Routine Fine-needle Aspiration Research Articles

Molecular testing of routine air-dried fine needle aspiration (FNA) smears improves pre-surgical diagnosis and supports the histological identification of follicular carcinomas

Molecular testing of routine air-dried fine needle aspiration (FNA) smears improves pre-surgical diagnosis and supports the histological identification of follicular carcinomas

Laser capture microdissection is a valuable tool in the preoperative molecular screening of follicular lesions of the thyroid: an institutional experience.

The application of molecular tests to thyroid fine needle aspiration (FNA) has been shown to be a valuable tool to better refine the pre-operative malignant risk of patients with indeterminate cytology results. In this study, we investigated the feasibility of using the laser capture microdissection (LCM) technique to obtain DNA and RNA for molecular tests in routine thyroid FNA smears. Nine coupled FNA and histological retrospective cases and 31 prospective FNA cases with a follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN) diagnosis were included in this study. Both cytological and histological specimens were investigated by direct sequencing and reverse transcription-polymerase chain reaction (RT-PCR) for BRAF and RAS mutations and for PAX8/PPARG and RET/PTC rearrangements, respectively. LCM yielded good DNA and RNA quality in all cases (100%) in both series, irrespective of the staining used (Giemsa, Papanicolaou, immunostain for thyroglobulin) and the cytology technique (conventional or liquid-based preparations). Total mutations found in the FNA and in the corresponding histological specimen in both series were: one PAX8/PPARG rearrangement in a follicular carcinoma (FC), four NRAS mutations [in two FCs, one papillary carcinoma and one follicular adenoma (FA)] and one HRAS mutation in one FA. The sensitivity was 67% and the specificity was 91%. LCM is a valuable tool to obtain good quality DNA and RNA for molecular tests in cytological material from thyroid FNA, and can be a useful option in the management of patients with an FN/SFN FNA diagnosis.

Forward-viewing linear echoendoscope: a new option in the endoscopic ultrasound armamentarium (with video).

The forward-viewing linear echoendoscope (FV-EUS) has been developed with the aim of overcoming limitations of standard curved linear-array echoendoscopes (CLA-EUS) and to further expand interventional applications of EUS. The main characteristic of the FV-EUS is a shifting in the orientation of both endoscopic and ultrasound views from oblique to forward, with the exit of the working channel at the tip of the instrument. This allows exit of the devices parallel to the longitudinal axis of the endoscope, thus resulting in a more direct and stable access to the lesion while increasing the precision and force applied to the target. Accumulating evidence has shown that the FV-EUS can be used instead of the standard CLA-EUS scope for routine fine needle aspiration, with extremely good performance for subepithelial lesions and for difficult to reach locations. Several areas of use of this echoendoscope are yet to be better defined, such as its potential for therapeutic and interventional procedures, as well as for natural orifice transluminal endoscopic surgery. The current report provides an updated overview of the available evidence for both diagnostic and interventional uses of the FV-EUS.

Molecular characterization of 54 cases of false-negative fine-needle aspiration among 1347 papillary thyroid carcinomas.

Fine-needle aspiration (FNA) has been widely accepted as the most crucial step in the preoperative assessment of thyroid nodules, but the false-negative rates are generally reported to be between 3.6% and 10.2%. To lower the overall incidence of this false-negative testing, new reporting systems encourage the molecular testing of thyroid nodules. However, to the authors' knowledge, the role of molecular testing in false-negative FNA has not yet been evaluated. In total, 1347 consecutive papillary thyroid carcinomas (PTCs) with both cytological and histological diagnoses were collected from the same center. A blinded revision of the false-negative cases was performed. An analysis of the BRAF and Ras genes in the false-negative cases was then performed. The false-negative rate at the time of primary FNA diagnosis was 4.8% (65 of 1347 cases). False-negative cases were 15 follicular variant PTCs, 2 classical variant, and 1 solid variant that lacked peculiar PTC cytomorphological features. Adequate cellular material for molecular analysis was available only in 54 of the 65 false-negative cases. Mutations were found in 6 cases (11%), and Ras alterations were present in 16 cases (29.6%). The addition of molecular analysis decreased the false-negative rate to 0.4% (5 of 1347 cases). The results of the current study confirm the feasibility of BRAF and Ras analysis in routine FNA. However, when the false-negative FNA rate is low, the cost-benefit analysis of the detection of BRAF and Ras mutations should be carefully evaluated. Consequently, the authors suggest that preoperative molecular assessment could be helpful for benign nodules, but only in the presence of clinical suspicion of malignancy.

Impact of integrated molecular diagnostics of air-dried Fine Needle Aspiration (FNA) smears of patients with nodular thyroid disease in a routine diagnostic setting

After a first retrospective study we now report the first 12 month results of molecular diagnostics analyzing BRAF, RAS, RET/PTC, and PAX8/PPARG mutations in routine air-dried FNA smears instead of fresh FNA material.

Impact of Molecular Screening for Point Mutations and Rearrangements in Routine Air-Dried Fine-Needle Aspiration Samples of Thyroid Nodules

The diagnostic limitations of thyroid fine-needle aspiration (FNA), such as the indeterminate category, can be partially overcome by molecular analyses. However, until now, rearrangements have only been detected in fresh FNA material and the number of follicular thyroid carcinomas (FTCs) was rather low in previous studies. We aimed at investigating the impact of point mutations and rearrangement detection in a set of routine air-dried FNA smears with a higher percentage of FTCs. RNA and DNA was extracted from 310 FNAs (164 indeterminate, 57 malignant, 89 benign) and corresponding formalin-fixed paraffin-embedded tissue (156 follicular adenomas [FAs], 32 FTCs, 44 papillary thyroid carcinomas [PTCs], 9 follicular variant PTCs, and 69 goiters). PAX8/PPARG and RET/PTC rearrangements were detected by qPCR, BRAF and RAS mutations by high-resolution melting PCR and by pyrosequencing. Forty-seven mutations were detected in the FNAs: 22 BRAF, 13 NRAS, and 3 HRAS mutations, 8 PAX8/PPARG, and one RET/PTC-rearrangement. While the presence of a BRAF and RET/PTC mutation was associated with cancer in 100% of samples each, the presence of a RAS and PAX8/PPARG mutation was associated with cancer in only 12% and 50% of samples, respectively. In the indeterminate group 4 of 25 carcinomas were identified by molecular FNA screening, which increased the sensitivity from 67% (cytology alone) to 75% (cytology plus molecular screening). Molecular screening for point mutations and rearrangements is feasible in air-dried FNAs. Although the impact of detecting point mutations and rearrangements in FNAs has most likely been overestimated in previous studies, molecular FNA analyses improve presurgical diagnostics. The detection of BRAF mutations in FNA may improve the choice of surgery and postsurgical treatment. Further data are necessary to elucidate the true impact of detecting RAS and PAX8/PPARG mutations in FNAs. The inclusion of additional rare somatic mutations and miRNA markers might further improve the impact of molecular FNA diagnostics.

The role of routine fine-needle aspiration in the diagnosis of infected necrotizing pancreatitis

Diagnosing infected necrotizing pancreatitis (INP) may be challenging. The aim of this study was to determine the added value of routine fine-needle aspiration (FNA) in addition to clinical and imaging signs of infection in patients who underwent intervention for suspected INP. We conducted a post hoc analysis of 208 consecutive patients from a prospective, multicenter database who underwent intervention because of suspected INP. In retrospect, 3 groups were constructed based on the patients preoperative characteristics: Clinical, imaging, and FNA. Patients in the clinical group had clinical signs of infection but no gas on preoperative computed tomography (CT) and no FNA performed before intervention. Patients in the imaging group had gas bubbles on the preoperative CT but no was FNA performed, whereas patients in the FNA group had a positive FNA before intervention. The reference standard for infection was the culture taken during the first intervention (either catheter drainage or necrosectomy). The initial intervention for INP was performed a median of 27 days (interquartile range, 20-39) after admission without difference between the 3 groups (P = .15). Infection was confirmed in 80% of 92 patients of the clinical group, in 94% of 88 patients of the imaging group, and in 86% of 28 patients of the FNA group (P = .07). Mortality was 19% and was not different between groups (P = .39). INP can generally be diagnosed based on clinical or imaging signs of infection. FNA may be useful in patients with unclear clinical signs and no imaging signs of INP.

BRAF and RAS Mutations in Follicular Variants of Papillary Thyroid Carcinoma

Follicular variants of papillary thyroid carcinoma (FVPTC), particularly the encapsulated subtype, often cause a diagnostic dilemma. Therefore, many FVPTCs are interpreted as "indeterminate" in preoperative fine-needle aspiration (FNA). The aim of this study was to analyze the genotypic changes in BRAF codons 600 and 601, as well as the N, H, and KRAS codons 12, 13, and 61 in FVPTCs and investigate the usefulness of preoperative BRAF and RAS mutation analysis as an adjunct diagnostic tool along with routine FNA. Surgically resected thyroid nodules were reviewed to establish the histological diagnosis of FVPTC. All preoperative FNA diagnoses were categorized according to the Bethesda Reporting System. Mutations in BRAF codons 600 and 601, and N, H, KRAS codons 12, 13, and 61 were analyzed by pyrosequencing. Of 132 cases, 81 (61.4 %) had a point mutation in one of the BRAF V600E, BRAF K601E, or RAS oncogenes; BRAF V600E in 43(32.6 %), BRAF K601E in three (2.3 %), and RAS in 35 (26.5 %) cases. All mutations were mutually exclusive. Of 78 cases with an FNA indeterminate category diagnosis, 51 (65.4 %) were positive for mutations: 24 for BRAF V600E, 3 for BRAF K601E, and 24 for the RAS gene. The KRAS mutation was more frequently found than the HRAS mutation, comprising 22.9 % of the RAS mutations, and all KRAS mutations were located at codon 61. This study demonstrated that either BRAF or RAS mutations were present in two thirds of FVPTCs and these mutations were mutually exclusive.

Impact of Different Methodologies on the Detection of Point Mutations in Routine Air-dried Fine Needle Aspiration (FNA) Smears

Currently the best method to select suspicious thyroid nodules for surgery is fine needle aspiration (FNA) cytology. However, FNA cytology has some inherent limitations, which can partly be overcome by molecular analysis. Therefore, molecular testing for somatic mutations has emerged as the most promising approach for molecular FNA diagnostics. The objective of this methodological study was to evaluate the feasibility of detecting BRAF, NRAS, HRAS, and KRAS mutations from routine air-dried thyroid FNA smears, and to find an optimal method for detecting these mutations in FNA samples. DNA was extracted from 110 routine air-dried FNA smears and the corresponding surgically obtained formalin-fixed paraffin-embedded tissues. The presence of BRAF, NRAS, HRAS, and KRAS mutations was assessed by real-time PCRs and high resolution melting analysis, and/or pyrosequencing in comparison to real-time PCRs using hybridization probes and fluorescence melting curve analysis. The high-resolution melting-PCRs revealed a significantly lower number of PCR failures and questionable results, and detected more mutations than the PCRs using hybridization probes. The number of PCR failures ranging from 14-16% by high-resolution melting-PCRs could be further reduced to 5-14% by adding pyrosequencing assays. Moreover, pyrosequencing increased the specificity of the assays, up to 98-100%, while the sensitivity ranged between 32-63%. In summary, the mutation detection, especially in air-dried FNA samples, improves when using PCR assays in combination with high resolution melting analysis. Additional improvement can be obtained by subsequent pyrosequencing in comparison to previously described real-time PCRs using hybridization probes and fluorescence melting curve analysis.

Molecular Biomarkers in Thyroid FNA Samples

In this issue of the JCEM, Walsh et al. (1) report the analyticalvalidationofamoleculardiagnosticmethod for indeterminate fine-needle aspiration (FNA) thyroid samples. Together with previous reports describing clinicalperformanceandcosteffectivenessofthismethod,this study highlights the capability of such a molecular test to reduce unnecessary surgery for benign thyroid diseases (2–5). Although rarely malignant, thyroid nodules are very common. FNA cytology is routinely used to assess whetherthyroidnodulesarebenignormalignant(6).Four majortypesofthyroidmalignancyarerecognized,includingpapillary(PTC),follicular(FTC),anaplastic,andmedullarycarcinomas(7).PTC,particularlyfollicular-variant PTC,andFTCcanbedifficulttodifferentiatewithrespect to benign thyroid nodules (7). According to the National Cancer Institute, FNA results stratify thyroid nodules as benign, malignant, nondiagnostic (when the aspirate contains scant cellularity), and indeterminate. Indeterminate lesions (nearly one third of the cases) represent the most challenging conditions and feature an overall risk of 20– 30%ofbeingmalignant.Indeterminatelesionsinclude:1) atypia of undetermined significance/follicular lesions of undeterminate significance (with a malignancy risk of 5–15%); 2) follicular or Hurthle/suspicious for follicular or Hurthle neoplasms (with a malignancy risk of 15– 30%); and 3) suspicious for malignancy (with a malignancy risk of 60–75%) (8). Commonly, patients with an indeterminateresultundergodiagnosticsurgicalresection of the thyroid, with the risk of performing unneeded operations if a lesion is revealed to be benign (9). Therefore, methodsareurgentlyneededtoguideclinicaldecisions,in adjuncttocytology,inthecaseofindeterminateFNAsamples, to reduce surgery-associated morbidity and additional costs. Understandingmolecularpathogenesisofthyroidnoduleshasgreatpotentialtodiscovernovelgeneticbiomarkersthatmightguidethedecisionforsurgery.Recently,two approaches based on nucleic acids determination have been proposed to improve FNA accuracy: 1) detection of cancer-drivingoncogenemutationstoidentifycancer;and 2)geneexpressionprofiling,aimedatexploitingtranscriptional reprogramming of malignant vs. benign cells to identify benign lesions. Nikiforov et al. (10–12) first proposed systematically applying oncogene mutation detection to molecularly classify FNA samples; this approach was further pursued by other investigators (13–15). Oncogene detection was proved feasible also in routine air-dried FNA smears (16). Thus,FNABdeterminationofBRAFV600Emutationand RET/PTC (RET/PTC1 and RET/PTC3) rearrangements (commonly associated to PTC), RAS (HRAS codon 61, KRAS codons 12/13, and NRAS codon 61) mutations (commonly associated to follicular-variant PTC and FTC), and PAX8/PPAR fusion (commonly associated to FTC) was shown to improve diagnostic accuracy and enable cancer identification. One important caveat is that RAS mutations (20–40% of the cases) and PAX8/PPAR rearrangement(2–10%ofthecases)canalsobeassociated

Diagnosing infected necrotizing pancreatitis: Clinical signs, gas bubbles or routine fine-needle aspiration?

Introduction: Infection of pancreatic necrosis in necrotizing pancreatitis increases the lethality. Aims/objectives: To examine the mechanisms underlying this clinical circumstance we used a model of primary infected pancreatic necrosis in taurocholate induced pancreatitis in mice. Materials and methods: Acute necrotizing pancreatitis with sterile necrosis (SN) was induced by retrograde injection of 4% taurocholate in the common bile duct of Balb/c mice, infected pancreatic necrosis (IN) was induced by co-injecting 108 CFU E. coli. For antibiotic therapy 10 mg/kg bodyweight moxifloxacin were administered intravenously (AIN). After 6, 12, 24, 48 and 120 hours animals were sacrificed and serum as well as SIRS related organs were examined. Results: Prolonged bacteremia occurred when infected acinar cell necrosis was induced (24h CFU E. coli in blood; bacteria only not detected, IN 121 63). Infection of pancreatic necrosis with E. coli further increased the pancreatic damage (histology score 24h: SN 17.8 2.6 vs. IN 23.7 2.2; p<0.001) and the systemic complications such as the pulmonary vascular leak (albumin in bronchoalveolary lavage 6h: SN 151.0 57.7 mg/ml vs. IN 219.5 76.2 mg/ml; p<0.05). Additionally, infected necrosis induced impaired hepatic function with reduced serum glucose concentrations (24h: SN 167.0 35.6 mg/dl vs. IN 106.9 12.7 mg/dl; p<0.001). Moxifloxacin treatment reduced the systemic inflammatory response (serum IL-6: IN 330.5 336.6 vs. AIN 38.7 25.5 pg/ml; p<0.001) and restored liver function (serum glucose: IN 105.8 12.7 vs. AIN 155.7 39.5 mg/dl; p<0.001). Conclusion: Infection of pancreatic necrosis induces sustained bacteremia and increases the systemic complications in acute necrotizing pancreatitis. Initial antibiotic therapy reduces the inflammatory response and restores liver function.

Detection of PAX8/PPARG and RET/PTC Rearrangements Is Feasible in Routine Air-Dried Fine Needle Aspiration Smears

The diagnostic limitations of fine needle aspiration (FNA), like the indeterminate category, can be partially overcome by molecular analysis. As PAX8/PPARG and RET/PTC rearrangements have been detected in follicular thyroid carcinomas (FTCs) and papillary thyroid carcinomas (PTCs), their detection in FNA smears could improve the FNA diagnosis. To date, these rearrangements have never been analyzed in routine air-dried FNA smears, but only in frozen tissue, formalin-fixed paraffin-embedded (FFPE) tissue, and in fresh FNA material. Fixed routine air-dried FNA samples have hitherto been judged as generally not suitable for testing these rearrangements in a clinical setting. Therefore, the objective of the present study was to investigate the feasibility of extracting RNA from routine air-dried FNA smears for the detection of these rearrangements with real-time polymerase chain reaction (RT-PCR). A new method for RNA extraction from routine air-dried FNA smears was established, which allowed analysis for the presence of four variants of PAX8/PPARG and RET/PTC 1 and RET/PTC 3, which were analyzed in 106 routine FNA smears and the corresponding surgically obtained FFPE tissues using real-time quantitative PCR (RT-qPCR). To assess RNA quality, an intron-spanning PAX8 cDNA was amplified. Acceptable RNA quality was obtained from 95% of the FNA samples and 92% of the FFPE samples. PAX8/PPARG was detected in 4 of 96 FFPEs and in 6 of 96 FNAs. PAX8/PPARG was present in 4 of 10 FTCs and in 3 of 42 follicular adenomas (FAs). Similarly, RET/PTC was found in 3 of 96 FFPEs and in 4 of 96 FNAs. Two of 21 PTC samples and 3 of 42 FA samples carried this rearrangement. These data are the first to show the feasibility of extracting RNA from routine air-dried FNA smears for the detection of PAX8/PPARG and RET/PTC rearrangements with RT-qPCR. These promising methodological advances, if confirmed in larger series of FNA and FFPE samples, may lead to the introduction of molecular analysis of routine air-dried FNA smears in everyday practice.

Microfilaria in cytological smears at rare sites coexisting with unusual pathology: A series of seven cases

Filariasis is a major public health problem in India and microfilaria is sometimes seen during routine fine needle aspiration cytology (FNAC) smears, but it is very rare to find microfilaria coexistent with neoplastic lesions. Here we report a series of seven cases in which microfilaria is associated with neoplastic lesions. Out of these seven cases one is benign and six are malignant. Also we first time report the microfilaria coexistent with parotid pleomorphic adenoma, undifferentiated carcinoma thyroid and gall bladder carcinoma.

Kikuchi-Fujimoto disease in fine needle aspiration smears: A clinico-cytologic study of 18 pediatric cases and correlation with 68 adult patients

Kikuchi-Fujimoto disease (KFD) is a self-limiting disorder which usually affects young women. There are only a few studies on pediatric KFD patients and their fine-needle aspiration (FNA) cytodiagnosis. We report a series of pediatric KFD patients diagnosed by FNA cytology and compare them with adults. By routine FNA cytology and through retrospective review smears initially diagnosed as reactive hyperplasia of lymph node during the years 2004-2009, 18 pediatric and 68 adult KFD cases were detected. The clinico-cytologic features of these two groups were compared. The age of the pediatric patients ranged from 6 to 18 years with a median of 13.5 years and adult cases were aged 19 to 54 years with a median of 30 years. Only 1 pediatric case (5.6%) and 20 (29.4%) adult cases were initially diagnosed as KFD (P = 0.0604). Arab:non-Arab ratios were 4.3:1 among the pediatric patients and 1:1.5 for the adults (P = 0.0043). FNA smears were highly cellular in 4 (22.2%) pediatric cases and 37 (54.4%) adult cases (P = 0.0180). More than 5% Kikuchi histiocytes was present in 8 (44.4%) pediatric and 49 (72.1%) adult cases (P = 0.0474). No significant difference was observed in male: female ratio, frequency of head & neck lymphadenopathy, time (season) of presentation, and presence of neutrophils and capillary networks, etc. Besides observation and interpretation errors, a significant difference between the two groups in respect of some clinico-cytomorphological features could have influenced the routine cytodiagnosis leading to lower pickup rate of pediatric KFD cases as compared to adults.

Is One Benign Fine Needle Aspiration Enough?

Fine needle aspiration (FNA) is used to diagnose thyroid nodules, but the follow-up of benign FNA is unclear. We sought to determine whether routine repeat FNAs after initial benign FNA reduces false negatives. We identified 265 patients who had at least one benign FNA that either progressed to surgery or had at least one repeat FNA. We reviewed their ultrasonography, FNA cytology, and surgical pathology. Of 127 patients with initial benign FNA that had surgery, 13 had a malignancy, yielding a 10.2% false-negative rate. Of 22 patients who had surgery after at least two benign FNAs, one had a malignancy, yielding a 4.5% false-negative rate. Initially benign cytology (Bethesda II) was upgraded to a cytology requiring surgical intervention (Bethesda IV-VI) in 7 of 129 (5.4%) patients after two FNAs. Suspicious features on ultrasound, including size >4 cm, calcifications, or increased vascularity were found in 90% of patients with a false-negative FNA. The overall false-negative rate of thyroid FNAs is 10.2%, which is reduced to 4.5% with a second benign FNA. Ninety percent of patients with a false-negative FNA had suspicious sonographic features. Reaspiration should be considered in patients with sonographically suspicious nodules.

FN1, GALE, MET, and QPCT overexpression in papillary thyroid carcinoma: Molecular analysis using frozen tissue and routine fine‐needle aspiration biopsy samples

Thyroid nodules are a common clinical problem, and fine-needle aspiration biopsy (FNAB) is widely used for its evaluation. Only 5% are malignant, being papillary carcinoma (PC) the most frequent neoplasia. Approximately 20% are classified as indeterminate or suspicious for malignancy. Gene-expression pattern may be useful for diagnosing PC in difficult or ambiguous cases. In our prior study, we were able to apply RT-PCR method in a series of routinely performed FNAB of thyroid nodules using individual, residual samples. In this study, a total of 70 thyroid samples were evaluated for the expression of MPPED2, H/HBA2, MET, FN1, GALE, and QPCT genes, including 24 cases of frozen thyroid tissue, 12 nodular hyperplasia and 12 PC, and the 46 consecutive thyroid FNAB samples, previously analyzed (3 positive, 10 indeterminate and 32 negative for malignancy, and 1 insufficient). FN1, GALE, MET, and QPCT mRNA expression were significantly different in benign and malignant samples, with similar pattern of overexpression in aspirates compared to frozen tissue. H/HBA2 and MPPED2 expression varied. Histological correlation was possible in five indeterminate cases, revealing one PC and four benign lesions. In conclusion, FN1, GALE, MET, and QPCT were significantly overexpressed in thyroid PC. RT-PCR method could be applied to routine FNAB, showing a similar pattern of overexpression. Despite the small number of cases evaluated, our results suggest that molecular analysis may be of assistance in patients with indeterminate/suspicious cytology, adding elements for preoperative diagnosis and better management of these patients.

Intrathyroid Parathyroid Carcinoma with Intrathyroidal Metastasis to the Contralateral Lobe: Source of Diagnostic and Treatment Pitfalls

Intrathyroidal parathyroid carcinoma is extremely rare clinical entity with potentially multiple diagnostic pitfalls. We report a case of 40-year-old man presented with classical manifestations of primary hyperparathyroidism, severe hypercalcemia and profoundly increased serum parathyroid hormone level. Neck ultrasonography demonstrated multinodular goiter with predominant 34 mm nodule in left thyroid lobe. Additional 16 mm nodule was found beneath the left lobe. Routine percutaneous fine-needle aspiration of predominant nodule indicated follicular thyroid carcinoma, while left inferior nodule was confirmed to be of parathyroid origin. The patient underwent surgery, during which frozen sections identified medullary thyroid carcinoma with metastasis to upper mediastinal lymph node. Permanent sections of the predominant left lobe nodule revealed intrathyroidal parathyroid carcinoma surrounded with multiple microscopic metastases. Left inferior nodule was metastatic lymph node. Additional 10 mm intrathyroidal metastasis of primary parathyroid carcinoma was found within right thyroid lobe. This case indicates that fine-needle-aspiration and intraoperative biopsy are of limited value in diagnosing parathyroid carcinoma, especially if localized intrathyroidally. Oncological en-block resection is treatment of choice, implying ipsilateral lobectomy in case of thyroid invasion. This firstly described case of intrathyroidal parathyroid carcinoma causing intrathyroidal dissemination may influence future treatment strategies.

Endoscopic Ultrasound Fine Needle Aspiration in the Diagnosis of Lymphoma

In recent years, endoscopic ultrasound techniques with Fine Needle Aspiration (FNA) have become an increasingly used diagnostic aid in the differentiation of mediastinal lymphadenopathy. Endobronchial ultrasound (EBUS) and endoesophageal ultrasound (EUS) are now available for clinicians to reach mediastinal and paramediastinal masses using a minimally invasive approach. These techniques are an established component for diagnosing and staging lung cancer and their benefit in the diagnosis of lymphoma's has been highlighted in a number of case studies. However, the lack of tissue architecture obtained by cytological FNA specimens decreases the diagnostic accuracy for benign causes of thoracic lymphadenopathies, lymphomas, and histopathological subtyping of lung cancer. Accordingly, our study group have adapted the FNA sampling technique, resulting in tissue fragments that can be used for histopathological examinations. As an illustration, we report a case of follicular non-Hodgkin lymphoma, diagnosed on tissue fragments obtained by adjusted EUS FNA. We believe that this relatively simple adjustment to routine FNA sampling can help to overcome the diagnostic limitations inherent in cytology obtained by routine FNA.

Tubulolobular carcinoma of the breast with grooved and cerebriform nuclei: Failure to identify this specific subtype in a case during routine fine needle aspiration cytology and histopathological diagnosis

Tubulolobular carcinoma (TLC) is a rare tumor of the breast in which histologic features of both tubular and lobular carcinoma are combined. We report a case of TLC, in which the specific subtype was missed at routine cytologic and histopathological examination. A 69-year-old woman presented with a right breast lump. Imaging studies indicated a malignant lesion in right upper quadrant. Routine fine needle aspiration (FNA) cytology diagnosis was a duct cell carcinoma (small cell type). In a setting of cystic thyroid lesions, presence of excessive nuclear grooves, and rare intranuclear cytoplasmic inclusion, metastatic papillary thyroid carcinoma was also considered. However, both these possibilities were not supported by immunocytochemical findings (estrogen receptor+, thyroglobulin-, and chromogranin-). The histopathology diagnosis was invasive duct cell carcinoma. Review of FNA smears and paraffin sections led to the diagnosis of TLC, which was supported by positive immunohistochemical stainings for markers like e-cadherin and β-catein.

Diagnostic Value and Cost Considerations of Routine Fine-Needle Aspirations in the Follow-Up of Thyroid Nodules with Benign Readings

Fine-needle aspiration (FNA) is the most accurate tool to identify malignancy in solitary thyroid nodules. Although some recommend routinely repeating FNA for nodules that are initially read as benign, there is no consensus. We evaluated clinical relevancy and considered costs of routine follow-up FNA in nodules initially read as benign. We reviewed the records of all 739 patients who underwent FNA of solitary thyroid nodules at our institution from 1988 to 2004. A total of 815 aspirations were required to obtain satisfactory specimens. According to their physicians practice, some patients had a "follow-up biopsy" after an initially benign FNA reading as a matter of routine (Group I approach) or if their clinical status changed (Group II approach). The outcome information for at least 4 years after the initial FNA in these two groups was compared. In addition, hypothetical costs relating to both methods for deciding whether to do a follow-up FNA were considered. The initial FNA was benign in 576 (78%), suspicious for follicular neoplasms in 106 (14.4%), and malignant in 57 patients (7.7%). Follow-up FNA was performed in 292 patients with initially benign lesions, 235 in Group I approach and 57 in Group II approach. The FNA diagnosis according to Group I approach remained benign on follow-up biopsy in 96.2% (226/235), was altered to follicular neoplasm in 3% (7/235), and was suspicious for malignancy in 0.8% (2/235). When following Group II approach, the follow-up FNA was benign in 93% (53/57), undetermined in 1.7% (1/57), and showed follicular neoplasm in 5.3% (3/57). Combining Groups I and II methods, 5 of 292 patients had a malignant nodule on histological examination, a false-negative rate of 1.7% for the initial FNA, but without a difference in prevalence of thyroid malignancy between the groups. Cost-consequence analysis showed no benefit in routine follow-up FNA after initially benign FNA readings. Routine follow-up FNA in patients whose initial FNA is benign has a low diagnostic upgrading value and is relatively costly. In patients whose initial FNA is benign, we recommend the FNA be repeated only if clinically suspicious signs or complaints develop.