This tumor of the thyroid was first described in 1987 as a hyalinizing trabecular adenoma. For many years, it was thought this was a distinct tumor of the thyroid gland. However, it has been noted that these tumors share both epidemiologic and morphologic similarity to papillary carcinoma of the thyroid. In addition, although the original descriptions were of a benign neoplasm, clearly malignant tumors have been described leading to the designation of hyalinizing trabecular tumors for this group of neoplasms.
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EPIDEMIOLOGY CHARACTERIZATION SYNONYMS
Paraganglioma-like adenoma of the thyroid
Hyalinizing trabecular adenoma
PATHOGENESIS CHARACTERIZATION RET/PTC activation
Am J Surg Pathol 2000;24:1615-1621
3/14 cases showed geen rearrangement
1/14 showed focal positivity by immunohistochemistry
1/14 showed positivity in a mixed HTT-papillary carcinoma, but only in the papillary component
Suggests that HTT may represent a hyalinizing trabecular variant of papillary carcinoma
Am J Surg Pathol 2000;24:1622-1626
Detected gene rearrangement in 6/8 cases suggesting that these tumors are a morphologic variant of papillary carcinoma
RET/PTC rearrangement in thyroid tumors.
Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45267-0529, USA.
Endocr Pathol 2002 Spring;13(1):3-16 Abstract quote
Rearrangement of the RET gene, also known as RET/PTC rearrangement, is the most common genetic alteration identified to date in thyroid papillary carcinomas.
The prevalence of RET/PTC in papillary carcinomas shows significant geographic variation and is approx 35% in North America. RET/PTC is more common in tumors in children and young adults, and in papillary carcinomas associated with radiation exposure. There are at least 10 different types of RET/PTC, all resulting from the fusion of the tyrosine kinase domain of RET to the 5' portion of different genes. RET/PTC1 and RET/PTC3 are the most common types, accounting for >90% of all rearrangements. There is some evidence that different types of RET/PTC may be associated with distinct biologic properties of papillary carcinomas. RET/PTC1 tends to be more common in tumors with typical papillary growth and microcarcinomas and to have a more benign clinical course, whereas RET/PTC3 in some populations shows a strong correlation with the solid variant of papillary carcinoma and more aggressive tumor behavior.
RET/PTC has recently been found in hyalinizing trabecular adenomas of the thyroid gland, providing molecular evidence in favor of this tumor to be a variant of papillary carcinoma. The occurrence of RET/PTC in Hashimoto thyroiditis and thyroid follicular adenomas and hyperplastic nodules reported in several studies has not been confirmed in other observations and remains controversial.
CLINICAL VARIANTS CHARACTERIZATION GENERAL
Hyalinizing trabecular tumors of the thyroid: a variant of papillary carcinoma?
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Adv Anat Pathol 2002 Jan;9(1):7-11 Abstract quote
Ret proto-oncogene rearrangements are common in papillary thyroid carcinoma. The relationship of hyalinizing trabecular tumors (HTT) to papillary thyroid carcinoma (PTC) was analyzed in a recent report in which the presence of RET rearrangements was detected by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry in several HTT.
This commentary examines this report and related studies in the literature emphasizing the limitations of these approaches and the practical implications of these findings.
HISTOPATHOLOGY CHARACTERIZATION GENERAL
- Am J Surg Pathol. 2006 Oct;30(10):1269-73 Abstract quote
BACKGROUND: 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.
DESIGN: 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.
RESULTS: 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.
CONCLUSIONS: 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: cytologic features in 29 cases.
Casey MB, Sebo TJ, Carney JA.
Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN. Dr. Carney is an Emeritus member.
Am J Surg Pathol. 2004 Jul;28(7):859-67. Abstract quote
Cytologic material (fine-needle aspiration biopsy smears, thin-layer preparations, cell block sections, and touch preparations) from 29 cases of hyalinizing trabecular adenoma was studied to 1) establish the cytologic profile of the neoplasm and 2) compare the profile with those of papillary and medullary carcinoma.
Papanicolaou- and Diff-Quik-stained smears of the hyalinizing trabecular adenomas were uniformly bloody. The smears featured cells in cohesive aggregates radially oriented around hyaline material, less frequently, singly. Cytoplasm was abundant, and the nucleocytoplasmic ratio was low. Intranuclear cytoplasmic inclusions, nuclear grooves, and nuclear overlapping were very common and best seen with the Papanicolaou method. Diff-Quik-stained smears highlighted the hyaline material (metachromatic), perinucleolar clearing, and cytoplasmic bodies.
The combination of a bloody background, radially oriented cohesive cells, cells with abundant cytoplasm, nuclei with very frequent cytoplasmic inclusions and grooves, and the presence of hyalin should suggest the presence of hyalinizing trabecular adenoma.
Hyalinizing trabecular adenoma of the thyroid gland--a report of two cases.
Lewy-Trenda I, Wierzchniewska-Lawska A.
Department of Pathomorphology, University Medical School, Lodz.
Pol J Pathol 1999;50(4):301-3 Abstract quote
Hyalinizing trabecular adenoma (HTA) is a specific variant of thyroid adenoma with a particular histological pattern. Immunohistochemistry is the best way of differentiating these adenomas.
Of special interest is a strong positive cytoplasmic reaction for MIB-1. In FNAB and intra-operative examination HTA is usually misdiagnosed as a papillary carcinoma. Histological examination of paraffin-embedded material and immunohistochemical stainings provide a correct diagnosis.
Accumulated basement membrane material in hyalinizing trabecular tumors of the thyroid.
Katoh R, Kakudo K, Kawaoi A.
Department of Pathology, Yamanashi Medical University, Tamaho, Japan.
Mod Pathol 1999 Nov;12(11):1057-61 Abstract quote
We report here four additional cases of hyalinizing trabecular adenoma of the thyroid and describe the findings of the accumulated basement membrane (BM) material. Focal lumpy depositions of BM material were noted in the stroma of all four tumors and were particularly prominent in two.
Antibodies against type IV collagen and laminin strongly immunoreacted with this material, which also showed diastase-resistant periodic acid-Schiff positivity. The ultrastructural findings of accumulated basement membrane was examined in detail. The most striking ultrastructural findings were seen at the periphery of the cell clusters, where the basal aspect of the tumor cells rested on a highly accumulated BM materials displaying mesh-like, fir-branching, or frame-like appearances. Intracytoplasmic BM islands were frequently observed in neoplastic cells. These BM islands were membrane-bounded and focally continuous with the cell surface membrane, suggesting pseudointracytoplasmic depositions of BM material due to marked cytoplasmic infoldings.
From the findings, electron microscopic features of accumulated BM material are very characteristic in hyalinizing trabecular adenomas and can be discernible from other histologic types of BM-producing tumors.
Hyalinizing trabecular carcinoma of the thyroid gland: report of two cases of follicular cell thyroid carcinoma with hyalinizing trabecular pattern.
Gonzalez-Campora R, Fuentes-Vaamonde E, Hevia-Vazquez A, Otal-Salaverri C, Villar-Rodriguez JL, Galera-Davidson H.
Hospital Universitario Virgen Macarena, University of Seville, Spain.
Ultrastruct Pathol 1998 Jan-Feb;22(1):39-46 Abstract quote
Recently tumors have been reported that have an architectural pattern and cellularity similar to hyalinizing trabecular adenoma and show either parafollicular differentiation or histological findings suggestive of malignant neoplasm of the follicular cells.
This study describes two cases of thyroid carcinoma of follicular cells that displayed a hylinizing trabecular pattern. The first case was a 25-year-old euthyroid woman with a cold thyroid nodule in the right lobe. On fine needle aspiration a diagnosis of papillary carcinoma was rendered. The thyroidectomy disclosed a 2-cm, firm, brown, encapsulated tumor in the right lobe. The tumor had a growth pattern and cytologic features similar to those described in hyalinizing trabecular adenoma. The differences between these neoplasms were the presence of mitotic figures, prominence of the nucleolus, capsular blood vessel invasion, and microtubule groups in the endoplasmic reticulum. The second case was a 19-year-old euthyroid woman with a cold thyroid nodule in the left lobe. A cytologic diagnosis of follicular proliferation was rendered. A 4-cm, firm, whitish, encapsulated nodule was found in the left lobectomy. The tumor cells were arranged in two clear-cut patterns: a trabecular hyalinizing pattern with a small focus of papillary growth, and a follicular pattern.
These findings confirm the existence of malignant thyroid tumors with a hyalinizing trabecular pattern and illustrate the nonspecificity of this peculiar pattern, since it may also be seen in papillary carcinomas of the thyroid. The relationship between hyalinizing trabecular adenoma and papillary carcinoma of the thyroid is commented on.
VARIANTS CYTOPLASMIC YELLOW BODIES
Prevalence and incidence of cytoplasmic yellow bodies in thyroid neoplasms.
Rothenberg HJ, Goellner JR, Carney JA.
Division of Anatomic Pathology, Mayo Clinic, Rochester, Minn.
Arch Pathol Lab Med 2003 Jun;127(6):715-7 Abstract quote
Context.-Cytoplasmic yellow bodies are a common and frequent histologic finding in hyalinizing trabecular adenoma of the thyroid gland, a morphologically distinctive neoplasm, and are visible in fine-needle aspiration biopsy of the tumor.
Objective.-To determine the prevalence and frequency of cytoplasmic yellow bodies in common thyroid tumors.
Design.-Microscopic slides of random cases of papillary carcinoma (61 cases), follicular adenoma (27 cases), and Hurthle cell adenoma (12 cases) were searched for cytoplasmic yellow bodies.
Setting and Patients.-Slides were from patients who had undergone surgery at Mayo Clinic, Rochester, Minn, and were obtained from the Mayo Clinic Tissue Registry.
Main Outcome Measure.-Presence or absence of cytoplasmic yellow bodies.
Results.-Cytoplasmic yellow bodies were found in papillary carcinoma (62%), follicular carcinoma (22%), and Hurthle cell adenoma (83%) but were very infrequent numerically in each tumor type.
Conclusions.-Cytoplasmic yellow bodies may be present in papillary carcinoma and in follicular and Hurthle cell adenomas, but because they are uncommon in these tumors, they are unlikely to be found in fine-needle aspiration biopsy smears. Therefore, cytoplasmic yellow bodies are a useful cytomorphologic indicator of hyalinizing trabecular adenoma of the thyroid gland.
Hyalinizing Trabecular Adenoma and Papillary Carcinoma of the Thyroid Gland Express Different Cytokeratin Patterns
Mitsuyoshi Hirokawa, M.D., Ph.D.; J. Aidan Carney, M.D., Ph.D.; Yuji Ohtsuki, M.D., Ph.D.
From the Department of Pathology, University of Tokushima School of Medicine, Tokushima, Japan (M.H.); Department of Laboratory Medicine and Pathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, U.S.A. (J.A.C.); and Second Department of Pathology, Kochi Medical School, Kochi, Japan (Y.O.).
Am J Surg Pathol 2000;24:877-881 Abstract quote
It has recently been suggested that hyalinizing trabecular adenoma of the thyroid is an encapsulated variant of papillary carcinoma because of certain similarities of their histology, the occasional occurrence of both tumors in the same gland, and their similar pattern of expression of cytokeratins, including staining for cytokeratin 19.
To investigate this notion further, we examined immunocytochemically the expression of a series of cytokeratins in 12 hyalinizing trabecular adenomas and six papillary carcinomas. Hyalinizing trabecular adenoma showed no or minimal reactivity for cytokeratin 19, whereas papillary carcinoma was almost always strongly reactive. Also, hyalinizing trabecular adenoma showed no staining for high-molecular-weight (HMW) cytokeratin, whereas papillary carcinoma was strongly positive.
Thus, there are different patterns of cytokeratin 19 and HMW cytokeratin expression in hyalinizing trabecular adenoma and papillary carcinoma. The findings do not support the suggestion that hyalinizing trabecular adenoma is an encapsulated variant of papillary carcinoma.
Cell Membrane and Cytoplasmic Staining for MIB-1 in Hyalinizing Trabecular Adenoma of the Thyroid Gland
Mitsuyoshi Hirokawa, M.D., Ph.D.; J. Aidan Carney, M.D., Ph.D.
From the Department of Pathology (M.H.), University of Tokushima School of Medicine, Japan; and the Department of Laboratory Medicine and Pathology (J.A.C.), Mayo Clinic and Mayo Foundation, Rochester, MN, U.S.A.
Am J Surg Pathol 2000;24:575-578 Abstract quote
The monoclonal MIB-1 antibody reacts with the nuclei of cells in the late G1, S, G2, and M phases of the cell cycle. Previously, we found two cases of hyalinizing trabecular adenoma that showed cell membrane and cytoplasmic immunopositivity for the antibody.
The purpose of this investigation was to confirm this exceptional reactive pattern of MIB-1 in hyalinizing trabecular adenoma. For the study, we collected 13 additional hyalinizing trabecular adenomas and stained a total of 15 tumors using MIB-1 antibody. Ten cases of papillary thyroid carcinoma were studied similarly. All hyalinizing trabecular adenomas showed strong positivity for the antibody in 90% or more of the tumor cells, localized especially to the cell membrane and also to the cytoplasm. There was no cell membrane or cytoplasmic MIB-1 positivity among the 10 papillary carcinomas. Luminal border of normal extratumoral thyroid follicles rarely showed faint immunopositivity.
Our findings indicate that strong cell membrane and cytoplasmic immunoreactivity for MIB-1 is a characteristic of the hyalinizing trabecular adenoma. Staining for MIB-1 will be useful in differentiating hyalinizing trabecular adenoma from papillary carcinoma, which shares a number of cytologic and histologic findings with hyalinizing trabecular adenoma.
PROGNOSIS CHARACTERIZATION GALECTIN-3 EXPRESSION
Galectin-3 expression in hyalinizing trabecular tumors of the thyroid gland.
Gaffney RL, Carney JA, Sebo TJ, Erickson LA, Volante M, Papotti M, Lloyd RV.
Am J Surg Pathol 2003 Apr;27(4):494-8 Abstract quote
Galectin-3, a beta-galactoside-binding lectin, is overexpressed in many neoplasms and may be useful when differentiating between benign and malignant thyroid neoplasms. Recently, interest has focused on the classification and biologic behavior of hyalinizing trabecular tumors (HTTs).
In this study we compared galectin-3 expression in a number of different thyroid neoplasms to gain insight into the biologic behavior of HTT. Formalin-fixed, paraffin-embedded tissues from 153 thyroid neoplasms were stained with a monoclonal antibody to galectin-3. These tumors included 58 HTTs, 60 papillary carcinomas, 21 follicular carcinomas, and 14 follicular adenomas. Reactivity was graded as negative, weak, or strong by three observers. The average patient age was similar in the patients with HTTs, papillary carcinomas, and follicular adenomas. The patients with follicular carcinomas were approximately a decade older than all other groups of patients. All groups of thyroid neoplasms occurred more frequently in female patients. Follow-up revealed metastatic disease in patients with papillary (36.6%) and follicular carcinomas (19%) but not in patients with follicular adenomas or HTTs. Galectin-3 immunostaining showed that 60% of the HTTs were negative or had weak (H) (1+) staining and 40% had strong (2-3+) staining.
In the majority of the reactive cases, staining was diffuse and predominantly cytoplasmic. Fifty of the 60 (83%) papillary carcinomas and 11 of the 21 (52%) follicular carcinomas showed strong immunostaining. The immunostaining was also diffuse in the majority of papillary and follicular carcinomas. The strong immunoreactivity seen in most of the carcinomas was in contrast to the relatively weak or negative immunostaining in the majority of follicular adenomas (93%). The immunophenotype of HTT, as characterized by galectin-3 expression, is intermediate between that of benign and malignant thyroid tumors, suggesting that some tumors with strong staining may behave like carcinomas, although this was not noted in our cases.
Our study suggests that the variable pattern of galectin-3 expression may reflect a difference in biologic behavior between HTT and papillary thyroid carcinoma.
TREATMENT CHARACTERIZATION GENERAL Surgical removal
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Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.
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