Deep convolutional neural network model ResNeSt for discrimination of papillary thyroid carcinomas and benign nodules in thyroid nodules diagnosed as atypia of undetermined significance.

Background: A deep convolutional neural network (DCNN) model was employed for the differentiation of thyroid nodules diagnosed as atypia of undetermined significance (AUS) according to the 2023 Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). The aim of this study was to investigate the efficiency of ResNeSt in improving the diagnostic accuracy of fine-needle aspiration (FNA) biopsy. Methods: Fragmented images were used to train and test DCNN models. A training dataset was built from 1,330 samples diagnosed as papillary thyroid carcinoma (PTC) or benign nodules, and a test dataset was built from 173 samples diagnosed as AUS. ResNeSt was trained and tested to provide a differentiation. With regard to AUS samples, the characteristics of the cell nuclei were compared using the Wilcoxon test. Results: The ResNeSt model achieved an accuracy of 92.49% (160/173) on fragmented images and 84.78% (39/46) from a patient wise viewpoint in discrimination of PTC and benign nodules in AUS nodules. The sensitivity and specificity of ResNeSt model were 95.79% and 88.46%. The κ value between ResNeSt and the pathological results was 0.847 (P<0.001). With regard to the cell nuclei of AUS nodules, both area and perimeter of malignant nodules were larger than those of benign ones, which were 2,340.00 (1,769.00, 2,807.00) vs. 1,941.00 (1,567.50, 2,455.75), P<0.001 and 190.46 (167.64, 208.46) vs. 171.71 (154.95, 193.65), P<0.001, respectively. The grayscale (0 for black, 255 for white) of malignant lesions was lower than that of benign ones, which was 37.52 (31.41, 46.67) vs. 45.84 (31.88, 57.36), P <0.001, indicating nuclear staining of malignant lesions were deeper than benign ones. Conclusions: In summary, the DCNN model ResNeSt showed great potential in discriminating thyroid nodules diagnosed as AUS. Among those nodules, malignant nodules showed larger and more deeply stained nuclei than benign nodules.

Utility of an anchored multiplex polymerase chain reaction-based fusion assay for diagnosis of soft tissue tumors in cytology.

BACKGROUND: Fine-needle aspiration specimens from soft tissue tumors are complicated by lack of tissue architecture and limited material for ancillary testing. There are little data on the feasibility of next-generation sequencing techniques for fusion detection on soft tissue cytology specimens. This study explored the role of an anchored multiplex polymerase chain reaction (PCR)-based gene fusion assay in aiding the diagnosis of mesenchymal neoplasms on cytology samples. METHODS: The laboratory information system was queried for cytology specimens that had undergone testing by anchored multiplex PCR. After exclusion of epithelial and hematolymphoid neoplasms, clinical and pathologic information was collected on the remaining cases. RESULTS: There were 1609 cytology specimens tested with anchored multiplex PCR. Of these, 48 (3%) were cytology specimens from mesenchymal tumors. Anchored multiplex PCR was positive for a reportable fusion transcript in 14 of 48 cases (29%); there was no fusion detected in 32 cases (67%), and there was insufficient tissue for analysis in two cases (4%). The detectable fusion partners included ALK (n = 4), STAT6 (n = 4), EWSR1 (n = 3), and one each of SS18, YAP1, and PHF1. Of the cases in which a fusion partner was detected, eight of 14 were disease-defining on cytology preparation, and six of 14 provided molecular confirmation of a metastatic focus of a previously diagnosed tumor. CONCLUSIONS: The anchored, multiplex PCR-based gene fusion assay is a powerful orthogonal tool in helping diagnose mesenchymal neoplasms on cytology specimens. The material obtained for cytologic analysis yields sufficient quality/quantity of tissue in the majority of cases tested.

The impact of nodule size on malignancy risk in indeterminate thyroid nodules.

Background: The association between malignancy risk and nodule size in indeterminate thyroid nodules (ITNs) remains controversial. Thus, we aimed to explore the impact of nodule size as a predictor of cancer in patients with ITNs. Methods: This cross-sectional study assessed 113 patients who underwent surgical intervention for ITNs, comparing two groups based on nodule size (≥4 or <4 cm). The correlation between nodule size and malignancy risk was examined. Other variables of interest included demographics, thyroid-stimulating hormone (TSH) levels, type of surgery, and ultrasound features. Results: Of the 113 patients, 88.5% were aged <55 years, 76.1% were women, and 65.5% had nodules <4 cm. Mean nodule size was 3.4±2.3 cm. There was no significant correlation between malignancy risk and nodule size (P=0.55). An association was observed between <4 cm nodules and elevated TSH levels (P=0.03) and between ≥4 cm nodules and the presence of hypervascularity (P=0.04). Nodules <4 cm were more likely to have extrathyroidal extension, lymphovascular invasion, and positive margins than those ≥4 cm; however, this was not significant. Conclusions: Our findings showed no association between nodule size and malignancy risk, suggesting that size alone is not a predictor of cancer development. Further prospective studies are required to confirm these results.

Analysis of flow cytometry data from ultrasound-guided lymph node biopsies with two types of needles.

BACKGROUND: In this study, we combined two techniques, ultrasound-guided needle biopsy and flow cytometry (FCM), to explore their value in patients with enlarged lymph nodes. METHODS: We compared the results of 198 needle biopsies on FCM and pathology. Forty-two were done by (fine needle aspiration, FNA), and the remaining 156 with (core needle biopsy, CNB), in 36 of 156 patients, a FNA was performed in the same lymph node after completion of the CNB. Except for five types of pathological entities, the rest were differentiated only detected or undetected tumours as the outcome distinction. RESULTS: Among the 198 needle biopsies, 13 were inadequate specimens, while the remaining 185 had pathological findings, including 47 benign and 138 neoplastic findings. Thirty-six patients underwent puncture with both FNA and CNB, both needles produced identical results by FCM, but more cells were obtained by FNA. Among the pathologically positive results, there were 23 missed diagnoses in FCM, in contrast, evidence of tumours was observed in the FCM images of 15 needle biopsies that reported benign or findings that were inconsistent with pathology, and the final diagnosis was consistent with the FCM in 10 cases. FCM detected haematolymphoid tumours with a sensitivity of 87.8% and a specificity of 91.9%. CONCLUSION: The combination of FCM and ultrasound-guided lymph node needle biopsy can quickly provide guidance for clinical decision-making. We recommend that all lymph node needle biopsies be sent for FCM, the specimen can be obtained by the last puncture with FNA.

The advent of the first electric driven EUS-guided 17 gauge core needle biopsy - A pilot study on subepithelial lesions.

BACKGROUND AND AIMS: This pilot study aimed to evaluate safety and tissue sampling from subepithelial lesions (SEL) in the upper gastrointestinal tract with a novel electric motor driven endoscopic ultrasonography (EUS)-guided 17-gauge (G) size core needle biopsy (CNB) instrument. METHODS: An investigator-led prospective open label, performance and safety control study, including seven patients (female n = 4, median 71 y, range 28-75) with a determined SEL (median size 30 mm, range 17-150 mm) in the upper digestive tract (stomach n = 6, duodenum n = 1) were eligible and later followed up 14 days after index procedure. All investigations were completed according to protocol with three FNB 22-G passes with four fanning strokes and two EndoDrill® 17-G passes with three fanning strokes. RESULTS: Quality of samples as 'visible pieces' (>5 mm): FNB (n = 5/7) (fragmented/blood imbibed n = 1, poor tissue quantity n = 1) compared with 17-G CNB (n = 7/7). Histological result which led to final diagnosis (leiomyoma n = 2, adenocarcinoma n = 1, schwannoma n = 1, neuroendocrine tumour n = 1, desmoid tumour n = 1 and gastrointestinal stromal tumour (GIST) n = 1) could be obtained with the 17-G CNB instrument in all seven patients. FNB technique reached correct diagnosis in six patients. No serious adverse event were recorded. CONCLUSIONS: By using an electric driven 17-G biopsy device, a true cylinder of core tissue can be obtained in one single puncture from the area of interest reducing the need for a second sampling. The absolute benefit of EUS-guided CNB is that the sample can be handled and histologically prepared in the same manner as standard percutaneous core needle sample, e.g., breast and prostate cancer.

Diagnostic interobserver agreement for thyroid fine-needle aspirates: Effects of reviewer experience and molecular diagnostics.

OBJECTIVES: Few cytologically indeterminate thyroid fine-needle aspirations (FNAs) harbor BRAF V600E. Here, we assess interobserver agreement for The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) category III (atypia of undetermined significance [AUS]) FNAs harboring BRAF V600E and contrast their features with those harboring non-BRAF V600E alterations, with attention to cytopathology experience. METHODS: Seven reviewers evaluated 5 AUS thyroid FNAs harboring BRAF V600E. To blind reviewers, cases were intermixed with 19 FNAs falling within other TBSRTC categories and in which genetic alterations other than BRAF V600E had been identified (24 FNAs total). Interobserver agreement against both "index" and most popular ("mode") diagnoses was calculated. Four additional BRAF V600E cases were independently reviewed. RESULTS: Reviewers included 3 trainees and 3 American Board of Pathology (board)-certified cytopathologists. Board-certified cytopathologists, whose experience ranged from 2 to more than 15 subspecialty practice years, had known AUS rates. BRAF V600E was identified in 5 of 260 (2%) AUS FNAs. Interobserver agreement was higher among cytopathologists with more experience. Mode diagnosis differed from index diagnosis in 6 of 11 cases harboring RAS-like alterations; mode diagnosis was AUS in 4 of 5 BRAF V600E FNAs. CONCLUSIONS: Atypia of undetermined significance of thyroid FNAs harboring BRAF V600E is uncommon yet relatively reproducible, particularly among pathologists with experience. It is advisable to sequence BRAF across V600 in such cases.

Determination of axillary lymph node status by fine-needle aspiration: preoperative axillary staging vs. postoperative surveillance for breast cancers.

Background: Despite the common use of ultrasound (US)-guided fine-needle aspiration (FNA) for axillary node (AN) in breast cancer patients, only a limited number of studies are available regarding the diagnostic performance of AN-FNA according to the suspicion level based on US findings. This study compares the outcomes of US-guided AN-FNA in breast cancer patients, differentiating between those undergoing staging and surveillance. Methods: A cross-sectional retrospective study with retrospective analysis was conducted on 767 consecutive AN-FNA procedures performed in 2017 at Samsung Medical Center in Seoul, with 654 for staging and 113 for surveillance in breast cancer patients. The radiologists performed axillary US and the specific finding was prospectively classified into the AN-reporting and data system (AN-RADS) category 3-5 before FNA. The malignancy rate of each category was evaluated. The chi-square test, with or without Bonferroni correction, or Fisher's exact test was used to compare the malignancy rates between the staging and surveillance groups for each category. Results: Among the 767 AN-FNAs, 424 (55.3%) were malignant. The malignancy rate was significantly higher in the staging group (59.5%) than in the surveillance group (31.0%, P<0.0001). The distribution of AN-RADS categories differed between the groups (P=0.015), with 4A being the most common. The malignancy rates in categories 3, 4A, 4B, 4C, and 5 were as follows: 5.6%, 36.0%, 77.4%, 87.7%, and 98.4% in the staging group, and 0.0%, 9.7%, 53.3%, 88.9%, and 100% in the surveillance group. The malignancy rate was significantly different between the two groups only in category 4A (P=0.0001). Conclusions: AN-FNA according to AN-RADS category appears to be an appropriate method for determination of axillary nodal status. Overall malignancy rate of AN-FNA in breast cancer patients was higher in the staging group than in the surveillance group. According to the suspicion level, the difference between two groups was significant only in category 4A.

Comparison of ultrasound risk stratification systems for pediatric thyroid nodules.

Background: There is currently insufficient data to validate adult-based US risk stratification systems (RSSs) for the identification of malignant thyroid nodules in a pediatric population. Methods: From October 2016 and May 2023, 173 thyroid nodules of pediatric patients (age ≤ 18 years) with definitive pathology results and ultrasound (US) examination within 1 month before surgery or fine-needle aspiration (FNA) biopsy in our institution were enrolled in this study. The clinical and US characteristics of these nodules were retrospectively reviewed and categorized according to the ACR-TIRADS, C-TIRADS, and ATA guidelines. The diagnostic performance of US-based FNA criteria (original and simulating) of the three guidelines in thyroid cancer detection was estimated. Results: The three RSSs had similar AUC according to the categories(0.849-0.852, all P > 0.05). When combined with the original FNA criteria of the three RSSs to manage the nodules, the FNA rate of ACR-TIRADS and C-TIRADS were significantly less than ATA guidelines (53.18% vs. 64.63%, P < 0.05, and 52.60% vs. 64.63%, P < 0.05). The missed malignancy rate (MMR) and unnecessary FNA rate (UFR) of ATA guidelines (50.00%, 35.85%) was highest among the three RSSs, followed by the C-TIRADS (37.80%, 19.57%) and the ACR-TIRADS (37.04%, 19.57%). When nodules < 1 cm with the highest category in each RSS biopsied, that is when using the simulating FNA thresholds, the MMR was reduced overall (all P < 0.001), without a change in the UFR (all P > 0.05). All the three RSSs showed a substantial improvement in accuracy and malignant detection rate (all P < 0.05). Conclusion: The ACR-TIRADS, C-TIRADS, and ATA guidelines showed high missed malignancy rates when using their original recommended FNA criteria. When nodules < 1 cm with the highest category in each RSS biopsied, the missed malignancy rate of each RSS was decreased. Decreasing the FNA thresholds for highly suspicious malignant nodules may therefore be an effective means of managing malignant thyroid nodules in pediatric patients.

Risks of malignancy in the major nongynecologic cytopathology reporting systems: Critiques and discussions.

The ever-increasing popularity of standardized systems for reporting cytopathology has led in part to much attention to and importance of the risk stratification schemes, especially the risks of malignancy (ROMs), which are associated with the different diagnostic categories and upon which recommendations for clinical management are based. However, it is well known that the ROM calculations are based on retrospective reviews of the existing literature, representing a heterogeneous patient population, and are plagued by significant biases and variations. Statistically, the ROM represents the post-test probability of malignancy, which changes with the test result and with the prevalence of malignancy (or pretest probability) in an individual practice setting and individual patient presentation. Therefore, the clinical utility of the ROM is questioned and likely needs a second look in the nongynecologic cytopathology reporting systems. In this communication, the authors discuss the status of the ROM estimates according to the most commonly used nongynecologic reporting systems, including for thyroid, salivary glands, and others, highlighting similarities and differences with a focus on the limitations of ROM estimates and their application in clinical practice.

Endoscopic Ultrasound-Guided Fine-Needle Biopsy Versus Aspiration for Tissue Sampling Adequacy for Molecular Testing in Pancreatic Ductal Adenocarcinoma.

BACKGROUND AND AIMS: There is limited literature on sample adequacy for molecular testing in pancreatic ductal adenocarcinoma obtained via endoscopic ultrasound (EUS) fine-needle aspiration (FNA) versus EUS fine-needle biopsy (FNB). We aimed to compare these two modalities regarding sample adequacy for molecular and genomic sequencing. METHODS: We reviewed all patients with pancreatic ductal adenocarcinoma who underwent EUS at Saint Luke's Hospital from 2018 to 2021. The patients were categorized based on the method of EUS tissue acquisition, specifically FNA or FNB. A comprehensive evaluation was conducted for all cases by cytotechnologists. RESULTS: Out of 132 patients who underwent EUS-guided biopsies, 76 opted for FNA, 48 opted for FNB, and 8 opted for a combination of both. The average number of passes required for FNB and FNA was 2.58 ± 1.06 and 2.49 ± 1.07, respectively (p = 0.704), indicating no significant difference. Interestingly, 71.4% (35) of FNB-obtained samples were deemed adequate for molecular testing, surpassing the 32.1% (26) adequacy observed with FNA (p < 0.001). Additionally, 46.4% (26) of FNB-obtained samples were considered adequate for genomic testing, a notable improvement over the 23.8% (20) adequacy observed with FNA (p = 0.005). CONCLUSION: Although the number of passes required for cytologic diagnosis did not differ significantly between EUS-FNB and EUS-FNA, the former demonstrated superiority in obtaining samples adequate for molecular testing. Tumor surface area and cellularity were crucial parameters in determining sample adequacy for molecular testing, irrespective of the chosen tissue acquisition modality.

Rapid on-site evaluation improves diagnostic performance of fine-needle aspiration cytology for salivary lesions: Comparison of data from two cancer centers in southern China.

OBJECTIVES: To evaluate the diagnostic performance of Milan system for reporting salivary gland cytopathology (MSRSGC) in two southern China tertiary cancer centers and investigate the impact of rapid on-site evaluation (ROSE) on FNAC performance. MATERIALS AND METHODS: Five hundred and forty-nine patients who underwent FNAC for salivary lesions with surgical follow-up from two centers were enrolled in this retrospective cohort study. All slides were recategorized using MSRSGC after consensus on diagnostic criteria for each category. The diagnostic performance of FNAC for salivary lesions was evaluated and compared and the impact of ROSE on FNAC performance was analyzed. RESULTS: The distribution of cases per category based on the MSRSGC criteria in the whole series was as followed: ND 49 (8.9%), NN 76 (14.4%), BN 262 (47.7%), AUS 20 (3.6%), SUMP 43 (7.8%), SM 21 (3.8%), M 78 (14.2%). The SUMC series had significantly more ND distributions than JXCH did (16.2% vs. 0, p = .000). Risk of malignancy for each category in the total series was as followed: 42.9% for ND, 9.2% for NN, 3.8% for BN, 30.0% for AUS, 23.3% for SUMP, 81.0% for SM, and 94.9% for M. When ND and AUS/SUMP were excluded, the sensitivity, specificity, PPV, NPV, and accuracy were 84.0%, 97.1%, 89.9%, 95.1%, and 94.0%, respectively; sensitivity, specificity, PPV, NPV, and accuracy were comparable between the two centers. CONCLUSIONS: FNAC using MSRSGC provides a good tool in preoperative evaluation for salivary lesions in southern China. ROSE improves its diagnostic performance by reducing the ratio of the ND category.

Thyroid storm triggered by thyroid nodule fine needle aspiration biopsy: a case report.

Background: Thyroid storm is a potentially fatal thyrotoxicosis triggered by an event, such as manipulation of the thyroid gland, acute iodine load, trauma, or infection. Prior to deciding on fine needle aspiration (FNA) biopsy, patients who have been diagnosed with hyperthyroidism or low thyroid stimulating hormone and multinodular goiter (MNG) should be imaged via radionuclide thyroid scan. Case Description: We present a case of a 62-year-old female patient with history of MNG, who had thyrotoxicosis on presentation due to medication noncompliance and was found to have Graves' disease. Computed tomography scan without intravenous iodine contrast injection showed a heterogeneously appearing and notably enlarged thyroid gland with a 6.2 cm × 5.8 cm right thyroid lobe and 5.5 cm × 5.0 cm left lobe. There was a resultant narrowing of the trachea measuring 6 mm in the transverse dimension at its narrowest point. Further evaluation with dedicated ultrasound of the thyroid showing bilateral MNG with coarse calcifications as well as a notable left thyroid cyst measuring 1.6 cm × 1.2 cm × 2.3 cm, isoechoic, with smooth margins. The patient was started on methimazole 40 mg/day, cholestyramine 4 mg four times per day, prednisone 20 mg/day, saturated solution of potassium iodide 50 mg three times daily, and propranolol for heart rate control. Another service recommended FNA biopsy of the right 3 cm thyroid nodule. Two days after undergoing an FNA, she experienced a thyroid storm, requiring emergent total thyroidectomy as a life-saving procedure. Conclusions: FNA is rarely needed in the case of a hyperfunctioning thyroid nodule, as it can be seen on radionuclide thyroid scan. However, when executed, a euthyroid state needs to be achieved before attempting to perform an FNA. Total thyroidectomy is warranted in a hyperthyroid state in an emergent setting without ample time for medical therapy to be effective, as seen in our reported case.

[Molecular and other ancillary tests proposed by The Bethesda system for reporting thyroid cytopathology 2023]. / Les tests moléculaires et autres techniques ancillaires en cytologie thyroïdienne selon Bethesda 2023.

For the first time the 2023 version of The Bethesda System for Reporting Thyroid Cytology dedicates a whole chapter (chapter 14) to ancillary studies almost exclusively represented by molecular testing. The latest data reported bring some evidence that molecular testing could help to optimize the diagnostic performance of « indeterminate ¼ categories (AUS and NF). Other studies suggest a promising role to guide the management of suspicious of malignancy and malignant categories. Indeed, the recognition of prognostic and predictive biomarkers analyzed on cytological samples, regardless of how it is collected, has progressed thanks to advances in our knowledge of molecular abnormalities of thyroid tumors. The chapter 14 is presented here highlighting the current and emerging roles of « in-house ¼ and commercialized molecular testing as presented by TSBRTC.

Fine-needle aspiration biopsy of axillary lymph nodes: A reliable diagnostic tool for breast cancer staging.

BACKGROUND: Pathologic evaluation of sentinel lymph node biopsy (SLNB) samples is crucial for axillary staging in patients newly diagnosed with breast cancer. Patients with pathologic evidence of nodal metastasis scheduled for upfront surgery typically also undergo axillary lymph node dissection (ALND). Although SLNB is the gold standard method for detecting nodal metastasis, axillary lymph node fine-needle aspiration biopsy (FNAB) utility has not been thoroughly explored. METHODS: Ultrasound-guided axillary lymph node FNAB samples along with concurrent ipsilateral breast tissue samples were searched and reviewed. The control group included histologic findings of axillary dissection or intraoperative SLNB results. RESULTS: A total of 354 axillary lymph node FNAB samples with matched histology were included. Of these, 187 (52.8%) were positive for metastatic carcinoma of breast origin; 143 (40.4%) were negative for metastasis; 12 (3.4%) showed atypical cells; six (1.7%) were suspicious for metastasis; and six (1.7%) were nondiagnostic because of a lack of lymphoid tissue and malignant cells. Of the 143 negative FNAB samples, 22 (15.4%) were positive on either intraoperative SLNB or ALND. When only the positive and negative FNAB samples were accounted for (n = 330; 93.2%), overall diagnostic sensitivity and specificity were 89.4% and 99.2%, respectively. CONCLUSIONS: Although axillary SLNB is the standard procedure for detecting nodal metastasis of breast origin, axillary lymph node FNAB appears to be a suitable alternative in a significant proportion of patients. A standard SLNB should be performed in cases of negative axillary lymph node FNAB findings, particularly nodes with abnormal imaging findings.

The Asian Thyroid Working Group, from 2017 to 2023.

The Asian Thyroid Working Group was founded in 2017 at the 12th Asia Oceania Thyroid Association (AOTA) Congress in Busan, Korea. This group activity aims to characterize Asian thyroid nodule practice and establish strict diagnostic criteria for thyroid carcinomas, a reporting system for thyroid fine needle aspiration cytology without the aid of gene panel tests, and new clinical guidelines appropriate to conservative Asian thyroid nodule practice based on scientific evidence obtained from Asian patient cohorts. Asian thyroid nodule practice is usually designed for patient-centered clinical practice, which is based on the Hippocratic Oath, "First do not harm patients," and an oriental filial piety "Do not harm one's own body because it is a precious gift from parents," which is remote from defensive medical practice in the West where physicians, including pathologists, suffer from severe malpractice climate. Furthermore, Asian practice emphasizes the importance of resource management in navigating the overdiagnosis of low-risk thyroid carcinomas. This article summarizes the Asian Thyroid Working Group activities in the past 7 years, from 2017 to 2023, highlighting the diversity of thyroid nodule practice between Asia and the West and the background reasons why Asian clinicians and pathologists modified Western systems significantly.

Sclerosing Angiomatoid Nodular Transformation of the Spleen: A Report of Rare Case and Literature Review.

Sclerosing angiomatoid nodular transformation (SANT) is a benign vascular lesion of the spleen with uncertain etiology. It predominantly affects women between the ages of 30 and 60 years. Clinically, it is asymptomatic or can cause abdominal pain, but usually discovered incidentally on imaging, which can identify a mass but may not provide a definitive diagnosis. In uncertain vascular lesions, there is always a risk of spontaneous rupture of large vessels and the potential for spreading malignancy. Hence, the final diagnosis is rendered on microscopy after splenectomy. A middle-aged female came to the clinic complaining of abdominal pain. Radiology showed a solid splenic mass and the patient underwent splenectomy. Gross examination showed a 3 cm white firm mass with focal hemorrhage. Microscopy revealed multiple nodules of variable sizes surrounded by fibrosclerotic stroma. The nodules showed round to slit-like vascular spaces with numerous red blood cells. The internodular stroma consisted of dense fibrous tissue with scattered plump myofibroblasts and lymphoplasmacytic inflammatory cells. These distinctive features lead to the diagnosis of SANT. SANT possesses characteristic histologic features with distinctive immunohistochemistry (IHC). IHC reveals three different types of vessels within the nodules as follows: (1) small veins (CD34-, CD31+, CD8-), (2) sinusoids (CD34-, CD31+, CD8+), and (3) capillaries (CD34+, CD31+, CD8-). All three types of vessels are negative for CD21/CD35 and CD68. Hemangioma and littoral cell angioma are two frequent vascular tumors in the spleen that should be considered differential diagnoses. Both lesions lack the microscopic features of SANT and have only a single type of vessel. The vessels in hemangioma are (CD31+, CD34+, CD8-), while in littoral cell angioma they are (CD31+, CD34-, CD8-, CD21+, CD68+). There are no specific clinical or radiologic findings for SANT. It is important to recognize these characteristic features and to differentiate them from other benign and malignant lesions, such as angiosarcoma. A thorough histopathologic examination and IHC are helpful in making the correct diagnosis.

Real-World Diagnostic Accuracy of the On-Site Cytopathology Advance Report (OSCAR) Procedure Performed in a Multidisciplinary One-Stop Breast Clinic.

Fine-needle aspiration (FNA) cytology has been widely used for the diagnosis of breast cancer lesions with the objective of differentiating benign from malignant masses. However, the occurrence of unsatisfactory samples and false-negative rates remains a matter of concern. Major improvements have been made thanks to the implementation of rapid on-site evaluation (ROSE) in multidisciplinary and integrated medical settings such as one-stop clinics (OSCs). In these settings, clinical and radiological examinations are combined with a morphological study performed by interventional pathologists. The aim of our study was to assess the diagnostic accuracy of the on-site cytopathology advance report (OSCAR) procedure on breast FNA cytologic samples in our breast OSC during the first three years (April 2004 till March 2007) of its implementation. To this goal, we retrospectively analyzed a series of 1820 breast masses (1740 patients) radiologically classified according to the American College of Radiology (ACR) BI-RADS lexicon (67.6% being either BI-RADS 4 or 5), sampled by FNA and immediately diagnosed by cytomorphology. The clinicoradiological, cytomorphological, and histological characteristics of all consecutive patients were retrieved from the hospital computerized medical records prospectively registered in the central information system. Histopathological analysis and ultrasound (US) follow-up (FU) were the reference diagnostic tests of the study design. In brief, we carried out either a histopathological verification or an 18-month US evaluation when a benign cytology was concordant with the components of the triple test. Overall, histology was available for 1138 masses, whereas 491 masses were analyzed at the 18-month US-FU. FNA specimens were morphologically nondiagnostic in 3.1%, false negatives were observed in 1.5%, and there was only one false positive (0.06%). The breast cancer prevalence was 62%. Diagnostic accuracy measures of the OSCAR procedure with their 95% confidence intervals (95% CI) were the following: sensitivity (Se) = 97.4% (96.19-98.31); specificity (Sp) = 94.98% (92.94-96.56); positive predictive value (PPV) = 96.80% (95.48-97.81); negative predictive value (NPV) = 95.91% (94.02-97.33); positive likelihood ratio (LR+) = 19.39 (13.75-27.32); negative predictive ratio (LR-) = 0.03 (0.02-0.04), and; accuracy = 96.45% (95.42-97.31). The respective positive likelihood ratio (LR+) for each of the four categories of cytopathological diagnoses (with their 95% CI) which are malignant, suspicious, benign, and nondiagnostic were 540 (76-3827); 2.69 (1.8-3.96); 0.03 (0.02-0.04); and 0.37 (0.2-0.66), respectively. In conclusion, our study demonstrates that the OSCAR procedure is a highly reliable diagnostic approach and a perfect test to select patients requiring core-needle biopsy (CNB) when performed by interventional cytopathologists in a multidisciplinary and integrated OSC setting. Besides drastically limiting the rate of nondiagnostic specimens and diagnostic turn-around time, OSCAR is an efficient and powerful first-line diagnostic approach for patient-centered care.

Use of molecular testing results to analyze the overuse of atypia of undetermined significance in thyroid cytology.

INTRODUCTION: The suggested atypia of undetermined significance (AUS) rate for thyroid fine-needle aspiration biopsies is 10% or less. Prompted by a high institutional AUS rate, we examined using molecular testing results (MTR) as a potential quality metric tool to reduce the AUS rate. We correlated MTR with AUS cytologic findings, surgical pathology follow-up, and individual pathologist AUS rates. MATERIALS AND METHODS: Demographic data, cytologic diagnoses, MTR, and surgical pathology diagnoses were retrospectively obtained. MTR were classified as either positive or negative. AUS rates and MTR proportions were compared among pathologists. The cytomorphologic features of 143 AUS cases were assessed and correlated with MTR. RESULTS: Between 2017 and 2022, 710 of 3247 thyroid fine-needle aspirations were classified as AUS, with a yearly average rate of 22% (range = 19%-26%). AUS cases included: 331 (47%) with architectural atypia; 204 (29%) with oncocytic (Hürthle cell) atypia; 99 (14%) with combined architectural and cytologic atypia; and 76 (10%) with isolated cytologic atypia. Most AUS cases with molecular testing had negative MTR (360/492, 73%). AUS with cytologic atypia had higher positive MTR risk (logarithm of odds ratio = 1.27, 95% credible interval [0.5-2.04], P = 0.001). The average positive MTR rate by pathologist was 21.5% (range 0%-35%); higher positive MTR rates had better correlation with subsequent neoplastic/malignant histologic diagnoses. The MTR sensitivity for malignant disease was 89% and the negative predictive value was 91%. CONCLUSIONS: MTR analysis reveals the importance of cytologic atypia as a determinant of malignancy risk in AUS cases. Periodic analysis of MTR data alongside individual pathologist AUS rates can help refine diagnostic criteria and potentially reduce AUS overuse.

Prediction of cytology-histology discrepancy when Bethesda cytology reports benign results for thyroid nodules in women: with special emphasis on pregnancy.

Objectives: Benign category of Bethesda classification is generally well known to carry a false-negative rate of 0-3%. The current study was designed to investigate the rate of false-negative cytology in patients who underwent thyroidectomy for presumably benign thyroid diseases. Predictive risk factors for false results and malignancy were evaluated along with cytology-histology discrepant cases.Materials and methods: Females who underwent thyroidectomy between May 2014 and December 2022 were included. Demographics, ultrasound (US) features, fine-needle aspiration (FNA) diagnosis, surgical indications and outcomes, final histology reports, risk factors, and malignancy rate were recorded. Cytology-histology discrepant cases were further evaluated for interpretation errors and risk factors. Statistical analyses were performed using Fisher's exact and Mann-Whitney U tests.Results: Of 581 women with a benign thyroid disease who underwent thyroidectomy, 91 was diagnosed as incidental carcinoma (15.6%) and most was T1a (4.9 ± 2.7 mm, 95.6%). Final histology reports revealed mostly papillary carcinoma (93.4%). Predictors of malignancy such as age, family history, previous radiation exposure, and iodine-deficient diet did not help in risk stratification (p > 0.05, for each). However, FNA taken during pregnancy was determined as a risk factor (n = 7, 7.6%, p < 0.05) since it may cause a delay in diagnosis. Cytology-histology discrepant cases were seen to be mostly due to sampling errors (45%, p < 0.05), followed by misinterpretations (37.3%, p < 0.05). There was no reason for discrepancy in 17.5%, and this was linked to inherent nature of thyroid nodule with overlapping cytologic features. Best identifiable risk factor for misinterpretation was pregnancy as well (n = 5, 14.7%, p < 0.05).Conclusions: Risk of malignancy in a presumably benign thyroid disease should not be ignored. Radiology-cytology correlation by an experienced dedicated team may help in decreasing sampling errors. Physiologic changes caused by pregnancy may shade malignant transformation in thyrocytes, and it would be appropriate to be cautious about benign FNA taken during this period.

Indeterminate Thyroid Nodules: From Cytology to Molecular Testing.

Thyroid cancer is the most common malignancy of the endocrine system. Fine-needle aspiration (FNA) biopsy of thyroid nodules has become the gold standard procedure, in terms of cost and efficacy, for guiding clinicians towards appropriate patients' management. One challenge for cytopathologists is to accurately classify cytological specimens as benign or malignant based on cytomorphological features. In fact, with a frequency ranging from 10% to 30%, nodules are diagnosed as indeterminate. In recent years, the mutational landscape of thyroid tumors has been extensively described, and two molecular profiles have been identified: RAS-like (NRAS, HRAS, and KRAS mutations; EIF1AX mutations; BRAF K601E mutation; and PPARG and THADA fusions) and BRAFV600E-like (including BRAFV600E mutation and RET and BRAF fusions). The purpose of this review is to discuss the latest molecular findings in the context of indeterminate thyroid nodules, highlighting the role of molecular tests in patients' management.