Periostin expression and its supposed roles in benign and malignant thyroid nodules: an immunohistochemical study of 105 cases

Abstract Background Thyroid tumors are often difficult to histopathologically diagnose, particularly follicular adenoma (FA) and follicular carcinoma (FC). Papillary carcinoma (PAC) has several histological subtypes. Periostin (PON), which is a non-collagenous extracellular matrix molecule, has been implicated in tumor invasiveness. We herein aimed to elucidate the expression status and localization of PON in thyroid tumors. Method We collected 105 cases of thyroid nodules, which included cases of adenomatous goiter, FA, microcarcinoma (MIC), PAC, FC, poorly differentiated carcinoma (PDCa), and undifferentiated carcinoma (UCa), and immunohistochemically examined the PON expression patterns of these lesions. Results Stromal PON deposition was detected in PAC and MIC, particularly in the solid/sclerosing subtype, whereas FA and FC showed weak deposition on the fibrous capsule. However, the invasive and/or extracapsular regions of microinvasive FC showed quite strong PON expression. Except for it, we could not find any significant histopathological differences between FA and FC. There were no other significant histopathological differences between FA and FC. Although PDCa showed a similar PON expression pattern to PAC, UCa exhibited stromal PON deposition in its invasive portions and cytoplasmic expression in its carcinoma cells. Although there was only one case of UCa, it showed strong PON immunopositivity. PAC and MIC showed similar patterns of stromal PON deposition, particularly at the invasive front. Conclusions PON may play a role in the invasion of thyroid carcinomas, particularly PAC and UCa, whereas it may act as a barrier to the growth of tumor cells in FA and minimally invasive FC.

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Periostin Expression and Its Roles in Benign and Malignant Thyroid Nodules: an Immunohistochemical Study of 105 Cases

10.21203/rs.3.rs-202219/v1 ◽

2021 ◽

Author(s):

Kimihide Kusafuka ◽

Masaru Yamashita ◽

Tomohiro Iwasaki ◽

Chinatsu Tsuchiya ◽

Aki Kubota ◽

...

Keyword(s):

Thyroid Nodules ◽

Expression Patterns ◽

Follicular Adenoma ◽

Follicular Carcinoma ◽

Undifferentiated Carcinoma ◽

Thyroid Tumors ◽

Tumor Invasiveness ◽

Adenomatous Goiter ◽

Extracellular Matrix Molecule ◽

Poorly Differentiated

Abstract Background. Thyroid tumors are often difficult to histopathologically diagnose, especially follicular adenoma (FA) and follicular carcinoma (FC). Papillary carcinoma (PAC) has several histological subtypes. Periostin (PON), which is a non-collagenous extracellular matrix molecule, is related to tumor invasiveness. We aimed to elucidate the role of PON in thyroid tumors.Method. We collected 105 cases of thyroid nodules, which included cases of adenomatous goiter, FA, microcarcinoma (MIC), PAC, FC, poorly differentiated carcinoma (PDCa), and undifferentiated carcinoma (UCa), and immunohistochemically examined the PON expression patterns of these lesions. Results. PAC and MIC exhibited stromal PON deposition, especially in the solid/sclerosing subtype, whereas FA and FC showed weak deposition on the fibrous capsule. However, the invasive and/or extracapsular regions of microinvasive FC demonstrated quite strong PON expression.Except for it, we could not find any significantly histopathological differences between FA and FC. Although PDCa showed a similar PON expression pattern to PAC, UCa exhibited stromal PON deposition in its invasive portions and cytoplasmic expression in its carcinoma cells. Although there was only one case of UCa, it demonstrated strong PON immunopositivity. PAC and MIC showed similar patterns of stromal PON deposition, especially at the invasive front.Conclusions. PON plays a role in the invasion of thyroid carcinomas, especially PAC and UCa, whereas it acts as a barrier against the growth of tumor cells in FA and minimally invasive FC.

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The Thyroid Gland: Recurring Problems in Histologic and Cytologic Evaluation

Archives of Pathology & Laboratory Medicine ◽

10.5858/2008-132-622-ttgrpi ◽

2008 ◽

Vol 132 (4) ◽

pp. 622-632

Author(s):

William C. Faquin

Keyword(s):

Thyroid Gland ◽

Follicular Adenoma ◽

Endocrine System ◽

Follicular Carcinoma ◽

Needle Aspiration ◽

Fine Needle ◽

Poorly Differentiated Carcinoma ◽

Different Types ◽

Poorly Differentiated ◽

Common Malignancy

Abstract Nodules of the thyroid gland are frequently encountered, occurring in up to 7% of the population, and although most of these nodules are benign, carcinomas of the thyroid gland are the most common malignancy of the endocrine system. Although the different types of thyroid carcinoma are few, a wide variety of recurring problems exists in both their histologic and cytologic evaluation. Here, I will review a selected group of problematic areas, including unusual histologic variants of follicular adenoma, criteria for diagnosing minimally invasive follicular carcinoma, the use of fine-needle aspiration as a screening test for follicular neoplasia, challenging variants of papillary carcinoma, and features of poorly differentiated carcinoma.

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Afirma Testing in Thyroid Nodules with Indeterminate Cytology: A single Medical Institute Experience

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqaa161.207 ◽

2020 ◽

Vol 154 (Supplement_1) ◽

pp. S94-S95

Author(s):

Z Yang ◽

T Zhang ◽

L Layfield ◽

M Esebua

Keyword(s):

Predictive Value ◽

Thyroid Nodules ◽

False Negative ◽

Follicular Adenoma ◽

Follicular Carcinoma ◽

Medical Institute ◽

Cell Adenoma ◽

Indeterminate Cytology ◽

Thyroid Fna

Abstract Introduction/Objective About 10 to 30% of thyroid fine needle aspiration (FNA) nodules have indeterminate cytology, including Bethesda III, IV, and V. Afirma Gene Expression Classifier (GEC) measuring the expression of 167 mRNA was designed to classify the indeterminate thyroid nodules into benign and suspicious categories. This study aimed to evaluate the clinical performance of the Afirma GEC testing in these indeterminate thyroid lesions. Methods Medical records of patients with indeterminate thyroid FNA results and corresponding Afirma GEC results from November 2012 to December 2019 were retrieved. Subsequent surgical follow-up results were obtained. GEC results were compared to the histologic diagnoses. Results 1. There were 77 cases with indeterminate thyroid FNA results. Cytology diagnosis included 67 Bethesda III and 10 Bethesda IV. Afirma GEC results were benign for 41 cases (53%), suspicious for 32 cases (42%), and non- diagnostic for 4 cases (5%). Twenty seven of 32 cases (84%) with suspicious GEC results had surgical follow-up which revealed 12 malignant and 15 benign histologic diagnoses. Only 11 of 41 cases (27%) with benign GEC results had surgery which showed 8 benign and 3 malignant diagnoses. Based on the data, the sensitivity of this test is 80% and specificity is 65%. Positive predictive value (PPV) is 44% and negative predictive value (NPV) is 73%. The false positive cases include 5 Hurthle cell adenoma, 4 nodular hyperplasia, 3 follicular adenoma, 2 Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFPT), and 1 lymphocytic thyroiditis. The false negative cases include 2 minimally invasive follicular carcinoma (from same patient) and 1 papillary thyroid carcinoma. Conclusion 1. We demonstrated in this study that a little more than half of the cases with indeterminate thyroid cytology had negative Afirma GEC results. 2.Afirma test has relatively low specificity (65%) and PPV (44%). The sensitivity (80%) and NPV (73%) is relatively higher but is lower than the values in most literature. This could be due to the fact that majority of the Afirma GEC negative cases in this study did not have surgical follow-up and the sample size is small. 3.Afirma GEC test is a relatively good “rule-out” molecular test for indeterminate thyroid nodules but is not a reliable “rule-in” test due to the low specificity and PPV.

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53BP1 expression as a biomarker to differentiate thyroid follicular tumors

Endocrine Connections ◽

10.1530/ec-20-0630 ◽

2021 ◽

Vol 10 (3) ◽

pp. 309-315

Author(s):

Ayako Sato ◽

Katsuya Matsuda ◽

Takahiro Motoyama ◽

Zhanna Mussazhanova ◽

Ryota Otsubo ◽

...

Keyword(s):

Predictive Value ◽

Follicular Adenoma ◽

Follicular Carcinoma ◽

Nuclear Staining ◽

Adenomatous Goiter ◽

Damage Response ◽

Liquid Based Cytology ◽

Follicular Tumors ◽

Sensitivity Specificity ◽

The Impact

We have previously reported that the expression of p53-binding protein 1 (53BP1) in nuclear foci (NF), a marker reflecting DNA damage response (DDR), detected using immunofluorescence (IF) is useful to estimate the malignant potency of diverse cancers. In this prospective study, we clarified the impact of 53BP1 expression via IF as a biomarker to differentiate thyroid follicular tumors (FTs) with liquid-based cytology (LBC). A total of 183 consecutively obtained-LBC samples, which were preoperatively suspected as FTs, were analyzed. Before histological diagnosis, the type of 53BP1 immunoreactivity in LBC was classified as follows: low DDR type, one or two NF; high DDR type, three or more NF; large foci type, larger than 1.0 μm; abnormal type, intense nuclear staining. Among the 183 cases, 136 cases were postoperatively diagnosed as FTs, including adenomatous goiter (AG, n = 30), follicular adenoma (FA, n = 60), FT-uncertain malignant potency (FT-UMP, n = 18), and follicular carcinoma (FC, n = 28), and 47 cases were diagnosed as tumors other than FTs or technically inadequate materials. Total 136 FT cases were collated with the type of 53BP1 immunoreactivity in LBC. The mean incidence expressing abnormal 53BP1 expression was significantly higher in FC than FA (9.5% vs 2.6%, P-value < 0.001). When adopting 4.3% as a cut-off value to distinguish FC from FA, the sensitivity, specificity, positive predictive value, and negative predictive value were 89.3, 83.3, 71.4, and 94.3%, respectively. Therefore, IF analysis of 53BP1 expression can be employed as a novel technique to diagnose FTs and to distinguish between different types of FTs using LBC.

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The Clinical and Pathological Presentation of Thyroid Nodules in Children and the Comparison with Adult Population: Experience of a Single Institution

International Journal of Endocrinology ◽

10.1155/2016/1256189 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Tamas Solymosi ◽

Gyula Lukacs Toth ◽

Laszlo Budai ◽

Istvan Gal

Keyword(s):

Thyroid Nodules ◽

Adult Population ◽

Follicular Adenoma ◽

Follicular Carcinoma ◽

Medullary Carcinoma ◽

Adult Patients ◽

Follicular Variant ◽

Central Type ◽

Region Data ◽

Follicular Tumors

The clinical and pathological presentation of thyroid nodules among younger and adult patients was compared in an iodine-deficient (ID) region. Data of 3,010 consecutive patients younger than 20 years and 3,010 patients older than 20 years were compared. The proportion of nodular goiters (22.8% versus 39.3%), the ratio of surgically treated nodules (33.2% versus 15.2%), and the proportion of malignant nodules (4.3% versus 2.1%) among diseased patients differed significantly between the two groups (younger versus adult). Nine papillary and 1 medullary carcinoma were found among children, while 15 papillary, 2 follicular, 1 insular, 1 anaplastic, and 1 medullary carcinomas occurred among adults. The ratio of follicular adenoma to hyperplastic nodules (3 : 1 to 1 : 1.67), the proportion of follicular variant (77.8% versus 26.7%), T4 tumors (77.8% versus 33.3%), and tumors with lymph node metastasis (88.9% versus 66.7%) were significantly higher among younger papillary carcinoma patients. No malignancies occurred among spongiform and central type cysts. Similarly to iodine-sufficient regions, more nodules are malignant and carcinomas have a clinically more aggressive presentation in children in comparison with adult patients in ID. Taking the significantly greater proportion of adenomas and the lack of follicular carcinoma into account, a conservative approach has to be considered in follicular tumors among children.

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Pathobiology of MicroRNAs and Their Emerging Role in Thyroid Fine-Needle Aspiration

Acta Cytologica ◽

10.1159/000442145 ◽

2015 ◽

Vol 59 (6) ◽

pp. 435-444 ◽

Cited By ~ 5

Author(s):

Marie Ludvíková ◽

David Kalfeřt ◽

Ivana Kholová

Keyword(s):

Posttranscriptional Regulation ◽

Regulation Of Gene Expression ◽

Follicular Adenoma ◽

Follicular Carcinoma ◽

Disease Status ◽

Needle Aspiration ◽

Thyroid Tumors ◽

Fine Needle ◽

Rna Molecules ◽

Distinct Disease

Objective: MicroRNAs (miRs) are noncoding, single-stranded regulatory RNA molecules involved in the posttranscriptional regulation of gene expression. They control the development and maintenance of the diverse cellular processes including proliferation, differentiation, motility and apoptosis. Expression of miRs is tissue-specific and each alteration of the tissue miR profile is associated with a distinct disease status. Study Design: We reviewed the literature on the expression of miRs in thyroid tumors, focusing on methodology and diagnostic and prognostic output. Separately, we analyzed 11 studies on miR profiles in thyroid cytological material. Results: Numerous studies have evaluated the miR profiles of thyroid tumors in an attempt to find a possible diagnostic and prognostic role. Both downregulation and upregulation of numerous miRs was found, but differences between the surgical pathology specimens and corresponding fine-needle aspirates in the expression of the same miRs were also reported. Conclusions: The results from surgically resected material cannot be extrapolated into preoperative use without validation. For diagnostic use, the strong overlap between follicular adenoma and follicular carcinoma miR profiles is challenging. In summary, miR-221 and miR-222 are consistently upregulated in different types of thyroid carcinomas and might be used as markers of malignancy.

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Correlation between fine needle aspiration cytology and histopathological examination in thyroid swellings-a pilot study

International Journal of Community Medicine and Public Health ◽

10.18203/2394-6040.ijcmph20204733 ◽

2020 ◽

Vol 7 (11) ◽

pp. 4381

Author(s):

Sanjay V. Gupta ◽

Manish Munjal ◽

Devyani Gupta ◽

Siddharth Gupta ◽

Shubham Munjal ◽

...

Keyword(s):

Papillary Carcinoma ◽

Fine Needle Aspiration ◽

Fine Needle Aspiration Cytology ◽

Thyroid Nodules ◽

Follicular Adenoma ◽

Follicular Carcinoma ◽

Needle Aspiration ◽

Aspiration Cytology ◽

Fine Needle ◽

Needle Aspiration Cytology

Background: Thyroid swellings are an enigma that necessitates either, a partial thyroidectomy and a tissue diagnosis to be followed by completion surgery or straightaway a radical intervention. A preoperative presumptive diagnosis of a thyroid swelling, solitary or otherwise is correlated with the post-surgical histopathological finding in the present study.Methods: 30 patients of thyroid nodules were selected from the head-neck tumour clinic of Dayanand medical college hospital, Ludhiana. Pre-operative fine needle aspiration cytology (FNAC) was performed and subjects taken for thyroidectomy, partial or total as the case maybe.Results: There were 20 (66.6%) females in the age group 25-65 years and 10 males (33.3%) 19-50 years with thyroid nodules. 86.6%, 26 patients were of follicular adenoma, 10% 3 patients of papillary carcinoma and 3.33% 1 patient of follicular carcinoma. No case in this study was reported as medullary carcinoma. In the cytological diagnosis of follicular neoplasm in 5 cases, 3 were diagnosed as thyroid adenoma, 2 were finally found to be papillary carcinoma. Overall sensitivity of fine needle aspiration was 40%. There was 84.6% agreement in follicular adenoma; 33% in papillary carcinoma and 100% in follicular carcinoma, and overall accuracy was 85.7%.Conclusion: FNAC is an ideal preoperative investigative modality in thyroid swellings with overall accuracy of 85 % and can differentiate preoperatively a benign from a malignant thyromegaly; and thereby plan extent of surgery, with or without a neck dissection, Maximum cases of follicular adenoma could be easily diagnosed with this aspiration modality.

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Evaluation of hypofunctioning thyroid nodules with technetium-99m MIBI and ultrasonography

South African Journal of Radiology ◽

10.4102/sajr.v21i1.1099 ◽

2017 ◽

Vol 21 (1) ◽

Author(s):

Abubakar Farate ◽

Aadil A. Gutta ◽

Karien De Graaf ◽

Trevor Mdaka

Keyword(s):

Predictive Value ◽

Thyroid Nodules ◽

Follicular Adenoma ◽

Follicular Carcinoma ◽

Needle Aspiration ◽

Regional Environment ◽

Technetium 99M ◽

Significant Difference ◽

99Mtc Mibi ◽

Mibi Scintigraphy

Background: Fine needle aspiration cytology (FNAC) cannot reliably differentiate follicular adenoma from follicular carcinoma (FC), which requires histological evidence of capsular or vascular invasion. FC is the most predominant thyroid cancer in our loco-regional environment, indicating the need for improvement in preoperative diagnostic accuracy of thyroid nodules to ensure appropriate and timely interventions.Objective: The purpose of this study was to assess the role of technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) scintigraphy and ultrasonography (USG) in the differential diagnosis of thyroid nodules.Methods: Forty-two patients with hypofunctioning thyroid nodules were prospectively studied with 99mTc-MIBI scintigraphy and USG to differentiate benign from malignant nodules. An injection of 740 MBq of 99mTc-MIBI was intravenously administered, followed by semiquantitative analysis of dual-phase scans using a 4-point (0 to 3) scoring system. USG was subsequently performed and interpretation was based on some sonographic criteria for malignancy. In the following days and weeks, patients underwent FNAC followed by surgery and histopathologic examination.Results: All malignant nodules were positive on 99mTc-MIBI and all but two malignant nodules were positive on USG. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy are, respectively, 100%, 70%, 65%, 100%, and 81% for 99mTc-MIBI scintigraphy; 87%, 78%, 68%, 91% and 81% for USG; and 83%, 100%, 100%, 96% and 64% for FNAC. There was no statistically significant difference between 99mTc-MIBI scintigraphy and USG performance for both benign (p = 0.317) and malignant (p = 0.573) nodules.Conclusion: 99mTc-MIBI scintigraphy and USG are important imaging modalities in the evaluation of thyroid nodules, particularly follicular neoplasms which are frequently associated with non-diagnostic cytology.

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Calcifications in Thyroid Tumors on Ultrasonography: Calcification Types and Relationship with Histopathological Type

Ultrasound International Open ◽

10.1055/a-0591-6070 ◽

2018 ◽

Vol 04 (02) ◽

pp. E45-E51 ◽

Cited By ~ 5

Author(s):

Kaoru Kobayashi ◽

Tomoko Fujimoto ◽

Hisashi Ota ◽

Mitsuyoshi Hirokawa ◽

Tomonori Yabuta ◽

...

Keyword(s):

Follicular Carcinoma ◽

Medullary Carcinoma ◽

Wide Distribution ◽

Undifferentiated Carcinoma ◽

Thyroid Tumors ◽

Thyroid Lymphoma ◽

Primary Thyroid Lymphoma ◽

Egg Shell ◽

The Relationship ◽

Histopathological Type

Abstract The purpose of the study is to clarify the prevalence of calcifications within thyroid tumors on ultrasonography as well as the relationship between the calcification and histopathological types. Calcifications were classified into 6 (or 8) types according to their shape, size, and region. The prevalence of calcifications and types were investigated in new outpatients and patients who underwent thyroid surgery.Among 2,902 nodules in 2,678 new outpatients, 747 nodules (26%) had calcifications. The types showed a wide distribution. Among 941 patients with papillary carcinoma (PC), 725 patients (77%) had calcifications, and the types showed a wide distribution. 18 patients with the diffuse sclerosing variant of PC only showed punctate microcalcifications in the parenchyma (100%), 32 patients with the cyst-forming type of PC mostly fragmentary and massive types (100%), and 161 metastatic lymph nodes from PC mostly punctate microcalcifications and fragmentary types (48%). Among 337 patients with follicular carcinoma, 79 patients (23%) had calcifications, and the types were mostly fragmentary, massive, and egg-shell types. Among 41 patients with undifferentiated carcinoma, 33 patients (80%) presented with calcifications, which were mostly the massive and egg-shell types. Among 137 patients with medullary carcinoma, 99 patients (72%) had calcification, and the types showed a wide distribution. None of 173 patients with primary thyroid lymphoma had calcifications (0%).Calcifications on ultrasonography can be one of the characteristic findings and a full understanding of the prevalence of calcifications and types will markedly contribute to the ultrasonic diagnosis of thyroid tumors.

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Prediction of thyroid nodule histopathology by expert ultrasound evaluation

Endocrine Connections ◽

10.1530/ec-21-0192 ◽

2021 ◽

Author(s):

Olav Inge Håskjold ◽

Henrik Stenestø Foshaug ◽

Therese Benedikte Iversen ◽

Helga Charlotte Kjøren ◽

Vegard Heimly Brun

Keyword(s):

Papillary Thyroid Carcinoma ◽

High Resolution ◽

Thyroid Carcinoma ◽

Thyroid Nodule ◽

Thyroid Nodules ◽

Follicular Adenoma ◽

Follicular Carcinoma ◽

Histopathological Diagnosis ◽

Papillary Thyroid ◽

Ultrasound Evaluation

Objective: The basis of thyroid nodule diagnostics is ultrasound guided fine needle biopsy with cytological evaluation (FNC), if US appearance is not clearly benign. The aim of this study was to investigate the predictive potential of dedicated, expert high resolution ultrasound, to see if histopathological entities of thyroid nodules can be diagnosed without invasive FNC biopsies. Design: Prospective case cohort study. Methods: 180 patients with 221 thyroid nodules were examined with ultrasound and prospectively assigned to the expected histopathological diagnosis: colloid nodule, adenomatoid colloid nodule, follicular adenoma, follicular carcinoma, follicular variant of papillary thyroid carcinoma, papillary thyroid carcinoma, or other thyroid cancer. In 101 of these, we later obtained histopathological reports for comparison. Results: Overall accuracy for classification into discrete histopathological categories by expert ultrasound was 71.3% and Cohen’s Kappa was 0.62. The sensitivity and specificity for detecting malignancy was 97.3% and 78.1%. The diagnostic accuracy for malignancy was 85.1%. ACR-TIRADS scores for the same nodules had a sensitivity of 97.3%, specificity of 26.6%, and accuracy of 52.5%. Conclusion: Dedicated expert high-resolution ultrasound without FNC can reliably distinguish benign versus malignant nodules, but also differentiate between several histopathological entities in thyroid nodules. There is potential for a reduction in the number of invasive FNC biopsies and diagnostic operations.

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