Sadiq Qandeel, Sekhri Radhika, Dibaba Daniel T, Zhao Qi, Agarwal Shweta
Department of Pathology, Methodist University Hospital, University of Tennessee Health Sciences Center, Memphis, TN, USA.
Department of Pathology, Montefiore Medical Center/Albert Einstein College of Medicine, New York City, NY, USA.
World J Surg Oncol. 2021 May 8;19(1):143. doi: 10.1186/s12957-021-02258-7.
Thyroid neoplasms with follicular architecture can have overlapping morphologic features and pose diagnostic confusion among pathologists. Various immunohistochemical stains have been investigated as potential diagnostic markers for PTC, among which HBME1 and CK19 have gained popularity. Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) poses similar diagnostic challenges with interobserver variability and is often misdiagnosed as adenomatoid nodule or follicular adenoma. This study aims to evaluate expression of HBME1 and CK19 in NIFTPs in comparison to other well-differentiated thyroid neoplasms and benign mimickers.
Seventy-three thyroid cases diagnosed over a period of 3 years at Methodist University Hospital, Memphis, TN, USA, were included in this study: 9 NIFTP; 18 papillary thyroid carcinoma (PTC); 11 follicular variant of papillary thyroid carcinoma, invasive (I-FVPTC); 24 follicular adenomas (FA); and 11 multinodular goiters/adenomatoid nodules (MNG). A tissue microarray (TMA) was constructed and HBME1 and CK19 immunohistochemistry was performed.
77.8% of NIFTPs, 88.9% of PTCs, 81.8% of I-FVPTCs, 16.7% of FAs, and 18.2% of MNGs showed HBME-1 expression. 66.7% of NIFTPs, 83.3% of PTCs, 81.8% of I-FVPTCs, 33.3% of FAs, and 45.4% of MNGs expressed CK19. Difference in expression of HBME1 and CK19 was statistically significant for NIFTP vs FA (qualitative; p < 0.05) and NIFTP vs MNG (p < 0.05). No statistically significant difference was found for HBME1 in NIFTP vs PTC (conventional and FVPTC), p ≥ 0.2. Sensitivity of HBME1 and CK19 for NIFTP were 78% and 67%, ~ 88% each for PTC, and 89% and 100% for FVPTC, respectively, while specificity of HBME1 and CK19 for NIFTP were 53% each, ~ 62% each for PTC, and ~55% each for FVPTC.
Our study indicated that HBME1 and CK19 are valuable markers in differentiating NIFTPs from morphologic mimics like follicular adenoma and adenomatoid nodules/multinodular goiter. While HBME1 and CK19 are both sensitive in diagnosing lesions with PTC-like nuclear features, CK19 stains a higher number of benign lesions in comparison to HBME1. No increase in sensitivity or specificity in diagnosis of NIFTP, PTC, or FVPTC was noted on combining the two antibodies.
具有滤泡结构的甲状腺肿瘤可具有重叠的形态学特征，给病理学家带来诊断上的困惑。已经研究了各种免疫组织化学染色作为PTC的潜在诊断标志物，其中HBME1和CK19受到广泛关注。具有乳头状核特征的非侵袭性滤泡性甲状腺肿瘤（NIFTP）在观察者间存在差异，也带来类似的诊断挑战，常被误诊为腺瘤样结节或滤泡性腺瘤。本研究旨在比较NIFTP与其他高分化甲状腺肿瘤及良性模仿病变中HBME1和CK19的表达情况。
本研究纳入了美国田纳西州孟菲斯市卫理公会大学医院3年内诊断的73例甲状腺病例：9例NIFTP；18例乳头状甲状腺癌（PTC）；11例侵袭性乳头状甲状腺癌滤泡变体（I-FVPTC）；24例滤泡性腺瘤（FA）；11例多结节性甲状腺肿/腺瘤样结节（MNG）。构建组织芯片（TMA）并进行HBME1和CK19免疫组织化学检测。
77.8%的NIFTP、88.9%的PTC、81.8%的I-FVPTC、16.7%的FA和18.2%的MNG显示HBME-1表达。66.7%的NIFTP、83.3%的PTC、81.8%的I-FVPTC、33.3%的FA和45.4%的MNG表达CK19。NIFTP与FA（定性；p<0.05）以及NIFTP与MNG（p<0.05）之间HBME1和CK19表达的差异具有统计学意义。NIFTP与PTC（传统型和FVPTC）之间HBME1无统计学显著差异，p≥0.2。HBME1和CK19对NIFTP的敏感性分别为78%和67%，对PTC均约为88%，对FVPTC分别为89%和100%，而HBME1和CK19对NIFTP的特异性均为53%，对PTC均约为62%，对FVPTC均约为55%。
我们的研究表明，HBME1和CK19是区分NIFTP与滤泡性腺瘤和腺瘤样结节/多结节性甲状腺肿等形态学模仿病变的有价值标志物。虽然HBME1和CK19在诊断具有PTC样核特征的病变时都很敏感，但与HBME1相比，CK19染色的良性病变更多。联合使用这两种抗体在诊断NIFTP、PTC或FVPTC时，敏感性和特异性均未增加。
