scholarly journals Intratumor heterogeneity and clonal evolution in an aggressive papillary thyroid cancer and matched metastases

2015 ◽  
Vol 22 (2) ◽  
pp. 205-216 ◽  
Author(s):  
Soazig Le Pennec ◽  
Tomasz Konopka ◽  
David Gacquer ◽  
Danai Fimereli ◽  
Maxime Tarabichi ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Primary Tumor ◽  
Clonal Evolution ◽  
Distant Metastases ◽  
Intratumor Heterogeneity ◽  
Gene Fusions ◽  
Thyroid Tumors ◽  
Papillary Thyroid ◽  
Rna Seq

The contribution of intratumor heterogeneity to thyroid metastatic cancers is still unknown. The clonal relationships between the primary thyroid tumors and lymph nodes (LN) or distant metastases are also poorly understood. The objective of this study was to determine the phylogenetic relationships between matched primary thyroid tumors and metastases. We searched for non-synonymous single-nucleotide variants (nsSNVs), gene fusions, alternative transcripts, and loss of heterozygosity (LOH) by paired-end massively parallel sequencing of cDNA (RNA-Seq) in a patient diagnosed with an aggressive papillary thyroid cancer (PTC). Seven tumor samples from a stage IVc PTC patient were analyzed by RNA-Seq: two areas from the primary tumor, four areas from two LN metastases, and one area from a pleural metastasis (PLM). A large panel of other thyroid tumors was used for Sanger sequencing screening. We identified seven new nsSNVs. Some of these were early events clonally present in both the primary PTC and the three matched metastases. Other nsSNVs were private to the primary tumor, the LN metastases and/or the PLM. Three new gene fusions were identified. A novel cancer-specific KAZN alternative transcript was detected in this aggressive PTC and in dozens of additional thyroid tumors. The PLM harbored an exclusive whole-chromosome 19 LOH. We have presented the first, to our knowledge, deep sequencing study comparing the mutational spectra in a PTC and both LN and distant metastases. This study has yielded novel findings concerning intra-tumor heterogeneity, clonal evolution and metastases dissemination in thyroid cancer.

scholarly journals MON-533 Diffuse Sclerosing Variant Papillary Thyroid Cancer: Clinical and Histopathological Features, Mutational Profile, Management and Outcome

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Abeer Abdulhadi Aljomaiah ◽  
Yosra Moria ◽  
Nora Aldaej ◽  
Meshael Alswailem ◽  
Ali Saeed Alzahrani
Keyword(s):  
Thyroid Cancer ◽  
Lymph Node ◽  
Molecular Genetics ◽  
Papillary Thyroid Cancer ◽  
Distant Metastases ◽  
The Other ◽  
Papillary Thyroid ◽  
Histopathological Features ◽  
Diffuse Sclerosing Variant

Abstract Diffuse sclerosing variant (DSV) is a rare subtype of papillary thyroid cancer (PTC). Whether it represents a higher grade subtype than conventional PTC is not quite clear. Furthermore, there are limited data on its long-term outcome and its molecular genetics. In this report, we studied all cases of DSV PTC seen at our center during the last 20 years. Out of more than 6000 patients (pts) with differentiated thyroid cancer, only 37 were DSV. We reviewed the clinical and histopathological features, management and outcome of these cases. In addition, molecular genetics is partially achieved; 17 out of these 37 cases have been genotyped for BRAFV600E, TERT promotor mutations, NRAS, HRAS and KRAS mutations. The molecular profiling of the other 20 cases is being done. A total of 37 pts were studied {(12 Males:25 Females, median age 21 years (8-89)}. One pt had lobectomy and the other 36 pts (97.3%) had a total thyroidectomy. Central only (4 pts) or central/lateral lymph node dissection (29 pts) were performed. The median tumor size was 4.5 cm (1.5-8.1). The tumor was multifocal in 27 cases (73%), with extrathyroidal invasion in 27 (73%) and lymphovascular invasion in 24 pts (64.8%). A background lymphocytic thyroiditis was present in 12 pts (32.4%). Lymph node metastases were present in 34 pts (92%) and distant metastases in 13 pts (35%). The sites of metastasis are lungs in 12 pts (32.4%) and lungs and bone in 1 pt. Twenty pts (54.1%) were in TNM8 stage 1, 10 pts (27%) in stage 2, 1 (2.7%) in stage 4a, 3 (8.1%) in stage 4b and 3 unstageable. The ATA risk classification for these pts was 4 pts (10.8%) in low, 12 (32.4%) in intermediate, 19 (51.4%) in high-risk groups and 2 could not be assessed. I-131 was administered to 33 pts (89.2%). The median administered activity was 136 mCi (46-218). Fifteen pts (40.5%) received additional therapies (3 surgeries, 7 RAI, 5 surgeries, and RAI). In 17 pts (46%) which were genotyped, only 3 tumors (8.1%) had BRAFV600E mutation, 1 (2.7%) had TERT promotor C228T mutation and none had RAS mutations. At the last follow up, 15 pts (40.5%) achieved an excellent response, 9 (24%) an indeterminate response, 6 (16.2%) with a structural disease, and 7 (19%) were lost for follow up. Conclusion: DSV PTC is a rare variant, occurs mostly in adolescent and young pts, characterized by aggressive histopathological features and high rates of lymph node and distant metastases but the commonly reported mutations in PTC are rare in DSV and mortality is absent.

scholarly journals Whole Exome Sequencing Identifies a Novel Hedgehog-Interacting Protein G516R Mutation in Locally Advanced Papillary Thyroid Cancer

2018 ◽  
Vol 19 (10) ◽  
pp. 2867 ◽  
Author(s):  
Woo Lee ◽  
Seul Lee ◽  
Seung Yim ◽  
Daham Kim ◽  
Hyunji Kim ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Exome Sequencing ◽  
Papillary Thyroid Cancer ◽  
Whole Exome Sequencing ◽  
Primary Tumor ◽  
Tumor Heterogeneity ◽  
Locally Advanced ◽  
Papillary Thyroid ◽  
Whole Exome ◽  
Advanced Thyroid Cancer

Locally advanced thyroid cancer exhibits aggressive clinical features requiring extensive neck dissection. Therefore, it is important to identify changes in the tumor biology before local progression. Here, whole exome sequencing (WES) using tissues from locally advanced papillary thyroid cancer (PTC) presented a large number of single nucleotide variants (SNVs) in the metastatic lymph node (MLN), but not in normal tissues and primary tumors. Among those MLN-specific SNVs, a novel HHIP G516R (G1546A) mutation was also observed. Interestingly, in-depth analysis for exome sequencing data from the primary tumor presented altered nucleotide ‘A’ at a very low frequency indicating intra-tumor heterogeneity between the primary tumor and MLN. Computational prediction models such as PROVEAN and Polyphen suggested that HHIP G516R might affect protein function and stability. In vitro, HHIP G516R increased cell proliferation and promoted cell migration in thyroid cancer cells. HHIP G516R, a missense mutation, could be a representative example for the intra-tumor heterogeneity of locally advanced thyroid cancer, which can be a potential future therapeutic target for this disease.

Clinical association of CXCR4 in primary tumor of papillary thyroid cancer and response to iodine-131 treatment

2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Korrakode Sirakriengkrai ◽  
Supatporn Tepmongkol ◽  
Somboon Keelawat ◽  
Usanee Techavijit
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Primary Tumor ◽  
Papillary Thyroid ◽  
Iodine 131

scholarly journals A case of papillary thyroid cancer with soft tissue metastasis

2018 ◽  
Vol 5 (10) ◽  
pp. 3425 ◽  
Author(s):  
Jayan Stephen ◽  
Mebin B. Thomas ◽  
Mathew B. Thomas
Keyword(s):  
Thyroid Cancer ◽  
Soft Tissue ◽  
Thyroid Carcinoma ◽  
Papillary Thyroid Cancer ◽  
Distant Metastases ◽  
Differentiated Thyroid Carcinoma ◽  
Metastatic Tumour ◽  
Papillary Thyroid ◽  
Soft Tissue Metastasis ◽  
Regional Lymph Nodes

Papillary thyroid cancer is the most common thyroid malignancy, and although metastatic spread is typically confined to regional lymph nodes, there are rare documented cases of distant spread of disease. Distant metastases of differentiated thyroid cancer are unusual; lung and bones are the most frequently affected sites. Soft tissue metastases are extremely rare. Here we present an unusual case of soft tissue metastasis of papillary thyroid cancer to skeletal muscle. Soft tissue metastasis is rarely seen in differentiated thyroid carcinoma. Differentiated thyroid carcinoma, although generally clinically indolent, may occasionally develop distant metastases and even manifest itself as a metastatic tumour.

scholarly journals Ultrasound diagnosis of cervical levels II–IV lymph node metastasis in patients with first diagnosed papillary thyroid cancer

2020 ◽  
Vol 9 (4) ◽  
pp. 17-23
Author(s):  
V. S. Parshin ◽  
A. A. Veselova ◽  
V. S. Medvedev ◽  
S. A. Ivanov ◽  
A. D. Kaprin
Keyword(s):  
Thyroid Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Papillary Thyroid Cancer ◽  
Predictive Value ◽  
Imaging Method ◽  
Thyroid Tumors ◽  
Papillary Thyroid ◽  
Cervical Lymph Nodes ◽  
Study Objective

The study objective is to explore the potentialities of ultrasound in the detection of metastasis from papillary thyroid cancer (PTC) to cervical lymph nodes in levels II–IV.Materials and methods. In 97 patients with first diagnosed PTC, surgical removal of the cervical lymph node-bearing fat at levels II–IV was performed. All patients underwent preoperative neck ultrasound. The results were verified by histology.Results. Cervical levels II–IV lymph node metastases were revealed in 82 (84,5 %) cases by sonography and in 86 (88,6 %) cases by histology. Ultrasound showed a sensitivity of 93 %, specificity of 81 %, accuracy of 91 %, positive predictive value of 97 % and negative predictive value of 60 %. Of 1620 removed lymph nodes, 443 (27,3 %) showed metastases confirmed by histology. Sonography revealed 422 (26,0 %) metastatic lymph nodes. Metastasis from intra-thyroid tumors was noted in 94,1 % and from extra-thyroid tumors in 87,5 % of patients. Metastasis from solitary tumors occurred in 86,5 % and from multicentric tumors in 92,1 % of cases. Multiple metastases made up 89,5 % and solitary metastases – 10,5 %.Conclusion. Sonography is a highly informative diagnostic imaging method in detecting metastasis from PTC to levels II–IV cervical lymph nodes and can be used for basic assessment of thyroid abnormalities.

scholarly journals Decreased apolipoprotein A4 and increased complement component 3 as potential markers for papillary thyroid carcinoma: A proteomic study

2018 ◽  
Vol 33 (4) ◽  
pp. 455-462 ◽  
Author(s):  
Reyhaneh Farrokhi Yekta ◽  
Afsaneh Arefi Oskouie ◽  
Mostafa Rezaei Tavirani ◽  
Mohammad R. Mohajeri-Tehrani ◽  
Ahmad R. Soroush
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Papillary Thyroid Cancer ◽  
Complement Component ◽  
Assay Method ◽  
Enzyme Linked Immunosorbent Assay ◽  
Thyroid Tumors ◽  
Papillary Thyroid ◽  
Complement Component 3

Background: Thyroid carcinomas have comprised the fastest rising incidence of cancer in the past decade. Currently, the diagnosis of thyroid tumors is performed by the fine-needle aspiration biopsy (FNAB) method, which still holds some challenges and limitations, mostly in discriminating malignant and benign lesions. Therefore, the development of molecular markers to distinguish between these lesion types are in progress. Methods: A 2D-PAGE separation of proteins was performed followed by tandem mass spectrometry with the aim of discovering potential serum protein markers for papillary thyroid carcinoma and multinodular goiter. Protein–protein interaction network analysis revealed the most important pathways involved in the progression of papillary thyroid cancer. The enzyme-linked immunosorbent assay method was used to confirm a part of the results. Results: The significantly altered proteins included C3, C4A, GC, HP, TTR, APOA4, APOH, ORM2, KRT10, AHSG, IGKV3-20, and IGKC. We also confirmed that increased complement component 3 and decreased apolipoprotein A4 occurred in papillary thyroid cancer. Network investigations demonstrated that complement activation cascades and PPAR signaling might play a role in the pathogenesis of thyroid cancer. Conclusion: The results demonstrated that serum proteomics could serve as a viable method for proposing novel potential markers for thyroid tumors. Surely, further research must be performed in larger cohorts to validate the results.

scholarly journals Lymphovascular invasion is associated with survival for papillary thyroid cancer

2016 ◽  
Vol 23 (7) ◽  
pp. 555-562 ◽  
Author(s):  
Lauren N Pontius ◽  
Linda M Youngwirth ◽  
Samantha M Thomas ◽  
Randall P Scheri ◽  
Sanziana A Roman ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Lymph Nodes ◽  
Papillary Thyroid Cancer ◽  
Lymphovascular Invasion ◽  
Distant Metastases ◽  
Cox Proportional Hazards Model ◽  
Papillary Thyroid ◽  
Metastatic Lymph Nodes ◽  
Cancer Data ◽  
Metastatic Lymph

Data are limited regarding the association between tumor lymphovascular invasion and survival for patients with papillary thyroid cancer (PTC). This study sought to examine lymphovascular invasion as an independent prognostic factor for patients with PTC undergoing thyroid resection. The National Cancer Data Base (2010–2011) was queried for patients with PTC who underwent total thyroidectomy or lobectomy. Patients were classified into two groups based on the presence/absence of lymphovascular invasion. Demographic, clinical and pathological features were evaluated for all patients. A Cox proportional hazards model was utilized to identify factors associated with survival. Results show that 45,415 patients met inclusion criteria; 11.6% had lymphovascular invasion. Patients with lymphovascular invasion were more likely to have larger tumors (2.8cm vs 1.5cm,P<0.01), metastatic lymph nodes (74.1% vs 32.5%,P<0.01), and distant metastases (3.0% vs 0.5%,P<0.01). They were also more likely to receive radioactive iodine (69.3% vs 44.9%,P<0.01). Unadjusted overall 5-year survival was lower for patients who had tumors with lymphovascular invasion (86.6% vs 94.5%) (log-rankP<0.01). After adjustment, increasing patient age (HR=1.06,P<0.01), male gender (HR=1.68,P<0.01), presence of metastatic lymph nodes (HR=1.77,P<0.01), distant metastases (HR=3.49,P<0.01), and lymphovascular invasion (HR=1.88,P<0.01) were associated with compromised survival. For patients with lymphovascular invasion, treatment with RAI was associated with reduced mortality (HR=0.43,P<0.01). The presence of lymphovascular invasion among patients with PTC is independently associated with compromised survival. Patients who have PTC with lymphovascular invasion should be considered higher risk, and adjuvant RAI should be more strongly considered.

scholarly journals The Outcome of Papillary Thyroid Cancer Associated with Graves’ Disease: A Case Control Study

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Riju Menon ◽  
C. Gopalakrishnan Nair ◽  
Misha Babu ◽  
Pradeep Jacob ◽  
G. Praveen Krishna
Keyword(s):  
Thyroid Cancer ◽  
Disease Progression ◽  
Papillary Thyroid Cancer ◽  
Case Control Study ◽  
Distant Metastases ◽  
Case Control ◽  
Graves Disease ◽  
Papillary Thyroid ◽  
Thyroid Cancers ◽  
Control Study

Introduction. Thyroidectomy is now a less popular therapeutic option for Graves’ disease. The frequency of thyroid nodule and the cancer risk of these nodules accompanying Graves’ disease are controversial. The outcome of thyroid cancers coexisting with Graves’ disease is debated. Study Design. Designed as retrospective case control study of papillary thyroid cancers associated with Graves’ disease and those with euthyroid background. Pathological characteristics and outcome of papillary thyroid cancers in the two groups were compared. Results. The tumour characteristics did not differ significantly in the groups. The patients were followed for a mean period of 77.32 months and found significant incidences of disease progression in patients with papillary thyroid cancer associated with Graves’ disease (p=0.034; OR 2.747, CI 1.078–7.004). Disease progression as new distant metastases mostly in skeletal locations was high in this group compared to euthyroid group (p=0.027; OR 4.121, CI 1.008–15.600). There was higher incidence of cumulative metastatic diseases in papillary thyroid cancer associated with Graves’ disease. Conclusion. Papillary thyroid cancers associated with Graves’ disease show aggressive biological behaviour and favoured site of distant metastases was osseous locations. Early diagnosis by routine screening of Graves’ disease patients with ultrasound imaging and aspiration studies is recommended.

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