Conventional Papillary Thyroid Carcinoma Research Articles

Solid variant of papillary thyroid carcinoma: an under-recognized entity.

Solid variant of papillary thyroid carcinoma (SVPTC) is a rare morphological variant of papillary thyroid carcinoma (PTC). SVPTC is histologically characterized by predominant solid, trabecular and insular nests of tumor cells while cytological features of PTC such as nuclear grooves and nuclear inclusions are preserved. In fine needle aspiration cytology smears, tumor cells of SVPTC may be presented in cohesive, syncytial or trabecular clusters accompanied by some discohesiveness in the absence of necrosis. Although SVPTC and poorly differentiated thyroid carcinoma (PDTC) share similar histological findings of solid nests, SVPTC can be differentiated from PDTC in the lack of tumor necrosis, severe nuclear atypia, and a higher mitotic index. Immunohistochemical expression of CK19 and HBME-1, common markers of PTC, is decreased in solid nests of SVPTC. In pediatric patients exposed to radiation after the Chernobyl nuclear accident, there was a higher prevalence of SVPTC with RET/PTC3 type rearrangement. BRAF mutations are also reported in a small number of adult patients with SVPTC without any prior radiation exposure. Patients with SVPTC may have a slightly higher incidence of metastasis and recurrence of the tumor compared to conventional PTC, although overall survival rate is comparable. In this article, the current knowledge of SVPTC will be reviewed and discussed with an emphasis on the histopathological feature.

Familiar tumor with multiple faces- A 5 yr study of papillary thyroid carcinoma

Papillary thyroid carcinoma (PTC) is the most common malignant tumour of thyroid. Papillary thyroid carcinoma, follicular, columnar, microcarcinoma, diffuse sclerosing. Several variants have been described considering size, architecture, cellular properties, additional tumour components, stromal features and combination of the above mentioned characteristics. Our aim is to study the histopathological variants of PTC. Age group of the patients ranged from 20-50yrs with female predominance. Of the total 44 cases of PTC, classical variant of PTC was the most common accounting for 48% (21) cases followed by 34% (15) of follicular variant. It is important to know all the possible morphological demonstrations of PTC to recognize this common tumour of the thyroid. Although some variants are just morphological challenges for the pathologists, some others may behave worse than conventional PTC and need a more aggressive clinical management. Keywords: Papillary thyroid carcinoma, Follicular, Columnar, Microcarcinoma, Diffuse sclerosing.

Cribriform-Morular Variant of Papillary Thyroid Carcinoma Shows High Ki-67 Labeling Indices, despite Its Excellent Prognosis

Objective: This study aimed to demonstrate that the cribriform-morular variant (CMV) of papillary thyroid carcinoma (PTC) has high Ki-67 labeling indices, despite its excellent prognosis. Methods: We examined 21 CMV-PTCs and 5 conventional PTCs (C-PTCs) resected at Kuma Hospital between 2008 and 2018. All of the patients with CMV-PTC were women. Their ages ranged from 17 to 35 years, with a mean of 25.2 years. An immunohistochemical study using β-catenin, estrogen receptor (ER), and Ki-67 was performed. For apoptotic analysis, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining was performed. Results: All CMV-PTCs were encapsulated with thick fibrous connective tissue. Eleven and one CMV-PTCs exhibited capsular invasion and extrathyroidal invasion, respectively. Two patients showed regional nodal metastasis. The Ki-67 labeling index ranged from 4.8 to 36.4% (mean 15.2%). Apoptotic cells were counted, which showed 2–52 positive cells (mean 12.6) per 10 high-power fields. The Ki-67 labeling index was positively correlated with the apoptotic cell count (r = 0.48, p = 0.030). Ki-67 labeling indices of CMV-PTCs were significantly higher than those of C-PTCs (p = 0.0027). Ages and tumor sizes did not have significant correlations with Ki-67 labeling indices or apoptotic cell counts. Conclusion: This study is the first to demonstrate disproportionally high Ki-67 labeling indexes in a large number of CMV-PTC cases, despite the fact that these cases had favorable prognoses. The favorable prognosis of CMV-PTC may be attributable to encapsulation and nuclear ER expression.

MON-628 Noninvasive Encapsulated Papillary RAS-Like Thyroid Tumor (NEPRAS) as a Possible Novel Subtype of Borderline Tumor

Background: A subset of thyroid tumors was classified into borderline/precursor tumors in the latest World Health Organization (WHO) classification. However, these tumors were defined only in terms of follicular structure, including hyalinizing trabecular tumor (HTT), noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), and uncertain malignant potential (UMP). As papillary microcarcinoma was proposed to be renamed to papillary microtumor (PMiT), there would be no reasons for restricting borderline/precursor tumors to the follicular growth pattern. Clinical Case: A 26-year-old man was incidentally found to have a 23 mm nodule in his thyroid. After undergoing left lobectomy, histological findings revealed extremely delicate nuclear changes in a noninvasive encapsulated papillary growth-patterned tumor. Tumor cells showed nuclear enlargement, irregularity, elongation, and overlapping as well as a few nuclear grooves. Nuclear pseudoinclusions were absent and chromatin characteristics were insufficient (nuclear score 2 according to Nikiforov et al. (1)). The patient was diagnosed with an encapsulated conventional papillary thyroid carcinoma by a local pathologist; however, a second-opinion consultation endorsed a follicular adenoma with papillary hyperplasia. In a third-opinion consultation, immunohistochemical analyses revealed a low MIB-1 labeling index and negative staining for cytokeratin 19 and BRAFV600E, which supported the expected indolent clinical behavior. Remarkably, mutational analysis identified a heterozygous point mutation of the KRAS gene but not the BRAF genes. Eventually, we speculated that this tumor could be a possible example of a novel borderline tumor with a papillary architecture, which does not qualify as NIFTP or UMP under the current WHO criteria. The patient refused additional surgery (complete thyroidectomy), and developed no recurrence or distant metastasis for 24 months. Conclusion: We reported a significant observer variation in a noninvasive encapsulated papillary growth-patterned tumor with delicate nuclear changes and a KRAS mutation. We speculated that our case could be an example of a novel borderline tumor with a papillary structure. Further studies using a larger number of patients are needed to elucidate this disease entity, because the possible introduction of terminology such as “noninvasive encapsulated papillary RAS-like thyroid tumor (NEPRAS)” without the word “cancer” could relieve psychological burdens of the patients similar to NIFTP. Reference: (1) Nikiforov YE, et al. Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma: A Paradigm Shift to Reduce Overtreatment of Indolent Tumors. JAMA Oncol. 2016;2:1023-9.

Association Between Radiomics Signature and Disease-Free Survival in Conventional Papillary Thyroid Carcinoma

Patients with papillary thyroid carcinoma (PTC) would benefit from risk stratification tools that can aid in planning personalized treatment and follow-up. The aim of this study was to develop a conventional ultrasound (US)-based radiomics signature to estimate disease-free survival (DFS) in patients with conventional PTC. Imaging features were extracted from the pretreatment US images of 768 patients with conventional PTC who were treated between January 2004 and February 2006. The median follow-up period was 117.3 months, with 85 (11.1%) events. A radiomics signature (Rad-score) was generated by using the least absolute shrinkage and selection operator (LASSO) method in Cox regression. The Rad-score was significantly associated with DFS (hazard ratio [HR], 3.087; P < 0.001), independent of clinicopathologic risk factors. A radiomics model which incorporated the Rad-score demonstrated better performance in the estimation of DFS (C-index: 0.777; 95% confidence interval [CI]: 0.735, 0.829) than the clinicopathologic model (C-index: 0.721; 95% CI: 0.675, 0.780). In conclusion, radiomics features from pretreatment US may be potential imaging biomarkers for risk stratification in patients with conventional PTC.

Parapharyngeal Dissection for Papillary Thyroid Cancer

Introduction: Although lymph node metastases are common with papillary thyroid cancer, parapharyngeal and retropharyngeal lymph node metastases are relatively rare. Although small metastatic parapharyngeal lymph nodes (e.g., <1 cm) may be treated with radioactive iodine or observed, larger lymph nodes may require surgical excision. Surgical approaches to the parapharyngeal and retropharyngeal space include transoral and transcervical.Materials and Methods: A 47-year-old female presented with a 2 cm conventional papillary thyroid cancer in the right thyroid lobe with central right lateral neck metastases, as well as a 2.5 cm right parapharyngeal lymph node metastasis extending to the skull base. Surgical technique for transcervical resection of the 2.5 cm parapharyngeal lymph node is illustrated, identifying important anatomical structures.Results: After opening the right neck and removing the right level 2 lymph nodes (not illustrated), the parapharyngeal space is exposed. First, the posterior belly of the digastric and stylohyoid muscles is divided. Next, the hypoglossal nerve is identified and mobilized. Branches of the external carotid artery are then divided and retracted. The sympathetic chain is visualized posterior to the internal carotid artery. The external branch of the superior laryngeal nerve is visualized as it courses posterior to the carotid artery. After gentle retraction of the hypoglossal nerve, superior laryngeal nerve, carotid artery, and sympathetic chain, the parapharyngeal space is exposed with the aforementioned metastatic lymph node. The metastatic lymph node is then freed from the alar fascial and skull base attachments and removed en bloc.Conclusion: To our knowledge, this is the first video demonstration of a transcervical parapharyngeal lymph node resection in the peer-reviewed literature. Transcervical excision of parapharyngeal and retropharyngeal lymph nodes requires a thorough understanding of the anatomy of the neck and parapharyngeal space, along with a stepwise surgical technique to safely expose the parapharyngeal space.No competing financial interests exist.Runtime of video: 8 mins 44 secs

Relationship between genetic alterations and clinicopathological characteristics of papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is characterized by proliferation of follicular cells with distinctive nuclear features such as ground glass appearance, nuclear groove and pseudoinclusion. From the proliferation pattern, PTC is divided into several histological subtypes; conventional histology is classified as papillary type, and there are also follicular and solid variants. PTC is heterogeneous in genetic alterations. PTC with BRAF mutation presents a histology of conventional PTC, and follows an aggressive clinical course. Most cases of PTC with RAS mutation show a follicular variant, and prognosis is favorable. RET/PTC1 is observed sporadically and in young cases, and prognosis is favorable. RET/PTC3 is associated with radiation exposure, and the solid variant is frequent. ETV6-NTRK3 may be associated with radiation exposure, and the clinical course is aggressive. Mutation in the telomerase reverse transcriptase promoter is observed in PTC cases involving elderly male patients. Tumor size is large, associated with distant metastasis and advanced stage. This mutation is found concomitantly with BRAF mutation, and the clinical course is aggressive. Genetic alterations form subsets of PTC with distinct clinicopathological features. Careful assessment of clinicopathological features is considered useful in predicting clinical course and when planning treatment.

Concomitant Thyroid Cancer in Patients with Multiple Endocrine Neoplasia Type 1 Undergoing Surgery for Primary Hyperparathyroidism.

Compared to those with sporadic primary hyperparathyroidism (SPHP), multiple endocrine neoplasia type 1 (MEN1) patients with primary hyperparathyroidism (MPHP) typically require more extensive dissection and have higher recurrence rates. Little is known about the risk of concomitant thyroid cancer in either setting. This study aimed to determine the rates and characteristics of thyroid cancer for MPHP versus SPHP patients undergoing parathyroidectomy. Patients with MPHP (diagnosed by clinical and/or genetic criteria) or SPHP who had initial or reoperative parathyroid exploration from 1967 to 2014 were identified via a prospective database. The thyroid cancer-specific data for MPHP patients (n = 29) were compared to a selected 2:1 age- and sex-matched SPHP cohort (n = 58) who all had concurrent thyroidectomy for any reason. Clinically significant thyroid cancer was defined as >1 cm in diameter. In the MPHP group, 24/29 (83%) thyroidectomies were preoperatively unplanned versus 20/58 (34%) in the SPHP matched cohort (p < 0.01), and in this setting there was no difference in the rate of histologic thyroid cancer (3/24 [13%] vs. 5/20 [25%], p = 0.44). Histologic thyroid cancer was identified in 8/29 (28%) MPHP versus 27/58 (47%) SPHP patients (p = 0.11). Despite observed differences in the time period and extent of thyroidectomy, MPHP patients did not have an increased likelihood of thyroid cancer (surgery before 2005: odds ratio [OR] = 2.57, p = 0.09; total thyroidectomy: OR = 5.47, p < 0.01; MPHP: OR = 1.14, p = 0.83). All MPHP thyroid cancers were characterized as conventional papillary thyroid cancer (PTC), while thyroid cancers in SPHP patients included both PTC (66%) and follicular-variant PTC (34%). No MPHP patient had clinically significant thyroid cancer compared to an incidence of 15/58 (26%) in SPHP patients (p < 0.01). Although patients with MEN1 have a substantial incidence of thyroid cancer (28%) and undergo more unplanned thyroidectomies during parathyroidectomy than do patients with SPHP, clinically significant thyroid cancer is proportionally uncommon.

High Preponderance of BRAF V600E Mutation in Papillary Thyroid Carcinoma Among Filipinos: A Clinicopathologic Study.

PurposeBRAF mutation in papillary thyroid carcinoma (PTC) is associated with an aggressive phenotype, with varying incidence. We evaluated the prevalence of BRAF mutations in PTC among Filipino patients and their correlation with clinicopathologic characteristics.Patients and MethodsClinicopathologic data were retrieved from 64 sequential patients who underwent thyroidectomy from June 2016 to December 2016. BRAF mutation testing was performed using Sanger sequencing.ResultsEighteen (28%) of 64 patients were diagnosed with PTC; 12 (70.59%) of 17 harbored a BRAF V600E mutation (no amplification in one patient). Demographics of patients with PTC were as follows: 13 women and five men, with median age of 46 years (range, 25 to 74 years). Fourteen patients had conventional subtype PTC; two, follicular variant; one, oncocytic variant; and one, tall-cell features. Tumor size ranged from 0.8 to 7.0 cm (median, 2.4 cm); extrathyroidal extension was present in seven (38.9%) of 18 patients, multifocality in six (33.33%) of eight, and lymph node involvement in eight (44.4%) of 18. Significant association between presence of a BRAF mutation and presence of extrathyroidal extension or lymph node involvement was not determined due to the limited sample size.ConclusionThe high preponderance of BRAF mutation (70.59%) suggests some correlation with the previously reported lower 5-year survival among Filipinos. This warrants further investigation in a larger-cohort prospective study.

Important cytological findings for distinction between follicular variant and conventional papillary thyroid carcinoma, including noninvasive follicular thyroid tumors with papillary-like nuclear features.

We studied cytological specimens of conventional papillary thyroid carcinoma (PTC), follicular variant papillary thyroid carcinoma (FVPTC), and noninvasive follicular thyroid tumor with papillary-like nuclear features (NIFTP) (formerly noninvasive FVPTC) to identify useful cytological parameters for their differentiation. Cytological findings of invasive FVPTC and NIFTP were very similar to each other but differed from those of conventional PTC. Intranuclear cytoplasmic inclusions, true papillary cell clusters, monolayered cell sheets, ropy colloids, multinucleate giant cells, psammoma bodies, and cystic background were the observed characteristic features of conventional PTC. Microfollicular cell clusters and dense globules of colloids were characteristic features of invasive FVPTC and NIFTP. Scoring the eight parameters (intranuclear cytoplasmic inclusions, nuclear grooves, powdery chromatin, true papillary cell clusters, ropy colloids, multinucleate giant cells, psammoma bodies, and cystic background) readily distinguished NIFTP from conventional PTC, but could not distinguish NIFTP from invasive FVPTC. The average total score of NIFTP, invasive FVPTC, and conventional PTC were 2.60 ± 0.55, 2.63 ± 0.62, and 4.57 ± 0.99, respectively. The difference between conventional PTC and NIFTP or invasive FVPTC was statistically significant (p < 0.001, Student's t-test). Individuals with more than three of the identified parameters likely harbor conventional PTC, rather than NIFTP. In this way, 87.5% (112/128) of conventional PTCs could be differentiated from NIFTP, and definitively diagnosed as malignant by cytology.

Survival of aggressive variants of papillary thyroid carcinoma in patients under 55 years old: a SEER population-based retrospective analysis.

Patients younger than 55 years of age with papillary thyroid carcinoma (PTC) have excellent survival. Diffuse sclerosing variant (DSV) and tall cell variant (TCV) of PTC are associated with aggressiveness; the survival of patients <55 years of age with these variants is still unclear. We aim to investigate the clinicopathological features and survival of these variants in the age group <55 years. All adult patients (<55 years old) with DSV, TCV and conventional PTC (CPTC) came from the Surveillance, Epidemiology, and End Results program (1988-2013). Kaplan-Meier method and log-rank test were used to analyze the survival. Prognostic factors associated with survival were analyzed by Cox multivariate regression. There were 280 DSV, 615 TCV, and 56287 CPTC in the age group <55 years. DSV and TCV were associated with multifocality, extrathyroidal extension, lymph node and distant metastasis (all p < 0.05). The 10-year disease-specific survival (DSS) of TCV was worse than CPTC (96.3 vs. 99.4%, p < 0.01), but there was no significant difference between DSV and CPTC (99.5 vs. 99.4%, p > 0.05). Cox multivariate regression showed TCV was the independent predictor of DSS (HR: 5.39, p < 0.01). In the age group <55 years, DSV and TCV are more likely to exhibit aggressive characteristics than CPTC. Patient <55 years of age with DSV have excellent survival likewise, while patients <55 years of age with TCV carry worse survival. Further investigation for the recurrence risk of patients <55 years with these variants would contribute to optimal clinical management making.

Thyroid nodules and cancer in children and adolescents affected by Hashimoto's thyroiditis.

To investigate the rates of thyroid nodules and cancer in pediatric cases of Hashimoto's thyroiditis (HT) in Korea. We retrospectively reviewed 89 pediatric and adolescent patients (age, 3-18.0 years) with HT who underwent thyroid ultrasonography (US) at our institution from February 2006 to July 2016. The diagnosis of HT was based on the presence of thyroid autoantibodies. The presence of any thyroid nodules with US and cytopathologic features was analyzed. The malignancy rate was also determined. Thyroid nodules were in 20 of the 89 patients (22.4%). Eight of these 20 patients (40%) had colloid cysts, two (10%) had nodular hyperplasia, one (5%) had follicular adenoma, and two (10%) had lymphocytic thyroiditis. Seven of the 89 patients (7.9%) were confirmed to have a malignancy, all of which were papillary thyroid carcinoma (PTC); of those, five patients had diffuse sclerosing variant PTC, and two had conventional PTC on pathology. The prevalence of thyroid nodules in children and adolescents with HT was 22.4%. The malignancy rate of children with HT was 7.9%. The malignancy rate among thyroid nodules was 35%, which is higher than the 26% rate generally reported for children with nodules. Therefore, using thyroid US to survey known or suspected thyroid nodules might be helpful in children and adolescents with HT and may provide further useful diagnostic information. Advances in knowledge: Thyroid US could help to assess HT patients who have known or suspected thyroid nodules.

Cytologic Diagnosis of Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features and Its Impact on the Risk of Malignancy in the Bethesda System for Reporting Thyroid Cytopathology: An Institutional Experience.

BackgroundThis study was performed to analyze cytologic diagnosis of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and its impact on the risk of malignancy (ROM) in the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). MethodsFive thousand five hundred and forty-nine cases of thyroid fine-needle aspiration cytology (FNAC) diagnosed between 2012 and 2014 were included in this study. Diagnostic categories based on TBSRTC were compared with final surgical diagnoses, and the ROM in each category was calculated both when NIFTP was included in malignant lesions and when excluded from malignant lesions. ResultsOf the 5,549 thyroid FNAC cases, 1,891 cases underwent surgical resection. In final diagnosis, 1,700 cases were revealed as papillary thyroid carcinoma (PTC), and 25 cases were reclassified as NIFTP. The cytologic diagnoses of NIFTP were non-diagnostic in one, benign in five, atypia of undetermined significance (AUS) in 14, follicular neoplasm in two, and suspicious for malignancy in three cases. Collectively, NIFTP/encapsulated follicular variant of PTC (EFVPTC) were more frequently classified as benign, AUS, or follicular neoplasm and less frequently categorized as malignant compared to conventional PTCs. Exclusion of NIFTP from malignant diagnoses resulted in a slight decrease in malignancy rates in non-diagnostic, benign, AUS, follicular neoplasm, and suspicious for malignancy categories without any statistical significance. ConclusionsThe decrease in the ROM was not significant when NIFTP was excluded from malignant lesions. In thyroid FNACs, NIFTP/EFVPTCs were mostly classified into indeterminate categories. Therefore, it might be feasible to separate NIFTP/EFVPTC from conventional PTC on FNAC to guide clinicians to conservative management for patients with NIFTP/EFVPTC.

DICER1 Mutations Are Frequent in Adolescent-Onset Papillary Thyroid Carcinoma.

Papillary thyroid carcinoma (PTC) is a common malignancy in adolescence and is molecularly and clinically distinct from adult PTC. Mutations in the DICER1 gene are associated with thyroid abnormalities, including multinodular goiter and differentiated thyroid carcinoma. In this study, we sought to characterize the prevalence of DICER1 variants in pediatric PTC, specifically in tumors without conventional PTC oncogenic alterations. Patients (N = 40) who underwent partial or total thyroidectomy and who were <18 years of age at the time of surgery were selected. The 40 consecutive thyroidectomy specimens (30 malignant, 10 benign) underwent genotyping for 17 PTC-associated variants, as well as full sequencing of the exons and exon-intron boundaries of DICER1. Conventional alterations were found in 12 of 30 (40%) PTCs (five BRAFV600E, three RET/PTC1, four RET/PTC3). Pathogenic DICER1 variants were identified in 3 of 30 (10%) PTCs and in 2 of 10 (20%) benign nodules, all of which lacked conventional alterations and did not recur during follow-up. DICER1 alterations thus constituted 3 of 18 (16.7%) PTCs without conventional alterations. The three DICER1-mutated carcinomas each had two somatic DICER1 alterations, whereas two follicular-nodular lesions arose in those with germline DICER1 mutations and harbored characteristic second somatic RNase IIIb "hotspot" mutations. DICER1 is a driver of pediatric thyroid nodules, and DICER1-mutated PTC may represent a distinct class of low-risk malignancies. Given the prevalence of variants in children, we advocate for inclusion of DICER1 sequencing and gene dosage determination in molecular analysis of pediatric thyroid specimens.

Thyroid lobectomy is not sufficient for T2 papillary thyroid cancers

BackgroundHistologic subtypes of papillary thyroid cancer affect prognosis. The objective of this study was to examine whether survival is affected by extent of surgery for conventional versus follicular-variant papillary thyroid cancer when stratified by tumor size. MethodsUsing the National Cancer Data Base, we evaluated 33,816 adults undergoing surgery for papillary thyroid cancer from 2004 to 2008 for 1.0-3.9 cm tumors and clinically negative lymph nodes. Conventional and follicular-variant papillary thyroid cancers were divided into separate groups. Cox regression models stratified by tumor size were used to determine if extent of surgery affected overall survival. ResultsA total of 30,981 patients had total thyroidectomy and 2,835 had thyroid lobectomy; 22,899 patients had conventional papillary thyroid cancer and 10,918 had follicular-variant papillary thyroid cancer. On unadjusted KM analysis, total thyroidectomy was associated with improved survival for conventional (P = 0.02) but not for follicular-variant papillary thyroid cancer patients (P = 0.42). For conventional papillary thyroid cancer, adjusted analysis showed total thyroidectomy was associated with improved survival for 2.0-3.9 cm tumors (P = 0.03) but not for 1.0-1.9 cm tumors (P = 0.16). For follicular-variant, lobectomy and total thyroidectomy had equivalent survival for 1.0-1.9 cm (P = 0.45) and 2.0-3.9 cm (P = 0.88) tumors. ConclusionTumor size, histologic subtype, and surgical therapy are important factors in papillary thyroid cancer survival. Total thyroidectomy was associated with improved survival in patients with 2.0-3.9 cm conventional papillary thyroid cancer, and should be considered for 2.0-3.9 cm papillary thyroid cancers when preoperative molecular analysis is not used to distinguish conventional from follicular-variant.

Preoperative Cytologic Diagnosis of Warthin-like Variant of Papillary Thyroid Carcinoma.

BackgroundWarthin-like variant of papillary thyroid carcinoma (WLV-PTC) is a relatively rare variant of papillary thyroid carcinoma with favorable prognosis. However, preoperative diagnosis using fine-needle aspiration (FNA) specimens is challenging especially with lymphocytic thyroiditis characterized by Hürthle cells and lymphocytic background. To determine a helpful cytological differential point, we compared WLV-PTC FNA findings with conventional papillary thyroid carcinoma with lymphocytic thyroiditis (PTC-LT) and conventional papillary thyroid carcinoma without lymphocytic thyroiditis (PTC) regarding infiltrating inflammatory cells and their distribution. Preoperative diagnosis or potential for WLV-PTC will be helpful for surgeons to decide the scope of operation.MethodsOf the 8,179 patients treated for papillary thyroid carcinoma between January 2007 and December 2012, 16 patients (0.2%) were pathologically confirmed as WLV-PTC and four cases were available for cytologic review. For comparison, we randomly selected six PTC-LT cases and five PTC cases during the same period. The number of intratumoral and background lymphocytes, histiocytes, neutrophils, and the presence of giant cells were evaluated and compared using conventional smear and ThinPrep preparations. ResultsWLV-PTC showed extensive lymphocytic smear with incorporation of thyroid follicular tumor cell clusters and frequent histiocytes. WLV-PTC was associated with higher intratumoral and background lymphocytes and histiocytes compared with PTC-LT or PTC. The difference was more distinct in liquid-based cytology. ConclusionsThe lymphocytic smear pattern and the number of inflammatory cells of WLV-PTC are different from those of PTC-LT or PTC and will be helpful for the differential diagnosis of WLV-PTC in preoperative FNA.

Guideline for therapy of malignant thyroid tumours: pleading for an actualization

Total (or near total) thyroidectomy (TE) followed by radioiodine ((131)I) ablation (RIA) of residual thyroid tissue is considered to be the ideal treatment for differentiated thyroid carcinoma. However, the actual guideline of the DGN (German Society of Nuclear Medicine) recommends for the so-called papillary micro-carcinoma of the thyroid (PMC) no further therapeutic strategy (no complete TE, no (131)I-ablation of the remaining lobe). PMC has been defined as papillary carcinoma measuring 1 cm (T1) in maximal diameter according to the World Health Organization classification system for thyroid tumours (1988). The new WHO-classification (starting in 2003) defines the T1-tumour measuring 2 cm in maximal diameter. The authors demand a new, modern guideline, following the new WHO classification. This includes, that despite the overall excellent prognosis for patients with PMC, the treatment of patients with T1-tumours of the new WHO-classification (including the "old" PMC) should be no different from the treatment of patients with conventional papillary thyroid carcinoma, i.e. complete surgery (TE and central lymph node dissection) followed by RIA of residual thyroid tissue. The authors argue that it is not appropriate to consider the tumour size as the single most important key factor for therapy and prognosis. Even small tumours may have poor prognostic factors, such as lymph node metastasis, multifocality or molecular characteristics (expression of oncogenes).

Characteristics of cribriform morular variant of papillary thyroid carcinoma in post-Chernobyl affected region

The aim is to study the characteristics of cribriform morular variant of papillary thyroid carcinoma (CMV-PTC) in patients living in the radiation-affected area of Belarus. The clinical and pathological features of 35 patients with CMV-PTC from Belarus were studied and compared with those of conventional papillary thyroid carcinoma diagnosed in the same period. The patients with CMV-PTC were all females and were younger at presentation (mean age = 24) than those with conventional papillary thyroid carcinoma. Familial adenomatous polyposis (FAP) was identified in 20% of the patients with CMV-PTC. The majority of the CMV-PTCs (29/35; 83%) were staged as pT1 and were less advanced than conventional papillary thyroid carcinoma. There was no evidence of lymph node metastases or distant metastases. CMV-PTCs were positive for β-catenin, APC (adenomatous polyposis coli) and p53 proteins. No psammoma bodies were identified on microscopic examination. Over a median follow-up of 9 years, all the patients were alive, and there was no cancer recurrence or mortality related to the thyroid cancer. To conclude, CMV-PTC in patients in the radiation-affected region behaves in an indolent fashion. They had distinctive features that are different from patients with conventional papillary thyroid carcinoma living in the same region.

Usefulness of dynamic risk stratification in pediatric patients with differentiated thyroid carcinoma.

PurposeRecently, the American Thyroid Association (ATA) dynamic risk stratification (DRS) has been verified to be more valuable than the static anatomical staging system for predicting prognosis in patients with differentiated thyroid carcinoma (DTC). The purpose of this retrospective study was to compare the clinical usefulness of DRS, which is based on the response to initial treatment, with that of ATA initial risk stratification in pediatric patients.MethodsA total of 144 pediatric patients underwent thyroid operation from August 1982 to December 2013 at Yonsei University Hospital (Seoul, Korea). Among them, 128 patients with complete clinical data were enrolled in this study. Clinicopathologic features and surgical outcomes were retrospectively analyzed by medical chart review. The mean follow-up duration was 11.5 years.ResultsThe mean tumor size was 2.1 cm; 80.4% of patients were diagnosed with conventional papillary thyroid carcinoma, and 7.0% of patients were diagnosed with follicular thyroid carcinoma. Low-risk patients had the highest probability of an excellent response to initial treatment (66.6%). High-risk patients had the highest probability of a structural incomplete response (100%) and the lowest probability of an excellent response (11.1%). The ATA risk stratification and the DRS system were independent risk factors for disease-free survival (DFS) (P = 0.041 and P < 0.001, respectively).ConclusionThe DRS system, which is based on the response to initial treatment, can offer more useful prognostic information compared with ATA risk stratification in pediatric patients with DTC.

The Hobnail Variant of Papillary Thyroid Carcinoma: Clinical/Molecular Characteristics of a Large Monocentric Series and Comparison with Conventional Histotypes.

The hobnail variant of papillary thyroid carcinoma (HPTC) has an aggressive behavior. The aims of this prospective study were to define the clinical/molecular characteristics of HPTC, and to compare them to those of conventional papillary thyroid carcinoma (PTC). From 2010 to 2016, 25 cases of HPTC, characterized clinically and molecularly (BRAF, RAS, TERT promoter, and TP53 mutations), were compared to a series of 165 consecutive cases of PTC. All patients underwent total thyroidectomy and received radioactive iodine treatment. Follow-up was available for 19 HPTC patients. Among the HPTC patients, 64% had a hobnail component ≥30%, and 64% had multifocal disease. The mean tumor size was 30 mm; 96% of tumors were angio-invasive; 68% were N1, and 12% were M1; 58% harbored the BRAFV600E mutation, 12% had a mutation in the TERT promoter, 17% had a TP53 mutation, and not had a RAS mutation. At a mean follow-up of 39 months, 32% of patients had biochemical and/or structural disease. Tumor size was the only significant difference between patients with persistent disease and those with an excellent response (40 mm and 24 mm, respectively; p = 0.02). Compared to the PTC control group, the HPTC patients had larger tumors (30 mm vs. 16 mm; p < 0.001), more frequent lymph node involvement (68% vs. 38%; p = 0.01), and remote disease (16% vs. 3%; p < 0.0001), a similar prevalence of the BRAFV600E mutation (58% vs. 59%), a higher prevalence of TP53 mutations (17% vs. 1%; p < 0.05), and a worse outcome (structural/biochemical disease: 32% vs. 9%; p < 0.0001). HPTC is an aggressive variant, characterized by large tumor size, lymph node involvement, a tendency to metastasize, and a worse outcome.