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SATB2 is an Emergent Biomarker of Anaplastic Thyroid Carcinoma: A Series with Comprehensive Biomarker and Molecular Studies. SATB2 是甲状腺无节细胞癌的新兴生物标志物:综合生物标志物和分子研究系列报告》(SATB2 is an Emergent Biomarker of Anaplastic Thyroid Carcinoma: A Series with Comprehensive Biomarker and Molecular Studies)。
IF 11.3 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-12-01 Epub Date: 2024-11-05 DOI: 10.1007/s12022-024-09833-0
Dingani Nkosi, William E Crowe, Brian J Altman, Zoltán N Oltvai, Ellen J Giampoli, Moises J Velez

Anaplastic thyroid carcinoma (ATC) is a rare and aggressive thyroid malignancy typically comprised of undifferentiated tumor cells with various histologic morphologies, which makes the diagnosis challenging. These tumors commonly show loss of thyroglobulin and TTF1 with preservation of cytokeratin (67%) and Paired Box Gene 8 (PAX8) (55%) expression. Identification of a sensitive immunohistochemical stain to aid in the diagnosis of ATC would be beneficial. Immunohistochemistry (IHC) against special AT-rich sequence-binding protein 2 (SATB2) protein is a sensitive and specific marker expressed in colorectal adenocarcinoma and bone or soft tissue tumors with osteoblastic differentiation. However, SATB2 is also expressed in other sarcomatous/undifferentiated neoplasms lacking osteoblastic differentiation. Using quantitative reverse transcription PCR (RT-qPCR) we showed that there is variable expression of SATB2 mRNA expression in ATCs. To evaluate the role of SATB2 protein expression in ATC, we performed PAX8, SATB2, pancytokeratin (AE1/AE3 & CAM5.2), claudin-4 and TTF1 immunostaining on 23 cases. ATCs showed retained expression of PAX8 in 65% (15/23); SATB2 was detected in 74% (17/23); pancytokeratin was expressed in 65% (15/23); claudin-4 was expressed in 35% (8/23) and TTF1 showed expression in 13% (3/23) of cases. Furthermore, 83% (5/6) of ATCs which lacked SATB2 expression, retained PAX8 expression, while 88% (7/8) of the tumors without PAX8 expression were positive for SATB2. Differentiated follicular cell-derived thyroid cancers (n = 30), differentiated high grade thyroid carcinoma (n = 3), and poorly differentiated thyroid carcinoma (n = 8) were negative for SATB2 immunoreactivity. Next-generation selected cases detected the commonly identified oncogenic variants including those in BRAF, RAS, TP53, and TERT promoter. Overall, we hereby demonstrate that SATB2 IHC may be used to support the diagnosis of ATC.

甲状腺无分化癌(ATC)是一种罕见的侵袭性甲状腺恶性肿瘤,通常由具有不同组织学形态的未分化肿瘤细胞组成,因此诊断具有挑战性。这些肿瘤通常表现为甲状腺球蛋白和TTF1的缺失,而细胞角蛋白(67%)和配对盒基因8(PAX8)(55%)的表达却得以保留。确定一种敏感的免疫组化染色方法来帮助诊断 ATC 将是有益的。针对特殊富AT序列结合蛋白2(SATB2)蛋白的免疫组化(IHC)是在结直肠腺癌和具有成骨细胞分化的骨或软组织肿瘤中表达的一种敏感而特异的标记物。然而,SATB2 在其他缺乏成骨细胞分化的肉瘤/未分化肿瘤中也有表达。通过使用定量反转录 PCR(RT-qPCR),我们发现 SATB2 mRNA 在 ATC 中的表达存在差异。为了评估 SATB2 蛋白表达在 ATC 中的作用,我们对 23 例病例进行了 PAX8、SATB2、泛型角蛋白(AE1/AE3 和 CAM5.2)、claudin-4 和 TTF1 免疫染色。结果显示,65%(15/23)的 ATC 保留表达 PAX8;74%(17/23)的 ATC 检测到 SATB2;65%(15/23)的 ATC 表达 pancytokeratin;35%(8/23)的 ATC 表达 claudin-4;13%(3/23)的 ATC 表达 TTF1。此外,83%(5/6)缺乏 SATB2 表达的 ATC 保留了 PAX8 表达,而 88%(7/8)没有 PAX8 表达的肿瘤 SATB2 呈阳性。分化型滤泡细胞源性甲状腺癌(30例)、分化型高级别甲状腺癌(3例)和分化不良型甲状腺癌(8例)的SATB2免疫反应均为阴性。经下一代筛选的病例检测出了常见的致癌变体,包括BRAF、RAS、TP53和TERT启动子中的变体。总之,我们在此证明 SATB2 IHC 可用于支持 ATC 的诊断。
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引用次数: 0
Clinicopathological Features of Epstein-Barr Virus-Positive Neuroendocrine Carcinoma: Analysis of Twenty-Two Cases. 爱泼斯坦-巴尔病毒阳性神经内分泌癌22例临床病理分析
IF 11.3 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-12-01 Epub Date: 2024-11-30 DOI: 10.1007/s12022-024-09837-w
Xiao-Ying Zhang, Jia Fu, Mei-Ling Chen, Xin-Chun Chen, Shi-Min Zhang, Yi-Ling Luo, Mao Fang, Han-Wen Jiang, Fang Chen, Hao Wang, Jin-Hua He, Yan Li

Epstein-Barr Virus (EBV)-positive neuroendocrine carcinoma (NEC) is a rare neoplasm with limited histopathological and therapeutic data. This report presents 22 cases of EBV-positive NEC, analyzing age distribution, morphology, and immunophenotype. The median patient age was 47 years (range: 27-67 years), with a male-to-female ratio of 17:5. Most cases (86%, 19/22) were localized to the nasal cavity or nasopharynx, while the remaining three (14%, 3/22) involved the lung, eyelid, and chest wall. Tumors were identified as small cell neuroendocrine carcinoma (SCNEC) or large cell neuroendocrine carcinoma (LCNEC) based on cellular morphology. Immunohistochemical analysis showed positivity for at least one, but generally, two neuroendocrine markers and INI1, while negativity for NUT and squamous cell carcinoma markers, such as p63, p40, and CK5/6. In situ hybridization consistently revealed EBV early RNAs (EBERs) in all cases. Notably, eight patients benefited from chemoradiotherapy. Recognizing this rare tumor is essential for optimizing treatment strategies.

eb病毒(EBV)阳性神经内分泌癌(NEC)是一种罕见的肿瘤,组织病理学和治疗资料有限。本文报告22例ebv阳性NEC,分析年龄分布、形态学和免疫表型。患者年龄中位数为47岁(范围:27-67岁),男女比例为17:5。大多数病例(86%,19/22)局限于鼻腔或鼻咽部,其余3例(14%,3/22)累及肺、眼睑和胸壁。根据细胞形态将肿瘤确定为小细胞神经内分泌癌(SCNEC)或大细胞神经内分泌癌(LCNEC)。免疫组化分析显示至少一种(但通常是两种)神经内分泌标志物和INI1呈阳性,而NUT和鳞状细胞癌标志物(如p63、p40和CK5/6)呈阴性。原位杂交在所有病例中一致显示EBV早期rna (EBERs)。值得注意的是,8名患者从放化疗中受益。认识到这种罕见的肿瘤对于优化治疗策略至关重要。
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引用次数: 0
Correction: Consensus Statement: Recommendations on Actionable Biomarker Testing for Thyroid Cancer Management. 更正:共识声明:关于甲状腺癌管理可操作的生物标志物检测的建议。
IF 11.3 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-12-01 DOI: 10.1007/s12022-024-09843-y
Ozgur Mete, Andrée Boucher, Kasmintan A Schrader, Omar Abdel-Rahman, Houda Bahig, Cheryl Ho, Olfat Kamel Hasan, Bernard Lemieux, Eric Winquist, Ralph Wong, Jonn Wu, Nicole Chau, Shereen Ezzat
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引用次数: 0
Glucagon-Producing Pancreatic Neuroendocrine Tumors (Glucagonomas) are Enriched in Aggressive Neoplasms with ARX and PDX1 Co-expression, DAXX/ATRX Mutations, and ALT (Alternative Lengthening of Telomeres). 分泌胰高血糖素的胰腺神经内分泌肿瘤(胰高血糖素瘤)是富含 ARX 和 PDX1 共表达、DAXX/ATRX 基因突变和 ALT(端粒替代性延长)的侵袭性肿瘤。
IF 11.3 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-12-01 Epub Date: 2024-09-27 DOI: 10.1007/s12022-024-09826-z
Paola Mattiolo, Michele Bevere, Andrea Mafficini, Anna Vera D Verschuur, Martina Calicchia, Wenzel M Hackeng, Michele Simbolo, Salvatore Paiella, Koen M A Dreijerink, Luca Landoni, Serena Pedron, Sara Cingarlini, Roberto Salvia, Michele Milella, Rita T Lawlor, Gerlof D Valk, Menno R Vriens, Aldo Scarpa, Lodewijk A Brosens, Claudio Luchini

Glucagonomas are functioning pancreatic neuroendocrine tumors (PanNETs) responsible for glucagonoma syndrome. This study aims to shed light on the clinicopathological and molecular features of these neoplasms. Six patients with glucagonomas were identified. All neoplasms were investigated with immunohistochemistry for neuroendocrine markers (Synaptophysin, Chromogranin-A), ATRX, DAXX, ARX, and PDX1 transcription factors. Fluorescent in situ hybridization (FISH) for assessing alternative lengthening of telomeres (ALT), and next-generation sequencing (NGS) for molecular profiling were performed. All cases were large single masses (mean size of 8.2 cm), with necrolytic migratory erythema as the most common symptom (6/6 cases, 100%). All neoplasms were well-differentiated G1 tumors, except one case that was G2. The tumors consistently showed classic/conventional histomorphology, with solid-trabecular and nested architecture. Lymphatic and vascular invasion (6/6, 100%), perineural infiltration (4/6, 66.6%), and nodal metastasis (4/6, 66.6%) were frequently observed. Transcription factors expression showed strong ARX expression in all tumors, and PDX1 expression in 5/6 cases (83.3%), indicating co-occurring alpha- and beta-cell differentiation. NGS showed recurrent somatic MEN1 and ATRX/DAXX biallelic inactivation. Cases with ATRX or DAXX mutations also showed matched loss of ATRX or DAXX protein expression and ALT. One case harbored somatic MUTYH inactivation and showed a high tumor mutational burden (TMB, 41.0 mut/Mb). During follow-up, one patient died of the disease, and four patients developed distant metastasis. Pancreatic glucagonomas are distinct PanNETs with specific clinicopathological and molecular features, including histological aspects of biological aggressiveness, co-occurring alpha- and beta-cell differentiation, MEN1 and DAXX/ATRX mutations enrichment, and the possible presence of high-TMB as an actionable marker.

胰高血糖素瘤是一种功能性胰腺神经内分泌肿瘤(PanNET),是胰高血糖素瘤综合征的罪魁祸首。本研究旨在阐明这些肿瘤的临床病理和分子特征。研究发现了六名胰高血糖素瘤患者。所有肿瘤均采用免疫组化方法检测神经内分泌标记物(突触素、嗜铬粒蛋白-A)、ATRX、DAXX、ARX 和 PDX1 转录因子。荧光原位杂交(FISH)用于评估端粒替代性延长(ALT),下一代测序(NGS)用于分子谱分析。所有病例均为单个大肿块(平均大小为 8.2 厘米),最常见的症状是坏死性移行性红斑(6/6 例,100%)。除一例为 G2 外,所有肿瘤均为分化良好的 G1 肿瘤。肿瘤的组织形态一致表现为经典/常规组织形态,具有实性-小叶和巢状结构。经常观察到淋巴和血管侵犯(6/6,100%)、神经周围浸润(4/6,66.6%)和结节转移(4/6,66.6%)。转录因子表达显示,所有肿瘤均有较强的 ARX 表达,5/6 例(83.3%)有 PDX1 表达,表明同时存在α细胞和β细胞分化。NGS 显示了复发性体细胞 MEN1 和 ATRX/DAXX 双倍性失活。ATRX或DAXX突变的病例也表现出ATRX或DAXX蛋白表达和ALT的匹配缺失。一个病例存在体细胞 MUTYH 失活,并显示出较高的肿瘤突变负荷(TMB,41.0 mut/Mb)。随访期间,一名患者因病死亡,四名患者出现远处转移。胰腺胰高血糖素瘤是一种独特的泛NET,具有特定的临床病理学和分子特征,包括组织学方面的生物侵袭性、共存的α细胞和β细胞分化、MEN1和DAXX/ATRX突变富集,以及可能存在的高TMB作为可操作标记物。
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引用次数: 0
Cauda Equina Neuroendocrine Tumors with Ganglioneuromatous Elements are Best Classified as Composite Gangliocytoma/Neuroma and Neuroendocrine Tumor (COGNET). 具有神经节细胞瘤成分的马尾神经内分泌肿瘤最好归类为复合神经节细胞瘤/神经瘤和神经内分泌肿瘤 (COGNET)。
IF 11.3 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-12-01 Epub Date: 2024-11-27 DOI: 10.1007/s12022-024-09840-1
Fatih Mert Dogukan, Ozgur Mete
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引用次数: 0
Insights into Biologic Evolution of Grade 3 Neuroendocrine Tumors Reflect Classification Challenges. 3级神经内分泌肿瘤的生物学进化反映了分类的挑战。
IF 11.3 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-12-01 DOI: 10.1007/s12022-024-09844-x
Ozgur Mete
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引用次数: 0
Endocrine Pathology Society Hubert Wolfe Award for 2024: Call for Nominations. 内分泌病理学会 2024 年休伯特-沃尔夫奖:征集提名。
IF 11.3 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-10-22 DOI: 10.1007/s12022-024-09831-2
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引用次数: 0
Transcriptomic Differences in Medullary Thyroid Carcinoma According to Grade. 不同等级甲状腺髓样癌的转录组差异
IF 11.3 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-01 Epub Date: 2024-07-03 DOI: 10.1007/s12022-024-09817-0
Ignacio Ruz-Caracuel, Tamara Caniego-Casas, Teresa Alonso-Gordoa, Irene Carretero-Barrio, Carmen Ariño-Palao, Almudena Santón, Marta Rosas, Héctor Pian, Javier Molina-Cerrillo, Patricia Luengo, José Palacios

Medullary thyroid carcinoma (MTC) is a rare cancer derived from neuroendocrine C-cells of the thyroid. In contrast to other neuroendocrine tumors, a histological grading system was lacking until recently. A novel two-tier grading system based on the presence of high proliferation or necrosis is associated with prognosis. Transcriptomic analysis was conducted on 21 MTCs, including 9 high-grade tumors, with known mutational status, using the NanoString Tumor Signaling 360 Panel. This analysis, covering 760 genes, revealed upregulation of the genes EGLN3, EXO1, UBE2T, UBE2C, FOXM1, CENPA, DLL3, CCNA2, SOX2, KIF23, and CDCA5 in high-grade MTCs. Major pathways differentially expressed between high-grade and low-grade MTCs were DNA damage repair, p53 signaling, cell cycle, apoptosis, and Myc signaling. Validation through qRT-PCR in 30 MTCs demonstrated upregulation of ASCL1, DLL3, and SOX2 in high-grade MTCs, a gene signature akin to small-cell lung carcinoma, molecular subgroup A. Subsequently, DLL3 expression was validated by immunohistochemistry. MTCs with DLL3 overexpression (defined as ≥ 50% of positive tumor cells) were associated with significantly lower disease-free survival (p = 0.041) and overall survival (p = 0.01). Moreover, MTCs with desmoplasia had a significantly increased expression of DLL3. Our data supports the idea that DLL3 should be further explored as a predictor of aggressive disease and poor outcomes in MTC.

甲状腺髓样癌(MTC)是一种罕见的癌症,源自甲状腺的神经内分泌C细胞。与其他神经内分泌肿瘤相比,直到最近才有了组织学分级系统。新的两级分级系统以是否存在高度增殖或坏死为基础,与预后相关。利用 NanoString Tumor Signaling 360 Panel 对 21 例 MTC 进行了转录组分析,其中包括 9 例已知突变状态的高级别肿瘤。该分析涵盖了 760 个基因,发现在高级别 MTC 中,EGLN3、EXO1、UBE2T、UBE2C、FOXM1、CENPA、DLL3、CCNA2、SOX2、KIF23 和 CDCA5 等基因上调。高级别和低级别 MTC 之间表达不同的主要通路包括 DNA 损伤修复、p53 信号传导、细胞周期、细胞凋亡和 Myc 信号传导。通过对 30 例 MTC 进行 qRT-PCR 验证,发现高级别 MTC 中的 ASCL1、DLL3 和 SOX2 上调,这一基因特征与小细胞肺癌分子亚组 A 相似。DLL3过表达(定义为≥50%的阳性肿瘤细胞)的MTC与较低的无病生存率(p = 0.041)和总生存率(p = 0.01)相关。此外,有脱落细胞的 MTC 的 DLL3 表达明显增加。我们的数据支持这样一种观点,即应进一步研究 DLL3 作为 MTC 侵袭性疾病和不良预后的预测因子的作用。
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引用次数: 0
Isolated Tumor Cells Node Micro-metastasis in Early-Stage Small Intestinal Neuroendocrine Tumor. 早期小肠神经内分泌瘤的孤立肿瘤细胞结节微转移
IF 11.3 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-01 Epub Date: 2024-08-22 DOI: 10.1007/s12022-024-09823-2
Giulia Scaglione, Pietro Fransvea, Enza Genco, Guido Rindi
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引用次数: 0
Primary Secretory Carcinoma of the Thyroid Gland with ETV6::NTRK3 Gene Fusion. 与 ETV6::NTRK3 基因融合的甲状腺原发性分泌性癌
IF 11.3 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-01 Epub Date: 2024-07-22 DOI: 10.1007/s12022-024-09820-5
Rumeal D Whaley, Lori A Erickson
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引用次数: 0
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Endocrine Pathology
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