Fine-needle Aspiration Biopsy Specimens Research Articles

Performance of MYC, BCL2, and BCL6 break-apart FISH in small biopsies with large B-cell lymphoma: a retrospective Cytopathology Hematopathology Interinstitutional Consortium study.

Fluorescence in situ hybridization (FISH) is an essential ancillary study used to identify clinically aggressive subsets of large B-cell lymphomas that have MYC, BCL2, or BCL6 rearrangements. Small-volume biopsies such as fine needle aspiration biopsy (FNAB) and core needle biopsy (CNB) are increasingly used to diagnose lymphoma and obtain material for ancillary studies such as FISH. However, the performance of FISH in small biopsies has not been thoroughly evaluated or compared to surgical biopsies. We describe the results of MYC, BCL2, and BCL6 FISH in a series of 222 biopsy specimens, including FNAB with cell blocks, CNBs, and surgical excisional or incisional biopsies from 208 unique patients aggregated from 6 academic medical centers. A subset of patients had FNAB followed by a surgical biopsy (either CNB or excisional biopsy) obtained from the same or contiguous anatomic site as part of the same clinical workup; FISH results were compared for these paired specimens. FISH had a low hybridization failure rate of around 1% across all specimen types. FISH identified concurrent MYC and BCL2 rearrangements in 20 of 197 (10%) specimens and concurrent MYC and BCL6 rearrangements in 3 of 182 (1.6%) specimens. The paired FNAB and surgical biopsy specimens did not show any discrepancies for MYC or BCL2 FISH; of the 17 patients with 34 paired cytology and surgical specimens, only 2 of the 49 FISH probes compared (4% of all comparisons) showed any discrepancy and both were at the BCL6 locus. One discrepancy was due to necrosis of the CNB specimen causing a false negative BCL6 FISH result when compared to the FNAB cell block that demonstrated a BCL6 rearrangement. FISH showed a similar hybridization failure rate in all biopsy types. Ultimately, MYC, BCL2, or BCL6 FISH showed 96% concordance when compared across paired cytology and surgical specimens, suggesting FNAB with cell block is equivalent to other biopsy alternatives for evaluation of DLBCL or HGBCL FISH testing.

The 15-gene expression profile test is independent from PRAME and 7-gene next-generation sequencing: Results from 3,267 clinically tested uveal melanomas.

9598 Background: The 15-gene expression profile (15-GEP) test is the gold standard in the US for metastatic risk prediction in uveal melanoma (UM). Studies have shown that the 15-GEP is superior to and independent of other clinicopathologic and molecular risk factors, including PRAME expression status and BAP1 mutation status. Supplemental tests for PRAME and the 7-gene NGS panel ( BAP1, SF3B1, EIF1AX, GNA11, GNAQ, CYSLTR2, PLCB4)are validated and can now be run clinically from the same biopsy specimen. However, the discordance between 15-GEP, PRAME and NGS in clinical specimens is unknown. This study aimed to determine whether PRAME status or DNA mutation status could be used to predict the 15-GEP result. Methods: Data from fine-needle aspiration biopsy or formalin-fixed paraffin-embedded UM specimens submitted for routine comprehensive clinical testing with all three commercial tests (15-GEP, PRAME, and NGS) between February 2018 and December 2023 were collected through an Institutional Review Board-approved protocol. Results: Overall, 3267 tumors with comprehensive molecular testing were analyzed. 15-GEP testing yielded 65.9% (n=2152/3267) Class 1 and 34.1% (n=1115) Class 2 tumors. While Class 2 tumors were more than twice as likely to be PRAME(+) vs Class 1, 54.3% (606/1115) of Class 2 cases were PRAME(–), and 20.9% (450/2152) of Class 1 cases were PRAME(+) resulting in a PRAME/15-GEP discordance rate of 32.3% (10-56/3267). Mutations in genes associated with increasing metastatic risk ( EIF1AX, SF3B1, and BAP1, respectively) were identified in 58.7% (1918/3267) of cases. Most EIF1AX mutations (569/623, 91.3%) occurred in Class 1 tumors that were PRAME(–), while most SF3B1mutations were found in Class 1, PRAME(+) tumors (244/404, 60.4%). Most BAP1 mutations (863/976, 88.4%) occurred in Class 2 (high risk) tumors, of which 53.9% (465/863) were PRAME(–). Importantly, 56.0% (1205/2152) of Class 1 tumors did not harbor detectable EIF1AX or SF3B1 mutations, and 22.6% (252/1115) of Class 2 tumors did not harbor a detectable BAP1 mutation, yielding an NGS/15-GEP discordance rate of 44.6% (1457/3267). Conclusions: The validated PRAME and NGS tests described here, which can be performed from the same initial biopsy sample taken for 15-GEP testing, provide results that are not systematically associated with 15-GEP class. Given that the 15-GEP has been shown to be superior to both PRAME and NGS in predicting metastatic outcomes, it is recommended that these supplemental tests only be considered in the context of a 15-GEP test result to prevent potentially over or under identifying high-risk biology. An ongoing prospective study with long term outcomes for over 1700 UM patients led by the Collaborative Ocular Oncology Group (COOG2) will provide insight into how best to effectively integrate these supplementary biomarkers with the 15-GEP class result.

The use of telecytology for the evaluation of thyroid nodules fine-needle aspiration biopsy specimens: a systematic review.

Fine needle aspiration biopsy (FNAB) is currently the gold standard for diagnosis and treatment of thyroid nodules, but the growing need for anatomic pathology services in small communities is becoming a challenge. Telecytology (TC) is defined as the electronic transmission of cytological digital images, and allows for the collection of samples, primary diagnosis, and other applications without the physical presence of a pathologist. Our aim is to systematically report, summarize, and critically analyze the most up to date applications of TC to thyroid nodules FNAB evaluation. We performed a systematic literature review by searching PubMed, Embase, and Cochrane Library databases. Only studies published in peer-reviewed scientific journals were included. Data were extracted using the PICO framework and critically analyzed. PRISMA guidelines were applied, and the risk of bias in the included studies was assessed using the ROBINS-I tools. The methodological quality was assessed following GRADE criteria. We included 13 observational studies, resulting in a total of 3856 evaluated FNAB specimens. The majority of studies (63.6%) showed an excellent concordance rate of diagnosis via TC and conventional cytology. TC can be used to perform preliminary assessment of samples with a concordance rate ranging from 74 and 100%, showing a significant reduction of the non-diagnostic rate. Image quality was referred to as perfect or nearly perfect in most cases, regardless of telecytology technique. Telecytology could be a valuable implementation for thyroid FNAB evaluation both for primary diagnosis and preliminary assessment of samples.

Interobserver agreement and risk of malignancy using the International Academy of Cytology Yokohama System for reporting breast FNA biopsy in a liquid-based exclusive cohort.

Per the College of American Pathologist's National Breast Fine Needle Aspiration Biopsy (FNAB) Practice Survey, ∼40% of laboratories use liquid-based cytology (LBC) for breast FNAB. The reproducibility of the International Academy of Cytology Yokohama System (YS) for reporting breast FNAB on LBC was explored. Breast FNAB specimens submitted as LBC only (all ThinPrep) between January 2017 and January 2021 were retrieved. Cases without histopathologic follow-up were excluded. Clinical and radiologic information was collected. One cytologist and six cytopathologists rendered diagnoses per YS. All reviewers were blinded to the original diagnosis and histopathologic follow-up. The risk of malignancy was calculated. Concordance rates were calculated by a weighted Cohen Kappa score (κ). Review of 110 cases demonstrated substantial to near-perfect agreement between each reviewer (κ=0.73-0.91) and follow-up histopathology (κ=0.66-0.85). The agreement was lowest in the inadequate (κ=0.05) and atypical (κ=0.04) categories. The lack of concordance in the atypical category was common in cases with low cellularity or incomplete structural features. The risk of malignancy for inadequate, benign, atypical, suspicious for malignancy, and malignant categories were 12.5% (2/16), 3% (2/65), 67%, (8/12) 100% (1/1), and 100% (16/16). Interobserver agreement is excellent using the five YS categories in LBC. Lack of cellularity and incomplete architectural features were barriers to perfect agreement. Established pitfalls in the interpretation of LBC were cause for atypical diagnoses. Continuous training and education are recommended to avoid misdiagnosis because of the nonconventional cytomorphologic features of LBC and to improve inadequate and atypical rates within YS.

REV7 is involved in outcomes of platinum-based chemotherapy in pancreatic cancer by controlling the DNA damage response.

REV7 is a multifunctional protein implicated in various biological processes, including DNA damage response. REV7 expression in human cancer cells affects their sensitivity to DNA-damaging agents. In the present study, we investigated the significance of REV7 in pancreatic ductal adenocarcinoma (PDAC). REV7 expression was immunohistochemically examined in 92 resected PDAC specimens and 60 endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) specimens of unresectable PDAC treated with platinum-based chemotherapy, and its association with clinicopathologic features was analyzed. Although REV7 expression was not significantly associated with the progression of primary tumors (T-factor and Stage) in either resected or unresectable PDAC, decreased levels of REV7 expression in EUS-FNAB specimens of unresectable PDAC were significantly associated with better outcomes of platinum-based chemotherapy and a favorable prognosis. REV7-deficient PDAC cell lines showed suppressed cell growth and enhanced sensitivity to cisplatin invitro. Tumor-bearing mice generated using REV7-deficient PDAC cell lines also showed enhanced sensitivity to cisplatin invivo. RNA sequencing analysis using WT and REV7-deficient PDAC cell lines revealed that REV7 inactivation promoted the downregulation of genes involved in the DNA repair and the upregulation of genes involved in apoptosis. Our results indicate that decreased expression of REV7 is associated with better outcomes of platinum-based chemotherapy in PDAC by suppressing the DNA damage response. It is also suggested that REV7 is a useful biomarker for predicting the outcome of platinum-based chemotherapy and the prognosis of unresectable PDAC and is a potential target for PDAC treatment.

Fine-needle aspiration biopsy possibilities in studying the molecular genetic landscape of breast tissue

Background. Core biopsy of the breast is currently considered to be the standard method of obtaining material for morphological and molecular genetic methods. Unfortunately, this method is associated with a number of problems, primarily the risk of complications (bleeding, pneumothorax) and discomfort during manipulation.Aim. To analyze transcriptional signatures of breast tissue samples obtained by fine-needle aspiration biopsy. Materials and methods. Using reverse transcriptase polymerase chain reaction, we studied the mRNA expression level of 60 target genes in 60 samples obtained by fine-needle aspiration biopsy and in 60 corresponding formalin-fixed paraffin-embedded (FFPE) surgical specimens of breast. Samples were obtained from the tumor, adjacent tissue, the so-called tumor bed and formally normal tissue at a distance from the primary lesion.Results. A comparative analysis of transcriptional signatures in samples obtained by fine-needle aspiration biopsy and FFPE specimens (120 samples in total) reveled the strongest correlations between transcriptional signatures in biopsy samples and FFPE specimens of tumors. Very strong correlation in tumor samples was established for one gene (CTSL2); strong for 18 genes (MKI67, MYBL2, NAT1, PTEN, TPX2, PTTG1, UBE2T, CCNB1, ESR1, CCND1, MYC, SCGB2A2, MIA, TRAC, FGFR4, ANLN, GSTM1, PRLR); averages for 28 genes (PGR, AURCA, KRT5, FOXA1, SFRP1, EMSY, EXO1, PAK1, KIF14, ERBB2, MMP11, BCL2, BAG1, TMEM45B, BIRC5, CD274/PDL1, ZNF703, TYMS, CCNE1, TPT1, TMEM45A, BRCA1, BRCA2, ESR2, STS, TNFSF11/RANKL, TNFRSF11B/OPG, TNF); weak for 4 genes (GRB7, EGFR, PGRMC1, CYP19A). The presence of correlations between transcriptional signatures in biopsy samples and FFPE specimens can be established in case of sufficient material corresponding to sample intake control (SIC) ≥5 lg for B2M gene.Conclusion. The ability to conduct molecular genetic research on small samples of breast tissue makes it possible to obtain the material using the most minimally invasive method. And this, in turn, expands the possibilities of “genetic monitoring” of cancer, as well as the possibility of more accurate assessment the risks of malignant tumor development in the settings of benign conditions in women with fibrocystic disease and increased mammographic density.

Facilitation of Definitive Cancer Diagnosis With Quantitative Molecular Assays of BRAF V600E and TERT Promoter Variants in Patients With Thyroid Nodules

Molecular testing of the presence of pathogenic genomic variants in a tumor without quantifying the variant allele fraction (VAF) does not differentiate the variation extent among tumors, often resulting in an inconclusive diagnosis because of interpatient variability. To examine the association between the quantification of VAFs of BRAF V600E and TERT promoter variants and a definitive cancer diagnosis of thyroid tumors. This diagnostic study analyzed a cohort of 378 surgically resected thyroid tumors with a maximum dimension of 1 cm or larger between March 15, 2016, and March 16, 2020, and a separate cohort of 217 residual thyroid fine-needle aspiration (FNA) biopsy specimens obtained from January 22, 2020, to March 2, 2021, at Mount Sinai Hospital, Toronto, Ontario, Canada. Data analysis was conducted between February 1, 2021, and February 1, 2023. Quantitative VAF assays of BRAF V600E and TERT promoter variants (C228T and C250T) were performed by digital polymerase chain reaction molecular assays. The VAFs of BRAF V600E and TERT promoter variants were correlated with tumor histologic diagnoses and histopathologic features to delineate the association of VAF assays with tumor malignancy. The receiver operating characteristic curve analysis, sensitivity, specificity, positive predictive value, negative predictive value, and logistic regression analysis based on follow-up histopathologic types were used to determine the diagnostic utility of the quantitative molecular assays. A total of 595 specimens, including 378 surgically resected thyroid tumors and 217 thyroid nodule FNA biopsy specimens, were collected from 580 patients (436 [75.2%] female with a mean [SD] age of 50 [16] years and 144 [24.8%] male with a mean [SD] age of 55 [14] years). Sensitive VAF assays of 378 thyroid tumors revealed the presence of the BRAF V600E variant in 162 tumors (42.9%), with 26 (16.0%) at a low VAF of 1% or less and 136 (84.0%) at a high VAF of greater than 1%, and the presence of TERT promoter variants in 49 tumors (13.0%), including 45 C228T variants (91.8%), 15 (33.3%) of which were quantified as having a low VAF (≤1%) and 30 (66.7%) as having a high VAF (>1%), and 4 C250T variants (8.2%) with VAFs between 40.0% and 47.0%. All tumors detected with BRAF V600E and/or TERT promoter variants, whether at low or high VAFs, received a definitive cancer diagnosis. Further analysis delineated a significant association between high VAFs of either variant individually or different VAF levels for both variants in coexistence and aggressive histopathologic features of tumors. Excluding low VAFs assisted in identifying patients at an intermediate-to-high risk of recurrence (odds ratio, 5.3; 95% CI, 1.9-14.6; P = .001). The VAF assays on the residual FNA biopsy specimens showed a high agreement to those on surgical tissues (κ = 0.793, P < .001) and stratified malignancy in 40 of 183 indeterminate FNA cases (21.9%), with a sensitivity of 93.8% (95% CI, 67.7%-99.7%), specificity of 90.0% (95% CI, 75.4%-96.7%), positive predictive value of 78.9% (95% CI, 53.9%-93.0%), and negative predictive value of 97.3% (95% CI, 84.2%-99.9%). This diagnostic study suggests that sensitive quantitative VAF assays of BRAF V600E and TERT promoter variants can elucidate the interpatient variability in tumors and facilitate a definitive cancer diagnosis of thyroid nodules by differentiating the variation extent of genomic variants, even at low VAFs.

Machine-learning-based diagnosis of thyroid fine-needle aspiration biopsy synergistically by Papanicolaou staining and refractive index distribution

We developed a machine learning algorithm (MLA) that can classify human thyroid cell clusters by exploiting both Papanicolaou staining and intrinsic refractive index (RI) as correlative imaging contrasts and evaluated the effects of this combination on diagnostic performance. Thyroid fine-needle aspiration biopsy (FNAB) specimens were analyzed using correlative optical diffraction tomography, which can simultaneously measure both, the color brightfield of Papanicolaou staining and three-dimensional RI distribution. The MLA was designed to classify benign and malignant cell clusters using color images, RI images, or both. We included 1535 thyroid cell clusters (benign: malignancy = 1128:407) from 124 patients. Accuracies of MLA classifiers using color images, RI images, and both were 98.0%, 98.0%, and 100%, respectively. As information for classification, the nucleus size was mainly used in the color image; however, detailed morphological information of the nucleus was also used in the RI image. We demonstrate that the present MLA and correlative FNAB imaging approach has the potential for diagnosing thyroid cancer, and complementary information from color and RI images can improve the performance of the MLA.

Genetic Considerations in the Tumorigenesis, Diagnosis, and Treatment of Differentiated Thyroid Cancer: Current State of the Science.

Thyroid nodules remain a common diagnosis encountered in general and endocrine surgical practice, and thyroid cancer appears to be increasing in incidence in both the United States and worldwide. The understanding of the complex genetics surrounding thyroid neoplasia has increased substantially in recent years and, consequently, has become a consideration in risk stratification, diagnosis, prognosis, and treatment. Molecular genetic analysis of thyroid nodules is now a readily available technology for diagnostic purposes via analysis of fine-needle aspiration biopsy (FNAB) specimens. Although their routine use is controversial, they may aid in selecting which patients require surgery and those who may be safely observed. In the following review, the genetics of the tumorigenesis of thyroid cancer are reviewed, focusing on the most common and clinically relevant of the literally hundreds of known mutations. Following this, the current status of the use of genetic analysis and molecular diagnostics in the workup of thyroid nodules and the diagnosis of differentiated thyroid cancer is explored. Finally, evolving concepts relating to the use of thyroid cancer genetics in individualizing treatment planning, follow-up, and management of recurrent disease is discussed. The goal is to provide the general surgeon with a working knowledge of the most common genetic alterations present in differentiated thyroid cancer, their relevance in clinical practice, and how they impact prognosis and treatment.

Combined Use of Cell Block and Smear Improves the Cytological Diagnosis of Malignancy in Non-Palpable Breast Lesions Screened by Imaging.

Currently, core needle biopsy is replacing fine needle aspiration biopsy (FNAB) for pathological diagnosis of breast lesions. However, FNAB is extensively used for diagnosing breast lesions, including screened lesions, at our hospital. Furthermore, direct smears as well as cell blocks (CBs) from the FNAB specimens have been used. To prepare the CBs, hematoxylin and eosin (HE) staining as well as immunostaining with a mixture of p63 and cytokeratin 5/6 antibodies are routinely used. Therefore, in the current study, we sought to assess the efficacy of diagnosing breast lesions using conventional smears and CB immunostaining. Breast FNAB reports of direct smears and CBs from The Nagoya Medical Center between December 2014 and March 2020, were reviewed. The efficiency of diagnoses made with direct smears and CBs were compared using histology-based diagnoses. Among the 169 histologically confirmed malignant lesions, 12 lesions that were reported as unsatisfactory, benign, or atypia probably benign, using direct smears were diagnosed as malignant using CB. Histologically, these lesions were diagnosed as carcinomas with mild atypia or papillary structures. Ten (83.3%) of the twelve lesions were non-palpable and only detected upon imaging. Combined use of CB and conventional smear leads to the detection of more malignant lesions in breast FNAB specimens, particularly in lesions detected by imaging alone. Immunostaining of CB sections using a mixture of p63 and cytokeratin 5/6 antibodies provides more information than HE staining alone. Breast FNAB with CB preparation can be successfully applied for evaluation of breast lesions in developed countries.

Salivary gland fine-needle aspiration biopsy: quality assurance results from a tertiary cancer center.

Fine-needle aspiration biopsy (FNAB) plays a critical role in the management of patients with salivary gland lesions. A specific diagnosis can be difficult due to the wide range of lesions with overlapping morphologic features, potentially leading to interpretation errors. We analyzed the cytologic-histologic discrepancies identified in the quality assurance program of a major cancer center in cases of salivary gland FNAB and performed a root cause analysis. Salivary gland FNAB specimens performed during a 12-year period at a major tertiary cancer center were reviewed. The inclusion criteria for this study included FNAB cases of salivary glands with subsequent histologic or flow cytometry follow up. The cytologic diagnoses for these cases were recategorized according to the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) based on the original reports. The risk of neoplasm and malignancy based on the cases with subsequent resection or flow cytometry and the most common causes of discrepancy were analyzed. The risk of neoplasm ranged from 41% to 99% and the risk of malignancy ranged from 22% to 99% among the different MSRSGC categories. Lymphoid and myoepithelial rich lesions were the most common miscategorized lesions using the MSRSGC. Reactive changes due to inflammation were associated with overcalls. The most common malignancy in the atypical category was mucoepidermoid carcinomas. Myoepithelial and lymphoid rich lesions arising in the salivary gland are associated with a higher risk of misclassification. The use of category IVB in the MSRSGC is appropriate for lesions with abundant myoepithelial cells. Reactive atypia seen in sialadenitis was the most common feature associated with overcall.

Assessing the accuracy of the International Academy of Cytology Yokohama System for reporting breast fine needle aspiration biopsy cytology at a Vietnamese oncology centre.

Fine needle aspiration biopsy (FNAB), accompanied by classification systems for cytology, can offer a cheap and convenient option for the diagnosis of breast cancer in women with suspicious breast lumps. In this study, we aimed to assess the accuracy of the International Academy of Cytology (IAC) Yokohama system in a Vietnamese oncology centre. A retrospective cross-sectional study was conducted from November 2021 to April 2022 at Vietnam National Cancer Hospital. We included patients with full hospital records regarding breast lesions for which FNAB was indicated. A total of 803 patients' FNAB specimens were assessed according to the IAC Yokohama system. The basic characteristics were summarised using the appropriate summary measurements. The risk of malignancy (ROM) was calculated for each classification category. The median age was 42.7 years (range: 14-85). The mean size of the lesions was 17.9 mm (range: 4-123 mm). We had 215 histopathological reports. The most common benign and malignant diagnoses were fibroadenoma and invasive carcinoma, respectively. The ROM for categories II, III, IV, and V was calculated as 3.4%, 37.5%, 95%, and 99.2% respectively. The sensitivity, specificity, positive predictive value, and negative predictive value were 96.4%, 97.2%, 98.5%, and 93.2%, respectively. The IAC Yokohama system offers a good option with which to predict underlying breast pathology using a simple and cheap procedure. However, pathologists require continuous training to ensure accurate interpretation of the slides.

Clinical application of Mycobacterium RT-PCR assay using various specimens for the rapid detection of lymph node tuberculosis: A diagnostic accuracy study.

To evaluate the diagnostic accuracy of the Capital Bio Mycobacterium real-time polymerase chain reaction assay Capital Bio assay for lymph node (LN) tuberculosis (LNTB), and to further compare the effect of different types of LN specimens on the detection capability of the test. We retrospectively analyzed the medical records of LNTB patients who met the inclusion criteria. The sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve of Capital Bio assay were calculated to evaluate its diagnostic accuracy compared with the final clinical diagnosis as reference standard. Three hundred sixty-four patients were included in the study. The overall sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve of the Capital Bio assay for LNTB were 74.4%, 100.0%, 100.0%, 34.9%, and 0.87, respectively. For the pus specimens, these values for Capital Bio assay were 93.2%, 100.0%, 100.0%, 27.3%, 0.97, respectively. For the core needle biopsy specimens, these values were 65.9%, 100.0%, 100.0%, 33.3%, and 0.83, respectively. For the fine-needle aspiration specimens, these values were 60.0%, 100.0%, 100.0%, 53.9%, and 0.80, respectively. For the tissue, these values were 59.3%, 100.0%, 100.0%, 33.3%, 0.80, respectively. The Capital Bio assay had good effective for the diagnosis of LNTB. Compared to LN fine-needle aspiration and core needle biopsy specimens and tissue specimens, pus specimens were more suitable for molecular testing and had the best diagnostic efficacy.

Chordoma: analysis of 47 fine-needle aspiration biopsy, cytologic imprint, and small biopsy specimens.

Fine-needle aspiration (FNA) and small tissue biopsy of chordoma have been reported in several small series, but no large series exists. We undertook an examination of 47 cases (with concurrent core needle biopsy in a subset) to analyze diagnostic accuracy, cytomorphology, and immunohistochemistry. Our cytopathology files were searched for examples of chordoma with histopathologic verification. FNA biopsy smears and core needle were performed using standard techniques. Forty-seven cases of chordoma were retrieved from 44 patients [M:F; 1.8:1; age range 5-81 years; mean age 55 years]. Twenty-seven presented with primary, 10 with locally recurrent, and 7 with metastatic tumors. Two aspirates were from the appendicular skeleton, 2 from the trunk, 1 from neck lymph node, and 42 aspirates (89%) from axial and peri-axial skeleton and surrounding soft tissues. Four were cytologic touch imprints while the remainder were FNA biopsy specimens. Specific cytologic diagnoses were chordoma/consistent with chordoma (44 cases, 94%), suspicious for chordoma (2), and malignant neoplasm (1). Along with a single case of benign notochordal tumor misdiagnosed as chordoma, our diagnostic accuracy was 91%. Concurrent tissue biopsy was performed in 51% of cases. Immunohistochemical staining of tumor in 29 (62%) cases showed expression of brachyury in 23 of 24 (96%) instances. Cytopathology consisted of cellular smears populated by large cells possessing enormous amounts of vacuolated and non-vacuolated cytoplasm with an abundant background myxoid/chondromyxoid stroma. FNA and small tissue biopsy specimens show a very high degree of diagnostic accuracy in recognition of chordoma.

Management of Thyroid Nodules.

Thyroid nodules are common and the prevalence varies between 4 and 7% by palpation and 19-68% by high-resolution USG. Most thyroid nodules are benign, and the malignancy rate varies between 7 and 15% of patients. Thyroid nodules are detected incidentally during clinical examination or, more often, during imaging studies performed for another reason. All detected thyroid nodules should be evaluated clinically. The main test in evaluating thyroid function is thyroid stimulating hormone (TSH). If the serum TSH level is below the normal reference range, a radionuclide thyroid scan should be performed to determine whether the nodule is hyperfunctioning. If the serum TSH level is normal or high, ultrasonography (US) should be performed to evaluate the nodule. US is the most sensitive imaging method in the evaluation of thyroid nodules. Computed tomography (CT) and magnetic resonance imaging are not routinely used in the initial evaluation of thyroid nodules. There are many risk classification systems according to the USG characteristics of thyroid nodules, and the most widely used in clinical practice are the American Thyroid Association guideline and the American College of Radiology Thyroid Imaging Reporting and Data System. Fine needle aspiration biopsy (FNAB) is the gold standard method in the evaluation of nodules with indication according to USG risk class. In the cytological evaluation of FNAB, the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is the most frequently applied cytological classification. TBSRTC is a simplified, 6-category reporting system and was updated in 2023. The application of molecular tests to FNAB specimens, especially those diagnosed with Bethesda III and IV, is increasing to reduce the need for diagnostic surgery. Especially in Bethesda III and IV nodules, different methods are applied in the treatment of nodules according to the malignancy risk of each category, these are follow-up, surgical treatment, radioactive iodine treatment, and non-surgical ablation methods.

Nondiagnostic Test Result Rates Following Thyroid Extra-Fine-Needle Aspiration.

The first Bethesda classification category of thyroid fine-needle aspiration biopsy (FNAB) is nondiagnostic (ND), which indicates that the specimen's cellularity is inadequate for evaluation. This work investigated the effect of needle diameter size on ND rates by comparing diagnostic outcomes of FNAB samples collected with 23-, 25-, and 27-gauge needles. This was a retrospective analysis of samples collected from patients undergoing FNAB between 2018 and 2021. It was conducted in an otolaryngology department in a university teaching hospital. Of the 699 aspirations, 144, 335, and 220 were performed using 23-, 25-, and 27-gauge needles, respectively. ND rates increased significantly when using 27-gauge compared with 23- to 25-gauge needles (P = .002), and a significantly lower ND rate was found for the 25-gauge needle compared with the 27-gauge needle (P = .001). Furthermore, increased nodule size was associated with reduced ND rate (odds ratio, 0.801; 95% confidence interval, 0.691-0.929). The 25-gauge needles are superior to 27-gauge needles in reducing ND rates of thyroid nodule FNAB specimens. Future prospective studies should be performed to confirm these findings.

ODP446 Where's the Nodule?: Atypical Presentation of an Occult Metastatic Papillary Thryoid Carcinoma

Abstract Papillary thyroid Carcinoma (PTC) with apparent distant metastasis but lacking a primary thyroid cancer on pre-operative ultrasonographic examination, is referred by some as occult PTC. In most cases, primary carcinomas are identified after careful pathologic examination of the specimen but in some rare cases the primary tumors were not detected. Hereby, we describe the rare case of a patient with metastatic PTC without initial visualization on imaging of primary tumor location along with inconsistent pathology results between fine needle aspiration (FNA) biopsy and gross specimen pathology results. A 60-year-old female with past medical history of Diabetes Mellitus type 2 and Hypothyroidism presenting for follow-up visit after being found with neck nodules on head and neck CT scan. Thyroid and neck Ultrasound (US) were performed finding three right irregularly shaped hypoechoic lymph nodes (LN's) measuring &amp;gt; 1 cm, concerning for metastatic disease, but no thyroid nodules were noted. Patient denies family history of thyroid cancer, and no head and neck radiation exposure. Physical examination did not reveal goiter or palpable nodules. Laboratory results: TSH: 2.95 and Total T4: 9.32, both within normal range. Cervical LN's FNA biopsy was performed, yielding results consistent with PTC tall cell variant. Chest CT scan showed suspicious lesions for pulmonary micrometastasis. Total thyroidectomy was performed and gross pathology findings showed an infiltrating, follicular variant PTC with multifocal tiny primary tumors of the thyroid, with lesions measuring up to 0.2 cm, dimension which explains why nodules could not be identified on imaging studies. LN's FNA biopsy results and thyroid pathology did not correlate. Thyroid gross pathology was clearly PTC with follicular variant, infiltrating a small area away from greatest dimension tumor, with cells with apparent dedifferentiation to tall cell cytologic features. Due to high risk of recurrence, radioactive iodine therapy was recommended as adjunctive therapy for metastatic disease and eradication of residual neck disease to be started with levels of TSH&amp;gt;30 mU/ml. Postopertative Thyroglobulin level (Tg) was adequate &amp;lt; 0. 01 ng/ml but unreliable based on above normal range antithyroglobulin antibody &amp;gt; 1000 IU/ml, which increases risk of recurrence. Whole body scan also done showing bilateral lung metastasis and small neck metastatic disease. Repeated postoperative thyroid US also demonstrated a suspicious cystic lymph node in right central neck for which FNA with saline washout of aspirate for Tg measurement was ordered. Metastatic thyroid carcinoma without primary tumor after extensive thyroid sampling is a rare but existent phenomenon that can be encountered in daily practice. Genotyping or immunostaining mestastatic lesions could help direct the Pathologist to the source of the metastasis. Patients with a higher risk of recurrence are monitored more aggressively as it is believed that early detection of recurrent disease offers the best opportunity for effective treatment. Presentation: No date and time listed

Incidence of non-diagnostic and undetermined cytologies in ultrasound-guided fine needle aspiration biopsy specimens of thyroid nodules - a single-center cohort

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

921P Application of machine learning algorithm for cytological diagnosis of thyroid cancer

The machine learning algorithm (MLA) is a promising tool for cytological diagnosis of thyroid cancer. We developed the MLA classifying human thyroid cell clusters using brightfield microscope-based color images and refractive index information-based (RI) images and evaluated the complementarity of the two types of images. Color and RI images of thyroid fine-needle aspiration biopsy (FNAB) specimen were taken using brightfield microscope and Optical Diffraction Tomography. MLA was designed to classify benign and malignant cell clusters using color images, RI images, or both. This study included 1295 thyroid cell clusters (benign: malignancy = 964: 331) obtained from 110 patients. The accuracies of MLA-classifiers using color images, RI images, and both were 99.0%, 97.5%, and 100%, respectively. In the model using color image, the correlation between the size of the nuclei and the prediction score for the probability of cancer was prominent. In contrast, the model using RI image showed high confidence when the degree of detail of the images surrounding the nuclei quantified using the Brenner gradient was high. Qualitative assessment using gradient-weighted class activation mapping and T-distributed stochastic neighbor embedding analysis also showed that the size of the nucleus was mainly used in the color image, but detailed morphological information of the nucleus was used in the RI image. MLA has great potential for diagnosing thyroid cancer based on imaging of FNAB specimens. Complementary information from color images and RI images can improve the performance of MLA.

Tuberculosis with tubercular osteomyelitis of skull

Tuberculous osteomyelitis of skull is a rare form of tuberculosis with an incidence of 0.2 – 1.3% of all skeletal tuberculosis. A 9-year-old boy presented with a history of prolonged fever, recurrent cough since 2 months before admitted and painless scalp swelling for the previous 1 month. A diagnosis of tubercular etiology was established with the rapid molecular test and histopathology of the fine needle aspiration biopsy specimen. The patient was kept on antitubercular treatment for 12 months. After 2 months treatment he responded well, with a marked resolution of symptoms and physical examination findings.