Classic Papillary Thyroid Carcinoma Research Articles

Cytological Features of "Non-Invasive Follicular Tumour with Papillary like Nuclear Features" - A Single Institutional Experience in India.

The term noninvasive follicular tumor with papillary-like nuclear features (NIFTP) was introduced as a surrogate for noninvasive encapsulated follicular variant of papillary thyroid carcinoma with a defined set of histopathologic criteria. There are very few studies depicting the cytological cues for the diagnosis of NIFTP. The objective of the study was to determine the spectrum of cytological features in fine needle aspiration cytology (FNAC) smears of cases histopathologically diagnosed as NIFTP. This was a retrospective cross-sectional study conducted over a duration of four years between January 2017 and December 2020. All surgically resected cases (n-21), who met the diagnostic criteria of NIFTP on histopathology and who underwent preoperative FNAC were included and reviewed in the study. Out of a total of 21 cases, at FNAC, diagnosis of benign, suspicious for malignancy, follicular variant of papillary thyroid carcinoma, and classic papillary thyroid carcinoma (PTC) was rendered in 14 (66.6%), 2 (9.5%), 2 (9.5%), and 3 (14.28%), respectively. Scanty cellularity was noted in 12 (57.1%) cases. Papillae, sheets, and microfollicles were seen in 1 (4.7%), 10 (47.6%), and 13 (61.9%) cases, respectively. Nucleomegaly, nuclear membrane irregularities, nuclear crowding, and overlapping were seen in 7 (33.3%), 9 (42.8%), and 9 (42.8%), respectively. Nucleoli, nuclear grooving, and inclusions were seen in 3 (14.2%) 10 (47.6%), and 5 (23.8%) cases, respectively. At FNAC, NIFTP can be found in every category of The Bethesda System for Reporting Thyroid cytopathology (TBSRTC). Nuclear membrane irregularities, nuclear grooving, mild nuclear crowding, and overlapping were noted in a modest number of cases. However, the absence or rare occurrence of features such as papillae, inclusions, nucleoli, and metaplastic cytoplasm may help prevent an overdiagnosis of malignancy.

Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: Pitfalls of Cytological and Histopathologic Diagnosis

Classical papillary thyroid carcinoma (PTC) is the commonest primary thyroid neoplasm. Besides PTC, significant histological variants that differ from classical PTC in regard to the morphological, cytologic and histologic features are mentioned; among them is follicular variant papillary thyroid carcinoma (FVPTC). The update WHO classification and the update Bethesda system reclassified FVPTC introduced a new entity which is "non-invasive follicular thyroid neoplasm with papillary like nuclear features" (NIFTP) that is characterized by an indolent behavior with encapsulated noninvasive growth features. Recently this entity is considering one of an indeterminate cytological categories (category III-IV-V). Update studies are found a combination of triple diagnostic procedures included sonographical, cytologic and molecular investigations can be suspecting preoperative diagnosis. Methods: A total of 150 selected cases of solitary thyroid nodules (STNs) with preoperative FNAC have an indeterminate follicular patterned cytological lesions with their underlying thyroidectomies that were collected in a 5-year period included in this article. Results: Majority of our cases were females and suffering from neck swelling. Cytollogically all the enrolled cases were lying in the indeterminate categories and histologically they were encapsulated with variable sizes follicles, nuclear features, no vascular invasion, no psammoma bodies, no tumor necrosis or mitosis. Also, there is no any extra-thyroid invasion. Conclusion: The accurate diagnosis of this entity “”NIFTP” carries many congratulations in regard that is “not malignant” category among both update TBSRTC and the final histopathological examination of the excised thyroid tissue.

PD-L1 expression in rare and aggressive thyroid cancers: A preliminary investigation for a role of immunotherapy.

Programmed cell death ligand-1 (PD-L1) immunoexpression status determines the response to immunotherapy in many cancers. Limited data exist on PD-L1 status in aggressive thyroid tumors. We investigated PD-L1 expression across thyroid cancers and correlated it with their molecular profile. Sixty-five cases of differentiated thyroid carcinoma, poorly differentiated thyroid carcinoma (PDTC), and anaplastic thyroid carcinoma (ATC) were assessed for PD-L1 expression (clone SP263, VENTANA). The differentiated cases encompassed the aggressive hobnail and tall cell subtypes of papillary thyroid carcinoma (PTC) besides classical PTC and follicular thyroid carcinoma (FTC). Ten nodular goiters (NG) were also evaluated. Tumor proportion score (TPS) and H-score were calculated. BRAFV600E and H-/K-/N-RAS were assessed using allele-specific real-time polymerase chain reaction (PCR). Fisher's exact and Kruskal-Wallis tests were used to investigate the associations between the categorical variables and compare PD-L1 scores with the mutation status. Most PTC (87%) and ATC (73%) cases were PD-L1 positive (TPS ≥1%), with significantly higher positivity rates than NG (20%). TPS >50% was seen in 60% ATC and 7% PTC cases. The median TPS and H-score of ATC were 56 (0-96.6) and 168 (0-275), respectively, and of PTC were 9.6 (4-16.8) and 17.8 (6.6-38.6), respectively. The scores were similar across the PTC subtypes. Only one case each of FTC and PDTC was PD-L1 positive. PD-L1 expression correlated significantly with BRAFV600E, but not with RAS mutation. ATC showed intense and diffuse PD-L1 staining. Although most PTCs were PD-L1 positive, the expression was weaker and patchy, irrespective of the histological subtype. Results of this pilot study indicate that ATC is most likely to respond to immunotherapy. PTC, FTC, and PDTC may be less amenable to immunotherapy. PD-L1 expression correlated significantly with BRAFV600E, allowing for combined targeted therapy.

Prostate-specific membrane antigen expression predicts recurrence of papillary thyroid carcinoma after total thyroidectomy

BackgroundProstate-specific membrane antigen (PSMA) overexpression has been observed in the endothelial neovasculature of several solid malignancies. This study aimed to identify PSMA expression in the primary tumor of classical papillary thyroid carcinoma (PTC) and assess the correlation between the degree of PSMA expression and recurrence.MethodsWe reviewed the electronic medical records of patients who underwent total thyroidectomy and central neck dissection, with or without lateral neck dissection, for classical PTC between 2009 and 2014 at our institution. Recurrence was defined as a structural disease based on histological confirmation on follow-up. Fifty-one patients with the recurrent structural disease were matched, using a propensity score matching method, to patients with no disease evidence during follow-up. Clinicopathological and follow-up data were collected for 102 patients. The monoclonal mouse anti-human PSMA/FOLH1/NAALADase I antibody was used for staining the primary tumor. The score of PSMA expression was classified as negative (< 5% positivity), weak (5–10 % positivity), moderate (11–49% positivity), and strong (more than 50% positivity). Clinicopathological factors were compared between patients with low and high PSMA expression. Moreover, whether the degree of PSMA expression and clinicopathological factors could predict recurrence was investigated. Cox proportional hazard regression models were used to evaluate the risk of recurrence.ResultsThere was no significant difference in clinicopathological factors between low (negative or weak) and high (moderate or strong) PSMA expression. Gross extrathyroidal extension (ETE), absence of chronic lymphocytic thyroiditis, and high PSMA expression were all associated with lower recurrence-free survival (RFS) rate in a univariate analysis. In multivariate analysis, gross ETE (hazard ratio [HR], 2.279; 95% confidence interval [CI], 1.257−4.132; p = 0.007) and high PSMA expression (HR, 1.895; 95% CI, 1.073−3.348; p = 0.028) were associated with poor RFS.ConclusionsHigh PSMA expression in the primary tumor was a significant factor in predicting recurrence in classic PTC. PSMA could be a potential biomarker for personalized management for PTC.

PSAT294 Black Thyroid – Is It a Benign or a Malignant Finding?: A Case Report and Review of the Literature

Abstract Background Black thyroid is a rare condition with fewer than 70 cases reported around the globe. Black thyroid is seen almost exclusively in patients upon minocycline ingestion, and the process has previously been thought to be generally benign. Despite the favorable impact of this drug on thyroid function, several studies have reported an association between black thyroid and thyroid cancer. Herein, we report a black thyroid associated with papillary thyroid cancer. Clinical Case A 30-year-old woman with no significant medical history and no risk factors for thyroid cancer, but with a history of acne treated with minocycline for 2 months 10 years ago, came to the office for a thyroid nodule found during a routine healthcare visit. The patient was asymptomatic and euthyroid. Physical examination was unremarkable. The thyroid ultrasonography showed a 1.4 × 1.0 cm hypoechogenic solid nodule with irregular borders and microcalcifications located in the right lobe. No cervical lymph nodules were found. Fine-needle aspiration of the nodule displayed a Bethesda VI category. Total thyroidectomy was performed. No lymph node dissection was implemented. During surgery, the thyroid parenchyma was diffusely black in color, increased in size, and multinodular. The patient was uneventfully discharged on postoperative day 1. Histopathology revealed a diffuse black discoloration of the specimen with a well-defined 1.2×0.8×0.6 cm nodule in the right upper lobe with features of classic papillary thyroid carcinoma. Recently the patient was seen at his 3-month follow-up, and there were no signs or symptoms of recurrence or metastasis. Clinical lessons: Although several studies describe a higher incidence of malignancy (being papillary thyroid carcinoma the most frequently associated) in black thyroid compared to non-black thyroid glands, a causal relationship has never been proven. Perhaps in this case the thyroid ultrasonography screening triggered the overdiagnosis and subsequently the overtreatment. Finally, having a "black organ" can be distressing for patients. Therefore, we should be meticulous in explaining "this disturbing fact". Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Surgical management of T1/T2 node-negative papillary thyroid cancer with tall cell histology: Is lobectomy enough?

BackgroundThe tall cell variant of papillary thyroid carcinoma has traditionally been treated more aggressively than classic papillary thyroid carcinoma. However, this may not be justified in patients with T1/T2 tall cell variant node-negative tumors. MethodsWe evaluated well-differentiated thyroid cancers treated surgically between 1985 and 2015 at our institution. We compared patients undergoing lobectomy for node-negative T1/T2 tall cell variant tumors with the same cohort with classic papillary thyroid carcinoma. Patients who underwent early planned completion thyroidectomy were excluded. Tall cell variant tumors were defined as those with ≥30% tall cells. Survival and recurrence outcomes were determined by the Kaplan-Meier method and groups compared using the log-rank test. ResultsThyroid lobectomy was performed for T1/T2 N0X disease in 70 (15%) tall cell cases and 429 (23%) classic papillary thyroid carcinoma cases. There was no significant difference in 10-year overall survival (P = .56) or locoregional recurrence-free probability (P = .52). Disease-specific survival and local or central nodal recurrence-free probability were 100% in both groups. In 9 papillary thyroid carcinoma cases, subsequent contralateral lobe tumors developed, and in 5, lateral neck metastases developed. No recurrences were seen in the tall cell group. ConclusionT1 node-negative tumors with tall cell histology can be satisfactorily managed with thyroid lobectomy, with equivalent oncological outcomes to classic papillary thyroid carcinoma.

DICER1 Mutations Occur in More Than One-Third of Follicular-Patterned Pediatric Papillary Thyroid Carcinomas and Correlate with a Low-Risk Disease and Female Gender Predilection.

Some pediatric papillary thyroid carcinoma (PPTC) cohorts have suggested a preliminary correlation with respect to DICER1 mutation status and histomorphology in both benign and malignant follicular cell-derived nodules; however, the data regarding correlates of DICER1-related sporadic PPTCs subtyped based on the 2022 WHO classification criteria are largely unavailable. The current study investigated the status of hotspot DICER1 mutations with clinical, histological and outcome features in a series of 56 patients with PPTCs with no clinical or family history of DICER1-related syndromic manifestation. Fifteen (27%) PPTCs harbored BRAF p.V600E. Eight (14%) cases ofPPTCs harbored DICER1 mutations with no associated BRAF p.V600E. DICER1 mutations were identified in exons 26 and 27. A novel D1810del (c.5428_5430delGAT) mutation was also detected. We also confirmed the absence of hotspot DICER1 mutations in the matched non-tumor tissue DNA in all 8 DICER1-related PPTCs. The mean age of DICER1-harboring PPTCs was 15.1 (range: 9-18) years whereas the rest of this cohort had a mean age of 14.8 (range 6-18) years. With the exception of one PPTC, all DICER1-related PPTCs were seen in females (female-to-male ratio: 7). The female to male ratio was 3.8 in 48 DICER1-wild type PPTCs. In terms of histological correlates, 5 of 8 (63%) DICER1-mutant PPTCs were invasive encapsulated follicular variant papillary thyroid carcinomas (FVPTCs) including 4 minimally invasive FVPTCs and 1 encapsulated angioinvasive FVPTC, whereas the remaining 3 PPTCs were infiltrative classic papillary thyroid carcinomas (p < 0.05). The incidence of DICER1 mutations was 19.5% in BRAF p.V600E-wild type PPTCs. Sixty-three percent ofDICER1 hotspot mutations occurred in invasive encapsulated FVPTCs, and this figure represents 38% of invasive encapsulated FVPTCs. Only one (12%) patient with DICER1-related disease showed a single lymph node with micro-metastasis. Unlike DICER1-wild type patients, no distant metastasis is identified in patients with DICER1-related PPTCs. The current series expands on the surgical epidemiology of somatic DICER1-related PPTCs by correlating the mutation status with the clinicopathological variables. Our findings underscore that female gender predilection and enrichment in low-risk follicular-patterned PTCs are characteristics of DICER1-related PPTCs.

A CASE OF ENCAPSULATED TYPE OF FOLLICULAR VARIANT OF PAPILLARY THYROID CARCINOMA

Papillary thyroid cancer is the most prevalent histologic type of thyroid carcinoma. There are numerous PTC subtypes that have been identified, with classical PTC being the most prevalent. The follicular variant of PTC (FVPTC) is the second most prevalent subtype of papillary thyroid carcinoma. A case of encapsulated type of follicular variant of papillary thyroid carcinoma was studied which showed a well encapsulated tumour with follicular thyroid cells arranged predominantly in a follicular architecture and a few areas showing solid architecture. There was no papillary architecture and capsular invasion. The tumour cells showed nuclear enlargement, overcrowding and nuclear clearing. Typical Orphan Annie eye nuclei were seen. The encapsulated type of follicular variant of papillary thyroid carcinoma, more so than other FVPTCs, has an indolent tendency and is associated with better prognosis and low risk of tumour invasiveness and metastasis.

Comparison of the clinicopathological features and oncologic outcomes of the classic papillary thyroid carcinoma with tall cell features and tall cell variant

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

PAPILLARY THYROID CARCINOMA IN THYROGLOSSAL DUCT CYST: A CASE SERIES

Papillary thyroid carcinoma (PTC) arising from a thyroglossal duct cyst (TGDC) is very rare and affected patients appear to have a favorable prognosis. In this report we describe an uncommon series of PTC arising from TGDC affecting 4 Guatemalan female patients, aged 23-50 years (mean, 33 years). The patients presented with painless nodules in the region of the thyroglossal tract located in the middle anterior region of neck. Evolution times ranging from 1 to 3 years were reported for 2 patients. Microscopically, the lesions demonstrated classic PTC, showing pseudo-inclusions and nuclear overlaps associated with the cystic lining containing remnants of thyroid follicles in the capsule. All lesions were surgically removed, and the patients are in follow-up.

Aggressive variants of follicular cell-derived thyroid carcinoma: an overview.

The incidence of thyroid carcinoma has increased globally in the past years. Papillary thyroid carcinoma (PTC) is the most frequent neoplasm of the thyroid gland comprehending the 90% of the thyroid carcinoma and has an indolent clinical behaviour. However, some variants of follicular cell-derived thyroid carcinoma, including variants of classic of PTC, have been identified that show a more aggressive biological behaviour. An accurate diagnosis of these entities is crucial for planning a more aggressive treatment and improving patients' prognosis of patients. The aim of this review is to present the main clinical, histological, and molecular features of aggressive variants of follicular cell-derived thyroid carcinoma, and to provide useful histological parameters for determining the most suitable therapeutic strategy for patients affected by these forms. Variants of classic PTC such as the diffuse sclerosing variant (DSV), the tall cell variant (TCV), the columnar cell variant (CCV), the solid/trabecular variant (STV) and the hobnail variant (HV), and other variants of follicular cell-derived thyroid carcinoma, such as poorly differentiated thyroid carcinoma (PDTC), and anaplastic thyroid carcinoma (ATC), are associated with aggressive behaviour. The correct identification and diagnosis of aggressive variants of follicular cell-derived thyroid carcinoma is important, as they allow the clinician to adopt the most refined therapeutic strategies in order to the survival of the patients.

Nomograms based on sonographic and clinicopathological characteristics to predict lateral lymph node metastasis in classic papillary thyroid carcinoma.

Lateral lymph node metastasis (LLNM) has been considered a risk factor of recurrence in papillary thyroid cancer (PTC). Preoperative detecting LLNM accurately is difficult. Solitary lateral lymph node metastasis is a special type of LLNM. We aimed to develop nomograms for predicting LLNM and multiple lateral lymph node metastasis (MLLNM). We retrospectively retrieved 528 classic PTC patients that underwent surgery between March 2019 and May 2020. Sonographic and clinicopathological features were collected. Risk factors of LLNM and MLLNM were determined by univariate and multivariate analysis. Nomograms for predicting LLNM and MLLNM were developed. LLNM was independently associated with tumor size, the number of foci, location, margin, central lymph node metastasis, and lymph node ratio. Independent predictors of MLLNM were age, margin, and the number of metastatic lymph nodes in central compartment. By using above variables, we constructed nomograms for predicting LLNM and MLLNM, with area under curves of 0.864 and 0.748, respectively. Through these accurate and easy-to-use nomograms, we can detect the risk of residual LLNM postoperatively for classic PTC patients who did not receive lateral neck dissection and provide an individualized plan for postoperative management of classic PTC patients.

Hashimoto's Thyroiditis Is Associated With Central Lymph Node Metastasis in Classical Papillary Thyroid Cancer: Analysis from a High-Volume Single-Center Experience.

PurposeCentral lymph node metastasis (CLNM) is regarded as a predictor for local recurrence in patients with papillary thyroid carcinoma (PTC) but the role of prophylactic central lymph node dissection (CLND) is controversial. Our study aims to identify the clinical factors associated with CLNM and develop a nomogram for making individualized clinical decisions.MethodThe perioperative data of 1,054 consecutive patients between Jan 2019 and April 2021, in our center, were reviewed and analyzed. A total of 747 patients with histopathologically confirmed classical PTC were included as the training cohort and 374 (50% training cases) patients were randomly selected to build a validating cohort via internal bootstrap analysis. Univariate and multivariate logistic regression were used to analyze the correlation between clinicopathological characteristics and CLNM.ResultIn the training cohort, 33.6% (251/747) of patients with classical PTC were confirmed with CLNM. And the CLNM was determined in 31.4% (168/535) of non-Hashimoto’s thyroiditis (HT) patients versus 39.2% (83/212) in HT patients (p=0.043). Four factors including gender, age, size, and HT status were confirmed significantly associated with CLNM. The established nomogram showed good discrimination and consistency with a C-index of 0.703, supported by the internal validation cohort with a C-index of 0.701. The decision curve analysis showed the nomogram has promising clinical feasibility.ConclusionOur study suggested that classical PTC patients with features like male gender, age<55 years old, tumor size>1cm, and HT condition had a higher risk of CLNM. And the nomogram we developed can help surgeons make individualized clinical decisions in classical PTC patients during preoperative and intraoperative management.

Diagnostic strategy of fine needle aspiration cytology of cystic cervical lymph node metastasis from papillary thyroid carcinoma.

Cystic cervical lymph node metastasis from papillary thyroid carcinoma (CLMPTC) initially presents as cervical cystic lesions, which are often underdiagnosed as other cystic cervical lesions. There is no comprehensive diagnostic strategy of fine needle aspiration (FNA) cytology for CLMPTC. The clinical and FNA cytomorphology data of 87 patients with CLMPTC were analyzed. Thyroglobulin (TG) immunostaining was performed in 40 cases; BRAF V600E mutation was evaluated in 42 cases; the thyroglobulin (Tg) levels of aspiration fluids were assessed in 46 cases. Correspondingly, the data of 42 cases with solid cervical lymph node metastasis from papillary thyroid carcinoma (SLMPTC) and 32 cases with other cystic cervical lesions were collected as controls. Compared with SLMPTC, CLMPTC has less classical PTC cytomorphology characteristics-for example, nuclear crowding/overlapping, nuclear irregular contours, etc. (p < .05). Additionally, micropapillary architecture and histiocyte-like tumor cells were more often observed in CLMPTC than in SLMPTC (p < .01). The positive rate of TG immunocytochemistry in CLMPTC was 100% (40/40). The positive rate of BRAF V600E mutation in CLMPTC was 81.0% (34/42), which was higher than that in SLMPTC (64.3%; 27/42) (p=.087). The Tg levels in aspiration fluids were significantly higher in CLMPTC (all>500 μg/L) than in other cervical cystic lesions (range: 2.9μg/L to 40.1μg/L) (p < .01). To reduce underdiagnoses of CLMPTC, a reasonable diagnostic strategy, as summarized in this study is needed: according to the number of tumor cells, choosing immunocytochemistry (TG) and/or thyroglobulin in fine needle aspirates testing as auxiliary diagnostic measures.

Tall Cell Histology – Comparison of T1 Tall Cell Variant and Classical Papillary Thyroid Carcinoma

<h3>Purpose/Objective(s)</h3> Tall cell histology in papillary thyroid carcinoma (PTC) is considered intermediate risk on ATA guidelines. However, it is unclear if patients with T1 tumors with tall cell histology require aggressive treatment. The objective of our study was to compare pathology and outcomes of patients with tall cell histology with that of classical PTC in T1 disease. <h3>Materials/Methods</h3> The study cohort was selected from our departmental database of differentiated thyroid cancers treated surgically between 1985 and 2015 (n=6,259). PTC cases demonstrating ≥30% tall cells were considered as tall cell variant (TCV). All T1 classical PTC and TCV were identified. Patient and tumor characteristics were compared between groups by Fisher exact test, chi-squared test or two sample t test. Survival and recurrence outcomes were compared using the log-rank test and Kaplan-Meier method. <h3>Results</h3> There were 712 TCV and 2,354 classical PTC patients with T1 tumors. Total thyroidectomy and lobectomy were done in 622 and 90 TCV patients compared to 1883 and 471 classical PTC patients. Central neck dissection was done in 140 TCV and 420 classical PTC patients. Lateral neck dissection was done in 89 TCV and 323 PTC patients. 208 and 87 TCV patients were N1a and N1b compared to 385 and 306 classical PTC patients. There was no significant difference between TCV and classical PTC in gender, age >55 years and vascular invasion. Compared to classical PTC, TCV cases were significantly more likely to demonstrate microscopic extrathyroidal extension (p<0.01), multifocality (p<0.01), larger size (mean 1.30cm in tall cell and 1.15cm in classical PTC) (p=0.02), less encapsulation (p<0.01) and treatment with radioactive iodine (p<0.01). Rates of central nodal disease were significantly higher in TCV cases (p<0.01), but there was no significant difference in rates of lateral nodal disease (p=0.61). There was no significant difference in overall survival (p=0.73), disease-specific survival (p=0.69) or locoregional recurrence (p=0.08). Of those that underwent lobectomy only, there was no significant difference in locoregional recurrence between classical PTC and TCV cases (p=0.79). For TCV cases only, there was no significant difference in locoregional recurrence between those that underwent lobectomy compared to those that had total thyroidecomy (p=0.08). <h3>Conclusion</h3> Despite having a higher rate of microscopic extrathyroidal extension and regional metastases, patients with T1 tall cell tumors have similar oncologic outcomes to patients with classical PTC.

Clinical-Pathological Features and Treatment Outcome of Patients With Hobnail Variant Papillary Thyroid Carcinoma.

Papillary thyroid carcinoma (PTC) with hobnail areas above 30% is classified as hobnail variant (HVPTC). Although it is widely accepted that HVPTC has a worse outcome than classical PTC, it is unclear whether PTC with hobnail features below 30% is as aggressive as HVPTC. We gathered the largest mono-institutional series of PTC with hobnail areas and HVPTC to evaluate differences in terms of pathological features of aggressiveness, molecular profile, and treatment outcome. A total of 99 PTC with hobnail features above 5% were retrospectively selected; 34 of them met the criteria for HVPTC (0.4% of all PTC diagnosed at our institution). All tumors showed high rates of extra-thyroidal extension (40.4%), lymph node metastasis (68.1% of patients with lymphadenectomy), and vascular emboli (49.5%), with no differences according to the 30% cutoff. On the other hand, distant metastases were present in HVPTC only (9.4%). Also, advanced age, advanced disease stage, and TERT promoter mutation were associated with HVPTC. More than half of the patients with follow-up had structural or biochemical persistence after 1 year from surgery. Structural persistence was significantly more common in patients with HVPTC (37.5% vs. 8.7%), while no differences were observed considering structural and biochemical persistence together. The presence of hobnail features identifies locally aggressive tumors, and, consequently, it should be always acknowledged in the pathological report. However, tumors with more than 30% hobnail areas frequently present TERT promoter mutations, advanced disease stage, and structural persistence after radioiodine ablation.

CD56 Expression in Papillary Thyroid Carcinoma Is Highly Dependent on the Histologic Subtype: A Potential Diagnostic Pitfall.

Loss of CD56 expression has been regarded as a diagnostic marker of papillary thyroid carcinoma (PTC). However, certain variants of PTC can aberrantly express CD56. Using a digital image analysis tool, we evaluated H-scores of CD56 immunostaining in 216 thyroid tumors. The H-score of the CD56 of all PTCs was lower than that of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) (P<0.001). The H-scores of CD56 were lower in classic PTC, the infiltrative follicular variant, and the diffuse sclerosing variant than in other PTC variants (P<0.001), whereas the H-scores were higher in tall cell variant, Warthin-like variant, and cribriform-morular variant than in classic PTC (P<0.001). The optimal cutoff value of H-scores for the CD56 expression was 180 for differentiating the NIFTP from the follicular adenoma and 30 for the differential diagnosis of NIFTP and infiltrative follicular variant PTC. CD56 expression is predominantly lost in classic and infiltrative follicular variants of PTCs and more preserved in the other histologic subtypes of PTC and NIFTP. CD56 is particularly useful for differentiating PTC from follicular-pattern thyroid neoplasms, but the aberrant expression in uncommon variants of PTC could be a diagnostic pitfall.

Locally invasive classical papillary thyroid carcinoma with TSH receptor I568T mutation: case report.

SummaryAutonomous thyroid adenomas are caused by activating mutations in the genes encoding the thyroid-stimulating hormone receptor (TSHR) or mutations in the Gas subunit of the TSHR. Nodules with suspicious sonographic features should be submitted to fine-needle aspiration. Additional molecular testing may be performed to characterize the thyroid nodule’s malignant potential further. We present a patient who underwent whole-transcriptome RNA-sequencing that indicated a TSHR I568T mutation after an ultrasound showed suspicious sonographic features and fine-needle aspiration was ‘suspicious for malignancy’. The patient underwent thyroid resection and was found to have a locally invasive classical papillary thyroid carcinoma. Most reports of TSHR I568T mutation have been seen in patients with benign thyroid conditions. While there is insufficient data to suggest that the TSHR I568T mutation causes aggressive thyroid malignancy, we believe clinicians who identify the presence of this mutation on genome sequencing should be cautious about the possibility of locally invasive thyroid malignancy, especially when associated with Bethesda V cytopathology.Learning pointsGermline and somatic activating mutations in the genes coding for the thyroid-stimulating hormone receptor (TSHR) have been frequently reported in familial and sporadic autonomous thyroid adenomas and non-autoimmune hyperthyroidism.Most reports of TSHR I568T mutation have been detected in patients with benign thyroid conditions.We present a patient who underwent whole-transcriptome RNA-sequencing that indicated a TSHR I568T mutation and subsequently underwent thyroid resection and was found to have a locally invasive classical papillary thyroid carcinoma.Clinicians who identify the presence of TSHR I568T mutation on genome sequencing should be cautious about the possibility of locally invasive thyroid malignancy, especially when associated with Bethesda V cytopathology.

Papillary Thyroid Carcinoma: Molecular Distinction by MicroRNA Profiling.

Papillary thyroid carcinoma (PTC) is a miscellaneous disease with a variety of histological variants, each with its own mutational profile, and clinical and prognostic characteristics. Identification of microRNA (miRNA) expression profiles represents an important benchmark for understanding the molecular mechanisms underlying the biological behavior of these unique PTC subtypes in order that they be better characterized. We considered a series of 35 PTC samples with a histological diagnosis of either hobnail (17 cases) or classical variant (nine cases) and with a specific BRAF p.K601E mutation (nine cases). We determined the overall miRNA expression profile with NanoString technology, and both quantitative reverse transcription–PCR and in situ hybridization were used to confirm selected miRNAs. The miRNA signature was found to consistently differentiate specific histotypes and mutational profiles. In contrast to the BRAF p.K601E mutation and classic PTCs, three miRNAs (miR-21-5p, miR-146b-5p, and miR-205-5p) were substantially overexpressed in the hobnail variant. The current study found that different miRNA signature profiles were linked to unique histological variants and BRAF mutations in PTC. Further studies focusing on the downstream pathogenetic functions of mRNAs in thyroid neoplasms are warranted.

What is the difference between the tall cell variant and the classic type of papillary thyroid carcinoma on ultrasonography?

PurposeThe prevalence of the tall cell variant of papillary thyroid carcinoma (TCVPTC), which has a poor prognosis, has increased as its definition has been modified. We sought to investigate whether TCVPTC is different from the classic type on ultrasonography (US).MethodsThis study included 46 consecutive TCVPTC patients and 92 classic papillary thyroid carcinoma (PTC) patients who were confirmed surgically at the authors’ institution. The US findings and pathologic reports of these patients were retrospectively reviewed. US features based on the Korean Thyroid Imaging Reporting and Data System, preoperative US suspicion for lymph node metastasis, and the presence of capsular location were evaluated.ResultsUnivariable and multivariable analyses identified that TCVPTC showed more frequent irregular tumor margin (odds ratio [OR], 6.62; 95% confidence interval [CI], 1.46 to 30.09; P=0.014) and capsular location (OR, 4.63; 95% CI, 1.49 to 14.41; P=0.008) than classic PTC. Capsular location was an independent predictor of TCVPTC for tumors less than or equal to 1.5 cm in size (OR, 4.23; 95% CI, 1.12 to 15.92; P=0.033). Irregular margin was an independent predictor of TCVPTC for tumors larger than 1.5 cm (OR, 10.46; 95% CI, 1.16 to 94.48; P=0.037). Extrathyroidal extension was not significantly different between the two groups.ConclusionThe two key features of TCVPTC on US are frequent capsular location for tumors less than or equal to 1.5 cm in size and the higher likelihood of an irregular margin for tumors larger than 1.5 cm.