Cases Of Papillary Thyroid Carcinoma Research Articles

Survival outcomes of low-risk papillary thyroid carcinoma at different risk levels: a corollary for active surveillance.

This study aims to compare the outcomes of active surveillance (AS) in low-risk papillary thyroid carcinoma (PTC) patients with different tumor sizes and lymph node metastasis status, in order to establish appropriate management strategies. By analyzing these results, this study provides valuable insights for the effective management of such patients, addressing the issues and challenges associated with AS in practical clinical practice. The study utilized the SEER database supported by the National Cancer Institute of the United States, extracting data of PTC diagnosed between 2000 and 2015. Statistical analyses were conducted using inverse probability weighting (IPTW) and propensity score matching (PSM), including Kaplan-Meier survival curves and Cox regression models, to evaluate the impact of different tumor sizes and lymph node metastasis status on thyroid cancer-specific survival (TCSS). A total of 57,000 PTC patients were included, with most covariates having standardized mean differences below 10% after IPTW and PSM adjustments. The TCSS of PTC with a diameter smaller than 13mm is significantly better than that of tumors with a diameter larger than 13mm, regardless of the presence of lymph node metastasis. Among PTC cases with a diameter smaller than 13mm, the TCSS of patients is similar, regardless of the presence of lymph node metastasis. However, in PTC cases with a diameter larger than 13mm, the presence of lateral neck lymph node metastasis (N1b stage) significantly impacts the TCSS, although the absolute impact on TCSS rate is minimal. The treatment strategy of AS is safe for patients with T1a stage papillary thyroid microcarcinoma (PTMC). However, for patients with T1b stage, if the tumor diameter exceeds 13mm or there is lymph node metastasis in the lateral neck region, the TCSS will be significantly affected. Nevertheless, the absolute impact on survival is relatively small.

Development and validation of nomograms for predicting the risk of central lymph node metastasis of solitary papillary thyroid carcinoma of the isthmus

BackgroundThis study was conducted to develop nomograms and validate them by assessing risk factors for the development of central lymph node metastasis (CLNM) in patients with solitary papillary thyroid carcinoma of the isthmus (PTCI) for predicting the probability of CLNM.MethodsDemographic and clinicopathological variables of patients with solitary papillary thyroid carcinoma (PTC) from May 2018 to May 2023 at the First Hospital of Shanxi Medical University were retrospectively analyzed, and the lobar group and the isthmus group were divided according to tumor location. Patients with the same sex, age difference of less than 3 years, and equal gross tumor diameter were selected from the lobar group and compared with the paraisthmic tumor group. Independent risk factors were determined using univariate and multivariate logistic regression analysis. On this basis, clinical predictive nomograms were developed and validated.ResultsClinical data from 326 patients with solitary PTCI and 660 cases of solitary lobar PTC were used for analysis in our study. The incidence of solitary tumors CLNM located in the median isthmus, paracentral isthmus, and lobes was 69.8%, 40.9%, and 33.6%, respectively. Statistical analysis revealed that gender, age, isthmus location, maximum nodal diameter, the presence of possible CLNM in advance on preoperative ultrasound, chronic lymphocytic thyroiditis, and the lymphocyte/monocyte ratio were independent risk factors for preoperative CLNM in patients with solitary PTCI. Age, isthmus location, chronic lymphocytic thyroiditis, gross tumor diameter, presence of intraoperative extrathyroidal extension, and presence of metastasis in the Delphian lymph node on frozen section were independent risk factors for intraoperative CLNM. The concordance indices of nomograms for preoperative and intraoperative are 0.871 and 0.894 in the training set and 0.796 and 0.851 in the validation set, calibration curve and decision curve analysis also demonstrated the strong reliability and clinical applicability of this clinical prediction model.ConclusionIn this study, we concluded that solitary PTCI is more aggressive compared to solitary lobar PTC, and we constructed nomograms and risk stratification to accurately identify patients with solitary PTCI who are at high risk of developing CLNM, which will help clinicians in personalized decision making.

Impact of BRAFV600E Mutation on Event-Free Survival in Patients with Papillary Thyroid Carcinoma: A Retrospective Study in a Romanian Population.

We aimed to evaluate the prognostic value of BRAFV600E mutation in a series of 127 papillary thyroid carcinoma (PTC) cases as a single factor, and in synergic interaction with other standard risk factors. BRAFV600E mutation was assessed by real-time PCR. Event-free survival (EFS) was calculated between the date of the first evaluation and the date of occurrence of an adverse event or the date of the last known status. The prevalence of BRAFV600E mutation was 57.2%. The Kaplan-Meier analysis showed a significant reduction of EFS among cases harboring BRAFV600E mutation compared to non-mutated cases (p = 0.010). In addition, BRAFV600E mutation was found to better predict adverse outcomes when associated with the following risk factors: age ≥ 55 years old (p < 0.001), male gender (p < 0.001), conventional (p = 0.005) and tall cell (p = 0.014) histology, tumor size > 40 mm (p = 0.001), extrathyroidal extension (p = 0.001), multifocality (p = 0.001) and lymph node metastasis (p < 0.001). In univariate analysis, a 3.74-fold increased risk for a reduced EFS (p = 0.018) was found for BRAFV600E-mutated cases, but no increased risk was further confirmed by multivariate analysis. Our results highlight that BRAFV600E mutation cannot be used alone as an independent predictive factor in PTC patients, but is prognostically valuable if integrated in the context of other clinicopathological risk factors.

IL-17 A correlates with disease progression in papillary thyroid carcinoma

BackgroundCancer progression can be promoted by chronic inflammation. Local immune response may be associated with favourable or unfavourable prognosis of Papillary Thyroid Carcinoma (PTC). Regulatory T (Treg) cells and T helper 17 (Th17) cells exert opposing function and their balance may have a vital role in promotion of tumor growth. Treg cells in tumor microenvironment (TME) may promote tumor progression and reduced survival of patients. Whereas, Th17 cells can promote or inhibit tumor progression depending on phenotypic characteristics of tumor. In this study, we aimed to analyse the kind of immune response developed and its prognostic impact in future therapeutics.MethodsCytometric Bead Array (CBA) analysis of pro and anti-inflammatory cytokines (IFN-gamma, IL-2, IL-6, IL-17 A, TNF-alpha and IL-4, IL-10) was done in 15 PTC irrespective of Lymphocytic Thyroiditis (LT) and 16 Hashimoto’s Thyroiditis (HT) cases. Immunohistochemical expression of FoxP3 and IL-17 A was studied in 27 cases of PTC with LT. Whereas, quantitative gene expression of both was analysed in 10 cases.ResultsAll the pro-inflammatory cytokines showed mild elevation in PTC with LT. On IHC, IL-17 A expression was observed in 74% PTC with LT. Whereas, FoxP3 was present in only 40% cases. Also, IL-17 A expression was significantly associated with age group (> 45 years), tumor size ≤ 1 cm and disease progression.ConclusionsIncreased expression of cytokines suggested correlation between inflammatory factors and progression of thyroid tumors. Along with this, the balance between IL-17 A and FoxP3 may play an important role in PTC development, prognosis and future management.

Association of High Serum Leptin Level with Papillary Thyroid Carcinoma: A Case-Control Study.

Background: Recently, the prevalence of thyroid cancer has increased. Although there are known risk factors for thyroid cancer, none of them can justify this recent increase. In addition to the known risk factors, other risk factors have been proposed. Leptin can be considered as one of these risk factors due to the recent increase in the prevalence of obesity in the population. Leptin is a common factor in obesity and thyroid cancer. Leptin exerts anti-apoptotic and mitogenic effects on cancer cells and also acts as an angiogenic factor. This study aimed to evaluate the serum leptin level in individuals who suffer from papillary thyroid carcinoma (PTC), cases with benign thyroid nodules (BTN), and a healthy group. Materials and Methods: In this study, newly diagnosed patients with PTC, BTNs, as well as euthyroid healthy control subjects without nodules were included. In all these participants, various clinical and laboratory parameters including thyroid function tests and serum leptin levels were measured and compared between the three study groups. For patients with PTC, leptin was assessed 12 weeks after total thyroidectomy. Results: Ninety-one cases with PTC, 90 cases with BTNs, and 88 controls were recruited. Serum leptin levels in the PTC group, benign group, and the control group were 22.34, 17.60, and 13.83 ng/ml, respectively, which was considerably higher in PTC cases compared to those with benign nodules and control group (P<0.001). There was a significant association between leptin with BMI, tumor size, and tumor stage in PTC patients. Also, in patients with BTNs, a correlation between BMI, tumor size, and leptin was observed. Conclusion: Serum leptin levels were considerably higher in cases with PTC than those with BTNs and controls and can be considered as a potential tumor marker for papillary thyroid cancer.

Regulatory role of Chitinase 3-like 1 gene in papillary thyroid carcinoma proved by integration analyses of single-cell sequencing with cohort and experimental validations

Papillary thyroid carcinoma (PTC) is one of the most common thyroid carcinomas. The gross extrathyroidal extension and extensive metastases of PTC lead to high rates of recurrence and poor clinical outcomes. However, the mechanisms underlying PTC development are poorly understood. In this study, using single-cell RNA sequencing, the transcriptome profiles of two PTC patients were addressed, including PTC1 with low malignancy and good prognosis and PTC2 with high malignancy and poor prognosis. We found that epithelial subcluster Epi02 was the most associated with the malignant development of PTC cells, with which the fold change of Chitinase 3-like 1 (CHI3L1) is on the top of the differentially expressed genes between PTC1 and PTC2 (P < 0.001). However CHI3L1 is rarely investigated in PTC as far. We then studied its role in PTC with a series of experiments. Firstly, qRT-PCR analysis of 14 PTC patients showed that the expression of CHI3L1 was positively correlated with malignancy. In addition, overexpression or silencing of CHI3L1 in TPC-1 cells, a PTC cell line, cultured in vitro showed that the proliferation, invasion, and metastasis of the cells were promoted or alleviated by CHI3L1. Further, immunohistochemistry analysis of 110 PTC cases revealed a significant relationship between CHI3L1 protein expression and PTC progression, especially the T (P < 0.001), N (P < 0.001), M stages (P = 0.007) and gross ETE (P < 0.001). Together, our results prove that CHI3L1 is a positive regulator of malignant development of PTC, and it promotes proliferation, invasion, and metastasis of PTC cells. Our study improves understanding of the molecular mechanisms underlying the progression of PTC and provides new insights for the clinical diagnosis and treatment of PTC.

An interesting case of papillary thyroid carcinoma with heterotrophic ossification

Calcification in thyroid gland is associated with both benign and malignant lesion. However calcification is most frequently seen in malignant lesions. Calcification can give rise to metaplasia and bone containing marrow tissue. Papillary carcinoma with heterotrophic ossification has been associated with high incidence extrathyroidal invasion, multifocality, lymphnode metastsasis and older age group than in those without heterotrophic ossification. It has not been described as a specific entity in WHO classification because of its rarity. Expression of both basic fibroblast growth factor and bone morphogenetic protein was highest in papillary carcinoma with intratumoral heterotrophic ossification. In this case report we described a 71-year-old female patient who sought medical care for swelling in the neck for the past 4 years. The cervical ultrasound showed a 2 well defined nodules measuring 2x2 cms and 4mm in the right lobe with larger lesion showing peripheral rim of calcification and left lobe and isthumus shows well defined lesions measuring 5mm and 4 mm each. The clinical diagnosis was multinodular goitre. Patient subsequently underwent thyroidectomy. On histopathological investigation right lobe showed follicular adenoma and papillary carcinoma thyroid with extensive heterotrophic ossification and calcification within the tumor. The margins were free of neoplasia and there was no extrathyroidal extension. No preineural/ vascular invasion noted. One lymphnode was identified which was free of tumor. pTNM staging was pT1bNxMx.

Papillary thyroid carcinoma post total thyroidectomy: a case report

Thyroid malignancies are considered rare but it is the most common type of endocrine malignancy that increase rapidly over the past decades. Specifically, papillary thyroid carcinoma (PTC) in the pyramidal lobe is extremely rare. Herein, we described a case of recurrence case of PTC in the pyramidal lobe post total thyroidectomy with category VI T2N1M1 (Bethesda classification) with right neck lymph nodes metastasis at once and attempt to determine both clinical presentation and therapeutical strategies to overcome this case to diminish the possibility of tumor recurrence and optimize therapeutic outcomes for PTC recurrence. It was reported a 28 yo female with a diagnosis of PTC from the pyramidal lobe post-total thyroidectomy procedure. A definite diagnosis of PTC is important to understand the patient's condition and as a consideration to decide the appropriate procedure to cure it. The management of PTC with total thyroidectomy followed by removing the possible root source of recurrent PTC, such as the pyramidal lobe, is mandatory to minimize the residual thyroid tissue that dan influenced PTC recurrent. Even though almost all PTC has an excellent prognosis, periodic follow-up after surgery, and patients’ adherence to their medication are still required.&#x0D;

Immunohistochemical Expression of Cytokeratin 19 in Patients with Papillary Thyroid Carcinoma and its Mimics in Erbil, Kurdistan Region, Iraq

Background and objective: Papillary thyroid carcinoma (PTC) is the most common primary thyroid cancer. PTC diagnosis is based on the presence of classic nuclear features in most cases. However, there are some mimics including both benign neoplastic and non-neoplastic lesions, therefore immune-histochemical stains are necessary for equivocal cases. This study aimed to evaluate the diagnostic expression of CK19 in different thyroid lesions and also to differentiate PTC from other mimicking thyroid lesions. Methods: A retrospective study of 90 cases of different thyroid lesions (56 patients with benign neoplastic and non-neoplastic lesions and 34 PTC) was investigated from January 2018 to January 2020. Immunohistochemical staining with CK19 was performed. Results: CK19 IHC expressed in about 94% of PTC cases as moderate and strong pattern of staining, while in benign neoplastic and non-neoplastic thyroid lesions only 7% expressed as moderate and non with strong pattern of staining, it showed a significant statistical difference (P &lt;0.001).The sensitivity and specificity of CK19 total estimated score for diagnosis of PTC were 94.1% and 92.9%, respectively. Conclusion: Although no single immunohistochemical marker is completely sensitive in differentiating benign from thyroid malignancy, this study found a significant and effective role of CK19 in distinguishing PTC from benign neoplastic and non-neoplastic mimickers’ lesions. In addition, lymph node metastatic tumor cells retained the same staining intensity of CK19.

The necessity of resection of suprasternal fossa fat in total endoscopic thyroidectomy via the areola approach.

The identification of a lower boundary for the central lymph node (CLN) of the neck in total endoscopic thyroidectomy via the areola approach (ETA) is important for its radical dissection. We found that resection of the suprasternal fossa fat (SFF) was beneficial for exposing the lower boundary and preventing suprasternal swelling after the operation. This retrospective analysis included 470 papillary thyroid carcinoma (PTC) cases, with some treated by unilateral lobectomy, some by central lymph node dissection (CLND) through ETA (n = 193), and the others by conventional open thyroidectomy (COT, n = 277). The main observation indicators included the total number of CLNs, CLND operative time, visualization of the upper pole of the thymus before removing the CLN, and postoperative suprasternal swelling. The SFF retention group and COT group had a similar percentage of women (78.65% vs. 79.42%, P = 0.876) lower than that in the SFF resection group (95.19%, P < 0.001). The percentage of the visualized upper pole of the thymus before CLN removal was notably higher in the SFF resection group than that in the SFF retention group (63.46 vs. 29.21%, P < 0.001) but notably lower than that in the COT group (63.46% vs. 100%, P < 0.001). A total of 43.82% and 23.1% of patients in the SFF retention and COT groups showed suprasternal swelling, respectively. No patient exhibited such swelling in the SFF resection group (23.1% vs. 0, P < 0.001). Resection of SFF in ETA easily identified the lower boundary for CLND and prevented suprasternal fossa swelling.

Expression of CK19 in papillary thyroid carcinoma in comparison with benign thyroid lesions

Background: The Papillary variant of thyroid carcinoma is one of the common types of thyroid malignancies , the commonest. Its diagnosis usually is microscopic which based on nuclear features. Objective: To assess the immunohistochemical expression of cytokeratin 19 (CK19) in PTC and compare its reactivity with other thyroid conditions to approve its importance as a useful test for diagnosing PTC. Patients and Methods: Twenty- cases of papillary thyroid carcinoma (with different variants), five follicular adenomas and ten multinodular goiters (MNG) were collected over three years (2018-2021).10% formalin-fixed sections were collected from thyroidectomy specimens. Stained with Hematoxylin and eosin then immunohistochemical staining for immune-marker CK 19 was done using standard techniques. The results were quantitatively scored as the following: score 0 (negative ), score 1+ (&lt;5%) positive cells), score 2+ (5- 25%), score 3+ (25-75%) ,finally score 4+ (&gt;75%) positive cells), and then calculated. Results: An 18 (90%) papillary carcinomas show diffuse and strong (3+ and 4+) expression of CK19 . ,three out of ten (30%) MNG were weakly positive(1+ and 2+) and focal in distribution while in follicular adenoma all cases were negative for CK19 . Conclusion: Ck 19 can stain benign and malignant thyroid tissue, but strong membranous staining applied in cases of papillary ca , thus can be used as confirmatorytool for PTC diagnosis.

Expression of CK19 in papillary thyroid carcinoma in comparison with benign thyroid lesions

Background: The Papillary variant of thyroid carcinoma is one of the common types of thyroid malignancies , the commonest. Its diagnosis usually is microscopic which based on nuclear features.&#x0D; Objective: To assess the immunohistochemical expression of cytokeratin 19 (CK19) in PTC and compare its reactivity with other thyroid conditions to approve its importance as a useful test for diagnosing PTC.&#x0D; Patients and Methods: Twenty- cases of papillary thyroid carcinoma (with different variants), five follicular adenomas and ten multinodular goiters (MNG) were collected over three years (2018-2021).10% formalin-fixed sections were collected from thyroidectomy specimens. Stained with Hematoxylin and eosin then immunohistochemical staining for immune-marker CK 19 was done using standard techniques. The results were quantitatively scored as the following: score 0 (negative ), score 1+ (&lt;5%) positive cells), score 2+ (5- 25%), score 3+ (25-75%) ,finally score 4+ (&gt;75%) positive cells), and then calculated.&#x0D; Results: An 18 (90%) papillary carcinomas show diffuse and strong (3+ and 4+) expression of CK19 . ,three out of ten (30%) MNG were weakly positive(1+ and 2+) and focal in distribution while in follicular adenoma all cases were negative for CK19 .&#x0D; Conclusion: Ck 19 can stain benign and malignant thyroid tissue, but strong membranous staining applied in cases of papillary ca , thus can be used as confirmatorytool for PTC diagnosis.

Unusual papillary thyroid carcinoma with hyalinizing trabecular tumor-like feature in a young female patient: a case report

BackgroundHyalinizing trabecular tumor is a rare follicular cell-derived thyroid neoplasm that is considered to be a borderline tumor with malignant potential rather than a benign tumor. The detection of RET/PTC rearrangements and nuclear cytologic features suggests a relationship between hyalinizing trabecular tumor and papillary thyroid carcinoma. Some recent observations of pathogenic genetic alterations in hyalinizing trabecular tumor have indicated that hyalinizing trabecular tumor is not related to papillary thyroid carcinoma, and should be considered an independent entity. Here we present a case of papillary thyroid carcinoma with hyalinizing trabecular tumor-like features and discuss its interesting aspects and diagnostic issues from a histopathological perspective.Case presentationA 19-year-old Japanese woman with an enlarged thyroid gland was admitted to our hospital. Based on fine-needle aspiration cytology, the enlarged nodule was suspected to be a follicular lesion or follicular tumor. A nodular lesion approximately 3 cm in diameter was detected in the left lobe of the thyroid gland. Histological analysis revealed that the tumor cells were mainly arranged in follicles. Solid nests with occasional trabecular arrangements and papillary structures were intermingled, and the tumor cells showed ground-glass nuclei and occasional nuclear grooving. Petaloid and block-like periodic-acid-Schiff and periodic-acid-methenamine-positive basement membrane components were observed in the interstitium of the solid portions of the tumor. Incomplete membranous immunoreactivity of MIB-1 (Ki-67 (cell prolferation marker)) was also observed in the cells within the solid areas. Moreover, this tumor displayed extracapsular invasion and metastasis to the perithyroidal lymph nodes, suggesting that it may be a malignant tumor. However, BRAFV600E mutation, RET/PTC rearrangements, and PAX8/GLIS 1 and PAX8/GLIS 3 rearrangements were not detected.ConclusionWe diagnosed the tumor as a papillary thyroid carcinoma with characteristic features of hyalinizing trabecular tumor. Importantly, this case may indicate a possible relationship between papillary thyroid carcinoma and hyalinizing trabecular tumor, although specific genetic alterations could not be detected. We also discuss the preoperative diagnostic difficulties with fine-needle aspiration cytology and the unusual pathological findings in this case.

Diagnostic value of CT enhancement degree in lymph node metastasis of papillary thyroid cancer: A comparison of enhancement, ratio, and difference.

To evaluate the value of computed tomography (CT) enhancement degree in diagnosing lymph node (LN) metastasis in papillary thyroid carcinoma (PTC) by determining the ratio and difference between the Hounsfield units (HU) of CT enhancement and plain scan of the LNs, as well as between the HU of CT-enhanced LNs and the sternocleidomastoid muscle. The plain and enhanced CT findings of 114 metastasis-positive LNs in 89 cases and 143 metastasis-negative LNs in 114 cases of PTC were analyzed retrospectively. Plain HU of LNs (PNHU), enhanced HU of LNs (ENHU), and enhanced HU of the sternocleidomastoid muscle (EMHU) were measured. The ENHU, difference between ENHU and PNHU (EN-PNHU), ratio of ENHU to PNHU (EN/PNHU), difference between ENHU and EMHU (EN-EMHU), and ratio of ENHU to EMHU (EN/EMHU) in metastasis-positive and metastasis-negative LN groups were calculated, the corresponding diagnostic efficacy for differentiating metastasis-positive from metastasis-negative LNs in PTC were sought using the receiver-operating curve. The interobserver agreement between readers was assessed using the interobserver correlation coefficient (ICC). The ENHU of 114 metastasis-positive LNs and 143 metastasis-negative LNs was 113.39 ± 24.13 and 77.65 ± 15.93, EN-PNHU was 65.84 ± 21.72 HU and 34.07 ± 13.63 HU, EN/PNHU was 2.36 (1.98, 2.75) and 1.76 (1.54, 2.02), EN-EMHU was 49.42 ± 24.59 HU and 13.27 ± 15.41 HU, and EN/EMHU was 1.79 ± 0.40 and 1.21 ± 0.24, respectively (all P < 0.001). The area under the curve, cutoff value, sensitivity, specificity, and accuracy of ENHU for identifying metastasis-positive and metastasis-negative LNs were 0.895, 97.3 HU, 0.746, 0.895, and 0.829, EN-PNHU was 0.894, 47.8 HU, 0.807, 0.874, and 0.844, EN/PNHU was 0.831, 1.9, 0.877, 0.650, and 0.751, EN-EMHU was 0.890, 26.4 HU, 0.807, 0.839, and 0.825, and EN/EMHU was 0.888, 1.5, 0.728, 0.902, and 0.825, respectively. The readers had an excellent interobserver agreement on these five parameters (ICC = 0.874-0.994). In the preoperative evaluation of LN metastasis in PTC, ENHU, EN-PNHU, EN-EMHU, and EN/EMHU had similarly high diagnostic efficacy, with ENHU, EN-PNHU, and EN/EMHU having higher specificity and EN-PNHU and EN-EMHU having higher sensitivity.

Accuracy of different cytoarchitectural features in the diagnosis of papillary thyroid carcinoma by fine needle aspiration

Fine needle aspiration (FNA) has about 90% diagnostic accuracy for papillary thyroid carcinoma (PTC) in an adequate sample. Ignorance of relative significance of individual cytologic features may lead to misdiagnosis due to reliance on a single or few features. Our objective was to determine the usefulness of individual and most appropriate combined cytologic features, for diagnosis of PTC. H&amp;E stained FNA smears of fifty cases each, of consecutive histologically confirmed PTC and benign thyroid cases (controls), reported over 3 years, were retrieved from the files. A total of 31 architectural, cytological and background features were assessed, blind to the final diagnosis and compared amongst the two groups. The statistical significance (p&amp;#60;0.05) of each parameter was determined by chi-square and odds ratio and combinations quality assessed by ROC curves.: Twenty features were found to be statistically significant. Fourteen highly significant (p&amp;#60;0.000) features included flat syncytial sheets, anatomical borders, true papillae, cellular swirls, individually dispersed cells with eosinophilic cytoplasm, anisonucleosis, elongated oval nuclei, powdery chromatin, nuclear outline irregularity, thickened nuclear membranes, crescent shaped nuclei, intranuclear inclusions, histocytoid cells and soap bubble cytoplasmic vacuolation. The six statistically significant features (p&amp;#60;0.05) included micro-acinar structures, cellular crowding, nuclear overlapping, nuclear grooves, squamoid cells and bubble gum colloid. The control group also showed some of these single cytologic features. All the combinations of ≥ 4 features had a statistical significance of p=0.000 and specificity and PPV of 100% with ROC showing excellent results. Using correct combination of cytologic features will increase accuracy of FNA diagnosis of PTC.

Lymph Node Metastases in Papillary Thyroid Carcinoma can be Predicted by a Convolutional Neural Network: a Multi-Institution Study.

The presence of nodal metastases in patients with papillary thyroid carcinoma (PTC) has both staging and treatment implications. However, lymph nodes are often not removed during thyroidectomy. Prior work has demonstrated the capability of artificial intelligence (AI) to predict the presence of nodal metastases in PTC based on the primary tumor histopathology alone. This study aimed to replicate these results with multi-institutional data. Cases of conventional PTC were identified from the records of 2 large academic institutions. Only patients with complete pathology data, including at least 3 sampled lymph nodes, were included in the study. Tumors were designated "positive" if they had at least 5 positive lymph node metastases. First, algorithms were trained separately on each institution's data and tested independently on the other institution's data. Then, the data sets were combined and new algorithms were developed and tested. The primary tumors were randomized into 2 groups, one to train the algorithm and another to test it. A low level of supervision was used to train the algorithm. Board-certified pathologists annotated the slides. HALO-AI convolutional neural network and image software was used to perform training and testing. Receiver operator characteristic curves and the Youden J statistic were used for primary analysis. There were 420 cases used in analyses, 45% of which were negative. The best performing single institution algorithm had an area under the curve (AUC) of 0.64 with a sensitivity and specificity of 65% and 61% respectively, when tested on the other institution's data. The best performing combined institution algorithm had an AUC of 0.84 with a sensitivity and specificity of 68% and 91% respectively. A convolutional neural network can produce an accurate and robust algorithm that is capable of predicting nodal metastases from primary PTC histopathology alone even in the setting of multi-institutional data.

“HISTOPATHOLOGICAL STUDY OF THYROID NEOPLASMS WITH SPECIAL REFERENCE TO EXPRESSION OF GALECTIN-3 IN THYROID NEOPLASMS IN A TERTIARY CARE CENTRE”

Background: Globally, the number of thyroid cancer cases was estimated to be 586,000, ranking it 9th in 2020 and the incidence rate in women is 10.1 per 100,000 which is 3-fold higher than that in men (1). Benign neoplasms outnumber thyroid carcinomas, commonly occurring during 3rd to 6th decades of life. Despite histopathology being the mainstay for diagnosis, immunohistochemical markers have been invariably used in the recent years to aid in cases posing morphological diagnostic dilemma. To st Aims and objectives: udy the histopathological spectrum of thyroid neoplasms and expression of Galectin-3 in thyroid neoplasms. This is a one-year c Methodology: ross-sectional study (2021-2022) carried out in a tertiary care hospital of North East India. A total of histopathologically diagnosed 70 cases were studied and evaluated for immunohistochemical expression of Galectin-3. Majority (58.50%) of thyroid neoplasms were found to be benign, mostly Results: affecting the age group of (31- 40) years with female: male ratio being 7.75:1. Amongst the benign cases, all were diagnosed as follicular adenoma and amongst the malignancies, conventional papillary thyroid carcinoma constituted majority of the cases (58.62%). Galectin-3 was expressed signicantly in the malignant cases and the maximum expression was noted in 15 out of 17 cases (88.23%) of conventional papillary thyroid carcinoma. Thyroid Conclusion: neoplasms are highly curable with early detection and appropriate management. Hence, in diagnostically challenging cases, the utility of immunohistochemical markers along with the histomorphological interpretation becomes important.

Overexpression of the pro-protein convertase furin predicts prognosis and promotes papillary thyroid carcinoma progression and metastasis through RAF/MEK signaling.

Furin belongs to the pro-protein convertases (PCs) family and its aberrant expression has been documented in various types of cancers; however, its role in thyroid cancer remains unclear. We investigated the expression of furin in a large cohort of Middle Eastern papillary thyroid carcinoma (PTC) patient samples and explored its functional role and mechanism in PTC cell lines in vitro and in vivo. Furin overexpression was observed in 44.6% of all PTC cases and was significantly associated with aggressive clinicopathological parameters and poor outcomes. We show that the knockdown of FURIN suppresses tumor growth, proliferation, migration, invasion, spheroid growth, and progression of epithelial-to-mesenchymal transition (EMT) in B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutant cells, whereas its overexpression in BRAF wild-type PTC cell lines reversed the effect. FURIN knockdown in the BRAF mutant cell line led to reduced tumor growth and increased apoptosis. Mechanistically, FURIN knockdown led to MEK/ERK pathway suppression in BRAF mutant cells, although inhibition of MEK did not affect furin expression, which suggests that furin acts through the MEK/ERK pathway. Furthermore, our study revealed the synergistic antitumor effect of furin depletion and anti-MEK inhibitor treatment. Overall, these results indicate that furin is an important prognostic marker in Middle Eastern PTC and that it plays a crucial role in BRAF-associated MAP/ERK pathway activation and tumorigenesis. Furin inhibition could be a potential therapeutic target for aggressive PTC.

Expanding the Spectrum of BRAF Non-V600E Mutations in Thyroid Nodules: Evidence-Based Data from a Tertiary Referral Centre.

The BRAF p.V600E mutation represents the most specific marker for papillary thyroid carcinoma and is potentially related to aggressive behavior and persistent disease. BRAF alterations other than the p.V600E are less common in thyroid carcinoma and represent an alternative mechanism of BRAF activation with unclear clinical significance. The study aims to describe the frequency and clinicopathologic characteristics of BRAF non-V600E mutations in a large cohort (1654 samples) of thyroid lesions characterized by next-generation sequencing. BRAF mutations have been found in 20.3% (337/1654) of thyroid nodules, including classic (p.V600E) mutation in 19.2% (317/1654) of samples and non-V600E variants in 1.1% of cases (19/1654). BRAF non-V600E alterations include 5 cases harboring p.K601E, 2 harboring p.V600K substitutions, 2 with a p.K601G variant, and 10 cases with other BRAF non-V600E alterations. BRAF non-V600E mutations have been reported in one case of follicular adenoma, three cases of conventional papillary thyroid carcinoma, eight cases of follicular variant of papillary carcinomas, one case of columnar cell variant papillary thyroid carcinoma, one case of oncocytic follicular carcinoma, and two bone metastasis of follicular thyroid carcinoma. We confirm that BRAF non-V600E mutations are uncommon and typically found in indolent follicular-patterned tumors. Indeed, we show that BRAF non-V600E mutations can be found in tumors with metastatic potential. However, in both aggressive cases, the BRAF mutations were concomitant with other molecular alterations, such as TERT promoter mutation.

An unusual case of papillary thyroid carcinoma presenting as Graves’ disease

ABSTRACT Thyroid cancer in patients with Graves’ disease (GD) was reported with incidences varying from 2.3% to 21.1%. The prognosis of thyroid cancer in patients with GD has been debatable. Here we present a rare case of papillary thyroid carcinoma associated with GD in a 23-year-old female presenting with goiter and thyrotoxicosis symptoms, diagnosed with GD, who because of suspicious findings, underwent further investigations and was found to have thyroid carcinoma. The patient underwent surgery preceded by antithyroid medications. Histopathological examination confirmed malignancy and further management was done.