Hyalinizing Trabecular Adenoma Research Articles

RET/PTC1 Rearrangement in Hashimoto Thyroiditis: Canonical WNT Expression Up-regulation for Neoplastic Promotion

Background More than half a century has passed since the association between papillary thyroid carcinoma (PTC), and Hashimoto thyroiditis (HT) has been described. The discovery of the RET/PTC oncogene 30 years later has further strengthened this argument, followed by the associations made between hyalinizing trabecular adenoma (HTA) and both PTC and HT. Numerous researchers studied these relationships, with some debating a valid link. Findings This case of a 28-year-old woman with HT-associated PTC and a coexisting HTA offers a unique opportunity to study these three lesions together in the same microenvironment. Fresh tissue analysis for gene expression showed that all three expressed RET/PTC1 transcripts, whereas this was not seen in the control normal thyroid tissue. There was also an increased expression of AKT, ERK1, nuclear β-catenin, and TCF4 in both the HTA and PTC sampled tissue. AKT plays a central role in regulating cell proliferation and survival by inhibiting apoptotic processes, whereas ERK1 leads to cell proliferation. Both β-catenin and TCF4 are linked to the canonical WNT/β-catenin pathway. Conclusions The expression of RET/PTC1 highlights the link between inflammatory processes such as HT and neoplastic conditions such as HTA and PTC. The limited expression of TCF4, AKT, ERK1, and β-catenin supports the notion that the canonical WNT/β-catenin pathway plays a pivotal role in the development of this neoplasm. It is important to note that at this time, gene expression alone is not sufficient to make a distinction between benign and malignant thyroid lesions.

Expression of Beta-catenin Oncoprotein in Nuclear Pseudo-inclusions of Papillary Thyroid Carcinoma

Introduction: Nuclear pseudoinclusions are one of the most specific pathologic features in diagnosing papillary thyroid carcinoma (PTC). However, the biologic nature of these pseudo-inclusions is largely unknown. Beta-catenin is an oncoprotein involved in Wnt signaling pathway which is activated in several malignancies including PTC. Using immunohistochemistry, we studied the expression of beta-catenin in PTC and hyalinizing trabecular adenoma (HTA), with particular focus on its expression in pseudoinclusions, both on histologic sections and on cytologic specimens. Materials and Methods: A cohort of 13 cases, including 8 cases of PTC and 5 cases of HTA, was applied in this study. Beta-catenin immunohistochemitry was performed on histology block recuts and cytology slides of each case. The beta-catenin labeling index of pseudoinclusions was counted in 15 high power fields and calculated in comparison with those counted on immediate next H&E stained histologic slides. Cytology slides were digitally scanned before destaining and restaining with beta-catenin. The number of beta-catenin-labeled pseudo-inclusions was compared with those digitally scanned slides. Results: On histologic sections, neoplastic cells from both PTC and HTA show much stronger membranous staining pattern of beta-catenin, compared to adjacent normal follicles or colloid nodules. However, labeling index of beta-catenin for nuclear pseudo-inclusions is significantly different between PTC and HTA. Strong intranuclear staining of beta-catenin was seen in 93.5% (range of 72-100%) of the pseudoinclusions in PTC, while only 6.4% (range of 0-13%) of pseudo-inclusions in HTA showed positive staining pattern (p<0.001). For cytologic slides, although it demonstrated similarly strong membranous staining pattern for beta-catenin in PTC cells, none of the nuclear pseudo-inclusions in both PTC and HTA was labeled with beta-catenin antibody on cytologic smears. Conclusions: Overexpression of the beta-catenin oncoprotein was seen in majority of the nuclear pseudo-inclusions in PTC, but only rarely seen in HTA. This differential expression suggests that activation of the betacatenin is likely involved in the formation of “malignant peudoinclusions” in PTC, but not in “benign peudoinclusions” in HTA. The failure of betacatenin labeling of pseudoinclusions on cytologic slides may be in part attributed to inability of the antibody to penetrate into nucleus through the intact cell membranes in cytologic preparations.

Thyroglobulin Measurement in Fine Needle Aspirates (Tg-FNA) of Cystic Neck Masses for Detection of Papillary Thyroid Carcinoma (PTC)

Introduction: Nuclear pseudoinclusions are one of the most specific pathologic features in diagnosing papillary thyroid carcinoma (PTC). However, the biologic nature of these pseudo-inclusions is largely unknown. Beta-catenin is an oncoprotein involved in Wnt signaling pathway which is activated in several malignancies including PTC. Using immunohistochemistry, we studied the expression of beta-catenin in PTC and hyalinizing trabecular adenoma (HTA), with particular focus on its expression in pseudoinclusions, both on histologic sections and on cytologic specimens. Materials and Methods: A cohort of 13 cases, including 8 cases of PTC and 5 cases of HTA, was applied in this study. Beta-catenin immunohistochemitry was performed on histology block recuts and cytology slides of each case. The beta-catenin labeling index of pseudoinclusions was counted in 15 high power fields and calculated in comparison with those counted on immediate next H&E stained histologic slides. Cytology slides were digitally scanned before destaining and restaining with beta-catenin. The number of beta-catenin-labeled pseudo-inclusions was compared with those digitally scanned slides. Results: On histologic sections, neoplastic cells from both PTC and HTA show much stronger membranous staining pattern of beta-catenin, compared to adjacent normal follicles or colloid nodules. However, labeling index of beta-catenin for nuclear pseudo-inclusions is significantly different between PTC and HTA. Strong intranuclear staining of beta-catenin was seen in 93.5% (range of 72-100%) of the pseudoinclusions in PTC, while only 6.4% (range of 0-13%) of pseudo-inclusions in HTA showed positive staining pattern (p<0.001). For cytologic slides, although it demonstrated similarly strong membranous staining pattern for beta-catenin in PTC cells, none of the nuclear pseudo-inclusions in both PTC and HTA was labeled with beta-catenin antibody on cytologic smears. Conclusions: Overexpression of the beta-catenin oncoprotein was seen in majority of the nuclear pseudo-inclusions in PTC, but only rarely seen in HTA. This differential expression suggests that activation of the betacatenin is likely involved in the formation of “malignant peudoinclusions” in PTC, but not in “benign peudoinclusions” in HTA. The failure of betacatenin labeling of pseudoinclusions on cytologic slides may be in part attributed to inability of the antibody to penetrate into nucleus through the intact cell membranes in cytologic preparations.

Hyalinizing trabecular adenoma of thyroid - a case report and review of literature

Hyalinizing trabecular adenoma of thyroid is a rare tumour first described in 1987. It’s cytological and histopathological features are very close to other thyroid neoplasms specially papillary and medullary carcinoma. So misinterpretation of cytological feature may lead to a total thyroidectomy whereas a lobectomy is enough to cure this benign condition. Here we present such a case in a 30-year-old female patient and review the diagnosis and management DOI: http://dx.doi.org/10.3329/bjo.v18i2.12018 Bangladesh J Otorhinolaryngol 2012; 18(2): 203-206

The Hyalinizing Trabecular Tumor of the Thyroid Gland-Case Report: Morphologic, Cytological and Immunohistochemical Features

Hyalinizing trabecular adenoma of the thyroid gland is a rare benign neoplasm. This can be confused with papillary carcinoma and thyroid medullary carcinoma in cytology from the permanent sections analysed. The female patient was clinically diagnosed as having euthyroid and radioactive iodine as a result of the scan performed which revealed a solitary qcoldq nodule in right lobe. The hypocellulary TIIAB consisted of cells that were features of papillar carcinoma. A final diagnosis of the TIIAB was reported as a suspicious papillary carcinomas of the thyroid. A total thyroidectomy was performed and requested to be frozen. In the frozen section analysed, It was thought to be compatible with papillary carcinoma due to having solid and trabecular patterns in the hyalinizing stroma, nucleer pseodoinclusions and microcalsifications. Histologically, prominent nesting, trabecular growth patterns and a hyaline stroma were found. In the permanent sections analysed, the tumor exhibited clear margins of thin, fibrous capsule cells that were features of papillar carcinoma. Tumor cells were diffusely positive for thyroglobulin, but negative for staining with antibodies to HBME-1, CK19 and calcitonin. The case was reported asqhyalinizing trabecular adenomaq. This rare tumor is presented to draw attention to the features of cytology, morphologic and immunohistochemical.

Hyalinizing trabecular adenoma of the thyroid gland

Hyalinizing trabecular adenoma (HTA) is a rare primary thyroid neoplasm. Ever since its initial descriptions, controversy has surrounded the lesion, particularly in regard to its malignant potential and most appropriate terminology. HTA shares many features with medullary thyroid carcinoma and particularly papillary thyroid carcinoma, making it an especially treacherous lesion on fine-needle aspiration (FNA). This manuscript reviews the history and pathologic features of HTA, with particular attention to cytologic findings and differential diagnosis.

Hyalinizing trabecular tumour of the thyroid—differential expression of distinct miRNAs compared with papillary thyroid carcinoma

To compare the expression pattern of five microRNAs (miRNAs) (146b, -181b, -21, -221, -222) of papillary thyroid carcinoma (PTC) and hyalinizing trabecular tumour of the thyroid (HTT). The expression pattern of five miRNAs known to be up-regulated in PTC was retrospectively analysed in 18 HTTs, adjacent normal thyroid tissue, 10 PTCs, 10 follicular adenomas and 10 non-toxic multinodular goitres (MNG) by reverse transcriptase-polymerase chain reaction using the TaqMan miRNA assay. Furthermore, the two common genetic alterations characteristic for PTC, the V600E mutation of the BRAF gene and RET/PTC 1 and 3 rearrangements, were determined in all HTTs. All miRNAs were significantly up-regulated in PTCs, whereas all miRNAs in HTT, normal thyroid tissue, adenomas, and MNGs were down-regulated. Calculating relative changes in gene expression, a 510-fold change of miRNA 146b between PTC and HTT could be observed followed by fold changes between 6.4 and 29 in the remaining miRNAs (P < 0.001). All HTTs lacked BRAF mutations and RET/PTC rearrangements. Our findings do not support the concept that a high proportion of HTT represents a variant of PTC. It is suggested that HTTs lacking both a miRNA expression pattern characteristic for PTC and RET/PTC rearrangements are re-designated as 'hyalinizing trabecular adenomas'.

A Case of Hyalinizing Trabecular Adenoma of the Thyroid Gland

Hyalinizing trabecular tumor is a rare benign thyroid tumor first described by Carney et al. in 1987. The tumor is characterized by an encapsulated nodule, trabecular arrangement of polygonal, oval, elongated cells, and hyalinized stroma. It is easily confused with papillary thyroid carcinoma or medullary thyroid carcinoma on surgical and cytologic specimens. A 45-year-old man presented with an incidentally detected left thyroid mass. Fine needle aspiration was performed and papillary thyroid carcinoma was suspected. However, the surgical specimen revealed a hyalinizing trabecular adenoma. We present this hyalinizing trabecular adenoma case to share our experience with physicians and specialists. (J Korean Endocr Soc 24:54~57, 2009)

Hyalinizing trabecular adenoma—an uncommon thyroid tumor frequently misdiagnosed as papillary or medullary thyroid carcinoma

Background Hyalinizing trabecular adenoma (HTA) is an uncommon benign thyroid tumor that can present as a solitary thyroid nodule, a prominent nodule in a multinodular goiter, or as an incidental finding in a thyroidectomy specimen. The clinical significance of the lesion is that it is frequently misdiagnosed as papillary carcinoma on fine-needle aspiration cytology or as papillary or medullary carcinoma on histopathological section. We reviewed our recent experience with 7 patients diagnosed with HTA. Methods Fine-needle aspiration biopsy was performed in 7 patients presenting with a solitary thyroid nodule (n = 4) or a multinodular goiter (n = 3). The patients underwent total thyroidectomy (n = 6) or hemithyroidectomy (n = 1). Results In 4 patients, the preoperative cytology was suggestive of papillary carcinoma, in 2 patients suspicious, and in 1 patient positive for papillary carcinoma. On histopathological section, 2 patients had a microscopic HTA, 2 patients had HTA in 1 or 2 nodules of a multinodular goiter, and 3 patients had HTA in a solitary nodule. Except in 1 patient, who had a microscopic focus (3.2 mm) of papillary carcinoma, there was no evidence of malignancy in the surgical specimens on permanent histopathological section. Conclusions Although HTA is a rare condition of the thyroid, the surgeon needs to be aware of this entity to be able to better discuss the pathological findings with the patient, particularly since some pathologists and endocrinologists believe that HTA may represent a malignant neoplasm of low metastatic potential.

Hyalinizing Trabecular Adenoma of the Thyroid Revisited: A Histologic and Immunohistochemical Study of Thyroid Lesions With Prominent Trabecular Architecture and Sclerosis

Since its description, hyalinizing trabecular adenoma (HTA) of the thyroid has been a controversial entity. Some have considered it a unique entity, some have considered it a variant of papillary carcinoma (PC), and still others have considered it a nonspecific pattern that may be seen with a variety of thyroid lesions. Complicating the matter, studies demonstrating metastases have shown entities that do not appear to be HTAs as originally described, and molecular studies showing changes of PC have used methods that are not specific. This study reviews our experience with thyroid lesions that showed at least some histologic features of HTA and presents the immunohistochemical findings for these lesions using antibodies employed for the diagnosis of PC. Our files were reviewed for all thyroid resection reports describing lesions with hyalinized or sclerotic stroma and a trabecular architecture within the diagnosis or diagnostic comment. All cases were reviewed and classified as either HTA or as different lesions based upon histologic features. Immunohistochemistry with antibodies to HBME1, CK19 and p63 was performed with all lesions and with a series of controls. Eighteen thyroid lesions with prominent sclerosis or hyalinization and trabecular architecture were identified. Only 4 of these were found to completely match the histologic and cytologic descriptions of HTA by HE review. The other cases showed histologic features more compatible with other diagnoses including cellular adenomatoid nodule (5), follicular adenoma (4), follicular variant of PC (FVPC) (3), and epithelial neoplasm with features of FVPC (2). All HTAs lacked immunoreactivity for HBME1, CK19 and p63. All cases deemed to be adenomatoid nodules, follicular adenomas and epithelial neoplasms showed no immunoreactivity for HBME1 and CK19 and, of these, only a single AN showed immunoreactivity for p63. Cases deemed to be FVPCs showed diffuse immunoreactivity for HBME1 and CK19 and 1 reacted with antibodies to p63. Of control PCs and other thyroid lesions, reactivity for HBME1, CK19, and p63 was observed in 8/8, 7/7, and 7/8 and 3/27, 7/27, and 7/27 cases, respectively. A sclerotic or hyalinized stroma with a trabecular growth pattern may be seen in a number of different thyroid lesions and, when seen, is usually a focal feature of a lesion other than HTA. Immunohistochemistry may be of assistance as cases of FVPC with prominent hyalinization and trabeculation will show immunoreactivity for HBME1 and CK19, whereas HTAs and other thyroid lesions with hyalinization and trabeculation will not.

Hyalinizing Trabecular Adenoma of the Thyroid Gland

Smears of fine-needle aspiration (FNA) biopsy specimens of 24 histologically proven and MIB-1–positive hyalinizing trabecular adenomas stained with Papanicolaou or Diff-Quik were stripped from the original slides, transferred to charged slides, destained, and restained with MIB-1. Positive immunoreactivity with MIB-1 in a peripheral cytoplasmic pattern was present in 17 specimens, no immunoreactivity was seen in 4 specimens, and equivocal staining was seen in 3 specimens. Papanicolaou-stained smears of papillary thyroid carcinoma, medullary thyroid carcinoma, thyroid follicular neoplasm, and Hurthle cell adenoma (5 specimens each) were treated similarly. None of the control cases stained with MIB-1 had the peripheral cytoplasmic pattern. Hyalinizing trabecular adenoma can be distinguished reliably from other thyroid neoplasms by MIB-1 staining of destained cells from FNA biopsy specimens.

Cytologic Features of Hyalinizing Trabecular Adenoma of the Thyroid

To clarify the cytologic findings of hyalinizing trabecular adenoma (HTA) in order to reduce erroneous diagnoses of papillary carcinoma. Review of aspiration cytologic smears of 16 HTA cases and comparison with those of 20 papillary carcinoma cases. The smears from HTA were slightly cellular, and 5 of 16 cases were insufficient for evaluation. Vague, curved nuclear palisading, radiating arrangement surrounding hyaline materials and yellow bodies were observed in 9 (81.8%) of 11 cases that had sufficient material. The tumor cells were mainly spindled; elongated, polygonal and stellate cells were also seen. In 9 of 11 cases, tumor cells with cytoplasmic processes were occasionally observed. The cytoplasm was faintly stained and somewhat filamentous. The cell border was indistinct. Neither papillary nor follicular structures were seen. Intranuclear cytoplasmic inclusions were identified in 100% of HTA and 75% of papillary carcinomas. The incidences of nuclear grooves in HTA and papillary carcinoma were 81.8% and 100%, respectively. Cytologic findings indicating HTA are vague, curved nuclear palsiading; radiating arrangement surrounding hyaline material; elongated cells; cell processes; ill-defined cell border; faintly stained and filamentous cytoplasm; yellow bodies; and hyaline material in the background. All are useful cytologic characteristics in distinguishing HTA from papillary carcinoma. A lack of papillary architecture and sheetlike arrangement may also suggest HTA rather than papillary carcinoma.

Hyalinizing trabecular adenoma versus papillary thyroid carcinoma in a child

Hyalinizing trabecular adenoma (HTA) of the thyroid gland is a rare, benign neoplasm predominantly diagnosed in middle-aged women. There is mounting evidence in the medical literature, however, to suggest that HTA may represent an encapsulated variant of papillary thyroid carcinoma (PTC). This report describes an unusual case of PTC in a child initially diagnosed as HTA. Establishing an accurate diagnosis has important management implications for the pediatric patient.

Hyalinizing trabecular tumor of the thyroid: a variant of papillary carcinoma proved by molecular genetics.

Hyalinizing trabecular tumors of the thyroid are interesting but uncommon neoplasms. They have been classified as benign hyalinizing trabecular adenomas or malignant hyalinizing trabecular carcinomas. They share both epidemiologic and morphologic features with papillary carcinoma, and there has been much speculation about the relationship between these two entities. Because RET/PTC gene rearrangements are specific to papillary thyroid carcinoma, the authors examined the presence of RET/PTC-1, -2, and -3 in eight hyalinizing trabecular tumors using reverse transcription-polymerase chain reaction with Southern hybridization and immunohistochemistry. They detected the presence of a RET/PTC gene rearrangement in six of the eight hyalinizing trabecular tumors. This confirms the long-standing suspicion that hyalinizing trabecular tumors do indeed represent a morphologic variant of papillary carcinoma.

Histology of familial thyroid tumours linked to a gene mapping to chromosome 19p13.2.

This paper describes the pathology of thyroid tumours showing an autosomal mode of inheritance linked to a gene that maps to chromosome 19p13.2. All the affected members from the family (seven males and two females; mean age 23 years) were clinically euthyroid and presented with nodular goitre; tumour recurrence after thyroidectomy was observed in four. In four of the five patients studied, the tumours were multifocal, bilateral well demarcated or encapsulated and composed of follicles, papillae, trabeculae/solid areas (often resembling hyalinizing trabecular adenoma of the thyroid) or an admixture, formed by cells with pale to intense cytoplasmic eosinophilia. A diagnosis of multiple adenomatous goitre was made in the thyroidectomy specimen from two patients, while the other two patients showed, in addition to multiple adenomas, a co-existent oxyphil papillary carcinoma. The fifth patient had an oxyphil cell carcinoma. All tumours were of follicular cell origin as shown by immunocytochemistry. Less than a third of the benign tumours and all three carcinomas showed a variable number of neoplastic cells diffusely immunostained for mitochondria. Histological findings of a 'multiple adenomatous goitre', non-endemic 'multinodular goitre' or multiple neoplasms of follicular cell origin with the morphology of those described here, particularly in young patients, should alert the pathologist and physician to the possibility of an inherited trait, with its implications for family screening. The tumours are usually benign and well demarcated but because of multicentricity and consequently increased risk of recurrence and/or progression to carcinoma, total thyroidectomy should be advocated.

Hyalinizing trabecular adenoma of the thyroid gland.

Hyalinizing trabecular adenoma is a follicular-derived tumor of the thyroid gland with a strong predilection for women. In the reported cases, the biologic course has been benign and without recurrences. The most important histologic differential diagnosis is medullary carcinoma, particularly the encapsulated form of the neoplasm.

Hyalinizing trabecular adenoma: A misnomer for a peculiar tumor of the thyroid gland.

We describe the clinical, histological, immunohistochemical, and electron microscopical features of 9 tumors fulfilling the criteria of the so-called hyalinizing trabecular adenoma (HTA) of the thyroid. Six tumors had the characteristic histology of HTA throughout, whereas in the remaining 3 tumors the classic pattern was identified focally in otherwise typical or atypical follicular adenomas. In one case, there was a focus of tumoral tissue outside the capsule, and in another there was a regional lymph node metastasis. Seven tumors were immunoreactive for thyroglobulin and cytokeratins, 1 tumor was positive for thyroglobulin and negative for cytokeratins, and another was negative for thyroglobulin and positive for cytokeratins. Scattered cells immunoreactive for neurotensin and somatostatin were found in 2 cases. Every tumor stained for S100 protein and neuron-specific enolase, but none showed immunoreactivity for calcitonin, calcitonin gene-related peptide, or chromogranin. The irregularity of the nuclear contours, the prominence of the cytoplasmic bundles of intermediate filaments, and the accumulation of basal lamina material around the neoplastic cells without the interposition of a well-defined basal lamina were the most distinctive electron microscopical features. The cytogenetic study performed in one case revealed, apart from cells with a normal karyotype, two abnormal clones: one with a translocation of chromosomes 2-3 and another with the same translocation and trisomies of chromosomes 7 and 12. Our results show that most HTAs display follicular cell differentiation and very low clinical aggressiveness. They also show that some HTAs are able to coexpress follicular cell and neuroendocrine markers and may behave like malignant neoplasms. We conclude that hyalinizing trabecular tumor is a more appropriate generic term than HTA to designate this relatively heterogenous group of lesions of the thyroid gland.

Hyalinizing trabecular adenoma‐like lesion in multinodular goitre

Hyalinizing trabecular adenoma, a recently characterized variant of thyroid adenoma, is often confused with a variety of lesions because of its unusual histological features (Carney, Ryan & Goellner 1987). We report a case of multinodular goitre in which there were several small nodules showing features of hyalinizing trabecular adenoma and peculiar nuclear rods.