Clinical-Pathological and Molecular Evaluation of 451 NIFTP Patients from a Single Referral Center

Background: Non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs) were introduced in thyroid pathology in 2016. NIFTPs are a group of follicular neoplasm with an indolent behaviour. In this study, we gathered a large retrospective cohort of NIFTPs and compared those presenting as solitary lesions and NIFTPs found in multifocal setting. Methods: A retrospective search of NIFTPs was performed, and the clinico-pathological features were recorded. For a subgroup of patients, pre-surgical ultrasound (US) evaluation, cytological diagnosis, and molecular analysis were available. Results: We collected 451 NIFTPs; 254 (56.3%) were truly solitary tumours, while 197 coexisted with one or more NIFTP/cancer. Contrasting unifocal and multifocal settings, NIFTPs size was the only significantly different parameter. Preoperatively, NIFTP nodules mostly showed low-risk US characteristics, indeterminate cytology and a RAS-like molecular profile. Conclusion: NIFTPs often coexist with collateral thyroid tumours. However, no clinical-pathological differences can be observed between solitary and “multifocal” NIFTPs. Despite the well-established clinical indolence of NIFTP, a careful monitoring of the contralateral lobe should not be excluded.

The Multifaceted Profile of Thyroid Disease in the Background of DICER1 Germline and Somatic Mutations: Then, Now and Future Perspectives

DICER1 protein is a member of the ribonuclease (RNAse) III family with a key role in the biogenesis of microRNAs (miRNA) and in microRNA processing, potentially affecting gene regulation at the post-transcriptional level. The role of DICER1 and its relevance to thyroid cellular processes and tumorigenesis have only recently been explored, following the acknowledgement that DICER1 germline and somatic changes can contribute not only to non-toxic multinodule goiter (MNG) lesions detected in individuals of affected families but also to a series of childhood tumours, including thyroid neoplasms, which can be identified from early infancy up until the decade of 40s. In a context of DICER1 germline gene mutation, thyroid lesions have recently been given importance, and they may represent either an index event within a syndromic context or the isolated event that may trigger a deeper and broader genomic analysis screening of individuals and their relatives, thereby preventing the consequences of a late diagnosis of malignancy. Within the syndromic context MNG is typically the most observed lesion. On the other hand, in a DICER1 somatic mutation context, malignant tumours are more common. In this review we describe the role of DICER protein, the genomic events that affect the DICER1 gene and their link to tumorigenesis as well as the frequency and pattern of benign and malignant thyroid lesions and the regulation of DICER1 within the thyroidal environment.

Performance of current ultrasound-based malignancy risk stratification systems for thyroid nodules in patients with follicular neoplasms

Objectives To investigate the ability of the currently used ultrasound-based malignancy risk stratification systems for thyroid neoplasms (ATA, AACE/ACE/AME, K-TIRADS, EU-TIRADS, ACR-TIRADS and C-TIRADS) in distinguishing follicular thyroid carcinoma (FTC) from follicular thyroid adenoma (FTA). Additionally, we evaluated the ability of these systems in correctly determining the indication for biopsy. Methods Three hundred twenty-nine follicular neoplasms with definitive postoperative histopathology were included. The nodules were categorized according to each of six stratification systems, based on ultrasound findings. We dichotomized nodules into the positive predictive group of FTC (high and intermediate risk) and negative group of FTC based on the classification results. Missed biopsy was defined as neoplasms that were diagnosed as FTCs but for which biopsy was not indicated based on lesion classification. Unnecessary biopsy was defined as neoplasms that were diagnosed as FTAs but for whom biopsy was considered indicated based on classification. The diagnostic performance and missed and unnecessary biopsy rates were evaluated for each stratification system. Results The area under the curve of each system for distinguishing follicular neoplasms was < 0.700 (range, 0.511–0.611). The missed biopsy rates were 9.0–22.4%. The missed biopsy rates for lesions ≤ 4 cm and lesions sized 2–4 cm were 16.2–35.1% and 0–20.0%, respectively. Unnecessary biopsy rates were 65.3–93.1%. In ≤ 4 cm group, the unnecessary biopsy rates were 62.2–89.7%. Conclusion The malignancy risk stratification systems can select appropriate nodules for biopsy in follicular neoplasms, while they have limitations in distinguishing follicular neoplasms and reducing unnecessary biopsy. Specific stratification systems and recommendations should be established for follicular neoplasms. Key Points • Current ultrasound-based malignancy risk stratification systems of thyroid nodules had low efficiency in the characterization of follicular neoplasms. • The adopted stratification systems showed acceptable performance for selecting FTC for biopsy but unsatisfactory performance for reducing unnecessary biopsy.

Emerging Biomarkers in Thyroid Practice and Research

Thyroid cancer is the most common endocrine malignancy. Recent developments in molecular biological techniques have led to a better understanding of the pathogenesis and clinical behavior of thyroid neoplasms. This has culminated in the updating of thyroid tumor classification, including the re-categorization of existing and introduction of new entities. In this review, we discuss various molecular biomarkers possessing diagnostic, prognostic, predictive and therapeutic roles in thyroid cancer. A comprehensive account of epigenetic dysregulation, including DNA methylation, the function of various microRNAs and long non-coding RNAs, germline mutations determining familial occurrence of medullary and non-medullary thyroid carcinoma, and single nucleotide polymorphisms predisposed to thyroid tumorigenesis has been provided. In addition to novel immunohistochemical markers, including those for neuroendocrine differentiation, and next-generation immunohistochemistry (BRAF V600E, RAS, TRK, and ALK), the relevance of well-established markers, such as Ki-67, in current clinical practice has also been discussed. A tumor microenvironment (PD-L1, CD markers) and its influence in predicting responses to immunotherapy in thyroid cancer and the expanding arena of techniques, including liquid biopsy based on circulating nucleic acids and plasma-derived exosomes as a non-invasive technique for patient management, are also summarized.

Immunohistochemistry Helps to Distinguish Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features/Noninvasive Encapsulated Follicular Variant of Papillary Thyroid Carcinoma with Other Follicular Thyroid Lesions

Background and Objectives: We aimed to assess the diagnostic value of various immunohistochemical (IHC) markers and panels for differentiation among benign follicular nodules (BFNs), noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs), noninvasive encapsulated follicular variants of papillary thyroid carcinoma (NEFVPTCs), and infiltrative FVPTC (IFVPTC). Materials and Methods: Sixty-three cases were classified as BFNs, NIFTPs, NEFVPTCs, or IFVPTCs and were evaluated using the following markers: CK19, CD56, galectin-3, CITED1, HBME-1, VE1, and TROP-2. Results: The IHC results for NIFTP and NEFVPTC exhibited no statistically significant differences. In differentiating IFVPTCs from BFNs and NIFTPs/NEFVPTCs, galectin-3 and TROP-2 were the markers with the highest sensitivity plus high specificity, respectively. In various combinations, panel co-expression of two markers, including galectin-3 and/or HBME-1 and/or TROP-2, and the combination of galectin-3 and TROP-2 co-expression could achieve 100% in all aspects. In terms of discrimination of BFNs from NIFTP/NEFVPTC, CK19 was the single most sensitive marker (81.3%), while CD56 was the most specific (100%). The panel consisting of CK19 and/or HBME-1 exhibited the greatest sensitivity (96.9%), but the panel with CD56 and/or HBME-1 exhibited the greatest specificity (90.5%). Conclusions: Our results broaden the use of IHC markers for differential diagnoses among the four groups of follicular-based lesions. In addition, the similar IHC profiles of NIFTP and NEFVPTC also suggest the original criterion of <1% papillae within tumors, providing a reliable NIFTP diagnosis. Their close relationship may represent a spectrum of progressing neoplasia.

SP4.2.13 The staging of head and neck cancers at presentation during the COVID-19 pandemic: a regional analysis

Aim The impact of COVID-19 on cancer presentations has been debated; this audit aimed to examine the stage at presentation of head and neck (H&N) cancers regionally during the COVID-19 pandemic compared to the identical time period during 2019. Methods Retrospective data was collected across 3 hospitals in the South West, identifying all H&N cancer patients discussed at Multi-disciplinary Team Meetings between 1st April-10th October 2019 and the same timeframe in 2020. Patients with lymphomas and thyroid neoplasms were excluded due to separate treatment pathways available. Results There were 234 and 272 patients identified in 2020 and 2019 respectively. The median stage at presentation for all cancers was 2 in both years. The commonest cancers in 2020 were oropharyngeal (28%) and oral cavity (22%), similar to that of 2019 (oral cavity-31%, oropharyngeal-22%). The absolute numbers of laryngeal cancers were similar but a greater percentage of those presented late (stages 3&4) in 2020 compared to 2019 (47% vs 35%). There were almost twice as many skin/lip cancers in 2020 proportionately (20% vs 12%) and a greater number of them presented at a later stage. Conclusion Overall, COVID-19 has not appeared to affect the stage at presentation of H&N cancers, reflecting an on-going continuity of care for cancer patients. Subgroup analysis revealed skin and laryngeal cancers was most adversely affected by the pandemic, possibly due to delayed presentation and reduced face-to-face consultations, highlighting the need for continued face-to-face appointments as a part of cancer care pathways.

Risk Benefit Analysis of Routine Thymectomy for Differentiated Thyroid Cancers: A Systematic Review

Background Central compartment lymph node dissection (CLND) is a part of the surgical management of differentiated thyroid cancer (DTC). Therapeutic CLND is done to address clinically significant central compartment nodes in patients with DTC, while prophylactic CLND is performed in the presence of high-risk features in the absence of clinically significant neck nodes. Removal of thymus—unilateral or bilateral—during CLND to achieve complete clearance of level VI and VII lymph node stations and address thymic metastasis is debatable. Objective The present systematic review was conducted to summarize the evidence, delineating the role of thymectomy during CLND in patients with DTC. Methods Electronic databases of PubMed, Embase, and Cochrane were searched from their inception to July 2020 using keywords—thyroid neoplasms or tumors, thyroidectomy, and thymectomy—to identify the articles describing the role of thymectomy during CLND in DTC. A pooled analysis of surgicopathological outcomes was performed using metaprop command in STATA software version 16. Result A total of three studies and 347 patients—total thyroidectomy (TT) with bilateral thymectomy in 154, TT with unilateral thymectomy in 166, and TT alone in 27 patients with DTC—were included in the systematic review. The pooled frequency of thymic metastasis was a mere 2% in patients undergoing either unilateral or bilateral thymectomy. The routine addition of thymectomy does not result in better lymph node clearance. Unilateral and bilateral thymectomy were associated with high chances of transient hypocalcemia (12.0% and 56.1%, respectively). Conclusion Routine thymectomy is not warranted during CLND, considering minimal oncological benefit and high risk of postoperative hypocalcemia.

Clinicopathologic features of thyroid neoplasm with THADA-IGF2BP3 fusion

Introduction/Objective Thyroid adenoma-associated (THADA)-IGF2BP3 fusions is related to strong overexpression of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) mRNA and protein, increased IGF2 translation and IGF1 receptor signaling via PI3K and MAPK pathways. THADA-IGF2BP3 have been identified as an oncogenic event in thyroid neoplasms, but the clinicopathologic features have not been greatly evaluated. The purpose of this cases review is to describe the clinical and pathologic findings of thyroid nodules with THADA-IGF2BP3 fusion on molecular testing. Methods/Case Report Surgical Pathology 220 cases of total and hemithyroidectomy from January 2018 to December 2019 were reviewed for cytology fine needle aspiration (FNA), molecular testing results and surgical resection pathology. Results (if a Case Study enter NA) Three cases of THADA-IGF2BP3 fusion identified by Thyroseq testing from FNA of thyroid nodules with all diagnosed as atypia of undetermined significance, Bethesda category 3. No other mutations or gene fusions are identified. Successive surgical interventions are performed. Case 1 is a 49-year-old female right hemithyroidectomy with pathologic diagnosis of papillary thyroid carcinoma (PTC) follicular variant with tumor capsular invasion and no lymphvascular invasion. The tumor is 2cm, two lymph nodes evaluated are not involved by tumor and pathological stage is pT1b pN0. Case 2 is a 71-year-old female total thyroidectomy and the pathologic diagnosis is PTC follicular variant with tumor capsular invasion and no lymphvascular invasion. The tumor is 2cm, one lymph node evaluated is not involved by tumor and pathologic stage is pT1b pN0. Case 3 is a 76-year-old male left hemithyroidectomy and pathologic diagnosis is PTC follicular variant with tumor capsular invasion and no lymphvascular invasion. The tumor is 2cm, two lymph nodes evaluated are not involved by tumor and pathologic stage is pT1b pN0. Conclusion THADA-GF2BP3 fusion is uncommon in thyroid neoplasms and only three cases are detected in 220 cases evaluated. The three cases of thyroid nodules are all diagnosed as AUS by FNA, and all are diagnosed as PTC follicular variant with capsular invasion upon resection without lymphvascular invasion or lymph node involvement. THADA-F2BP3 fusion is associated with thyroid carcinoma, with low-risk non-aggressive behavior, conservative surgery appears necessary and lobectomy is likely adequate.