine-needle
At present only few studies directly compare the diagnostic yield of endobronchial ultrasound guided fine needle aspiration (EBUS-FNA) and transcervical video-assisted mediastinoscopy (TM) for mediastinal lymph node staging in patients with NSCLC. If and when EBUS-FNA may replace TM as Gold Standard remains controversial.
From April 2008 to December 2009, 36 patients with mediastinal lymphadenopathy underwent simultaneous EBUS-FNA/ TM at our institution. Among them were 26 patients with confirmed or suspected NSCLC.
A total of 133 samples were obtained by EBUS-FNA and 157 samples by TM. EBUS-FNA achieved significantly less conclusive, but more indeterminate pathological results in comparison to TM (78.7% vs. 98.6%, p < 0.001; 14.9% vs. 1.4%, p = 0.007). Less paratracheal nodes were sampled by EBUS-FNA (right: 46.2% vs. 88.5%, p = 0.003; left: 23.1% vs. 65.4%, p = 0.005), while sampling rates in the subcarinal localisation were comparable (96.2% vs. 80.8%, p = NS). Among patients with confirmed NSCLC and conclusive EBUS-FNA/ TM findings (n = 18), the prevalence of N2/N3 disease was 66.7% (n = 12) according to TM findings. Diverging nodal stages were found in five patients (27.8%). Three patients who were N2 negative in EBUS-FNA were upstaged to N2 or N3 by TM, two patients with N2 status in EBUS-FNA were upstaged to N3 by TM.
Compared to TM, EBUS-FNA had a lower diagnostic yield and resulted in systematic mediastinal nodal understaging. At this point we suggest corroborating negative EBUS-FNA results by transcervical mediastinoscopy.
EBUS-FNA; Mediastinoscopy; NSCLC; Nodal staging
The pancreas is surrounded by soft tissue known as the peripancreatic space (PPS). Pathologic lesions of the PPS are infrequent and have only rarely been reported in the cytopathology literature.
A retrospective review of cytopathology files at two large institutions revealed 42 cases of PPS lesions obtained by transabdominal fine needle aspiration (FNA) or endoscopic ultrasound-guided FNA over a 16-year period. Clinicoradiologic findings and follow-up information were also reviewed.
Patients ranged in age from 23-83 years (mean, 60 years) with an equal gender distribution. The major clinical presentations included pain, jaundice, nausea/vomiting, and abnormal liver enzymes. Radiographic characteristics included lymphadenopathy and cystic/solid soft tissue masses with a size range of 1.5 to 8 cm. Cytologically, 4 (9.5%) cases were nondiagnostic, 9 (21.5%) were diagnosed as benign, 4 (9.5%) were atypical or suspicious for cancer, and 25 (59.5%) were malignant. Six of 25 (24%) patients had metastasis of a prior known malignancy.
FNA of PPS masses is a rare occurrence. The majority of lesions are metastatic carcinomas from a variety of primary sites. Flow cytometry and immunoperoxidase studies are useful adjuncts to determine the tumor origin. The sensitivity of PPS aspiration for a malignant diagnosis is 90% with a positive predictive value of 100%.
Peripancreatic space; Cytopathology; Fine needle aspiration; Adenocarcinoma
To determine the yield of endoscopic ultrasound–guided fine-needle aspiration (EUS–FNA) in combination with immunostains in diagnosing unusual solid pancreatic masses (USPM) in comparison with pancreatic adenocarcinoma (ACP).
Patients and Methods:
All EUS–FNA of solid pancreatic masses performed with a 22-gauge needle were included. Data on clinical presentations, mass characteristics, presence of pancreatitis, yield of tissue, and final diagnosis were compared between the two groups. On site cytopathology was provided and additional passes were requested to perform immunostains.
Two hundred and twenty-nine cases with either adenocarcinoma or USPM were included. The median age of the cohort was 65 years. ACP (210/229, 92%) accounted for the majority of the cases. The USPM included neuroendocrine (NET) masses (n=13), metastatic renal carcinoma (n=3), metastatic melanoma (n=1), lymphoma (n=1), and malignant fibrous histiocytoma (n=1). Subjects with ACP were significantly more likely to present with loss of weight (P=0.02) or obstructive jaundice (P<0.001). Subjects with ACP were more likely to have suspicious/atypical FNA biopsy results as compared with USPM (10% vs 0%). The sensitivity of EUS–FNA with immunostains was 93% in ACP as compared with 100% in USPM. Diagnostic accuracy was higher in USPM as compared with ACP (100% vs 93%).
EUS–FNA using a 22-gauge needle with immunostains has excellent diagnostic yield in patients with USPMs, which is comparable if not superior to the yield in pancreatic adenocarcinoma.
Cytology; endoscopic ultrasound; fine needle aspiration; immunostains; metastasis; neuroendocrine tumors; pancreas
To evaluate the characteristic ultrasonographic (US) features of metastatic carcinoma to the thyroid, and how accurate US features and ultrasonography-guided fine-needle aspiration (US-FNA) are for the diagnosis of thyroid metastases.
Twenty-three thyroid lesions in 23 patients (mean age, 66.7 years; range, 46 to 85 years) that had been diagnosed as thyroid metastases were included. The composition, echogenicity, margin, shape, presence of calcifications, underlying parenchymal echotexture, and vascularity were analyzed in US images of the thyroid metastases. Final US assessments were categorized into probably benign and suspicious malignancy. The presence of suspicious metastatic cervical lymph nodes was noted. The medical records, US-FNA cytology, and pathology reports of these patients were retrospectively reviewed.
Of the 23 thyroid lesions, the general US appearance was mass-forming in 21 (91.3%) and non-mass-forming in 2 (8.7%). All 23 lesions showed a solid tumor composition. Common US features among the 21 mass-forming thyroid metastases were hypoechogenicity (81.0%), non-circumscribed margins (90.5%), no calcifications (76.2%), and parallel shape (81.0%). Suspicious cervical lymph nodes were present in 18 patients (78.3%). Of the 23 lesions, 21 (91.3%) were classified as suspicious malignancy, and 2 (8.7%) as probably benign. US-FNA showed diagnostic results specific for metastases in 21 of the 22 patients (95.5%) who had undergone US-FNA.
Common US features in thyroid metastasis were hypoechogenicity, non-circumscribed margins, no calcifications, parallel shape, and the presence of suspicious cervical lymph nodes. US-FNA can be effectively used in the diagnosis of thyroid metastasis, preventing unnecessary surgery.
Thyroid gland; Ultrasonography; Neoplasm metastasis; Biopsy, fine needle
AIMS: To evaluate all thyroid fine needle aspirations (FNA) done over a six year period to assess the accuracy and value of the technique. METHODS: There were 335 FNAs of which 184 had subsequent histology and 49 others had clinical follow up, providing 233 patients for analysis. All cytology and histology was reviewed with no significant alterations in diagnosis. The FNAs were classified into three groups: benign, suspicious (recommend excision), and malignant. The histology and medical records were reviewed to determine whether the cytology was accurate. RESULTS: There were 130 benign FNAs, 126 had non-malignant histology or normal clinical follow up, and four had malignancies on histology (two lymphomas, one follicular carcinoma, and one carcinoma not otherwise specified). There were 45 suspicious FNAs. Of these five had either follicular or papillary carcinoma, 14 had follicular adenomas, and 26 had colloid nodular goitres or normal clinical follow up. Of the 21 malignant FNAs, 11 had carcinoma and 10 had either a non-malignant histology or normal follow up. There were 126 true negatives, 30 true positives, 4 false negatives, and 36 false positives. This gives a sensitivity of 88%, a specificity of 78%, a positive predictive value of 46%, a negative predictive value of 97%, and an accuracy of 80%. CONCLUSIONS: FNA cytology of the thyroid has a high negative predictive value, which is useful to reassure the majority of patients presenting with thyroid enlargement. However, a negative FNA should never exclude malignancy if there is a strong clinical suspicion. If this rule is adhered to a large number of patients will be spared unnecessary surgery and no malignant nodule will go untreated.
The reported reliability of core needle biopsy (CNB) is high in assessing thyroid nodules after inconclusive fine-needle aspiration (FNA) attempts. However, first-line use of CNB for nodules considered at risk by ultrasonography (US) has yet to be studied. The aim of this study were: 1) to evaluate the potential merit of using CNB first-line instead of conventional FNA in thyroid nodules with suspicious ultrasonographic features; 2) to compare CNB and FNA as a first-line diagnostic procedure in thyroid lesions at higher risk of cancer.
Seventy-seven patients with a suspicious-appearing, recently discovered solid thyroid nodule were initially enrolled as study participants. No patients had undergone prior thyroid fine-needle aspiration/biopsy. Based on study design, all patients were proposed to undergo CNB as first-line diagnostic aspiration, while those patients refusing to do so underwent conventional FNA.
Five patients refused the study, and a total of 31 and 41 thyroid nodules were subjected to CNB and FNA, respectively. At follow-up, the overall rate of malignancy was of 80% (CNB, 77%; FNA, 83%). However, the diagnostic accuracy of CNB (97%) was significantly (P < 0.05) higher than that of FNA (78%). In one benign lesion, CNB was inconclusive. Four (12%) of the 34 cancers of the FNA group were not initially diagnosed because of false negative (N = 1), indeterminate (N = 2) or not adequate (N = 1) samples.
CNB can reduce the false negative and inconclusive results of conventional FNA and should be considered a first-line method in assessing solid thyroid nodules at high risk of malignancy.
Thyroid cancer; Core needle biopsy (CNB); Ultrasonography; Fine-needle aspiration (FNA)
Endoscopic ultrasound guided fine needle aspiration biopsy (EUS‐FNA) has proven to be an effective diagnostic modality for the detection and staging of pancreatic malignancies. In recent years EUS‐FNA has also been used to diagnose lesions of non‐pancreatic sites such as structures in close proximity to the gut wall within the mediastinum, abdomen, pelvis and retro‐peritoneum.
To evaluate experience with EUS‐FNA of non‐pancreatic sites at a large university medical centre.
The study cohort included 234 patients who underwent EUS‐FNA of 246 lesions in non‐pancreatic sites (122 peri‐pancreatic and coeliac lymph nodes; 9 peri‐pancreatic masses; other sites: mediastinum 12, gastric 25, liver 27, oesophagus 17, duodenum/colon/rectum 15, retro‐peritoneum 8, lung 7, miscellaneous 4).
The cytology diagnoses were classified as non‐neoplastic/reactive in 82 (33%), atypical/suspicious for malignancy in 25 (10%), malignant in 86 (35%) and non‐diagnostic in 53 (22%) cases. Surgical pathology follow‐up was available in 75 (31%) cases. Excluding the non‐diagnostic cases there were 7 false negative and 3 false positive cases. The sensitivity, specificity and positive predictive value of EUS‐FNA in the diagnosis of lesions of non‐pancreatic sites was 92%, 98% and 97%, respectively.
EUS‐FNA can be effectively used as a diagnostic modality in the diagnosis of lesions from non‐pancreatic sites.
endoscopy; ultrasound; fine needle biopsy
Distinguishing benign and malignant lymph nodes by the findings of endoscopic ultrasonography (EUS) is still controversial. We tried to evaluate EUS findings of benign mediastinal and abdominal lymphadenopathy (BLAP) confirmed by EUS-guided fine needle aspiration (FNA).
A total of 37 patients with enlarged mediastinal or abdominal lymph nodes (diameter ≥1 cm) were enrolled and EUS-FNA was performed. Final diagnosis was based on FNA cytology and follow up imaging studies (CT scans or EUS).
Thirteen patients were confirmed to have BLAP by EUS-FNA. Causes of BLAP were as follows; (i) extrapulmonary tuberculosis in six cases including patients with postoperative states due to cervical cancer and advanced gastric cancer, (ii) Kikuchi disease in one case, (iii) hypereosinophilic syndrome in one case, (iv) reactive hyperplasia in five cases including patients with postoperative states due to thyroid cancer, lung cancer, and EGC with ESD. EUS findings of BLAP revealed that median lymph node size was 24.7 mm. Lymph nodes were oval or round shaped in 9 cases, sharp borders in 9 cases, hypoechoic echo pattern in 7 cases, heterogenous internal echo pattern in 7 cases. Other findings included internal septation, calcification, multiplicity, attachment to the gastrointestinal tract wall, and conglomeration.
EUS findings of BLAP were not different from those of malignant lymphadenopathy previously reported in other studies.
Lymphadenopathy; Endoscopic ultrasonography, Fine needle aspiration
The purpose of this study was to identify the spectrum of cytological diagnoses and evaluate the diagnostic effectiveness of fine needle aspiration cytology (FNA) in patients less than 20 years old. The subjects were selected by retrospectively reviewing records from 1999 to 2009. Selected patients less than 20 years old underwent FNA. Cytological and histological slides of samples from the subjects were reviewed. Our study included a total of 909 subjects with a mean age of 14.6 years. The majority of the FNA samples were taken from lymph nodes (n = 448, 49.3%), with the remaining aspirates obtained from the thyroid gland (n = 247, 27.2%), soft tissues of head and neck masses (n = 106, 11.7%), salivary glands (n = 75, 8.3%), breasts (n = 18, 1.9%), skins (n = 9, 1.0%) and soft tissues of extremity (n = 6, 0.7%). The majority (87.6%, n = 796) of the FNA samples were categorized as ‘benign’, with the remaining designated as ‘atypical lesion’ (n = 18, 2.0%), ‘malignant’ (n = 24, 2.6%), or ‘inadequate specimen’ (n = 71, 7.8%). FNA accuracy was 92% for diagnosing cancer. Specificity and sensitivity were 99% and 63%, respectively. Our study first revealed that FNA has a high specificity for diagnosing cancer in various anatomical locations in young patients and can be confidently used as an effective tool for diagnosing malignancies in young individuals with a clinically suspicious lesion.
Fine needle aspiration; cytology; children and adolescents; sensitivity; specificity
Seventy-five percent of thyroid nodules with indeterminate fine-needle aspiration (FNA) cytology are found to be benign postoperatively. A novel genomic test, the Afirma® gene expression classifier (AGEC), has been available for clinical use in the United States, since late 2010. In 2010, two modest-sized validation studies showed that the AGEC could identify a benign gene expression signature in indeterminate cytology thyroid FNA samples with a negative predictive value >95%. The objective of this study was to evaluate how the AGEC impacted the joint decision of the endocrinologist and patient to operate when FNA cytology was indeterminate, but the AGEC reading of the nodule was benign.
In this cross-sectional cohort study, data were contributed retrospectively by 51 endocrinologists at 21 practice sites that had previously obtained ≥3 benign AGEC readings in ≥1 cm nodules with indeterminate FNA cytology readings. Information regarding demographic data, nodule size and location, decision to operate, surgery type (hemithyroidectomy [HT] or total thyroidectomy [TT]), and reason for recommending surgery was retrospectively collected.
Compared to a 74% previous historical rate of surgery for cytologically indeterminate nodules, the operative rate fell to 7.6% during the period that AGEC were obtained in the clinical practices, a highly significant reduction in the decision to operate (p<0.001). The rate of surgery on cytologically indeterminate nodules that were benign by the AGEC reading did not differ from the historically reported rate of operation on cytologically benign nodules (p=0.41). The four primary reasons reported by the physicians for operating on nodules with a benign AGEC reading, in descending order: large nodule size (46.4%), symptomatic nodules (25.0%), rapidly growing nodules (10.7%), or a second suspicious or malignant nodule in the same patient (10.7%). These reasons are concordant with those typically given for operation on cytologically benign nodules.
In a substantial group of medical practices, obtaining an AGEC test in patients with cytologically indeterminate nodules was associated with a striking reduction in the rate of diagnostic thyroidectomy. Approximately, one surgery was avoided for every two AGEC tests run on thyroid FNAs with indeterminate cytology.