Preoperative Cytology Research Articles

The Paris System for reporting urinary cytology improves the negative predictive value of high-grade urothelial carcinoma

BackgroundThe Paris System (TPS) for reporting urinary cytology differs from conventional systems (CS) in that it focuses on the diagnosis of high-grade urothelial carcinoma (HGUC). This study investigated the impact of TPS implementation on the diagnostic accuracy of HGUC by comparing it with our institutional CS.MethodsA total of 649 patients who underwent transurethral resection of bladder tumor (TURBT) between January 2009 and December 2020 were included in this study. Our institution adopted TPS to report urinary cytology in February 2020. The diagnostic accuracy of HGUC in preoperative urinary cytology was compared with the presence or absence of HGUC in resected specimens of TURBT before and after TPS implementation.ResultsAfter implementing TPS in urinary cytology, 89 patients were reviewed and compared with 560 patients whose urinary cytology was diagnosed by CS. TPS and CS for detecting HGUC had 56.0% and 58.2% sensitivity, 97.8% and 91.2% specificity, and 93.3% and 87.9% positive predictive values, respectively. There were no significant differences between TPS and CS in terms of sensitivity, specificity, and positive predictive value for HGUC (P = 0.83, 0.21, 1.00). On the other hand, the negative predictive value for HGUC using TPS was 80.0%, which was significantly higher than that of CS (66.4%, P = 0.04) The multivariate logistic regression analysis indicated that not using TPS was one of the independent predictive factors associated with false-negative results for HGUC (odds ratio, 2.26; 95% confidence interval, 1.08–4.77; P = 0.03).ConclusionIn instances where urinary cytology is reported as negative for HGUC by TPS, there is a low probability of HGUC, indicating that TPS has a potential diagnostic benefit.

Molecular testing in the diagnosis and management of thyroid malignancy: a feasibility study

Abstract Background NHS England’s reorganization of genomic testing has provided an opportunity to explore molecular testing as part of thyroid nodule diagnostics and the routine postoperative histology. Aim Routine molecular testing in an NHS service has not previously been explored. This study aims to evaluate whether (1) there is sufficient material to perform this on an FNAC in cytologically indeterminate nodules (2) what the yield is from indeterminate nodules (3) whether post-operative testing is feasible and (4) whether management is altered. Methods This in an ongoing feasibility study in a UK tertiary institution commenced in January 2021. Data until May in presented. Two groups are enrolled: those with indeterminate pre-operative cytology and those who have undergone thyroidectomy for malignancy. FNAC samples were sent for a routine panel including BRAFv600e, H-K-NRAS and histology for TP53, RET and NTRK in addition. Results Out of 30 patients with indeterminate cytology, molecular testing was requested in eight. The material was insufficient for added molecular testing in six and the panel of mutations tested was negative in two. Thirty-one patients underwent thyroidectomy for malignancy and 11 surgical specimens underwent molecular testing. Mutations were detected in 54.5%(n=6). BRAFv600e mutation was found in four specimens with PTC, whereas NRAS mutation was detected in one Hobnail variant of PTC and one minimal invasive follicular carcinoma. Conclusion Addition of molecular testing to preoperative cytology was shown to require a further FNAC in a majority of cases. In postoperative specimens, molecular testing is feasible but further follow-up is required to determine whether clinical management is altered.

Construction and Evaluation of a Clinical Prediction Scoring System for Positive Cervical Margins Under Colposcopy.

IntroductionCurrently, the commonly used surgical methods for cervical lesions include loop electrosurgical excision procedure (LEEP) and cold knife conization (CKC). However, the positive rate of surgical margins after LEEP is relatively high, which leads to disease recurrence and places further demand on clinical treatment. This study investigated factors related to positive margins after LEEP and established a scoring system to enhance preoperative risk assessment and surgical selection.Materials and MethodsA retrospective analysis of the clinical data of 411 patients undergoing LEEP surgery for cervical lesions in the First Affiliated Hospital of University of Science and Technology of China (USTC), from January 2016 to March 2021, was performed. Cases were divided into a negative margin group (349 cases) and a positive margin group according to postoperative pathology. In the positive group (62 cases), single-factor and multi-factor analyses screened influencing factors; a logistic and additive scoring system was established; furthermore, a ROC curve was used to evaluate scoring effectiveness.ResultsThe positive rate of resection margins after LEEP was 15.1%. Univariate analysis indicated a relationship to patient age, menopause, preoperative ThinPrep Cytology Test (TCT) results, lesion quadrant number under colposcopy, cervical biopsy, and the result of endocervical curettage (ECC). Multivariate analysis showed that age >35 y, menopause, preoperative TCT being high-grade squamous intraepithelial lesion (HSIL), four quadrants being involved under colposcopy, and ECC being HSIL were all independent influencing factors of positive margins after LEEP (P < 0.05). These were included with the above factors to establish a logistic and additive scoring system. When the logistic score was 17, the sensitivity and specificity of predicting positive margins after LEEP were 80.6 and 61.6%, respectively. When the additive score was 6, the sensitivity and specificity were 74.2 and 66.2%, respectively. Both scoring systems had good predictability (area under the curve AUC >0.75).ConclusionsThis study quantified factors influencing positive margins after LEEP and established a scoring system for evaluating patients before surgery to provide a basis for individualized treatment and selection of surgical methods.

Synchronous lateral lymph node metastases from papillary and follicular thyroid carcinoma: case report and review of the literature

BackgroundFollicular thyroid carcinomas (FTCs) rarely metastasize to regional lymph nodes, and descriptions of synchronous lateral lymph node metastases of FTC and papillary thyroid carcinoma (PTC) are lacking.Case PresentationWe describe a 43-year-old female with a preoperative cytology indicating a right-sided PTC with lateral lymph node metastases. She underwent a total thyroidectomy and central and lateral lymph node dissection, and histopathology confirmed a multifocal tall cell variant PTC together with a 12 mm minimally invasive FTC in the ipsilateral lobe. While the central compartment demonstrated metastatic PTC, the lateral compartment contained PTC metastases alongside a 15 mm large follicular-patterned mass in a separate lymph node. As the cells lacked PTC associated nuclear changes, the possibility of a lateral lymph node metastasis of FTC was considered, with the possibility of ectopic thyroid tissue as a differential diagnosis. By utilizing next-generation sequencing, a Q61R NRAS mutation was pinpointed, thus proving the tissue as tumorous. The patient underwent radioiodine treatment and is currently monitored following a negative whole-body scan.ConclusionsThis is probably the first case report of a patient with co-existing lateral lymph node PTC and FTC metastases. Consulting previous publications, there is currently a gap of knowledge in terms of how patients with regional FTC metastases should be followed-up and treated, especially when co-occurring with spread high-risk PTC subtypes. Moreover, what guides a seemingly indolent FTC to spread via the lymphatic system remains to be defined from a molecular standpoint.

Assessment of demographic characteristics and histopathological pattern of thyroidectomies patients in a resource-limited setting: a retrospective cross-sectional study.

Thyroid disorders are prevalent among Yemenis. However, there is limited data regarding thyroid disease burden, surgical intervention outcomes, and predictive factors in our country. This study aims to review the indications, histopathology, and complications of thyroid surgery in a resource-limited setting where the management is provided primarily by general surgeons. A retrospective study between Jun 2010 and March 2019 included 246 cases who underwent thyroid operations for a thyroid disorder in Al-Nasr Hospital, Ibb, Yemen. The patient's demographic characteristics, operative findings, complications, fine needle aspiration biopsy (FNAB) results, final pathology, and outcomes were gathered and analyzed. The mean age was 41.60± 8.31 years. The prevalence was high (30.1%) in the age group of 31-40 years and females (87.8%) with a female-to-male ratio of 7.2: 1. The main indication for thyroidectomy was compressional symptoms (35%), and the main preoperative cytology findings were multimodular goiter (89%). There was thyroid cancer in 18(7.3%) patients, and the most type was follicular thyroid carcinoma (FTC) in 9 patients. The most typical type of surgery was near-total thyroidectomy in 186 (75.6%) patients. Complications were presented in 47 patients (19.1%), and total mortality was observed in 5(2.03%) patients. Intraoperative bleeding was the most typical complication in 36 (14.6%) patients. The sensitivity, specificity, and accuracy of FNAB were 96.34%, 44.44%, and 96.34%, respectively. Fine needle aspiration biopsy (FNAB) was not precise enough in diagnosing FTC with a sensitivity of 55%. Our result showed a considerable rate of postoperative complications of thyroid surgery, and thyroidectomy may be a viable option even in a resource-limited setting or performed by general surgeons.

Risk factor analysis of intravesical recurrence after retroperitoneoscopic nephroureterectomy for upper tract urothelial carcinoma

BackgroundOne of the major concerns of patients with upper tract urothelial carcinoma (UTUC) treated with nephroureterectomy is intravesical recurrence (IVR). The purpose of the present study was to investigate the predictive risk factors for IVR after retroperitoneoscopic nephroureterectomy (RNU) for UTUC.MethodsClinicopathological and surgical information were collected from the medical records of 73 patients treated with RNU for non-metastatic UTUC, without a history of or concomitant bladder cancer. The association between IVR after RNU and clinicopathological and surgery-related factors, including preoperative urine cytology and pneumoretroperitoneum time, was analyzed using the Fisher exact test.ResultsDuring the median follow-up time of 39.1 months, 18 (24.7%) patients had subsequent IVR after RNU. The 1- and 3-year IVR-free survival rates were 85.9% and 76.5%, respectively. The Fisher exact test revealed that prolonged pneumoretroperitoneum time of ≥ 210 min was a risk factor for IVR in 1 year after RNU (p = 0.0358) and positive urine cytology was a risk factor for IVR in 3 years after RNU (p = 0.0352).ConclusionsIn UTUC, the occurrences of IVR in 1 and 3 years after RNU are highly probable when the pneumoretroperitoneum time is prolonged (≥ 210 min) and in patients with positive urine cytology, respectively. Strict follow-up after RNU is more probable recommended for these patients.

Papillary hyperplasia of the gallbladder diagnosed as gallbladder cancer before surgery: A case report.

Introduction and importanceGallbladder cancer has a poor prognosis. Therefore, an accurate diagnosis is required, for which various tests are performed. However, in some cases, it is difficult to distinguish between benign and malignant diseases before surgery. Papillary hyperplasia of the gallbladder is known for its secondary changes. Papillary hyperplasia of the gallbladder, which is known for its secondary changes, is a benign disease. We encountered papillary hyperplasia of the gallbladder with morphological changes over the course of 1 year. In addition, the tumor was suggested to be malignant during various examinations. We present a case of papillary hyperplasia of the gallbladder showing an increasing tendency and findings indicative of malignancy on imaging.Presentation of caseA 70-year-old man underwent routine abdominal ultrasonography every year. We observed that the gallbladder wall was thickened. The tumor size was 24 mm. FDG-PET and other examinations indicated malignancy requiring surgery.Clinical discussionAccurate diagnosis of gallbladder tumor is difficult only by diagnostic imaging. There are problems with preoperative cytology and histology. FS can be an important test to avoid extended surgery.ConclusionWe report a rare case of papillary hyperplasia of the gallbladder, which was difficult to diagnose. Even when morphological changes and imaging findings suggest malignancy, similar findings could appear in papillary hyperplasia of the gallbladder owing to chronic inflammation.

Utility of droplet digital polymerase chain reaction for TERT and BRAF mutational profiling of thyroid nodules

BackgroundMutations involving BRAF and TERT are important predictors of disease severity in thyroid cancer, but molecular testing is limited by cost and lack of adequate tissue sample. This study aimed to assess the utility of BRAFV600E and TERT testing using droplet digital PCR (ddPCR) as a diagnostic and prognostic tool for thyroid fine needle aspirate biopsy (FNAB).MethodsPatients with thyroid nodules were prospectively enrolled from March 2015 to September 2018. Pre-operative FNAB was collected for standard cytology and molecular testing. BRAFV600E and TERT levels were analyzed by ddPCR. Cytology (Bethesda system) and ddPCR results were correlated to surgical pathology.ResultsA total of 222 patients were enrolled, of which 124 received thyroid surgery. Pre-operative cytology alone with Bethesda ≥5 was 100% specific and 70% sensitive for malignancy on final surgical pathology. BRAFV600E positivity or TERT overexpression was 100% specific and 60.0% sensitive. Combining cytology (Bethesda ≥5) with BRAFV600E and TERT testing increased the sensitivity of a malignant diagnosis to 80.0%. High TERT levels and/or BRAFV600E was associated with aggressive or advanced stage pathology.ConclusionsCombining cytology with ddPCR analysis of BRAFV600E and TERT can improve the diagnostic accuracy of thyroid FNAB, and help predict aggressive pathology.

Predictive Value of Preoperative Positive Urine Cytology for Development of Bladder Cancer After Nephroureterectomy in Patients With Upper Urinary Tract Urothelial Carcinoma: A Prognostic Nomogram Based on a Retrospective Multicenter Cohort Study and Systematic Meta-Analysis.

BackgroundUpper urinary tract urothelial carcinoma (UUT-UC) is a rare and severe urinary malignancy. Several studies have explored the relationship between preoperative urine cytology and intravesical recurrence (IVR) in patients with UUT-UC. However, the results of these studies are controversial or even contradictory, and investigations with UUT-UC patients in northeast China are rare.MethodsWe first estimated the prognostic significance of preoperative urine cytology in the outcomes of intravesical recurrence in 231 UUT-UC patients (training cohort = 142, validation cohort = 89) after radical nephroureterectomy (RNU) by the nomogram model. Subsequently, we quantitatively combined our results with the published data after searching several databases to assess whether preoperative positive urine cytology was associated with poor intravesical recurrence-free survival and a high risk of tumor malignant biological behavior.ResultsFirstly, the multicenter retrospective cohort study demonstrated that preoperative positive urine cytology correlated with poor intravesical recurrence-free survival and can serve as significant independent predictors of IVR by Kaplan–Meier curves and Cox regression analysis. The construction of the nomogram demonstrated that predictive efficacy and accuracy were significantly improved when preoperative urine cytology was combined. Meanwhile, meta-analysis showed that preoperative positive urine cytology was associated with a 49% increased risk of IVR. In the subgroup analysis by region, study type, and sample size, the pooled hazard ratios (HRs) were statistically significant for the Japan subgroup (HR 1.32), China subgroup (HR 1.88), cohort study subgroup (HR 1.45), and the single-arm study subgroup (HR 1.63).ConclusionsPreoperative urine cytology was validated as a potential predictor of intravesical recurrence in patients with UUT-UC after RNU, although these results need to be generalized with caution. Large, prospective trials are required to further confirm its significance in prognosis and tumor malignant biological behavior.

Gain of TPPP as a predictor of progression in patients with bladder cancer.

The present study investigated the role of tubulin polymerization promoting protein (TPPP) in the regulation of bladder cancer (BC) cell proliferation and migration, in addition to the association between TPPP gene copy number amplification and clinicopathological characteristics of BC. TPPP gene amplification was measured in human BC epithelial cells and samples obtained from 52 patients with BC via fluorescence in situ hybridization. TPPP gain was defined as mean TPPP copy number >2.2 per nucleus (cutoff). The neutrophil-to-lymphocyte ratio (NLR) was also obtained from the preoperative data of the patients. For in vitro assays, BC cell lines were transfected with either TPPP small interfering RNAs or scrambled control, following which cell proliferation and migration were determined using Cell Counting Kit-8 and Transwell migration assays, respectively. The percentage of cells with TPPP copy number amplification in the four BC epithelial cell lines (MGH-U1, -U1R, -U3, -U4) examined (86.0-100.0%) was found to be higher compared with that in the normal human uroepithelial cell lines (3.0 and 9.0%). Patients were divided into one- (1.9%), two- (55.8%), three- (7.7%), four- (26.9%) and five-copy (7.7%) types. Results calculated using Fisher's exact test indicated that the gain of TPPP in patients with BC associated significantly with age (P<0.05), advanced histological grade (P<0.001), tumor stage (P<0.05), histological type (P<0.001) and NLR (P<0.05). In MGH-U1R and MGH-U4 cells, cell proliferation and migration were revealed to be significantly lower following TPPP knockdown compared with those in cells transfected with the scrambled control. In conclusion, findings from the present study suggest that TPPP is important for cell proliferation, cell migration and BC progression, such that TPPP copy number assessment would be advised for preoperative urine cytology for urothelial neoplasia diagnosis.

Serum circulating miRNA-342-3p as a potential diagnostic biomarker in parathyroid carcinomas: A pilot study.

ObjectiveTo compare the serum miRNA expression profiles between patients with benign and malignant parathyroid tumours.BackgroundDespite recent advances in molecular biology, a histological tissue biopsy is still the method of choice used to diagnose most cancers. The preoperative cytology is not an applicable method for diagnosis of parathyroid cancer (PC); therefore, huge interest exists in terms of finding alternative methodologies to seek specific cancer biomarkers.DesignA retrospective cross‐sectional study.Patients and MethodsSerum samples of patients with PC (n = 13) and parathyroid adenoma (PA) (n = 11), age (p = .999) and sex (p = .999) were matched and examined via the simultaneous comparative expression analysis of 754 microRNAs (miRNAs). The «TaqMan OpenArray Human MicroRNA Panel» (Applied Biosystems) was used to conduct real‐time PCRs using the «QuantStudio 12К Flex» station (Life Technologies).ResultsAccording to the results of a pilot study, significant changes in expression levels between the PC group and the PA group (control) (p < .05) were observed for 17 miRNAs. Among them, the downregulation of miRNA‐342‐3p met the Benjamini‐Hochberg adjustment criteria for multiple comparisons (p = .02).ConclusionsSerum miRNA‐342‐3p could be a promising biomarker for PC to improve diagnosis and prognosis.

Next-Generation Sequencing Enhances the Diagnosis Efficiency in Thyroid Nodules.

BackgroundThough fine-needle aspiration (FNA) improved the diagnostic methods of thyroid nodules, there are still parts of nodules that cannot be determined according to cytology. In the Bethesda system for reporting thyroid cytopathology, there are two uncertain cytology results. Thanks to the development of next-generation sequencing technology, it is possible to gain the genetic background of pathological tissue efficiently. Therefore, a combination of the cytology and genetic background may enhance the accuracy of diagnosis in thyroid nodules.MethodsDNA from 73 FNA samples of thyroid nodules belonging to different cytology types was extracted and exome sequencing was performed by the ThyroLead panel. Test for BRAF mutation was also performed by ARMS-qPCR. Information including age, sex, preoperative cytology, BRAF mutation status tested by ARMS-qPCR, and surgical pathology was collected in electronic medical record system.ResultsA total of 71 single nucleotide variants, three fusion gene, and two microsatellite instability-high status were detected in 73 FNA samples. BRAF V600E mutation is the most common mutation in these malignant thyroid nodules. After combining the cytology and genetic background detected by next-generation sequencing, the diagnosis sensitivity was increased from 0.582 (95% CI: 0.441–0.711) to 0.855 (95% CI: 0.728–0.930) (P < 0.001) in our group, while the specificity, 1,000 (95% CI: 0.732–1.000) compared to 0.857 (95% CI: 0.562–0.975) (P = 0.25), did not get affected.ConclusionsNext-generation sequencing in thyroid nodules can enhance the preoperative diagnosis sensitivity by fine-needle aspiration alone. It can also provide genetic background for direction of medication. It is possible for clinicians to combine cytology with genetic alterations for a more precise diagnosis strategy of thyroid nodules.

Significance of 5-Aminolevulinic Acid-mediated Photodynamic Diagnosis Following Standard Transurethral Resection in Non-muscle Invasive Bladder Cancer.

Transurethral resection of bladder tumors (TURBT) guided by photodynamic diagnosis (PDD) with 5-aminolevulinic acid (5-ALA) has been shown to be superior to conventional white light (WL) cystoscopy with regard to diagnostic accuracy, for non-muscle invasive bladder cancer (NMIBC); however, PDD is usually performed prior to WL TURBT. The objective of this study was to investigate the diagnostic significance of 5-ALA-mediated PDD following TUR of NMIBC. In 83 NMIBC patients, all visible tumors were completely resected under the conventional WL guidance followed by additional resection if fluorescent lesions were observed under the blue light (BL) guidance, and random biopsy was further conducted. With the BL source, 39 (47.0%) patients were judged to have fluorescent lesions. Twenty (51.3%) of the 39 patients with positive findings by PDD were diagnosed with residual cancer by additional resection, while random biopsy detected cancers in 2 (4.5%) of the 44 patients with negative findings by PDD. Accordingly, the sensitivity, specificity, positive predictive value and negative predictive value in diagnosing residual cancer by our PDD system were 90.9, 68.9, 51.3 and 95.5%, respectively. Univariate analysis showed that the presence of residual cancers shown by WL TURBT was significantly associated with the preoperative findings of urinary cytology, tumor multiplicity, pathological T stage and tumor grade, of which only the preoperative finding on urinary cytology was shown to have an independent impact on the diagnosis of residual cancer. 5-ALA-mediated PDD following standard WL TURBT could improve the diagnostic accuracy in NMIBC patients, particularly those who are positive for preoperative urinary cytology.

Surgery for Submandibular Gland Diseases: 14-years of Experience of a Single Tertiary Center

Objective: Surgical removal is a valid option in the treatment of submandibular gland diseases but there are still operative and diagnostic pitfalls. We aimed to review and investigate the long-term clinical, surgical, and pathologic outcomes of our cases that had undergone submandibular gland removal. Materials and Methods: Retrospective analysis was conducted on patients who underwent submandibular gland excision via the transcervical approach with minimal skin incision between January 2007 and April 2020. Demographic data, preoperative FNA cytology results, clinical findings, surgical procedure, postoperative histopathological diagnosis, and postoperative morbidity were reviewed and analyzed. Results: 66 patients (41.7%) had sialolithiasis, 47 patients (29.7%) had chronic sialadenitis. Pleomorphic adenoma was found in 30 of the 44 patients that been operated on for submandibular mass. Gland derived carcinoma was found in 9 patients. The sensitivity of FNA biopsy in our case series was 83.3% (10/12), specificity was 78.1% (25/32), positive predictive value was 71.4% (10/14), and the negative predictive value was 96.1% (25/26). Permanent facial nerve marginal mandibular branch palsy was found in two patients (1.2%). Conclusion: The transcervical approach to the submandibular gland offers safe and reliable removal of the submandibular gland with a minimal risk of complications. FNA cytology was found to be useful in the preoperative evaluation of the submandibular masses.

The role of fine-needle aspiration biopsy and post-operative histology in the evaluation of thyroid nodules

Thyroid nodules present a serious problem, and mostly they do not carry neoplastic characteristics. Thus, they do not need to be surgically treated. The risk of malignancy varies from 5 to 15 %. Steps to diagnose malignancy should include a careful clinical evaluation, laboratory tests, a thyroid ultrasound exam and a fine-needle aspiration biopsy. Fine-needle aspiration biopsy (FNAB) is the most important diagnostic tool in the assessment of thyroid nodules. Today it is considered the gold standard for malignancy diagnosis in thyroid cancer. In this review we evaluate the role of FNAB and post-operative cytology in the evaluation of thyroid nodules. FNA results are classified as diagnostic (satisfactory) or nondiagnostic (unsatisfactory). Unsatisfactory smears (5–10 %) result from hypocellular specimens usually caused by cystic fluid, bloody smears, or suboptimal preparation. Diagnostic smears are conventionally subclassified into benign, indeterminate, or malignant categories. Benign cytology (60–70 %) is negative for malignancy, and includes cysts, colloid nodule, or Hashimoto thyroiditis. Malignant cytology (5 %) is almost always positive for malignancy, and includes primary thyroid tumors or nonthyroid metastatic cancers. Indeterminate or suspicious specimens (10–20 %) include atypical changes, Hurthle cells or follicular neoplasms. The new Bethesda Cytologic Classification has a 6-category classification, subdividing indeterminate further by risk factors. Considering the increasing worldwide incidence of thyroid microadenomas, recently it is recommended to undergo FNAB under ultrasound guidance even in small (&lt; 1cm) nodules if they are correlated with suspicious ultrasonographic features or suspicious neck lymph nodes. FNAB is a cheap and reliable diagnostic tool that can be used in the selection candidates for surgery and pre-operative diagnosis of thyroid carcinomas. It was concluded that FNAB is the gold standard in the evaluation of thyroid nodules and can prevent many unnecessary surgeries. False-negative FNA cytology remains a concern for clinicians treating patients with thyroid nodules. Post-operative histology give the definitive diagnosis and studies confirm that it has a significant discordance between pre-operative cytology and post-operative histology in patients with thyroid nodule. Cytopathologists should strengthen their criteria for the identification of adenomatous hyperplasia, thyroiditis, cystic lesions or suspicious thyroid nodules to avoid misdiagnoses.

Positive Correlation of Thyroid Nodule Cytology with Molecular Profiling-a Single-Center Experience.

Despite several reports on the association between molecular profiling, aggressive histology, and clinical outcomes, the association between mutation expression and pre-operative cytology is yet to be demonstrated. Therefore, we performed a retrospective, single-center study, including all patients who underwent molecular profiling of thyroid nodules in Bethesda System for Reporting Thyroid Cytopathology (BSRTC) categories III to VI, between 2018 and 2019. Medical records were reviewed to collect demographics, cytology results according to BSRTC, final pathology (presence of malignancy and its type, as well as presence of aggressive features, including extrathyroidal extension, positive neck lymph nodes, and multifocality), and the identified genetic variants stratified by risk levels, according to the 2015 ATA guidelines. We supplemented this analysis with a systematic review to identify the variant distributions across the literature. We included data on 55 nodules from 48 patients for the final analysis. A significant positive correlation was found between BSRTC categories and the mutation risk level, shown by an increase in the intermediate to high-risk mutation rate in the higher BSRTC categories (Rs=0.660, p ≤ 0.001). A significant positive correlation was also found between mutation risk levels and the presence of malignancy and aggressive tumor features (Rs=0.637, p<0.001 and Rs=0.459, p=0.006, respectively). This novel positive and significant correlation between BSRTC categories and the mutation risk level provides additional insight to aid clinicians in the interpretation of BSRTC results and may contribute to the discussion of appropriate management of thyroid nodule with patients.

Follicular Epithelial Dysplasia as Hashimoto Thyroiditis-Related Atypia: a Series of 91 Specimens

Follicular epithelial dysplasia (FED) is described as Hashimoto thyroiditis-related atypia and is thought to be a possible precancerous lesion. Dysplasia as an interface between normal state and carcinoma is described in a wide range of diseases and carcinogenesis chains. On the other hand, inflammation-related atypia and cancerogenesis is also widely studied. In this study, we retrospectively analyzed 91 specimens of thyroid gland surgical resections with FED during a 10-year-period at the university hospital pathology department. The study population consisted of 68 females and 15 males aged between 22 and 86 years. The preoperative cytology diagnoses had mainly been in the indeterminate categories with prevailing AUS/FLUS results in the FED-only group (p = 0.005) and suspicious for malignancy and malignant in the group with FED plus adjacent malignancy. The decision for surgery was malignancy related in 48.2% of the cases. The lesions were sized 0.1–3.5 mm and multifocal in 45.1% of the cases. Immunohistochemically, the atypical cells were cyclin D1-positive in 67.5%, galectin-3 in 72.7%, CK19 in 85.7%, and HBME-1 in 87.0% of cases. In conclusion, FED is suggested to be a pathogenetic link between inflammation-related atypia and papillary carcinoma and thus a premalignant precursor of papillary carcinoma in HT as 36.1% of the specimens contained also papillary carcinoma in the present study. Both histopathological nuclear features and the immunoprofile of FED are widely shared with that of papillary carcinoma.

Can we still consider thyroid hyperfunction a protective condition for the onset of thyroid cancer?

Thyroid cancer is the ninth most commonly diagnosed cancer in the world, and the most common endocrine carcinoma. It was originally believed to be a rare event in patients with thyroid hyperfunction and it was reported that hyperthyroidism had a protective role against thyroid neoplasms. However, in recent years, several studies have hypothesized that differentiated thyroid carcinomas and hyperthyroidism may coexist. Our study aims therefore to evaluate the incidence of differentiated thyroid carcinomas on definitive histological examination, in patients undergoing total thyroidectomy or hemithyroidectomy with coexisting hyperfunctioning thyroid disease, to understand whether hyperthyroidism can be considered a protective condition against the onset of thyroid neoplasms. The study involved 1,449 patients underwent to thyroid surgery from 2010 to 2018 at the General Surgery Unit, Department of Surgery, University Hospital of Parma, Parma, Italy, presenting thyroid cancer at postoperative histological exam. Patients were divided in two groups based on the presence (Group A) or absence (Group B) of hyperfunction. All data were collected in a dedicated database and include demographic data, such as age and sex, preoperative cytology, date and type of surgery, postoperative diagnosis, characteristics of aggressiveness of the neoplasm and postoperative complications. For data analysis, a P value of less than 0.05 was considered statistically significant. The incidence of thyroid carcinomas was lower in patients suffering from hyperfunction compared to the incidence found in non-hyperthyroid patients, both in preoperative cytological examination and in postoperative diagnosis through histological examination. Furthermore, the tumors that have developed in patients with hyperfunction had a comparable degree of aggression and invasiveness in the two groups studied. However, we have found an equal incidence of microcarcinomas and occult carcinomas on postoperative histological examination. Postoperative complications in patients with cancer were similar, regardless of the presence or absence of hyperfunctioning thyroid disease. Our study confirms that hyperthyroidism is a protective condition against thyroid carcinoma, but the finding of an equivalent incidence of occult carcinomas in the two groups stresses the need to perform a cytological examination in case of a nodular pathology in a hyperthyroid patient before performing a treatment.

Pancreatic Frozen Section Guides Operative Management With Few Deferrals and Errors.

Pancreatic adenocarcinoma is the third leading cause of cancer death in the United States. Surgery remains the mainstay of treatment, and frozen section analysis is used to confirm diagnosis and determine resectability and margin status. To evaluate use and accuracy of frozen section and how diagnosis impacts surgical procedure. We reviewed patients with planned pancreatic resections between January 2014 and March 2019 with at least 1 frozen section. Pathology reports including frozen sections, preoperative cytology, and operative notes were reviewed. Frozen sections were categorized by margin, primary pancreatic diagnosis, metastasis, or vascular resectability. The deferral and error rates and surgeons' response were noted. We identified 898 planned pancreatic resections and 221 frozen sections that were performed on 152 cases for 102 margins, 94 metastatic lesions, 20 primary diagnoses, and 5 to confirm vascular resectability. The diagnosis was deferred to permanent sections in 13 of 152 cases (8.6%) on 16 of 221 frozen sections (7.2%): 6 for metastasis, 8 for margins, and 2 for primary diagnosis. Discrepancies/errors were identified in 4 of 152 cases (2.6%) and 4 of 221 frozen sections (1.8%). Surgeons' responses were different than expected in 8 of 221 frozen sections (3.6%), but their actions were explained by other intraoperative findings in 6 of 8. Frozen section remains an important diagnostic tool used primarily for evaluation of margins and metastasis during pancreatectomy. In most cases, a definitive diagnosis is rendered, with occasional deferrals and few errors. Intraoperative findings explain most cases where surgeons act differently than expected based on frozen section diagnosis.

Is there a Role for Frozen Section Evaluation of Parotid Masses After Preoperative Cytology or Biopsy Diagnosis?

Fine-needle aspiration (FNA) biopsy reliably diagnoses parotid gland lesions preoperatively, whereas intraoperative frozen section (FS) has the additional benefit of assessing surgical margins and refining diagnoses; however, the role of FS in the setting of prior FNA diagnosis is not well established. Our aim was to determine whether FS should still be performed after a prior FNA/ CNB diagnosis. Parotid gland resections from January 2009 to January 2020 were identified; however, only patients who had both FNA and FS constituted our study population. For the purpose of statistical analysis, FNA diagnoses were classified into non-diagnostic (ND), non-neoplastic (NN), benign neoplasm (BN), indeterminate, and malignant. FS diagnoses were classified into benign, indeterminate, or malignant. Resections were dichotomized into benign and malignant and regarded as the gold standard to subsequently calculate diagnostic accuracy of FNA and FS. A total of 167 parotid gland resections were identified, but only 76 patients (45.5%) had both FNA and FS. In 35 cases deemed as benign preoperatively, three (8.6%) were reclassified as malignant on FS. Out of 18 lesions reported as malignant on FNA, four (22.2%) were interpreted as benign on FS, with three of these benign lesions confirmed on permanent slides. In addition, in patients with both FNA and FS, compared to FNA, FS was able to provide a definitive diagnosis in all five ND cases and in 61.1% (11/18) of indeterminate tumors. Intraoperative assessment provided a relative increase of 33.3% in specificity and 38.5% in positive predictive value when compared to preoperative FNA. The addition of FS to FNA was helpful to further refine the diagnoses of parotid gland lesions, which may provide better guidance for surgical intervention.