Routine Fine-needle Aspiration Research Articles

8012 A Severe Thrombotic Event Following Blood Thinner Interruption for Thyroid Fine Needle Aspiration Biopsy: A Case Report

Abstract Disclosure: V.A. Mendpara: None. P.P. Rao: None. M.V. Kellis: None. M.D. Lundholm: None. Background: This case highlights the potential severe thrombotic consequences of blood thinner medication interruption for thyroid fine needle aspiration (FNA). Case Presentation: A 77-year-old woman came to the endocrinology clinic for follow-up on thyroid nodules. She was a former smoker with controlled type 2 diabetes, hypertension, hyperlipidemia, and atrial fibrillation with patent foramen ovale on apixaban. She had no family history of thyroid cancer and no radiation exposure. Thyroid nodules were found incidentally, and she denied compressive symptoms. She had annual surveillance for the past 4 years, and her latest thyroid US redemonstrated 4 solid, hypoechoic nodules. The largest nodule, previously biopsied and benign in 2020, remained stable on the right. The next largest nodule in the left mid-thyroid was now 1.1 x 0.8 x 0.9 cm—a 30% growth from the previous year—with new punctate echogenic foci consistent with the TIRADS 5 classification. This finding was shared with the patient, who favored investigating with an FNA. At the recommendation of her PCP and the performing provider, she held her apixaban for approximately 48 hours before the FNA procedure.The US-guided thyroid FNA biopsy was uneventful, and the results indicated a benign nodule. However, 4 hours post-procedure, the patient suddenly became unresponsive while in the middle of cooking dinner. She was taken to the ED and found to have an ischemic stroke by basilar embolism, attributed to her interruption in apixaban therapy. Tenectaplase led to initial improvement but had subsequent hemorrhagic transformations affecting the midbrain, thalamus, and pons. This marked the beginning of a complex 2-month hospitalization requiring tracheostomy and percutaneous endoscopic gastrostomy (PEG) placement, followed by nearly a year of physical, occupational, and speech rehabilitation. Despite these efforts, she has not been able to return to her pre-stroke level of function and independence. Discussion: There is no consensus on the safety of performing a thyroid fine needle aspiration (FNA) biopsy for patients on blood thinner medications. Providers who favor holding blood thinners before FNA cite concerns for post-procedural hematoma formation or increased risk of non-diagnostic results. However, there is less discussion about the risks of interrupting these medications. This case emphasizes the potential for severe consequences from interrupting medically-indicated blood thinner therapy. The temporary discontinuation of apixaban for a routine thyroid FNA led to a life-threatening thrombotic event in our patient’s case. This outcome highlights the importance of carefully weighing the risks and benefits of medication interruptions for vulnerable populations. Further study is needed to investigate the safety of thyroid FNA on uninterrupted blood thinner therapy. Presentation: 6/2/2024

Diagnostic performance of fine-needle aspiration in soft tissue tumors: Application of the World Health Organization System for Reporting Soft Tissue Cytopathology and risk of malignancy assessment.

Recently, a new World Health Organization Reporting System for Soft Tissue Cytopathology (WHO System) was introduced. To analyze the value of this system, routine fine-needle aspiration soft tissue tumor (STT) cases were reviewed. Cytology samples of STTs collected between 1954 and 2022 at the Institut Curie were used (2214 cases, including 1376 primary tumors). All specimens were classified according to the predominant cytomorphological pattern and the WHO System. The diagnostic accuracy and risk of malignancy (ROM) in each category were calculated. Final diagnoses revealed 1236 malignancies and 978 benign or low-risk tumors. The original cytological evaluation led to 21 false-negative results (0.85%) and 29 false-positive results (1.17%). Sensitivity, specificity, positive predictive value, and negative predictive value were 98.3%, 92.1%, 97.5%, and 94.2%, respectively. Overall diagnostic accuracy was 94.2%. The ROM calculated according to the WHO System was 29.87%, 2.49%, 39.62%, 51.43%, 68.42%, and 97.69% in the nondiagnostic, benign, atypical, soft tissue neoplasm of uncertain malignant potential, suspicious for malignancy, and malignant categories, respectively; however, it varied broadly depending on the morphological pattern (62.78% in spindle cell tumors, 84.58% in myxoid tumors, 3.00% in lipomatous tumors, 78.15% in epithelioid tumors, 94.26% in pleomorphic tumors, and 100% in round cell tumors). Cytology of STTs is a powerful diagnostic method. Some cytological patterns overlap in different morphological groups, and the possibility of false-negative and false-positive diagnoses may persist. This analysis evidenced utility of the WHO System, especially when combined with morphological pattern assessment. Subclassification in particular diagnostic categories allowed for calculation of the ROM, which is crucial for optimal patient management.

Zinc in microscopic calcifications isolated from thyroid fine needle aspiration may serve as a biomarker of thyroid nodule malignancy: A promising proof-of-concept.

Thyroid nodules (TNs) are common neck ultrasonography (US) findings, yet only 5-10% of these nodules harbor thyroid cancer (TC). When US characteristics are consistent with an intermediate or high suspicion for TN malignancy, fine needle aspiration for cytology (FNAC) is indicated. The main limitation of FNAC is that cytological results can be indeterminate in up to 30% of cases, necessitating reevaluation through repeated FNAC, expensive molecular testing, or diagnostic thyroid lobe resection. As such, there is a need for further refinement of current diagnostic algorithms for TNs without subjecting patients to additional invasive procedures. As calcifications detected during thyroid US are considered a high-risk feature for malignancy, we used the material remaining following routine thyroid FNAC to isolate microscopic calcifications (MCs). We then characterized the elemental composition, morphology, and crystal phases of these MCs, ultimately revealing differences between the MCs from benign and malignant TNs. Specifically, thyroid MCs were identified as calcium phosphate crystals containing varying levels of magnesium, sodium, iron, and zinc. MCs obtained from malignant TNs, mainly papillary thyroid carcinoma, were composed of sub-micrometer spherical particles, whereas MCs from benign TNs consisted of faceted particles. While samples from most patients with a final diagnosis of malignant TNs (50% of them with indeterminate cytology) harbored zinc-containing MCs, zinc was largely absent in MCs from benign TNs (23% with indeterminate or non-diagnostic cytology). Together, these data suggest that the presence of zinc in MCs isolated from samples collected during routine FNAC may potentially offer value as a biomarker of TN malignancy. STATEMENT OF SIGNIFICANCE: As up to 40% of patients assessed for thyroid malignancy do not receive a definite diagnosis following thyroid nodule (TN) fine needle aspiration (FNA), there is a pressing need to improve the accuracy of current diagnostic algorithms. Chemical analyses of microscopic calcifications (MCs) may serve as a diagnostic target. We developed a straightforward protocol to chemically characterize MCs from excess material collected from TNs during routine FNA and found that these MCs differed between benign and malignant TNs. Specifically, zinc in TN-derived MCs may indicate a higher nodule malignancy risk, thus increasing the diagnostic accuracy of the FNA procedure, reducing the need for recurrent biopsies and diagnostic surgical procedures, and decreasing the costs, uncertainty, and stress faced by affected patients.

Multicoloured flow cytometry to detect metastatic carcinoma in lymph node by epithelial cell adhesion molecule.

The metastatic carcinoma in the lymph node may be missed in routine fine needle aspiration cytology (FNAC). There are limited studies on the role of epithelial cell adhesion molecule (EpCAM) in detecting metastatic carcinoma in the FNAC of lymph nodes by flow cytometry (FCM). To evaluate the role of EpCAM in flow cytometry detecting metastatic carcinoma in the fine needle aspiration cytology (FNAC) of the lymph node. In this prospective study, successive 42 cases of lymph nodes were subjected to FNAC followed by flow cytometry to detect the EpCAM positive cell population. The sample was used for cytology and FCM (CD45, CD14, and EpCAM antibodies tagged with fluorochromes). The percentage of EpCAM positive cell population in each case was calculated and compared in the metastatic carcinomas and reactive lymphoid hyperplasia (RLH) cases. There were 29 cases of metastatic carcinoma and 13 non-neoplastic cases (12 RLH and one granulomatous inflammation). The average percentages of EpCAM in metastatic carcinoma and reactive lymphoid cells were 11.37 and 1.24, respectively. The independent sample t-test showed a significant difference (0.001) in the percentage of EpCAM in the two groups. The cut of value of 3% EpCAM in FCM showed 97% sensitivity and 92% specificity to detect metastatic carcinoma in FNAC of the lymph node. The percentage of EpCAM in FCM may be helpful in detecting metastatic carcinoma in the lymph node. The FCM is a rapid and quantitative test with high sensitivity and specificity.

Effectiveness of core needle biopsy in the diagnosis of thyroid lymphoma and anaplastic thyroid carcinoma: A systematic review and meta-analysis.

BackgroundBoth anaplastic thyroid carcinoma (ATC) and thyroid lymphoma (TL) clinically present as rapidly enlarging neck masses. Unfortunately, in this situation, like in any other thyroid swelling, a routine fine-needle aspiration (FNA) cytology is the first and only diagnostic test performed at the initial contact in the average thyroid practice. FNA, however, has a low sensitivity in diagnosing ATC and TL, and by the time the often “inconclusive” result is known, precious time has evolved, before going for core-needle biopsy (CNB) or incisional biopsy (IB) as the natural next diagnostic steps.ObjectivesTo determine the diagnostic value of CNB in the clinical setting of a rapidly enlarging thyroid mass, via a systematic review and meta-analysis of the available data on CNB reliability in the differential diagnosis of ATC and TL.MethodsA PubMed, Embase and Web of Science database search was performed on June 23th 2021. Population of interest comprised patients who underwent CNB for clinical or ultrasonographical suspicion of ATC or TL, patients with a final diagnosis of ATC or TL after CNB, or after IB following CNB.ResultsFrom a total of 17 studies, 166 patients were included. One hundred and thirty-six were diagnosed as TL and 14 as ATC following CNB. CNB, with a sensitivity and positive predictive value of 94,3% and 100% for TL and 80,1% and 100% for ATC respectively, proved to be superior to FNA (reported sensitivity for TL of 48% and for ATC of 61%). Furthermore, the need for additional diagnostic surgery after CNB was only 6.2% for TL and 17.6% for ATC.ConclusionsImmediately performing CNB for a suspected diagnosis of ATC and TL in a rapidly enlarging thyroid mass is more appropriate and straightforward than a stepped diagnostic pathway using FNA first and awaiting the result before doing CNB.

Abstract 1967: Potential of aqueous humor as a liquid biopsy for uveal melanoma

Abstract Introduction: Uveal melanoma (UM) is the most common primary intraocular tumor in adults and arises from the uvea (iris, ciliary body and choroid). Although there are prognostic biomarkers available, identifying them requires intraocular tumor biopsy. Blood biopsy has emerged as a significantly less invasive alternative that also offers the ability to longitudinally track disease. However, blood biopsy has been unsuccessful for clinical use in identifying prognostic biomarkers in UM due to low detection rates. Thus, eye-specific aqueous humor (AH) biopsy may be a better alternative. Methods: This case series includes 20 primary UM patients with 13 (65%) choroid and 7 (35%) ciliary body (CB) tumors. AH samples were collected prior to brachytherapy plaque placement (n = 17), after brachytherapy (n = 19) and at enucleation (n = 1). A tumor wash sample (n = 1) was collected after routine fine needle aspiration biopsy. Nucleic acids ([NA], dsDNA, RNA, ssDNA and miRNA) were quantitated by Qubit Assay Kits. All AH samples and cells from tumor washing underwent DNA isolation and was followed by shallow whole-genome sequencing for copy-number profiling. Results: Comparison of pre- and post-radiation samples revealed significantly higher concentration of ssDNA (n = 10 pairs, P = 0.039) and miRNA (n = 10 pairs, P = 0.008) in choroid post- samples and significantly higher concentration of dsDNA (n = 7 pairs, P = 0.031) and miRNA (n = 7 pairs, P = 0.016) in CB post- samples. Between choroid (n = 12) and CB (n = 7) post- samples, there was a significantly higher concentration of dsDNA (P = 0.022) and RNA (P = 0.009) in post- CB samples, suggesting NA content is released from the disturbance of tumor cells by radiation and due to the proximity of the tumor to the AH in CB. Highly recurrent UM somatic copy number alterations (SCNAs) of monosomy 3, 6p gain, 6q loss and 8q gain were identified in post- AH samples. There was a significant difference between altered SCNA profiles in CB and choroid (P= 0.038). Altered SCNA profiles were found in 1/12 (8.3%) and 4/7 (57.1%) post-radiation AH samples of choroid and CB, respectively. No SCNAs were found in the same eyes’ pre-radiation sample. A high concordance of DNA profiles between a tumor wash and post- AH sample was identified (r = 0.978) and UM mutations GNAQ and BAP1 were detected in 3/6 (50%) post- AH with 2/5 (40%) matching tumor samples, demonstrating AH dsDNA’s tumor-origin. Conclusions: The AH is a source of cfDNA, with a higher yield of NAs after radiation in UM. Given the significant increase in NA concentration after radiation and in CB compared to choroid tumors, we hypothesize that all detected NAs post-radiation are tumor-derived due to apoptosis of tumor cells and subsequent release of cfDNA and due to the proximity of the CB tumor to AH. These results represent the first time that UM SCNAs and mutations were identified in cfDNA isolated from the AH, and this suggests that the AH can serve as a liquid biopsy for UM, especially in CB tumors. Citation Format: Deborah H. Im, Chen-Ching Peng, Liya Xu, Mary E. Kim, Dejerianne Ostrow, Venkata Yellapantula, Moiz Bootwalla, Jaclyn A. Biegel, Xiaowu Gai, Peter Kuhn, James Hicks, Jesse L. Berry. Potential of aqueous humor as a liquid biopsy for uveal melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1967.

Types and role of cytological molecular analysis in thyroid carcinomas

Estimates show that thyroid nodules are commonly reported among populations residing in iodine-sufficient countries, with estimated prevalence rates of 1%, and 4% of palpable nodules among men and women in these countries, respectively. Furthermore, early diagnosis can effectively direct clinicians to the right management modality, especially in cases with malignant lesions. In this literature review, we have discussed the types and roles of cytological molecular analysis in thyroid carcinomas. Our findings indicate the molecular analysis can significantly add to the diagnostic accuracy of cytological analysis and can greatly add to the efficacy of differentiating benign from malignant lesions. We have discussed the roles of different genetic mutations that were reported among the various studies in the literature, including BRAF, RAS, PAX8/PPARγ, and RET mutations. BRAF mutations are the most validated mutations among the current studies in the literature, which has been reported to greatly increase the positive predictive values in detecting thyroid carcinomas. Some genetic mutations can be used to diagnose difficult to differentiate malignancies by fine needle aspiration (FNA) analysis. For instance, RAS mutations were reported to accurately diagnose follicular variants of papillary thyroid carcinomas that are difficult to detect using routine FNA analysis.

Classic polymorphous adenocarcinoma: Fine needle aspiration cytopathology of eight cases.

The cytopathology and diagnostic accuracy of salivary gland (SG) polymorphous adenocarcinoma (PAC) is the subject of a limited number of reports. We undertook a review of our experience with fine needle aspiration (FNA) biopsy and PAC. A search was made of our cytopathology files for PAC cases that also had histopathological confirmation. FNA biopsy smears and cell-blocks were performed and examined using standard techniques. Eight FNA biopsy cases of histologically proven PAC from 7 patients [F:M=1.3:1, age 39-75years, mean=58] met study inclusion. Metastatic aspirates were most common (4), followed by 3 primary cases and 1 locally recurrent neoplasm. Primary FNA sites included hard palate (1 case), lip (1), and lateral tongue (1); all metastatic sites were in the neck. A precise cytologic diagnosis was made in 38% of cases; however, when applying the Milan classification system, 100% could be categorised as either malignant or of uncertain malignant potential. Ancillary immunohistochemical testing performed in 44% of the cases was non-specific. Cytologic smears showed cellular uniformity and structural variety of cell groups with tubular, branching, cribriform, and convex patterns as well as variable, but occasionally abundant globular myxoid stroma leading to confusion with adenoid cystic carcinoma. The imitative cytopathology of PAC with other SG neoplasms as well as its infrequency in routine FNA biopsy practice makes specific interpretation difficult, but using a classification system allows for appropriate patient management. Molecular testing in future specimens holds promise for enhancing diagnostic accuracy.

Moving towards a local testing solution for undetermined thyroid fine-needle aspirates: validation of a novel custom DNA-based NGS panel

AimsIn thyroid cytopathology, the undetermined diagnostic categories still pose diagnostic challenges. Although next-generation sequencing (NGS) is a promising technique for the molecular testing of thyroid fine-needle aspiration (FNA) specimens, access...

Negative images of mycobacteria revisited in rapid on-site evaluation

Rapid on-site evaluation (ROSE) with routine fine-needle aspiration cytology (FNAC) is a simple, economical, highly accurate tool in the diagnosis of tuberculous lesions. The sample collected can be used for ancillary studies, i.e., Ziehl–Neelsen stain, Cartridge-based nuclei acid amplification testing (CB-NAAT) and bacterial culture for confirmation of the tubercular species. We report a case of a 31-year-old male who presented with left supraclavicular lymphadenopathy. ROSE with FNAC helped in the diagnosis of the patient. FNAC is a rapid minimally invasive method for the early detection of tubercular lesions and helps in proper treatment.

Utility of rapid brillant cresyl blue stained wet mount preparation in routine fine needle aspiration cytology

Fine Needle Aspiration Cytology is the preliminary investigation employed for superficial and deep swelling in the body. It provides early information regarding the lesions before performing biopsy and aid in the treatment plan of the patient. However sample inadequacy from representative lesion may render patients to repeat aspirations and may also cause delay in reports. There is an ever increasing demand for rapid diagnosis in cytology. The present study was conducted to assess the utility of brilliant cresyl blue as a rapid stain in fine needle aspiration cytology. To assess the utility of rapid Brilliant cresyl blue (BCB) stained wet mount preparation in routine fine needle aspiration cytology. The study was carried out in the Cytology laboratory, Govt. Medical College Thiruvananthapuram and PG Pathology Lab, Department of MLT, Govt. Medical College Thiruvananthapuram for a period of six months. A total of 50 cases referred to cytology laboratory for FNAC were included in this study. A wet mount preparation with Brilliant cresyl was prepared immediately after aspiration and examined for cellular adequacy and cytomorphology, which was then compared with the routine Papanicolau stained smear . In situations for rapid diagnosis, and to assess the cellular adequacy of a lesion Brilliant cresyl blue staining method is very helpful. Most of the cases diagnosed as malignant on Brilliant cresyl blue staining correlate with the Pap stain. All the cases diagnosed as benign on rapid brilliant cresyl blue stain were also diagnosed as benign with Pap stain. The result clearly indicate that the brilliant cresyl blue stained wet mount preparation can be used as a rapid supplementary diagnostic procedure in FNAC at least for urgent reporting and sample adequacy assessment.

Evaluation of BRAF, RAS, RET/PTC, and PAX8/PPARg alterations in different Bethesda diagnostic categories: A multicentric prospective study on the validity of the 7-gene panel test in 1172 thyroid FNAs deriving from different hospitals in South Italy.

Thyroid fine-needle aspiration (FNA) is a reliable and cost-effective diagnostic tool for establishing the nature of thyroid nodules, although up to 30% of FNAs are still classified as "indeterminate." Molecular testing of FNAs could improve preoperative diagnosis, thereby reducing unnecessary surgery. In this multicenter prospective studythe authors investigated,using a 7-gene assay, the distribution and diagnostic impact of BRAF, RAS, RET/PTC, and PAX8/PPARg, themost frequent genomic alterations occurring during thyroid oncogenesis. In total, of 1172 routine FNAs from 7 centers in southern Italy were classified according to the Bethesda System for Reporting Thyroid Cytopathology. Each specimen was tested, and molecular data were compared with available histology or cytologic follow-up. In particular, for atypia of undetermined significance/follicular lesion of undetermined significance cases, the 7-gene test confirmed the high positive predictive value of BRAFV600E and BRAF-like mutations (80%) and the moderate positive predictive value of RAS-like alterations (32.4%), suggesting different surgical management, depending on the type of mutation. The rate of mutation-positive FNAs was strictly related to the risk of malignancy of each diagnostic class, supporting the identification of prognostically relevant diagnostic categories. The 7-gene panel test improves the preoperative risk stratification of indeterminate thyroid FNAs, especially when considering the biologic significance of the different types of mutations. Moreover, the rate of mutation-positive FNAs is related to the risk of malignancy of each diagnostic class.

A randomized trial comparing health-related quality-of-life and utility measures between routine fine-needle aspiration cytology (FNAC) and surveillance alone in patients with thyroid incidentaloma measuring 1-2 cm.

To present the impact of treatment on health-related quality-of-life (HRQOL) and health utility measures from the randomized controlled trial (ClinicalTrials.gov Identifier: NCT02398721) that investigated the FNAC versus watchful surveillance in patients with incidental benign thyroid nodules. Health utility and HRQOL were evaluated using the EQ-5D 5-level (EQ-5D-5L), 6-item Short-Form Health Survey (SF-6D), and generic 12-item Short-Form Health Survey (SF-12v2) at baseline, 3-month, 6-month, and 12-month assessments. A repeated measure analysis of variance evaluated differences in HRQOL scores between treatment groups over time. Multiple imputations were used to impute missing data at each time point. HRQOL data completion rates were 99.7% at baseline, 92.7% at 3-month, 93.9% at 6-month, 92.7% at 12-month, and 88.6% at 18-month follow-up after baseline. There were significant mean differences in SF-6D, EQ-5D-5L, and SF-12v2 over time except the domain of vitality and mental health of SF-12v2. Mean change of SF-12v2 scores and utility scores from baseline between groups did not exceed minimal important difference. No significant treatment group by time interactions were found in all HRQOL and utility scores except in the vitality domain and PCS of SF-12v2 (p value = 0.033; 0.024). When compared with watchful surveillance, FNAC intervention was associated with better vitality and physical-related HRQOL scores but did not provide better preservation of utility score improvement over the 18-month period. These findings support the routine FNAC approach for nodules that have a low-suspicion sonographic pattern and measure between 1.0 and 2.0 cm.

Acute Parotitis: A Rare Complication of Fine Needle Aspiration in Warthin Tumour.

Salivary gland tumours are a group of neoplasms with considerable heterogeneity regarding their histology and biological behaviour. Warthin tumour (WT) is the second most common benign parotid tumour. Options for tissue diagnosis include fine needle aspiration (FNA) and ultrasound-guided core needle biopsy. Complications related to FNA are rare. We present the case of a 49-year-old man admitted with parotitis after FNA and discuss management and an alternative investigative approach when WT is strongly suspected.LEARNING POINTSWarthin tumour (WT) can be clinically suspected based on location (parotid gland tail), cystic texture, patient sex (male) and age (fifth and sixth decades of life), after exclusion of features related to malignancy.Complications of fine-needle aspiration (FNA) for WT diagnosis are rare and most commonly include haemorrhage, facial nerve injury, cellulitis at the needle puncture site and, less frequently, parotitis.When diagnosing tumours strongly suspected of being WT, the clinician should avoid routine FNA and instead use combined imaging studies.

Usefulness of core needle biopsy for the diagnosis of thyroid Burkitt\u2019s lymphoma: a case report and review of the literature

BackgroundThyroid lymphomas are an exceptional finding in patients with thyroid nodules. Burkitt’s lymphoma is one of the rarest and most aggressive forms of thyroid lymphomas, and its prognosis depends on the earliness of medical treatment. Given the rarity of this disease, making a prompt diagnosis can be challenging. For instance, fine-needle aspiration (FNA) cytology, which is the first-line diagnostic test that is performed in patients with thyroid nodules, is often not diagnostic in cases of thyroid lymphomas, with subsequent delay of the start of therapy.Case presentationHere we report the case of a 52-year-old woman presenting with a rapidly enlarging thyroid mass. Thyroid ultrasonography demonstrated a solid hypoechoic nodule. FNA cytology was only suggestive of a lymphoproliferative disorder and did not provide a definitive diagnosis. It is core needle biopsy (CNB) that helped us to overcome the limitations of routine FNA cytology, showing the presence of thyroid Burkitt’s lymphoma. Subsequent staging demonstrated bone marrow involvement. The early start of an intensive multi-agent chemotherapy resulted in complete disease remission. At 60 months after the diagnosis, the patient is alive and has not had any recurrence.ConclusionsClinicians should be aware that thyroid Burkitt’s lymphoma is an aggressive disease that needs to be treated with multi-agent chemotherapy as soon as possible. To diagnose it promptly, they should consider to order/perform a CNB in any patient with a rapidly enlarging thyroid mass that is suspicious for lymphoma.

Short Call Abstracts

Short Call Abstracts

Utility of Rapid Brilliant Cresyl Blue Stain in Routine Fine Needle Aspiration Cytology

Utility of Rapid Brilliant Cresyl Blue Stain in Routine Fine Needle Aspiration Cytology

Diagnostic Limitation of Fine-Needle Aspiration (FNA) on Indeterminate Thyroid Nodules Can Be Partially Overcome by Preoperative Molecular Analysis: Assessment of RET/PTC1 Rearrangement in BRAF and RAS Wild-Type Routine Air-Dried FNA Specimens.

Molecular markers are helpful diagnostic tools, particularly for cytologically indeterminate thyroid nodules. Preoperative RET/PTC1 rearrangement analysis in BRAF and RAS wild-type indeterminate thyroid nodules would permit the formulation of an unambiguous surgical plan. Cycle threshold values according to the cell count for detection of the RET/PTC1 rearrangement by real-time reverse transcription-polymerase chain reaction (RT-PCR) using fresh and routine air-dried TPC1 cells were evaluated. The correlation of RET/PTC1 rearrangement between fine-needle aspiration (FNA) and paired formalin-fixed paraffin-embedded (FFPE) specimens was analyzed. RET/PTC1 rearrangements of 76 resected BRAF and RAS wild-type classical PTCs were also analyzed. Results of RT-PCR and the Nanostring were compared. When 100 fresh and air-dried TPC1 cells were used, expression of RET/PTC1 rearrangement was detectable after 35 and 33 PCR cycles, respectively. The results of RET/PTC1 rearrangement in 10 FNA and paired FFPE papillary thyroid carcinoma (PTC) specimens showed complete correlation. Twenty-nine (38.2%) of 76 BRAF and RAS wild-type classical PTCs had RET/PTC1 rearrangement. Comparison of RET/PTC1 rearrangement analysis between RT-PCR and the Nanostring showed moderate agreement with a κ value of 0.56 (p = 0.002). The RET/PTC1 rearrangement analysis by RT-PCR using routine air-dried FNA specimen was confirmed to be technically applicable. A significant proportion (38.2%) of the BRAF and RAS wild-type PTCs harbored RET/PTC1 rearrangements.

Role of Cell Block in Guided FNAC of Abdominal Masses.

Fine Needle Aspiration (FNA) of space occupying lesions in superficial or deep anatomic sites is an increasingly common procedure, providing rapid and safe diagnosis. However, sometimes FNA does not yield sufficient information for a precise diagnosis and the risk of false negatives and indeterminate diagnosis is always present. Therefore, we attempted to obtain additional information via the preparation of Cell Block (CB) from the residual material of aspirates and thus enhance the diagnostic accuracy. This study was carried out to evaluate the role of CB as a useful adjunct to smears for establishing a more definitive cytopathologic diagnosis and for its utility in special staining and Immuno-histochemistry (IHC). A total of 66 cases of image-guided FNA of abdominal masses were studied. In addition to the routine smears, CBs were prepared from the residual tissues for all possible cases and its diagnostic efficacy was analysed. Further, the use of CBs for special staining and IHC was also established. This study included a total of 66 patients with abdominal masses who were referred for guided FNA cytology. Out of these cases, adequate material was obtained on FNAC in 64 cases (96.96%) and on CB in 45 cases (68.18%) and the diagnosis was provided. There was a good agreement between the FNA smear diagnosis and CB diagnosis. The histopathology of CB sections further helped in precise final cytopathological diagnosis. Two FNA smears were unsatisfactory for evaluation and hence the diagnosis was done on CB sections alone. With FNA cytology and CB in combination, a cytopathological diagnosis was given for all the 66 cases. The sensitivity of FNA in comparison to the histopathology of CB was 91.6% and specificity was 88.8%. The diagnostic accuracy was 62% and the discordance was 6%. CB in addition to the routine FNA is a simple, reliable and cost-effective technique that further contributes to the final cytopathological diagnosis.

Detection of BRAF c.1799T > A (p.V600E) mutation using residual routine fine-needle aspiration specimens of papillary thyroid carcinoma.

BRAF p.V600E mutation is the most common genetic alteration in papillary thyroid cancer (PTC) and has been used as a diagnostic and prognostic marker in PTC. The aim of this study was to investigate the utility of preoperative BRAF p.V600E mutation analysis as an adjunctive diagnostic and prognostic tool to routine fine-needle aspiration (FNA). Specimens were collected from thyroid nodules by FNA. Cytology diagnosis and BRAF p.V600E testing were performed on these specimens. Molecular and cytological results were correlated with histology outcomes. A total of 195 patients with thyroid nodules were enrolled, including 25 benign lesions and 170 PTCs. BRAF p.V600E testing was successfully performed in all specimens. The combination of BRAF p.V600E testing and cytology improved the sensitivity of cytology from 70% to 85.3% (P = 0.001). This significant increase in sensitivity was due to the detection of PTC by BRAF p.V600E testing in the nodules with atypical or suspicious PTC cytology results. Patients with BRAF p.V600E-positive tumors were significantly older than those who did not harbor mutations (45.6 years vs. 39.8 years, P = 0.002). No correlations between BRAF p.V600E mutation and other clinical-pathology parameters were observed. Detection of BRAF p.V600E mutation can be successfully carried out using residual liquid-based materials. It can be performed as a diagnostic tool to supplement traditional thyroid FNA, especially in cases with atypical or suspicious PTC. However, the role of BRAF p.V600E in guidance of the extent of thyroidectomy and nodal clearance requires further study.