BRAF K601E Mutation in Oncocytic Carcinoma of the Thyroid: A Case Report and Literature Review

Overview

Journal J Clin Med

Specialty General Medicine

Date 2023 Nov 25

PMID 38002585

Authors

Antonio Matrone

Fabrizia Citro

Carla Gambale

Alessandro Prete

Elisa Minaldi

Raffaele Ciampi

Teresa Ramone

Gabriele Materazzi

Liborio Torregrossa

Rossella Elisei

Affiliations

Soon will be listed here.

Abstract

Background: Thyroid carcinoma (TC) is the most common endocrine cancer, with papillary thyroid carcinoma (PTC) being the most common subtype. BRAF and RAS oncogene were characterized as the most frequently altered genes in PTC, with a strong association between genotype and histotype. The most common mutation in BRAF gene is V600E and is prevalent in classic and aggressive variants of PTC, while BRAF K601E mutation is the most common among the other rare BRAF mutations. BRAF K601E mutated thyroid carcinomas are usually characterized by low aggressiveness, except for anecdotal cases of poorly differentiated TC.

Case Presentation: We described a case of oncocytic carcinoma of the thyroid (OCA) with an aggressive clinical course, including widespread metastasis and resistance to radioiodine treatment. Molecular analysis revealed the exclusive presence of the BRAF K601E mutation in both primary tumor and metastatic lesions. Accordingly, a revision of the literature about aggressive TC cases carrying BRAF K601E mutation was performed.

Conclusion: Although rare, this case emphasizes the relevance of considering BRAF K601E mutation in advanced non-PTC thyroid carcinomas, since it can be considered an actionable mutation for target therapies.

Citing Articles

Biomarkers in Thyroid Cancer: Emerging Opportunities from Non-Coding RNAs and Mitochondrial Space.

Cabane P, Correa C, Bode I, Aguilar R, Elorza A Int J Mol Sci. 2024; 25(12).

PMID: 38928426 PMC: 11204084. DOI: 10.3390/ijms25126719.

References

McFadden D, Sadow P . Genetics, Diagnosis, and Management of Hürthle Cell Thyroid Neoplasms. Front Endocrinol (Lausanne). 2021; 12:696386. PMC: 8223676. DOI: 10.3389/fendo.2021.696386. View

Matrone A, Campopiano M, Nervo A, Sapuppo G, Tavarelli M, De Leo S . Differentiated Thyroid Cancer, From Active Surveillance to Advanced Therapy: Toward a Personalized Medicine. Front Endocrinol (Lausanne). 2020; 10:884. PMC: 6961292. DOI: 10.3389/fendo.2019.00884. View

Cabanillas M, Ryder M, Jimenez C . Targeted Therapy for Advanced Thyroid Cancer: Kinase Inhibitors and Beyond. Endocr Rev. 2019; 40(6):1573-1604. PMC: 7341904. DOI: 10.1210/er.2019-00007. View

Schulten H, Salama S, Al-Mansouri Z, Alotibi R, Al-Ghamdi K, Al-Hamour O . BRAF mutations in thyroid tumors from an ethnically diverse group. Hered Cancer Clin Pract. 2012; 10(1):10. PMC: 3434056. DOI: 10.1186/1897-4287-10-10. View

Romei C, Tacito A, Molinaro E, Piaggi P, Cappagli V, Pieruzzi L . Clinical, pathological and genetic features of anaplastic and poorly differentiated thyroid cancer: A single institute experience. Oncol Lett. 2018; 15(6):9174-9182. PMC: 5958691. DOI: 10.3892/ol.2018.8470. View

Censi S, Cavedon E, Bertazza L, Galuppini F, Watutantrige-Fernando S, De Lazzari P . Frequency and Significance of Promoter, and Mutations in Cytologically Indeterminate Thyroid Nodules: A Monocentric Case Series at a Tertiary-Level Endocrinology Unit. Front Endocrinol (Lausanne). 2017; 8:273. PMC: 5650698. DOI: 10.3389/fendo.2017.00273. View

Macerola E, Torregrossa L, Ugolini C, Bakkar S, Vitti P, Fadda G . BRAF Mutation in a Follicular Thyroid Adenoma: A Case Report. Int J Surg Pathol. 2017; 25(4):348-351. DOI: 10.1177/1066896916688083. View

Jung C, Kim Y, Jeon S, Jo K, Lee S, Bae J . Clinical utility of EZH1 mutations in the diagnosis of follicular-patterned thyroid tumors. Hum Pathol. 2018; 81:9-17. DOI: 10.1016/j.humpath.2018.04.018. View

Parpounas C, Constantinides V . Advances in Molecular Profiling and Their Potential Influence on the Extent of Surgery in Well-Differentiated Thyroid Carcinoma (WDTC). Life (Basel). 2023; 13(6). PMC: 10304148. DOI: 10.3390/life13061382. View

10.

Sinno S, Choucair M, Nasrallah M, Wadi L, Jabbour M, Nassif S . Activating BRAF Mutations Detected in Mixed Hürthle Cell Carcinoma and Multifocal Papillary Carcinoma of the Thyroid Gland: Report of an Unusual Case and Review of the Literature. Int J Surg Pathol. 2016; 24(6):519-24. DOI: 10.1177/1066896916639377. View

11.

Matrone A, De Napoli L, Torregrossa L, Aghababyan A, Papini P, Ambrosini C . Core Needle Biopsy Can Early and Precisely Identify Large Thyroid Masses. Front Oncol. 2022; 12:854755. PMC: 9022105. DOI: 10.3389/fonc.2022.854755. View

12.

Pennelli G, Vianello F, Barollo S, Pezzani R, Merante Boschin I, Pelizzo M . BRAF(K601E) mutation in a patient with a follicular thyroid carcinoma. Thyroid. 2011; 21(12):1393-6. DOI: 10.1089/thy.2011.0120. View

13.

Monti E, Bovero M, Mortara L, Pera G, Zupo S, Gugiatti E . BRAF Mutations in an Italian Regional Population: Implications for the Therapy of Thyroid Cancer. Int J Endocrinol. 2015; 2015:138734. PMC: 4674605. DOI: 10.1155/2015/138734. View

14.

. Integrated genomic characterization of papillary thyroid carcinoma. Cell. 2014; 159(3):676-90. PMC: 4243044. DOI: 10.1016/j.cell.2014.09.050. View

15.

Crescenzi A, Baloch Z . Immunohistochemistry in the pathologic diagnosis and management of thyroid neoplasms. Front Endocrinol (Lausanne). 2023; 14:1198099. PMC: 10266214. DOI: 10.3389/fendo.2023.1198099. View

16.

Ciampi R, Romei C, Ramone T, Prete A, Tacito A, Cappagli V . Genetic Landscape of Somatic Mutations in a Large Cohort of Sporadic Medullary Thyroid Carcinomas Studied by Next-Generation Targeted Sequencing. iScience. 2019; 20:324-336. PMC: 6817656. DOI: 10.1016/j.isci.2019.09.030. View

17.

Jaber T, Waguespack S, Cabanillas M, Elbanan M, Vu T, Dadu R . Targeted Therapy in Advanced Thyroid Cancer to Resensitize Tumors to Radioactive Iodine. J Clin Endocrinol Metab. 2018; 103(10):3698-3705. PMC: 6179172. DOI: 10.1210/jc.2018-00612. View

18.

Pozdeyev N, Gay L, Sokol E, Hartmaier R, Deaver K, Davis S . Genetic Analysis of 779 Advanced Differentiated and Anaplastic Thyroid Cancers. Clin Cancer Res. 2018; 24(13):3059-3068. PMC: 6030480. DOI: 10.1158/1078-0432.CCR-18-0373. View

19.

Baloch Z, Asa S, Barletta J, Ghossein R, Juhlin C, Jung C . Overview of the 2022 WHO Classification of Thyroid Neoplasms. Endocr Pathol. 2022; 33(1):27-63. DOI: 10.1007/s12022-022-09707-3. View

20.

Pearson G, Robinson F, Beers Gibson T, Xu B, Karandikar M, Berman K . Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev. 2001; 22(2):153-83. DOI: 10.1210/edrv.22.2.0428. View