Turchini John, Sioson Loretta, Clarkson Adele, Sheen Amy, Delbridge Leigh, Glover Anthony, Sywak Mark, Sidhu Stan, Gill Anthony J
Anatomical Pathology, Douglass Hanly Moir Pathology, 14 Giffnock Avenue, Macquarie Park, NSW, 2113, Australia.
Discipline of Pathology, Macquarie Medical School, Macquarie University, Macquarie Park, NSW, 2109, Australia.
Endocr Pathol. 2023 Mar;34(1):112-118. doi: 10.1007/s12022-022-09747-9. Epub 2023 Jan 28.
Papillary thyroid carcinomas (PTCs) are driven by a variety of molecular abnormalities including BRAF, RAS, ALK, RET, and NTRK alterations. PTCs driven by the BRAFV600E mutation, or tumours which demonstrate a similar gene expression profile to PTCs driven by this mutation, have been reported to demonstrate specific morphological features sometimes termed "BRAFV600E-like" atypia. BRAFV600E-like atypia is characterised by a well-developed papillary architecture, infiltrative growth, marked nuclear clearing, prominent intranuclear pseudoinclusions, abundant eosinophilic cytoplasm, and scattered psammoma bodies. We sought to investigate the sensitivity and specificity of these morphological features for the presence of BRAFV600E mutation in PTCs as determined by mutation specific immunohistochemistry. An unselected cohort of 495 PTCs was reviewed by a single pathologist and categorised into three groups: typical BRAFV600E-like atypia (145 cases, 29%), possible BRAFV600E-like atypia (166 cases, 33%) and little/no BRAFV600E-like atypia (184 cases, 37%). The specificity and sensitivity of typical BRAFV600E-like atypia for the BRAFV600E mutation was 97.2% and 44.3%, respectively. When typical and possible BRAFV600E-like atypia were analysed together, the specificity was 70.6% and the sensitivity was 81.7%. In the morphologically little/no BRAFV600E-like atypia group, 58 cases (31.5%) had a BRAFV600E mutation. We conclude that typical BRAFV600E-like atypia is highly specific for the presence of the BRAFV600E mutation; however, the absence of BRAFV600E-like atypia does not exclude this mutation.
甲状腺乳头状癌（PTC）由多种分子异常驱动，包括BRAF、RAS、ALK、RET和NTRK改变。据报道，由BRAFV600E突变驱动的PTC，或表现出与由该突变驱动的PTC相似基因表达谱的肿瘤，具有特定的形态学特征，有时被称为“BRAFV600E样”异型性。BRAFV600E样异型性的特征是乳头结构发育良好、浸润性生长、明显的核空泡化、显著的核内假包涵体、丰富的嗜酸性细胞质和散在的砂粒体。我们试图通过突变特异性免疫组化研究这些形态学特征对PTC中BRAFV600E突变存在情况的敏感性和特异性。由一名病理学家对495例未经选择的PTC队列进行回顾，并分为三组：典型BRAFV600E样异型性（145例，29%）、可能BRAFV600E样异型性（166例，33%）和很少/无BRAFV600E样异型性（184例，37%）。典型BRAFV600E样异型性对BRAFV600E突变的特异性和敏感性分别为97.2%和44.3%。当将典型和可能BRAFV600E样异型性一起分析时，特异性为70.6%，敏感性为81.7%。在形态学上很少/无BRAFV600E样异型性组中，58例（31.5%）有BRAFV600E突变。我们得出结论，典型BRAFV600E样异型性对BRAFV600E突变的存在具有高度特异性；然而，无BRAFV600E样异型性并不排除该突变。
