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Primary Versus Secondary Anaplastic Thyroid Carcinoma: Perspectives from Multi-institutional and Population-Level Data

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Abstract

Primary (or de novo) anaplastic thyroid carcinoma (ATC) is ATC without pre-existing history of differentiated thyroid carcinoma (DTC) and no co-existing DTC foci at the time of diagnosis. Secondary ATC is diagnosed if the patient had a history of DTC or co-existing DTC components at time of diagnosis. This study aimed to investigate the incidence, clinical presentations, outcomes, and genetic backgrounds of primary versus secondary ATCs. We searched for ATCs in our institutional databases and the Surveillance, Epidemiology, and End Result (SEER) database. We also performed a systematic review and meta-analysis to analyze the genetic alterations of primary and secondary ATCs. From our multi-institutional database, 22 primary and 23 secondary ATCs were retrieved. We also identified 620 and 24 primary and secondary ATCs in the SEER database, respectively. Compared to primary ATCs, secondary ATCs were not statistically different in terms of demographic, clinical manifestations, and patient survival. The only clinical discrepancy between the two groups was a significantly larger tumor diameter of the primary ATCs. The prevalence of TERT promoter, PIK3CA, and TP53 mutations was comparable between the two subtypes. In comparison to primary ATCs, however, BRAF mutations were more prevalent (OR = 4.70; 95% CI = 2.84–7.78) whereas RAS mutations were less frequent (OR = 0.43; 95% CI = 0.21–0.85) in secondary tumors. In summary, our results indicated that de novo and secondary ATCs might share many potential developmental steps, but there are other factors that suggest distinct developmental pathways.

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References

  1. Deeken-Draisey A, Yang GY, Gao J, Alexiev BA (2018) Anaplastic thyroid carcinoma: an epidemiologic, histologic, immunohistochemical, and molecular single-institution study. Hum Pathol 82:140-148. https://doi.org/10.1016/j.humpath.2018.07.027

    Article  CAS  PubMed  Google Scholar 

  2. de Ridder M, Nieveen van Dijkum E, Engelsman A, Kapiteijn E, Klümpen HJ, Rasch CRN (2020) Anaplastic thyroid carcinoma: a nationwide cohort study on incidence, treatment and survival in the Netherlands over 3 decades. Eur J Endocrinol 183 (2):203-209. https://doi.org/10.1530/eje-20-0080

    Article  CAS  PubMed  Google Scholar 

  3. Lin B, Ma H, Ma M, Zhang Z, Sun Z, Hsieh IY, Okenwa O, Guan H, Li J, Lv W (2019) The incidence and survival analysis for anaplastic thyroid cancer: a SEER database analysis. Am J Transl Res 11 (9):5888-5896

    PubMed  PubMed Central  Google Scholar 

  4. Akslen LA, Haldorsen T, Thoresen SO, Glattre E (1990) Incidence of thyroid cancer in Norway 1970–1985. Population review on time trend, sex, age, histological type and tumour stage in 2625 cases. Apmis 98 (6):549–558

  5. Are C, Shaha AR (2006) Anaplastic thyroid carcinoma: biology, pathogenesis, prognostic factors, and treatment approaches. Ann Surg Oncol 13 (4):453-464. https://doi.org/10.1245/aso.2006.05.042

    Article  PubMed  Google Scholar 

  6. McIver B, Hay ID, Giuffrida DF, Dvorak CE, Grant CS, Thompson GB, van Heerden JA, Goellner JR (2001) Anaplastic thyroid carcinoma: a 50-year experience at a single institution. Surgery 130 (6):1028-1034. https://doi.org/10.1067/msy.2001.118266

    Article  CAS  PubMed  Google Scholar 

  7. Oishi N, Kondo T, Ebina A, Sato Y, Akaishi J, Hino R, Yamamoto N, Mochizuki K, Nakazawa T, Yokomichi H, Ito K, Ishikawa Y, Katoh R (2017) Molecular alterations of coexisting thyroid papillary carcinoma and anaplastic carcinoma: identification of TERT mutation as an independent risk factor for transformation. Mod Pathol 30 (11):1527-1537. https://doi.org/10.1038/modpathol.2017.75

    Article  CAS  PubMed  Google Scholar 

  8. Nel CJ, van Heerden JA, Goellner JR, Gharib H, McConahey WM, Taylor WF, Grant CS (1985) Anaplastic carcinoma of the thyroid: a clinicopathologic study of 82 cases. Mayo Clin Proc 60 (1):51-58. https://doi.org/10.1016/s0025-6196(12)65285-9

    Article  CAS  PubMed  Google Scholar 

  9. Venkatesh YS, Ordonez NG, Schultz PN, Hickey RC, Goepfert H, Samaan NA (1990) Anaplastic carcinoma of the thyroid. A clinicopathologic study of 121 cases. Cancer 66 (2):321–330.

  10. Lam KY, Lo CY, Chan KW, Wan KY (2000) Insular and anaplastic carcinoma of the thyroid: a 45-year comparative study at a single institution and a review of the significance of p53 and p21. Ann Surg 231 (3):329-338. https://doi.org/10.1097/00000658-200003000-00005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Harada T, Ito K, Shimaoka K, Hosoda Y, Yakumaru K (1977) Fatal thyroid carcinoma. Anaplastic transformation of adenocarcinoma. Cancer 39 (6):2588-2596.

  12. Molinaro E, Romei C, Biagini A, Sabini E, Agate L, Mazzeo S, Materazzi G, Sellari-Franceschini S, Ribechini A, Torregrossa L, Basolo F, Vitti P, Elisei R (2017) Anaplastic thyroid carcinoma: from clinicopathology to genetics and advanced therapies. Nat Rev Endocrinol 13 (11):644-660. https://doi.org/10.1038/nrendo.2017.76

    Article  CAS  PubMed  Google Scholar 

  13. Quiros RM, Ding HG, Gattuso P, Prinz RA, Xu X (2005) Evidence that one subset of anaplastic thyroid carcinomas are derived from papillary carcinomas due to BRAF and p53 mutations. Cancer 103 (11):2261-2268. https://doi.org/10.1002/cncr.21073

    Article  CAS  PubMed  Google Scholar 

  14. Xu B, Fuchs T, Dogan S, Landa I, Katabi N, Fagin JA, Tuttle RM, Sherman E, Gill AJ, Ghossein R (2020) Dissecting Anaplastic Thyroid Carcinoma: A Comprehensive Clinical, Histologic, Immunophenotypic, and Molecular Study of 360 Cases. Thyroid 30 (10):1505-1517. https://doi.org/10.1089/thy.2020.0086

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Landa I, Ibrahimpasic T, Boucai L, Sinha R, Knauf JA, Shah RH, Dogan S, Ricarte-Filho JC, Krishnamoorthy GP, Xu B, Schultz N, Berger MF, Sander C, Taylor BS, Ghossein R, Ganly I, Fagin JA (2016) Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers. J Clin Invest 126 (3):1052-1066. https://doi.org/10.1172/jci85271

    Article  PubMed  PubMed Central  Google Scholar 

  16. National Cancer Institute (2012) 2007 Multiple Primary and Histology Coding Rules. https://seer.cancer.gov/tools/mphrules/. Accessed 24 April 2021

  17. Chen TY, Lorch JH, Wong KS, Barletta JA (2020) Histological features of BRAF V600E-mutant anaplastic thyroid carcinoma. Histopathology 77 (2):314-320. https://doi.org/10.1111/his.14144

    Article  PubMed  Google Scholar 

  18. Lai WA, Liu CY, Lin SY, Chen CC, Hang JF (2020) Characterization of Driver Mutations in Anaplastic Thyroid Carcinoma Identifies RAS and PIK3CA Mutations as Negative Survival Predictors. Cancers (Basel) 12 (7). https://doi.org/10.3390/cancers12071973

  19. Mochizuki K, Kondo T, Nakazawa T, Iwashina M, Kawasaki T, Nakamura N, Yamane T, Murata S, Ito K, Kameyama K, Kobayashi M, Katoh R (2010) RET rearrangements and BRAF mutation in undifferentiated thyroid carcinomas having papillary carcinoma components. Histopathology 57 (3):444-450. https://doi.org/10.1111/j.1365-2559.2010.03646.x

    Article  PubMed  Google Scholar 

  20. Nikiforova MN, Kimura ET, Gandhi M, Biddinger PW, Knauf JA, Basolo F, Zhu Z, Giannini R, Salvatore G, Fusco A, Santoro M, Fagin JA, Nikiforov YE (2003) BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas. J Clin Endocrinol Metab 88 (11):5399-5404. https://doi.org/10.1210/jc.2003-030838

    Article  CAS  PubMed  Google Scholar 

  21. Rao SN, Zafereo M, Dadu R, Busaidy NL, Hess K, Cote GJ, Williams MD, William WN, Sandulache V, Gross N, Gunn GB, Lu C, Ferrarotto R, Lai SY, Cabanillas ME (2017) Patterns of Treatment Failure in Anaplastic Thyroid Carcinoma. Thyroid 27 (5):672-681. https://doi.org/10.1089/thy.2016.0395

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Rashid M, Agarwal A, Pradhan R, George N, Kumari N, Sabaretnam M, Chand G, Mishra A, Agarwal G, Mishra SK (2019) Genetic Alterations in Anaplastic Thyroid Carcinoma. Indian J Endocrinol Metab 23 (4):480-485. https://doi.org/10.4103/ijem.IJEM_321_19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Takano T, Ito Y, Hirokawa M, Yoshida H, Miyauchi A (2007) BRAF V600E mutation in anaplastic thyroid carcinomas and their accompanying differentiated carcinomas. Br J Cancer 96 (10):1549-1553. https://doi.org/10.1038/sj.bjc.6603764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Tiedje V, Ting S, Herold T, Synoracki S, Latteyer S, Moeller LC, Zwanziger D, Stuschke M, Fuehrer D, Schmid KW (2017) NGS based identification of mutational hotspots for targeted therapy in anaplastic thyroid carcinoma. Oncotarget 8 (26):42613-42620. https://doi.org/10.18632/oncotarget.17300

    Article  PubMed  PubMed Central  Google Scholar 

  25. Wang HM, Huang YW, Huang JS, Wang CH, Kok VC, Hung CM, Chen HM, Tzen CY (2007) Anaplastic carcinoma of the thyroid arising more often from follicular carcinoma than papillary carcinoma. Ann Surg Oncol 14 (10):3011-3018. https://doi.org/10.1245/s10434-007-9503-8

    Article  PubMed  Google Scholar 

  26. Wong KS, Lorch JH, Alexander EK, Marqusee E, Cho NL, Nehs MA, Doherty GM, Barletta JA (2020) Histopathologic Features and Clinical Outcome of Anaplastic Thyroid Carcinoma with a Minor Anaplastic Component. Endocr Pathol 31 (3):283-290. https://doi.org/10.1007/s12022-020-09627-0

    Article  PubMed  Google Scholar 

  27. Tan RK, Finley RK, 3rd, Driscoll D, Bakamjian V, Hicks WL, Jr., Shedd DP (1995) Anaplastic carcinoma of the thyroid: a 24-year experience. Head Neck 17 (1):41–47; discussion 47–48.https://doi.org/10.1002/hed.2880170109

  28. Rodriguez JM, Piñero A, Ortiz S, Moreno A, Sola J, Soria T, Robles R, Parrilla P (2000) Clinical and histological differences in anaplastic thyroid carcinoma. Eur J Surg 166 (1):34-38. https://doi.org/10.1080/110241500750009672

    Article  CAS  PubMed  Google Scholar 

  29. Kapp DS, LiVolsi VA, Sanders MM (1982) Anaplastic carcinoma following well-differentiated thyroid cancer: etiological considerations. Yale J Biol Med 55 (5-6):521-528

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Gétaz EP, Shimaoka K (1979) Anaplastic cardcinoma of the thyroid in a population irradiated for Hodgkin disease, 1910–1960. J Surg Oncol 12 (2):181-189. https://doi.org/10.1002/jso.2930120213

    Article  PubMed  Google Scholar 

  31. Nishiyama RH, Dunn EL, Thompson NW (1972) Anaplastic spindle-cell and giant-cell tumors of the thyroid gland. Cancer 30 (1):113-127.

  32. Lai WA, Hang JF, Liu CY, Bai Y, Liu Z, Gu H, Hong S, Pyo JY, Jung CK, Kakudo K, Bychkov A (2020) PAX8 expression in anaplastic thyroid carcinoma is less than those reported in early studies: a multi-institutional study of 182 cases using the monoclonal antibody MRQ-50. Virchows Arch 476 (3):431-437. https://doi.org/10.1007/s00428-019-02708-4

    Article  CAS  PubMed  Google Scholar 

  33. Hirokawa M, Sugitani I, Kakudo K, Sakamoto A, Higashiyama T, Sugino K, Toda K, Ogasawara S, Yoshimoto S, Hasegawa Y, Imai T, Onoda N, Orita Y, Kammori M, Fujimori K, Yamada H (2016) Histopathological analysis of anaplastic thyroid carcinoma cases with long-term survival: A report from the Anaplastic Thyroid Carcinoma Research Consortium of Japan. Endocr J 63 (5):441-447. https://doi.org/10.1507/endocrj.EJ15-0705

    Article  CAS  PubMed  Google Scholar 

  34. Wiseman SM, Loree TR, Rigual NR, Hicks WL, Jr., Douglas WG, Anderson GR, Stoler DL (2003) Anaplastic transformation of thyroid cancer: review of clinical, pathologic, and molecular evidence provides new insights into disease biology and future therapy. Head Neck 25 (8):662-670. https://doi.org/10.1002/hed.10277

    Article  PubMed  Google Scholar 

  35. Odate T, Oishi N, Kawai M, Tahara I, Mochizuki K, Akaishi J, Ito K, Katoh R, Kondo T (2021) Progression of Papillary Thyroid Carcinoma to Anaplastic Carcinoma in Metastatic Lymph Nodes: Solid/Insular Growth and Hobnail Cell Change in Lymph Nodes Are Predictors of Subsequent Anaplastic Transformation. Endocr Pathol. https://doi.org/10.1007/s12022-021-09674-1

    Article  PubMed  PubMed Central  Google Scholar 

  36. Ragazzi M, Torricelli F, Donati B, Ciarrocchi A, de Biase D, Tallini G, Zanetti E, Bisagni A, Kuhn E, Giordano D, Frasoldati A, Piana S (2021) Coexisting well-differentiated and anaplastic thyroid carcinoma in the same primary resection specimen: immunophenotypic and genetic comparison of the two components in a consecutive series of 13 cases and a review of the literature. Virchows Arch 478 (2):265-281. https://doi.org/10.1007/s00428-020-02891-9

    Article  CAS  PubMed  Google Scholar 

  37. Roche AM, Fedewa SA, Shi LL, Chen AY (2018) Treatment and survival vary by race/ethnicity in patients with anaplastic thyroid cancer. Cancer 124 (8):1780-1790. https://doi.org/10.1002/cncr.31252

    Article  PubMed  Google Scholar 

  38. Bible KC, Kebebew E, Brierley J, Brito JP, Cabanillas ME, Clark TJ, Jr., Di Cristofano A, Foote R, Giordano T, Kasperbauer J, Newbold K, Nikiforov YE, Randolph G, Rosenthal MS, Sawka AM, Shah M, Shaha A, Smallridge R, Wong-Clark CK (2021) 2021 American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer. Thyroid 31 (3):337-386. https://doi.org/10.1089/thy.2020.0944

    Article  PubMed  Google Scholar 

  39. Smallridge RC, Marlow LA, Copland JA (2009) Anaplastic thyroid cancer: molecular pathogenesis and emerging therapies. Endocr Relat Cancer 16 (1):17-44. https://doi.org/10.1677/erc-08-0154

    Article  CAS  PubMed  Google Scholar 

  40. Xu B, Ghossein R (2016) Genomic Landscape of poorly Differentiated and Anaplastic Thyroid Carcinoma. Endocr Pathol 27 (3):205-212. https://doi.org/10.1007/s12022-016-9445-4

    Article  CAS  PubMed  Google Scholar 

  41. Pozdeyev N, Gay LM, Sokol ES, Hartmaier R, Deaver KE, Davis S, French JD, Borre PV, LaBarbera DV, Tan AC, Schweppe RE, Fishbein L, Ross JS, Haugen BR, Bowles DW (2018) Genetic Analysis of 779 Advanced Differentiated and Anaplastic Thyroid Cancers. Clin Cancer Res 24 (13):3059-3068. https://doi.org/10.1158/1078-0432.ccr-18-0373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Wallin G, Bäckdahl M, Tallroth-Ekman E, Lundell G, Auer G, Löwhagen T (1989) Co-existent anaplastic and well differentiated thyroid carcinomas: a nuclear DNA study. Eur J Surg Oncol 15 (1):43-48

    CAS  PubMed  Google Scholar 

  43. Capdevila J, Mayor R, Mancuso FM, Iglesias C, Caratù G, Matos I, Zafón C, Hernando J, Petit A, Nuciforo P, Cameselle-Teijeiro JM, Ålvarez CV, Recio JA, Tabernero J, Matias-Guiu X, Vivancos A, Seoane J (2019) Early evolutionary divergence between papillary and anaplastic thyroid cancers. Ann Oncol 30 (11):1843. https://doi.org/10.1093/annonc/mdz216

    Article  CAS  PubMed  Google Scholar 

  44. Paulsson JO, Backman S, Wang N, Stenman A, Crona J, Thutkawkorapin J, Ghaderi M, Tham E, Stålberg P, Zedenius J, Juhlin CC (2020) Whole-genome sequencing of synchronous thyroid carcinomas identifies aberrant DNA repair in thyroid cancer dedifferentiation. J Pathol 250 (2):183-194. https://doi.org/10.1002/path.5359

    Article  CAS  PubMed  Google Scholar 

  45. Luo H, Xia X, Kim GD, Liu Y, Xue Z, Zhang L, Shu Y, Yang T, Chen Y, Zhang S, Chen H, Zhang W, Li R, Tang H, Dong B, Fu X, Cheng W, Zhang W, Yang L, Peng Y, Dai L, Hu H, Jiang Y, Gong C, Hu Y, Zhu J, Li Z, Caulin C, Wei T, Park J, Xu H (2021) Characterizing dedifferentiation of thyroid cancer by integrated analysis. Sci Adv 7 (31).https://doi.org/10.1126/sciadv.abf3657

  46. Capdevila J, Mayor R, Mancuso FM, Iglesias C, Caratù G, Matos I, Zafón C, Hernando J, Petit A, Nuciforo P, Cameselle-Teijeiro JM, Ålvarez C, Recio JA, Tabernero J, Matias-Guiu X, Vivancos A, Seoane J (2018) Early evolutionary divergence between papillary and anaplastic thyroid cancers. Ann Oncol 29 (6):1454-1460. https://doi.org/10.1093/annonc/mdy123

    Article  CAS  PubMed  Google Scholar 

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Author notes

  1. Tam N. M. Ngo and Trang T. B. Le have equal contribution.

Authors and Affiliations

  1. Faculty of Medicine, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, 700-000, Vietnam

    Tam N. M. Ngo

  2. Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, 700-000, Vietnam

    Trang T. B. Le & Thoa Le

  3. Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand

    Andrey Bychkov

  4. Department of Pathology, Kameda Medical Center, Kamogawa, Chiba, 296-8602, Japan

    Andrey Bychkov

  5. Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8523, Japan

    Andrey Bychkov

  6. Department of Pathology, University of Yamanashi, Chuo, Yamanashi, 409-3898, Japan

    Naoki Oishi

  7. Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    Chan Kwon Jung

  8. Department of Pathology, Oklahoma University Health Sciences Center, Oklahoma City, OK, 73104, USA

    Lewis Hassell & Huy Gia Vuong

  9. Department of Pathology and Thyroid Disease Center, Izumi City General Hospital, Wake-cho 4-5-1, Izumi-city, 594-0073, Japan

    Kennichi Kakudo

  10. Department of Neurosurgery, Oklahoma University Health Sciences Center, Oklahoma City, OK, 73104, USA

    Huy Gia Vuong

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Contributions

TNMN: data curation, formal analysis, investigation, methodology, writing—original, writing—review. TTBL: data curation, formal analysis, investigation, methodology, writing—original, writing—review. TTBL: data curation, formal analysis, investigation, methodology, writing—review. AB: data curation, formal analysis, investigation, methodology, writing—review, editing. NO: data curation, formal analysis, investigation, methodology, writing—review, editing. CKJ: data curation, formal analysis, investigation, methodology, writing—review, editing. LH: data curation, formal analysis, investigation, methodology, writing—review, editing. KK: data curation, formal analysis, investigation, methodology, writing—review, editing. HGV: conceptualization, data curation, formal analysis, investigation, methodology, project administration, software, validation, writing—original, review, and editing. All authors have read and approved the manuscript.

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Correspondence to Huy Gia Vuong.

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Ngo, T.N.M., Le, T.T.B., Le, T. et al. Primary Versus Secondary Anaplastic Thyroid Carcinoma: Perspectives from Multi-institutional and Population-Level Data. Endocr Pathol 32, 489–500 (2021). https://doi.org/10.1007/s12022-021-09692-z

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