Histopathology Follow-up Research Articles

ThyroSeq v3 for Bethesda III and IV: An institutional experience.

The ThyroSeq v3 genomic classifier is a commercial molecular test that examines a wide spectrum of genomic alterations in a thyroid fine-needle aspiration (FNA) sample and reports test results as either negative or positive. The authors report their institutional experience with ThyroSeq v3. Thyroid FNA specimens diagnosed as either atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) (Bethesda category III [Bethesda III] according to The Bethesda System for Reporting Thyroid Cytopathology) or follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) (Bethesda IV) that had ThyroSeq v3 results available from December 2017 through October 2019 were retrieved for analysis. FNA diagnoses were correlated with ThyroSeq v3 results and follow-up histopathology. In total, 415 cases (AUS/FLUS, n = 251; FN/SFN, n = 164) were retrieved: 294 (71%) were reported as ThyroSeq v3-negative, and 121 (29%) were reported as ThyroSeq v3-positive. The benign call rate (BCR) of ThyroSeq v3 for AUS/FLUS (82%; 206 of 251 cases) was significantly higher (P < .001) than that for FN/SFN (BCR, 54%; 88 of 164 cases). Histopathologic follow-up was available for 127 cases (ThyroSeq v3-positive, 96; ThyroSeq v3-negative, 31), of which 57 were benign and 70 were malignant (including noninvasive follicular thyroid neoplasm with papillary-like nuclear features). The negative predictive value of ThyroSeq v3 was significantly higher for AUS/FLUS (99.5%) than for FN/SFN (95.4%; P < .0294), given malignancy rates of 10% for AUS/FLUS and 30% for FN/SFN. Forty-five unique combinations of genetic alterations were detected in the operated ThyroSeq-positive cases, and there were only 5 false-negative cases, comprised of 4 low-risk neoplasms. The high BCR of ThyroSeq v3 for AUS/FLUS prevents surgery in a majority of patients. The ThyroSeq v3 genomic classifier reveals the complexity of the genetic signature of indeterminate nodules.

Endoscopic ultrasound-guided fine needle aspiration cytology diagnosis of upper gastrointestinal tract mesenchymal tumors: Impact of rapid onsite evaluation and correlation with histopathologic follow-up.

Mesenchymal tumors (MTs) of upper gastrointestinal tract (UGIT) can show morphologic overlap thus posing a diagnostic challenge. This study evaluated the role of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) cytology in the diagnosis of UGIT-MTs and impact of rapid onsite evaluation (ROSE). We retrospectively search our electronic database between January 2001 and August 2019 for cases that underwent EUS-FNA for a submucosal/or intramural upper GI tract mass forming lesions. Data pertinent to immunostain expression in UGIT-MTs was also collected. We identified 139 cases, of which 72 cases had subsequent surgical resection. The cytologic diagnoses included nondiagnostic, negative, atypical, suspicious for neoplasm and positive for neoplasm (PFN) in 11, 7, 11, 10, and 100 cases, respectively. Diagnosis of PFN was rendered in 51 of 69 cases with ROSE (74%) and in 49 of 70 cases without ROSE (70%). However, the cases with ROSE had a higher percentage of cases being precisely classified than without ROSE (86% vs 61%, P < .05). On comparison of cytologic cases with cell block (CB) (n = 118) and without CB (n = 21), ROSE was performed in 67 (57%) and 2 (10%) cases, respectively (P < .01). All the cases with diagnosis of PFN were confirmed on subsequent surgical resection. EUS-FNA has a diagnostic yield of 72% for UGIT-MTs. ROSE could improve diagnostic performance by further classifying MTs, probably via securing adequate lesional material for cell block for additional ancillary testing and precise diagnosis.

Utility of fine needle aspiration cytology in head and neck lesions and its correlation with histopathology- a study in tertiary care hospital

Background: Fine Needle Aspiration Cytology has rapidly gained acceptance due to the easy accessibility of target sites and minimally invasive nature. It is a very simple, quick, cost-effective method of sampling alternative to the time consuming complicated and invasive excision biopsy. The study aimed to access the utility of fine needle aspiration cytology in the diagnosis of various head and neck lesions and also to establish the diagnostic accuracy between the cytological and histopathological diagnosis.&#x0D; Materials and Methods: A retrospective observational study of 380 cases of FNACs on head and neck swellings performed in various age groups in the Department of Pathology of a tertiary care hospital from January 2018 to December 2019. &#x0D; Results: Out of 380 patients, the maximum number of cases were seen in the thyroid (40.8%), followed by lymph nodes (39.5%), skin, soft tissue, miscellaneous (10.8%) and salivary glands (8.9%). Benign and non-neoplastic cases outnumbered (88.1%) the malignant (10.8%) cases. Histopathological follow-up was available in 28 (7.4%) cases among which 25 (89.3%) cases were consistent with the cytodiagnosis. The sensitivity, specificity, and diagnostic accuracy were evaluated to be 80%, 94.4%, and 89.3% respectively.&#x0D; Conclusions: The majority of the cases of head and neck swellings were seen in the thyroid followed by lymph nodes, skin, soft tissue, miscellaneous, and salivary glands. In thyroid, colloid goiter and papillary carcinoma were the commonest benign and malignant lesions respectively. In the lymph node, reactive lymphadenitis, and metastatic squamous cell carcinoma were the commonest benign and malignant lesions respectively.

Role of Diffusion-Weighted and Chemical Shift Magnetic Resonance Imaging in Differentiation of Benign and Malignant Spinal Fractures

Atraumatic spinal compression fractures are common clinical problem. Differentiating benign osteoporotic fractures from pathological fractures due to malignant/metastatic lesions affects the management and prognoses in patients with known extraspinal malignancy. The objective of the research was to assess the role of conventional magnetic resonance imaging sequences with diffusion-weighted imaging and chemical-shift imaging in differentiating benign and malignant acute spinal compression fractures.&#x0D; Materials and Methods. The study included 40 patients with acute spinal compression fractures. Patients were evaluated using magnetic resonance imaging with diffusion-weighted imaging and chemical-shift imaging to differentiate benign etiology from malignant one. The results obtained were compared with histopathological follow-up for 6 months for definite clinical diagnoses.&#x0D; Results. No significant difference was noted in signal characteristics of benign and malignant fractures on T1, T2 and short-tau inversion recovery. However, posterior element involvement, soft tissue component and post-contrast enhancement were seen more frequently in malignant fractures (p&lt;0.05). On diffusion-weighted images, 77.8% of malignant fractures were hyperintense and 59.1% of benign fractures were hypointense (p&lt;0.05). The mean apparent diffusion coefficient value was 0.81 ± 0.19 for malignant and 1.24 ± 0.24 for benign fractures (p&lt;0.5). The mean signal intensity ratio for malignant fractures was 0.91 ± 0.125, whereas the signal intensity ratio for benign fractures was 0.64 ± 0.096 (p&lt;0.001).&#x0D; Conclusions. Signal characteristics on T1, T2 and short-tau inversion recovery sequences do not differentiate benign from malignant fractures; however, posterior element involvement, soft tissue and post contrast enhancement help in differentiating the etiology. Diffusion-weighted imaging and apparent diffusion coefficient values, as well as using chemical shift imaging further improve the diagnostic accuracy of magnetic resonance imaging.

Fine-needle aspiration cytomorphology of papillary thyroid carcinoma with NTRK gene rearrangement from a case series with predominantly indeterminate cytology.

Neurotrophic tyrosine kinase receptor (NTRK) rearrangement has been reported in a subset of papillary thyroid carcinoma (PTC) cases. Little is known about the cytomorphologic features of NTRK-rearranged PTC. We report an institutional series of 13 fine-needle aspiration (FNA) specimens of NTRK-rearranged PTC with a predominantly indeterminate cytology diagnosis. NTRK3 or NTRK1 rearrangements were detected on FNA or surgical specimens by next-generation sequencing. The 13 patients had a median age of 18 years; 10 patients were female and 3 patients were male. In 10 (77%) cases, cytology was indeterminate, and histopathologic follow-up was predominantly the follicular variant of PTC (n=8 [62%]), mostly infiltrative subtype. Of 12 FNA specimens available for review, a predominant loosely cohesive group pattern was the most commonly encountered architectural pattern (n=5 [41%]), followed by single cell (n=3 [25%]), thick cord (n=2 [17%]), and microfollicular pattern (n=2 [17%]). Background lymphocytic thyroiditis was observed in 9 cases. At the cellular level, the cytoplasm was moderate and granular, occasionally vacuolated. Classic PTC nuclear features (eg, nuclear enlargement, elongation, grooves, and nuclear membrane irregularity) were present but were often focal and subtle. Chromatin was often granular. Intranuclear pseudoinclusions were absent or rare. Our study demonstrates that most cases of NTRK rearrangement lack classic PTC cytomorphologic characteristics. Loosely cohesive groups and single cells with granular, sometimes vacuolated cytoplasm and subtle nuclear features are often seen on FNA specimens. Recognizing these characteristics may be helpful to preoperatively prompt molecular testing, including NTRK rearrangement analysis.

Impact of the Milan System for Reporting Salivary Gland Cytology on risk assessment when used in routine practice in a real-time setting

Several retrospective studies across the world have validated the role of the Milan System for Reporting Salivary Gland Cytology (MSRSGC) in improving communication between pathologists and clinicians. In this study, we evaluated the applications of MSRSGC in a real-time setting for 2 years. All salivary gland lesions that underwent fine-needle aspiration (FNA) from January 2018 to December 2020 were categorized according to MSRSGC guidelines. The risk of malignancy (ROM) was calculated for each category and compared with the ROM proposed by MSRSGC and recent retrospective studies. A total of 160 FNA of salivary gland lesions were categorized as: nondiagnostic (ND) 30 (18%), non-neoplastic (NN) 7 (10.6%), atypia of undetermined significance (AUS) 5 (3.1%), benign neoplasm (BN) 59 (36.8%), salivary gland of uncertain malignant potential (SUMP) 21 (13%), suspicious for malignancy (SM) 3 (1.84%), and malignant (M) 25 (15.6%). Histopathologic follow-up was available for 94 (57.5%) cases. The ROM for each category was ND 54%, NN 0%, AUS 66%, BN 0%, SUMP 37.56%, SM 100%, and M 100%. With strict adherence to the diagnostic criteria and MSRSGC guidelines, a ROM of 100% in SM and M categories and a ROM of 0% in NN can be achieved in a real-time setting. The high ROM in the ND category in our study highlights the value of repeat FNA/biopsy for this category. High ROM for AUS indicates the tendency to classify high-grade tumors as AUS, calling for refinement in its criteria.

The importance of risk of neoplasm as an outcome in cytologic-histologic correlation studies on thyroid fine needle aspiration.

The introduction of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) altered the practice of thyroid pathology and reduced the risk of malignancy (ROM) associated with the indeterminate categories in the Bethesda system for reporting thyroid cytopathology (TBSRTC). It has been proposed that the evaluation of the risk of neoplasm (RON) is important in cytologic-histologic correlation studies. A total of 5224 thyroid aspirates were performed at our institution during an 8-year period. Of the 1475 cases (28%) with surgical follow-up, the histologic diagnoses comprised benign non-neoplastic (BNN, n = 669), follicular adenoma (FA, n = 188), NIFTP (n = 42), papillary microcarcinoma (PMC) (n = 223), and malignant neoplasm excluding PMC (n = 353). The RON was calculated to include neoplasia with low risk biologic behavior (FA, NIFTP, PMC) and malignant neoplasms. In contrast, the ROM was reserved for malignant neoplasms excluding PMC. The RON for each TBSRTC category was: nondiagnostic (ND) 38.3%, benign 20.9%, atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) 63.2%, follicular neoplasm or suspicious for follicular neoplasm (FN/SFN) 83.9%, suspicious for malignancy (SFM) 94%, and malignant 100%. The ROM excluding PMC was: ND 14%, benign 1.6%, AUS/FLUS 17.8%, FN/SFN 28.4%, SFM 84.4%, and malignant 99.5%. The RON and ROM support the recommended management guidelines from TBSRTC for all categories, except for FN/SFN. Histopathologic follow-up of FN/SFN aspirates in our study contain a very high rate of neoplasm (83.9%), which might support the management preference of conservative surgery.

Abdominal extranodal lymphoma detection: positron emission tomography/computed tomography can help

BackgroundLymphoid neoplasms that present with masses are broadly referred to as lymphomas, and they can be classified to two main groups: Hodgkin’s (HL) and non-Hodgkin’s lymphoma (NHL); they are mainly characterized by enlargement of lymph nodes (nodal disease) although any organ in the body can be involved in different settings of the disease (extranodal disease). Adequate staging, which has a direct impact on prognosis, is essential to properly plan therapy. Stage IV disease with extranodal dissemination should be treated by long-term systemic chemotherapy.By adding the metabolic changes to the conventional CT morphologic changes, combined positron emission tomography (PET) and computed tomography (CT) may offer clinically useful addition in staging of lymphomas and detection of extranodal lesions.ResultsThe study included thirty nine patients, with forty-eight extranodal sites with lymphomatous infiltration, twenty-four males (61.5%), and fifteen females (38.4%). The patients showed forty-eight extranodal abdominal lymphomatous infiltration.The study included twelve gastric lymphomatous lesions (25%), twelve splenic lymphomatous lesion (25%), three ileo-caecal lymphomatous lesions (6.25%), three patients (6.25%) with skin infiltration, three adrenal lymphomatous lesions (6.25%), three patients with hepatic lymphoma, and twelve bone marrow infiltrations (25%).The most accurate SUV max cutoff value among studied cases was 3.5, the highest SUV max value noted was 21 in gastric lesions, and the lowest SUV max noted was 4.1 in adrenal lesions.Confirmation of PET/CT results was done by histopathological assessment and post-management follow-up.ConclusionPET/CT study is an effective tool for evaluation of extranodal lymphomas. PET/CT fusion images can affect the clinical management plan by detection of extranodal lymphomas with lymphoma staging modification.

Role of nuclear morphometry in diagnosis of salivary gland neoplasms.

Fine needle aspiration cytology is an important diagnostic tool in salivary gland cytopathology. However, cytology of salivary gland neoplasms shows diversity with morphological overlap, heterogeneity and subjective variability, posing diagnostic challenge. Nuclear cytomorphometric image analysis turns the subjective criteria into quantitative parameters, which may aid not only in differentiating between benign and malignant tumours but also can aid in categorising challenging cases with morphological overlap. A retrospective analysis of Papanicolaou stained fine needle aspirate smears from 50 patients with salivary gland neoplasms, with available follow-up histopathology, was performed. The aspirates were categorised in to three neoplastic categories of Milan system for reporting salivary gland cytology (MSRSGC) that is benign neoplasm, salivary gland neoplasm with uncertain malignant potential, and malignant. The smears were subjected to cytomorphometric image analysis using Image Pro Software (version 10). Each nucleus was analysed for 13 parameters including aspect ratio, intensity, diameter, perimeter, roundness, area, Feret diameter, circularity, radii, Fournier description and chromatin texture characteristics such as margination, heterogeneity and clumpiness. The data obtained was compared through relevant statistical methods. The comparative morphometric data obtained for parameters using ANOVA, for the three categories showed statistically significant P values (<0.001). The post hoc test (Games-Howel) test also showed significant P values (<.001). Cytomorphometric image analysis is an important tool in diagnosis of salivary gland neoplasms and can improve the diagnostic accuracy for better treatment and improved prognosis. However, more studies with larger sample size may be needed in future for further affirming its role.

Utility of fine needle aspiration cytology (FNAC) in diagnosis of papillary lesions of the breast

Background: Diagnosis of lesions of the breast using Cytological screening is difficult. Understanding the common cytological features of papillary lesions of the breast can be useful for the diagnosis. Aims and objectives:To determine the utility of Fine Needle Aspiration Cytology (FNAC) in the diagnosis of papillary lesions of the breast Materials and methods: A retrospective study was performed from January 2010 to December 2015 in the cytology section, Department of Pathology of a tertiary care and referral hospital including patients diagnosed as papillary lesion on FNAC. Eight four cases were found (includes 44 cases which had histopathology follow-up, 36 cases which didn’t had follow-up), 4 cases were removed because of non-availability of slides. Thus, a total of 44 breast aspirates and their corresponding histology were reviewed. All the observations were done on total 44 cases. Results:Papillary Neoplasms on FNAC (n= 33): 13 cases (29.54%) were histologically confirmed as papillary neoplasms. All 13 cases (100%) showed true papillae with fibrovascular cores. 76% showed presence of columnar cells. 4 were benign and 9 malignant. Dyscohesion and severe atypia was only seen in malignant neoplasms. 20 cases were non papillary lesion on histopathology. Out of the 20 cases, 11 cases (55%) were infiltrating duct carcinoma (IDC), 4 were fibroadenomas (FA), 3 fibrocystic disease and one each was ductal carcinoma in situ (DCIS) and lobular carcinoma. Presence of papillaroid fragments and columnar cells was the most common cause for false positive diagnosis. Papillary Neoplasms Not Suspected Cytologically (n=11): In 5 cases cellularity was scanty and unsatisfactory for opinion. Missing fibrovascular cores in the aspirate was the cause of false negative diagnosis. The overall incidence of false positive was 25% and false negative was 13.75%. Sensitivity of FNAC to diagnose papillary lesions was 54.1%.Conclusion: Cytodiagnosis of papillary lesions is challenging and identification of true fibrovascular cores is essential for accurate diagnosis.

Salivary gland fine-needle aspiration cytology with the application of the Milan system for risk stratification and histological correlation: A retrospective 6-year study.

The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is based on risk stratification. We presented our experience with fine-needle aspiration cytology (FNAC) for the diagnosis of salivary glands lesions by applying the MSRSGC categorization to the cytological diagnoses, and determined risk of malignancy (ROM) for each category. Fine-needle aspiration cytology of salivary gland lesions performed over a 6-year period was retrieved. FNAC results were retrospectively categorized according to the MSRSGC criteria, and correlated with corresponding histologic follow-up. ROM for each diagnostic category was calculated. A total of 208 FNAC of salivary gland lesions were reviewed and retrospectively categorized as: non-diagnostic (ND) 23 (11%), non-neoplastic (NN) 54 (26%), atypia of undetermined significance (AUS) 10 (4.8%), benign neoplasms (BN) 77 (37%), salivary gland of uncertain malignant potential (SUMP) 13 (6.3%), suspicious for malignancy (SM) 7 (3.4%), and malignant (M) 24 (11.5%). Histopathological follow-up was available for 84 of 208 cases (40.4%). Overall concordance rate between FNAC and histology was 78.8%. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated as 93.3%, 94.6%, 82.4%, and 98.2%, respectively. Diagnostic accuracy to distinguish benign from malignant disease was 94.4%. ROM for each category was ND 0%, NN 0%, AUS 75%, BN 2.2%, SUMP 28.6%, SM 50%, and M 100%. Fine-needle aspiration cytology continues to be an accurate diagnostic tool for most salivary gland neoplasms showing classical morphologic features. However, difficult cases with unusual or overlapping features will occur. In these situations, the use of MSRSGC risk-stratification could be helpful to define appropriate management.

MON-498 Thyroseq V3 GC for Bethesda III and IV: An Institutional Experience

Background:Molecular testing of thyroid nodules classified as indeterminate on fine-needle aspiration (FNA) is used for patient management. ThyroSeq® v3 genomic classifier is a commercially available test that examines a wide spectrum of genomic alterations in a thyroid FNA sample based on algorithmic analysis and reports test results as either negative (including currently negative) or positive. This study reviews our institutional experience with Thyroseq® V3 to distinguish between benign disease versus cancer in thyroid nodules diagnosed as Bethesda III or IV on cytology.Methods:Thyroid nodules with Bethesda III or IV cytology diagnoses and available Thyroseq® V3 results from 12/17 to 8/19 were retrieved from the pathology database. Cytopathology diagnoses were correlated with molecular testing and histopathology.Results:416 cases (Bethesda III n=252, Bethesda IV n=164) were retrieved: 295 (71%) were reported as Thyroseq® V3 negative and 121 (29%) as positive. The 82.1% (207/252) benign call rate (BCR) of Thyroseq® v3 for Bethesda III was significantly higher (p<0.001) than that for Bethesda IV, BCR 54% (88 /164). Histopathologic follow-up was available for 128 cases (96 ThyroSeq® v3 positive, 32 ThyroSeq® v3 negative): 57 benign and 71 malignant (including NIFTP). For Bethesda III and IV diagnoses respectively, the test demonstrated 91.7 % (95% Cl 73%-99%) and 91.5% (95% Cl 80%-98%) sensitivity, 94% (95% Cl 90%-97%) and 82.4% (95% Cl 74%-89%) specificity, 99% (95% Cl 96%-99%) and 95% (95% Cl 89%-98%) negative predictive value and 63% (95% Cl 50%-74%) and 70.5% (95% Cl 61%-79%) positive predictive value, given malignancy rates 10% Bethesda III; 32% Bethesda IV. 45 unique combinations of genetic alterations were detected in the 96 operated ThyroSeq® v3 positive cases—34 combinations (76%) were present in <2 cases and only 3 combinations occurred 7 or more cases. Forty-six (48%) nodules had RAS mutations, either combined with other mutations 31% (23/30, 77% malignant) or alone, 17% (10/16, 63% malignant), followed byTHADA/IGF2BP3 gene fusion changes,11.5% (10 /11 malignant). Three cases with BRAF mutations (1 V600E, 1 K601E, 1 K601N) were malignant. Copy numbers alterations alone were present in 10 (5/ 10 malignant) and the gene expression profile alone was positive in 5 cases (all malignant). Mutations that were associated with benign pathology were PTEN, DICER1, E1F1AX and TP53. There were 6 false negative cases, 5 low risk cancers by American Thyroid Association criteria and 1 NIFTP.Conclusion:The high BCR of Thyroseq® v3 for Bethesda III category avoids surgery for majority of patients. A more comprehensive mutational and fusion panel reveals the complexity of the genetic signature of indeterminate nodules. Future larger and likely multicenter studies will be required to define the associated cancer risk and potential prognosis associated with adjunct molecular testing.

HPV detection rates and histopathologic follow-up of patients with HSIL cytology in a large academic women’s hospital laboratory

High risk (hr) human papillomavirus (HPV) testing has been proposed as a possible replacement for Papanicolaou (Pap) cytology for cervical screening. The aim of the present study was to assess the hrHPV detection rates using 3 available Food and Drug Administration-approved HPV assays in patients with high-grade squamous intraepithelial lesion (HSIL) cytology results and to correlate the cervical screening test results with the immediate histopathologic findings. Cases with positive HSIL ThinPrep cytology findings, concurrent hrHPV testing results, and histopathologic follow-up results obtained within 6 months of the Pap/HPV co-testing were identified from July 2010 to April2018. A total of 943 HSIL Pap tests were identified with adjunctive hrHPV co-testing, and hrHPV was detected in 883 (93.6%) of these 943 cases. Cervical intraepithelial neoplasia ≥2 (CIN2+) lesions were diagnosed in 71.5% of patients, including 3.2% with invasive squamous cell carcinoma (SCC). In all hrHPV testing platforms, the detection rate for CIN2+ was significantly greater for the patients with positive HPV testing (72.7%) than for those with negative HPV testing (53.4%). However, CIN2+ lesions, including 3 cases of SCC, were found in 24 of 45 women (53.4%) with HSIL Pap and negative HPV testing results. The risk of CIN2+ histopathologic findings was significantly greater for patients with hrHPV-positive HSIL results. However, a subset of patients with HPV-negative HSIL results were found to have CIN2+ lesions, including SCC. The long-term effects of primary HPV screening on cervical cancer incidence, stage, and prognosis remain uncertain.

Preoperative Role of RAS or BRAF K601E in the Guidance of Surgery for Indeterminate Thyroid Nodules.

RAS and K601E BRAF mutations are not a reliable indicator of malignancy in fine-needle aspirations (FNA) of thyroid indeterminate cytologic nodules. We aimed to evaluate the histologic characteristics, the risk of malignancy associated with such mutations in FNA and their potential interest for preoperative clinical management of nodules. We evaluated 69 indeterminate thyroid nodules with RAS or K601E BRAF mutations with available histopathologic follow-up. All FNA specimens were indeterminate according to the thyroid Bethesda system. Diagnosis of malignant, benign or indolent neoplasms was classified according to 2017 WHO classification. Carcinoma, NIFTP (noninvasive follicular thyroid neoplasm with papillary-like features) and WDTUMP (well-differentiated tumor of uncertain malignant potential) were considered "surgical," as they require surgical excision. Adenoma was considered "non-surgical." The risk of malignancy and the risk of "surgical disease" were evaluated. Pathologic evaluation of the 69 mutated nodules demonstrated benign, indolent and malignant histology in 17 cases (25%), 21 cases (30%) and 31 cases (45%), respectively. The risk of malignancy was 45%, and the risk of surgical disease was 75%. The majority of carcinomas were a follicular variant of papillary thyroid carcinoma. On follow-up, there have been no recurrences to date. Preoperative RAS or BRAF K601E mutations detection in cytologic indeterminate thyroid nodules carries a high risk of surgical disease and may benefit from surgical management. Most surgical lesions harboring those mutations are low-risk tumors, which may be in favor of an initial lobectomy.

Value of MRI in the differential diagnosis of uveal melanoma and other intraocular masses in adults

Objective To compare MRI findings of uveal melanomas and other intraocular masses in adults and to evaluate the optimal MRI features for the differential diagnosis. Methods The MRI data of 254 patients with intraocular masses confirmed by histopathologic or clinical follow-up results from March 2005 to December 2015 in Beijing Tongren Hospital, Capital Medical University was analyzed retrospectively. A total of 128 patients with uveal melanoma and 126 patients with other intraocular masses were enrolled. MRI findings of the masses including the location, shape, margin, signal intensity on T1WI and T2WI compared to the gray matter and vitreous body, homogeneity and degree of enhancement of the mass, secondary retinal detachment, height, and ratio of basal diameter to height were compared between uveal melanoma and other intraocular masses by χ2 test or independent t test. The logistic regression analysis was performed to identify the most discriminating MRI features. The diagnostic performance of different predictive models was analyzed by receiver operating characteristic (ROC) curve. The model of multiple parameters was established by logistic analysis, and the diagnostic efficacy was evaluated. Results The location, shape, margin, signal intensity on T1WI and T2WI compared to the gray matter and vitreous body, homogeneity and degree of enhancement of the mass, secondary retinal detachment, height and ratio of basal diameter to height were significantly different between the uveal melanoma and other intraocular masses (all P<0.05). The results of logistic regression analysis showed that the signal intensity on T1WI and T2WI compared to the gray matter, height, shape, location, degree of enhancement of the mass, and secondary retinal detachment were associated with higher likelihood of uveal melanoma. The mass with hypointense on T2WI (compared with gray matter) was the best MRI feature in the differential diagnosis of uveal melanoma and other intraocular masses (odds ratio 12.237), with the accuracy of 86.2%. The diagnostic accuracy of low signal on T2WI and high signal on T1WI (compared with gray matter) was significantly higher than those of vitreous (Delong test, P<0.001). The sensitivity, specificity and accuracy of the combination of height, degree of enhancement, T1WI and T2WI signal compared to the gray matter were 90.6%, 92.1% and 96.1%, respectively. The diagnostic performance of combination features was higher than that of each single sign (P<0.001). Conclusion MRI features including the signal intensity on T1WI and T2WI compared to the gray matter, height, shape, degree of enhancement of the mass, and secondary retinal detachment are helpful in the differential diagnosis between uveal melanoma and other intraocular masses. In addition, the gray matter as the reference is superior to the vitreous body in the evaluation of the signal intensity of intraocular masses. Key words: Melanoma; Eye neoplasms; Magnetic resonance imaging; Diagnosis, differential

Correlation of histopathology of patients with negative human papillomavirus (Hpv) and high-grade liquid-based cytology results following introduction of primary Hpv cervical screening in Australia

Aim: The study correlates histopathology in patients with negative human papillomavirus (HPV) and high-grade liquid-based cytology (LBC) testing following the introduction of primary HPV screening for cervical cancer in Australia. Methods: Retrospective audit of cervical samples submitted to Capital Pathology, ACT, between 1 December 2017 and 30 April 2019. HPV testing performed by Roche Cobas 6800 (Roche Diagnostics). HPV and LBC results, patient age and histopathology follow-up within 6 months of cytology was documented. Low grade cytology included low-grade intraepithelial lesion (LSIL) and possible LSIL. High-grade included all other abnormal cytology results. Results: A total of 365 cases of HPV-negative, abnormal cytology were identified: 297 of 365 (81.4%) were low-grade and 68 of 385 (18.6%) were high-grade. 14 of 68 (20.5%) cases with HPV-negative and high-grade cytology had histopathology within 6 months: 3 endometrioid adenocarcinoma, 2 endometrial malignancy, 1 adenocarcinoma (endocervical), 2 serous adenocarcinoma, 2 squamous cell carcinoma, 3 high-grade intraepithelial lesion (HSIL) and 1 adenosquamous carcinoma. The median age was 64 years. Discussion: This study identified 14 patients with HPV-negative, high-grade cytology confirmed on histopathology. This data may support co-testing of patients in their sixth decade as an alternative to primary HPV testing.

Milan System for Reporting Salivary Gland Cytopathology- An Experience from Western Indian Population.

Introduction:Fine-needle aspiration cytology (FNAC) can be challenging to provide a precise diagnosis in salivary gland cytopathology due to diversity of lesions and cytomorphological convergence between the tumors and within the same tumor of salivary gland. The recently proposed Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) provides a risk stratification-based classification system with an intrinsic risk of malignancy (ROM) for each diagnostic category, which aims to furnish useful information to the clinicians. This study was undertaken to evaluate the diagnostic utility and validity of MSRSGC.Methods and Material:In this retrospective study, FNAC done for all salivary gland lesions over a period of two years were retrieved. All cases were categorized according to MSRSGC and correlated with histopathological follow-up, wherever available. ROM was calculated for each category.Results:The cases belong to following categories: non-diagnostic (1.27%), non-neoplastic (30.38%), atypia of undetermined significance (5.06%), benign neoplasm (46.84%), salivary gland neoplasm of uncertain malignant potential (1.27%), suspicious for malignancy (1.27%), and malignant (13.92%). Out of 79 cases, 50.63% had follow-up. The ROM were 0% for category II and IVa, 50% for category III, and 100% for category IVb, V, and VI. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were recorded as 77.78%, 100%, 100%, 91.3%, and 93.33%, respectively.Conclusions:Application of MSRSGC has immense value for standardization of reporting of salivary gland FNAC. Our data corresponds to the studies done worldwide and recommends the use of MSRSGC for future diagnostic purposes.

Utility of cell block as an adjunct to liquid-based cytology for diagnosing papillary thyroid carcinoma.

Although liquid-based cytology (LBC) has gained popularity among clinical laboratories, it is unclear whether it is equivalent to conventional smears for making a definite diagnosis of papillary thyroid carcinoma (PTC). The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) suggests a definite diagnosis of PTC is preferred when there are at least one of three features (papillary architecture, psammomatous calcifications, and frequent pseudonuclear inclusions) plus other typical cytomorphological findings. This study evaluated whether an additional cell block (CB), prepared from the residual LBC material, could help improve the diagnosis of PTC. A total of 62 cases with both ThinPrep LBC and CB preparations and histopathological follow-up of PTC were retrieved between November 2016 and March 2019. The ThinPrep LBC and CB slides were reviewed separately to identify any papillary architecture, psammomatous calcifications, or pseudonuclear inclusions for diagnosing PTC. Among the 51 cases with cytological diagnosis of PTC in the LBC+CB slides, the CB provided additional diagnostic information in 15 cases, which were initially diagnosed as suspicious for PTC based on the LBC slides alone. This information included papillary architecture (n=11), psammomatous calcification (n=1) and pseudonuclear inclusions (n=5). The number of specimens in the 51 cases containing at least one of the three features increased from 42 (LBC) to 51 (LBC+CB). The accuracy for diagnosing PTC increased from 58.1% for LBC alone to 82.3% for the LBC+CB examination. An adjunctive CB preparation may improve the LBC technique for diagnosing PTC.

Fine-Needle Aspiration Cytology of Salivary Gland Lesions: A Revised Classification Based on "Milan System"-4years Experience of Tertiary Care Cancer Center of South India.

Background:Fine-needle aspiration cytology plays role in preoperative diagnosis of any salivary gland mass lesions. Because of heterogeneity of salivary gland lesions and cytomorphology overlap, a uniform 6-tier Milan classification proposed which could be helpful in better communication of reports for patient's management.Methods:Study included 4 years (2011–2015) retrospective data retrieval from cytology department of our Institute, which is a tertiary care cancer center of South India. Histopathology correlation was done wherever possible.Result:Total 253 cases were studied. Histopathological follow-up was available in 115 cases. Cases were categorized as nondiagnostic (1.58%), nonneoplastic (13.43%), benign (30%), atypia (0.8%), and suspicious for malignancy and malignant cytology (51.8%). The risk for malignancy was high for suspicious for malignancy and malignant cytological categories ranged from 96–100%. The sensitivity, specificity, and accuracy for diagnosing malignancy varied from 86.76%, 93.75%, and 89%, respectively.Conclusion:Risk stratification approach in classifying salivary gland cytology aspirate as per Milan system provides a standardized reporting and better communication to clinician.

Diagnostic utility of thyroid fine needle aspiration cytology using The Bethesda System for Reporting Thyroid Cytopathology: A one year prospective study

Introduction: Fine Needle Aspiration Cytology (FNAC) is the first line diagnostic procedure for evaluating thyroid lesions. The present study was carried out to assess the diagnostic utility of thyroid FNAC using The Bethesda System for Reporting Thyroid Cytopathology. Materials and Methods: It was a one year prospective study conducted in the Department of Pathology, Government Medical College, Jammu and included all patients presenting with thyroid swelling referred to this department. The thyroid fine needle aspirates from these patients were classified into six categories according to The Bethesda System for Reporting Thyroid Cytopathology. The Risk of Malignancy was calculated for each Bethesda category by follow-up histopathology. Sensitivity, Specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) were also calculated using histopathology diagnosis as gold standard. Results: Thyroid fine needle aspirates from a total of 300 patients were classified according to Bethesda system as Nondiagnostic (ND)- 17cases(5.67%), Benign- 264cases(88%), Atypia of Undetermined Significance (AUS)- 1case(0.33%), Follicular Neoplasm(FN)-6cases(2%), Suspicious for malignancy(SFM)- 0case( 0%) and Malignant- 12cases(4%). The Risk of Malignancy was Nondiagnostic- 50%, Benign-0%, AUS-0%, FN-50%, Suspicious for malignancy-not possible, Malignant-100%. Sensitivity, Specificity, PPV and NPV were 100%, 100%, 100%, 100% (FN excluded); 80%, 100%, 100%, 96% (FN included as benign); and 100%, 95.83%, 83.33%, 100% (FN included as malignant). Conclusion: The present study concludes Bethesda system to be an effective reporting system for thyroid cytology, FNAC to be a sensitive and specific test for evaluation of thyroid lesions and FNAC using Bethesda guidelines is useful in risk assessment of thyroid nodules thereby guiding appropriate management. Keywords:Thyroid fine needle aspiration cytology, Bethesda system, Risk of malignancy, Sensitivity, Specificity.