Wallander Michelle, Layfield Lester J, Jarboe Elke, Emerson Lyska, Liu Ting, Thaker Harshwardhan, Holden Joseph, Tripp Sheryl
Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah, USA.
Appl Immunohistochem Mol Morphol. 2010 May;18(3):231-5. doi: 10.1097/PAI.0b013e3181c61cdd.
Despite the recognition of the follicular variant of papillary carcinoma of the thyroid (FVPTC) for over 50 years, reproducibility of this diagnostic category has remained poor. Architectural features have been of variable utility as some FVPTC seem encapsulated, whereas others are multifocal and may be confused with nodular hyperplasia. Nuclear features are important for diagnosis of FVPTC, but some authors have discounted the utility of nuclear grooves and inclusions. More recently, BRAF and HBME-1 (Human Bone Marrow Endothelial Cell-1) have been suggested as markers for FVPTC.
To investigate the frequency of BRAF mutations and HBME-1 immunopositivity, in a series of FVPTCs in which the diagnosis was established by 100% consensus among a panel of 6 surgical pathologists.
Twenty-eight specimens with an original diagnosis of FVPTC and 10 cases with other diagnoses were obtained from the surgical pathology files of the University of Utah School of Medicine. All specimens were independently reviewed by 6 surgical pathologists. Tissue blocks were analyzed for BRAF exon 15 mutations and HMBE-1 expression.
Complete agreement among pathologists for the diagnosis of FVPTC was obtained in 28.6% (8/28) of cases originally diagnosed as FVPTC. Mutations in BRAF exon 15 were found in 25% (2/8) of cases with a 100% consensus diagnosis of FVPTC and 32% (6/19) of cases unanimously diagnosed as a type of papillary carcinoma (classic or follicular variant). HBME-1 was expressed in 87.5% (7/8) of lesions with a 100% consensus diagnosis of FVPTC and 84.2% (16/19) of lesions with a unanimous diagnosis of a type of papillary carcinoma of the thyroid (classic or follicular variant).
Interobserver agreement for the diagnosis of FVPTC is poor and testing for the BRAF mutation is only marginally helpful because a minority of FVPTCs possess the mutation. HBME-1 expression when coupled with a BRAF mutation, results in 100% specificity but low sensitivity for the presence of papillary carcinoma of the thyroid including the follicular variant.
尽管甲状腺乳头状癌滤泡变体（FVPTC）已被认识超过50年，但该诊断类别的可重复性一直很差。结构特征的实用性各不相同，因为一些FVPTC似乎有包膜，而另一些则是多灶性的，可能与结节性增生混淆。核特征对FVPTC的诊断很重要，但一些作者对核沟和核内假包涵体的实用性表示怀疑。最近，BRAF和HBME-1（人骨髓内皮细胞-1）被认为是FVPTC的标志物。
在一组由6名外科病理学家达成100%共识确诊的FVPTC病例中，研究BRAF突变频率和HBME-1免疫阳性情况。
从犹他大学医学院外科病理档案中获取28例最初诊断为FVPTC的标本和10例其他诊断的病例。所有标本均由6名外科病理学家独立复查。分析组织块中的BRAF第15外显子突变和HMBE-1表达。
最初诊断为FVPTC的病例中，28.6%（8/28）的病例在病理学家之间达成了FVPTC诊断的完全一致。在100%达成共识诊断为FVPTC的病例中，25%（2/8）发现BRAF第15外显子突变，在一致诊断为某种乳头状癌（经典型或滤泡变体）的病例中，32%（6/19）发现该突变。在100%达成共识诊断为FVPTC的病变中，87.5%（7/8）表达HBME-1，在一致诊断为某种甲状腺乳头状癌（经典型或滤泡变体）的病变中，84.2%（16/19）表达HBME-1。
FVPTC诊断的观察者间一致性较差，BRAF突变检测仅略有帮助，因为少数FVPTC具有该突变。HBME-1表达与BRAF突变结合时，对包括滤泡变体在内的甲状腺乳头状癌的存在具有100%的特异性，但敏感性较低。
