Fine Needle Aspiration Cytology Biopsy Research Articles

Fine Needle Aspiration and Medullary Thyroid Carcinoma: The Risk of Inadequate Preoperative Evaluation and Initial Surgery when Relying upon Fnab Cytology Alone

ObjectivesTo evaluate the diagnostic accuracy of fine-needle aspiration biopsy (FNAB) to preoperatively diagnose medullary thyroid cancer (MTC) among multiple international centers and evaluate how the cytological diagnosis alone could impact patient management. MethodsWe performed a retrospective chart review of sporadic MTC (sMTC) patients from 12 institutions over the last 29 years. FNAB cytology results were compared to final pathologic diagnoses to calculate FNAB sensitivity. To evaluate the impact of cytology sensitivity for MTC according to current practice and to avoid confounding results by local treatment protocols, changes in treatment patterns over time, and the influence of ancillary findings (e.g., serum calcitonin), therapeutic interventions based on FNAB cytology alone were projected into 1 of 4 treatment categories: total thyroidectomy (TT) and central neck dissection (CND), TT without CND, diagnostic hemithyroidectomy, or observation. ResultsA total of 313 patients from 4 continents and 7 countries were included, 245 of whom underwent FNAB. FNAB cytology revealed MTC in 43.7% and possible MTC in an additional 2.4%. A total of 113 (46.1%) patients with surgical pathology revealing sMTC had FNAB findings that supported TT with CND, while 37 (15.1%) supported TT alone. In the remaining cases, diagnostic hemithyroidectomy and observation were projected in 32.7% and 6.1%, respectively. ConclusionFNAB is an important diagnostic tool in the evaluation of thyroid nodules, but the low sensitivity of cytological evaluation alone in sMTC limits its ability to command an optimal preoperative evaluation and initial surgery in over half of affected patients. (Endocr Pract. 2013;19:920-927)

Thyroglobulin in the Washout Fluid of Lymph-Node Biopsy: What Is Its Role in the Follow-Up of Differentiated Thyroid Carcinoma?

The clinical evaluation of enlarged local lymph nodes (LNs) is difficult at the beginning and throughout the follow-up of differentiated thyroid carcinoma (DTC). Although the examination of samples collected from LNs by fine-needle aspiration biopsy cytology (FNAB-C) is extremely specific for the diagnosis of metastases, its sensitivity is low, especially in paucicellular samples. The measurement of thyroglobulin (Tg) in the fine-needle aspiration biopsy (FNAB) washout fluid (FNAB-Tg) increases the diagnostic performance of cytology to up to 100% sensitivity and specificity. However, the application of FNAB-Tg is currently hindered by the absence of methodological standardization, a lack of definite cutoff points, and the ongoing debate regarding its accuracy in nonthyroidectomized patients, those with elevated serum Tg, and those with circulating anti-Tg antibodies. FNAB-Tg improves the diagnostic performance of FNAB-C in LN metastases, even when the latter is unable to diagnose the metastases. For that reason, FNAB-Tg should be included in the monitoring of DTC.

Thyroid Nodules (≥4 cm): Can Ultrasound and Cytology Reliably Exclude Cancer?

Whether a threshold nodule size should prompt diagnostic thyroidectomy remains controversial. We examined a consecutive series of patients who all had thyroidectomy for a≥4cm nodule to determine (1) the incidence of thyroid cancer (TC) and (2) if malignant nodules could accurately be diagnosed preoperatively by ultrasound (US), fine needle aspiration biopsy (FNAB) cytology and molecular testing. As a prospective management strategy, 361 patients with 382 nodules≥4cm by preoperative US had thyroidectomy from 1/07 to 3/12. The incidence of a clinically significant TC within the≥4cm nodule was 22% (83/382 nodules). The presence of suspicious US features did not discriminate malignant from benign nodules. Moreover, in 86 nodules≥4cm with no suspicious US features, the risk of TC within the nodule was 20%. US-guided FNAB was performed for 290 nodules, and the risk of malignancy increased stepwise from 10.4% for cytologically benign nodules, 29.6% for cytologically indeterminate nodules and 100% for malignant FNAB results. Molecular testing was positive in 9.3% (10/107) of tested FNAB specimens, and all ten were histologic TC. In a large consecutive series in which all≥4cm nodules had histology and were systematically evaluated by preoperative US and US-guided FNAB, the incidence of TC within the nodule was 22%. The false negative rate of benign cytology was 10.4%, and the absence of suspicious US features did not reliably exclude malignancy. At minimum, thyroid lobectomy should be strongly considered for all nodules≥4cm.

Indications for renal fine needle aspiration biopsy in the era of modern imaging modalities

Background:Renal fine needle aspiration biopsy (FNAB) has become an uncommon procedure in the era of renal helical computed tomography (CT), which has high diagnostic accuracy in the characterization of renal cortical lesions. This study investigates the current indications for renal FNAB. Having knowledge of the specific clinico-radiologic scenario that led to the FNAB, cytopathologists are better equipped to expand or narrow down their differential diagnosis.Materials and Methods:All renal FNABs performed during a 6 year interval were retrieved. Indication for the procedure was determined from the clinical notes and radiology reports.Results:Forty six renal FNABs were retrieved from 43 patients (14 females and 29 males with a mean age of 52 years [range, 4-81 years]). Twenty one cases (45.6%) were performed under CT-guidance and 25 cases (54.4%) under US-guidance. There were four distinct indications for renal FNAB: (1) solid renal masses with atypical radiological features or poorly characterized on imaging studies due to lack of intravenous contrast or body habitus (30.2%); (2) confirmation of radiologically suspected renal cell carcinoma in inoperable patients (advanced stage disease or poor surgical candidate status) (27.9%); (3) kidney mass in a patient with a prior history of other malignancy (27.9%); and (4) miscellaneous (drainage of abscess, indeterminate cystic lesion, urothelial carcinoma) (14.0%). 36 patients (83.7%) received a specific diagnosis based on renal FNAB cytology.Conclusions:Currently, renal fine needle aspiration remains a useful diagnostic tool in selected clinico-radiologic scenarios.

Preoperative Discrimination of Benign from Malignant Disease in Thyroid Nodules With Indeterminate Cytology Using Elastic Light-Scattering Spectroscopy

Thyroid nodules are common and often require fine needle aspiration biopsy (FNAB) to determine the presence of malignancy to direct therapy. Unfortunately, approximately 15-30% of thyroid nodules evaluated by FNAB are not clearly benign or malignant by cytology alone. These patients require surgery for the purpose of diagnosis alone; most of these nodules ultimately prove to be benign. Elastic light scattering spectroscopy (ESS) that measures the spectral differences between benign and malignant thyroid nodules has shown promise in improving preoperative determination of benign status of thyroid nodules. We describe the results of a large, prospective, blinded study validating the ESS algorithm in patients with thyroid nodules. An ESS system was used to acquire spectra from human thyroid tissue. Spectroscopic results were compared to the histopathology of the biopsy samples. Sensitivity and specificity of the ESS system in the differentiation of benign from malignant thyroid nodules are 74% and 90% respectively, with a negative predictive value of 97%. These data suggest that ESS has the potential for use in real time diagnosis of thyroid nodules as an adjunct to FNAB cytology.

Cervical lymph node metastases from thyroid cancer: does thyroglobulin and calcitonin measurement in fine needle aspirates improve the diagnostic value of cytology?

BackgroundMeasurement of thyroglobulin (Tg) protein in the washout of the needle used for fine needle aspiration biopsy cytology (FNAB-C) has been shown to increase the sensitivity of FNAB-C in identifying cervical lymph node (CLN) metastasis from well-differentiated thyroid cancer (TC). In this study, we evaluated whether routine measurement of Tg protein (FNAB-Tgp), Tg mRNA (FNAB-Tgm) and calcitonin (CT) mRNA (FNAB-CTm) in the FNAB washout of CLN increases the accuracy of FNAB-C in the diagnosis of suspicious metastatic CLN.MethodsIn this prospective study 35 CLN from 28 patients were examined. Histology showed metastatic papillary TC (PTC) in 26 CLN, metastatic medullary TC (MTC) in 3 CLN, metastatic anaplastic TC (ATC) in 3 CLN and 3 metastatic CLN from extra-thyroidal cancers.ResultsThe overall accuracy of FNAB-C was 84.4%, reaching 95.7% when the analysis was restricted to PTC. Both FNAB-Tgp and FNAB-Tgm compared favorably with FNAB-C and shown diagnostic performances not statistically different from that of FNAB-C. However, FNAB-Tgp and FNAB-Tgm/FNAB-CTm were found useful in cases in which cytology results were inadequate or provided diagnosis inconsistent with patient's clinical parameters.ConclusionsWe demonstrated that FNAB-C, Tg/CT mRNA and Tg protein determination in the fine-needle washout showed similar accuracy in the diagnosis of metastatic CLN from TC. The results of this study suggest that samples for Tg protein and Tg/CT mRNA measurements from CLN suspicious for metastatic TC should be collected, but their measurements should be restricted to cases in which FNAB-C provides uninformative or inconsistent diagnosis with respect to patient's clinical parameters.

A Resectable Pancreatic Metastasis from Pulmonary Adenocarcinoma

A 67-year-old man, diagnosed as primary pulmonary adenocarcinoma by intraoperative fine-needle aspiration biopsy cytology, underwent right lower lobectomy with radical lymphadenectomy. The pathological stage was Stage IIA (pT1bN1M0, N-reason: 12L positive). After surgery, nodular shadows without intrathoracic lymph node or distant metastasis were demonstrated metachronously three times by follow-up CT. Wedge resection was performed for each of the tumors, and the pathological diagnosis in each case was primary pulmonary adenocarcinoma, Stage IA (T1b), IA (T1a) and IA (T1a), respectively. Five years after the initial pulmonary resection, a follow-up abdominal CT revealed a20-mm nodular shadow. We suspected that this pancreatic tumor might be a primary rather than metastatic one, therefore, pancreatoduodenectomy was performed. Pathological examination revealed adenocarcinoma that was positive for thyroid transcription factor (TTF)-1, allowing a final diagnosis of metastatic pulmonary adenocarcinoma.This case is very rare, because most cases of pancreatic metastasis from lung cancer have already widespread disease at the time of diagnosis.This case illustrates that pancreatic metastasis from pulmonary adenocarcinoma should be borne in mind, even if the pancreatic tumor is a solitary lesion without additional organ metastasis.

Diagnostic accuracy of fine needle aspiration biopsy cytology and ultrasonography in patients with thyroid nodules diagnosed as benign or indeterminate before thyroidectomy

Fine-needle aspiration biopsy cytology (FNABC) and ultrasonography (US) play an important role in differentiating benign thyroid nodules from malignant nodules. We retrospectively investigated the prevalence of follicular thyroid carcinoma (FTC) in patients with thyroid nodules whose FNABC and US readings were not malignant before thyroidectomy. Between 2007 and 2008, 3333 patients underwent thyroidectomy at our institution, and the 737 of them who had thyroid nodule that had been diagnosed as hyperplastic nodule or follicular tumor by FNABC and US preoperatively were the subjects in this study. Postoperative histopathology showed hyperplastic nodule in 416 patients, follicular adenoma in 200 patients, FTC in 99 patients, and other disease in 22 patients. By FNABC, 34 (6.7%) of the 505 patients with diagnosis as benign and 65 (28%) of the 232 patients with diagnosis as indeterminate, were diagnosed as having FTC. The diagnosis was FTC in 56 (9.6%) of the 582 patients with a preoperative diagnosis of hyperplastic nodule by US and 43 (27.7%) of the 155 patients with a diagnosis of follicular tumor by US. The diagnosis of FTC was made in 21 (4.8%) of 438 patients who were concurrently diagnosed as benign by FNABC and as hyperplastic nodule by US, and in 30 (34.1%) of 88 patients who were diagnosed as indeterminate by FNABC and follicular tumor by US. FNABC has been the mainstay for the preoperative evaluation of thyroid nodule. The results of this study showed that US can also be a useful tool for diagnosing FTC.

Quality assurance of rapid on-site evaluation of CT-guided fine-needle aspiration cytology of lung nodules

The methods available for the diagnosis of lung cancer include radiologic, cytologic and pathologic procedures. The aim of this study was to determine the quality assurance of CT guided fine needle aspiration cytology of lung nodules. Cytology results were rated to 4 categories (positive; suspicious; negative; not representative). All cytology reports were compared with the final histology diagnosis. A total of 128 patients underwent CT-guided percutaneous fine-needle aspiration biopsy cytology (63 males; 65 females; mean age 62.8 years). Smears were adequate in 99 cases and inadequate in 29 cases. The average diameter of the nodules was 3.28 cm. Thirty three (25.6%) of the cases were histologically verified and 2 falsely negative and 2 falsely positive cases were detected. The sensitivity and the positive predictive value were 88.8% and 88.8%, respectively. Pneumothorax developed in 7 (5.4%) cases. These results suggest that CT-guided transthoracic fine needle aspiration cytology has a high diagnostic accuracy and an acceptable complication rate. The auditing valves of the results meet the proposed threshold values.

Thyroid nodules in pediatrics: which ones can be left alone, which ones must be investigated, when and how

Thyroid nodules are less frequent in childhood than in adulthood, but are more often malignant. Recent estimates suggest that up to 25% of thyroid nodules in children are malignant, therefore, a more aggressive approach is recommended. In this review, we suggest an approach based on a first-step clinical, laboratory, and sonographic evaluation. A history of irradiation of the neck, cranium or upper thorax, previous thyroid diseases or thyroid neoplasms in the family should alert clinicians as being associated with a greater likelihood of malignant nodules. Signs or symptoms of hyperthyroidism and dysmorphic features should be carefully considered during the physical examination. Palpable firm lymph nodes, found in some 70% of cases, are the most significant clinical finding in children with malignant nodules. Although the routine determination of calcitonin levels is not uniformly practiced, it can help recognize sporadic or familial medullary thyroid neoplasms. Blood thyroid stimulating hormone, free thyroxine, and free triiodothyronine determinations (the latter in case of symptoms of hyperthyroidism) are aimed at identifying the few hyperthyroid patients, for whom the next step should be scintiscan. Hyperthyroid patients usually disclose an increased uptake, and a diagnosis of toxic adenoma is commonly made. Cases with normal thyroid function or hypothyroidism (which is usually subclinical) should be evaluated by fine-needle aspiration biopsy (FNAB). In eu/hypo-thyroid patients, scintiscan provides poor diagnostic information and should not be routinely employed. Thyroid ultrasonography is used to select cases for FNAB. Although ultrasound cannot reliably discriminate between benign and malignant lesions, it does provide an index of suspicion. Sonographic features that increase the likelihood of malignancy are microcalcifications, lymph node alterations, nodule growth under levothyroxine treatment, and increased intranodular vascularization demonstrated by color Doppler. There is growing evidence that elastography may provide further information on nodule characteristics. FNAB is indicated in all cases with a likelihood of malignancy. FNAB has a diagnostic accuracy of approximately 90% and is used in selection of patients which require surgery. Recently, histological markers and elastography have been introduced to increase the specificity of FNAB and ultrasound, respectively. The pitfall in FNAB cytology is the follicular cytology, in which it is not possible to distinguish between adenoma and carcinoma and therefore thyroidectomy is advised. Conflict of interest:None declared.

Use of molecular biomarkers in FNA specimens to personalize treatment for thyroid surgery

Accurate preoperative assessment of thyroid nodules with fine-needle aspiration biopsy (FNAB) continues to be a challenge, often resulting in unnecessary diagnostic surgical intervention. The detection of several novel gene mutations in differentiated thyroid cancer (DTC) over the last decade has led to the diagnostic use of these oncogenic alterations to improve FNAB sensitivity and specificity. Thyroid oncogene mutations including BRAF, RAS, and RET/PTC are reviewed. The potential benefit of using this panel on fine-needle aspiration (FNA) cytology samples will be described. Our use of ''reflexive'' molecular testing demonstrates its clinical value in conjunction with FNAB cytology, representing an application of personalized molecular medicine to guide appropriate surgical therapy.

Expanded Role of Cytopathology in Breast Cancer Diagnosis, Therapy and Research: The Impact of Fine Needle Aspiration Biopsy and Imprint Cytology

Expanded Role of Cytopathology in Breast Cancer Diagnosis, Therapy and Research: The Impact of Fine Needle Aspiration Biopsy and Imprint Cytology

Diagnostic Performance of Thyroglobulin Value in Indeterminate Range in Fine Needle Aspiration Washout Fluid from Lymph Nodes of Thyroid Cancer

PurposeThe purpose was to compare the frequency of metastatic and nonmetastatic lymph nodes diagnosed by fine needle aspiration biopsy cytology (FNAC) and thyroglobulin concentration from fine needle aspiration biopsy washout fluid (FNAB-Tg) in an indeterminate range (0.2-100 ng/mL), and to evaluate the most appropriate threshold value of FNAB-Tg in an indeterminate range.Materials and MethodsWe performed ultrasound-guided FNAB and FNAB-Tg in suspicious metastatic cervical lymph nodes of papillary thyroid carcinoma and performed surgery. Ninety-five lymph nodes with indeterminate values of FNAB-Tg ranging from 0.2-100 ng/mL in ninety-two patients were included in this study. The diagnostic performances in multiple Tg levels (0.7, 1.0, 5.0, 10.0, 20.0, 50.0) were evaluated to compare with FNAB cytology using sensitivity, specificity, and accuracy with area under the curve (AUC) analysis.ResultsForty-two were metastatic lymph nodes and fifty three were nonmetastatic lymph nodes. FNAB-Tg ranged from 0.22 to 90.9 ng/mL in metastatic lymph nodes (mean; 34.3±33.3 ng/mL) and 0.20 to 56.7 ng/mL in nonmetastatic lymph nodes (mean; 4.9±11.1 ng/mL) (p<0.001). The most excellent diagnostic performance was displayed in 5 ng/mL of FNAB-Tg with AUC of 0.76, sensitivity, specificity, accuracy, 69.0, 83.0, and 76.8, respectively. However, there was no significant difference from 10 ng/mL FNAB.ConclusionWe ascertained that 5 ng/mL yielded the most excellent diagnostic performance among FNAB-Tg levels in the present setting with a large series with the indeterminate range (0.2-100 ng/mL) of FNAB-Tg values. These results need additional confirmation under different laboratory conditions.

Fine-Needle Aspiration Cytology: An Advancing Horizon

The current practice of “Fine Needle Aspiration Cytology (FNAC) has established itself as an important modality in the diagnosis and management of superficial and deep seated lesions throughout the body. With this wide employment of FNAC, the cytopathologists play a pivotal role in the management and therapeutic decisions that are based on the diagnosis of these limited FNAC samples. Furthermore, the use of FNAC samples for biomarker research is advancing rapidly and is being widely investigated and applied for the treatment and prognostic purposes. In this special issue, we have made an attempt to provide a “flavor” of the current practice of FNAC with an emphasis on correlation of tissue biopsies with PET results, FNAC of breast, liver, pulmonary, and head and neck lesions. Similarly, the use of FNAC in the diagnosis of Langerhans cell histiocytosis, neuritic leprosy, and granulomatous inflammation is also discussed. With the increasing use of image-assisted FNAC, pathologists are now an integral part in the diagnosis and management of the deep seated lesions. In lieu of this, it has become important for the pathologists to be aware of the limitations of different imaging techniques. The paper on the correlation of tissue biopsies with PET results discusses the limitations of an increased SUV value on PET scan. The use of fine needle aspiration cytology has been proven to give fast, economical, and valuable diagnosis of palpable breast lumps. In this issue, the role of FNAC in the evaluation of breast lump in a high patient volume center is addressed with emphasis on the importance of skill and training for both pathologists and technicians to prevent suboptimal sampling, thus, increasing the reliability of the procedure. Another important but not commonly discussed aspect of breast FNAC—the nonmalignant categories—is also addressed, with a review of the cytomorphology of benign breast lumps, some of which could be mistaken for malignancy due to the diaphanous appearance and overlapping cytologic features. The false negative and false positive FNAC is further discussed in detail so as to avert misinterpretation. These provide practical information for readers when dealing with FNAC of breast lesions. The paper on liver FNAC covers various aspects and discusses the role of FNAC in liver lesions. There is an active debate about the preoperative/pretransplantation diagnostic role of FNAC of hepatocellular carcinoma (HCC) and precursor lesions, especially in the face of advances in dynamic imaging techniques. New trends in personalized molecular targeted therapy require better characterization and prediction of HCC behavior. FNAC biopsy technique is still the most minimally invasive approach for the procurement of tumor and peritumoral tissue for molecular studies. Thus, in the near future, hepatic FNAC is likely to become a point of care in the management of HCC patients, especially inoperable cases. In the current era of personalized medicine, the FNAC diagnosis of nonsmall cell carcinoma for a pulmonary nodule is no longer considered an adequate diagnosis. Pathologists are often required to further subclassify these in to adenocarcinoma and squamous cell carcinoma. With the increasing use of image-assisted FNAC including endobronchial ultrasound guided FNAC (EBUS-FNA), cytologic or small biopsy material has become the only form of tissue available for diagnosis. The paper on FNAC of pulmonary lesions reviews the current concepts in the suitability and accuracy of FNAC in lung cancers including diagnosis, classification, use of ancillary techniques, and prognostic marker assessment. FNAC is a valuable technique in the workup of nodules and masses arising within the head and neck region. It is primarily utilized to confirm or exclude the diagnosis of malignancy involving head and neck organs especially lymph nodes, thyroid, and salivary glands. It has been shown that FNAC of salivary gland lesions is a valuable way to preoperatively assess lesional tissue, determine the need for surgical intervention, and assist in planning the appropriate surgical approach prior to resection. In this issue, the manuscript on cytologic diagnosis of mucoepidermoid carcinoma discusses the role of FNAC in the diagnosis of mucoepidermoid carcinoma (MEC), the common malignant tumor affecting parotid gland. In addition, it also brings forth how the rare and recently described oncocytic variant can pose problems in the diagnosis of MEC. In conclusion, this special issue includes a potpourri of topics which provides a thoughtful glimpse into various techniques, diagnostic ability, and limitations of the current practice of FNAC. Darshana Jhala Aileen Wee Gary Tse Zubair Baloch

Nodular sclerosing classical Hodgkin lymphoma masquerading as acute suppurative‐necrotizing lymphadenitis

The diagnosis of nodular sclerosing classical Hodgkin lymphoma (NSCHL) by fine-needle aspiration (FNA) biopsy has historically been a diagnostic challenge due to the usual paucicellularity of the specimen. This case report, and other previously published reports, suggests that there is another facet to the potentially challenging diagnosis of this particular variant of Hodgkin lymphoma (HL): the presence of suppurative-necrotizing changes mimicking an infectious etiology. The patient presented here underwent FNA biopsy of an acutely enlarged supraclavicular lymph node and cytologic smears showed marked acute inflammation in a background of necrosis. A diagnosis of infectious suppurative lymphadenitis was made at that time. After a negative infectious work-up with infectious disease consultation, an excisional biopsy was performed and the patient was definitively diagnosed with NSCHL. The presence of neoplastic Hodgkin and Reed-Sternberg cells in the purulent exudate was minimal and only appropriately identified after retrospective review. This particular subtype of classical HL represents a potential pitfall in FNA biopsy cytology. Consequently, the cytopathologist and surgeon should always consider this entity in the differential diagnosis of a suppurative, lymphadenitis-like aspirate, and pursue repeat FNA or an excisional biopsy if there is any clinical index of suspicion.

Current State and Future Perspective of Molecular Diagnosis of Fine-Needle Aspiration Biopsy of Thyroid Nodules

Fine-needle aspiration biopsy (FNAB) is the most sensitive and specific tool for the differential diagnosis of thyroid malignancy. Some limitations of FNAB can be overcome by the molecular analysis of FNAB. This review analyzes the current state and problems of the molecular analysis of FNAB as well as possible goals for increasing the diagnostic rate, especially in the indeterminate/follicular lesion cytological group. Twenty publications were evaluated for the diagnostic material and assay systems used, the type, and the number of mutations screened. Sensitivity, specificity, and false-negative and false-positive rates were calculated for all publications. Testing for a panel of somatic mutations is most promising to reduce the number of indeterminate FNAB. A mean sensitivity of 63.7% was achieved for indeterminate lesions. However, there is a broad sensitivity range for the investigation of mutations in the indeterminate lesions. Therefore, additional molecular markers should be defined by mRNA and microRNA expression studies and evaluated in FNAB samples of thyroid carcinomas without known somatic mutations, and especially for the many benign nodules in the indeterminate/follicular lesion fine-needle aspiration cytology category. This approach should improve the differential diagnosis of indeterminate/follicular lesion FNAB samples. Testing for a panel of somatic mutations has led to an improvement of sensitivity/specificity for indeterminate/follicular proliferation FNAB samples. Further methodological improvements, standardizations, and further molecular markers should soon lead to a broader application of molecular FNAB cytology for the differential diagnosis of thyroid nodules and to a substantial reduction of diagnostic surgeries.

Development of a MicroRNA-Based Molecular Assay for the Detection of Papillary Thyroid Carcinoma in Aspiration Biopsy Samples

Although thyroid nodules are common and diagnosed in over 5% of the adult population, only 5% harbor malignancy. Patients with clinically suspicious thyroid nodules need to undergo fine-needle aspiration biopsy (FNAB). The main limitation of FNAB remains indeterminate cytopathology. Only 20%-30% of the indeterminate nodules harbor malignancy, and therefore up to 80% of patients undergo unnecessary thyroidectomy. The aim of this study was to identify and validate a panel of microRNAs (miRNAs) that could serve as a platform for an FNAB-based diagnostic for thyroid neoplasms. The study population included 27 consecutive patients undergoing total thyroidectomy for FNAB-based papillary thyroid cancer (n = 20) and benign disorders (n = 7). Aspiration biopsy was performed from the index lesion and from the opposite lobe normal tissue in all study patients at the time of operation. RNA was extracted from all aspiration biopsy samples. Quantitative polymerase chain reaction on a panel of previously selected miRNAs was performed. Polymerase chain reaction results were compared with final histopathology. miRNA from tumor tissues was amplified using the highest value of each miRNA expression in normal tissue as a threshold for malignancy detection. Diagnostic characteristics were most favorable for mir-221 in differentiating benign from malignant thyroid pathology. mir-221 was overexpressed in 19 patients (p < 0.0001) with a sensitive yield of 95%. Specificity, negative and positive predictive value, and accuracy of the miRNA panel were 100%, 96%, 100%, and 98%, respectively. miRNA quantification for differential diagnosis of thyroid neoplasms within aspiration biopsy samples is feasible and may improve the accuracy of FNAB cytology.

An evaluation of nondiagnostic fine needle aspiration biopsy results: the importance of having an experienced cytopathologist

To compare nondiagnostic fine needle aspiration biopsy cytology results between pathologists and clinicians. Fine needle aspiration biopsy has proven to be a safe, economical, accurate, and rapid diagnostic technique. A successful aspiration biopsy requires a specimen with adequate cellularity, high-quality preparation, an experienced physician, and a cytopathologist. Up to 32% of fine needle aspiration biopsies of various organs (thyroid, breast, etc.) may ultimately be nondiagnostic due to scant cellularity and poor preparation. Materials and methods: A total of 2247 reports of fine needle aspiration biopsies were reviewed, all obtained from files in the Pathology Laboratory of the İzmir Atatürk Training and Research Hospital. The reports included specimens from thyroids, breasts, lymph nodes, and salivary glands. Data from the fine needle aspiration biopsies were reviewed by physicians; for each case, both clinicians and cytopathologists were consulted in order to determine the clinical utility and the cost-effectiveness of the evaluation of aspiration biopsies. Results: Our database showed that nondiagnostic cytology results obtained by clinicians alone were higher (34.1%) than those of cytopathologists (2.8%). Conclusion: We conclude that the evaluation of fine needle aspiration biopsies involving cytopathologists not only substantially increases the adequacy of cytology specimens and decreases the number of nondiagnostic specimens, but it also increases the cost-effectiveness of the procedure.

A prospective study evaluating the accuracy of using combined clinical factors and candidate diagnostic markers to refine the accuracy of thyroid fine needle aspiration biopsy

Approximately 30% of fine needle aspiration biopsies of the thyroid have inconclusive results. We conducted a prospective trial to determine whether clinical and molecular markers could be used in combination to improve the accuracy of thyroid fine needle aspiration biopsy. Clinical, tumor genotyping for common somatic mutations (BRAF V600E, NRAS, KRAS, RET/PTC1, RET/PTC3, and NTRK1), and the gene expression levels of 6 candidate diagnostic markers were analyzed by univariate and multivariate methods in 341 patients to determine whether they could distinguish reliably benign from malignant thyroid neoplasms, and a scoring model was derived. By a multivariate analysis, fine needle aspiration biopsy cytology classification, the presence of a NRAS mutation, and the tissue inhibitor of metalloproteinase 1 expression level were associated jointly with malignancy. The overall accuracy of the scoring model, including these 3 variables, to distinguish benign from malignant thyroid tumors was 91%, including 67% for the indeterminate and 77% for the suspicious FNA subgroups. Fine needle aspiration biopsy cytology classification, the presence of NRAS mutation, and tissue inhibitor of metalloproteinase 1 messenger RNA expression levels in combination provide a greater diagnostic accuracy than fine needle aspiration biopsy cytology alone to allow selection of more definitive initial operative treatment. The sensitivity of the scoring model, however, was too low to avoid the need for diagnostic thyroidectomies for indeterminate fine needle aspiration biopsy findings.

Syphilitic lymphadenitis diagnosed via fine needle aspiration biopsy

Syphilis is coming back in the recent a few decades especially in the gay and HIV populations. Since syphilis can be "the great mimic" clinically and pathologically, a case report with updated review can be helpful to the medical community. We report, a case of syphilitic lymphadenitis diagnosed via fine needle aspiration biopsy (FNAB). The pitfalls associated with the diagnosis of syphilitic lymphadenitis will be discussed. The patient's medical records were reviewed. The pertinent history, clinical course, and ancillary studies including FNAB cytology with special stains are presented. In addition to the case report, we discuss the diagnosis of syphilitic lymphadenitis and the role of FNAB cytology. This was a 37-year-old man presenting with a two-month history of a growing neck mass, night sweats, and a ten pound weight loss. The patient had been treated one month earlier for primary syphilis. Examination of the head and neck revealed a 3 cm right level II mass. FNAB cytology showed heterogeneous population of lymphocytes and plasma cells suggesting reactive changes. Modified silver staining of the cell block slide was performed and revealed spirochetes, consistent with syphilis. The patient's lymphadenitis resolved with a course of antibiotic treatment. Although lymphadenopathy is a rare presentation of syphilis, it should be included in the differential diagnosis for patients who offer a suspect history. FNAB with silver staining is an effective, minimally invasive way to confirm the diagnosis.