Detection of PAX8/PPAR fusion gene by FISH Technique in follicular thyroid lesions

Author(s):  
Ban J Qasim ◽  
Alaa G Hussein ◽  
Wijdan B Abid ◽  
Buthinah I Hameed

The main problem established by a discovery of a thyroid nodule is to discriminate between a benign and malignant lesion. Differential diagnosis between follicular thyroid cancer (FTC) and benign follicular thyroid adenoma (FTA) is a great challenge for even an experienced pathologist and requires special effort.The purpose of the study was to detect PAX8/PPAR G gene rearrangement by fluorescent in situ hybridization (FISH) technique,the present study is the first time in Iraq used this technique to detect fusion gene in follicular thyroid lesions,follicular carcinoma (FC) follicular variant papillary of carcinoma (FVPC), follicular adenoma (FA) and follicular hyperplasia. A total of 120 paraffin block were included in the study,30 blocks were (FC),30 blocks were (FVPC). 30 blocks were (FA),30 blocks were blocks thyroid follicular hyperplasia.20 blocks endocervical epithelium.20 paraffin blocks of colonic epithelium. The clinicopathological parameters were obtained from patients’ admission case sheets and pathology reports (age,gender). The description of measures regarding fluorescent instu hybridization of PAX8/ PPAR G fusion gene there was significantly highest in follicular carcinoma,followed by follicular variant of papillary carcinoma,then follicular adenoma and lastly by follicular hyperplasia The area under the curve for all three markers was >0.8.The p-value was highly significant for all three markers (P<0.001). Cutoff values that predict malignant thyroid follicles lesion were as following: score of >1 for Galectin-3 marker,score of >2 for HBME-1 marker and number of positive cells per 50 of >13 (>26%) for PAX8 /PPAR G fusion gene marker. The sensitivities for the three markers were 100.00 %,90.00 % and 66.67 %,respectively,whereas the specificities were 88.30 %,98.33 % and 100.00 % respectively.

The main problem encountered in thyroid nodule is difficult to differentiate between a benign and malignant lesion. Differential between follicular thyroid cancer (FTC) and benign follicular thyroid adenoma (FTA) is a great challenge for even an experienced pathologist and requires special effort. A total of 120 paraffin block were included in the study, 30 blocks were (FC), 30 blocks were (FVPC). 30 blocks were (FA), 30 blocks were blocks thyroid follicular hyperplasia.20 blocks endocervical epithelium.20 paraffin blocks of colonic epithelium as control. From each paraffin block, 4 slides, each of thicken were taken, stained with Hematoxylin and Eosin (H&E) for revision of histopathological diagnosis. The histological arrangement in follicular carcinoma and follicular adenoma was significant (P= 0.001) in trabecular pattern and the difference was significant (P= 0.016) in mixed pattern while no significance with microfollicular, macrofollicular and normofollicular pattern in both follicular carcinoma and adenoma. There was no significant difference in size follicular lesion among FA, FVPC and follicular hyperplasia (P> 0.05) while, the size follicular lesion in of (FC) was significantly higher from all other groups (P< 0.05).


2018 ◽  
Vol 33 (2) ◽  
pp. 161-167 ◽  
Author(s):  
Jung-Soo Pyo ◽  
Dong-Hoon Kim ◽  
Jungho Yang

Purpose: The present study aimed to evaluate the diagnostic roles of CD56 immunohistochemistry in differentiating various thyroid lesions. Methods: A meta-analysis was performed to evaluate the rate of loss of CD56 immunohistochemistry expression from 13 eligible studies regarding various thyroid lesions, including papillary thyroid carcinoma, follicular carcinoma, and follicular adenoma. To confirm the value of CD56 immunohistochemistry in differentiating various thyroid lesions, a diagnostic test accuracy review was conducted. Results: An 87.8%, 79.1%, 11.9%, 25.5%, and 19.6% loss of CD56 immunohistochemistry expression was identified in papillary thyroid carcinoma, follicular carcinoma, follicular adenoma, benign follicular nodule, and Hashimoto’s thyroiditis, respectively. In the normal thyroid tissue, the rate of loss of CD56 expression was 1.6%. Classical, follicular, diffuse sclerosing, tall cell, and encapsulated variants of papillary thyroid carcinoma showed an 88.4%, 75.3%, 97.2%, 91.7%, and 91.7% loss of CD56 expression, respectively. In the comparison between the follicular variant of papillary thyroid carcinoma and follicular adenoma, the pooled sensitivity and specificity of CD56 immunohistochemistry was 0.82 (95% confidence interval (CI) 0.70, 0.90) and 0.94 (95% CI 0.83, 0.99), respectively. The diagnostic odds ratio and the area under curve on summary receiver operating characteristic curve was 51.43 (95% CI 5.83, 453.88) and 0.9387, respectively. Conclusion: Collectively, these results indicate that the rate of loss of CD56 immunohistochemistry expression was significantly higher in malignant tumors, such as papillary thyroid carcinoma and follicular carcinoma, than in follicular adenoma, benign follicular nodule, and Hashimoto’s thyroiditis. As such, CD56 immunohistochemistry can be useful in differentiating follicular variant papillary thyroid carcinoma from follicular adenoma.


Author(s):  
Amal Abd El-Halim El-Dakrany ◽  
Yomna Abd El-Monem Zamzam ◽  
Rania Elsayed Wasfy ◽  
Assia Mahfouz Abd El-Raouf

Background: Thyroid nodules are common finding, only 5% of nodules are malignant and the vast majority is non-neoplastic lesions or benign neoplasms. Thyroid cancer incidence is increasing faster than any other cancer types, thus representing one of the most common and clinically worrying malignant tumors of the endocrine system. Trophoblast antigen 2 (TROP2) is a transmembrane receptor glycoprotein encoded by the tumor-associated calcium signal transducer 2(Tacstd2) gene, which is located on chromosome 1p32. Although the biological function of TROP2 is unclear, accumulating evidence has demonstrated that its expression is elevated in various malignant tissues, whereas in human normal tissues relatively low or no TROP2 expression is observed. C-Kit is a type III receptor tyrosine kinase. C-Kit expression and signaling have been well characterized in several tumors, including gastrointestinal stromal tumors (GISTs). However, few studies have investigated c-Kit in the thyroid gland or in thyroid malignancies. The aim of this study was to investigate the diagnostic utility of TROP-2 on a large set of neoplastic thyroid lesions & to investigate the utility of TROP-2 & c-Kit markers to distinguish between benign and malignant thyroid neoplasms on Paraffin blocks. Methods: Immunohistochemistry for TROP2 and c-Kit was carried out on 85 different thyroid lesions (40 benign, 7 borderline and 38 malignant). Results: Malignant thyroid lesions were found to have negative expression of c-Kit in contrast to 80% of benign thyroid neoplasms. TROP2 was strong positive in 87.5% of papillary thyroid carcinomas (PTC), but there was no TROP2 expression in benign thyroid neoplasms, non-invasive follicular thyroid neoplasm with papillary like nuclear features, follicular carcinoma, anaplastic and poorly differentiated thyroid carcinoma. Conclusions: TROP2 is a good diagnostic tool for PTCs to differentiate between PTCs & other lesions with papillary like nuclear features as NIFTP, c-Kit is a good diagnostic tool for follicular adenoma & to differentiate between follicular adenoma & follicular carcinoma.


2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Tamas Solymosi ◽  
Gyula Lukacs Toth ◽  
Laszlo Budai ◽  
Istvan Gal

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.


2018 ◽  
Vol 5 (5) ◽  
pp. 1217
Author(s):  
Sheela K. M. ◽  
Sreedevi A. R.

Background: Diseases of thyroid are one of the most common endocrine disorders affecting general population which range from non-neoplastic to neoplastic lesions. The incidence and pattern of thyroid lesions depend on various factors which include sex, age, ethnic and geographical patterns. Majority of thyroid lesions are non-neoplastic only <5% are malignant. The aim of the present study was to determine the frequency and histomorphological pattern of thyroidectomy specimens and their relationship with age and sex of the patient.Methods: This retrospective study was conducted in the department of pathology, Govt. Medical College, Alappuzha for a period of 2 years. The study included 620 thyroidectomy specimens received in the Department of Pathology. All the biopsy reports were reviewed, and different lesions were categorised according to age and gender distribution. The data was analysed by standard statistical methods.Results: The commonest of the non-neoplastic lesions was nodular colloid goiter followed by lymphocytic thyroiditis, Hashimoto thyroiditis Nodular hyperplasia and thyroglossal cyst. Most common malignant lesion in this study is papillary carcinoma and benign lesion is follicular adenoma. Age group of patients ranged from 6 ½ to 84 years. The study showed a female predominance of 88.38%.Conclusions: Thyroid disorders are commonly encountered endocrine diseases. The study showed a female predominance. Peak age of incidence of thyroid lesions was between 40 and 50 years. Most common lesion was follicular adenoma and most common malignant lesion was papillary carcinoma.Histopathological examination is the mainstay for definite diagnosis and management of thyroid neoplasms.


2019 ◽  
Vol 26 (5) ◽  
pp. R259-R266 ◽  
Author(s):  
Pedro Weslley Rosario ◽  
Gabriela Franco Mourão

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is an encapsulated or clearly delimited, noninvasive neoplasm with a follicular growth pattern and nuclear features of papillary thyroid carcinoma (PTC). It is considered a ‘pre-malignant’ lesion of the RAS-like group. Ultrasonography (US), cytology and molecular tests are useful to suspect thyroid nodules that correspond to NIFTP but there is wide overlap of the results with the encapsulated follicular variant of PTC (E-FVPTC). In these nodules that possibly or likely correspond to NIFTP, if surgery is indicated, lobectomy is favored over total thyroidectomy. The diagnosis of NIFTP is made after complete resection of the lesion by observing well-defined criteria. In the case of patients who received the diagnosis of FVPTC and whose pathology report does not show findings of malignancy (lymph node metastasis, extrathyroidal invasion, vascular/capsular invasion), if the tumor was encapsulated or well delimited, the slides can be revised by an experienced pathologist to determine whether the diagnostic criteria of NIFTP are met, but special attention must be paid to the adequate representativeness of the capsule and tumor. Since NIFTP is not ‘malignant’, tumor staging is not necessary and patients are not submitted to thyroid cancer protocols or guidelines. We believe that patients with NIFTP without associated malignancy and without nodules detected by US of the remnant lobe (if submitted to lobectomy) can be managed like those with follicular adenoma.


2017 ◽  
Vol 42 (1) ◽  
pp. 21-27
Author(s):  
Mohammad Mosiur Rahman ◽  
Sultana Gulshan Banu ◽  
Ashim Ranjan Barua ◽  
Mohammed Kamal ◽  
Muhammod Nazmul Baqui ◽  
...  

A significant increase in incidence of papillary thyroid carcinoma (PTC) has been noticed in recent decades worldwide. This is due to advances in medical surveillance, increased use of ancillary tests, and a minor component due to over diagnosis of PTC. Follicular variant of papillary thyroid carcinoma (FVPTC) is the second most common variant of PTC and comprises about 23-41%. It is difficult to diagnose histologically when the distinctive nuclear features are either not well developed or present focally within the lesion. Several immunohistochemical markers (CD56, HMCK, GAL3, HBME-1 and CK19) either alone or combined in panels can be used to improve diagnostic accuracy. This study was aimed to differentiate FVPTC from other follicular patterned lesion of thyroid by histopathology and immunohistochemistry (IHC). A total of 50 histologically diagnosed cases of thyroid neoplasm were studied. The neoplastic cases included 40 cases of follicular variant papillary carcinoma (FVPC), 04 classic papillary carcinoma (PTC), 04 follicular carcinoma and 02 follicular adenoma. All cases were evaluated by IHC for the expression of CD56 and CK19 antibody. In case of FVPTC (n=40), 21 cases (52.5%) were CK19 positive and CD56 negative as expected. Both markers were found positive in 06 (15%) cases and CD56+ alone was found positive in 11 (27.5%) cases of FVPTC, and a finding that goes against the diagnosis of FVPTC. The histopathological slides of these cases were reviewed and findings were recorded. All cases (n=4) of classic PTC were CK19 positive and 03 (75%) cases were found CD56 negative. Diagnoses of thyroid follicular lesions are primarily based on histological and cytomorphological criteria. However, there was a subset of follicular patterned tumors like FVPTC which lack unequivocal features of malignancy. Immunohistochemistry can improve diagnostic accuracy but needs additional studies for controversial cases. It may be considered these lesions as differentiated tumor of uncertain malignant potential (WDT-UMP) to avoid the using term carcinoma. Additional studies are needed for establishing more precise morphologic criteria and for identifying useful markers for differentiating benign from borderline or malignant thyroid lesions.


2019 ◽  
Vol 10 (1) ◽  
pp. 54-59
Author(s):  
Wasim Selimul Haque ◽  
Shamoli Yasmin ◽  
SK Md Jaynul Islam ◽  
Susane Giti

Background: Diseases involving thyroid gland are myriad- they span from functional to goiterous which again can be non-neoplastic or neoplastic. The pattern and prevalence of these disorders depend on various factors like age, sex, ethnicity and geographic location of residence. The aim of the present study was to determine the pattern of thyroid lesions in surgically resected thyroid specimens. Methods: This retrospective study was conducted at Department of Histopathology ofArmed Forces Institute of Pathology (AFIP), Dhaka, Bangladesh. All thyroidectomy specimens received in the Department of Histopathology over the period from 1st January 2018 to 30th June 2019 were included in the study. Data including age, sex and histopathological diagnosis were collected from the records and histopathology slides of all cases were reviewed to verify diagnosis. Data were then analyzed by standard statistical methods. Results: A total of 377 specimens were collected, 301 specimens were from females and 76 from males (female to male ratio 4.01:1). The age ranged from 13 years to 82 years (mean 38.44±12.89 years). Nodular goiter (274, 72.62%) was the commonest thyroid lesion; other benign lesions included follicular adenoma (18) and Hashimoto thyroiditis (17). Overall malignancy was 18.03% (68). Papillary carcinoma (61, 89.70%) constituted majority of the malignant neoplasms. Other malignant neoplasms included follicular carcinoma (3 cases including 1 case of Hurthle cell carcinoma), anaplastic carcinoma (2) and medullary carcinoma and non-Hodgkin lymphoma 1 each. Conclusion: Our study revealed that the prevalent form of thyroid diseases is nodular goiter that mostly affects females. Papillary carcinoma is the commonest malignancy of thyroid gland which also predominantly affects females. Birdem Med J 2020; 10(1): 54-59


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Jung Hyun Yoon ◽  
Eun-Kyung Kim ◽  
Ji Hyun Youk ◽  
Hee Jung Moon ◽  
Jin Young Kwak

Background.To evaluate the role of ultrasonography (US), US-guided fine-needle aspiration (USFNA) and intraoperative frozen section (FS) in follicular neoplasm.Methods. US features, USFNA cytology, and FS results were compared based on the pathology results of patients with follicular adenoma (FA), follicular carcinoma (FC), and follicular variant of papillary thyroid carcinoma (FVPTC).Results. FC and FVPTC showed significantly higher rates of suspicious US features (P<0.05) and positive findings on either US or cytology, 80.0% and 90.7%, compared to FA, 64.5% (P=0.001). Intraoperative FS showed higher malignant rates in FVPTC and FC (81.8% and 75.0%, resp.), compared to FA (3.8%,P<0.001).Conclusion. Suspicious US features were more significantly seen in FC and FVPTC compared to FA. Intraoperative FS is useful in the differential diagnosis of these lesions and supplements cytology results of USFNA.


2019 ◽  
Vol 8 (11) ◽  
pp. 1529-1538 ◽  
Author(s):  
Ana Carolina de Jesus Paniza ◽  
Thais Biude Mendes ◽  
Matheus Duarte Borges Viana ◽  
Débora Mota Dias Thomaz ◽  
Paula B O Chiappini ◽  
...  

The recent reclassification of a follicular variant of papillary thyroid carcinoma (FVPTC), subset as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), aims to avoid overtreatment of patients with an indolent lesion. The diagnosis of NIFTP has recently been revisited using more rigid criteria. This study presents histological and molecular findings and a long clinical follow-up of 94 FVPTC, 40 cases of follicular adenoma (FTA) and 22 cases of follicular carcinoma (FTC) that were classified before the advent of the NIFTP reclassification. All slides were reviewed using these rigid criteria and analysis of numerous sections of paraffin blocks and reclassified as 7 NIFTPs, 2 EFVPTCs, 29 infiltrative FVPTC (IFVPTCs), 57 invasive EFVPTC (I-EFVPTCs), 39 FTAs and 22 FTCs. Remarkably, EFVPTC and NIFTP patients were all free of disease at the end of follow-up and showed no BRAF mutation. Only one NIFTP sample harbored mutations, an NRAS Q61R. PAX8/PPARG fusion was found in I-EFVPTCs and FTC. Although additional studies are needed to identify a specific molecular profile to aid in the diagnosis of lesions with borderline morphological characteristics, we confirmed that the BRAF V600E mutation is an important tool to exclude the diagnosis of NIFTP. We also show that rigorous histopathological criteria should be strongly followed to avoid missing lesions in which more aggressive behavior is present, mainly via the analysis of capsule or vascular invasion and the presence of papillary structures.


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