Hyalinizing Trabecular Tumor Research Articles

Diagnostic clues for hyalinizing trabecular tumor on fine needle aspiration cytology.

The hyalinizing trabecular tumor (HTT) is a rare benign neoplasm of the thyroid gland. This neoplasm has overlapping cytological features with Papillary Thyroid Carcinoma, Medullary Carcinoma and Follicular Neoplasm with Nuclear Features of Papillary Carcinoma. This can lead to misdiagnosis of malignancy in fine needle aspiration (FNA) cytology specimens with unnecessary total thyroidectomy. The aim of this study is to determine if there are some cytological features that could help us to suspect HTT on FNA specimens and avoid radical surgery. With this purpose we have collected 6 cases diagnosed of HTT in Hospital Clínico San Carlos of Madrid (Spain) in the last 10 years and reviewed the cytological specimens. We conclude that the presence of hyaline material in FNA specimens of HTT is a constant feature being a diagnostic clue. We must be cautious not to confuse it with dense colloid or amyloid material, the latter seen in Medullary Carcinoma. Papillary architecture and fibrovascular cores are not present in a HTT. Special stains as ki-67, calcitonin and Congo Red staining could help us in achieving the correct diagnosis. We feel the cytopathologists must be aware of the distinguishing features of this lesion, mainly the typical hyaline material to achieve a proper diagnosis and be able to reduce unnecessary aggressive management of these patients.

A case of hyalinizing trabecular tumor of the thyroid gland

The patient was a 63-year-old man. In year X-3, neck ultrasonography (US), performed as part of a complete medical checkup, revealed a mass in the right thyroid lobe. Fine-needle aspiration (FNA) cytology was performed at the Otolaryngology department. Although papillary carcinoma could not be ruled out, the mass was classified as a class III tumor. Although neck US performed in years X-2 and X-1 showed no changes in the thyroid mass, the patient noted discomfort in the neck and requested the resection of the thyroid mass. Thus, surgery (right hemi-thyroidectomy) was performed in year X. The right hemi-thyroidectomy was conventionally performed; however, lymph node dissection was not performed because no swollen regional lymph nodes were observed. The mass was pathologically diagnosed as a hyalinizing trabecular tumor (HTT) based on hematoxylin-eosin staining and immunostaining. HTT of the thyroid is a rare tumor exhibiting peculiar features, as proposed by Carney et al. in 1987. It is a special type of tumor originating from the follicular epithelium that cytologically and histologically resembles a papillary carcinoma. While this tumor is often suspected to be a papillary carcinoma by FNA cytology, a definite diagnosis is often made based on intraoperative or postoperative pathological examination. Our case suggests that when preoperative FNA cytology reveals many intranuclear inclusions and nuclear grooves, HTT should be considered, in addition to papillary carcinoma.

Fine Needle Aspiration Cytology of Hyalinizing Trabecular Tumor of the Thyroid

Objective To investigate the fine needle aspiration cytology and differential diagnosis of hyalinizing trabecular tumor (HTT) of the thyroid.Methods The fine needle aspiration smears of four HTT cases with histopathological controls were analyzed,which were then combined with the histopathological changes and immunophenotypes for diagnosis.The key points of cytological diagnosis and the differential diagnosis of HTT were then summarized.Results The fine needle aspiration cytology showed that the tumor cells were scattered,presenting as partially cohesive clusters or clusters with trabecular manifestations.The tumor cells were polygonal or spindle,with medium or rich cytoplasm.The nuclei were oval or short spindle,with fine granular chromatin,visible small nucleoli,common nuclear grooves and nuclear pseudoinclusions,and irregular outline,which demonstrated the nucleus characteristics of papillary thyroid carcinoma.The interstitium showed transparent basement membrane-like material deposition,loose tumor cell clusters,trabecular or syncytial structure,radially distributed tumor cells around the hyaline-like material,rich eosinophilic or dichromophile cytoplasm,elongated nuclei,no papillary structure or fibrovascular axis,and no psammoma bodies.Histopathology showed tumor cells arranged in beam and organoid,transparent basement membrane-like material deposition between trabecular beams,and polygonal or spindle cells containing fine granular eosinophilic cytoplasm and round or oval nuclei with common nuclear grooves and nuclear pseudoinclusions.Conclusion Combining the ultrasound results with the arrangement,interstitial components,and cytological characteristics of tumor cells,we suggest that Ki-67(MIB-1)staining can be employed to assist diagnosis and improve the diagnostic accuracy of HTT or intraoperative freezing can be adopted for further diagnosis.

Follicular Neoplasm of Thyroid Revisited: Current Differential Diagnosis and the Impact of Molecular Testing.

The diagnosis of "follicular neoplasm" (FN) in thyroid cytopathology has a long history that originated not long after the practice of fine-needle aspiration (FNA) of thyroid nodules. From the outset, this interpretive category was intended to convey a set of differential diagnoses rather than a precise diagnosis, as key diagnostic features, such as capsular and vascular invasion, were not detectable on cytology preparations. Cytologic-histologic correlation studies over the past several decades have shown that FN interpretation can be applied to the spectrum of nonneoplastic tumors to carcinomas. Most tumors classified as FN include follicular adenoma, follicular carcinoma, noninvasive follicular thyroid tumor with papillary-like nuclear features, and follicular variant of papillary thyroid carcinoma. Less common entities that may be classified as FN on FNA include hyalinizing trabecular tumor (HTT), poorly differentiated thyroid carcinoma, medullary carcinoma, and nonthyroidal lesions such as parathyroid tissue, paraganglioma, and metastatic tumors. Advances in our ability to detect characteristic molecular alterations (eg, GLIS gene rearrangements for hyalinizing trabecular tumor) in FNA samples may assist in the identification of some of these entities. In this review, we summarize the pathophysiology, history, and evolution of the terminology and the current differential diagnosis according to the recently published 2022 World Health Organization classification, molecular testing, and management of nodules classified as FN.

Hyalinizing Trabecular Adenoma: A Diagnostic Dilemma on Cytology

Hyalinizing trabecular tumors (HTT) are rare and almost universally benign neoplasms of the thyroid gland. Its challenging cytologic diagnosis by FNAC is ascribed to its cytomorphologic features which overlap with papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC). Due to the diagnostic difficulty, many patients receive overtreatment for what is primarily a benign disease. Here, we share our case report of HTT with cytologic evaluation by FNAC in a 28 years old female. Keywords: HTT, PTC, MTC.

다소성 갑상선 유리질소주형 종양 1예

Hyalinizing trabecular tumor (HTT) of the thyroid gland is a rare benign tumor that is characterized by thick trabeculae with intra-trabecular hyaline material. This tumor is often classified as indeterminate/suspicious according to the Bethesda system on fine-needle aspiration (FNA) cytology, because of HTT cells and papillary thyroid carcinoma (PTC) cells overlapped cytologic features. Recently, we experienced a case of multifocal HTTs of the thyroid gland. A 61-year-old woman present with multiple thyroid nodules. FNA cytology showed suspicious PTC, and we performed left hemithyroidectomy. However, the pathology after surgery indicated multifocal HTTs. We present this HTTs case with a brief review. (J Clinical Otolaryngol 2021;32:308-311)

Total thyroidectomy can still remain the method of choice in some Bethesda III cases.

The latest WHO classification of tumours of endocrine organs defines new units of borderline thyroid tumours (BTT). The aim of our study was to evaluate ultrasonographic and cytological features, mutation profile and surgery treatment in rare thyroid tumours. An analysis of 8 BTT out of 487 patients, who underwent thyroid surgery between June 2016 and June 2020. The definitive diagnosis was made postoperatively by extensive histopathological examination. Molecular genetic analysis of genes associated with thyroid oncology (BRAF, HRAS, KRAS, NRAS, TERT, TP53, fused genes) were performed from one FNAB, and 7 formalin-fixed paraffin-embedded (FFPE) samples. BTT were found in a total of 8 patients (1.6%), with a predominance of men with respect to other operated patients. FNAB samples were classified in the Bethesda system as Bethesda I, Bethesda II and Bethesda III in one, four and three cases, respectively. Hemithyroidectomy and total thyroidectomy were performed equally in four patients. The histopathological diagnosis revealed non-invasive encapsulated follicular neoplasm with papillary-like nuclear features (NIFTP) in three patients, follicular tumour of uncertain malignant potential (FT-UMP) in three patients, well differentiated tumour of uncertain malignant potential (WDT-UMP) in one patient, and hyalinizing trabecular tumour (HTT) in one case. In NIFTP cases mutation in HRAS gene in one patient together with probable pathogenic variant in TP53 gene and in NRAS gene in two patients were detected. In HTT patient PAX8/GLIS3 fusion gene was detected. The surgical treatment of BTT is necessarily individual influenced by preoperative clinical, ultrasonographic, cytological and molecular genetic findings, and the presence of other comorbidities.

Two cases of rare thyroid cancer• Hyalinizing trabecular tumor and Warthin like papillary carcinoma.

Two cases of rare thyroid cancer• Hyalinizing trabecular tumor and Warthin like papillary carcinoma.

Two cases of rare thyroid cancer• Hyalinizing trabecular tumor and Warthin like papillary carcinoma.

Two cases of rare thyroid cancer• Hyalinizing trabecular tumor and Warthin like papillary carcinoma.

Two cases of rare thyroid cancer• Hyalinizing trabecular tumor and Warthin like papillary carcinoma.

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

Diagnosis and management of hyalinizing trabecular tumor of the thyroid: a single-institution experience.

Hyalinizing trabecular tumor (HTT) of the thyroid is a mostly benign disease. Its cytological and pathological diagnosis is often difficult, because HTT cells and papillary thyroid carcinoma (PTC) cells share similar features (e.g., intranuclear cytoplasmic inclusions and nuclear grooves). At our institution, 38 patients were diagnosed as or highly suspected of having HTT without the possibility of PTC, based on cytology: 19 of these patients underwent immediate surgery (surgery group) and the remaining 19 underwent active surveillance without surgery (AS group). The surgery-group patients' tumor sizes were significantly larger (p < 0.0001) than those in the AS group. During AS (median 38 months), only one patient (5%) showed tumor enlargement by ≥3 mm; the AS was continued. Of the 34 patients pathologically diagnosed with HTT, 22 (65%) were cytologically diagnosed or highly suspected as having HTT without the possibility of PTC. Of the nine patients who were suspected to have HTT but PTC was possible and surgery was performed, two (22%) and seven (78%) were pathologically diagnosed as having PTC and HTT, respectively. Five patients were cytologically diagnosed with PTC, but pathologically diagnosed as having HTT. No patients showed HTT recurrence during postoperative follow-up (median 60 months). These findings suggest that (1) active surveillance can be a valid strategy for managing tumors that are cytologically diagnosed as HTT with no possibility of PTC; (2) surgery is recommended for tumors suspected of being HTT but may be PTC, and (3) the prognosis of HTT in both the AS and surgery groups was excellent.

Hyalinizing Trabecular Tumor of the Thyroid

An adult female presented with a thyroid mass. The tumor was diagnosed by pathology as a hyalinizing trabecular tumor of the thyroid. What statement is most accurate regarding hyalinizing trabecular tumor of the thyroid?a.Hyalinizing trabecular tumor is a biologically aggressive thyroid tumorb.PAX8-GLIS3 gene fusion was recently described as a characteristic genetic alteration in hyalinizing trabecular tumor of the thyroidc.Hyalinizing trabecular tumor of the thyroid is usually associated with syndromes such as multiple endocrine neoplasiad.Hyalinizing trabecular tumor of the thyroid has a similar immunophenotype as medullary thyroid carcinoma (immunopositive for chromogranin A, synaptophysin, and calcitonin) Answer: b. PAX8-GLIS3 gene fusion was recently described as a characteristic genetic alteration in hyalinizing trabecular tumor of the thyroid Hyalinizing trabecular tumor of the thyroid is a follicular derived neoplasm that occurs more commonly in females and generally has a benign biologic course, with only an exceptional case showing malignant behavior.1Lloyd R.V. Osamura R.Y. Kloppel G. Rosai J. WHO Classification of Tumours of Endocrine Organs.4th Edition. IARC, Lyon, France2017Google Scholar,2Carney J.A. Hirokawa M. Lloyd R.V. Papotti M. Sebo T.J. Hyalinizing trabecular tumors of the thyroid gland are almost all benign.Am J Surg Pathol. 2008; 32: 1877-1889Crossref PubMed Scopus (64) Google Scholar Most individuals with hyalinizing trabecular tumor are asymptomatic, and this tumor is not known to be syndrome associated. As follicular derived neoplasms, hyalinizing trabecular tumors show immunopositivity for thyroglobulin and are not positive for neuroendocrine markers chromogranin A or synaptophysin. Recently, PAX8-GLIS3 gene fusion was described as a characteristic genetic alteration in hyalinizing trabecular tumor of the thyroid.3Nikiforova M.N. Nikitski A.V. Panebianco F. Kaya C. Yip L. Williams W. et al.GLIS rearrangement is a genomic hallmark of hyalinizing trabecular tumor of the thyroid gland.Thyroid. 2019; 29: 161-173Crossref PubMed Scopus (23) Google Scholar,4Marchio C. Da Cruz Paula A. Gularte-Merida R. Basili T. Brandes A. da Silva E.M. et al.PAX8-GLIS3 gene fusion is a pathognomonic genetic alteration of hyalinizing trabecular tumors of the thyroid.Modern Pathol. 2019; 32: 1734-1743Crossref PubMed Scopus (13) Google Scholar

Oncogenic properties and signaling basis of the PAX8‐GLIS3 fusion gene

Hyalinizing trabecular tumors of the thyroid are rare and mostly benign epithelial neoplasms of follicular cell origin, which have recently been shown to be underpinned by the PAX8-GLIS3 fusion gene. In our study, we sought to investigate the potential oncogenic mechanisms of the PAX8-GLIS3 fusion gene. Forced expression of PAX8-GLIS3 was found to increase proliferation, clonogenic potential and migration of human nonmalignant thyroid (Nthy-ori 3-1) and embryonic kidney (HEK-293) cells. Moreover, in xenografts, Nthy-ori 3-1 PAX8-GLIS3 expressing cells generated significantly larger and more proliferative tumors compared to controls. These oncogenic effects were found to be mediated through activation of the Sonic Hedgehog (SHH) pathway. Targeting of smoothened (SMO), a key protein in the SHH pathway, using the small molecule inhibitor Cyclopamine partially reversed the increased proliferation, colony formation and migration in PAX8-GLIS3 expressing cells. Our data demonstrate that the oncogenic effects of the PAX8-GLIS3 fusion gene are, at least in part, due to an increased activation of the SHH pathway.

PAX8–GLIS3 gene fusion is a pathognomonic genetic alteration of hyalinizing trabecular tumors of the thyroid

The hyalinizing trabecular adenoma/tumor is a rare and poorly characterized follicular-derived thyroid neoplasm recently shown to harbor recurrent PAX8–GLIS1 or PAX8–GLIS3 gene fusions. Here we sought to define the repertoire of genetic alterations of hyalinizing trabecular tumors, and whether PAX8–GLIS3 fusions are pathognomonic for hyalinizing trabecular tumors. A discovery series of eight hyalinizing trabecular tumors was subjected to RNA-sequencing (n = 8), whole-exome sequencing (n = 3) or targeted massively parallel sequencing (n = 5). No recurrent somatic mutations or copy number alterations were identified in hyalinizing trabecular tumor, whereas RNA-sequencing revealed the presence of a recurrent genetic rearrangement involving PAX8 (2q14.1) and GLIS3 (9p24.2) genes in all cases. In this in-frame fusion gene, which comprised exons 1–2 of PAX8 and exons 3–11 of GLIS3, GLIS3 is likely placed under the regulation of PAX8. Reverse transcription RT-PCR and/or fluorescence in situ hybridization analyses of a validation series of 26 hyalinizing trabecular tumors revealed that the PAX8–GLIS3 gene fusion was present in all hyalinizing trabecular tumors (100%). No GLIS1 rearrangements were identified. Conversely, no PAX8–GLIS3 gene fusions were detected in a cohort of 237 control thyroid neoplasms, including 15 trabecular thyroid lesions highly resembling hyalinizing trabecular tumor from a morphological standpoint, as well as trabecular/solid follicular adenomas, solid/trabecular variants of papillary carcinoma, and Hurthle cell adenomas or carcinomas. Our data provide evidence to suggest that the PAX8–GLIS3 fusion is pathognomonic for hyalinizing trabecular tumors, and that the presence of the PAX8–GLIS3 fusion in thyroid neoplasms may be used as an ancillary marker for the diagnosis of hyalinizing trabecular tumor, thereby avoiding overtreatment in case of misdiagnoses with apparently similar malignant tumors.

The Diagnosis of Hyalinizing Trabecular Tumor: A Difficult and Controversial Thyroid Entity.

Hyalinizing trabecular tumor (HTT) is a benign, follicular-derived neoplasm composed of thick trabeculae with round or elongated cells having irregular and clear nuclei, and containing intra-trabecular hyaline material. The cytological features of HTT resemble those of papillary carcinoma, which helps explain why these lesions are usually classified as indeterminate/suspicious according to the Bethesda system for reporting thyroid cytology. A review of the literature indicates that reaching the correct preoperative cytologic diagnosis of HTT remains elusive, as the correct interpretation was achieved in only 8% of cases. In contrast, the correct diagnosis posed a less significant diagnostic challenge in the majority of histological series, despite the reported controversy on the relationship of this tumor with papillary and medullary thyroid carcinomas. The aim of this review is to highlight the cytological and histological clues in the diagnosis of HTT, as well as its molecular profile.

GLIS rearrangements in thyroid nodules: A key to preoperative diagnosis of hyalinizing trabecular tumor.

Hyalinizing trabecular tumor (HTT) is a rare thyroid neoplasm with peculiar morphologic features that overlap with those of papillary thyroid carcinoma (PTC). Specifically, the presence of enlarged oval nuclei, nuclear grooves, and intranuclear pseudoinclusions makes precise cytopathologic diagnosis challenging. If the cytopathologic diagnosis is suspicious for malignancy (Bethesda V) or is malignant (Bethesda VI), a total thyroidectomy, which would be considered an overtreatment, may follow. The recent discovery of the strong association between GLIS fusions and HTT sheds light on its pathogenesis and offers a pathway for its presurgical identification. Although the number of cases analyzed is limited, the recent landmark study shows that GLIS fusions are highly specific for HTT and that lobectomy is the likely appropriate surgical treatment, because these neoplasms, which lack invasion, are benign. For overall success, cytopathologic recognition of the subtle features is important to avoid false-positive diagnoses and directing potential HTT cases toward indeterminate cytopathologic diagnoses, which would trigger further molecular testing. Additional studies are needed to determine whether a malignant counterpart of GLIS fusion-positive HTT exists and if more conservative approaches may be taken.

A large series of hyalinizing trabecular tumors: Cytomorphology and ancillary techniques on fine needle aspiration.

Hyalinizing trabecular tumors (HTTs) are rare, essentially benign, follicular cell-derived thyroid neoplasms characterized by a trabecular growth pattern and nuclear pseudoinclusions. Their cytological findings are misleading, because these tumors are often misinterpreted on fine needle aspirate cytology as malignant lesions, such as papillary thyroid cancer and/or medullary thyroid cancer, leading to unnecessary total thyroidectomy. The aim of this study was to analyze the cytomorphological features and application of ancillary techniques in a series of HTTs. Of 26 histological cases of HTT collected from September 2001 to December 2018, 18 cases had concomitant cytopathology. Cytological cases were processed with liquid-based cytology (LBC). Immunocytochemistry for HBME-1 and galectine-3 as well as molecular testing for BRAFV600E mutation were performed on both LBC and histological specimens. The 18 lesions with fine needle aspirate cytology ranged in size from 5 to 45mm. Cytological diagnoses included: 1 benign lesion favoring goiter (5.5%), 4 atypia of undetermined significance (22.2%), 6 follicular neoplasms (33.3%), 5 suspicious for malignancy favoring papillary thyroid cancer (28%), and 2 malignant (11%). Hence, 89% HTT had a negative concordant immunopanel, and they were 100% wild-type BRAFV600E . The majority of our HTTs (83.3%) were diagnosed in the indeterminate Bethesda categories, suggesting that their cytomorphological features pose issues for reaching a conclusive cytological diagnosis. The ancillary test results in our series support the fact that HTT is a benign neoplasm.

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.

GLIS Rearrangement is a Genomic Hallmark of Hyalinizing Trabecular Tumor of the Thyroid Gland.

Hyalinizing trabecular tumor (HTT) is a rare thyroid neoplasm with a characteristic trabecular growth pattern and hyalinization. This lesion has been the subject of long-term controversy surrounding its genetic mechanisms, relationship to papillary thyroid carcinoma (PTC), and malignant potential. Due to the presence of nuclear features shared with PTC, HTT frequently contributes to a false-positive cytology, which hampers patient management. The goal of this study was to apply genome-wide sequencing analyses to elucidate the genetic mechanisms of HTT and its relationship to PTC. Whole-exome, RNA-Seq, and targeted next-generation sequencing analyses were performed to discover and characterize driver mutations in HTT. RNA-Seq results were used for pathway analysis. Tissue expression of GLIS3 and other proteins was detected by immunohistochemistry. The prevalence of GLIS fusions was studied in 17 tumors initially diagnosed as HTT, 220 PTC, and 10,165 thyroid fine-needle aspiration samples. Using whole-exome and RNA-Seq analyses of the initial three HTT, no known thyroid tumor mutations were identified, while in-frame gene fusion between PAX8 exon 2 and GLIS3 exon 3 was detected in all tumors. Further analysis identified PAX8-GLIS3 in 13/14 (93%) and PAX8-GLIS1 in 1/14 (7%) of HTT confirmed after blind pathology review. The fusions were validated by Sanger sequencing and FISH. The fusions resulted in overexpression of the 3'-portion of GLIS3 and GLIS1 mRNA containing intact DNA-binding domains of these transcription factors and upregulation of extracellular matrix genes including collagen IV. Immunohistochemistry confirmed upregulation and deposition of collagen IV and pan-collagen in HTT. The analysis of 220 PTC revealed no PAX8-GLIS3 and one PAX8-GLIS1 fusion. PAX8-GLIS3 was prospectively identified in 8/10,165 (0.1%) indeterminate cytology fine-needle aspiration samples; 5/5 resected fusion-positive nodules were HTT on surgical pathology. This study demonstrates that GLIS rearrangements, particularly PAX8-GLIS3, are highly prevalent in HTT but not in PTC. The fusions lead to overexpression of GLIS, upregulation of extracellular matrix genes, and deposition of collagens, which is a characteristic histopathologic feature of HTT. Due to unique genetic mechanisms and an indolent behavior, it is proposed to rename this tumor as "GLIS-rearranged hyalinizing trabecular adenoma."

Borderline Thyroid Tumors: a Surgeon's Perspectives

Borderline thyroid tumors are composed of hyalinizing trabecular tumor (HTT), well differentiated tumor of uncertain malignant potential (WDT-UMP), follicular tumor of uncertain malignant potential (FT-UMP) and non-invasive follicular tumor with papillary like nuclear feature (NIFTP) by World Health Organization (WHO) definition. They have different pathological feature from each other. However, it is difficult to diagnose with diagnostic imaging, fine needle aspiration (FNA) or core biopsy preoperatively. Thus, the diagnosis is usually made after diagnostic lobectomy. Main surgical concerns about borderline tumor are not performing total thyroidectomy because of relatively indolent nature of these tumors. Unfortunately, some of these tumors can be diagnosed as malignant tumor preoperatively. The other surgical concern is performing completion thyroidectomy or not after diagnostic lobectomy. Decision making is difficult even though it is generally considered that lobectomy alone is enough. In this article, we will discuss clinical features of borderline malignant tumors and surgical strategy for these tumors.