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Modern Pathology : An Official Journal... Jan 2017Follicular variants of papillary thyroid carcinoma include encapsulated (with or without capsular/vascular invasion) and infiltrative forms, which have different...
miRNA expression profiling of 'noninvasive follicular thyroid neoplasms with papillary-like nuclear features' compared with adenomas and infiltrative follicular variants of papillary thyroid carcinomas.
Follicular variants of papillary thyroid carcinoma include encapsulated (with or without capsular/vascular invasion) and infiltrative forms, which have different clinical behaviors. The encapsulated forms that lack capsular invasion have an indolent clinical behavior that is similar to benign lesions; therefore, they were recently reclassified as 'noninvasive follicular thyroid neoplasms with papillary-like nuclear features' (NIFTPs). Because NIFTPs have nuclear features of papillary carcinomas, distinguishing between NIFTPs and infiltrative follicular variant of papillary thyroid carcinoma is almost impossible with cytological examination. The aim of this study is to determine whether miRNA expression profiles may help distinguish between NIFTPs versus follicular adenomas and infiltrative follicular variant of papillary thyroid carcinomas. The expression profiling of 798 miRNAs was tested in 54 thyroid tumors, including 18 follicular adenomas, 19 NIFTPs and 17 infiltrative follicular variant of papillary thyroid carcinomas, using nCounter Nanostring. We found that miR-146-5p, miR-221-5p, miR-222-3p, miR-30e-3p, and miR-152-3p could discriminate between benign and malignant lesions with a very high level of significance (P-value<0.001). High expression levels of miR-146-5p, miR-199a-5p, miR-199b-5p, miR-1285-5p, miR-1915-3p, and miR-4516, and low miR-148b-3p expression were associated with infiltrative growth of follicular variant of papillary thyroid carcinomas. Interestingly, miR-152-3p, miR-185-5p, and miR-574-3p were significantly downregulated in NIFTPs compared with follicular adenomas, whereas miR-10a-5p and miR-320e can discriminate between NIFTPs and infiltrative forms of follicular variant of papillary thyroid carcinomas. In conclusion, a panel of these markers could have high diagnostic potential as well as could be applied to presurgical fine-needle aspiration, especially for lesions classified as indeterminate thyroid nodules.
Topics: Adenocarcinoma, Follicular; Adenoma; Biomarkers, Tumor; Carcinoma, Papillary, Follicular; Gene Expression Profiling; Humans; MicroRNAs; Thyroid Neoplasms
PubMed: 27586203
DOI: 10.1038/modpathol.2016.157 -
Thyroid : Official Journal of the... Jul 2016
Topics: Adenoma; Carcinoma, Papillary; Carcinoma, Papillary, Follicular; Humans; Neoplasm Invasiveness; Predictive Value of Tests; Prognosis; Terminology as Topic; Thyroid Cancer, Papillary; Thyroid Neoplasms; Tumor Burden
PubMed: 27214083
DOI: 10.1089/thy.2016.0244 -
Oncotarget May 2016The precursor for nerve growth factor (proNGF) is expressed in some cancers but its clinicopathological significance is unclear. The present study aimed to define the...
The precursor for nerve growth factor (proNGF) is expressed in some cancers but its clinicopathological significance is unclear. The present study aimed to define the clinicopathological significance of proNGF in thyroid cancer. ProNGF expression was analysed by immunohistochemistry in two cohorts of cancer versus benign tumors (adenoma) and normal thyroid tissues. In the first cohort (40 thyroid cancers, 40 thyroid adenomas and 80 normal thyroid tissues), proNGF was found overexpressed in cancers compared to adenomas and normal samples (p<0.0001). The area under the receiver-operating characteristic (ROC) curve was 0.84 (95% CI 0.75-0.93, p<0.0001) for cancers versus adenomas, and 0.99 (95% CI 0.98-1.00, p<0.0001) for cancers versus normal tissues. ProNGF overexpression was confirmed in a second cohort (127 cancers of various histological types and 55 normal thyroid tissues) and using a different antibody (p<0.0001). ProNGF staining intensity was highest in papillary carcinomas compared to other histological types (p<0.0001) and there was no significant association with age, gender, tumor size, stage and lymph node status. In conclusion, proNGF is increased in thyroid cancer and should be considered as a new potential diagnostic biomarker.
Topics: Adenoma; Adult; Aged; Area Under Curve; Biomarkers, Tumor; Carcinoma; Female; Humans; Male; Middle Aged; Nerve Growth Factor; Protein Precursors; ROC Curve; Sensitivity and Specificity; Thyroid Neoplasms
PubMed: 27074571
DOI: 10.18632/oncotarget.8652 -
Modern Pathology : An Official Journal... Feb 2007Although cystic tumors of the pancreas are relatively rare, they constitute an increasingly important category. Advances in imaging and interventional techniques and the...
Although cystic tumors of the pancreas are relatively rare, they constitute an increasingly important category. Advances in imaging and interventional techniques and the sharp drop in the mortality rate of pancreatic surgery have rendered pancreatic biopsies and resections commonplace specimens. Consequently, in the past two decades, the nature of many cystic tumors in this organ has been better characterized. The names of some existing entities were revised; for example, what was known as papillary-cystic tumor is now regarded as solid-pseudopapillary tumor. New entities, in particular, intraductal papillary mucinous neoplasm and its variants, such as oncocytic and intestinal subtypes were recognized. The importance of clinical and pathologic correlation in the evaluation of these lesions was appreciated, in particular, with regards to the multifocality of these lesions, their association with invasive carcinomas, and thus their 'preinvasive' nature. Consensus criteria for the distinction of these from the ordinary precursors of adenocarcinoma, the pancreatic intraepithelial neoplasia, were established. The definition of mucinous cystic neoplasms was refined; ovarian-like stroma has now become almost a requirement for the diagnosis of mucinous cystic neoplasia, and defined as such, the propensity of these tumors to occur in perimenopausal women became even more striking. The validity and clinical value of classifying the pancreatic cysts of mucinous type as adenoma, borderline, CIS and invasive have been established. Related to this, the importance of thorough sampling in accurate classification of these mucinous lesions was recognized. Greater accessibility of the pancreas afforded by improved invasive as well as noninvasive modalities has also increased the detection of otherwise clinically silent cystic tumors, which has led to the recognition of more innocuous entities such as acinar cell cystadenoma and squamoid cyst of pancreatic ducts. As the significance of the cystic lesions emerged, cystic forms of otherwise typically solid tumors were also better characterized. Thus, significant developments have taken place in the classification and our understanding of pancreatic cystic tumors in the past few years, and experience with these lesions is likely to grow exponentially in the coming years.
Topics: Adenoma; Carcinoma in Situ; Cystadenocarcinoma, Mucinous; Cystadenocarcinoma, Papillary; Humans; Pancreas; Pancreatic Ducts; Pancreatic Neoplasms; Pancreatic Pseudocyst; Precancerous Conditions
PubMed: 17486054
DOI: 10.1038/modpathol.3800706 -
Bulletin Du Cancer Jun 2002Benign and malignant thyroid tumors constitute a wide range of neoplasias showing recurrent chromosome abnormalities. Cytogenetic studies of thyroid hyperplasias and... (Review)
Review
Benign and malignant thyroid tumors constitute a wide range of neoplasias showing recurrent chromosome abnormalities. Cytogenetic studies of thyroid hyperplasias and follicular adenomas revealed hyperdiplo d karyotypes with a characteristic sequence of trisomies (7, 5, 12, 14, 16, 17, 20 and 22) starting with trisomy 7. Comparative genomic hybridization (CGH) findings on thyroid oncocytic tumors showed similar chromosomal gains with no difference observed between adenomas and carcinomas. Follicular thyroid carcinomas exhibit losses of 3p25-pter predominantly or of 22,13 and 1p segments. Formation of fusion genes PAX8 - PPARgamma1 caused by a t(2;3)(q13;p25) has been observed in several cases of follicular carcinomas only. Loss of chromosome 22 has been found most frequently associated with widely invasive follicular carcinomas. Activation of the RET protooncogene through chromosome rearrangements involving subband 10q11.2 represent the most common and specific genetic alteration in papillary thyroid carcinoma. Several chimeric genes resulting in the fusion of the tyrosine kinase domain of RET with the 5' sequences of different genes have been described. Germline mutations in RET are associated with medullary thyroid carcinoma in multiple endocrine neoplasia type 2 (MEN2). Cytogenetics of thyroid tumors, using conventional and molecular methods (FISH, CGH) demonstrated that particular chromosome aberrations may be related to the clinical behavior of these tumors and may provide informations for their diagnosis or prognosis.
Topics: Adenoma; Carcinoma, Medullary; Carcinoma, Papillary; Chromosome Aberrations; Humans; Hyperplasia; Thyroid Gland; Thyroid Neoplasms
PubMed: 12135859
DOI: No ID Found -
Endocrine Journal Jul 2016Parathyroid and thyroid lesions appear morphologically similar in cytological smears, and their differentiation can be difficult. The purpose of this study was to...
Parathyroid and thyroid lesions appear morphologically similar in cytological smears, and their differentiation can be difficult. The purpose of this study was to determine the diagnostic value of T-cell-specific transcription factor GATA-3 as a marker of parathyroid differentiation in cytology specimens, and to examine the utility of liquid-based cytology (LBC). Cytology smears obtained from surgically removed parathyroid and thyroid specimens, including 15 normal parathyroid glands, 12 cases of parathyroid hyperplasia, 55 parathyroid adenomas, 2 follicular thyroid adenomas, and 3 papillary thyroid carcinomas, were examined by immunocytochemistry using antibodies against GATA-3, parathyroid hormone (PTH), chromogranin A, and thyroid transcription factor 1 (TTF-1). All normal and hyperplastic parathyroids and 98.2% of parathyroid adenomas were positive for GATA-3, while 33.3%, 66.7%, and 60.0% of them, respectively, were positive for PTH. The positive rates for chromogranin A among normal parathyroids (80.0%) and parathyroid adenomas (87.3%) were lower than those for GATA-3. At the same time, all thyroid-derived tumours were positive for TTF-1 and negative for GATA-3, PTH, and chromogranin A. LBC smears of 35 parathyroid lesions indicated that the positive rates for GATA-3, PTH, and chromogranin A were 97.1 %, 97.1%, and 100%, respectively, while in conventional smears, those for PTH (25.5%) and chromogranin A (78.7%) were significantly lower (p < 0.01). Our results suggest that GATA-3 is a more reliable biomarker than PTH or chromogranin A in differentiating parathyroid from thyroid lesions in cytology smears and that LBC is useful in detecting cytoplasmic antigens such as PTH and chromogranin A.
Topics: Adenoma; Adult; Biomarkers; Biopsy, Fine-Needle; Chromogranin A; Cytodiagnosis; Diagnosis, Differential; GATA3 Transcription Factor; Humans; Hyperplasia; Immunohistochemistry; Parathyroid Glands; Parathyroid Hormone; Parathyroid Neoplasms; Predictive Value of Tests; Thyroid Gland
PubMed: 27097544
DOI: 10.1507/endocrj.EJ15-0700 -
Indian Journal of Cancer 2010Specific criteria are used to diagnose thyroid neoplasms; however, the distinction between certain neoplasms, such as follicular adenoma and carcinoma, could be...
BACKGROUND
Specific criteria are used to diagnose thyroid neoplasms; however, the distinction between certain neoplasms, such as follicular adenoma and carcinoma, could be difficult. Thus, additional diagnostic features that can assist in this distinction would have great clinical usefulness.
AIMS
To evaluate the role of the proliferative marker Ki-67 in nonneoplastic and neoplastic lesions of the thyroid, with a special emphasis on the distinction between follicular adenoma and follicular carcinoma.
SETTINGS AND DESIGN
A retrospective study from a tertiary care center.
MATERIALS AND METHODS
One hundred cases of thyroid lesions, including 50 nonneoplastic and 50 neoplastic lesions, were retrieved from the archives of the Department of Pathology, Pt. BD Sharma PGIMS, Rohtak, Ki-67 immunostaining was performed by peroxidase-antiperoxidase method and compared with mitotic counts.
RESULTS
Ki-67 labeling index (LI) showed a progressive rise from multinodular goiter to benign to malignant neoplasms. A statistically significant difference was observed in Ki-67 counts between multinodular goiter vs papillary carcinoma (P < 0.05) and follicular adenoma vs follicular carcinoma (P < 0.05). The correlation between mitotic counts and Ki-67 LI was found to be significant.
CONCLUSIONS
In the present study, Ki-67 was found to be useful in differentiating between follicular adenoma and follicular carcinoma, but since the sample size of our study was small, larger studies are needed to confirm this observation as well as to assign a cutoff value for differentiating benign from malignant tumors.
Topics: Adenoma; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Cell Proliferation; Diagnosis, Differential; Disease Progression; Female; Goiter, Nodular; Humans; Immunohistochemistry; Ki-67 Antigen; Male; Middle Aged; Retrospective Studies; Thyroid Gland; Thyroid Neoplasms
PubMed: 20587907
DOI: 10.4103/0019-509X.64727 -
Cancer Cytopathology Jun 2017Noninvasive encapsulated follicular variant of papillary thyroid carcinoma, a diagnosis implying malignancy as a variant of papillary thyroid carcinoma (PTC), has...
Can noninvasive follicular thyroid neoplasm with papillary-like nuclear features be distinguished from classic papillary thyroid carcinoma and follicular adenomas by fine-needle aspiration?
BACKGROUND
Noninvasive encapsulated follicular variant of papillary thyroid carcinoma, a diagnosis implying malignancy as a variant of papillary thyroid carcinoma (PTC), has recently been reclassified to noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) on surgical pathology. Due to the effects of such a recategorization on rate of malignancy and clinical management algorithms, it is imperative that we explore whether presurgical fine-needle aspiration can differentiate NIFTP from PTC and follicular adenoma (FA).
METHODS
Cytology slides from subjects with final surgical pathology resection diagnoses of NIFTP/encapsulated follicular variant of papillary thyroid carcinoma, classic PTC, and FA made between January 2013 and August 2016 were assessed. The Bethesda System diagnoses were tabulated and cytomorphologic features were analyzed for an association with surgical pathology diagnoses.
RESULTS
A total of 56 NIFTP, 67 classic PTC, and 30 FA cases were included. The presurgical NIFTP diagnosis according to The Bethesda System was most often atypia of undetermined significance (37.5%) followed by suspicious for follicular neoplasm/follicular neoplasm (26.8%), suspicious for malignancy (17.9%), benign (10.7%), and positive for malignancy (7.1%). The most common NIFTP cytomorphologic features were nuclear enlargement (83.9%), nuclear crowding (82.1%), nuclear clearing (69.6%), and microfollicles (73.2%). All cytomorphologic features demonstrated statistically significant associations (P value range, <.001-.002) between NIFTP and PTC, whereas select cytomorphologic features demonstrated significant associations between NIFTP and FA.
CONCLUSIONS
Several statistically significant associations appear to be present between cytomorphologic features and surgical diagnosis that may be used as clues to distinguish NIFTP, PTC, and FA on fine-needle aspiration. Although diagnostic confirmation of NIFTP must occur at the time of excision, similar to follicular neoplasms, the possibility of NIFTP may be raised preoperatively on cytology. Cancer Cytopathol 2017;125:378-88. © 2017 American Cancer Society.
Topics: Adenocarcinoma, Follicular; Adenoma; Biopsy, Fine-Needle; Carcinoma; Carcinoma, Papillary; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Neoplasm Invasiveness; Retrospective Studies; Thyroid Cancer, Papillary; Thyroid Neoplasms
PubMed: 28296267
DOI: 10.1002/cncy.21848 -
Asian Pacific Journal of Cancer... Oct 2021The follicular-patterned thyroid lesions (FPTLs) include hyperplastic nodules (HN), follicular adenoma (FA), non-invasive follicular neoplasm with papillary-like nuclear...
BACKGROUND
The follicular-patterned thyroid lesions (FPTLs) include hyperplastic nodules (HN), follicular adenoma (FA), non-invasive follicular neoplasm with papillary-like nuclear features (NIFTP), follicular carcinoma (FC), and the follicular variant of papillary carcinoma (FVPTC). Sometimes the pathologists cannot accurately separate these lesions from each others on a histological basis.
AIMS
To evaluate the utility of immunohistochemistry in the diagnosis of FPTLs.
MATERIALS AND METHODS
Immunohistochemical analysis, incorporating 83 cases of histologically confirmed FPTLs out of which 20 carcinomas, 51 benign FPTLs (38 HN and 13 FA), and 12NIFTP were separated from each others using four immunostains (HBME-1, CK19, Galectin-3, and CD56).
RESULTS
We found statistically significantly more frequent expression of HBME-1, CK19, Galectin-3 proteins in carcinomas as compared to benign FPTLs (p = <0.01). HBME-1 and Galectin-3 were the most sensitive markers for the diagnosis of malignant FPTLs (75%). Galectin-3 was the most specific marker for the diagnosis of carcinoma (90.3%).
CONCLUSIONS
The histomorphological features remain the cornerstone of the diagnosis of FPTN. Although HBME-1, Galectin-3, and CK19 immunostains have some diagnostic value in the separation of malignant from benign FPTLs, they are variably expressed in the benign and malignant FPTLs. No single immunostain has sufficient sensitivity and specificity and therefore their diagnostic use is controversial. Future studies are mandated to find more reliable markers that can separate between benign and malignant FPTLs.
Topics: Adenocarcinoma, Follicular; Adenoma; Adolescent; Adult; Biomarkers, Tumor; CD56 Antigen; Female; Galectin 3; Humans; Immunohistochemistry; Keratin-19; Male; Middle Aged; Thyroid Cancer, Papillary; Thyroid Neoplasms; Thyroid Nodule; Young Adult
PubMed: 34711014
DOI: 10.31557/APJCP.2021.22.10.3365 -
Significance of AgNORs and ki-67 proliferative markers in differential diagnosis of thyroid lesions.Pathology Oncology Research : POR Apr 2013We aimed to assess the utility of quantitative analysis of AgNORs and Ki67 labeling index (LI) in the differential diagnosis of different thyroid lesions. This study...
We aimed to assess the utility of quantitative analysis of AgNORs and Ki67 labeling index (LI) in the differential diagnosis of different thyroid lesions. This study included: 25 papillary carcinomas, 7 follicular carcinomas, 21 follicular adenomas and 27 nodular goiters. Using a semiautomatic image analysis system, Ag NORs parameters were measured and calculated including: total area of AgNORs, mean Ag NOR number in nuclei, nuclear area, mean area of AgNOR dots per each nucleus, number of central and marginal AgNOR dots, and the relative ratio of total area of AgNOR dots/total area of nucleus. Ki67 immunostaining was performed and the LI was determined. There was a significant difference between groups of thyroid lesions regarding total area of AgNORs, Ag NOR number and number of marginal Ag NOR dots. According to receiver operating characteristic curve, Ag NORs number =2.91 and marginal Ag NORs = 2.67 were useful cut off values above which follicular carcinoma can be diagnosed with 100 % sensitivity, 79 % specificity, 76 % PPV, 100 % NPV and 85 % diagnostic accuracy for both parameters. Mean Ki67 LI in our study was 14.12 ± 2.29, 61.42 ± 3.77, 34.90 ± 3.49 and 18.60 ± 1.96 for papillary carcinoma, follicular carcinoma, follicular adenoma and nodular goiter respectively. Ki67 LI showed statistically significant difference between follicular carcinoma and follicular adenoma (p = 0.026) and between papillary carcinoma and follicular adenoma (p = 0.007). Quantification of Ag NORs and Ki67 LI could be used as helpful ancillary methods in the differentiation between different thyroid lesions.
Topics: Adenocarcinoma, Follicular; Adenoma; Adolescent; Adult; Aged; Biomarkers; Carcinoma, Papillary; Cell Growth Processes; Child; Diagnosis, Differential; Female; Goiter, Nodular; Humans; Immunohistochemistry; Ki-67 Antigen; Male; Middle Aged; Silver Staining; Thyroid Diseases; Thyroid Neoplasms; Young Adult
PubMed: 23055017
DOI: 10.1007/s12253-012-9565-1