Clinically Relevant Prognostic Parameters in Differentiated Thyroid Carcinoma

Although differentiated thyroid carcinomas typically pursue an indolent clinical course, it is important to identify the subset of tumors that are most likely to behave aggressively so that patients with these tumors are counseled and treated appropriately. Extent of disease is fundamental to the prognostication for differentiated thyroid carcinoma; however, there are additional histologic features of the tumor separate from extent of disease that have been shown to affect clinical course. This review will start with a discussion of aggressive variants of papillary thyroid carcinoma, move to the prognostic significance of vascular invasion in follicular thyroid carcinoma, and finish with a discussion of Hürthle cell carcinoma, with an emphasis on why it is not considered a subtype of follicular thyroid carcinoma in the 2017 WHO Classification of Tumors of Endocrine Organs.     

138例131I治疗分化型甲状腺癌的回顾性分析

目的 评价131I治疗分化型甲状腺癌(DTC)术后及合并甲状腺外转移患者的疗效,并分析其常见副作用发生情况.方法 对138例经病理及影像学检查确诊为分化型甲状腺癌及合并甲状腺外转移的患者采用131I进行治疗,“清甲”、淋巴结转移、远处脏器或骨转移剂量分别为3.7GBq、5.55 GBq、7.4 GBq.结果 通过1～2次131I治疗,89例清甲患者中完全清除残留甲状腺者86例,完全清除率96.6％,不完全清除者3例.合并甲状腺外转移49例患者中,通过3～6次治疗后治愈或好转者43例.结论 分化型甲状腺癌术后应根据术后分期及复发危险度分层选择性应用131I进行清甲及对合并甲状腺外转移患者进行治疗具有较好的疗效,常见副作用相对较少,一般轻微可逆.     

Anaplastic Thyroid Carcinoma: An Ultrastructural Study of 10 Cases

Anaplastic carcinoma of the thyroid is an aggressive, rapidly fatal neoplasm that is generally believed to arise from the epithelium of the thyroid follicle. When differentiated carcinoma is not present, the diagnosis can be difficult and confusion with a sarcoma is frequently a problem. Ten anaplastic thyroid carcinomas have been examined by light and electron microscopy and compared with two biologically aggressive, solid follicular carcinomas. Ultrastructural study revealed evidence of epithelial differentiation in all the anaplastic carcinomas, confirming their origin from thyroid follicular cells. The study illustrates the value of electron microscopy in establishing the diagnosis of anaplastic carcinoma and in differentiating it from sarcoma.     

Poorly Differentiated Thyroid Carcinoma: Diagnostic Features and Controversial Issues

Poorly differentiated thyroid carcinomas are a heterogeneous group of tumors occupying an area intermediate between well-differentiated follicular or papillary carcinoma and anaplastic carcinomas, from both a histopathogenetic and a clinical point of view. Large tumor series selected on the basis of structural and/or other morphological criteria showed that poorly differentiated carcinomas have a distinct biological behavior, and the classification of these tumors into a separate group appears justified, although strict homogeneous diagnostic criteria should be achieved and widely accepted to better characterize such tumor entity. Moreover, the identification of the prognostic parameters segregating aggressive from indolent cases has important clinical implications. Molecular data in the literature, although limited by the heterogeneous case series analyzed, identify ras alterations as the most common molecular alteration in poorly differentiated carcinomas, thus, depicting a peculiar molecular pathway in this tumor type as compared to well-differentiated follicular and papillary carcinomas. The present paper aims to review the various aspects of this tumor type, from morphology to immunohistochemistry and molecular abnormalities from a practical and daily practice-oriented point of view.     

Ultrastructural Features of Solid/Trabecular Areas in Differentiated Thyroid Carcinoma

The presence of areas exhibiting a solid/trabecular pattern of growth within an otherwise differentiated thyroid carcinoma represents a source of controversy as regards its proper classification and biologic and prognostic significance. The aim of the current study was to investigate the ultrastructural features of solid/trabecular areas in differentiated thyroid carcinoma and to compare those features with the submicroscopic profile of differentiated, poorly differentiated (insular), and undifferentiated (anaplastic) variants of thyroid cancer. The study series included differentiated carcinoma with solid/trabecular areas (3 cases), conventional papillary carcinoma (4 cases), follicular variant of papillary carcinoma (4 cases), poorly differentiated (insular) carcinoma (3 cases), and undifferentiated (anaplastic) carcinoma (3 cases). It was found that the solid/trabecular areas in differentiated carcinoma and poorly differentiated (insular) carcinoma share similar ultrastructural features and overall retain, even if attenuated, many of the submicroscopic attributes of differentiated carcinomas. In particular, nests of neoplastic cells were observed showing a highly developed cytosecretory apparatus and the presence of numerous abortive/rudimentary follicles, and intercellular and intracellular (intracytoplasmic) lumina/canaliculi of variable morphology. The study supports the hypothesis that the solid/trabecular areas do not merely represent an architectural pattern but rather should be regarded as the expression of a process of reduced differentiation similar to that of poorly differentiated (insular) carcinoma.     

Undifferentiated (Anaplastic) Thyroid Carcinoma and Iodine Intake in Salta, Argentina

This study was conducted to investigate the natural history of undifferentiated thyroid carcinoma (UTC) in the iodine-deficient province of Salta, Argentina, in relation to salt iodization and health care standards. Five hundred ninety-three thyroid cancers diagnosed from 1958 to2012 were reviewed based mainly on the WHO classification and grouped into three periods, one before and two after iodine prophylaxis. The incidence of UTC was analyzed in relation to changing concentrations of potassium iodide (KI) in salt during the prophylaxis period (from 40 to 33.3 mg KI/kg salt), establishment of primary health care centers throughout the region, and use of fine needle aspiration (FNA) cytology. Twenty-nine UTCs were found in the whole series. The frequency of UTC decreased from 15.2 % (9/59 cases) in the first period to 2.6 % (10/381 cases) well after salt iodination (x ² Fisher's test, p?<?0.0002), and the incidence from 1.4/10⁶/year to 0.1/10⁶/year (Student's t test, p?<?0.06), respectively. The decline of UTC after iodine prophylaxis occurred even after decreasing concentrations of KI in salt and timely coincided with the establishment of primary health care centers throughout the region and routine use of FNA. The lower rate of UTC after iodine prophylaxis in the province of Salta is mostly related to earlier detection of more differentiated thyroid tumors rather than higher salt iodization.     

Clinicopathological and Molecular Histochemical Review of Skull Base Metastasis from Differentiated Thyroid Carcinoma

Skull base metastasis from differentiated thyroid carcinoma including follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma (PTC) is a rare clinical entity. Eighteen FTC cases and 10 PTC cases showing skull base metastasis have been reported. The most common symptom of skull base metastasis from FTC and PTC is cranial nerve dysfunction. Bone destruction and local invasion to the surrounding soft tissues are common on radiological imaging. Skull base metastases can be the initial clinical presentation of FTC and PTC in the presence of silent primary sites. The possibility of skull base metastasis from FTC and PTC should be considered in patients with the clinical symptoms of cranial nerve dysfunction and radiological findings of bone destruction. A variety of genetic alterations in thyroid tumors have been identified to have a fundamental role in their tumorigenesis. Molecular histochemical studies are useful for elucidating the histopathological features of thyroid carcinoma. Recent molecular findings may provide novel molecular-based treatment strategies for thyroid carcinoma.     

131I去除分化型甲状腺癌术后残余组织的疗效观察

目的 观察131I去除分化型甲状腺癌（DTC）术后残余组织的疗效.方法 采用131I去除甲状腺癌术后残余组织115例,131I剂量为2.96 ～ 3.7GBq（80 ～ 100 mCi）,服131 I后3个月停用甲状腺片,改服三碘甲状腺原氨酸片50μg/d,连续15天,再停药15天以上,做全身131I显像.结果 甲状腺癌术后残余组织去除率达70％.结论 131I去除甲状腺癌术后残余组织的疗效较好,可以有效防止甲状腺癌的复发和转移.     

Metronomic Chemotherapy in Anaplastic Thyroid Carcinoma: A Potentially Feasible Alternative to Therapeutic Nihilism

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive malignancies and prognostic outlook remains very dismal. Treatment most often is palliative in intent attempting to relieve the patients from local compressive symptoms in the neck. Radical surgery, radiotherapy (RT), and chemotherapy have not been tested in large prospective trials, and current evidence from retrospective series and small trials indicate only marginal survival benefits. Given the poor prognostic and therapeutic outlook, patients must be encouraged to be actively involved in the decision making process. We report the case of an elderly patient who had no response to palliative RT, and was treated with oral metronomic chemotherapy. The response to oral metronomic chemotherapy was dramatic, and the patient has enjoyed complete freedom from symptoms as well as radiologically exhibits a complete regression. Thus, we document the first ever use of a simple, cost-effective, and convenient oral metronomic chemotherapeutic regimen delivering a remarkable response in an elderly patient with ATC.     

暂停甲状腺激素替代治疗对分化型甲状腺癌患者血脂的影响

目的：探讨分化型甲状腺癌（DTC）患者暂停左旋甲状腺素（优甲乐）替代治疗后血脂的变化。方法：分别检测55例接受131I放射性治疗的DTC患者在激素替代治疗期间和停药4周后甲状腺功能全套（全自动化学发光法）和血脂全套7项（生化法）（三酰甘油、胆固醇、低/高密度脂蛋白、载脂蛋白A、B和E）,并对结果进行相关性分析。结果：暂停激素替代治疗4周后,患者均出现程度不同的甲减表现,TSH水平（中位数及范围）由0.45（0.07-27.13）mIU/L上升到92.4（8.4〉150）mIU/L;血脂7项指标水平亦升高,除三酰甘油外,其余6项与TSH水平相关,有显著性（rs=0.453-0.601,P〈0.002）。结论：暂停甲状腺激素替代治疗4周后,甲状腺癌患者血脂水平普遍升高,表明脂代谢水平受到一定程度的抑制。     

老年分化型甲状腺癌肺转移危险因素分析

目的 探讨老年分化型甲状腺癌(DTC)发生肺转移的危险因素.方法 回顾性分析72例年龄≥60岁DTC患者的临床资料.通过甲状腺球蛋白水平、131Ⅰ全身显像、胸部平片、胸部CT或肺部病灶病理确诊肺转移.对性别、年龄、病理类型、肿瘤大小、病灶数量、甲状腺包膜侵犯、颈淋巴结转移7个因素进行单因素和多因素分析,寻找影响老年DTC发生肺转移的危险因素.结果 72例老年DTC中,肺转移率为27.8％.单因素分析结果显示:甲状腺滤泡状癌、肿瘤直径≥4cm、甲状腺包膜侵犯、颈淋巴结转移是预测肺转移的显著性因素(P＜0.05).多因素Logistics回归分析结果显示,滤泡状癌、肿瘤直径≥4cm、甲状腺包膜侵犯、颈淋巴结转移是老年DTC肺转移的独立危险因素(P＜0.05).结论 老年DTC肺转移发生率较高.肺转移与多种临床病理因素相关,滤泡状癌、肿瘤直径≥4cm、甲状腺包膜侵犯、颈淋巴结转移的患者更容易发生肺转移,应加强对这类患者的治疗与随访.     

Anaplastic Thyroid Carcinoma with Rhabdomyoblastic Differentiation: A Case Report with a Good Clinical Outcome

Anaplastic thyroid carcinoma is a rare and highly malignant disease. Usually, this type of tumor is irresectable, and almost all patients die within 1 year after diagnosis. We present a case of anaplastic thyroid carcinoma with rhabdomyoblastic differentiation and good therapeutic outcome. A 76-year-old female was referred to our hospital with a growing, painless neck mass which existed for 3 months. Biopsy of the mass showed microscopically and immunohistochemically a follicular (Hürthle cell) carcinoma of the thyroid, dedifferentiated to an anaplastic carcinoma with divergent differentiation along rhabdomyoblastic cell lines. The patient underwent a total thyroidectomy with additional lymph node dissection, followed by two episodes of 150 mC I¹³¹ therapy and external radiotherapy. After a follow-up of 3 years, the patient still remains in a good condition without any signs of recurrent disease. Other cases of rhabdomyoblastic and rhabdoid anaplastic thyroid carcinomas have been described. Both types of carcinoma are associated with an aggressive clinical course. In our case, the patient is still alive without evidence of disease 3 years after primary therapy. The good clinical outcome of our patient suggests that surgical resection, radiotherapy, and I-131 ablation therapy with curative intent seems to be an adequate treatment option in patients with anaplastic thyroid carcinoma with rhabdoid and rhabdomyoblastic differentiation.     

131I治疗儿童和青少年分化型甲状腺癌肺转移疗效的系统评价

目的 对131I治疗儿童和青少年分化型甲状腺癌（DTC）肺转移的疗效进行系统评价.方法 计算机检索1990年1月至2013年8月国内外公开发表的有关131I治疗儿童和青少年DTC肺转移的中英文文献,从中提取患者疗效及预后的相关资料.结果 共纳入10篇符合标准的回顾性研究报道,合计患者117例.按照131I治疗儿童和青少年DTC肺转移的疗效评价标准,完全缓解、好转或稳定、无效或进展的患者分别为47.0％、37.6％、15.4％;患者随访期内生存率为97.4％.1例患者出现了继发性肿瘤.结论 131I治疗儿童和青少年DTC肺转移是一种安全有效的治疗方法.     

SPECT/CT融合显像在分化型甲状腺癌转移灶诊断中的应用价值分析

目的 探讨SPECT/CT 131I显像在诊断分化型甲状腺癌转移灶中,以及在131I放射治疗后复发和转移中的应用价值,为临床诊断和治疗甲状腺癌提供依据.方法 选择2013年5月至2016年5月我院住院治疗经病理证实的分化型甲状腺癌住院患者90例,分别实施131I-WBS,131I-SPECT/CT显像诊断,观察显像诊断结果以及Tg水平.结果 131 I-WBS共诊断出125个复发和转移病灶,其中113个经病理检查证实,其诊断灵敏度和准确度分别为85.03％,78.62％:131I-SPECT/CT共诊断出134个复发和转移病灶,其中128个经病理检查证实,其诊断灵敏度和准确度分别为91.16％,87.58％;说明131I-SPECT诊断的灵敏度要优于131 I-WBS显像,两组数据比较差异有统计学意义(P＜0.05);此外131I-WBS显像、131I-SPECT/CT显像阳性的Tg水平与阴性患者比较明显升高,且差异有统计学意义(P＜0.05).结论 SPECT/CT显像在诊断分化型甲状腺癌转移灶方面具有重要价值,值得临床广泛的应用.     

分化型甲状腺癌清甲后患者甲状腺素撤药后血清TSH观察

目的:通过对分化型甲状腺癌患者甲状腺素撤药后的血清TSH的分期、定量检测,研究血清TSH在甲状腺素撤药后的变化规律及最合适撤药时间。方法:145例131I清甲治疗后6个月的分化型甲状腺癌术后患者,在甲状腺素撤药后(2～4)周,每周测定其血清TSH浓度。分组比较不同性别、年龄、病理类型患者在甲状腺素撤药后(2～4)周时血清TSH水平的差异,P>0.05表示差异有显著性。结果:①甲状腺素撤药后(2～4)周,男性组TSH水平均高于女性组,撤药时间越长,组间差异越明显(P=0.037、0.006、0.001);<45岁年龄组TSH水平均高于≥45岁年龄组,撤药时间越长,组间差异越明显(P=0.010、0.006、0.001);滤泡状癌组TSH水平均高于乳头状癌组,组间比较无统计学差异。②甲状腺素撤药后(2～4)周,男性组分别有72.2%(26/36),91.7%(33/36),100%(36/36)血清TSH>25μIU/ml,女性组分别有64.2%(70/109),86.2%(94/109),96.3%(105/109)血清TSH>25μIU/ml;<45岁年龄组分别有62.1%(36/58),93.1%(54/58),100%(58/58)血清TSH>25μIU/m,≥45岁年龄组分别有51.7%(45/87),80.5%(70/87),97.7%(85/87)血清TSH>25μIU/ml。结论:分化型甲状腺癌术后并行131I清甲治疗后的患者在甲状腺素撤药后,血清TSH水平的变化因性别及年龄而不同,甲状腺素撤药时间需根据性别和年龄而异,建议男性患者和<45岁患者在撤药后3周及时检测TSH,避免不必要的TSH水平过高及甲减副作用。     

Metastatic Anaplastic Thyroid Carcinoma in Complete Remission: Morphological,Molecular, and Clinical Work-Up of a Rare Case

Anaplastic thyroid carcinoma (ATC) exhibits an exceedingly poor prognosis, and the current treatment options are, for most cases, palliative by nature. Few reports of long-time survivors exist, although in these patients, tumors often were limited to the thyroid and/or regional lymph nodes. We describe a 64-year-old male who developed a rapidly growing mass in the left thyroid lobe. A fine-needle aspiration biopsy (FNAB) was consistent with ATC, and the patient underwent preoperative combined chemo- and radiotherapy followed by a hemithyroidectomy. The ensuing histopathological investigation was consistent with ATC adjoined by an oxyphilic well-differentiated lesion, likely a Hürthle cell carcinoma. Tumor margins were negative, and no extrathyroidal extension was noted. Focused next-generation sequencing analysis of the primary tumor tissue identified a TP53 gene mutation but could not identify any potential druggable targets. Additional Sanger sequencing detected a C228T TERT promoter mutation. The tumor was found to be microsatellite stable and displayed PDL1 expression in 80% of tumor cells. Following a CT scan 1 month postoperatively, metastatic deposits were suspected in the lung as well as in the left adrenal gland, of which FNAB verified the latter. Remarkably, upon radiological follow-up, the disease had gone into apparent complete remission. The patient is alive and well with no signs of residual disease after 12 months of follow-up. We here summarize the clinical, histological, and molecular data of this highly interesting patient case and review the literature for possible common denominators with other patients with disseminated ATC.     

大剂量131I治疗36例分化型甲状腺癌转移灶的临床分析

目的 :评价分化型甲状腺癌 (以下简称甲癌 )并远处转移患者接受多次大剂量1 3 1 I治疗的临床效果及其副作用。方法 :根据甲癌转移部位给予患者每次口服1 3 1 I (5 5 5～ 9 2 5 )GBq ,两次治疗间隔 6个月。根据1 3 1 I显像 ,血甲状腺球蛋白 (Tg)水平判断治疗效果 ;观察治疗对血像、甲状旁腺功能等的影响。结果 :①疗效 :36例甲癌转移患者治愈 5 5 5 % (2 0例 ) ,有效 38 9% (1 4例 ) ,无效 5 6 % (2例 )。②副作用 :仅 1例患者在治疗后 2周出现甲状旁腺素 (PTH)一过性下降。结论 :采用1 3 1 I多次大剂量治疗甲癌转移灶疗效佳 ,副作用小 ,不会发生甲状旁腺功能减退症等并发症