Clinical Utility of Cytology from Preoperative Percutaneous Fine Needle Aspirates of Solitary Liver Masses in 220 Dogs: A Retrospective Study (2009-2019).

When a solitary liver mass is identified in a dog, a fine-needle aspirate (FNA) is commonly employed to attempt to obtain a diagnosis. Little information is provided in the literature evaluating the sensitivity/specificity of FNA cytology for solitary liver masses. We hypothesized that liver lesion size nor the presence of cavitation would impact the success of cytological diagnosis. Medical records were obtained for 220 client-owned dogs. Inclusion criteria included preoperative abdominal imaging, percutaneous FNA of a solitary hepatic mass with cytologic interpretation by a board-certified pathologist, and a surgical biopsy or mass excision yielding a histopathological diagnosis. Six dogs (2.7%) experienced a complication after FNA, none considered severe. The agreement rate for correct cytologic diagnosis was 22.9% (49/220). Of the neoplastic masses 18.9% (35/185) were correctly diagnosed via cytology. The overall sensitivity was 60%, and the specificity was 68.6%. Neither institution (P = 0.16), lesion size (P = 0.88), cavitation (P = 0.34), or needle gauge (P = 0.20) had an association with correct diagnosis. This study demonstrates that, although there is a low risk of complications following FNA of a hepatic mass, overall success rate for correct cytologic diagnosis based on FNA was low compared to histopathologic diagnosis.

Outcomes of the Bethesda system for reporting thyroid cytopathology in community- vs. institution-performed cytology.

OBJECTIVES: Despite the important role of the community in the assessment and risk stratification of patients with thyroid nodules, evidence-based data on the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) performance in community clinics is lacking. We aim to evaluate BSRTC performance of aspirations taken in community clinics compared with primary referral center. METHODS: Patients who underwent thyroid surgery between 2013 and 2018 at our institution were divided according to the fine needle aspirations (FNA) settings: community FNA (cFNA) vs. institutional FNA (iFNA). Demographics, BSRTC results and final pathology were collected. Diagnostic values were calculated for BSRTC categories (sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV]), and were compared between the groups. RESULTS: A total of 268 nodules were included in the study; 77% (207) cFNA and 23% (61) iFNA. Patients in the community were younger (51.7 ± 15.1 vs. 56.6 years±14.8, p = 0.03) and with less epidemiology risk factors for thyroid cancer (1.9% vs 13.1%, p < 0.001). cFNA malignancy rate for BSRTC I-VI was 0%, 6.4%, 11.8%, 32.1%, 91.6% and 93.8% respectively. Best sensitivity was found for BSRTC III-VI in both groups (88% and 83%, cFNAs and iFNAs, respectively). Overall best performance was obtained for BSRTC V-VI for both groups (cfNA: 85%, 97%, 93%, 94% and 93%; iFNAs: 81%, 100%, 100%, 87% and 91%, for sensitivity, specificity, PPV, NPV and accuracy, respectively). CONCLUSIONS: Community-performed FNAs demonstrate acceptable BSRTC distribution and malignancy rates, comparable with a primary referral academic hospital. This supports the universality of the BSRTC 2017 and its recommendations also in the community.

Fine-needle Aspiration Washout Precipitation Specimens: An Acceptable Supplement to Genetic Mutation Detection of Thyroid Nodules.

Objectives: Thyroid nodules are common in adults, but only some of them are malignant. Ultrasound-guided fine-needle aspiration (FNA) is widely applied as a reliable and minimally invasive technique for evaluating thyroid nodules. However, the scarcity of FNA biopsy specimens poses a challenge to molecular diagnosis. This study aimed to evaluate the feasibility of FNA washout precipitation specimens as an effective supplement to the thyroid genetic test. Methods: A total of 115 patients with thyroid nodules were enrolled in our study. The BRAF V600E mutation status was detected in all FNA washout precipitation specimens and biopsy formalin-fixed paraffin-embedded (FFPE) specimens using an amplification refractory mutation system PCR (ARMS-PCR). All patients underwent cytological diagnoses; 79 patients also underwent surgery for histopathological analysis. Results: All the 115 samples were successfully analyzed using both FNA washout precipitation and biopsy FFPE specimens. The results showed that the BRAF V600E status detected in 96 FNA washout precipitation specimens were consistent with that in FNA biopsy FFPE specimens, including 41 BRAF V600E positive and 55 BRAF V600E negative, achieving a concordance rate of 84.4% (kappa = 0.689). Furthermore, the BRAF V600E mutation status using FNA washout precipitation specimens provided a 100.0% positive predictive value for diagnosing papillary thyroid carcinoma in patients with The Bethesda system for reporting thyroid cytopathology (TBSRTC) V. Besides, the BRAF V600E mutation status was positive in 90.9% (10/11) FNA washout precipitation specimens from patients with capsule invasion, achieving a higher overall sensitivity of 100.0%, compared with 57.1% of FNA washout precipitation specimens from patients without capsule invasion. Conclusion: These results suggested that FNA washout precipitation specimens might be a valuable supplementary sample type for detecting the BRAF V600E mutation in patients with thyroid nodules, especially with thyroid capsule invasion.

Development of a Molecular Assay for Detection and Quantification of the BRAF Variation in Residual Tissue From Thyroid Nodule Fine-Needle Aspiration Biopsy Specimens.

Importance: Thyroid cancer, predominantly papillary thyroid carcinoma (PTC), is common, but an estimated 30% of ultrasonography-guided fine-needle aspiration (FNA) biopsies of thyroid nodules are indeterminate. BRAF variation, associated with poor clinicopathological characteristics, is a useful molecular marker for diagnostics. Objective: To develop a sensitive molecular assay for BRAF V600E detection in remaining tissue of thyroid FNA biopsies to identify patients with cancer carrying a BRAF variation. Design, Setting, and Participants: This diagnostic study used tumor tissue from surgical formalin-fixed, paraffin-embedded (FFPE) specimens and residual tissue from thyroid FNA biopsies for genomic DNA extraction. FFPE specimens served as the validation set, and residual tissue from FNA biopsies served as the test set. A molecular assay was developed for accurate detection of BRAF V600E variation using locked nucleic acid (LNA) probe-based droplet digital polymerase chain reaction (dPCR), and the assay was validated by BRAF V600E immunohistochemical staining (IHC). The study was conducted between February 2019 and May 2021. Results: A total of 271 specimens, including 77 FFPE specimens (with a follow-up of 48 matched surgical specimens) and 146 residual FNA samples, were collected from 223 patients (mean [SD] age, 53.8 [15.3] years; 174 [78.0%] women; 49 [22.0%] men). The molecular assay by dPCR was first established to specifically and accurately detect and quantify wild-type BRAF and variant BRAF in DNA from human follicular thyroid carcinoma-derived FTC-133 and papillary thyroid carcinoma-derived BCPAP cells. The linearity of quantification of BRAF V600E was calculated (y = 0.7339x; R2 = 0.9996) with sensitivity at 0.02 copies/µL and reproducibility in detecting variant DNA at various dilutions(coefficient of variance in 0.3% DNA, 9.63%; coefficient of variance in 1.0% DNA, 7.41%). In validation testing, the dPCR assay and IHC staining exhibited 100% specificity in concordantly identifying BRAF V600E in PTCs (κ = 0.873; P < .001) and sensitivity of 32.0% (95% CI, 19.1% to 44.9%) in dPCR and 26.0% (95% CI, 13.1% to 38.9%) in IHC staining, with an improvement by 23.08% in dPCR compared with the IHC staining. The dPCR assay further detected BRAF V600E in 39 of 146 residual FNA specimens (26.7%). At short-term follow-up, 48 patients, including 14 of 39 patients with BRAF variation and 34 of 107 patients without BRAF variation on residual FNA specimens, underwent resection. The dPCR assay of BRAF status in the matched surgical specimens showed BRAF V600E variations in 12 patients and wild-type BRAF in 36 patients, with a high agreement to that in residual tissue of FNA specimens (κ = 0.789; P < .001). Among 14 patients with BRAF variations on residual FNA, 13 were diagnosed with PTC and 1 was diagnosed with anaplastic thyroid cancer at the thyroidectomy. Conclusions and Relevance: This diagnostic study developed a sensitive molecular assay for detection and quantification of BRAF V600E variation in residual tissue from thyroid FNA biopsies to identify patients with cancer harboring BRAF V600E in a cost-effective manner, highlighting the clinical value of molecular assay of the remaining FNA tissue in the management of thyroid nodules.

A retrospective analysis of 512 cases of breast fine needle aspiration cytology utilizing the recently proposed IAC Yokohama system for reporting breast cytopathology.

BACKGROUND: Recently the International Academy of Cytology (IAC) introduced a new reporting system for breast fine-needle aspiration cytology that classifies cytologic diagnoses into five-categories: (I) insufficient material, (II) benign, (III) atypical, (IV) suspicious of malignancy, and (V) malignant. The current study was undertaken to categorize the breast lesions utilizing the newly proposed IAC Yokohama classification system and evaluate the risk of malignancy (ROM) for respective categories and the diagnostic yield of this technique. METHODS: All FNAs of breast lesions over 2.5 years were categorized retrospectively using the newly proposed IAC Yokohama reporting system. The ROM was calculated along with sensitivity, specificity, positive and negative predictive value, diagnostic accuracy, false positive, and false-negative rate using the histological diagnosis as the gold standard. RESULTS: The 512 cases were distributed as follows: Category I (insufficient material) 7.4%, Category II (benign) 74%, Category III (atypical) 5.7%, Category IV(suspicious) 1.4%, and Category V (malignant) 11.5%. Histopathological correlation was available in 285 (55.7%) cases. The respective ROM calculated was 33.3%, 0.5%, 13.3%, 83.3%, and 100% for Category I-V. The Sensitivity, Specificity, Positive and Negative Predictive Value, and Diagnostic accuracy were 95%, 99.5%, 98.27%, 98.6, and 98.5% respectively. CONCLUSIONS: Despite previous attempts to establish a standardized diagnostic terminology, there has been a lack of a single internationally approved standardized reporting system allowing substantial diagnostic clarity and incorporating distinct diagnostic categories, each linked with a specific ROM and recommended management. This System also provides enhanced communication between pathologists and attending clinicians for the benefit of the patient.

Diagnostic accuracy of fine-needle aspiration cytology for lymphoma: A systematic review and meta-analysis.

BACKGROUND: Fine-needle aspiration cytology (FNAC) has become one of the most useful modalities for diagnosis and staging of lymphoma. However, diagnostic accuracy of this technique has been reported with varying results across several studies around the world. Hence, this meta-analysis was done to assess the accuracy of FNAC for lymphoma diagnosis. METHODS: We conducted a systematic search for all studies reporting the diagnostic accuracy of FNAC for lymphoma in the databases of PubMed Central, MEDLINE, EMBASE, MEDLINE, SCOPUS and Cochrane library from inception till January 2021. Meta-analysis was performed using STATA software "midas" package. RESULTS: Forty-seven studies with 7268 patients were included. The pooled sensitivity and specificity of FNAC for diagnosing lymphoma were 93% (95% CI, 90%-95%) and 97% (95% CI, 95%-98%), respectively. Likelihood ratio positive was 33.5 (95% CI, 18.5-60.7) and likelihood ratio negative was 0.07 (0.05-0.11) making the technique to occupy the left upper quadrant in LR scattergram indicating that FNAC can be used for confirmation and exclusion. There was significant heterogeneity with significant chi-square test and I2 statistic >75%. There was significant publication bias as per Deek's test and funnel plot. CONCLUSION: To summarize, our study found that FNAC has a vital role as a diagnostic tool for lymphoma with higher sensitivity and specificity. Further studies assessing the accuracy of FNAC on specific types of lymphoma is required.

Utility of fine needle aspiration cytology to diagnose intraoral lymphoma: 7 years study from a tertiary care center.

OBJECTIVE: Fine needle aspiration (FNA) cytology has been successfully utilized in the preoperative diagnosis of oral masses. Lymphoma involving other sites has also been diagnosed frequently on FNA. Oral cavity lymphoma (OL) is rare and is clinically indistinguishable from other lesions of the mouth. A complete excision of these may be difficult. Our experience with FNA diagnosis of 11 OLs along with histopathological correlation is reported herein in a tertiary health care setting. METHODS: In this retrospective study, clinico pathological characteristics of patients with final diagnosis of non-Hodgkin's lymphoma (NHL) were reviewed over a 7 year period. Routine cytological giemsa staining was performed in all cases along with immunocytochemistry (ICC) wherever possible. The gold standard for diagnosis of NHL was based on: (1) Histopathology and immunohistochemistry and/or (2) Flow cytometry (FC). RESULTS: A total of 11 cases were diagnosed as NHL. All showed B cell immunophenotype. Two of them were diagnosed as follicular lymphoma on histopathology. Male to female ratio was 7:4 and ranged in age from 37 to 70 years. The most common site was tonsillar fossa (N = 5), followed by hard palate (N = 3), soft palate (N = 2), and buccal mucosa (N = 1). Size ranged from 1 to 6 cm. CONCLUSIONS: Diagnosis of OLs may be hampered by its rarity and difficulties in obtaining sufficient cellularity in oral FNA but there is need for immediate and accurate diagnostic procedures, including immunohistochemical analysis to avoid delay in treatment. FNA along with ICC helps in early diagnosis of this rare entity and can also provide sample for FC.

Contribution of small tissue biopsy and flow cytometry to preoperative cytological categorization of salivary gland fine needle aspirates according to the Milan System: Single center experience on 287 cases.

BACKGROUND: Milan system for reporting salivary gland cytopathology (MSRSGC) was proposed to provide a standardized reporting system for salivary gland fine needle aspiration biopsies. Modified Menghini type semi-automatic aspiration biopsy needles provide small tissue fragments (STFs), as well as cellular smears, and immunohistochemical and molecular studies can be performed using the STFs. AIMS: We aimed to evaluate the contribution of STFs and ancillary techniques to pre-operative diagnosis of salivary gland lesions. MATERIALS AND METHODS: In this study, smears of 287 cases with histopathological correlation were re-reviewed and assigned to one of the MSRSGC categories. In the second step, histopathological and immunohistochemical findings in STFs were evaluated together with cytological findings. Final diagnoses were obtained with the inclusion of flow cytometry (FC) results when available. Risk of malignancy (ROM) was calculated for each diagnostic category. RESULTS: In the evaluation based on smears, a specific diagnosis could be obtained in 64.8% of the cases. ROMs were 0% for nondiagnostic (ND), 5.6% for non-neoplastic (NN), 55% for atypia of undetermined significance (AUS), 0.6% for benign neoplasm (BN), 27.8% for salivary gland neoplasm of uncertain malignant potential (SUMP), and 100% for suspicious for malignancy (SFM) and malignant (M) categories. With the addition of histopathological and immunohistochemical findings and FC results, a specific diagnosis could be obtained in 75.2% of the cases. ROMs were 0% for ND, 4.5% for NN, 53.8% for AUS, 0.6% for BN, 0% for SUMP, and 100% for SFM/M categories. CONCLUSIONS: STFs contribute correct categorization of salivary gland lesions. The major contribution of ancillary methods is in the SUMP category.

Utility of the Milan system for reporting salivary gland cytopathology: A retrospective 5 years study.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is an established technique for preoperative diagnosis of salivary gland lesions; however, lack of a uniform reporting system has been a handicap. The main aims of this study were to evaluate the utility of the - "The Milan System for Reporting Salivary Gland Cytopathology" (MSRSGC) and ascertain the risk of malignancy (ROM) for each category. METHODS: All salivary gland FNACs over 5 years (January 2014-December 2018) were reviewed and assigned a diagnostic category from the MSRSGC. Clinical data were taken from Cytology records. Cytodiagnosis was correlated with histopathology wherever available and ROM was calculated. RESULTS: A total of 120 salivary gland FNACs were studied. Age ranged between 5 and 85 years, male:female ratio was 2:1 and parotid was the commonest gland aspirated. Cases were reclassified as I non-diagnostic (2.5%), II non-neoplastic (15%), III atypia of uncertain significance-AUS (1.7%), IV A neoplasm benign (50%), IV B neoplasm of uncertain malignant potential (12.5%), V suspicious for malignancy (5%), and VI malignant (13.3%). Follow-up was available in 70 (58.3%) cases. The sensitivity, specificity, negative predictive value, and positive predictive value were 92.3%, 100%, 100%, and 98.27% respectively. ROM was non-neoplastic (0%), AUS (50%), neoplasm benign (0%), neoplasm of uncertain malignant potential (28.6%), suspicious for malignancy (100%), and malignant (100%). CONCLUSION: Salivary gland FNAC is a reliable diagnostic tool and the "Milan system" will further increase FNA reliability, help risk stratification, and improve patient care.

Malignancy is in the eye of the beholder: Pathologic diagnosis of challenging follicular neoplasms in the era of noninvasive follicular thyroid neoplasms with papillary-like nuclear features and immunohistochemical and molecular adjuncts.

BACKGROUND: Classification of thyroid follicular neoplasms can be challenging for pathologists. Introduction of noninvasive follicular thyroid neoplasms with papillary-like nuclear features, the utilization of immunohistochemistry, and molecular analysis are all thought to be valuable diagnostic adjuncts. Our aim was to determine whether interobserver variability for follicular neoplasms has improved since the application of these adjuncts. METHODS: One representative section from a cohort of follicular neoplasms previously proven difficult for pathologists were examined independently by 7 pathologists and assigned to 1 of 3 diagnostic categories (benign, neoplasms with papillary-like nuclear features, or malignant). This process was carried out separately 3 times: (1) after viewing hematoxylin and eosin stain slides, (2) hematoxylin and eosin stain in conjunction with immunohistochemistry, and (3) hematoxylin and eosin stain/immunohistochemistry in conjunction with molecular analysis. The interobserver variability and overall agreement were then calculated using the free-marginal kappa coefficient. RESULTS: Agreement on hematoxylin and eosin stain was 57%, with a kappa coefficient of 0.36 (minimal agreement). The agreement improved slightly with the application of immunohistochemistry (kappa coefficient = 0.49 [weak agreement] and a percentage agreement 67%). The level of agreement decreased slightly after the addition of molecular analysis (kappa coefficient = 0.43 [weak agreement] and percentage agreement 62%). CONCLUSION: Despite attempts to standardize the diagnostic criteria for neoplasms with papillary-like nuclear features and the utilization immunohistochemistry and molecular analysis, attaining pathologic consensus for difficult follicular neoplasms of the thyroid remains a challenge.

Accuracy of fine-needle aspiration cytology in the diagnosis of salivary gland masses according to the Milan reporting system and to an in-house system.

BACKGROUND: This study aims to assess in our institutional experience the accuracy of fine needle aspiration cytology (FNAC) in the diagnosis of salivary gland masses (SGM) according to the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) and to an in-house system. METHODS: The study included 189 FNACs conducted between January 2011 and December 2019. The FNACs, classified according to the in-house system, were reclassified according the MSRSGC. Taking histopathology as gold standard, the measures of diagnostic accuracy of FNAC were determined for suspicion for malignancy (SFM) and malignant categories. RESULTS: According to the in house system, FNAC diagnoses were classified as: 23 (12.2%) non-diagnostic (ND), 23 (12.2%) non-neoplastic (NN), 119 (62.9%) benign neoplasm (BN), 10 (5.2%) indefinite neoplasm (IN), 2 (1.1%) SFM, and 12 (6.4%) malignant (M). Based on the MSRSGC, there were 3 (1.5%) cases of atypia of undetermined significance (AUS) and 7 (3.7%) neoplasms of uncertain malignant potential (SUMP). The number of ND, NN, BN, SFM, and M cases were identical in the two systems. For both systems, the sensitivity, the specificity, the positive predictive value, the negative predictive value, and the accuracy for malignancy diagnosis were 77.8%, 100%, 100%, 97.6%, and 97.8%, respectively. CONCLUSION: According to the MSRGC and to our in-house reporting system, FNAC is an accurate technique for the diagnosis of malignant salivary tumors with excellent specificity and good sensitivity. However, MSRGC has the advantage of standardization of salivary gland cytology reporting.

Sternocleidomastoid tumor of infancy-Importance of cytopathological diagnosis and challenges.

OBJECTIVE: Sternocleidomastoid tumor of infancy (SCMI) is a rare, benign self-limiting condition which occurs in the perinatal period. The goal of our study is to highlight clinicoradiological and cytopathological findings in these cases. MATERIAL AND METHODS: A study was done at a tertiary level hospital, from January 2016 to December 2019. Thirteen cases were studied, out of which 11 were clinically suspected cases of SCMI tumor and two cases were clinically suspected as cervical lymph node tuberculosis which were finally diagnosed as SCMI on fine needle aspiration cytology (FNAC) evaluation. Drs. N. K., S. Z., S. S. K., and S. R. independently reviewed the original diagnosis. Clinical, ultrasonographical, and cytopathological features are highlighted along with follow-up of the cases. RESULTS: There were a total of 13 cases, out of which 11 cases were neonates and two cases were more than 1 month of age (2 months and 2.5 months). Male: female ratio was 10:3 and swelling was present more commonly on the right side of the neck. Ultrasonography predominantly showed non-cystic, bulky, and heterogenous echotexture of the sternocleidomastoid muscle. Smears were moderately cellular showing mainly singly scattered oval to spindle shaped fibroblasts along with degenerating and regenerating muscle fibers. CONCLUSION: FNAC along with adequate clinic-radiological correlation aids in early and reliable diagnosis and can help curtail complications.

Preoperative diagnostic categories of fine needle aspiration cytology for histologically proven thyroid follicular adenoma and carcinoma, and Hurthle cell adenoma and carcinoma: Analysis of cause of under- or misdiagnoses.

Cytologic diagnosis of thyroid follicular adenoma and carcinoma, and Hurthle cell adenoma and carcinoma (FACHAC) is challenging due to cytomorphologic features that overlap with other follicular-patterned lesions. This study was designed to analyze diagnostic categories (DCs) of preoperative fine needle aspiration cytology (FNAC) of histologically proven thyroid FACHACs to evaluate under- or misdiagnoses in FNAC and elucidate potential causes for such phenomena. A total of 104 thyroid nodules with preoperative FNAC which were diagnosed as FACHAC in resection specimens were included in this study. Of these, 66 cases had also undergone thyroid core needle biopsy (CNB); FNAC and CNB DCs were compared in these cases. Various cytologic and histologic parameters were compared between the nodules with different FNAC DCs. After a review of FNAC slides, DCs were re-assigned in 20 (19.2%) out of the 104 cases. Of the 66 cases with CNB diagnoses which were mostly classified as lower DCs in FNAC, 31 (47.0%) were diagnosed as suspicious for a follicular neoplasm in CNB. Cases which were underdiagnosed in FNACs were associated with lower cellularity, predominant macrofollicular pattern, absence of microfollicles arranged in trabecular pattern, and absence of transgressing vessels in cytology smears. High cellularity, microfollicles arranged in trabecular pattern, nucleolar prominence, and large cell dysplasia were more frequently found in malignancy than in benign neoplasm. In conclusion, thyroid FACHACs seem to be under- and misdiagnosed in preoperative FNAC. Innate characteristics of the nodules were associated with under-diagnosis as well as the quality of the FNAC specimens. Certain cytomorphologic features can be helpful in differentiating malignancy among FACHACs.

Excellent diagnostic performance of FNA-Tg in detecting lymph nodes metastases from papillary thyroid cancer.

Background: Thyroglobulin washout of fine needle aspiration (FNA-Tg) has proved to be useful in detecting lymph node metastases from papillary thyroid cancer; however, the influences of thyroid gland, Hashimoto thyroiditis, serum thyroglobulin (Tg) and anti-TG antibody on the diagnostic performance of FNA-Tg are controversial. Patients & methods: We retrospectively collected the FNA-Tg results of 176 preoperative or postoperative patients (356 lymph nodes) who finally were diagnosed with papillary thyroid cancer. The diagnostic abilities of FNA-Tg were evaluated and compared under different circumstances. Results: The diagnostic performance of FNA-Tg was uninfluenced irrespective of the status of thyroid gland or serum anti-TG antibody. However, high serum Tg was positively correlated with FNA-Tg (Exp(B) = 1.57; 95% CI: 1.209-2.309; p = 0.001). Conclusion: FNA-Tg was an excellent diagnostic tool, but it should be interpreted with caution only if serum Tg is higher than 10 ng/ml.

An audit of cytopathology in the oral and maxillofacial region: 18 years of experience.

INTRODUCTION: The aim of this study was to perform an audit of oral and maxillofacial specimens submitted for cytological diagnosis to verify the importance of this complementary examination. METHODS: A retrospective analysis of our institutional cytopathology database was performed over an 18-year period. Clinical information and cytological data were collected. Associations between independent variables and outcomes were assessed using the Pearson χ2 test or Fisher's test, with a 5% significance level. When available, the histological diagnosis was compared with cytological diagnosis to identify the percentage of agreement and the specificity, sensitivity and accuracy of cytology in identifying malignant neoplasms. RESULTS: A total of 1082 cases were identified, which included 65 different cytological diagnoses. Exfoliative cytology (EC) was performed in 312 cases (29.1%) and fine needle aspiration cytology (FNAC) in 770 cases (70.9%). EC was mainly employed to diagnose oral infectious diseases (P < 0.001) and FNAC to diagnose neoplasms, cystic, reactive and miscellaneous lesions (P < 0.001). Cell-block was performed in 555 FNAC cases (51.3%). Panoptic, Papanicolaou and haematoxylin-eosin staining were performed in FNAC and periodic acid-Schiff in EC (P < 0.001). In 211 cases (19.5%), the histological diagnosis was available and the percentage agreement with the cytological diagnosis was 41.2%. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy to identify malignant neoplasms were 84.6%, 100%, 100%, 77.8% and 90.0%, respectively. CONCLUSIONS: EC was mainly performed for diagnosis of infectious diseases and FNAC for diagnosis of salivary gland tumours, odontogenic lesions, reactive lesions and cervical metastasis.

Exploring the Inter-observer Agreement Among the Members of the Italian Consensus for the Classification and Reporting of Thyroid Cytology.

Classification schemes for reporting thyroid cytology of fine needle aspiration (FNA) of thyroid nodules are largely used in clinical practice, but the level of inter-observer agreement among cytopathologists is poorly acknowledged. The present study aimed to explore the inter-observer agreement among the experienced authors of the 2014 Italian Consensus for Classification and Reporting of Thyroid Cytology (ICCRTC). A stratified randomization was performed in order to obtain a sample homogeneously distributed and representative of all ICCRTC classes. Four high-experience raters were randomly selected among the extensors of the Italian consensus. They independently reviewed 60 FNA samples blindly of the initial cytological report and clinical features. Their overall agreement was evaluated according to Fleiss' kappa. The overall inter-observer agreement was moderate (κ 0.46). Specifically, a good agreement was found when the samples were consistent for malignancy (TIR5) or were not adequate for diagnosis (TIR1) (κ 0.67 and κ 0.73, respectively). A moderate agreement was present for suspicious-for-malignant category (TIR4), and a fair agreement was recorded in the two intermediate ones (TIR3A and TIR3B) (κ 0.36 and κ 0.35, respectively). For clinical purposes, the agreement was good (κ 0.74) in differentiating cases with surgical indication (TIR4/TIR5) from those in which surgery is not essential or requires limited extension (TIR3B/TIR3A/TIR2). In conclusion, the present study confirms the reliability of ICCRTC. These data represent a reference for cytopathologists using this system and are useful for the practice of clinicians and surgeons.

Discordance Between the American Thyroid Association and the American College of Radiology Guideline Systems for Thyroid Nodule Biopsy.

BACKGROUND: Previously, fine-needle aspiration biopsy was recommended for any thyroid nodule >1.0 cm in size. In 2015, the American Thyroid Association (ATA) introduced a pattern-based approach for biopsy recommendations based on size and ultrasound (US) characteristics. In 2016, the American College of Radiology (ACR) published the Thyroid Imaging Reporting and Data System, using a point-based system that assesses risk of US characteristics. METHODS: This study aims to compare recommendations for thyroid nodule biopsy between the ATA and ACR systems and identify outcomes of nodules with discordant recommendations (DRs). US characteristics, fine-needle aspiration biopsy, and surgical pathology results were evaluated for all patients with >1.0 cm thyroid nodules treated at a single tertiary-care institution from 2010 to 2018. RESULTS: Inclusion criteria were met by 1100 nodules from 687 patients; 42.8% (n = 471) had DR between the ATA and ACR guidelines. All (100%) DR nodules were not recommended for biopsy by ACR, though 53% were recommended to have follow-up. A majority (79%) of DR nodules were recommended for biopsy by ATA, with the remaining 21% recommended for follow-up. Among surgically excised DR nodules (n = 292), 10.3% (n = 30) nodules were found to be malignant, with the vast majority (90.3%) being well-differentiated carcinoma. Among malignant nodules, the ACR would not have recommended biopsy or follow-up for 26.7% (n = 8). CONCLUSIONS: The ACR classification system is more restrictive compared with the ATA system for recommending thyroid nodule biopsy. This discrepancy could result in confusion for clinicians and delay in diagnosis or therapy for patients with thyroid cancer.

Indeterminate thyroid nodules in the era of molecular genomics.

BACKGROUND: Indeterminate thyroid nodules are diagnosed in up to 30% of fine-needle aspirations and the risk of malignancy in these cases are highly variable. Consequently, managing these nodules has been a challenge. While a diagnostic thyroidectomy would help clarify the pathology, there is the risk of developing surgical-related complications for a procedure that may not have been necessary and associated high costs. Genomic testing of indeterminate thyroid nodules may help better guide management. METHODS: We present an unbiased comprehensive review of available molecular testing for classifying indeterminate thyroid nodules, as well as their strengths and limitations, with the objective to allow practitioners to choose the best testing modality for their patients. RESULTS: Molecular testing of these nodules provided a platform to help distinguish benign versus malignant nodules, providing more confidence to rule in or rule out the likelihood of thyroid cancer in indeterminate nodules. CONCLUSION: Genomic testing has evolved to more comprehensive panels to better stratify indeterminate nodules, including Hürthle cell neoplasms and noninvasive follicular neoplasm with papillary-like nuclear features. Understanding the methodology of each available test improves patient care and reduces unnecessary costs.