Problems and Controversies in the Histopathology of Thyroid Carcinomas of Follicular Cell Origin

2009 ◽  
Vol 133 (5) ◽  
pp. 683-691
Author(s):  
Ronald Ghossein
Keyword(s):  
Thyroid Carcinoma ◽  
English Language ◽  
Follicular Carcinoma ◽  
Molecular Data ◽  
Follicular Cell ◽  
Clinical Value ◽  
Thyroid Carcinomas ◽  
Poorly Differentiated ◽  
Disease Entities

Abstract Context.—Despite past and recent efforts, many problems and controversies remain in the classification of thyroid carcinomas of follicular cell origin. These controversies have an impact on the prognosis and therapy of patients with thyroid carcinoma as well as on the development of robust cutting-edge research aimed at better outcome and quality of life. Objective.—To focus on 3 contentious areas with significant clinical value: the follicular variant of papillary thyroid carcinoma, the extent of invasion in follicular carcinoma, and the poorly differentiated thyroid carcinomas. Data Sources.—The published English language literature was reviewed. Conclusions.—Recent data show that prognosis and therapy for many disease entities can be better delineated if a meticulous microscopic examination is performed. An accurate assessment of the extent of invasion (especially vascular) is crucial. Proliferative grading (ie, mitosis and necrosis) is of high prognostic value and should be looked for in every specimen. In addition, molecular data gathered to date can help reassess these tumors at the histologic level. Classification proposals based on personal experience rather than adequate and careful clinical follow-up should be discouraged.

scholarly journals RAS Mutations Are the Predominant Molecular Alteration in Poorly Differentiated Thyroid Carcinomas and Bear Prognostic Impact

2009 ◽  
Vol 23 (10) ◽  
pp. 1715-1715
Author(s):  
Marco Volante ◽  
Ida Rapa ◽  
Manoj Gandhi ◽  
Gianni Bussolati ◽  
Daniela Giachino ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Diagnostic Criteria ◽  
Molecular Data ◽  
Genetic Alteration ◽  
Prognostic Impact ◽  
Genetic Event ◽  
Thyroid Carcinomas ◽  
Ras Mutations ◽  
Poorly Differentiated Carcinoma ◽  
Poorly Differentiated

ABSTRACT Context Poorly differentiated carcinomas represent an aggressive group of thyroid tumors with controversial classification placement and poorly understood pathogenesis. Molecular data in this group of tumors are extremely heterogeneous, possibly reflecting different inclusion criteria. Recently homogeneous diagnostic criteria have been proposed by our group (Turin proposal) that need to be complemented by detailed molecular characterization. Objective The objective of the study was to define a comprehensive molecular typing of poorly differentiated thyroid carcinomas classified following homogeneous diagnostic criteria. Design Sixty-five cases of poorly differentiated carcinoma selected following the Turin proposal have been screened for N-, K-, H-RAS, BRAF, RET/PTC1 and 3, and PAX8/PPARγ mutations-rearrangements using alternative techniques and in two different laboratories. Molecular data were compared with clinical pathological parameters and survival by univariate and multivariate analysis. Results RAS mutations in codon 61 were by far the most common genetic alteration in poorly differentiated carcinomas (23% of cases), with all mutation in NRAS except one in the HRAS gene. A single BRAF mutation was found in a poorly differentiated carcinoma with a residual component of a tall cell variant of papillary carcinoma. No KRAS, RET/PTC, or PAX8/PPARγ genetic alteration was detected. In this series, the presence of RAS mutations was a unique negative prognostic parameter at multivariate analysis. Conclusions The present study demonstrates that strictly classified poorly differentiated carcinomas are genetically homogeneous, RAS mutations being the almost exclusive genetic event. Moreover, the detection of RAS mutations might be clinically relevant for the prognostic stratification of these tumors.

Circulating Cytokeratin 19 Fragments in Patients with benign Nodules and Carcinomas of the Thyroid Gland

2008 ◽  
Vol 23 (1) ◽  
pp. 54-57 ◽  
Author(s):  
L. Giovanella ◽  
L. Ceriani ◽  
A. Ghelfo ◽  
M. Maffioli
Keyword(s):  
Thyroid Carcinoma ◽  
Thyroid Nodules ◽  
Differentiated Thyroid Carcinoma ◽  
Cytokeratin 19 ◽  
Thyroid Carcinomas ◽  
Poorly Differentiated ◽  
Benign Nodules ◽  
Thyroid Malignancies ◽  
Benign Thyroid Nodules ◽  
Benign Thyroid

Cytokeratin 19 (CK19) is an acidic protein of 40 kDa that is part of the cytoskeleton of epithelial cells and is highly expressed by differentiated thyroid carcinomas, mainly of the papillary subtype. The soluble fragments of CK19 (Cyfra 21.1) can be measured by immunometric assays employing specific monoclonal antibodies. The present study was planned to assess the serum expression of Cyfra 21.1 in patients with benign thyroid nodules and thyroid malignancies. We enrolled 135 patients with histologically proven benign thyroid nodules (n=79) and thyroid carcinomas (n=56). No differences were found in serum Cyfra 21.1 levels between patients with benign nodules and patients with carcinomas. When thyroid malignancies were subdivided according to tumor histology, serum Cyfra 21.1 increased significantly from classical differentiated thyroid carcinomas (papillary or follicular) to less differentiated or undifferentiated carcinomas (poorly differentiated or anaplastic). CK19 release into the bloodstream is strongly related to the apoptotic pathway, and particularly to hyperproliferation-related apoptosis. These pathways characterized anaplastic and poorly differentiated thyroid carcinoma but not classical forms of differentiated thyroid carcinoma. Consequently, Cyfra 21.1 may be regarded as a circulating marker of poorly differentiated and anaplastic thyroid carcinoma. Additionally, a role of Cyfra 21.1 as a dedifferentiation marker in patients with classical differentiated thyroid carcinomas may be postulated and should be explored by further focused studies.

Genetic profile of advanced thyroid cancers in relation to distant metastasis

2020 ◽  
Vol 27 (5) ◽  
pp. 285-293 ◽  
Author(s):  
Eyun Song ◽  
Dong Eun Song ◽  
Jonghwa Ahn ◽  
Tae Yong Kim ◽  
Won Bae Kim ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Distant Metastasis ◽  
Distant Metastases ◽  
Thyroid Tumors ◽  
Primary Tumors ◽  
Thyroid Cancers ◽  
Histone Methyltransferases ◽  
Thyroid Carcinomas ◽  
Poorly Differentiated

Major clinical challenges exist with differentiated thyroid cancers with distant metastases or rare but aggressive types, such as poorly differentiated thyroid carcinomas and anaplastic thyroid carcinomas. The precise characterization of the mutational profile in these advanced thyroid cancers is crucial. Samples were collected from primary tumors and distant metastases of 64 patients with distant metastases from differentiated thyroid cancer, poorly differentiated thyroid carcinoma, or anaplastic thyroid carcinoma. Targeted next-generation sequencing was performed with 50 known thyroid-cancer-related genes. Of the 82 tissues, 63 were from primary tumors and 19 from distant metastases. The most prevalent mutation observed from the primary tumors was TERT promoter mutation (56%), followed by BRAF (41%) and RAS (24%) mutations. TP3 was altered by 11%. Mutations in histone methyltransferases, SWI/SNF subunit–related genes, and PI3K/AKT/mTOR pathway-related genes were present in 42%, 12%, and 22%, respectively. When the mutational status was analyzed in 15 matched pairs of thyroid tumors and their matched distant metastases and one pair of distant metastases with two distinct sites, the concordance was high. A similar frequency of mutations in TERT promoter (58%) and BRAF (42%) as well as histone methyltransferases (37%), SWI/SNF subunits (10%), and PI3K/AKT/mTOR pathway (26%) were noted. The same main, early and late mutations were practically always present in individual primary tumor–metastasis pairs. Enrichment of TERT promoter, BRAF, and RAS mutations were detected in highly advanced thyroid cancers with distant metastasis. The genetic profiles of primary thyroid tumors and their corresponding distant metastases showed a high concordance.

scholarly journals Deregulation of microRNA expression in follicular cell-derived human thyroid carcinomas

2010 ◽  
Vol 17 (1) ◽  
pp. F91-F104 ◽  
Author(s):  
Pierlorenzo Pallante ◽  
Rosa Visone ◽  
Carlo Maria Croce ◽  
Alfredo Fusco
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Thyroid Tissue ◽  
Endocrine System ◽  
Follicular Carcinoma ◽  
Thyroid Neoplasms ◽  
Anaplastic Thyroid Cancer ◽  
Microrna Expression ◽  
Human Thyroid ◽  
Thyroid Carcinomas

Carcinoma of the thyroid gland is an uncommon cancer, but one of the most frequent malignancies of the endocrine system. Most thyroid cancers are derived from the follicular cells. Follicular carcinoma is considered more malignant than papillary thyroid carcinoma (PTC), and anaplastic thyroid cancer (ATC) is one of the most lethal human cancers. Even though several genetic lesions have been already described in human thyroid cancer, particularly in the papillary histotype, the mechanisms underlying the development of these neoplasias are still far from being completely elucidated. Some years ago, several studies were undertaken to analyze the expression of microRNAs (miRNAs or miRs) in thyroid carcinoma to evaluate a possible role of their deregulation in the process of carcinogenesis. These studies showed an aberrant microRNA expression profile that distinguishes unequivocally among PTC, ATC, and normal thyroid tissue. Here, other than summarizing the current findings on microRNA expression in human thyroid carcinomas, we discuss the mechanisms by which microRNA deregulation may play a role in thyroid carcinogenesis, and the possible use of microRNA knowledge in the diagnosis and therapy of thyroid neoplasms.

Thyroid and Parathyroid Neoplasms with Lipomatous Stroma: Report of Three Cases and Review of the Literature

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S33-S33
Author(s):  
M Toprak ◽  
M Kashi ◽  
J Villanueva ◽  
M Wrzolek ◽  
G Tong ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Thyroid Carcinoma ◽  
Malignant Tumors ◽  
Diagnostic Error ◽  
Needle Aspiration ◽  
Parathyroid Glands ◽  
Fatty Tissue ◽  
Thyroid Carcinomas ◽  
Preoperative Diagnostic ◽  
Poorly Differentiated

Abstract Introduction/Objective Tumors with mixed adipose tissue and epithelial components are rare in thyroid and parathyroid glands. Most of them are benign and referred to as adenolipoma (or lipoadenoma). A handful of malignant tumors of thyroid follicular cell origin have been reported with abundant adipose tissue known as thyroid carcinoma with lipomatous stroma (TCLS). Adenolipomas of thyroid or TCLS are usually manifested as large thyroid nodules and evaluated by fine needle aspiration biopsy (FNAB) which frequently yield low-cellularity samples due to abundant adipose tissue. On FNAB, the adipose tissue usually interpreted as contamination of subcutaneous or perithyroid origin. Similarly, adenolipomas of the parathyroid are not frequently identified because of presence of adipose tissue which is a feature associated with normal parathyroid glands. Therefore, these tumors are not often correctly diagnosed preoperatively. For that reason, pathologist should report additional cases about this rare entity to increase our understanding and to decrease preoperative diagnostic error. Methods We report three cases of thyroid and parathyroid tumors with abundant adipose tissue with sonographic, cytologic and histologic features along with literature review. Results Among the reported cases in the literature and our cases; 10 out of 17 cases of thyroid carcinoma with lipomatous stroma are papillary thyroid carcinomas (58.8%), 3 out of 17 cases are papillary microcarcinomas (17.6%), 2 out of 17 cases are noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) (11.7%), and 2 out of 17 cases are minimally invasive follicular carcinomas (11.7%). No cases of poorly differentiated or anaplastic thyroid carcinomas have been reported. Conclusion Lipomatous stroma in thyroid carcinoma appears to be associated with differentiated carcinomas since no reported cases of poorly differentiated or anaplastic thyroid carcinomas are present to our knowledge. Although the presence of fatty tissue does not appear to alter the prognosis of these lesions, the question of the histogenesis of the adipose component is intriguing. Awareness of this unusual feature and increased utilization of multimodal approaches in the evaluation of this entity may increase preoperative detection and the understanding of the histogenesis and its possible significance.

scholarly journals Etiopathogenesis of Differentiated Thyroid Carcinomas

2016 ◽  
Vol 4 (3) ◽  
pp. 517-522
Author(s):  
Tanja Makazlieva ◽  
Olivija Vaskova ◽  
Venjamin Majstorov
Keyword(s):  
Thyroid Carcinoma ◽  
Epidemiological Studies ◽  
Genetic Alterations ◽  
Anaplastic Thyroid Carcinoma ◽  
Epigenetic Alterations ◽  
Thyroid Carcinomas ◽  
Etiological Factors ◽  
Appropriate Treatment ◽  
Poorly Differentiated ◽  
Thyroid Malignancies

INTRODUCTION: Thyroid malignomas are a heterogeneous group of neoplasm consisting of most frequent differentiated encountered carcinomas, papillary and follicular thyroid carcinoma, then medullary thyroid carcinoma originating from neuroendocrine calcitonin-producing C-cells and rare forms of thyroid lymphomas arising from intrathyroidal lymphatic tissue, thyroid sarcomas and poorly differentiated anaplastic thyroid carcinoma. There are increasing numbers of epidemiological studies and publications that have suggested increased incidence rate of thyroid carcinomas. We have read, analysed and compare available reviews and original articles investigating different etiological factors in the development of thyroid carcinomas through Google Scholar and PubMed Database.DISCUSSION: Aetiology involved in the development of thyroid carcinomas is multifactorial and includes external influences, as well as constitutional predispositions and genetic etiological factors. The actual effect of environmental and constitutional factors is on promoting genetic and epigenetic alterations which result in cell proliferation and oncogenesis. Until now are identified numerous genetic alterations, assumed to have an important role in oncogenesis, with MAPK and PI3K-AKT as crucial signalling networks regulating growth, proliferation, differentiation and cell survival/apoptosis. CONCLUSION: This new molecular insight could have a crucial impact on diagnosis and also on improving and selecting an appropriate treatment to the patients with thyroid malignancies.

Bone Metastases From Thyroid Carcinoma

2000 ◽  
Vol 124 (10) ◽  
pp. 1440-1447
Author(s):  
Satish K. Tickoo ◽  
Anastassios G. Pittas ◽  
Michael Adler ◽  
Melissa Fazzari ◽  
Steven M. Larson ◽  
...  
Keyword(s):  
Bone Metastasis ◽  
Thyroid Carcinoma ◽  
Bone Metastases ◽  
Tumor Type ◽  
Metastatic Tumors ◽  
Thyroid Carcinomas ◽  
Hürthle Cell ◽  
Significant Difference ◽  
Poorly Differentiated ◽  
Worse Prognosis

Abstract Context.—Only limited information exists on the pathologic aspects of thyroid carcinomas with bone metastases, most large studies having concentrated mainly on their clinical features. Objective.—To study in detail the morphologic features of thyroid carcinomas with skeletal metastases. Design.—Seventy-nine cases of thyroid carcinoma with bone metastases treated at Memorial Sloan-Kettering Cancer Center, New York, NY, between 1964 and 1998 were investigated, with emphasis on the pathology of the primary and/or metastatic tumors and comparison of the morphologic features of the tumors at both the sites, wherever possible. The tumors were also compared for various clinical parameters. Results.—The cohort consisted of 22 papillary, 17 follicular, 16 insular, 10 anaplastic, 9 Hürthle cell, and 5 medullary carcinomas. Of these cases, 68% had poorly differentiated or undifferentiated features in the primary and/or metastatic tumors. The metastatic tumors were better differentiated than the primary in one third of the cases (6 of 18). Only one case showed a less differentiated metastasis. The overall 5- and 10-year survival probabilities after the bone metastases were 29% and 13%, respectively (Kaplan-Meier method). Although both the tumor type and differentiation seemed to affect survivals after bone metastasis (P = .007 and .012, respectively) (log-rank test), this was primarily due to the much worse prognosis in the cases of anaplastic and medullary carcinoma. Cases of Hürthle cell carcinoma showed the longest median survival. There was no significant difference in survival among patients up to or older than 45 years at the time of metastases (P = .31). Conclusions.—Most thyroid carcinomas with bone metastases are of papillary type, and most have poorly differentiated or undifferentiated features. The influence of the microscopic tumor type and tumor differentiation on survival after bone metastasis primarily appears to be due to the much worse prognosis among anaplastic and medullary carcinomas. Age at diagnosis of bone metastases does not influence survivals.

scholarly journals Incidental Poorly Differentiated Thyroid Cancer in Trauma Patient

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A892-A892
Author(s):  
Alberto Javier Grana Santini ◽  
Milliette Alvarado ◽  
Loida Alejandra Gonzalez-Rodriguez ◽  
Margarita Ramirez ◽  
Nydia Ivette Burgos Ortega ◽  
...  
Keyword(s):  
Lymph Node ◽  
Thyroid Carcinoma ◽  
Distant Metastases ◽  
Whole Body ◽  
Thyroid Lobe ◽  
Thyroid Carcinomas ◽  
Level 3 ◽  
Poorly Differentiated ◽  
Left Thyroid Lobe

Abstract Poorly differentiated carcinomas tend to arise de novo or transform from differentiated thyroid carcinomas. Females, middle-aged and elderly adults are most commonly affected. Patients present with an enlarging thyroid mass which is often locally advanced at presentation. This is a case of 30-year-old male patient admitted after burn injury who presented with neck enlarging mass. He had no family history of thyroid CA, no radiation exposure and normal thyroid function tests. Neck CT imaging found with heterogeneous enhancing mass arising from the left thyroid lobe. Thyroid ultrasound consistent with a large left thyroid lobe lesion described as a complex solid component measures at least 5.2 cm long x 4.0 cm AP by 5.0 cm transverse with coarse scattered echogenic foci, and smaller bright echoes with comet-tail artifacts. Fine needle biopsy was non-diagnostic or unsatisfactory. Second FNA with Atypia of undetermined significance. Left hemithyroidectomy performed consistent with a 5cm Poorly differentiated thyroid carcinoma arising in a preexisting papillary thyroid carcinoma with extensive necrosis, pT3aNx, TTF1 +, PAX 8 +, CK7 +. Right thyroid was negative for malignancy. A Therapeutic dose of 135.7 mCi of 131-iodine was given. Subsequent whole body scan with focal findings in the thyroid bed region is consistent with residual functional thyroid tissue. Follow up with normal thyroglobulin levels and negative thyroglobulin antibodies. Neck ultrasound without abnormal tissue or nodules seen at either thyroid bed. Follow up with 18-F-FDG PET/CT scan abnormal study with avid lymph node in the right side of the neck, Level 3. FNA lymph node, cervical right level 3, 1.1cm, ultrasound guided biopsy negative for metastatic carcinoma. Poorly differentiated thyroid carcinomas present as large thyroid masses. The tumor spreads by local invasion into perithyroidal tissues and by distant metastases. Poorly differentiated carcinoma is supported by immunohistochemical staining for Tg, TTF1, and paired box protein Pax 8 (PAX8). There is no standardized treatment for PDTC to date. If possible, a total thyroidectomy including lymph node dissection should be performed to improve survival rates. Due to the higher rate of ETE, positive margins, neck disease, and distant metastases, adjuvant treatment should be considered. Some experts recommended considering adjuvant RAI in all PDTC patients, giving the potential benefit and lack of morbidity. However, despite the capability of RAI uptake in a high percentage of PDTC, no significant impact on survival has been reported. It is important to recognize prognosis of PDTC is distinctly less favorable than that of PTC or FTC. Several factors have been identified to affect patient prognosis such as extensive tumor necrosis, >45 year of age, tumor size (>5 cm), extrathyroidal extension and distant metastases are unfavorable prognostic factors.

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