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Prognostic Value of Microscopic Tumor Necrosis in Adrenal Cortical Carcinoma. 肾上腺皮质癌显微肿瘤坏死的预后价值。
IF 4.4 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2023-06-01 DOI: 10.1007/s12022-023-09760-6
Michaela Luconi, Giulia Cantini, Rachel S van Leeuwaarde, Rogina Roebaar, Laura Fei, Arianna Pia Propato, Raffaella Santi, Tonino Ercolino, Massimo Mannelli, Letizia Canu, Ronald R de Krijger, Gabriella Nesi

Adrenal cortical carcinoma (ACC) is an uncommon neoplasm with variable prognosis. Several histologic criteria have been identified as predictors of malignancy in adrenal cortical tumors. The Weiss score is the system most widely employed for diagnostic purposes, but also possesses prognostic value. We aim to determine the relative impact of each Weiss parameter on ACC patient survival. A multicenter retrospective analysis was conducted on a series of 79 conventional ACCs surgically treated at the Florence and Utrecht centers of the European Network for the Study of Adrenal Tumors (ENSAT). Weiss classification was recapitulated using principal component analysis (PCA). The Kaplan-Meier and Cox multivariate regression analyses were applied in order to estimate the prognostic power of Weiss versus other clinical parameters. PCA reduced the nine Weiss parameters to the best fitting 4-component model, each parameter clustering with a single component. Necrosis and venous invasion clustered together with the highest scores, thus establishing the most relevant component (Component 1) to explain Weiss distribution variability. Only Component 1 significantly predicted overall survival (OS, log-rank = 0.008) and disease-free survival (DFS, log-rank < 0.001). When considering the prognostic power of Weiss parameters, necrosis alone could independently assess OS (log-rank = 0.004) and DFS (log-rank < 0.001) at both the Kaplan-Meier and multivariate Cox regression analyses [hazard ratio (HR) = 7.8, 95% confidence interval [CI] = 1.0-63.5, p = 0.05, and HR = 12.2, 95% CI = 1.6-95.0, p = 0.017, respectively]. The presence of necrosis significantly shortened time to survival (TtS) and time to recurrence (TtR), 57.5 [31.5-103.5] vs 34 [12-78] months (p = 0.05) and 57.5 [31.5-103.5] vs 7 [1.0-31.5] months (p < 0.001), respectively. Our study suggests that, of the Weiss parameters, necrosis is the most powerful adverse factor and the best predictor of OS and DFS in ACC patients.

摘要肾上腺皮质癌是一种少见的肿瘤,预后不一。几个组织学标准已被确定为肾上腺皮质肿瘤恶性的预测因素。Weiss评分是最广泛用于诊断目的的系统,但也具有预后价值。我们的目的是确定每个Weiss参数对ACC患者生存的相对影响。对欧洲肾上腺肿瘤研究网络(ENSAT)佛罗伦萨和乌得勒支中心接受手术治疗的79例常规ACCs进行了多中心回顾性分析。采用主成分分析(PCA)对Weiss分类进行概括。应用Kaplan-Meier和Cox多变量回归分析来评估Weiss与其他临床参数的预后能力。PCA将9个Weiss参数简化为最适合的4分量模型,每个参数与单个分量聚类。坏死和静脉侵入聚集在一起得分最高,从而建立了最相关的成分(成分1)来解释Weiss分布变异性。只有成分1能显著预测总生存期(OS, log-rank = 0.008)和无病生存期(DFS, log-rank)
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引用次数: 2
Pediatric Adrenocortical Neoplasms: A Study Comparing Three Histopathological Scoring Systems. 儿童肾上腺皮质肿瘤:比较三种组织病理学评分系统的研究。
IF 4.4 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2023-06-01 DOI: 10.1007/s12022-023-09767-z
Hemlata Jangir, Isheeta Ahuja, Shipra Agarwal, Vishesh Jain, Jagdish Prasad Meena, Sandeep Agarwala, Rajni Sharma, Mehar Chand Sharma, Venkateswaran K Iyer, Kalaivani Mani

Adrenocortical neoplasms are rare in childhood. Their histopathological categorization into benign and malignant is often challenging, impacting further management. While the AFIP/Wieneke scoring system is widely used for the prognostic classification of these tumors, it has limitations. Few other tumor scoring systems have evolved over the past few years. These have been validated in adults but not yet in pediatric patients. We evaluated a cohort of pediatric adrenocortical neoplasms to assess the applicability of AFIP/Wieneke criteria and the recently introduced Helsinki score and reticulin algorithm in predicting clinical outcomes. A tumor was considered 'clinically aggressive' in the presence of any of the following: metastases, recurrence, progressive disease, or death due to disease. Cases without any such event were considered 'clinically good'. Event-free survival time was the duration from the date of clinical presentation to any post-operative adverse event. For overall survival analysis, the endpoint was either the last follow-up or death due to disease.Using ROC curve analysis, the obtained cut-off Helsinki score of 24 could stratify the cases into two prognostically relevant groups. Survival analysis showed significant differences in the event-free and overall survival of these two groups of patients, validating the proposed cut-off. None of the three histopathological scoring systems could predict an unfavorable outcome with 100% accuracy. All showed a sensitivity of ≥ 80%, with the reticulin algorithm achieving 100% sensitivity. The specificity and accuracy of the AFIP/Wieneke criteria were the lowest (62.5% and 73.08%, respectively). While the Helsinki score (at the cut-off score of 24) and the reticulin algorithm had similar accuracy rates (80.77%, and 80%, respectively), the specificity of the former was higher (81.25%) than the latter (68.75%). A separate analysis revealed that the Ki-67 index at a cut-off of 18% had a sensitivity of 80% and a specificity of 81.25% for predicting an unfavorable outcome.

肾上腺皮质肿瘤在儿童期是罕见的。他们的组织病理学分类为良性和恶性往往是具有挑战性的,影响进一步的管理。虽然AFIP/Wieneke评分系统被广泛用于这些肿瘤的预后分类,但它有局限性。在过去的几年中,很少有其他肿瘤评分系统得到发展。这些已在成人中得到证实,但尚未在儿科患者中得到证实。我们评估了一组儿童肾上腺皮质肿瘤,以评估AFIP/Wieneke标准以及最近引入的赫尔辛基评分和reticulin算法在预测临床结果方面的适用性。如果出现以下任何一种情况,肿瘤被认为具有“临床侵袭性”:转移、复发、疾病进展或因疾病死亡。没有任何此类事件的病例被认为是“临床良好”。无事件生存时间是指从临床表现到任何术后不良事件的持续时间。对于总生存分析,终点为最后一次随访或因病死亡。通过ROC曲线分析,得到的赫尔辛基分值为24分,可以将病例分为两个预后相关的组。生存分析显示,两组患者的无事件生存期和总生存期存在显著差异,验证了建议的截止日期。三种组织病理学评分系统都不能100%准确地预测不良结果。所有算法的灵敏度均≥80%,其中reticulin算法的灵敏度达到100%。AFIP/Wieneke标准的特异性和准确性最低(分别为62.5%和73.08%)。赫尔辛基评分(临界值为24)与reticulin算法准确率相近(分别为80.77%和80%),但前者的特异性(81.25%)高于后者(68.75%)。另一项分析显示,Ki-67指数在18%的临界值下预测不良预后的敏感性为80%,特异性为81.25%。
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引用次数: 1
Mucinous Amphicrine Carcinoma of the Pancreas: A Diagnostic Pitfall. 胰腺黏液性两性癌:诊断陷阱。
IF 11.3 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2023-06-01 Epub Date: 2023-05-03 DOI: 10.1007/s12022-023-09766-0
Hirofumi Watanabe, Yuto Yamazaki, Shin Miura, Satoshi Higuchi, Fumiyoshi Fujishima
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引用次数: 0
3rd Edition of Diagnostic Pathology: Endocrine by Vania Nosé. 第三版诊断病理学:内分泌由Vania nos<s:1>。
IF 4.4 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2023-06-01 DOI: 10.1007/s12022-023-09774-0
Ozgur Mete
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引用次数: 0
FLCN-Driven Functional Adrenal Cortical Carcinoma with High Mitotic Tumor Grade: Extending the Endocrine Manifestations of Birt-Hogg-Dubé Syndrome. flcn驱动的功能性肾上腺皮质癌伴高有丝分裂肿瘤分级:扩展birt - hogg - dub<s:1>综合征的内分泌表现。
IF 4.4 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2023-06-01 DOI: 10.1007/s12022-023-09748-2
Renee Hofstedter, María Carolina Sanabria-Salas, Maria Di Jiang, Shereen Ezzat, Ozgur Mete, Raymond H Kim

Adrenal cortical carcinoma is an aggressive and rare malignancy of steroidogenic cells of the adrenal gland. Most adult adrenal cortical carcinomas are sporadic, but a small fraction may be associated with inherited tumor syndromes, such as Li-Fraumeni, multiple endocrine neoplasia 1, Lynch syndrome, and Beckwith-Wiedemann syndrome, as well as isolated case reports of non-syndromic manifestations occurring in the context of other pathogenic germline variants. Birt-Hogg-Dubé (BHD) is a rare autosomal dominant syndrome caused by germline pathogenic variants in the FLCN gene. BHD syndrome causes a constellation of symptoms, including cutaneous manifestations, pulmonary cysts and pneumothorax, and risk of renal tumors. With the exception of a single case of adrenal cortical carcinoma, very few reports on the occurrence of adrenal cortical neoplasia in patients with BHD syndrome have been described. However, information on variant allele fraction in the tumor was not available in the index case, which precludes any mechanism supporting loss of heterozygosity. Here we present a case of an adult-onset adrenal cortical carcinoma in a 50-year-old female, found to harbor a germline likely pathogenic variant in the FLCN gene, denoted as c.694C > T (p.Gln232Ter). Genetic testing on the tumor revealed the same FLCN variant at an allele fraction of 83%, suggesting a contributory role to the pathogenesis of the adrenal cortical carcinoma. This case further supports the expansion of the clinical presentation and tumor spectrum of BHD syndrome and the need to consider germline FLCN testing in the clinical genetic workup of patients with adrenal cortical carcinomas.

肾上腺皮质癌是一种侵袭性且罕见的肾上腺类固醇细胞恶性肿瘤。大多数成人肾上腺皮质癌是散发的,但一小部分可能与遗传性肿瘤综合征有关,如Li-Fraumeni、多发性内分泌瘤1、Lynch综合征和Beckwith-Wiedemann综合征,以及在其他致病性种系变异背景下发生的非综合征表现的孤立病例报告。birt - hogg - dub (BHD)是一种罕见的常染色体显性综合征,由FLCN基因的种系致病变异引起。BHD综合征引起一系列症状,包括皮肤表现、肺囊肿和气胸,以及肾肿瘤的风险。除了一例肾上腺皮质癌外,很少有关于BHD综合征患者发生肾上腺皮质瘤变的报道。然而,在索引病例中没有关于肿瘤中变异等位基因分数的信息,这排除了支持杂合性丧失的任何机制。本文报告一例50岁女性成人发病肾上腺皮质癌,发现FLCN基因可能存在种系致病变异,标记为c.694C > T (p.Gln232Ter)。肿瘤的基因检测显示相同的FLCN变异的等位基因分数为83%,提示在肾上腺皮质癌的发病机制中起一定作用。本病例进一步支持了BHD综合征临床表现和肿瘤谱的扩展,以及在肾上腺皮质癌患者的临床遗传学检查中考虑种系FLCN检测的必要性。
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引用次数: 2
Thyroid Nodules and Follicular Cell-Derived Thyroid Carcinomas in Children. 儿童甲状腺结节和滤泡细胞衍生的甲状腺癌。
IF 4.4 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2023-06-01 DOI: 10.1007/s12022-023-09764-2
Jonathan C Slack, Monica Hollowell, Justine A Barletta

Although pediatric thyroid tumors have many similarities to those occurring in adults, significant differences are also recognized. For example, although thyroid nodules in children are much less common than in adults, a higher percentage is malignant. Moreover, while pediatric papillary thyroid carcinoma (PTC) is associated with more advanced disease, death due to disease in children and adolescents is very rare, even when distant metastases are present. Some subtypes of thyroid carcinoma, like diffuse sclerosing variant, are especially common in children and adolescents. Moreover, certain histologic findings, such as a tall cell morphology or increased mitotic activity, may not carry the same prognostic significance in children as in adults. Recent studies exploring the molecular underpinnings of pediatric thyroid carcinoma indicate that while driver alterations of thyroid tumorigenesis in children and adults are essentially the same, they occur at very different frequencies, with translocation-associated tumors (most commonly harboring RET and NTRK fusions) comprising a sizable and distinct group of pediatric PTC. DICER1 mutations, an infrequent mutation in adult thyroid tumors, are relatively frequent in pediatric encapsulated follicular-patterned thyroid tumors (with or without invasion or nuclear features of PTC). Additionally, tumor predisposition syndromes (most notably DICER1 syndrome and PTEN hamartoma tumor syndromes such as Cowden syndrome) should be considered in children with thyroid tumors, especially follicular-patterned thyroid tumors and poorly differentiated thyroid carcinoma. This review will explore the current state of knowledge of thyroid nodules and carcinomas in children and adolescents.

虽然儿童甲状腺肿瘤与成人甲状腺肿瘤有许多相似之处,但也认识到显著的差异。例如,虽然儿童甲状腺结节比成人少得多,但恶性结节的比例较高。此外,虽然儿童乳头状甲状腺癌(PTC)与更晚期的疾病相关,但儿童和青少年因疾病导致的死亡非常罕见,即使存在远处转移。甲状腺癌的某些亚型,如弥漫性硬化变体,在儿童和青少年中特别常见。此外,某些组织学发现,如高细胞形态或有丝分裂活性增加,在儿童中可能不具有与成人相同的预后意义。最近探索儿童甲状腺癌分子基础的研究表明,虽然儿童和成人甲状腺肿瘤发生的驱动因素改变本质上是相同的,但它们发生的频率却截然不同,易位相关肿瘤(最常见的是RET和NTRK融合物)构成了一个相当大的儿科PTC群体。DICER1突变在成人甲状腺肿瘤中并不常见,但在儿童囊泡型甲状腺肿瘤(伴有或不伴有PTC侵袭或核特征)中相对常见。此外,对于患有甲状腺肿瘤的儿童,尤其是滤泡型甲状腺肿瘤和低分化甲状腺癌,应考虑肿瘤易感综合征(最明显的是DICER1综合征和PTEN错构瘤肿瘤综合征,如Cowden综合征)。这篇综述将探讨儿童和青少年甲状腺结节和癌的知识现状。
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引用次数: 1
Primary Thyroid Mucoepidermoid Carcinoma (MEC) Is Clinically, Prognostically, and Molecularly Different from Sclerosing MEC with Eosinophilia: A Multicenter and Integrated Study. 原发性甲状腺黏液表皮样癌(MEC)在临床、预后和分子上不同于硬化性MEC伴嗜酸性粒细胞增多:一项多中心综合研究
IF 4.4 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2023-03-01 DOI: 10.1007/s12022-022-09741-1
Hieu Trong Le, Truong P X Nguyen, Mitsuyoshi Hirokawa, Ryohei Katoh, Norisato Mitsutake, Michiko Matsuse, Ayaka Sako, Tetsuo Kondo, Nilesh Vasan, Young Mi Kim, Ying Liu, Lewis Hassell, Kennichi Kakudo, Huy Gia Vuong

Mucoepidermoid carcinoma (MEC) and sclerosing MEC with eosinophilia (SMECE) are rare primary thyroid carcinomas. In this study, we aimed to present our multicenter series of MEC and SMECE and integrated our data with published literature to further investigate the clinicopathological characteristics and prognoses of these tumors. We found 2 MECs and 4 SMECEs in our multicenter archives. We performed fluorescence in situ hybridization (FISH) to determine the MAML2 gene rearrangement. We screened for mutations in BRAF, TERT promoter, and RAS mutations using Sanger sequencing and digital polymerase chain reaction. Histopathologically, MECs and SMECEs were composed of two main cell types including epidermoid and mucin-secreting cells, arranged in cords, nests, and tubules. SMECEs were characterized by a densely sclerotic stroma with abundant eosinophils. We did not detect any MAML2 fusion in any of our cases. Two MEC cases harbored concomitant BRAF p.V600E and TERT C228T mutations. RAS mutations were absent in all cases. Concurrent foci of another thyroid malignancy were more commonly seen in MECs (p < 0.001), whereas SMECEs were associated with chronic lymphocytic thyroiditis (p < 0.001). MECs and SMECEs had equivalent recurrence-free survival (RFS) but MECs conferred significantly dismal disease-specific survival (DSS) as compared to SMECEs (p = 0.007). In conclusion, MECs and SMECEs not only shared some similarities but also demonstrated differences in clinicopathological characteristics, prognoses, and molecular profiles. SMECEs had a superior DSS in comparison to MECs, suggesting that they are low-grade cancers. This could help clinicians better evaluate patient outcomes and decide appropriate treatment plans.

黏液表皮样癌(MEC)和硬化性MEC伴嗜酸性粒细胞增多症(SMECE)是罕见的原发性甲状腺癌。在本研究中,我们旨在展示我们的多中心MEC和SMECE系列,并将我们的数据与已发表的文献相结合,以进一步研究这些肿瘤的临床病理特征和预后。我们在我们的多中心档案中发现了2个mec和4个SMECEs。我们进行了荧光原位杂交(FISH)来确定MAML2基因重排。我们使用Sanger测序和数字聚合酶链反应筛选BRAF、TERT启动子和RAS突变的突变。组织病理学上,mec和SMECEs主要由表皮样细胞和粘液分泌细胞两种类型组成,排列成索状、巢状和小管状。SMECEs的特点是间质致密硬化,含有丰富的嗜酸性粒细胞。我们在所有病例中均未发现任何MAML2融合。2例MEC患者伴有BRAF p.V600E和TERT C228T突变。所有病例均无RAS突变。同时发生另一种甲状腺恶性病灶在mec中更为常见(p
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引用次数: 4
TOP2A Expression in Pheochromocytoma and Abdominal Paraganglioma: a Marker of Poor Clinical Outcome? TOP2A在嗜铬细胞瘤和腹部副神经节瘤中的表达:临床预后差的标志?
IF 4.4 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2023-03-01 DOI: 10.1007/s12022-022-09746-w
Karolina Solhusløkk Höse, Adam Stenman, Fredrika Svahn, Catharina Larsson, C Christofer Juhlin

Pheochromocytoma and abdominal paraganglioma (PPGL) are rare neuroendocrine tumors originating from chromaffin cells. Even though only 10-15% of the tumors metastasize, all PPGLs are considered potentially malignant. Topoisomerase 2A (TOP2A) is a protein involved in cell proliferation and has been found to be over-expressed in metastatic PPGL. To provide support whether TOP2A could serve as a prognostic marker, 88 PPGLs (of which 8 metastatic/relapsing) and 10 normal adrenal gland samples were assessed for TOP2A mRNA expression using quantitative real-time PCR (qRT-PCR) and TOP2A immunohistochemistry. Comparisons to clinical parameters connected to metastatic behavior were made, and The Cancer Genome Atlas was used for validation of the results. A significant association between high TOP2A mRNA expression in primary PPGL and subsequent metastatic events (p = 0.008) was found, as well as to specific histological features and clinical parameters connected to metastatic behavior and mutations in SDHB. TOP2A immunoreactivity was calculated as an index of positive nuclei divided by the total amount of nuclei, and this index associated with TOP2A mRNA levels (p = 0.023) as well as the Ki-67 labeling index (p = 0.001). To conclude, TOP2A is a potential prognostic marker as it is frequently elevated in PPGL displaying subsequent metastatic disease, and future studies in larger cohorts are warranted to determine if a TOP2A index as assessed by immunohistochemistry could be a marker of poor outcome. Additionally, elevated levels of TOP2A could indicate a potential actionable event, and future studies with topoisomerase inhibitors would be of interest.

嗜铬细胞瘤和腹腔副神经节瘤是罕见的起源于嗜铬细胞的神经内分泌肿瘤。尽管只有10-15%的肿瘤转移,但所有的ppgl都被认为是潜在的恶性肿瘤。拓扑异构酶2A (TOP2A)是一种参与细胞增殖的蛋白,在转移性PPGL中被发现过表达。为了支持TOP2A是否可以作为预后标志物,我们采用实时荧光定量PCR (qRT-PCR)和TOP2A免疫组化技术检测了88例PPGLs(其中8例转移/复发)和10例正常肾上腺样本的TOP2A mRNA表达。将与转移行为相关的临床参数进行比较,并使用癌症基因组图谱来验证结果。发现原发性PPGL中TOP2A mRNA的高表达与随后的转移事件之间存在显著关联(p = 0.008),以及与SDHB转移行为和突变相关的特定组织学特征和临床参数。TOP2A免疫反应性计算为阳性细胞核指数除以细胞核总数,该指数与TOP2A mRNA水平(p = 0.023)和Ki-67标记指数(p = 0.001)相关。综上所述,TOP2A是一种潜在的预后标志物,因为它在PPGL中经常升高,显示随后的转移性疾病,未来有必要在更大的队列中进行研究,以确定免疫组织化学评估的TOP2A指数是否可能是预后不良的标志物。此外,TOP2A水平升高可能预示着潜在的可操作事件,未来对拓扑异构酶抑制剂的研究将会引起人们的兴趣。
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引用次数: 0
Update on C-Cell Neuroendocrine Neoplasm: Prognostic and Predictive Histopathologic and Molecular Features of Medullary Thyroid Carcinoma. c细胞神经内分泌肿瘤的最新进展:甲状腺髓样癌的预后和预测组织病理学和分子特征。
IF 4.4 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2023-03-01 DOI: 10.1007/s12022-023-09753-5
Chan Kwon Jung, Shipra Agarwal, Jen-Fan Hang, Dong-Jun Lim, Andrey Bychkov, Ozgur Mete

Medullary thyroid carcinoma (MTC) is a C-cell-derived epithelial neuroendocrine neoplasm. With the exception of rare examples, most are well-differentiated epithelial neuroendocrine neoplasms (also known as neuroendocrine tumors in the taxonomy of the International Agency for Research on Cancer [IARC] of the World Health Organization [WHO]). This review provides an overview and recent evidence-based data on the molecular genetics, disease risk stratification based on clinicopathologic variables including molecular profiling and histopathologic variables, and targeted molecular therapies in patients with advanced MTC. While MTC is not the only neuroendocrine neoplasm in the thyroid gland, other neuroendocrine neoplasms in the thyroid include intrathyroidal thymic neuroendocrine neoplasms, intrathyroidal parathyroid neoplasms, and primary thyroid paragangliomas as well as metastatic neuroendocrine neoplasms. Therefore, the first responsibility of a pathologist is to distinguish MTC from other mimics using appropriate biomarkers. The second responsibility includes meticulous assessment of the status of angioinvasion (defined as tumor cells invading through a vessel wall and forming tumor-fibrin complexes, or intravascular tumor cells admixed with fibrin/thrombus), tumor necrosis, proliferative rate (mitotic count and Ki67 labeling index), and tumor grade (low- or high-grade) along with the tumor stage and the resection margins. Given the morphologic and proliferative heterogeneity in these neoplasms, an exhaustive sampling is strongly recommended. Routine molecular testing for pathogenic germline RET variants is typically performed in all patients with a diagnosis of MTC; however, multifocal C-cell hyperplasia in association with at least a single focus of MTC and/or multifocal C-cell neoplasia are morphological harbingers of germline RET alterations. It is of interest to assess the status of pathogenic molecular alterations involving genes other than RET like the MET variants in MTC families with no pathogenic germline RET variants. Furthermore, the status of somatic RET alterations should be determined in all advanced/progressive or metastatic diseases, especially when selective RET inhibitor therapy (e.g., selpercatinib or pralsetinib) is considered. While the role of routine SSTR2/5 immunohistochemistry remains to be further clarified, evidence suggests that patients with somatostatin receptor (SSTR)-avid metastatic disease may also benefit from the option of 177Lu-DOTATATE peptide radionuclide receptor therapy. Finally, the authors of this review make a call to support the nomenclature change of MTC to C-cell neuroendocrine neoplasm to align this entity with the IARC/WHO taxonomy since MTCs represent epithelial neuroendocrine neoplasms of endoderm-derived C-cells.

甲状腺髓样癌(MTC)是一种源自c细胞的上皮性神经内分泌肿瘤。除极少数病例外,大多数为分化良好的上皮性神经内分泌肿瘤(在世界卫生组织(WHO)国际癌症研究机构(IARC)的分类中也称为神经内分泌肿瘤)。本文综述了分子遗传学、基于临床病理变量(包括分子谱和组织病理变量)的疾病风险分层以及晚期MTC患者的靶向分子治疗方面的最新循证数据。虽然MTC不是甲状腺中唯一的神经内分泌肿瘤,但甲状腺中的其他神经内分泌肿瘤包括甲状腺内胸腺神经内分泌肿瘤、甲状腺内甲状旁腺肿瘤、原发性甲状腺副神经节瘤以及转移性神经内分泌肿瘤。因此,病理学家的首要责任是使用适当的生物标志物将MTC与其他模拟物区分开来。第二项职责包括仔细评估血管浸润状态(定义为肿瘤细胞侵入血管壁并形成肿瘤纤维蛋白复合物,或血管内肿瘤细胞与纤维蛋白/血栓混合)、肿瘤坏死、增殖率(有丝分裂计数和Ki67标记指数)、肿瘤分级(低级别或高级别)以及肿瘤分期和切除边缘。鉴于这些肿瘤的形态学和增生性异质性,强烈建议进行彻底的抽样检查。通常在所有诊断为MTC的患者中进行致病性种系RET变异的常规分子检测;然而,多灶c细胞增生与至少一个灶MTC和/或多灶c细胞瘤的关联是种系RET改变的形态学先兆。在没有致病性种系RET变异的MTC家族中,评估涉及RET以外基因(如MET变异)的致病性分子改变的状态是有意义的。此外,应在所有晚期/进展性或转移性疾病中确定体细胞RET改变的状态,特别是在考虑选择性RET抑制剂治疗(例如,selpercatinib或pralsetinib)时。虽然常规SSTR2/5免疫组化的作用仍有待进一步阐明,但有证据表明,生长抑素受体(SSTR)依赖型转移性疾病患者也可能受益于177Lu-DOTATATE肽放射性核素受体治疗。最后,本综述的作者呼吁支持将MTC命名为c细胞神经内分泌肿瘤,以使其与IARC/WHO的分类保持一致,因为MTC代表内胚层来源的c细胞上皮性神经内分泌肿瘤。
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引用次数: 4
The Thyroid Pathologist Meets Therapeutic Pharmacology. 甲状腺病理学家与治疗药理学。
IF 4.4 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2023-03-01 DOI: 10.1007/s12022-023-09749-1
Christopher M Sande, Isabella Tondi Resta, Virginia A Livolsi

The effects of many pharmacological agents on thyroid function are well known. Direct influences on measurements of thyroid function tests are also described. However, certain classes of drugs produce morphological changes in the gland. This review focuses on the significance of the following drug classes for the thyroid pathologist: iodine, antithyroid drugs, psychotropic drugs, antibiotics, cardiotropic drugs, antidiabetic drugs, and immunomodulatory agents. Radioactive iodine initially induces mild histologic changes; however, the long-term effects include marked follicular atrophy, fibrosis, and nuclear atypia-changes that vary depending on the pre-therapy condition of the gland. Some psychotropic drugs have been associated with a spectrum of inflammatory changes throughout the gland. The tetracycline class of antibiotics, namely minocycline, can lead to a grossly black thyroid gland with pigment seen in both colloid and follicular epithelial cells while variably present within thyroid nodules. The surgical pathologist most commonly sees an amiodarone-affected gland removed for hyperthyroidism, and the histologic findings again depend on the pre-therapy condition of the gland. While GLP-1 receptor agonists carry an FDA black box warning for patients with a personal or family history of multiple endocrine neoplasia or medullary thyroid carcinoma, the C cell hyperplasia originally noted in rats has not borne out in human studies. Finally, thyroiditis and hypothyroidism are well known complications of checkpoint inhibitor therapy, and rare cases of severe thyroiditis requiring urgent thyroidectomy have been reported with unique histologic findings. In this review, we describe the histologic findings for these drugs and more, in many cases including their functional consequences.

许多药物对甲状腺功能的影响是众所周知的。还描述了对甲状腺功能测试测量的直接影响。然而,某些种类的药物会引起腺体的形态改变。本文就碘、抗甲状腺药物、精神药物、抗生素、促心药物、降糖药和免疫调节剂等药物对甲状腺病理学家的意义作一综述。放射性碘最初会引起轻微的组织学改变;然而,长期影响包括明显的滤泡萎缩、纤维化和核非典型性——这些变化取决于治疗前腺体的状况。一些精神药物与整个腺体的一系列炎症变化有关。四环素类抗生素,即二甲胺四环素,可导致甲状腺呈粗黑色,在胶体和滤泡上皮细胞中均可见色素,而在甲状腺结节中不同程度地存在。外科病理学家最常看到因甲状腺功能亢进而切除胺碘酮影响的腺体,组织学结果再次取决于腺体的治疗前状况。虽然GLP-1受体激动剂对个人或家族有多发性内分泌瘤或甲状腺髓样癌病史的患者有FDA黑盒警告,但最初在大鼠中发现的C细胞增生尚未在人类研究中得到证实。最后,甲状腺炎和甲状腺功能减退是检查点抑制剂治疗的众所周知的并发症,罕见的严重甲状腺炎需要紧急甲状腺切除术的病例已经报道了独特的组织学表现。在这篇综述中,我们描述了这些药物的组织学发现,在许多情况下,包括它们的功能后果。
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引用次数: 3
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Endocrine Pathology
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