Review
Medicine, General & Internal
D. E. Zantut-Wittmann, A. C. Laus, D. A. Moreno, I. S. Barreto, C. A. Moma, F. F. R. Maia, E. C. S. C. Etchebehere, L. V. M. Assumpcao, R. M. Reis
Summary: BRAF and TERT oncogenes hotspot mutations are associated with a more aggressive outcome in thyroid carcinomas. TERT promoter (pTERT) mutations (C228T and C250T) are related to cancer growth and reduced overall-and disease-free survivals in TC. This report describes a patient with a poorly differentiated thyroid carcinoma (PDTC) who developed a large volume of metastases in a short period, and molecular analysis revealed two pTERT mutations (C228T and C250T), suggesting a relationship between pTERT mutations and aggressive course in PDTC.
AMERICAN JOURNAL OF THE MEDICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Miguel A. Zaballos, Adrian Acuna-Ruiz, Marta Morante, Garcilaso Riesco-Eizaguirre, Piero Crespo, Pilar Santisteban
Summary: The study demonstrates that BRAF- and RAS-mutant thyroid cells respond differently to DEL-22379, which cannot be explained by the previously described mechanism of action of the inhibitor. Nonetheless, DEL-22379 exhibits significant anti-tumor effects against BRAF-mutant cells in vivo, while the anti-tumor effects are mild for RAS-mutant cells.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Medicine, General & Internal
Yun-Suk Choi, Seong-Woon Choi, Jin-Wook Yi
Summary: This study identified TERT promoter mutations in PTC and found that they are associated with more aggressive behavior. Patients with TERT promoter mutations were older, had larger tumors, and exhibited other adverse clinical features, resulting in a poorer prognosis compared to those with wild-type TERT gene status.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Oncology
Sama Alohali, Alexandra. E. E. Payne, Marc Pusztaszeri, Mohannad Rajab, Veronique-Isabelle Forest, Michael. P. P. Hier, Michael Tamilia, Richard. J. J. Payne
Summary: As molecular testing of thyroid nodules becomes more common, it is important for thyroid specialists to understand the clinical implications of the results. This study found that patients with both TERT promoter mutations and other concurrent mutations were 10 times more likely to have aggressive thyroid cancers. These findings can assist thyroid specialists in accurately interpreting molecular testing and providing appropriate counseling and management options.
Article
Cell Biology
Bin Xu, Julia David, Snjezana Dogan, Inigo Landa, Nora Katabi, Maelle Saliba, Anjanie Khimraj, Eric J. Sherman, Robert Michael Tuttle, Giovanni Tallini, Ian Ganly, James A. Fagin, Ronald A. Ghossein
Summary: This study found that high-grade non-anaplastic thyroid carcinomas (HGTC) can be classified into two distinct subtypes, HGTC-PDTC and HGTC-nonPDTC, based on clinicopathological and molecular features. Factors such as age, gender, tumor characteristics, and molecular alterations have significant impact on prognosis, with the coexistence of BRAF V600E and TERT increasing the risk of metastasis.
Article
Oncology
Sabine Waechter, Pietro Di Fazio, Elisabeth Maurer, Jerena Manoharan, Corinna Keber, Andreas Pfestroff, Damiano Librizzi, Detlef K. Bartsch, Markus Luster, Friederike Eilsberger
Summary: The study found that F-18-FDG-PET/CT has higher diagnostic sensitivity and superiority in the diagnosis of ATC and PDTC compared to Ga-68-PSMA-PET/CT. However, Ga-68-PMSA-PET/CT can be considered as a beneficial adjunct to F-18-FDG-PET/CT for selected individual patients to detect lesions not discovered by F-18-FDG-PET/CT and to determine eligibility for radioligand therapy.
Review
Endocrinology & Metabolism
Vincent Cracolici, Nicole A. Cipriani
Summary: Poorly differentiated thyroid carcinoma (PDTC) and high-grade differentiated thyroid carcinoma (HGDTC) are high-grade follicular-derived thyroid carcinomas with intermediate prognosis. They share similar characteristics such as invasion, thyroid follicular-cell origin, and increased mitoses. PDTC must possess certain growth patterns and lack certain nuclear features, while HGDTC can have various architectural and nuclear morphologies. These carcinomas often present with metastases or wide local invasion and may require targeted chemotherapy due to resistance to radioactive iodine. Early recognition of high-grade features is important for patient prognosis and guiding treatment.
ENDOCRINE PATHOLOGY
(2023)
Article
Endocrinology & Metabolism
Li Zhang, Shanshan Zheng, Yan Qin, Xuelian Chen, Shengyu Zhou
Summary: This study aimed to explore the efficacy of immune checkpoint inhibitors (ICIs) combined with kinase inhibitors (KIs) or chemotherapy (CT) for anaplastic thyroid carcinoma (ATC) or poorly differentiated thyroid carcinoma (PDTC). The results suggest that the combination therapy of ICIs with CT or KIs may achieve a better therapeutic effect and early use of ICIs could be beneficial for patients with ATC or PDTC.
JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS
(2023)
Article
Endocrinology & Metabolism
Hee Young Na, Hyeong Won Yu, Woochul Kim, Jae Hoon Moon, Chang Ho Ahn, Sang Il Choi, Yeo Koon Kim, June Young Choi, So Yeon Park
Summary: This study reveals a relatively low frequency of TERT promoter mutations in Korean patients with PTC. Certain clinicopathological features including old age, tall cell variant, increased mitoses, tumour necrosis, and gross extrathyroidal extension were found to be indicative of TERT promoter mutations in PTCs.
CLINICAL ENDOCRINOLOGY
(2022)
Review
Oncology
Alessandro Prete, Antonio Matrone, Carla Gambale, Liborio Torregrossa, Elisa Minaldi, Cristina Romei, Raffaele Ciampi, Eleonora Molinaro, Rossella Elisei
Summary: Researchers have produced promising data on the genetics and tumor microenvironment of poorly differentiated thyroid cancer and anaplastic thyroid cancer. Despite their rarity, these cancers pose a significant clinical problem due to poor survival and the inefficacy of traditional therapies. New evidence is changing the treatment landscape for these cancers.
Article
Endocrinology & Metabolism
Christine Dierks, Jochen Seufert, Konrad Aumann, Juri Ruf, Claudius Klein, Selina Kiefer, Michael Rassner, Melanie Boerries, Andreas Zielke, Paul la Rosee, Philipp Tobias Meyer, Matthias Kroiss, Christian Weissenberger, Tilmann Schumacher, Patrick Metzger, Harald Weiss, Constantin Smaxwil, Katharina Laubner, Justus Duyster, Nikolas von Bubnoff, Cornelius Miething, Oliver Thomusch
Summary: The combination therapy of lenvatinib and pembrolizumab may be safe and effective in patients with ATC/PDTC, resulting in complete and long-term remissions.
Article
Endocrinology & Metabolism
Zhuan-Zhuan Mu, Ying-Qiang Zhang, Di Sun, Tao Lu, Yan-Song Lin
Summary: Based on the research conducted on patients with differentiated thyroid cancer, it was found that the coexistence of BRAF V600E mutation and TERT promoter mutation leads to a poor response to radioactive iodine therapy in distant metastatic cancers.
ENDOCRINE PRACTICE
(2022)
Article
Oncology
Caitlin O. Caperton, Lee Ann Jolly, Nicole Massoll, Andrew J. Bauer, Aime T. Franco
Summary: Advancements in thyroid cancer research rely on access to experimental models for laboratory investigation. The development and characterization of three novel follicular thyroid cancer (FTC) cell lines from relevant animal models have been demonstrated. These cell lines exhibit potential for in vitro applications and transplantation into immunocompetent hosts, providing insights into the heterogeneity of pathogenesis in thyroid cancer.
Review
Oncology
Jiaqian Yuan, Yong Guo
Summary: Anaplastic thyroid carcinoma (ATC) is a rare and highly aggressive tumor that is resistant to traditional antitumor therapies. In recent years, targeted therapy has emerged as a promising treatment strategy, offering hope to patients with this malignant disease. This review summarizes the efficacy and adverse effects of various targeted drugs, providing valuable information for future research and clinical decision-making.
Article
Multidisciplinary Sciences
Jayoung Moon, Jeong Hoon Lee, Jin Roh, Da Hyun Lee, Eun Ju Ha
Summary: This study develops a predictive model using radiomics feature analysis to distinguish anaplastic thyroid carcinoma/poorly differentiated thyroid carcinoma (ATC/PDTC) from differentiated thyroid carcinoma (DTC) in patients with large thyroid malignancies. The diagnostic performance of the model, based on radiomics features alone, achieves an area under the receiver operating characteristic (AUROC) curve value of 0.883. By incorporating both radiomics and clinicoradiological information, the model achieves an AUROC of 0.908. The most useful factors for differential diagnosis include distant metastasis, moment, shape, age, and gray-level size zone matrix features.
SCIENTIFIC REPORTS
(2023)
Article
Pathology
Bin Xu, Maelle Saliba, Alan Ho, Kartik Viswanathan, Bayan Alzumaili, Snjezana Dogan, Ronald Ghossein, Nora Katabi
Summary: This study aimed to establish a histologic grading scheme for low-grade acinic cell carcinoma (AciCC) and found that factors such as age, tumor necrosis, and nuclear anaplasia were adverse prognostic factors. High-grade AciCC defined by mitotic count and/or necrosis was associated with worse overall survival. NR4A3 immunohistochemical stain showed high sensitivity and specificity for diagnosing AciCC. Further studies are needed to assess the prognostic value of intermediate grade.
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
(2022)
Article
Pathology
Bayan Alzumaili, Bin Xu, Maelle Saliba, Abderhman Abuhashem, Ian Ganly, Ronald Ghossein, Nora Katabi
Summary: This study investigates the prognostic features of primary and recurrent pleomorphic adenoma (PA) and finds that age, mitosis, and resection quality are key factors in predicting recurrence.
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
(2022)
Article
Oncology
Bin Xu, Talia L. Fuchs, Sara Ahmadi, Mohammed Alghamdi, Bayan Alzumaili, Mohamed-Amine Bani, Eric Baudin, Angela Chou, Antonio De Leo, James A. Fagin, Ian Ganly, Anthony Glover, Dana Hartl, Christina Kanaan, Pierre Khneisser, Fedaa Najdawi, Aradhya Nigam, Alex Papachristos, Andrea Repaci, Philip M. Spanheimer, Erica Solaroli, Brian R. Untch, Justine A. Barletta, Giovanni Tallini, Abir Al Ghuzlan, Anthony J. Gill, Ronald A. Ghossein
Summary: This study aimed to establish an internationally recognized grading system for medullary thyroid carcinoma (MTC) to predict adverse outcomes by evaluating mitotic activity, Ki67 proliferative index, and tumor necrosis in MTC.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Oncology
Mark Lee, Brian R. Untch, Bin Xu, Ronald Ghossein, Catherine Han, Fengshen Kuo, Cristina Valero, Zaineb Nadeem, Neal Patel, Vladimir Makarov, Snjezana Dogan, Richard J. Wong, Eric J. Sherman, Alan L. Ho, Timothy A. Chan, James A. Fagin, Luc G. T. Morris
Summary: Targeted inhibition of BRAF V600E can control a subset of advanced thyroid tumors, but nearly all the tumors develop resistance and some undergo dedifferentiation. Through analysis of next-generation sequencing data, this study identified molecular alterations associated with thyroid cancer dedifferentiation in the setting of BRAF inhibition. These findings provide insights into the mechanisms of resistance and tumor dedifferentiation.
MOLECULAR CANCER RESEARCH
(2022)
Article
Oncology
Yiyu Dong, Yongxing Gong, Fengshen Kuo, Vladimir Makarov, Ed Reznik, Gouri J. Nanjangud, Omer Aras, Huiyong Zhao, Rui Qu, James A. Fagin, Eric J. Sherman, Bin Xu, Ronald Ghossein, Timothy A. Chan, Ian Ganly
Summary: Hurthle cell carcinomas (HCCs) are resistant to radioactive iodine and chemotherapy, but targeting mTOR signaling can suppress tumor growth and proliferation, making it a potential novel treatment strategy for HCC.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Multidisciplinary Sciences
Ian Ganly, Eric Minwei Liu, Fengshen Kuo, Vladimir Makarov, Yiyu Dong, Jinsung Park, Yongxing Gong, Alexander N. Gorelick, Jeffrey A. Knauf, Elisa Benedetti, Jacqueline Tait-Mulder, Luc G. T. Morris, James A. Fagin, Andrew M. Intlekofer, Jan Krumsiek, Payam A. Gammage, Ronald Ghossein, Bin Xu, Timothy A. Chan, Ed Reznik
Summary: This study analyzed genomic, metabolomic, and immunophenotypic data of HCC and other thyroid cancers. The results showed that HCC and other thyroid malignancies commonly exhibit mtDNA mutations and depletion of citrate pools, while HCC specifically has elevated metabolites in the reduced form of NADH-dependent lysine degradation pathway. The presence of gLOH is associated with reduced immune infiltration. Additionally, unsupervised clustering identified four clusters of HCC with distinct clinical, metabolomic, and microenvironmental phenotypes.
Review
Pathology
Bin Xu, Ronald A. Ghossein
Summary: This review summarizes the major evolutions of HGFCTC and ATC. HGFCTC is a nonanaplastic carcinoma, which can be divided into poorly differentiated thyroid carcinoma and differentiated high grade thyroid carcinoma. ATC can show a wide range of histologic features. There is a stepwise molecular progression from well-differentiated carcinoma to HGFCTC to ATC.
ADVANCES IN ANATOMIC PATHOLOGY
(2023)
Article
Pathology
Maelle Saliba, Bayan A. Alzumaili, Nora Katabi, Snjezana Dogan, Robert M. Tuttle, Antal Zoltan, Neeta Pandit-Taskar, Bin Xu, Ronald A. Ghossein
Summary: This study found that the prognosis of pediatric thyroid carcinomas (TCs) differs from that of adults with similar histologic features. High-risk histologic variants, such as PTC-DSV and tumors with necrosis, are associated with worse disease-free survival (DFS) in pediatric TCs.
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
(2022)
Article
Pathology
Justine A. Barletta, Steven D. Gilday, Michelle Afkhami, Diana Bell, Theresa Bocklage, Pierre Boisselier, Nicole G. Chau, Nicole A. Cipriani, Valerie Costes-Martineau, Ronald A. Ghossein, Hans J. Hertzler, Alan M. Kramer, Sewanti Limaye, Carlos A. Lopez, Tony L. Ng, Annikka Weissferdt, Bin Xu, Songlin Zhang, Christopher A. French
Summary: In this study of 14 cases of NUT carcinoma of the thyroid, we found that the morphological types of NUT tumors varied, with some cases resembling other thyroid tumors. Immunohistochemistry results showed a high positivity rate for NUT, with differences in positivity for other markers in comparison to tumors with a non-NUT morphology. We also found a high rate of NSD3-NUTM1 fusion and a relatively protracted clinical course compared to other thyroid NUT carcinomas.
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
(2022)
Article
Endocrinology & Metabolism
Ronald Ghossein, Ian Ganly, R. Michael Tuttle, Bin Xu
Summary: This retrospective cohort study of 88 patients with large encapsulated thyroid carcinoma showed that there is a negligible risk of recurrence for tumors without vascular invasion. For this selected group of patients, lobectomy alone may be the appropriate treatment strategy.
Review
Oncology
Albert J. H. Suurmeijer, Bin Xu, Dianne Torrence, Brendan C. Dickson, Cristina R. Antonescu
Summary: This article describes the clinicopathologic and molecular data of eight bone tumors with various kinase fusions, and combines them with previously reported cases for analysis. These tumors mainly occur in the head and neck area, and most commonly affect young children and teenagers. The fusions involve a variety of kinase genes and show different expression patterns in different tumor types. The findings provide further insights into these tumors.
GENES CHROMOSOMES & CANCER
(2023)
Article
Cell Biology
Nora Katabi, Purvil Sukhadia, Sara E. Dinapoli, Ilan Weinreb, Elan Hahn, Ronald Ghossein, Bin Xu
Summary: Salivary gland neoplasms with HMGA2::WIF1 fusion exhibit histological and immunohistochemical features similar to CAA, and these tumors are not always benign, with approximately 20% showing malignancy.
Article
Cell Biology
Ying-Hsia Chu, Kerry Mullaney, Sara E. Dinapoli, Marc A. Cohen, Bin Xu, Ronald Ghossein, Nora Katabi, Snjezana Dogan
Summary: FHNC is a type of head and neck cancer with squamous features, occurring in different locations of the head and neck. Sinonasal cases may harbor FGFR rearrangement along with high-risk HPV infection. Timely recognition of FHNC could help select patients for targeted therapy with FGFR inhibitors.
Article
Medicine, Research & Experimental
Cristina Valero, Mahdi Golkaram, Joris L. Vos, Bin Xu, Conall Fitzgerald, Mark Lee, Shannon Kaplan, Catherine Y. Han, Xin Pei, Reith Sarkar, Lillian A. Boe, Abhinav Pandey, Elizabeth S. Koh, Charlotte L. Zuur, David B. Solit, Traci Pawlowski, Li Liu, Alan L. Ho, Diego Chowell, Nadeem Riaz, Timothy A. Chan, Luc G. T. Morris
Summary: This study analyzed the clinical and genomic features of 133 ICB-treated patients with R/M HNSCC and identified 6 molecular subtypes that determine the response to ICB therapy. A predictive model based on clinical and genomic features outperformed the current biomarker of TMB alone. This validated predictive tool can help with clinical risk stratification in patients with R/M HNSCC considering ICB treatment.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Oncology
Ian Ganly, Fengshen Kuo, Vladimir Makarov, Yiyu Dong, Ronald Ghossein, Bin Xu, Luc G. T. Morris, Timothy A. Chan
Summary: Hurthle cell carcinoma (HCC) is a rare type of thyroid cancer with poorly defined immunologic features and unknown response rates to immunotherapy. This study analyzed the immune microenvironment of HCC and found low levels of immune infiltration, which were associated with chromosomal uniparental disomy and haploidization. These findings are significant for understanding the functional immune landscape of HCC and identifying potential immunologic vulnerabilities.
CANCER RESEARCH COMMUNICATIONS
(2023)