Conventional Papillary Thyroid Carcinoma Research Articles

Unifocal Conventional Papillary Thyroid Carcinoma with Coexisting Caseating Granulomatous Inflammation in India

Unifocal Conventional Papillary Thyroid Carcinoma with Coexisting Caseating Granulomatous Inflammation in India

Predictors of distant metastatic recurrence in intermediate-risk papillary thyroid carcinoma.

Patients with intermediate-risk papillary thyroid carcinoma (PTC) have a favorable prognosis with standard treatment of total thyroidectomy (TT) and adjuvant radioactive iodine therapy (RAIT). However, the benefits of TT or adjuvant RAIT remain undetermined, and they are often omitted in Japan. We investigated risk factors for life-threatening distant recurrence in patients with intermediate-risk PTC who are optimal candidates for adjuvant RAIT. Outcomes without RAIT were retrospectively examined in 4030 intermediate-risk conventional PTC cases underwent initial surgery from 2005 to 22 (IRB approval 20200709-1). Lobectomy (LT) and TT was performed in 11.5% and 88.5%, respectively. Recurrent laryngeal nerve paralysis and hypoparathyroidism was less commonly observed in LT (1.3% and 0%) than TT (2.4% and 3.5 %). Fifty-six cases (1.4%) had distant recurrence. Recurrence-free survival rates at 10years was 93.5%. There was no significant difference in recurrence rate between LT and TT. Age ≥55, cN1b, and tumor diameter >30mm significantly associated with distant recurrence. There was a strong relationship between the number of positive risk factors and recurrence; the distant recurrence rate in cases of 0, 1, 2, and 3 positive factors was 0.3% (4/1203), 1.3% (25/1889), 2.7% (23/830) and 7.1% (4/52) (HR 6.46 (2.34-17.86), Log-rank <0.001). For intermediate-risk conventional PTC, there is no difference in prognosis even if LT was selectively conducted. However, in patients with risk factors for distant metastatic recurrence, such as age ≥55years, cN1b, and tumor size >30mm, adjuvant RAIT was considered eligible.

Can thyroid histomorphology identify patients with PTEN hamartoma tumour syndrome?

The phosphatase and tensin homologue (PTEN) hamartoma tumour syndrome (PHTS) is a genetic disorder with variable clinical presentation and increased lifetime risk of multiorgan malignancies. The thyroid gland is commonly affected with follicular nodular disease (FND) and follicular cell-derived carcinomas. Histopathological and immunohistochemical assessment of thyroid disease in PHTS is essential to identify patients at-risk. In all, 30 PHTS patients with available thyroidectomy specimen material (2000-2023) and 31 control patients with FND and "adenomatous nodules" were retrieved. Histologic criteria, including the frequency of adenomatous-type nodules versus hyperplastic-type nodules, background and nodular lipomatous metaplasia, chronic lymphocytic thyroiditis, cytoplasmic clearing of follicular cells in nodules, nodule-in-nodule appearance, and spectrum of nuclear atypia between nodules were evaluated in both cohorts and a Thyroid Histomorphologic PHTS Score (THiPS) system was established with a cutoff of 4 points or higher being considered concerning for PHTS. In all, 27 PHTS (90%) and five control (16.1%) cases had THiPS ≥4. A PTEN immunohistochemical stain was evaluated in 25 cases of each cohort and showed nuclear and cytoplasmic loss of expression in all or most of the nodules of 24/25 PHTS cases. In 3/25 control cases, two with THiPS ≥4, had loss of expression in one to multiple nodules. Conventional papillary thyroid carcinomas in PHTS patients retained PTEN cytoplasmic expression. Our study supports that, although not specific, the finding of multiple histologic features is found more frequently in patients with PHTS compared to the non-PHTS control group. The THiPS system has high sensitivity for thyroid specimens from patients with PHTS.

Availability of Serum Levels of Carbohydrate Antigen 19-9 (CA19-9) as a Surrogate Tumor Marker for Papillary Thyroid Carcinoma.

Thyroglobulin (Tg) is a very sensitive and specific marker in patients who have undergone total thyroidectomy for papillary thyroid carcinoma (PTC). However, the presence of a Tg antibody (TgAb) interferes with Tg immunometric assays, making Tg levels unreliable indicators. There are currently no other tumor markers to monitor in patients with PTC whose serum is TgAb-positive. Thus, we investigated whether carbohydrate antigen 19-9 (CA19-9) can be used as a tumor marker for PTC. We retrospectively analyzed 196 consecutive patients with PTC (maximum diameter ≥ 2 cm). The serum CA19-9 and Tg values of each patient were obtained before and 0.5-1 month postsurgery. Immunohistochemical staining for PTC was performed using an antibody against CA19-9. High pre-surgery serum levels of CA19-9 were observed in 6.1% of the patients. Postsurgery, serum CA19-9 levels in all 196 patients decreased considerably and were within the normal range. CA19-9 expression was detected in 28 of 62 PTCs (45.2%) and was detected at various degrees and ranges in conventional PTC histology. Although further studies with longer follow-ups are necessary, serum CA19-9 levels may serve as a surrogate tumor marker for PTC in place of serum Tg levels sin some patients.

Demographic, clinical, and surgical features of patients undergoing thyroidectomy due to thyroid lesions in Southern Iran: A cross-sectional study.

The incidence of thyroid cancer has witnessed a significant global increase and stands as one of the most prevalent cancers in Iran. This surge is primarily attributed to the escalating incidence of papillary thyroid cancer (PTC), with overdiagnosis emerging as an equally noteworthy factor. Consequently, this study aims to ascertain the incidence of thyroid cancer, along with its clinical presentation, demographic characteristics, and surgical features in patients undergoing thyroid surgery. This cross-sectional study involved the evaluation of patient files from referral centers in Shiraz spanning the years 2015-2020. Demographic and clinical information pertaining to thyroid cancer was extracted and subsequently analyzed using SPSS software. A total of 533 documented cases of thyroid cancer undergoing surgery revealed an annual rate of 89 cases in our location. The average age of the patients was 43.9 ± 13.4 years (ranging from 13 to 92), with females constituting 429 (83.5%) of the cases, and 278 (54.1%) being malignant. Conventional PTC emerged as the most prevalent pathology, accounting for 239 (45.0%) of the cases. Patients with thyromegaly exhibited significantly higher incidences of nonmalignant tumors (p = 0.01), while those with malignant tumors were notably younger than those with nonmalignant tumors (p = 0.001). Our study revealed a progressive rise in the number of patients undergoing thyroidectomy over the years, with PTC constituting the majority of cases. Malignant cases were more frequently observed in younger patients, and in smaller lesion sizes, highlighting the importance of early screening and optimizing detection methods, especially in high-risk populations.

Relationship between recurrence and age in the diffuse sclerosing variant of papillary thyroid carcinoma: clinical significance in pediatric patients.

The diffuse sclerosing variant (DSV) is among the aggressive variants of papillary thyroid carcinoma (PTC) and is more prevalent in pediatric patients than in adult patients. Few studies have assessed its characteristics owing to its low incidence. We aimed to evaluate the relationship between recurrence and age in the DSV of PTC. We retrospectively reviewed patients diagnosed with the DSV or conventional PTC (cPTC) after surgery at a medical center between May 1988 and January 2019. We compared the clinico-pathological characteristics and surgical outcomes of the DSV and cPTC groups and between adult and pediatric patients with DSV. Among the 24,626 patients, 202 had the DSV, and 24,424 were diagnosed with cPTC. The recurrence rate was significantly higher in the DSV group than in the cPTC group. In the DSV group, the recurrence rate was significantly higher in the pediatric patient group than in the adult patient group. Moreover, the association between recurrence and age group showed different patterns between the DSV and cPTC groups with restricted cubic splines (RCS). While both RCS curves showed a U-shaped distribution, the RCS curve tended to be located within the younger age group. This study demonstrated that pediatric patients with DSV are at a greater risk for recurrence compared with adult patients; moreover, the pattern of recurrence risk according to age is different from that of cPTC.

Columnar Cell Variant of Papillary Thyroid Carcinoma: Cytological and Histopathologic Correlation

Abstract Of all primary thyroid neoplasm, papillary thyroid carcinoma (PTC) is the commonest one. Beside the conventional PTC, there are various histological variants, among them columnar cell variant of papillary thyroid carcinoma (PTC-CCV), which is a rare entity that demonstrates a more aggressive clinical course compared with the other variants of PTC. Cytologically, its diagnosis is by exclusion of any cellular papillary fragments whereas, histologically by its unique features. Methods: A total of twelve thyroidectomies mainly of PTC-CCV with their preoperative FNAC were included and collected over a 5-year period. All the aspirated materials were stained previously by H&E stains. Results: All cases were demonstrating the presence of papillary malignant structures. Majority of the studied cases FNAC was revealing hypercellularity with variable superposition in association with paucity of nuclear pseudoinclusions and grooves.

Prevalence and Impact of BRAF mutation in patients with concomitant papillary thyroid carcinoma and Hashimoto's thyroiditis: a systematic review with meta-analysis.

Evidence suggests that patients with Hashimoto thyroiditis (HT) are at significantly higher risk of developing papillary thyroid cancer (PTC). However, the course of PTC in patients with both diseases concomitantly has been found to be more indolent than conventional PTC. Additionally, it has been well proven that BRAF mutation results in an aggressive course of PTC. The aims of this meta-analysis were to identify prevalence of BRAF mutation and its impact on clinicopathological features in patients with concomitant PTC-HT. Medline, Cochrane Library, Scopus, and Web of Science were searched until 16.09.2022, resulting in 227 articles, of which nine studies were included. Summary estimates, comparing patients with (A) BRAF (+) PTC-HT versus BRAF (+) PTC, and (B) BRAF (+) PTC-HT versus BRAF (-) PTC-HT, were generated with Review Manager 5.0. In total, 6395 patients were included in this review. PTC-HT patients had significantly less BRAF mutation than PTC patients (Odds Ratio (OR) (95% Confidence Interval (CI))=0.45 (0.35-0.58), P<0.001). BRAF (+) PTC-HT patients were significantly more likely to have multifocal lesions (OR (95% CI)=1.22 (1.04-1.44), P=0.01) but less likely to have lymph node metastasis (OR (95% CI)=0.65 (0.46-0.91), P=0.01) and extrathyroidal extension (OR (95% CI)=0.55 (0.32-0.96), P=0.03) compared to BRAF (+) PTC patients. BRAF (+) PTC-HT patients were more likely to have multifocal lesions (OR (95% CI)=0.71 (0.53-0.95), P=0.02), lymph node metastasis (OR (95% CI)=0.59 (0.44-0.78), P<0.001) and extrathyroidal extension (OR (95% CI)=0.72 (0.56-0.92), P=0.01) compared to BRAF (-) PTC-HT patients. This meta-analysis highlights that the lower prevalence of BRAF mutation in patients with PTC-HT than conventional PTC may explain the indolent clinicopathological course in this cohort.

SAT551 Significantly Elevated Thyroglobulin Levels with Negative Whole-Body Scan and PET/CT After Treatment of Thyroid Cancer: A Case Report

Abstract Disclosure: A. Bassatne: None. J.T. Chaiban: None. Background: Thyroglobulin (Tg) levels are used to monitor recurrence or persistence of disease after treatment of differentiated thyroid cancer. Some cases may have persistently elevated Tg and negative whole-body scans (WBS). We present a case of substantially elevated Tg levels despite negative WBS and PET/CT after thyroidectomy and radioactive iodine (RAI) treatment in a patient with papillary thyroid carcinoma (PTC). Clinical Case: A 66 years old lady was referred to the endocrinology clinic almost 5 years ago after incidental findings of calcified thyroid nodules on CT. Thyroid US confirmed 2cm aggregate calcified nodules. FNA revealed PTC for which she underwent thyroidectomy. Pathology showed a unifocal 3.5 cm left lobe conventional PTC without angioinvasion nor extrathyroidal extension, 3/13 positive lymph nodes (LN) on the lateral dissection of the left neck as well as multiple small LN on the central dissection. 6 days postop, her Tg was still significantly high at 40.5ng/mL (Ref 1.2-35 ng/mL) and then increased to 397ng/mL after thyrogen preparation for RAI ablation, antithyroglobulin antibodies were negative. WBS post RAI was negative except for the physiologic neck uptake. Almost a year later, a diagnostic WBS after thyrogen stimulation was still negative but the stimulated Tg increased again to 235 ng/mL with negative thyroglobulin antibodies. Tg result were confirmed by LC-MS method. Heterophile Antibodies were negative. Patient confirmed that every single time she followed at least 2 weeks of low iodine diet in preparation for the WBS. Unfortunately, we were not able to get a 24 hour urine collection for iodine. A PET/CT was reassuring. CT neck/chest did not show any suspicious metastases. TSH was maintained at an adequately suppressed level all through and Tg levels were ranging around 6-8 ng/mL. After another year, a stimulated Tg was 302.4 ng/mL with a TSH of 198 mcU/mL (Ref 0.35-5.0 mcU/mL). At that time, a repeat WBS was negative and a repeat PET/CT demonstrated an interval development of a small thyroid focus thought to be consistent with recurrence of malignancy. However, a CT of neck/chest did not reveal any abnormal thyroid findings or metastases. Patient received 100 mCi of RAI after thyroid hormone withdrawal. Subsequent WBS was negative. Currently her Tg levels are stable at around 8-9ng/mL for the past 6 months with a suppressed TSH. Patient had another PET/CT through her breast surgeon to follow on a previous breast lesion and no thyroid abnormality was noted. Conclusion: Elevated Tg levels despite negative imaging may be seen in patients with PTC as illustrated in this case. We are reporting it due to the extent of elevation of Tg levels seen on more than one occasion in the absence of structural recurrence. Evaluation and treatment of such patients remain controversial. Presentation Date: Saturday, June 17, 2023

SAT558 Papillary Thyroid Carcinoma With Anaplastic Transformation in a Filipino Male Treated With Radioactive Iodine and Radiotherapy: A Case Report

Abstract Disclosure: A.A. Apa-ap: None. P. Abarquez: None. M.B. Sedurante: None. A. Ongbit: None. P. Carlos Miguel: None. F. Acenas: None. J. Gacula: None. V. Lee: None. S. Estreller: None. INTRODUCTION. Papillary thyroid carcinoma (PTC) is an epithelial malignancy showing follicular differentiation and distinctive nuclear features, with a generally excellent prognosis. On the other hand, anaplastic thyroid cancer (ATC) is rare and highly lethal, with an incidence of only 0.7% in the Philippines. CASE DESCRIPTION. This paper describes a 43year old Filipino male with a 3-year history of anterior neck mass with an initial fine needle aspiration biopsy read as probable PTC. He underwent total thyroidectomy and bilateral radical lymph node dissection and histopathology revealed conventional PTC, solid variant with 5% focal anaplastic transformation. Metastatic workup revealed multiple sub-centimeter pulmonary nodules and a tiny hypodense nodule on left adrenal gland on CT scan. Bone scintigraphy showed increased tracer uptake in the posterior 10th rib and the sphenoid's greater wing. While the multidisciplinary team wanted to proceed with Radiation therapy (RT) first to address the more aggressive histology, this was not possible logistically and thus RAI was performed first. This slight deviation from guidelines was deemed acceptable by Nuclear Medicine due to the possible decrease in iodine absorption from post radiation fibrosis. After a dose of 150 mci, 4 weeks after surgery, patient then completed 33 fractions of RT. Surveillance revealed stable pulmonary nodules and adrenal mass but increasing TSH-stimulated thyroglobulin and antithyroglobulin. Patient underwent another cycle RAI and is currently stable on his 16th month from diagnosis, 15th month post initial RAI, and 13th month post-RT. DISCUSSION. In several case series, patients with minor anaplastic component had 1- and 2-year survival rates of 88% and 43%, respectively with a median survival of 17 months. The overall prognosis of patients with PTC with minor ATC component points to the value of active surveillance compared to more aggressive treatment modalities in the setting of conventional ATC. Presentation Date: Saturday, June 17, 2023

Geometric characteristics and design optimization of parabolic trough concentrators with a flat mirror as the secondary reflector designed based on two components of a solar source

Parabolic trough concentrators with a tubular receiver (PTCs) are widely used for the production of solar thermal power. However, the geometric concentration ratio (CR) of PTCs falls short of thermodynamic concentration limit (C0) by a factor larger than π, and restricted by the angle subtended by solar sources (Δs = 2θa). To increase CR, a novel idea by dividing a solar source into two components in the open angle is proposed for the design of PTC equipped with a secondary reflector (SR), and PTC with a flat mirror (FM) is designed as a trial of the idea. For such design idea, rays incident at rims of primary parabolic reflector (PR) from one component (S1) are required to directly redirect onto on the absorber tube (AT) and those from another component (S2) are required to arrive on the AT after reflections from PR first then from FM. To investigate effects of the angular division factor (k) of solar sources (Δs2 = kΔs) and rim angle (ϕe) of PR on the effective CR (Cg), a mathematical procedure to characterize the geometry is suggested and examined by ray-tracing technique. The analysis shows that the geometry of PTC-FM is dependent on k, ϕe and θa, and a set of optimal k and ϕe for maximizing Cg can be obtained when θa is given. Calculation results show that the optimal k for maximizing Cg is 0.5 regardless of θa, but the optimal ϕe of PTC-FM for maximizing Cg, is sensitive to θa. As compared to conventional PTCs, the Cg of optimized PTC-FM is increased more than 80%, larger than 56.5% of C0, for k = 0.5 and θa < 1.0°. Empirical expressions for a quick estimation of optimal ϕe are also proposed based on numerical calculations. Results by ray-tracing analysis indicate that the optimal ϕe for maximizing CR and average solar concentration ratio are almost identical when the reflectivity of PR and FM is higher than 0.8. In principle, the novel idea is applicable for the design of other solar concentrators, therefore a further increase of Cg of PTCs is possible by using other imaging and non-imaging optics as the SR.

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.

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.

Combined Cyclin D2 and Protein Convertase 2 Genes in Differentiating Various Follicularpatterned Lesions and Neoplasms of the Thyroid: A Cross-sectional Study

Introduction: A pretherapeutic distinction between benign and malignant thyroid nodules is critical for the clinical management of patients presenting with thyroid nodules. However, certain follicular-patterned lesions, such as adenomatous nodules, follicular neoplasms comprising Follicular Adenoma (FA) and Follicular Carcinoma (FC), as well as the Follicular Variant of Papillary Thyroid Carcinoma (FVPTC), can pose a significant dilemma during pre-therapeutic Fine Needle Aspiration Cytology (FNAC) evaluation. The present (pilot) study explores the possible utility of messenger Ribonucleic Acid (mRNA) and the protein expression of the two relatively less-explored genes, Cyclin D2 (CCND2) and Protein Convertase 2 (PCSK2), in distinguishing various follicular-patterned thyroid lesions and neoplasms by testing these molecular markers initially on histopathological sections. Aim: To assess the RNA and protein expressions of CCND2 and PCSK2 genes in differentiating follicular-patterned thyroid neoplasms. Materials and Methods: This was a cross-sectional analytical study conducted over 6 years, from August 2014 to August 2020, at the Department of Pathology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India. Real-Time quantitative Polymerase Chain Reaction (RT-qPCR) along with Immunohistochemistry (IHC) was performed on a total of 75 tissue samples from follicularpatterned thyroid lesions and neoplasms, including 19 Follicular Hyperplasias (FHs), 10 Nodular Goitres (NGs), 17 FAs, 8 FCs, and 12 FVPTCs, along with nine Conventional Papillary Thyroid Carcinomas (CPTCs). After confirming the RNA and protein expression levels in each of these lesions, Immunoreactive Scoring (IRS) was performed to assess their IHC expression. The Kruskal-Wallis and Analysis of Variance (ANOVA) tests were used to analyse the mRNA expression data, and Pearson analysis was conducted to correlate the IHC data between the study groups. A p-value of &lt;0.05 was considered statistically significant. Results: Among the 75 thyroid lesions studied, both NG and FA showed a relatively higher cyclinD2 mRNA expression, with fold changes of 1.21 and 1.46, respectively. This was also reflected in IHC, with moderate nuclear expression observed in these cases. The PCSK2 mRNA expression was similar to that of CCND2, with the only difference noted between FH and FA. On IHC, eight out of 75 cases had positive PCSK2 expression, including five FHs, two FVPTCs, and one FA, while the remaining 67 cases were negative. Conclusion: The CCND2 and PCSK2 genes assessed in the present study, regarding their mRNA and protein expressions, were not found to be of any practical value in distinguishing benign and malignant follicular lesions or neoplasms of the thyroid.

Role of GDF-15 as an Immunohistochemical Marker in Follicular Neoplasms and Lesions of Thyroid

Introduction: A pre-therapeutic distinction between benign and malignant thyroid nodules is critical for deciding the therapeutic strategy, wherein fine-needle aspiration cytology plays a major role. However, there are grey-zone categories in the Bethesda system for reporting thyroid cytopathology, which is currently, the universally accepted pattern for reporting thyroid FNAC. Several immunomarkers studied in these ‘indeterminate’ lesions have proven to be of limited value. Recent molecular studies have shown the growth differentiation factor-15 (GDF-15) gene to be a promising marker in various malignancies; though, there is sparse literature regarding its use as a surrogate immunohistochemical marker, especially in thyroid neoplasms. The present (pilot) study explores its possible utility in the pre-therapeutic distinction of follicular-patterned lesions and neoplasms of the thyroid by testing it initially on histopathologic sections. Objective: To assess the utility of GDF-15 as an immunohistochemical marker in distinguishing common follicular-patterned thyroid neoplasms and lesions. Materials and Methods: GDF-15 immunohistochemistry was performed on 75 surgical specimens of thyroid lesions, comprising 19 adenomatous nodules or follicular hyperplasias, 10 nodular goitres, 17 follicular thyroid adenomas, 8 follicular thyroid carcinomas, 12 follicular variant of papillary thyroid carcinomas, and 9 conventional papillary thyroid carcinomas. All these cases were histologically proven, and their immunohistochemical interpretation was performed using the immunoreactive scoring system. Pearson’s analysis was performed for the immunohistochemical correlation among the study groups. Results: The findings were inconsistent; 16 follicular-patterned malignancies (5 follicular carcinomas and 11 cases of follicular variant of papillary carcinoma) and seven conventional papillary thyroid carcinomas revealed both cytoplasmic and membranous expression of GDF-15. All benign lesions were negative except one follicular adenoma and three follicular hyperplasias, which exhibited patchy or focal GDF-15 positivity. However, three follicular carcinomas, one follicular variant of papillary carcinoma, and two conventional papillary carcinomas were found to be GDF-15-negative. Conclusion: Though there is a literature backup supporting the use of GDF-15 gene analysis in differentiating various follicular-patterned neoplasms, the GDF-15 protein, as an immunohistochemical marker failed to distinguish not only between benign and malignant follicular-patterned neoplasms but also between follicular carcinoma and follicular variant of papillary carcinoma.

Thyroid Oncocytic (Hürthle Cell) Nodules With Longitudinal Nuclear Grooves: Clinicopathologic, Immunohistochemical, and Molecular Genetic Study of 15 Cases.

Thyroid nodules with longitudinal nuclear grooves have been widely regarded as synonymous with papillary thyroid carcinoma (PTC). To study a series of cases of thyroid nodules that exhibited oncocytic (Hürthle cell) features and contained longitudinal nuclear grooves yet failed to display aggressive behavior or the full features of papillary thyroid carcinoma. The clinicopathologic, immunohistochemical, and molecular genetic features of 15 patients with these features were studied. Next-generation sequencing was performed to examine 161 genes for oncogenic driver alterations associated with thyroid neoplasia. The lesions occurred in 11 women and 4 men aged 27 to 80 years and measured 0.2 to 2.3 cm in diameter (mean, 1.1 cm). The tumors were well circumscribed and noninvasive and showed a proliferation of large cells with abundant granular cytoplasm and centrally placed nuclei displaying scattered longitudinal nuclear grooves. Immunohistochemical stains were negative for HBME-1, galectin-3, and CK19 in all cases. NRAS pQ61R was detected in 6 cases, KRAS p.Q61E in 1 case, and AKT2 p.E17K in 1 case. None of the genetic changes classically associated with conventional PTC or with high-grade thyroid malignant neoplasms were identified. Clinical follow-up in 9 patients showed no evidence of recurrence or metastases between 2 and 13 years (mean, 5.7 years). Longitudinal nuclear grooves can be occasionally encountered in oncocytic (Hürthle cell) tumors and should not lead to a diagnosis of PTC in the absence of other features supporting that diagnosis.

Conventional papillary thyroid carcinoma with intraglandular lymphatic dissemination shows more aggressive features.

To investigate the invasive capability and other clinicopathological features of conventional papillary thyroid carcinoma (CVPTC) with intraglandular lymphatic dissemination. Seventy-three conventional papillary thyroid carcinoma patients receiving total thyroidectomy were analyzed in this study. The expression of BRAF-V600E, D2-40 and CD31 in all thyroid samples was detected by immunohistochemical staining. The results were evaluated by two pathologists and were statistically analyzed. The rate of positive BRAF-V600E expression and the clinical invasiveness of CVPTC with intraglandular dissemination, multifocal non-intraglandular dissemination-CVPTC and single focus-CVPTC were evaluated. The correlation between BRAF-V600E expression, lymphatic vessel density, microvessel density and the clinicopathological characteristics of conventional papillary thyroid carcinoma were assessed. Twenty-five intraglandular dissemination-CVPTC, 17 multifocal non-intraglandular dissemination-CVPTC and 31 single focus-CVPTC cases were included in this study. The results showed that BRAF-V600E expression was independently correlated with intraglandular dissemination, age and pN staging (P<0.05). The lymphatic vessel density in the intraglandular dissemination-CVPTC group was higher than that in the non-intraglandular dissemination-CVPTC group (P<0.05). Compared with cases without intraglandular dissemination, intraglandular dissemination-CVPTC was associated with a younger age, higher lymph node metastasis rate, pN staging, the expression of BRAF-V600E and increased Capsule invasion and lymphovascular tumor thrombus (P<0.05). During the follow-up of 30months (median 15months), two patients in the intraglandular dissemination-CVPTC group had cervical lymph node metastasis after the first operation. Intraglandular dissemination-CVPTC shows more aggressive features, and intraglandular lymphatic dissemination may be a potential biological indicator of poor prognosis.

Artificial Neural Network-Based Ultrasound Radiomics Can Predict Large-Volume Lymph Node Metastasis in Clinical N0 Papillary Thyroid Carcinoma Patients.

Objective To evaluate the ability of artificial neural network- (ANN-) based ultrasound radiomics to predict large-volume lymph node metastasis (LNM) preoperatively in clinical N0 disease (cN0) papillary thyroid carcinoma (PTC) patients. Methods From January 2020 to April 2021, 306 cN0 PTC patients admitted to our hospital were retrospectively reviewed and divided into a training (n = 183) cohort and a validation cohort (n = 123) in a 6 : 4 ratio. Radiomic features quantitatively extracted from ultrasound images were pruned to train one ANN-based radiomic model and three conventional machine learning-based classifiers in the training cohort. Furthermore, an integrated model using ANN was constructed for better prediction. Meanwhile, the prediction of the two models was evaluated in the papillary thyroid microcarcinoma (PTMC) and conventional papillary thyroid cancer (CPTC) subgroups. Results The radiomic model showed better discrimination than other classifiers for large-volume LNM in the validation cohort, with an area under the receiver operating characteristic curve (AUROC) of 0.856 and an area under the precision-recall curve (AUPR) of 0.381. The performance of the integrated model was better, with an AUROC of 0.910 and an AUPR of 0.463. According to the calibration curve and decision curve analysis, the radiomic and integrated models had good calibration and clinical usefulness. Moreover, the models had good predictive performance in the PTMC and CPTC subgroups. Conclusion ANN-based ultrasound radiomics could be a potential tool to predict large-volume LNM preoperatively in cN0 PTC patients.

Minimal extrathyroidal extension is associated with lymph node metastasis in single papillary thyroid microcarcinoma: a retrospective analysis of 814 patients

BackgroundExtrathyroidal extension (ETE) is considered a major prognostic factor in papillary thyroid carcinoma (PTC). Patients with gross ETE are at increased risk of recurrence and mortality. The importance of minimal ETE still remains controversial, especially in patients with papillary thyroid microcarcinoma (PTMC). The purpose of this study was to evaluate the association between ETE and lymph node (LN) metastasis in single PTMC.MethodsA retrospective analysis was performed of 1994 patients underwent thyroidectomy for PTC between 2012 and 2016 in a single institution. Patients with combined thyroid carcinoma of other types and those who underwent completion thyroidectomy were excluded. After further exclusion of PTC larger than 1 cm and multifocal tumors, 814 patients with single PTMC were included in the study.Results72.9% patients had no ETE, 25.1% minimal ETE, and 2.1% gross ETE. ETE was associated with lymphatic invasion, perineural invasion, and vascular invasion. Patients with minimal and gross ETE were also more likely to have LN metastasis, including lateral neck metastasis, compared to those without ETE. In univariate analysis, LN metastasis was associated with male gender, conventional PTC, lymphatic invasion, perineural invasion, and ETE. In multivariate analysis, male gender (OR = 1.987; 95% CI 1.369–2.884), lymphatic invasion (OR = 4.389; 95% CI 1.522–12.658), perineural invasion (OR = 6.545; 95% CI 1.262–33.948), and minimal ETE (OR = 1.852; 95% CI 1.298–2.643) were found to be independent risk factors of LN metastasis.ConclusionsMinimal ETE is associated with LN metastasis in single PTMC, compared to no ETE. Minimal ETE should be considered in the management of patients with single PTMC, whether surgical or during active surveillance.