Anaplastic and poorly differentiated thyroid carcinoma: therapeutic strategies and treatment outcome of 52 consecutive patients

Anaplastic thyroid carcinoma (ATC) is one of the most lethal malignancies; poorly differentiated thyroid carcinoma (PDTC) is a new diagnosis for rare aggressive thyroid tumours. Surgery is often considered the only chance for survival, but the benefit of surgery and subsequent multimodal therapy is unclear. We retrospectively analyzed the outcome of 44 ATC and 8 PDTC consecutive patients treated at Helsinki University Central Hospital between 1990 and 2008. All ATC and PDTC cases were re-examined and reclassified histologically. Median survival was only 3.1 months for ATC, but 3.7 years for PDTC. Most patients in both groups eventually died of cancer. ATC patients were older than PDTC patients (74 vs. 66 years). Nodal and distant metastases had a negative impact on survival (ATC; p = 0.038, p = 0.008). Long-term survivors in both groups were stage N0M0 at presentation. Multimodal therapy was successful for 9 (20%) ATC patients, and their median survival was the longest (11.6 months) among treatment groups. Most PDTC patients (88%) underwent total thyroidectomy followed by radioiodine ablation; the only 2 who received chemotherapy survived longest. Although ATC and PDTC are both aggressive thyroid carcinomas, multimodal therapy for both can provide a chance of prolonged survival in patients with locoregional disease.     

Poorly differentiated and anaplastic thyroid cancer.

BACKGROUND: Poorly differentiated thyroid carcinoma (PDTC) and anaplastic (undifferentiated) thyroid carcinoma (ATC) comprise a small subset of thyroid tumors that are associated with a poor prognosis and account for a significant portion of the morbidity and mortality related to thyroid cancer. Since management strategies vary between these two entities, it is important for clinicians to be able to differentiate PDTC from ATC. METHODS: We reviewed the literature on PDTC and ATC and compared clinical and histopathologic features important in defining the disease process. RESULTS: Both PDTC and ATC display aggressive behavior with increased locoregional and distant disease. In most cases, patients are older and have large, locally advanced tumors. PDTC may represent an intermediate entity in the progression of well-differentiated thyroid carcinoma to ATC. The use of surgical management may be curative or palliative and differs between PDTC and ATC. The roles of radiotherapy and chemotherapy have not been well described. CONCLUSIONS: PDTC and ATC are rare diseases that carry a poor prognosis. Recognition of their different clinicopathologic features is important to the optimal management of these tumors.     

Thyrocyte-specific inactivation of p53 and Pten results in anaplastic thyroid carcinomas faithfully recapitulating human tumors

Anaplastic thyroid carcinoma (ATC) is the most aggressive form of thyroid cancer, and often derives from pre-existing well-differentiated tumors. Despite a relatively low prevalence, it accounts for a disproportionate number of thyroid cancer-related deaths, due to its resistance to any therapeutic approach. Here we describe the first mouse model of ATC, obtained by combining in the mouse thyroid follicular cells two molecular hallmarks of human ATC: activation of PI3K (via Pten deletion) and inactivation of p53. By 9 months of age, over 75% of the compound mutant mice develop aggressive, undifferentiated thyroid tumors that evolve from pre-existing follicular hyperplasia and carcinoma. These tumors display all the features of their human counterpart, including pleomorphism, epithelial-mesenchymal transition, aneuploidy, local invasion, and distant metastases. Expression profiling of the murine ATCs reveals a significant overlap with genes found deregulated in human ATC, including genes involved in mitosis control. Furthermore, similar to the human tumors, [Pten, p53]thyr-/- tumors and cells are highly glycolytic and remarkably sensitive to glycolysis inhibitors, which synergize with standard chemotherapy. Taken together, our results show that combined PI3K activation and p53 loss faithfully reproduce the development of thyroid anaplastic carcinomas, and provide a compelling rationale for targeting glycolysis to increase chemotherapy response in ATC patients.     

Three-dimensional nuclear architecture distinguishes thyroid cancer histotypes

Molecular markers can serve as diagnostic tools to support pathological analysis in thyroid neoplasms. However, because the same markers can be observed in some benign thyroid lesions, additional approaches are necessary to differentiate thyroid tumor subtypes, prevent overtreatment and tailor specific clinical management. This applies particularly to the recently described variant of thyroid cancer referred to as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). This variant has an estimated prevalence of 4.4% to 9.1% of all papillary thyroid carcinomas worldwide. We studied 60 thyroid lesions: 20 classical papillary thyroid carcinoma (CPTC), 20 follicular variant of PTC (FVPTC) and 20 NIFTP. We examined morphological and molecular features to identify parameters that can differentiate NIFTP from the other PTC subtypes. When blindly investigating the nuclear architecture of thyroid neoplasms, we observed that NIFTP has significantly longer telomeres than CPTC and FVPTC. Super-resolved 3D-structured illumination microscopy demonstrated that NIFTP is heterogeneous and that its nuclei contain more densely packed DNA and smaller interchromatin spaces than CPTC and FVPTC, a pattern that resembles normal thyroid tissue. These data are consistent with the observed indolent biological behavior and favorable prognosis associated with NIFTP, which lacks BRAF^V600E mutations. Of note, next-generation thyroid oncopanel sequencing was unable to distinguish the thyroid cancer histotypes in our study cohort. In summary, our data suggest that 3D nuclear architecture can be a powerful analytical tool to diagnose and guide clinical management of NIFTP.     

PD-L1 expression and immune cells in anaplastic carcinoma and poorly differentiated carcinoma of the human thyroid gland: A retrospective study

Anaplastic thyroid carcinoma (ATC) and poorly differentiated thyroid carcinoma (PDTC) have limited treatment options, and immune profiling may help select patients for immunotherapy. The prevalence and relevance of programmed death-1 ligand (PD-L1) expression and the presence of immune cells in ATC and PDTC has not yet been well established. The present study investigated PD-L1 expression (clone 22C3) and cells in the tumor microenvironment (TME), including tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs) and dendritic cells, in whole tissue sections of 15 cases of ATC and 13 cases of PDTC. Immunohistochemical PD-L1 expression using a tumor proportion score (TPS) with a 1% cut-off was detected in 9/15 (60%) of ATC cases and 1/13 (7.7%) of PDTC cases (P=0.006). PD-L1 expression in TILs was limited to the ATC group (73.3 vs. 0% in ATC and PDTC, respectively). In the ATC group, the TPS for tumor positive PD-L1 expression revealed a non-significant trend towards worse survival, but no difference was observed when investigating PD-L1 expression in TILs and TAMs. In addition to increased PD-L1 expression, all ATC cases exhibited significantly increased CD3⁺ and CD8⁺ T cells, CD68⁺ and CD163⁺ macrophages, and S100⁺ dendritic cells compared with the PDTC cases. Loss of mutL homolog 1 and PMS1 homolog 2 expression was observed in one ATC case with the highest PD-L1 expression, as well as in the only PDTC case positive for PD-L1. Notably, the latter was the only PDTC case exhibiting positivity for p53 and a cellular microenvironment similar to ATC. The current results indicated that PD-L1 expression was frequent in ATC, but rare in PDTC. In addition to PD-L1, the present study suggested that microsatellite instability may serve a role in both the TME and the identification of immunotherapy candidates among patients with PDTC.     

Early evolutionary divergence between papillary and anaplastic thyroid cancers

BackgroundPapillary thyroid cancer (PTC) is the most common thyroid carcinoma and exhibits an almost uniformly good prognosis, while anaplastic thyroid cancer (ATC) is less frequent and is one of the most aggressive cancers usually resistant to conventional treatment. Current hypothesis posits that ATC derives from PTC through the progressive acquisition of a discrete number of genomic alterations and implies that the mutational landscape of ATC resembles that of PTC. However, the clinical behaviour of ATC and PTC is radically different. We decided to address the disconnection between the clinical behaviour of ATC and PTC and the proposed model of the progressive development of ATC from PTC.Patients and methodsWe carried out exome sequencing of DNA from 14 ATC specimens including three cases of concomitant ATC and PTC as well as their corresponding normal DNA from 14 patients. The sequencing results were validated using droplet digital PCR. We carried out immunohistochemistry and immunofluorescence studies of the concomitant ATC and PTC cases. In addition, we integrated our sequencing results with the existing TCGA data.ResultsMost of the somatic mutations identified in the ATC component differed from the ones in PTC in the cases of concomitant ATC and PTC. The trunks of the phylogenetic trees representing the somatic mutations were short with long branches. In one case of concomitant PTC and ATC specimens, we observed an infiltration of PTC cells within the ATC component. Moreover, we integrated our results with data obtained from TCGA and observed that the most frequent mutations found in ATC presented high cancer cell fraction values and were significantly different from the PTC ones.ConclusionATC diverge from PTC early in tumour development and both tumour types evolve independently. Our work allows the understanding of the relationship between ATC and PTC facilitating the clinical management of these malignancies.     

Anaplastic thyroid carcinoma: Current diagnosis and treatment

Background:Anaplastic thyroid carcinoma (ATC), accounting for5% to 15% of primary malignant thyroid neoplasms, is one of themost aggressive solid tumors in humans. Generally, it is rapidly fatal, witha mean survival of six months after diagnosis. Multimodality treatment withsurgery and/or external beam radiotherapy and chemotherapy are of fundamentalimportance for local control of disease and to enhance survival. Design:We evaluated consecutive patients with ATC observed at theMayo Clinic from 1971 to 1993 and reviewed relevant articles published inmajor English-language medical journals. We used the MEDLINE database,selected bibliographies, and articles available in our personal files. Results:ATC usually does not concentrate radioiodine or expressthyroglobulin. It is essential to verify the diagnosis histologically becauseinsular thyroid cancer, lymphomas, and medullary thyroid cancer areoccasionally confused with undifferentiated neoplasms. Immunohistochemicalstudy is helpful in establishing the diagnosis. Multimodal therapy and thedevelopment of effective systemic chemotherapeutic agents should result inimprovements in survival, although no single agent has yet been identified. Conclusions:Aggressive multimodality treatment regimens showpromise in improving local control in patients with ATC. However, survivalrates remain low. Despite intense application of such therapy, no standardizedsuccessful treatment protocol has been established.     

1954-2009年间天津市肿瘤医院收治的甲状腺癌构成分析

目的 分析天津市肿瘤医院1954-2009年间住院患者甲状腺癌构成方面的变化趋势及其原因.方法 回顾性分析天津市肿瘤医院头颈科1954-2009年间不同时间段收治的4342例甲状腺癌患者的发病情况、病理类型及临床特征.结果 4342例甲状腺癌患者中,1954-1969年、1970-1979年、1980-1989年、1990-1999年、2000-2009年间甲状腺乳头状癌占同期收治甲状腺癌的比例分别为68.1%、78.3%、81.3%、82.1%和85.8%,呈上升趋势.其中甲状腺乳头状癌并发桥本氏甲状腺炎例数增多,肿瘤直径≤2 cm所占比例呈上升趋势;甲状腺滤泡癌、甲状腺未分化癌所占比例呈减少趋势;甲状腺髓样癌所占比例变化不明显.结论 1954-2009年间天津市肿瘤医院收治的甲状腺癌的构成比有显著变化,其中甲状腺乳头状癌所占比例升高,甲状腺滤泡癌及甲状腺未分化癌所占比例下降,其变化原因可能与检诊水平提高及高碘饮食等因素有关.

Abstract：

Objective To investigate and analyze the variation trends in the pathological composition of thyroid cancer patients treated in Tianjin Cancer Hospital from 1954 to 2009. Methods To retrospectively analyze the incidence and clinical features of different pathological types of thyroid cancers in 4342 patients between different time periods from 1954 to 2009. Results In the four main pathological types of thyroid cancers, the component ratio of papillary thyroid cancer in every period was 68. 1%,78.3%, 81.3%, 82.1%, 85.8%, respectively, while the morbidity of patients with papillary thyroid carcinoma concurrent with Hashimoto's thyroiditis was increased, so was the proportion of tumors in diameter ≤ 2 cm. The proportion of follicular thyroid carcinoma and anaplastic thyroid carcinoma was decreasing accordingly; however, the proportion of medullary thyroid carcinoma did not change significantly.Conclusions The pathological classification of the thyroid carcinoma patients has significant changes in the 4342 cases treated in our Hospital from 1954 to 2009. The proportion of papillary carcinoma is increased,while that of follicular carcinoma and anaplastic carcinoma is decreased. The reasons might attribute to theimproved level of consultations and iodized diet or other factors.     

Chromosomal imbalances associated with anaplastic transformation of follicular thyroid carcinomas

The genetic alterations that underlie the progression of follicular thyroid carcinoma towards anaplasia are still largely uncharacterised. We compared the Comparative Genomic Hybridization (CGH) profiles of 20 follicular (FTCs), 12 poorly differentiated (PDTCs) and seven anaplastic thyroid carcinomas (ATCs), in order to identify the chromosomal imbalances potentially associated with cancer progression. We found: (i) when considering that a 'direct' transformation of FTC towards anaplasia occurs, the defined significantly important alterations were the increase of gains at 3q (P<0.05) and 20q (P<0.01), and the increase of losses at 7q (P<0.05) and Xp (P<0.01); (ii) regarding poorly differentiated carcinomas as an intermediate independent entity in the anaplastic transformation of follicular cancers, evidenced as important alterations towards anaplasia, were the proportional decrease in copy sequences at 7p, 7q, 12q and 13q resulting from the significant decrease of DNA gains at 7p and 12q (P<0.05), and the significant increase of losses at 7q and 13q (P<0.05). These results unveil the chromosomal regions where genes of interest in thyroid anaplastic transformation are to be located, and demonstrate that different gene dosage copy sequence imbalances are associated to the 'direct' pathway of transformation of follicular into anaplastic cancers and to the progressive FTC --> PDTC --> ATC pathway.     

Proteome analysis identified maspin as a special feature of papillary thyroid carcinoma

This study aimed at investigating new mechanisms of carcinogenesis in thyroid cancer at the molecular level and at finding potential protein markers involved in the initiation of the different histological subtypes. For this, we performed differential proteome analysis on primary cultured thyrocytes (PT) and transformed thyrocytes (TT) derived from 238Pu alpha-particle irradiation using 2-dimensional electrophoresis (2-DE) and peptide mass fingerprinting (PMF) with matrix-assisted laser desorption/ionisation-time of flight mass spectrometry (MALDI-TOF MS). Image analysis showed that one protein was very strongly expressed in TT; 55 proteins were weaker, different in intensity, including 26 spots that were increased in PT, and 29 spots were decreased. The hot spot was identified as maspin, a unique member of the serpin family considered to be a class II tumor suppressor gene. To clarify the role of maspin in thyroid carcinogenesis we searched for protein expression in 20 normal (tumor-free) tissues, as well as in 20 follicular adenomas (FAD), 20 papillary carcinomas (PTC), 20 follicular carcinomas (FTC), 20 poorly differentiated carcinomas (PDTC), and 20 undifferentiated carcinomas (UTC). Maspin protein expression was detectable in none of the cases of normal tumor-free thyroid tissue, nor in FAD, FTC, PDTC and UTC. In contrast 14 of 20 PTC (70%) showed a moderate or strong cytoplasmic staining; 4 of these 14 cases had a moderate cytoplasmic and nuclear staining. In conclusion, we hypothesize that maspin protein expression is a special feature in the cascade of PTC genesis and that the way of initiating PTC is different from other thyroid carcinoma types.     

Poorly differentiated and anaplastic thyroid carcinomas: chromosomal and oligo-array profile of five new cell lines

Information on gene alterations associated to poorly differentiated (PDTC) and anaplastic thyroid carcinomas (ATC) is scarce. Using human cancer cell lines as a tool for gene discovery, we performed a cytogenetic and oligo-array analysis in five new cell lines derived from two PDTC and three ATC. In PDTC we evidenced, as important, the involvement of the MAPK/ERK kinase pathway, and downregulation of a group of suppressor genes that include E-cadherin. In ATC, downregulation of a specific group of oncosuppressor genes was also observed. Our ATC cell lines presented chromosomal markers of gene amplification, and we were able to identify for the first time the nature of the involved amplicon target genes. We found that the main molecular differences between the two cell line types were related to signal transduction pathways, cell adhesion and motility process. TaqMan experiments performed for five amplicon target genes and for two genes, which allowed a clear distinction between ATC and PDTC: CDH13 and PLAU corroborated array results, not only in the cell lines, but also in an additional set of primary 14 PDTC and three ATC. We suggest that our findings may represent new tools for the development of more effective therapies to the hitherto untreatable ATC.     

中国抗癌协会甲状腺癌整合诊治指南（2022精简版）

甲状腺癌（thyroid cancer,TC）是内分泌系统和头颈部最常见的恶性肿瘤。既往的30年中,全球范围内TC发病率大幅增加,成为十大恶性肿瘤之一。如何对TC进行筛查、诊断、规范化治疗,如何对持续/复发/转移性TC基于多学科会诊（multi-disciplinary team,MDT）客观评估地系统性整合治疗,以及规范、有效的治疗后动态评估及系统随访,将是提高中国TC患者生存率、改善生存质量的重要保证,也是甲状腺领域专家肩负的重要责任。为了更好地推动中国TC的临床管理,中国抗癌协会甲状腺癌专业委员会组织相关专家结合中国经验,撰写了《中国肿瘤整合诊治指南》。本指南涵盖不同病理类型TC的疾病管理,包括甲状腺乳头状癌、滤泡癌、髓样癌、未分化癌,旨在为中国TC的规范化诊治提供指导与参考。     

Histopathologic characterization of radioactive iodine-refractory fluorodeoxyglucose-positron emission tomography-positive thyroid carcinoma

BACKGROUND: Radioactive iodine-refractory (RAIR) 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) positive thyroid carcinomas represent the major cause of deaths from thyroid carcinomas (TC) and are therefore the main focus of novel target therapies. However, to the authors' knowledge, the histology of FDG-PET-positive RAIR metastatic thyroid carcinoma has not been described to date. METHODS: Metastatic tissue from RAIR PET-positive patients identified between 1996 and 2003 at the study institution were selected for histologic examination. The biopsied metastatic site corresponded to a FDG-PET positive lesion sampled within 2 years (87% of which were sampled within 1 year) of the PET scan. Detailed microscopic examination was performed on the metastatic deposit and the available primary tumors. Poorly differentiated thyroid carcinomas (PDTC) were defined on the basis of high mitotic activity (> or =5 mitoses/10 high-power fields) and/or tumor necrosis. Other types of carcinomas were defined by conventional criteria. The histology of the metastases and primary were analyzed, with disease-specific survival (DSS) as the endpoint. RESULTS: A total of 70 patients satisfied the selection criteria, 43 of whom had primary tumors available for review. Histologic characterization of the metastasis/recurrence in 70 patients revealed that 47.1% (n = 33 patients) had PDTC, 20% (n = 14 patients) had the tall cell variant (TCV) of papillary thyroid carcinoma, 22.9% (n = 16 patients) had well-differentiated papillary thyroid carcinoma (WDPTC), 8.6% (n = 6 patients) had Hurthle cell carcinoma (HCC), and 1.4% (n = 1 patient) had anaplastic carcinomas. The histopathologic distribution of the tumor in the primaries was: PDTC, 51%; TCV, 19%; WDPTC, 23%; and widely invasive HCC, 7%. A differing histology between the primary tumor and metastasis was observed in 37% of cases (n = 16 patients). In the majority of instances (63%; 10 of 16 patients) this was noted as transformation to a higher grade. Of the primary tumors classified as PTC, 70% progressed to more aggressive histotypes in the metastasis. Tumor necrosis and extensive extrathyroid extension in the primary tumor were found to be independent predictors of poorer DSS in this group of patients (P = .015). Approximately 68% of the PDTC primary tumors were initially classified by the primary pathologist as better-differentiated tumors on the basis of the presence of papillary and/or follicular architecture or the presence of typical PTC nuclear features. CONCLUSIONS: Several observations can be made based on the results of the current study. The majority of metastases in patients with RAIR PET-positive metastases are of a histologically aggressive subtype. However, well-differentiated RAIR metastatic disease is observable. Poorly differentiated disease is underrecognized in many cases if defined by architectural and nuclear features alone. The presence of tumor necrosis was found to be a strong predictor of aggressive behavior, even within this group of clinically aggressive tumors. Finally, there is a significant amount of histologic plasticity between primary tumors and metastases that may reflect the genetic instability of these tumors.     

Thyroid cancer after hysterectomy on benign indications: Findings from an observational cohort study in Sweden

To investigate the association between hysterectomy and thyroid cancer subtypes based on histopathology. They did a nationwide, population‐based, cohort study from 1973 to 2009 in Sweden. All women above 18 years of age during the period between January 1, 1973 and December 31, 2009 from the Register of Population (n = 5.704,202) were identified as the study population. Individual case ascertainment of primary thyroid cancer subtypes were restricted to 1993–2009 based on histological pathologic–anatomical‐diagnosis from the Cancer Register. Thyroid cancer subtypes were categorized based on histological morphology as: papillary, follicular and others (including anaplastic and medullary thyroid carcinoma). Information on benign hysterectomy derived from the Swedish Inpatient Register. Women with a hysterectomy (exposed) were compared with women not having had a hysterectomy (unexposed) using Cox's proportional hazard ratios (HRs). The adjusted HR for papillary thyroid cancer was significantly increased in exposed as compared with unexposed women (HR 1.70, 95% CI 1.04–2.79). There was no significant association between hysterectomy and follicular carcinoma or other thyroid cancers. There was a clear shift in the occurrence of thyroid cancer toward a lower attained age at the time of diagnosis among the exposed but no significant difference in overall survival when comparing exposed and unexposed (HR 1.02, 95% CI 0.48–2.16) Hysterectomy was associated with an increased risk for subsequent papillary thyroid cancer and diagnosis at a younger age compared with women not having had a hysterectomy but there were no differences in survival.     

以骨折骨痛为首发症状的滤泡状甲状腺癌骨转移1例临床探讨并文献复习

目的:探讨滤泡状甲状腺癌骨转移的临床特征和治疗方法。方法:回顾性分析1例以左侧锁骨病理性骨折及骨痛为首发症状的滤泡状甲状腺癌患者的临床影像学资料、病理学资料,随访治疗效果,并复习相关文献。结果:患者左侧甲状腺肿物考虑为滤泡状甲状腺癌。C5、T10椎体、左侧锁骨考虑为转移癌。行左侧锁骨部分切除术,术后病理提示:滤泡状甲状腺癌骨转移。结论:对以病理性骨折和骨痛为主要症状的滤泡状甲状腺癌,影像学与组织活检相结合有利于降低误诊率,治疗方案取决于对患者局部病灶和全身状况的全面评估。     

山东省沿海与内陆甲状腺癌患病模式变迁

目的：观察沿海城市（青岛市）和内陆城市（临沂市）11年来甲状腺乳头状癌（PTC）、滤泡型癌（FTC）、髓样癌（MTC）、未分化癌（ATC）患病率的变化趋势,并将内陆城市与沿海城市进行比较,以探讨碘营养与甲状腺癌的关系。方法：根据国际肿瘤分类标准,利用石蜡切片等方法对青岛大学医学院附属医院病理科、临沂市人民医院病理科和临沂市第二人民医院病理科1998年-2008年间收检的甲状腺恶性肿瘤进行重新分类,回顾性分析患者的平均确诊年龄、性别比例、构成比。结果：11年来4类甲状腺恶性肿瘤沿海城市（青岛）的总例数为734例,其中PTC占85.56%、FTC占8.86%、MTC占4.36%、ATC占1.22%。4类中女性发病均高于男性（男女比例1∶1.25-3.94）。PTC的平均确诊年龄最低（45.39岁）,ATC最高（61.56岁）。内陆城市（临沂）的总例数为421例,其中PTC占82.90%、FTC占9.74%、MTC占4.75%、ATC占2.61%。4类甲状腺癌中女性发病均高于男性（男女比例1∶2.33-7.20）。PTC的平均确诊年龄最低（42.09岁）,ATC最高（67.91岁）。沿海与内陆的PTC均呈逐年递增趋势,FTC、MTC和ATC递增趋势不明显。结论：11年来沿海与内陆的PTC均呈逐年递增趋势,FTC、MTC和ATC递增趋势不明显。内陆PTC患病年龄低于沿海。碘营养等因素可能参与PTC的发生,其确切机制值得进一步研究。     

Thyroid cancer: emerging role for targeted therapies

The histology and clinical behavior of thyroid cancer are highly diverse. Although most are indolent tumors with a very favorable outcome with the current standard of care therapy, a small subset of tumors may be among the most lethal malignancies known to man. While surgery and radioactive iodine are the standard of care for differentiated thyroid cancers (DTC) and are effective in curing a majority of such patients, those with iodine-resistant cancers pose a great challenge for clinicians, as these patients have limited treatment options and poor prognoses. Medullary thyroid carcinoma (MTC) has no effective systemic therapy despite the genetic and signaling defects that have been well characterized for the last two decades. Anaplastic thyroid cancer (ATC) is one of the most aggressive solid tumors that remains fatal despite conventional multimodality therapy. Increased understanding of the pathogenesis of papillary thyroid carcinoma, the most common type of DTC, as well as ATC, has led to the development of targeted therapies aimed at signaling pathways and angiogenesis that are critical to the development and/or progression of such tumors. Development of tyrosine kinase inhibitors targeting known pathogenetic defects in MTC has led to testing of such agents in the clinic. Numerous clinical trials have been conducted over the last 5 years to examine the effects of these targeted molecular therapies on the outcomes of patients with iodine-refractory DTC, MTC and ATC. Conduction of such trials in the last few years represents a major breakthrough in the field of thyroid cancer. Several trials testing targeted therapies offer promise for setting new standards for the future of patients with progressive thyroid cancer. The purpose of this paper is to outline the recent advances in understanding of the pathogenesis of thyroid cancer and to summarize the results of the clinical trials with these targeted therapies.     

Anaplastic thyroid cancer and primary thyroid lymphoma: a review of these rare thyroid malignancies

BACKGROUND: To review the current literature on the treatment of anaplastic thyroid cancer (ATC) and thyroid lymphoma (TL). RESULTS: Both anaplastic carcinoma (ATC) and TL represent rare forms of thyroid cancer. ATC behaves in a highly aggressive manner, resulting in significant morbidity and mortality. Multimodality therapy consisting of both radiotherapy (RT) and chemotherapy is essential in obtaining local/regional control. Although ATC has been relatively chemo resistant, newer agents such like taxotere show promise. The role of surgery in the treatment of ATC continues to evolve, presently it should be reserved for patients who have shown an initial response to multimodality therapy and in patients in whom a complete macroscopic resection can be achieved with minimal morbidity. The successful treatment of TL currently lies in accurately diagnosing the histological subtype. Both large B-cell and mixed lymphomas are best treated with multimodality therapy consisting of CHOP combined with hyper-fractioned RT. MALT lymphomas with there more indolent course may be amenable to single modality RT or total thyroidectomy if diagnosed at an early stage IE. DISCUSSION: Although both ATC and TL are rare, it is important for surgeons to be aware of the need for multimodality therapy when treating these patients and to understand the limited role surgery plays in diagnosis and treatment.