scholarly journals Hobnail variant of papillary thyroid carcinoma: molecular profiling and comparison to classical papillary thyroid carcinoma, poorly differentiated thyroid carcinoma and anaplastic thyroid carcinoma

Oncotarget ◽  
2017 ◽  
Vol 8 (13) ◽  
pp. 22023-22033 ◽  
Author(s):  
Lianghong Teng ◽  
Wanglong Deng ◽  
Junliang Lu ◽  
Jing Zhang ◽  
Xinyu Ren ◽  
...  
2021 ◽  
Vol 12 ◽  
Author(s):  
Jelena Lukovic ◽  
Irina Petrovic ◽  
Zijin Liu ◽  
Susan M. Armstrong ◽  
James D. Brierley ◽  
...  

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.


2018 ◽  
Vol 27 (3) ◽  
pp. 294-304 ◽  
Author(s):  
Jessica Corean ◽  
Larissa V. Furtado ◽  
Sabah Kadri ◽  
Jeremy P. Segal ◽  
Lyska L. Emerson

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.


2012 ◽  
Vol 20 (1) ◽  
pp. 23-37 ◽  
Author(s):  
Debora Degl'Innocenti ◽  
Paola Romeo ◽  
Eva Tarantino ◽  
Marialuisa Sensi ◽  
Giuliana Cassinelli ◽  
...  

Thyroid carcinomas derived from follicular cells comprise papillary thyroid carcinoma (PTC), follicular thyroid carcinoma, poorly differentiated thyroid carcinoma (PDTC) and undifferentiated anaplastic thyroid carcinoma (ATC). PTC, the most frequent thyroid carcinoma histotype, is associated with gene rearrangements that generateRET/PTCandTRKoncogenes and withBRAF-V600Eand RAS gene mutations. These last two genetic lesions are also present in a fraction of PDTCs. The ERK1/2 pathway, downstream of the known oncogenes activated in PTC, has a central role in thyroid carcinogenesis. In this study, we demonstrate that theBRAF-V600E,RET/PTC, andTRKoncogenes upregulate the ERK1/2 pathway's attenuator cytoplasmic dual-phase phosphatase DUSP6/MKP3 in thyroid cells. We also show DUSP6 overexpression at the mRNA and protein levels in all the analysed PTC cell lines. Furthermore,DUSP6mRNA was significantly higher in PTC and PDTC in comparison with normal thyroid tissues both in expression profile datasets and in patients' surgical samples analysed by real-time RT-PCR. Immunohistochemical and western blot analyses showed that DUSP6 was also overexpressed at the protein level in most PTC and PDTC surgical samples tested, but not in ATC, and revealed a positive correlation trend with ERK1/2 pathway activation. Finally,DUSP6silencing reduced the neoplastic properties of four PTC cell lines, thus suggesting thatDUSP6may have a pro-tumorigenic role in thyroid carcinogenesis.


2022 ◽  
Vol 5 (1) ◽  
Author(s):  
Kusum L. Sharma ◽  
Ravi B. Singh ◽  
Nisreen Fidda ◽  
Ricardo V. Lloyd

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.


2018 ◽  
Vol 62 (5-6) ◽  
pp. 371-379 ◽  
Author(s):  
Prerna Guleria ◽  
Ravi Phulware ◽  
Shipra Agarwal ◽  
Deepali Jain ◽  
Sandeep R. Mathur ◽  
...  

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.


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