Comparison of cytological results obtained by repeated US‐guided fine‐needle aspiration biopsies of thyroid nodules: Focus on the rate of malignancy and diagnostic concordance

The debate still continues on the repeated fine‐needle aspiration biopsies (FNABs) for thyroid nodule in clinical practice. In this study, we determined the rate of cytological change to malignancy and the diagnostic concordance of repeated FNABs when the same nodules were targeted under US‐guidance. We retrospectively reviewed data for 187 thyroid nodules (173: twice, 14: three times) from 160 patients who underwent repeated US‐guided FNABs, which were performed by one skilful radiologist targeting for the same nodules at a mean interval of 7.5 months. Their initial cytological findings were compared with second or third results and histopathologic follow‐up. The initial FNABs findings of 187 nodules were unsatisfactory, benign, and indeterminate in 56, 52, and 79 cases, respectively. The rate of a second cytological diagnosis changed to malignancy was significantly higher in the unsatisfactory aspirates (10.7%; 6/56), when compared with those of the benign (0.0%; 0/52) or of indeterminate aspirates (3.8%; 3/79) (P = 0.022). However, there was no change to malignancy at third cytological findings of all 14 nodules. After the second US‐guided FNABs, 30.8% (16/52) of the initially diagnosed as benign aspirates were reclassified as indeterminate, while 26.6% (21/79) of the initially diagnosed as indeterminate were reclassified as benign. In conclusion, to identify malignancies, repeated US‐guided FNABs are recommended for thyroid nodules initially classified as unsatisfactory aspirates. However, although US‐guidance is applied, a discrepancy might be unavoidable in the cytological interpretation of the nodules classified as benign or as indeterminate aspirates because of overlapping cytological criteria. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Diagnostic value of B‐RAFV600E in difficult‐to‐diagnose thyroid nodules using fine‐needle aspiration: Systematic review and meta‐analysis

Fine‐needle aspiration (FNA) is routinely used in the preoperative evaluation of thyroid nodules. However, approximately 5–20% of thyroid nodules are considered indeterminate or suspicious cases that do not meet clinical standards. The B‐RAF^V600E mutation has been reported in FNA specimens. We conducted a systematic review to evaluate the diagnostic value of testing for B‐RAF^V600E in thyroid nodules that are difficult to diagnose by FNA. A systematic literature search was performed from January 1, 2002 to June 30, 2012. Articles were obtained by searching two electronic databases (MEDLINE and EMBASE), hand searching selected journals, and contacting authors. Article quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. Sensitivity, specificity, and other measures of accuracy were pooled using random effects models. Summary receiver operating characteristic (SROC) curves were used to summarize overall diagnostic accuracy. A total of 16 studies incorporating 1131 patients were included in a meta‐analysis on diagnostic accuracy of B‐RAF^V600E tests. Pooled sensitivity was 0.60 (95% confidence interval [CI]: 0.556–0.634), pooled specificity was 0.99 (95% CI 0.976–0.997), and the area under the curve of the SROC curve was 0.8376. Q index value was 0.7696. Our data suggest a potentially useful adjunct to evaluating thyroid nodules that are difficult to diagnose. The B‐RAF^V600E test has a high positive predictive value and could help clinicians formulate a more individualized treatment schedule. When supplemented with other noninvasive test methods, the B‐RAF^V600E test could be a powerful adjunct with extensive clinical applications. Diagn. Cytopathol. 2014;42:94–101. © 2013 Wiley Periodicals, Inc.     

Endoscopic ultrasound‐guided fine‐needle aspiration biopsy of gastric schwannoma: Cytomorphologic features and diagnostic pitfalls

Schwannoma rarely occurs in the stomach. We present a case of gastric schwannoma, which was initially evaluated by endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) biopsy and confirmed by surgical resection. The patient was a 57‐years‐old woman with history of dyspepsia, who was found to have a large submucosal mass in the stomach. EUS‐FNA showed scant spindle cells with abundant lymphocytes. The spindle cells were immunoreactive with S100, while negative for CD117, desmin, and CD34. The lymphocytes were mixed B‐cells and T‐cells. Immunostaining, flow cytometry, and molecular testing showed no evidence of B‐cell lymphoma. The diagnosis of gastric schwannoma was confirmed by histopathological evaluation of the resected tumor. Gastric schwannoma has unique features of mixed spindle cells and lymphocytes. The tumor should be differentiated from other gastric mesenchymal tumors, and lymphoproliferative disorder is a pitfall.     

Comparison of the diagnostic accuracy of thyroid fine‐needle aspiration in follicular‐patterned lesions using a 5‐tiered and a 6‐tiered diagnostic system: A double‐blind study of 140 cases with histological confirmation

Five‐tiered and 6‐tiered systems for reporting thyroid fine‐needle aspiration (FNA) results are used widely throughout the world. In this study, we present a double‐blind study of histologically confirmed follicular‐patterned neoplasms and evaluate the cytological classification of the same lesions according to both systems. One hundred and forty consecutive surgically resected thyroid follicular‐patterned lesions with a diagnostic preoperative FNA were retrieved from our archive. Two cytopathologists, who were blinded to all clinical information, classified each FNA case according to their respective routine diagnostic reporting system (5‐tiered or 6‐tiered). Interobserver variability was assessed using Cohen's Kappa (K) coefficient. Diagnostic accuracy was determined by measuring sensitivity and specificity. Receiver operator characteristic (ROC) curves were calculated for each cytopathologist. The 140 thyroid FNAs included histologically confirmed nodular hyperplasia, follicular adenomas, follicular carcinomas, and papillary carcinomas, follicular variant (35 cases for each) obtained from 104 females and 36 males with a mean age of 48.8 years and a mean tumor diameter of 27.8 mm. Negative predictive values (PV) for benign cases were 72.2% and 68.8% in the 5‐tiered and 6‐tiered systems, respectively (P = 0.7009). Positive PV were 100% for malignant cases in both systems. The sensitivity (78.6% vs. 72.9%, P = 0.4305), specificity (55.7% vs. 47.1%, P = 0.3103), and diagnostic accuracy (67.1% vs. 60.0%, P =0.2143) were similar between the systems. ROC curves almost entirely overlapped (P = 0.8937). Both the 5‐tiered and 6‐tiered systems show similar diagnostic accuracy in follicular‐patterned lesions, further supporting the adoption of a common reporting system for thyroid cytopathology. Diagn. Cytopathol. 2014;42:744–750. © 2014 Wiley Periodicals, Inc.     

Ultrasonography-guided fine-needle aspiration cytology for thyroid nodules: an emphasis on one-sampling and biopsy techniques

The aim of this study was to assess the adequacy and efficacy of ultrasonography (US)-guided fine-needle aspiration cytology (US-FNAC) with one-sampling technique (only one specimen through a single needle pass was obtained during the procedure on each thyroid nodule in each study patient) for the cytological diagnosis of thyroid nodules. In this study, US-FNAC techniques, including "free two-hand," "mixed sampling," "flipping-extraction," and "single-needle-pass" procedures were used to collect thyroid cells from July 2007 to June 2009. The cytopathology results and patients' complications were reviewed retrospectively. Of the 1456 thyroid-nodule samples obtained from 977 patients (1.49 per patient), the incidence of adequate and inadequate samplings was 88.5% (1289/1456) and 11.5% (167/1456), respectively. After thyroid surgery in 396 patients, 568 nodules were confirmed as 353 papillary thyroid carcinomas including one diffuse sclerosing variant, five follicular thyroid carcinomas, three medullary thyroid carcinomas, one anaplastic thyroid carcinoma, one metastatic renal cell carcinoma, two poorly differentiated carcinomas, 17 follicular adenomas, two nodular thyroiditis, two pseudonodules related to thyroiditis, and 182 cases of nodular hyperplasia. Sensitivity, specificity, positive predictive value, negative predictive value, accuracy, false-negative rate, and false-positive rate for the US-FNAC were 94.3%, 91.9%, 96.2%, 88.3%, 93.6%, 3.9%, and 2.6%, respectively. There were no significant patients' complications, but 87 patients (8.9%) reported mild pain during or after the procedure. This study showed a good adequacy and efficacy of US-FNAC for thyroid nodules despite one-sampling.     

Cytotechnologist screening of fine‐needle aspiration specimens

Fine‐needle aspiration (FNA) is widely utilized due to its short turnaround time (TAT), diagnostic accuracy, and low cost. Controversy exists as to what role cytotechnologists should play in evaluation of FNAs. Some authorities believe all FNAs should be screened by cytotechnologists while others believe that cytotechnologist review is unnecessary. Sixty sequentially performed FNAs without initial review by cytotechnologists were selected from the files of the University of Utah, Department of Pathology. The slides were obtained along with the associated final diagnoses. The slides were reviewed by cytotechnologists given patient history and specimen site but were blinded to the initial pathologist's diagnoses. The initial cytopathologist's diagnoses and subsequent cytotechnologists' diagnoses were recorded and correlated. TATs for these cases were calculated and compared with TATs in a second set of randomly selected FNAs where cytotechnologists had initially screened the cases. Correlation of initial cytopathologists' diagnoses with those of cytotechnologists' revealed no instances where cytotechnologists identified diagnostically significant findings not noted by the original pathologist. TAT for the FNAs reviewed only by a cytopathologist averaged 25.9 hours with a mode of 6 hours. TATs for cases with initial cytotechnologist screening averaged 44.1 hours with a mode of 25 hours. Pre‐sign‐out screening of FNA specimens by cytotechnologists does not appear to increase detection of cytologic abnormalities. Cytotechnologist screening does substantially increased TAT from a mean of 26 hours to approximately 44 hours. Such an extensive delay may reduce the overall clinical utility of the FNA technique. Diagn. Cytopathol. 2014;42:606–608. © 2014 Wiley Periodicals, Inc.     

EUS‐guided 22‐gauge fine‐needle aspiration versus core biopsy needle in the evaluation of solid pancreatic neoplasms

Endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) is widely used for diagnosis of pancreatic lesions. The Echotip Procore Needle (Wilson‐Cook Medical) is a new 22G fine biopsy needle (FNB) for obtaining core biopsy material at time of EUS. This study aimed to compare the technical and diagnostic performance of conventional FNA and FNB. Thirty‐two patients met the design criteria for this prospective paired cohort study. All lesions sampled were solid (non‐cystic) pancreatic masses by EUS appearance. Patients were randomized to receive FNA or FNB by first attempt. A cytopathologist performed on‐site evaluations. Samples were assessed for accuracy of diagnosis, cellularity, contamination, and sufficiency for ancillary studies. Technical and diagnostic performances were compared. Compared to FNA, there was a statistically significant decreased ability of FNB to achieve a diagnosis (FNA 93.8%, FNB 28.1%, P < 0.001). FNB was diagnostically superior to FNA in 1 of 32 cases. Technical failures were observed in five cases due to resistance to advancement of the FNB needle. Regarding operator perceived ease‐of‐use, FNA outperformed FNB (P < 0.001). Eight cases had insufficient FNB material to survive tissue processing. There was no significant difference in mean specimen cellularity between devices. FNA samples showed an increased amount of contaminant (P = 0.036) but were more sufficient for ancillary studies (P = 0.502). Although deemed comparable to FNA when providing material for cytology, the pledged advantage of FNB acting like a core biopsy needle was not apparent in our series. Additional studies are needed before routine adoption of 22G FNB can be recommended. Diagn. Cytopathol. 2014;42:751–758. © 2014 Wiley Periodicals, Inc.     

Putting an eye on cytological specimens: An audit of the clinical impact of thyroid fine‐needle aspiration in different health care settings

There is published evidence showing less cost‐benefit approaches in the evaluation of thyroid nodules. We performed an institutional audit of the cytologic diagnosis of thyroid fine‐needle aspiration (FNA) in an attempt to perceive the clinical impact of this technique on the management of thyroid nodules and to compare it in two different types of health care: Primary Care Medicine and Endocrinology. We performed a retrospective analysis to the electronic records of patients referred from General Practitioners (GP) and Endocrinologists (E) for thyroid FNA between 2010 and 2012. Request forms for cytological reports where retrieved for analysis of clinical and cytological data. The database search retrieved 1655 patients (female gender: 88.2%; GP references: 51.8%). Preprocedure clinical information was available from 157 out of 2005 nodules (7.8%). Significant differences in cytological diagnosis were seen in “Nondiagnostic” (GP: 11.6%; E: 7.5%, χ² = 0.002) and “Benign” categories (GP: 75%; E: 81.8%, χ² < 0.001). The main potential cause of “Nondiagnostic” samples was nodules smaller than one centimeter (total: 14 cases; GP: 7; E: 7). Reasons to request FNA for these nodules were provided in 6 out of 27 cases (GP: 0/16; E: 6/11, P < 0.001). The rate of insufficient samples was inversely correlated with nodule size (τ = ?0.242, P = 0.001). When evaluating thyroid nodules, clinicians should take into account the limitations of FNA, the international recommendations for better cost‐benefit approaches and the importance of a well‐informed cytopathologist for better cytological diagnostic results. Diagn. Cytopathol. 2014;42:1009–1012. © 2014 Wiley Periodicals, Inc.     

Papillary thyroid carcinoma with atypical histiocytoid cells on fine‐needle aspiration

Although papillary thyroid carcinoma (PTC) usually has classic cytological characteristics on fine‐needle aspiration (FNA), it can present rarely with aberrant features resembling those of histiocytes in a cystic nodule. The aim of the current study was to describe PTC with atypical histiocytoid cells and distinguish it from benign histiocytes. A retrospective computerized search for FNAs with atypical features suggestive of PTC and cystic degeneration was performed, and if available, the corresponding resection specimens were compared. Four cases met the criteria for FNAs and three had surgical pathology follow‐up, which showed PTC. One aspirate had some features typical of PTC, but the remaining FNAs had atypical histiocytoid cells, which had traits intermediate between those of PTC and histiocytes. Large cell size, pseudoinclusions, nuclear grooves, and multiple well‐defined vacuoles in atypical histiocytoid cells favor PTC over benign histiocytes. Ancillary immunocytochemical studies can also be useful in confirming the diagnosis. Histiocytic cells are frequently present in thyroid aspirates, and occasionally, they have atypical features that represent an unusual presentation of PTC. Closer examination of these cells can provide diagnostic clues for preventing false‐negative diagnosis of PTC. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Medullary thyroid carcinoma presenting as rectangular cell type on fine‐needle aspiration

Medullary thyroid carcinoma typically presents as dyscohesive plasmacytoid, spindled, or polygonal cells on fine‐needle aspiration smears. We recently encountered a case of sporadic medullary thyroid carcinoma that presented as a hypercellular aspirate composed of cohesive aggregates of rectangle‐shaped cells. The case was mistakenly reported as a hypercellular follicular neoplasm on cytology. Subsequent thyroidectomy revealed medullary carcinoma. We draw attention to this distinctive rectangular cell type as an additional morphology for medullary thyroid carcinoma. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Malignant teratoma of the thyroid: A difficult diagnosis by fine‐needle aspiration

Primary thyroid teratomas are rare, usually benign, and typically occur in children. We report the unusual occurrence of a malignant thyroid teratoma in a young man. Initial ultrasound and CT studies revealed an 8.5 heterogeneous mass involving the entire right thyroid lobe causing tracheal compression and deviation. Fine‐needle aspiration (FNA) revealed malignant cells with possible neuroendocrine features. Similar findings have been previously reported, with an occasional interpretation as possible medullary thyroid carcinoma. In no report, as with our case, has the correct diagnosis been suggested with FNA. The surgical specimen contained abundant primitive neuroepithelium with a very minor component of mature ectodermal tissue in one area. Like this case, an abundance of immature neuroepithelium has been reported in essentially all previous reports of primary malignant thyroid teratoma, sometimes creating a challenge to find another type of germ cell tissue. Array comparative genomic hybridization studies in this case revealed a markedly complex karyotype including gain of chromosome 12 and loss of 17p. Amplification of MYCN, EWSR1 rearrangement and isochromosome 12p were not identified, providing no evidence for neuroblastoma or Ewing sarcoma/peripheral neuroectodermal tumor, both of which have also rarely been reported as primary thyroid tumors. With the use of cisplatinum‐based chemotherapy combined with radiation, survival times have increased dramatically. Our patient is now disease free and back to his normal activities after relatively short follow‐up. Although rare, it is important to be aware that teratomas may present as a thyroid nodule. Recognition by FNA is challenging, and requires multiple modalities for full identification.     

Endoscopic ultrasound‐guided fine‐needle aspiration diagnosis of merkel cell carcinoma metastatic to the pancreas

Merkel cell carcinoma (MCC) is a rare and highly aggressive primary neuroendocrine carcinoma of the skin with a high propensity for local, regional, and distant spread. Distant metastasis of MCC to the pancreas is uncommonly seen and may impose a diagnostic challenge cytologically. Here we report a case of MCC with pancreatic metastasis, which was diagnosed by endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA). The aspirates revealed both single and clustered epithelial cells with scant cytoplasm and round nuclei with stippled chromatin and inconspicuous nucleoli. Immunocytochemically, the tumor cells were positive for CK20, synaptophysin, CD56, and CD117. The neoplastic cells were also identified by flow cytometry as non‐hematopoietic cells which were positive for CD56 and negative for CD45. To our knowledge, this is only the second case report of MCC metastatic to the pancreas diagnosed by EUS‐FNA. There have been several reports of MCC metastatic to the pancreas diagnosed only at the time of surgical resection. However, a preoperative diagnosis allows for appropriate management while sparing a patient the morbidity of unnecessary procedures. Diagn. Cytopathol. 2014;247–252. © 2012 Wiley Periodicals, Inc.     

Utility of endoscopic ultrasound‐guided fine‐needle aspiration in the diagnosis and staging of colorectal carcinoma

The objective of this study is to assess the utility of endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) in the diagnosis and staging of colorectal cancer. The study includes patients who underwent EUS‐FNA at our institution for staging of colorectal carcinoma or for evaluation peri‐rectal masses or distal metastases from August 2000 to November 2010. We assessed the frequency with which EUS‐FNA procedure confirms the diagnosis of malignancy and the percent of cases in which it modifies staging of colorectal carcinoma. Using histology as a reference standard, we also assessed the diagnostic performance. We identified 79 cases of EUS‐FNA from 77 patients, mean (SD) age of 60 (12.5), 44 males. Twenty‐seven (34%) aspirates were from patients with primary rectal/peri‐rectal masses, 15 (19%) were from patients with suspected regional lymph node metastasis, and 37 (47%) were cases of suspected of distal metastasis. All lesions were clinically suspicious for primary or metastatic colorectal carcinoma. On cytologic examinations, 43 (54%) cases were confirmed as malignant, 6 (8%) were benign neoplasms, 4 (5%) were suspicious for malignant neoplasm, 2 (3%) showed atypical cells, and the rest 24 (30%) were negative for neoplasms. Fourteen of 27 (52%) of the local rectal masses were confirmed as colorectal carcinoma. Eleven of 15 (73%) regional lymph nodes were positive for metastasis—all, but two of these metastases, were of colorectal origin. Twenty of 37(54%) distal lesions were metastatic neoplasms and 15 of those were colorectal in origin. Diagnosis of primary colorectal carcinoma was confirmed in 52% of the clinically suspicious primary lesions and in 42% regional or distal metastatic lesions. Using histology as a reference standard in 27 of 79 (29%) cases, we calculated an overall sensitivity, specificity, and positive and negative predictive values (C.I) of EUS‐FNA of 89% (74–100%), 79% (50–100%) 89% (74–100%), and 79% (51–100%). EUS‐FNA is useful for assessing primary and metastatic colorectal lesion. This technique improves staging of suspected nodal or distant metastases. Diagn. Cytopathol. 2013;41:1031–1037. © 2011 Wiley Periodicals, Inc.