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Background: Thyroid cancer is the most common endocrine malignancy accounting for >90% of malignancies of endocrine glands. The inter and intraobserver variation in the histomorphological diagnosis of Papillary Thyroid Carcinomas may sometimes pose a diagnostic difficulty. Application of IHC biomarkers may play an active or complementary role in their accurate classification. Aim: The present study was conducted to evaluate if HBME-1 and TPO immunohistochemical analysis can reliably differentiate papillary carcinomas from other thyroid lesions. Material and Methods: 50 cases of benign and malignant thyroid lesions were taken. Immunohistochemical staining for HBME-1 and TPO was performed. HBME-1 and TPO score was interpreted as absent and positive. Medical records were retrieved and their clinical data, surgical treatment, and pathological findings were noted. Results: Out of 50 cases, 19 (73.1%) cases were diagnosed PTC, 4 (15.4%) cases were FTC, 3(11.5%) cases were of MTC and 24 cases of benign thyroid lesions. TPO expression was found positive in 91.7% of cases of Benign thyroid lesions. In malignant thyroid lesions, negative expression of TPO was seen in 63.16%, 0% and 33.33% of PTC, FCT, and MCT respectively. HBME-1 showed negative expression in 83.3% of cases of benign thyroid lesions. Whereas, in malignant thyroid lesion HBME-1 expression was positive in 78.95%, 50% and 0% cases of PTC, FCT, and MCT respectively. Conclusion: Testing for expression of HBME-1 has been shown to improve the diagnostic accuracy for thyroid malignant nodules. The combination of HBME-1, and TPO may contribute to an accurate diagnosis of papillary thyroid carcinoma.
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@#Cystic nodule is an unusual presentation of Papillary Thyroid Carcinoma (PTC), seen in less than 10% of cases. Even by ultrasound, finding a thyroid cyst carries a less than 5% chance of malignancy. We present a case of a 45-year-old male, who came in for incidental finding of a palpable thyroid mass with no significant predisposing history. Thyroidectomy was done and immunohistochemical staining confirmed it to be papillary thyroid cancer. He underwent high dose radiation therapy with post therapy whole body scan showing no evidence of radioavid foci aside from the thyroid bed.The malignant potential of cystic nodule(s) should never be overlooked in certain select patients even if it carries a low chance of malignancy. The diagnosis of PTC relies primarily on the typical nuclear features, however in cases of histologic uncertainty, immunohistochemical stains such as HBME-1 may be used to help classify unusual presentations of PTC. Treatment and monitoring of Cystic Papillary Thyroid Carcinoma follows the conventional guideline on solid PTC.
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Thyroid Cancer, PapillaryABSTRACT
BACKGROUND: Fine-needle aspiration cytology serves as a safe, economical tool in evaluating thyroid nodules. However, about 30% of the samples are categorized as indeterminate. Hence, many immunocytochemistry markers have been studied, but there has not been a single outstanding marker. We studied the efficacy of CD56 with human bone marrow endothelial cell marker-1 (HBME-1) in diagnosis in the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) category III. METHODS: We reviewed ThinPrep liquid-based cytology (LBC) samples with Papanicolaou stain from July 1 to December 31, 2016 (2,195 cases) and selected TBSRTC category III cases (n = 363). Twenty-six cases were histologically confirmed as benign (six cases, 23%) or malignant (20 cases, 77%); we stained 26 LBC slides with HBME-1 and CD56 through the cell transfer method. For evaluation of reactivity of immunocytochemistry, we chose atypical follicular cell clusters. RESULTS: CD56 was not reactive in 18 of 20 cases (90%) of malignant nodules and showed cytoplasmic positivity in five of six cases (83%) of benign nodules. CD56 showed high sensitivity (90.0%) and relatively low specificity (83.3%) in detecting malignancy (p = .004). HBME-1 was reactive in 17 of 20 cases (85%) of malignant nodules and was not reactive in five of six cases (83%) of benign nodules. HBME-1 showed slightly lower sensitivity (85.0%) than CD56. The specificity in detecting malignancy by HBME-1 was similar to that of CD56 (83.3%, p = .008). CD56 and HBME-1 tests combined showed lower sensitivity (75.0% vs 90%) and higher specificity (93.8% vs 83.3%) in detecting malignancy compared to using CD56 alone. CONCLUSIONS: Using CD56 alone showed relatively low specificity despite high sensitivity for detecting malignancy. Combining CD56 with HBME-1 could increase the specificity. Thus, we suggest that CD56 could be a useful preoperative marker for differential diagnosis of TBSRTC category III samples.
Subject(s)
Humans , Biopsy, Fine-Needle , Bone Marrow , Cytoplasm , Diagnosis , Diagnosis, Differential , Endothelial Cells , Immunohistochemistry , Methods , Sensitivity and Specificity , Thyroid Gland , Thyroid NoduleABSTRACT
Due several overlapping histomorphological features and pitfalls in thyroid pathology, there is need to establish a panel of immunomarkers that would aid in proper diagnosis. This study was carried out to investigate the ability of HBME-1, CK19, and S100 in differentiating between hyperplastic, benign and malignant thyroid lesions. Materials and Methods: Immunohistochemical analysis of 60 thyroidectomy specimens (10 hyperplastic nodules, 14 follicular adenomas and 36 malignant thyroid neoplasms) was carried out. The extent and intensity of HBME-1, CK19, and S100 immunoreactivity was assessed in each case. Results: HBME-1 positivity was noted in 86.1% of malignant cases while the majority of the benign lesions were negative. Diffuse strong CK19 positivity was documented in 27/31 papillary carcinoma whereas all cases of follicular carcinoma and medullary carcinoma were negative. Most of the hyperplastic nodules and follicular adenomas were also CK19 negative, although focal weak staining was noted in a few cases. S100 was positive only in medullary carcinoma. HBME-1 was most sensitive (86.1%) and specific (87.5%) in distinguishing between benign and malignant thyroid lesions. The diagnostic accuracy was further increased when HBME-1 was used simultaneously with CK19/S100/CK19+S100. The sequential use of HBME-1 and CK19 also proved beneficial in discriminating between the various follicular-patterned thyroid lesions. Conclusion: HBME-1 immunolabeling suggests malignancy, whereas strong diffuse CK19 positivity substantiates papillary differentiation. The utilization of these markers (alone or in combination) along with histomorphological evaluation is helpful in the differential diagnosis. S100 has minimal utility in this regard.
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[ABSTRACT]OBJECTIVETo study the expressions of 34βE12, Galectin-3 and HBME-1 in thyroid nodules, and to explore its diagnostic value for papillary thyroid carcinoma (PTC).METHODSEn VisionTM immunohistochemical technique was used to detect the expression of 34βE12, Galectin-3 and HBME-1 in 352 thyroid lesions. The correlation between the expressions of the 3 protein markers and clinicopathological characteristics was evaluated. The receiver operating characteristic area under the curve (ROC-AUC) and their index for diagnosis evaluation were also calculated.RESULTSThe positive rates of 34βE12, Galectin-3 and HBME-1 in 246 PTC lesions were significantly higher than those in benign nodules (P<0.001). There was no relationship between the expression of the 3 protein markers and clinicopathological characteristics (eg. gender, age, numbers of lesions, tumor size, capsular invasion, lymph node metastasis, TNM staging). The ROC-AUC of 34βE12, Galectin-3 and HBME-1 for diagnosis of PTC was 0.936, 0.915 and 0.898 respectively. The sensitivity of 34βE12, Galectin-3 and HBME-1 for diagnosis of PTC was 94.3%, 95.5% and 91.1% respectively, while the specificity was 81.1%, 71.7% and 83.0% respectively, and the diagnostic accuracy rate was 90.3%, 88.4% and 88.6% respectively.CONCLUSION The expressions of 34βE12, Galectin-3 and HBME-1 are statistically different between PTC and benign lesions, but no associations are found with clinicopathological characteristics, indicating the three protein markers have important diagnostic value for PTC.
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Objective To explore the value of three antibodies in the differential diagnosis of papillary thyroid carcinoma ,by de‐tecting the expression of HBME‐1 ,CK19 and CD117 in papillary thyroid cacinoma ,thyroid follicular adenoma and Hashimoto′s thy‐roiditis tissues .Methods Totally 85 cases were collected from January 2013 to December 2015 ,including papillary thyroid cacino‐ma ,thyroid follicular adenoma and Hashimoto′s thyroiditis .They were immunohistochemical stained by HBME‐1 ,CK19 and CD117 .SPSS16 .0 software was used to analyze the relationship between the staining results with different pathological changes . Results The positive rates of HBME‐1 ,CK19 and CD117 were 87 .3% ,98 .2% ,and 7 .3% ,respectively .The positive expression of them in benign and malignant groups had significant difference (P< 0 .05) and their consistency checking Kappa were 0 .582 , 0 .551 ,and 0 .874 ,respectively .Conclusion In the differential diagnosis of papillary thyroid carcinoma and benign lesions ,CD117 is better than HBM E‐1 and CK19 .It′s possible to use a combination of them in practice .
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Aim: Fine Needle Aspiration Cytology is the cost effective, quick and minimally invasive method for the initial evaluation of thyroid nodule. But it poses a diagnostic challenge in differentiating benign follicular adenoma from follicular carcinoma and follicular variant of papillary carcinoma as they have similar cytological appearance. Present study focused on the identification of a biological marker for the differential diagnosis of thyroid malignancy in indeterminate cases. Place and Duration of the Study: Division of cancer Research, Regional Cancer Centre, Kerala, India, between August 2009 to September 2014. Methodology: Immunohistochemistry was performed using Ret (Rearranged during transfection), Hector Battifora Mesothelial Cell Antigen-1 (HBME-1), Cytokeratin-19 (CK-19), Keratan sulphate (KS), Thyroid peroxidase (TPO), Estrogen receptor (ER) and Progesterone receptor (PR) on cell block prepared from FNA material and corresponding tissue sections on 153 samples. Western blot analysis of ER and PR was performed in surgically excised fresh tissue specimens. Results: The present study found that HBME-1 is highly significant (P < .001) for the differential diagnosis with a diagnostic accuracy of 95.96%. Ret immunostaining may serve as good indicator of PTC whereas its sensitivity is very low in other lesions. The diagnostic accuracy of CK-19 was 90.91%. Intense positive staining of TPO was noted in majority of follicular epithelial cells of benign lesions (42.42%). Females had an increased prevalence in our study population so we examined the estrogen and progesterone receptors status in thyroid lesions. The specificity of KS, ER and PR are very low for the differentiation of adenoma from carcinomas of the thyroid. Conclusion: Present study found that the combination of two markers may give a more accurate way in the differentiation of thyroid nodules in problematic cases. So we suggest morphological evaluation along with immunocytochemistry of HBME-1 and CK19 can help the differential diagnosis of thyroid lesions in FNAs.
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Objective Hyalinizing trabecular tumor ( HTT) is often mistaken as thyroid papillary carcino-ma( TPC) ,which shares some morphological features with TPC .The aim of this study is to investigate HTT and TPC with immunohistochemical methods .Methods we detected the expression of the three Immunohistochemical index((CK19,HBME-1,MIB-1)in thirteen cases HTT and twenty cases TPC.Results In HTT samples, CK19:three of the thirteen were positive and focal positivity (1+);HBME-1:None of the thirteen samples was stained.MIB-1:ten in thirteen cases were stained in nucleus .In TPC samples,CK19:all of the twenty samples were intensely stained;HBME-1:nineteen of twenty samples were intensely stained;MIB-1:all of the twenty samples were stained in nucleus .The sensitivity and specific degrees of CK 19 and HBME-1 combination to diag-nosis HTT and TPC were 90.0%and 69.2%.Conclusion Our research could provide potent aid to differential diagnosis of HTT and TPC .The combination of CK19 and HBME-1 are adequate to identify HTT and TPC .
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Background: The cytological diagnoses of serous effusions are usually made by routine cytomorphology with certainty. However, overlapping cases sometimes exist between reactive mesothelial and adenocarcinoma cells. We tried to evaluate the diagnostic utility of HBME-1 in distinguishing between reactive mesothelial cells and adenocarcinoma in serous effusions. Materials and Methods: Fifty-two cytologic specimens processed by cell-block technique were retrieved from the archive and were assigned to two groups: Group I: 26 effusions containing reactive/benign mesothelial cells; Group II: 26 effusions containing carcinoma cells. Immunostaining with HBME-1 was performed using an Envision technique. The staining intensity of cells, according to proportion of immunoreactive cells, was scored as: 0 (negative), 1+ (<10%), 2+ (10-50%), and 3+ (≥50%); and the predominant staining pattern of positive cells were determined. Statistical analysis and tests of significance were performed using SPSS software. Results: The calculated mean values (in percentile) for stained cells in adenocarcinoma and reactive mesothelial cells were 25.57 and 67.88, respectively ( P = 0.001). Thin membranous, thick membranous, thick and thin membranous, cytoplasmic and combined patterns of staining in adenocarcinoma cells were respectively 4 cases (21.1%), 0 case, 0 case, 8 cases (42.1%), and 7 cases (36.8%), and in reactive mesothelial cells, these were 7 cases (26.9%), 1 case (3.8%), 18 cases (69.2%), 0 case, and 0 case, respectively. The intensity of staining in majority (88.5%) of reactive mesothelial cells was scored 3+, but the distribution varied in the other group. Conclusions: The staining pattern and intensity for HBME-1 is a useful panel for differentiation of adenocarcinoma and mesothelial cells.
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Objective To study the difference of galectin-3 and HBME-1 expression between benign and malignant thvreid nodules and to evaluate their clinical value.Methods Using immunohistochemical SP method,the paraffin-embedded tissues of 30 ewes papillary thyroid carcinoma(PTC)and 30 cases nodular goiter(NG) were examined to deteet the expression of Galectin-3 and HBME-1.Results The rates of positive staining of Galectin-3.HBME-1.Galectin-3 combined with HBME-1 in PTC were 93.3%(28/30),83.3%(25/30)and 100.0%(30/30),respectivdy,were higher than that of NG[20.0%(6/30),6.7%(2/30)and 26.7%(8/30)].There were significant differences between PTC and NG(X2＝32.85,35.65,34.74,all P＜0.01).The sensitivity,specificity,positive predietive value.negative predictive value and accuracy rate of using Galectin-3,HBME-1,Galectin-3 combined with HBME-1 in differentiation NG from FrIE were 93.3%,83.3%,100.0%;80.0%,93.3%,73.3%;82.3%,92.6%,78.9%:92.3%,84.8%,1 00%;86.7%,88.3%,86.7%,respectively.Conclusion Immunohistochemical stains of Galectin-3 and HBME-1 may be used as two lnarkel's for differentiating PTC and NG,it is especially sensitive when the two markers are jointly used.
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The distinction between benign and malignant thyroid tumors is critical for the management of patients with thyroid nodules. We applied immunohistochemical staining for galectin-3, HBME-1, cytokeratin 19 (CK19), high molecular weight cytokeratin (HMWCK), cyclin D1 and p27(kip1) in 295 thyroid lesions to determine their diagnostic accuracy. The expression of all markers was significantly associated with differentiated thyroid carcinoma (DTC).The sensitivity for the diagnosis of DTC was 94.7% with galectin-3, 91.3% with HBME-1, and 90.3% with CK19. The specificities of these markers were 95.5%, 69.7%, and 83.1%, respectively. Combining these markers, co-expression of galectin-3 and CK19 or galectin-3 and HBME-1 was seen in 93.2% of carcinomas but in none of the benign nodules. Comparing follicular variant of papillary carcinoma (FVPC) with follicular carcinoma (FC), the expression of galectin-3, CK19, and HMWCK was significantly higher in FVPC. When comparing FC with FA, the expression of galectin-3 and HBME-1 was significantly higher in FC. These results suggest that 1) galectin-3 is a useful marker in the distinction between benign and malignant thyroid tumors, 2) the combined use of HBME-1 and CK19 can increase the diagnostic accuracy, and 3) the use of CK19 and HMWCK can aid in the differential diagnosis between PC and FC.
Subject(s)
Humans , Adenocarcinoma, Follicular/diagnosis , Carcinoma, Papillary, Follicular/diagnosis , Cyclin D1/analysis , Cyclin-Dependent Kinase Inhibitor p27/analysis , Diagnosis, Differential , Galectin 3/analysis , Immunohistochemistry , Intracellular Signaling Peptides and Proteins/analysis , Keratin-19/analysis , Keratins/analysis , Sensitivity and Specificity , Thyroid Gland/chemistry , Thyroid Nodule/diagnosis , Biomarkers, Tumor/analysisABSTRACT
PURPOSE: Galectin-3 and HBME-1 have been recognized as useful markers for the diagnosis of the thyroid lesions. In this study, we investigated whether they have a diagnostic value for nodular lesions of the thyroid. METHODS: We investigated the galectin-3 and HBME-1 expressions in 14 nodular hyperplasias, 30 papillary carcinomas, 17 follicular adenomas and 8 follicular carcinomas with using immunochemistry. RESULTS: Galectin-3 was positive in 96.7% of the papillary carcinomas and this incidence was significantly higher (P=0.0001) than that of nodular hyperplasia, 7.1%. However, the galectin-3 expressions of follicular adenoma and follicular carcinoma were not significantly different. HBME-1 was positive in 50.0% of the follicular carcinomas and this incidence was significantly higher (P=0.0001) than that of follicular adenoma. CONCLUSION: Galectin-3 and HBME-1 may be useful markers to diagnose papillary carcinoma. Although HBME-1 contributes to differential diagnosis of follicular adenoma and follicular carcinoma, further study is required.
Subject(s)
Adenoma , Carcinoma, Papillary , Diagnosis , Diagnosis, Differential , Galectin 3 , Hyperplasia , Immunochemistry , Incidence , Thyroid GlandABSTRACT
To examine the immunohistochemical alterations associated with the histological dedifferentiation of thyroid carcinomas, we performed staining for HBME-1, high molecular weight cytokeratin (HCK), CK 19, thyroid transcription factor-1 (TTF-1) and E-cadherin (E-CD) on 125 various types of thyroid carcinomas. The HBME-1 staining was strong and diffuse in follicular carcinoma (FC), papillary carcinoma (PC), and poorly differentiated carcinoma (PDC), while it was rare in undifferentiated carcinoma (UC) as well as in benign lesions. Strong, diffuse staining for CK19 and HCK was predominantly found in PC, and these markers were not much found in other carcinomas. TTF-1 uniformly stained the tumor cells of all cases of PC, FC and Hurthle cell carcinoma (HC) and 42% of the PDC, while there was only focal staining in one case of the UC. Compared to the strong, diffuse reactivity in the benign lesions, E-CD staining was noted in 67% of PC, 80% of FC, 83% of HC, 58% of PDC and none of the UC. These results suggest that HBME-1 may be a marker for well-differentiated carcinomas while CK19 and HCK are phenotypic markers for papillary carcinoma. The loss or reduced expression of TTF-1 and E-CD may be markers for dedifferentiation.