Background. We report the case of a 74-year-old woman with BRAF and TERT promoter double-mutation, with an aggressive papillary thyroid carcinoma (PTC) with a focal undifferentiated component. Case presentation. PTC was diagnosed via cytological analysis and total thyroidectomy and lymph node dissection were performed 15 months before her death. Pathological diagnosis revealed stump-positive PTC pT4aN1bM1, Stage IVB. An initial radioiodine ablative dose (150 mCi) was administered. Thereafter, the mediastinal lymph node and multiple bilateral lung metastases were observed upon computed tomography. Six months later, recurrent lesions were irradiated with external beam radiation (39 Gy/13 fr). Within the next five months, she developed multiple-organ metastases. A month before death, recurrent lesions increased rapidly and an undifferentiated cancer was diagnosed upon biopsy. The multifocal disease was rendered inoperable. After gradual progression of respiratory failure, the patient died. During initial resection, a focal invasion component with severe nuclear atypia and spindle-shaped, giant cells were noted, thereby increasing the probability of focal undifferentiated transformation. A focal hobnail pattern and minor necrosis were observed. Upon autopsy, lung and multiple-organ metastases and massive mediastinal invasion were observed. The immunohistochemically undifferentiated lung cancer expressed vimentin, AE1/AE3, CK7, and p53, but not thyroglobulin, TTF-1, and Napsin A. Furthermore, a PTC component was observed in the lung, showing micropapillary architecture with a prominent hobnail pattern. Molecular analysis revealed a double-mutation in BRAF (V600E) and TERT (C228T) promoters. The Ki-67 labeling index of surgical papillary carcinoma tissue was 34%. BRAF mutations associated with p53 mutations triggered an additional TERT promoter mutation with upregulated Ki-67 in primary PTC, which can be a network of genetic alterations driving tumor progression and distant metastasis to the undifferentiated/anaplastic phenotype. Conclusions. The above mentioned molecular genetic features with the histologically hobnail component should be considered and tumor recurrence should be assessed carefully.
Akbota Targynova1, Zhanna Mussazhanova1,2, Nozomi Ueki2, Saltanat Bolsynbekova3, Zhanar Yeleubayeva4, Zhanna Kalmatayeva1, Raushan Issayeva1, Lazzat Sarsenova1, Raushan Umirova5, Dulat Serikbaiuly6, Aray K. Mukanova7, Madina R. Madiyeva7, Masahiro Nakashima2 1 Al-Farabi Kazakh National University, Faculty of Medicine and Health Care, Almaty, Republic of Kazakhstan; 2 Atomic Bomb Disease Institute, Department of Tumor and Diagnostic Pathology, Nagasaki University, Japan; 3 National Research Oncology Center, Department of Diagnostic Pathology and Laboratory, Nur-Sultan, Republic of Kazakhstan; 4 Kazakh Institute of Oncology and Radiology, Center of Morphological Examination, Almaty, Republic of Kazakhstan; 5 Asfendiyarov Kazakh National Medical University, Department of Obstetrics and Gynecology, Almaty, Republic of Kazakhstan; 6 National Research Oncology Center, Multidisciplinary surgery department, Nur-Sultan, Republic of Kazakhstan. 7 Semey Medical University, Department of Radiology, Semey, Republic of Kazakhstan.
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Targynova A., Mussazhanova Z., Ueki N., Bolsynbekova S., Yeleubayeva Z., Kalmatayeva Z., Issayeva R., Sarsenova L., Umirova R., Serikbaiuly D., Nakashima M., Mukanova A.K., Madiyeva M.R. Anaplastic transformation of BRAF and TERT promoter double mutant Papillary Thyroid Carcinoma: clinical, morphological, and molecular genetic features // Nauka i Zdravookhranenie [Science & Healthcare]. 2021, (Vol.23) 5, pp. 248-256. doi 10.34689/SH.2021.23.5.026