Papillary Thyroid Carcinoma with High-Grade Features Versus Poorly Differentiated Thyroid Carcinoma: An Analysis of Clinicopathologic and Molecular Features and Outcome

Thyroid ◽  
2020 ◽  
Author(s):  
Kristine S Wong ◽  
Fei Dong ◽  
Milhan Telatar ◽  
Jochen Lorch ◽  
Erik K Alexander ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Differentiated Thyroid Carcinoma ◽  
High Grade ◽  
Papillary Thyroid ◽  
Poorly Differentiated Thyroid Carcinoma ◽  
Molecular Features ◽  
Poorly Differentiated

scholarly journals Oncocytic Papillary Thyroid Carcinoma and Oncocytic Poorly Differentiated Thyroid Carcinoma: Clinical Features, Uptake, and Response to Radioactive Iodine Therapy, and Outcome

2021 ◽  
Vol 12 ◽  
Author(s):  
Jelena Lukovic ◽  
Irina Petrovic ◽  
Zijin Liu ◽  
Susan M. Armstrong ◽  
James D. Brierley ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Differentiated Thyroid Carcinoma ◽  
Papillary Thyroid ◽  
Clinicopathologic Characteristics ◽  
Large Tumor ◽  
Poorly Differentiated Thyroid Carcinoma ◽  
Increased Risk ◽  
Poorly Differentiated ◽  
Widely Invasive

ObjectiveThe main objective of this study was to review the clinicopathologic characteristics and outcome of patients with oncocytic papillary thyroid carcinoma (PTC) and oncocytic poorly differentiated thyroid carcinoma (PDTC). The secondary objective was to evaluate the prevalence and outcomes of RAI use in this population.MethodsPatients with oncocytic PTC and PDTC who were treated at a quaternary cancer centre between 2002 and 2017 were retrospectively identified from an institutional database. All patients had an expert pathology review to ensure consistent reporting and definition. The cumulative incidence function was used to analyse locoregional failure (LRF) and distant metastasis (DM) rates. Univariable analysis (UVA) was used to assess clinical predictors of outcome.ResultsIn total, 263 patients were included (PTC [n=218], PDTC [n=45]) with a median follow up of 4.4 years (range: 0 = 26.7 years). Patients with oncocytic PTC had a 5/10-year incidence of LRF and DM, respectively, of 2.7%/5.6% and 3.4%/4.5%. On UVA, there was an increased risk of DM in PTC tumors with widely invasive growth (HR 17.1; p<0.001), extra-thyroidal extension (HR 24.95; p<0.001), angioinvasion (HR 32.58; p=0.002), focal dedifferentiation (HR 19.57, p<0.001), and focal hobnail cell change (HR 8.67, p=0.042). There was additionally an increased risk of DM seen in male PTC patients (HR 5.5, p=0.03).The use of RAI was more common in patients with larger tumors, angioinvasion, and widely invasive disease. RAI was also used in the management of DM and 43% of patients with oncocytic PTC had RAI-avid metastatic disease. Patients with oncocytic PDTC had a higher rate of 5/10-year incidence of LRF and DM (21.4%/45.4%; 11.4%/40.4%, respectively). Patients with extra-thyroidal extension had an increased risk of DM (HR 5.52, p=0.023) as did those with angioinvasion. Of the patients with oncocytic PDTC who received RAI for the treatment of DM, 40% had RAI-avid disease.ConclusionWe present a large homogenous cohort of patients with oncocytic PTC and PDTC, with consistent pathologic reporting and definition. Patients with oncocytic PTC have excellent clinical outcomes and similar risk factors for recurrence as their non-oncocytic counterparts (angioinvasion, large tumor size, extra-thyroidal extension, and focal dedifferentiation). Compared with oncocytic PTCs, the adverse biology of oncocytic PDTCs is supported with increased frequency of DM and lower uptake of RAI.

Cribriform-Morular Variant of Papillary Thyroid Carcinoma With Poorly Differentiated Features: A Case Report With Immunohistochemical and Molecular Genetic Analysis

2018 ◽  
Vol 27 (3) ◽  
pp. 294-304 ◽  
Author(s):  
Jessica Corean ◽  
Larissa V. Furtado ◽  
Sabah Kadri ◽  
Jeremy P. Segal ◽  
Lyska L. Emerson
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Familial Adenomatous Polyposis ◽  
Thyroid Carcinoma ◽  
Differentiated Thyroid Carcinoma ◽  
Apc Gene ◽  
Adenomatous Polyposis ◽  
Papillary Thyroid ◽  
Poorly Differentiated Thyroid Carcinoma ◽  
Poorly Differentiated ◽  
Cribriform Morular Variant

Cribriform-morular variant of papillary thyroid carcinoma (CMVPTC) is usually an inherited malignancy and may be a presenting indicator of familial adenomatous polyposis syndrome although it may occasionally be sporadic. Known CMVPTC mutations include adenomatous polyposis coli ( APC) and β-catenin ( CTNNB1) genes. Despite its malignant classification, CMVPTC is considered to be a well-differentiated thyroid tumor with a generally good behavior. In contrast, poorly differentiated thyroid carcinoma is an aggressive tumor. We report a case of CMVPTC with poorly differentiated features in a young female without phenotypic features of familial adenomatous polyposis but with known germline alterations of the APC gene. High throughput sequencing showed germline chromosome 5q deletion encompassing the APC gene in all components with additional unique genetic alterations in the somatic components. A single nucleotide substitution (c.1548+1G>A, NM_000038.5) located one base pair downstream of exon 12 of the APC gene was identified in the CMVPTC component, and a pathogenic frameshift deletion in exon 14 of APC (c.3642del, p.Ser1214Argfs*51, NM_000038.5) was identified in the poorly differentiated thyroid carcinoma component. No other cancer-associated genes were identified by our techniques. Our case represents a rare phenomenon of poorly differentiated features in association with CMVPTC. To our knowledge, ours is the only such report of poorly differentiated features arising in association with an inherited CMVPTC.

scholarly journals Cribriform-morular variant of papillary thyroid carcinoma with poorly differentiated features: report of a case and review of the literature

2022 ◽  
Vol 5 (1) ◽  
Author(s):  
Kusum L. Sharma ◽  
Ravi B. Singh ◽  
Nisreen Fidda ◽  
Ricardo V. Lloyd
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Differentiated Thyroid Carcinoma ◽  
Disease Spread ◽  
Beta Catenin ◽  
Papillary Thyroid ◽  
Ki 67 ◽  
History Of ◽  
Poorly Differentiated ◽  
Cribriform Morular Variant

Abstract Introduction Cribrifrom-morular variant of papillary thyroid carcinoma (CMVPTC) is an uncommon thyroid neoplasm that occurs predominantly in women and is sometime associated with familial adenomatous polyposis (FAP). Some of these tumors may undergo dedifferentiation to poorly differentiated thyroid carcinoma (PDTC). We describe a rare case of this carcinoma in a women without a history of FAP. Case presentation A 49-year-old woman with a history of breast carcinoma presented with a thyroid mass. A CMVPTC was diagnosed after excision. There was no history of FAP. Histological examination showed classical features of CMVPTC in most areas, but about 20% of the carcinoma showed features of a poorly differentiated carcinoma with a solid pattern of growth, increase mitotic activity and a high Ki-67 proliferative index (25%). Immunohistochemical stains were positive for nuclear and cytoplasmic beta catenin staining. These special studies supported the diagnosis. Conclusion CMVPTC with dedifferentiation to PDTC is a rare carcinoma with only 4 previous documented cases in the literature. This aggressive variant of thyroid carcinoma is more common in females, as is CMVPTC, and is often associated with an aggressive biological course. The cases usually express nuclear beta catenin and estrogen, progesterone and androgen receptors have been reported in some cases. Some cases may have somatic alterations of the APC gene and TERT promoter mutations. These carcinomas may metastasize to lung, bones and lymph nodes. Because of its aggressive behavior, patient with this diagnosis should be treated aggressively to control disease spread and mortality from the carcinoma.

Cytopathology of Solid Variant of Papillary Thyroid Carcinoma: Differential Diagnoses with other Thyroid Tumors

2018 ◽  
Vol 62 (5-6) ◽  
pp. 371-379 ◽  
Author(s):  
Prerna Guleria ◽  
Ravi Phulware ◽  
Shipra Agarwal ◽  
Deepali Jain ◽  
Sandeep R. Mathur ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Preoperative Diagnosis ◽  
Differentiated Thyroid Carcinoma ◽  
Follicular Neoplasm ◽  
Thyroid Tumors ◽  
Papillary Thyroid ◽  
Follicular Variant ◽  
Poorly Differentiated ◽  
Nuclear Features

Objectives: Solid variant of papillary thyroid carcinoma (SVPTC) is rare, differing from classical PTC (cPTC) in architecture and outcome. We evaluated the cytomorphology of SVPTC cases to assess the feasibility of a preoperative diagnosis. Study Design: SVPTC cases were evaluated for architecture, nuclear features, and Bethesda category and were compared with noninvasive follicular thyroid neoplasm with papillary-like nuclear features/follicular variant of PTC (NIFTP/FVPTC), cPTC, and poorly differentiated thyroid carcinoma (PDTC). Results: Nine SVPTCs, 29 NIFTP/FVPTCs, 12 cPTCs, and 4 PDTCs were included. The predominant architecture in most SVPTCs was solid fragment, which is helpful in differentiating them from NIFTP/FVPTC (p < 0.001) and cPTC (p = 0.006) but not from PDTC. The presence of microfollicles led to misinterpretation as NIFTP/FVPTC/follicular neoplasm in 4 patients. All but 1 SVPTC showed diffuse nuclear features. Intranuclear pseudoinclusions (INIs) were seen in 67% of SVPTCs as compared to 83% of cPTCs, 14% of NIFTP/FVPTCs (p = 0.005), and none of PDTCs. SVPTC cases were commonly (78%) categorized as intermediate/suspicious. Conclusions: The presence of solid fragments and lack of true papillae are helpful in differentiating SVPTC from cPTC. Solid fragments, trabeculae, the extent of nuclear features, and INIs should be looked for in cases with prominent microfollicles for distinguishing SVPTC from NIFTP/FVPTC. None of the features were helpful in differentiating SVPTC from PDTC.

scholarly journals Development of metastatic poorly differentiated thyroid cancer from a sub-centimeter papillary thyroid carcinoma in a young patient with a germline MET mutation – association or random chance?

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Klara Johansson ◽  
Adam Stenman ◽  
Johan O. Paulsson ◽  
Na Wang ◽  
Catharina Ihre-Lundgren ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Young Patients ◽  
Gene Mutations ◽  
Differentiated Thyroid Carcinoma ◽  
Papillary Thyroid ◽  
Lateral Lymph Node ◽  
Plasmid Construct ◽  
Poorly Differentiated

Abstract Background Thyroid cancer dedifferentiation is an unusual observation among young patients and is poorly understood, although a recent correlation to DICER1 gene mutations has been proposed. Case presentation A 28-year old patient presented with a sub-centimeter cytology-verified primary papillary thyroid carcinoma (PTC) and a synchronous lateral lymph node metastasis. Following surgery, histopathology confirmed a 9 mm oxyphilic PTC and a synchronous metastasis of poorly differentiated thyroid carcinoma (PDTC). Extensive molecular examinations of both lesions revealed wildtype DICER1 sequences, but identified a somatic ETV6-NTRK3 gene fusion and a MET germline variant (c.1076G > A, p.Arg359Gln). MET is an established oncogene known to be overexpressed in thyroid cancer, and this specific alteration was not reported as a single nucleotide polymorphism (SNP), suggestive of a mutation. Both the primary PTC and the metastatic PDTC displayed strong MET immunoreactivity. A validation cohort of 50 PTCs from young patients were analyzed using quantitative real-time PCR, revealing significantly higher MET gene expression in tumors than normal thyroid controls, a finding which was particularly pronounced in BRAF V600E mutated cases. No additional tumors apart from the index case harbored the p.Arg359Gln MET mutation. Transfecting PTC cell lines MDA-T32 and MDA-T41 with a p.Arg359Gln MET plasmid construct revealed no obvious effects on cellular migratory or invasive properties, whereas overexpression of wildtype MET stimulated invasion. Conclusions The question of whether the observed MET mutation in any way influenced the dedifferentiation of a primary PTC into a PDTC metastasis remains to be established. Moreover, our data corroborate earlier studies, indicating that MET is aberrantly expressed in PTC and may influence the invasive behavior of these tumors.

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