Nonmedullary Thyroid Carcinoma Research Articles

Clinicopathologic Features of Familial Nonmedullary Thyroid Carcinoma

Background:Familial nonmedullary thyroid carcinoma (FNMTC) is a variant of nonmedullary thyroid carcinoma(NMTC) with particular clinicopathologic features. In recent years, a number of studies have shown that FNMTC is more invasive than sporadic NMTC(SNMTC). The purpose of this study was to explore the differences in clinicopathologic features of FNMTC between different types of families and to determine in which of these families more invasive FNMTC occurred.Methods:We retrospectively reviewed all patients with thyroid carcinoma admitted to Peking Union Medical College Hospital from January 2009 to July 2013 in the database. Of all 2000 cases, 55 met the inclusive criteria for FNMTC and were studied. There are two different grouping methods. The first is that all samples were allocated to families with three or more first-degree relatives affected (FNMTC-3 group) and families with only two affected first-degree relatives (FNMTC-2 group). The second is that all patients were divided into families with three or more affected first-degree relatives over two generations (FNMTC-3-2 group) and the other families. We compared the clinicopathologic features such as sex, age, tumor size, multifocality, location, complications by thyroiditis, complications by benign thyroid nodules, surgical procedure, capsule invasion, histological type, lymph node metastases, tumor node metastasis stage, and BRAF mutation between FNMTC-2 group and FNMTC-3 group. We also made the same comparison between FNMTC-3-2 group and other families.Results:No pronounced differences in clinicopathological features were present between FNMTC-2 group and FNMTC-3 group. The proportion of FNMTC-3-2 group aged <45 years was significantly higher than that in the other families (58.8% vs. 26.3%, P = 0.021). A similar difference was found in the proportion of lymph node metastasis (64.7% vs. 34.2%, P = 0.035).Conclusions:FNMTC-3-2 is more invasive than the other families. Early screening and positive treatment for members of these families are recommended.

Endocrine tumours: familial nonmedullary thyroid carcinoma is a more aggressive disease: a systematic review and meta-analysis.

There is controversy as to whether familial nonmedullary thyroid carcinoma (FNMTC) is more aggressive than sporadic NMTC (SNMTC). The aim of the study was to evaluate the biological characteristics of patients with FNMTC by a meta-analysis. Four databases (PubMed, EMBASE, the Cochrane library databases, and the Web of Science) were searched to identify studies published before September, 2014. All original studies that compared clinical characteristics and prognosis of patients with FNMTC and SNMTC were included. The pooled effect sizes of interesting parameters were calculated by odds ratio (OR), standard mean difference (SMD), or hazard ratio (HR). Twelve studies with a total of 12 741 participants were included in this analysis. FNMTC patients had an increased rate of recurrence (OR=1.72, 95% CI: 1.34 to 2.20) and decreased disease-free survival (DFS) (HR=1.83, 95% CI: 1.34 to 2.52) in comparison with SNMTC patients. FNMTC possessed more aggressive biological behaviors, characterized by younger age at diagnosis (SMD=-0.91, 95% CI: -1.59 to -0.22), higher risk of multifocal (OR=1.50, 95% CI: 1.32 to 1.71), bilateral (OR=1.29, 95% CI: 1.00 to 1.66), extrathyroidal invasion (OR=1.20, 95% CI: 1.02 to 1.41), and lymph node metastasis (OR=1.18, 95% CI: 1.01 to 1.38). FNMTC is a more aggressive disease and possesses higher recurrence rate and lower DFS. More attention and careful consideration should be paid regarding the decision about treatment for patients with FNMTC.

Identification of a novel germline FOXE1 variant in patients with familial non-medullary thyroid carcinoma (FNMTC).

The familial forms of non-medullary thyroid carcinoma (FNMTC) represent approximately 5 % of thyroid neoplasms. Nine FNMTC susceptibility loci have been mapped; however, only the DICER1 and SRGAP1 susceptibility genes have been identified. The transcription factors NKX2-1, FOXE1, PAX8, and HHEX are involved in the morphogenesis and differentiation of the thyroid. Recent studies have identified NKX2-1 germline mutations in FNMTC families. However, the role of high-penetrant FOXE1 variants in FNMTC etiology remains unclear. The aim of this study was to investigate the role of FOXE1 germline mutations in the pathogenesis of FNMTC. We searched for molecular changes in the FOXE1 gene in the probands from 60 Portuguese families with FNMTC. In this series, we identified nine polymorphisms and one variant (c.743C>G, p.A248G) which was not previously described. This variant, which involved an amino acid residue conserved in evolution, segregated with disease in one family, and was also detected in an apparently unrelated case of sporadic NMTC. Functional studies were performed using rat normal thyroid cells (PCCL3) clones and human papillary thyroid carcinoma cell line (TPC-1) pools, expressing the wild type and mutant (p.A248G) forms of FOXE1. In these experiments, we observed that the p.A248G variant promoted cell proliferation and migration, suggesting that it may be involved in thyroid tumorigenesis. Additionally, somatic p.V600E BRAF mutations were also detected in the thyroid tumors of two members of the family carrying the p.A248G variant. This study represents the first evidence of involvement of a germline FOXE1 rare variant in FNMTC etiology and suggests that mutations in MAPK pathway-related genes may contribute to tumor development in these familial cases.

Formas familiares de carcinoma não medular da tiroide

IntroductionNon‐medullary thyroid carcinoma (NMTC) represents over 90% of thyroid neoplasms. This may be associated to various syndromes or arise in non‐syndromic families called, in this case, familial non‐medullary thyroid carcinoma (FNMTC). ObjectivesThis paper aims to review the incidence, pathogenesis and clinical guidance of the familial forms of NMTC. MethodThe literature research, made at the PubMed database, was conducted between January 2008 and December 2013 using as key search terms: «familial nonmedullary thyroid carcinoma» and « FNMTC ». ConclusionThis theme has been target of intense research; however the genes involved in its pathogenesis are still poorly known. Consequently, in order to understand the mechanisms involved and eventual therapeutic modifications, new tests and studies are needed.

External beam radiotherapy with or without concurrent chemotherapy in advanced or recurrent non-anaplastic non-medullary thyroid cancer.

To review clinical outcomes and toxicities in locally advanced differentiated thyroid cancer patients treated with external beam radiotherapy (EBRT) with or without concurrent chemotherapy (CCRT). Between 1990 and 2012, 66 patients with gross residual/unresectable non-anaplastic non-medullary thyroid cancer were treated with EBRT. The median overall survival was 42.0 months. The overall locoregional progression-free survival (LPFS) at 3 years was 77.3%. CCRT resulted in a non-significant improvement in LPFS (90.0% vs. 73.0%, P = 0.347). Poorly differentiated histology had significantly improved LPFS (89.4% vs. 66.1%, P = 0.020), despite a significantly worse distant metastasis-free survival (43.9% vs. 82.5%, P = 0.023). Acute treatment-related toxicity included dermatitis, mucositis, and dysphagia with grade three rates of 12.1%, 19.7%, and 16.7%, respectively. The incidence of late toxicity was low. CCRT was only associated with a significant greater rate of acute grade 3 hoarseness (10.0% vs. 0.0%, P = 0.033), but with no difference in the rate of grade 2 late toxicity. EBRT is a safe and effective treatment modality with 90% LPFS at 3 years in patients with gross residual or unresectable non-anaplastic, non-medullary thyroid carcinoma treated with CCRT. Further incorporation of EBRT with concurrent chemotherapy may result in improved disease control.

MTOR Inhibition Promotes TTF1-Dependent Redifferentiation and Restores Iodine Uptake in Thyroid Carcinoma Cell Lines

Redifferentiation of thyroid carcinoma cells has the potential to increase the efficacy of radioactive iodine therapy in treatment-refractory, nonmedullary thyroid carcinoma (TC), leading to an improved disease outcome. Mammalian target of rapamycin (mTOR) is a key regulator of cell fate affecting survival and differentiation, with autophagy and inflammation as prominent downstream pathways. The effects of mTOR inhibition were studied for its redifferentiation potential of the human TC cell lines BC-PAP, FTC133, and TPC1 by assessment of mRNA and protein expression of thyroid-specific genes and by performance of iodine uptake assays. In thyroid transcription factor 1 (TTF1)-expressing cell lines, mTOR inhibition promoted redifferentiation of TC cells by the up-regulation of human sodium-iodine symporter mRNA and protein expression. Furthermore, these cells exhibited markedly elevated iodine uptake capacity. Surprisingly, this redifferentiation process was not mediated by autophagy induced during mTOR inhibition or by inflammatory mediators but through transcriptional effects at the level of TTF1 expression. Accordingly, small interfering RNA inhibition of TTF1 completely abrogated the induction of human sodium-iodine symporter by mTOR inhibition. The present study has identified the TTF1-dependent molecular mechanisms through which the inhibition of mTOR leads to the redifferentiation of TC cells and subsequently to increased radioactive iodine uptake.

Brain and bone metastasis from malignant thyroid carcinomas originating in western Saudi Arabia

Background We have previously investigated the frequency of gene mutations in RET and HRAS affecting medullary thyroid carcinomas (MTCs) and gene mutations in BRAF, HRAS, KRAS, and NRAS affecting non-medullary thyroid carcinomas (non-MTCs). Non-MTCs include follicular TCs (FTCs), anaplastic TCs (ATCs), and papillary TCs (PTCs) and its histological variants. In this study we surveyed the frequency of metastasis to the brain or bone in our case series of MTCs and non-MTCs.

Genetics of thyroid lesions updated

Advances in research into molecular biology of thyroid cancers have made exciting progress in the understanding of genetic pathways of the cancers. Despite the huge amount of genetic information of thyroid cancers, only a few genetic changes are of clinical value in the current settings. The best known genetic change is the roles of RET mutation in the diagnosis of the familial form of medullary thyroid carcinoma. The other important mutation of some clinical use is the detection of BRAF mutation in papillary thyroid carcinoma. BRAF mutation is associated with aggressive pathological parameters, radioiodine-refractory and increased cancer mortality. Other than these genetic changes in thyroid cancer, familial predisposition of non-medullary thyroid carcinoma is beginning to emerge. This includes a group that is syndromic which is characterized by predominance of non-thyroidal tumours such as familial adenomatous polyposis and PTEN hamartoma syndromes. The other group non-medullary thyroid carcinoma includes familial syndromes of thyroid cancers. Greater than 85% of these are papillary thyroid carcinoma. Overall, new genetic information continues to emerge in thyroid cancers and applications of the information would be expected in the diagnosis, prognosis and molecular target therapies.

Clinical and biological features of familial nonmedullary thyroid carcinoma

To analyze the clinical and biological features of familial nonmedullary thyroid carcinoma (FNMTC). Clinical data of 66 FNMTC cases of 32 pedigrees was retrospectively analyzed, compared with that of 182 control cases taken randomly from the patients with sporadic papillary thyroid carcinoma (SPTC), who were diagnosed and treated in Tianjin Cancer Hospital between January 2008 and November 2012. The features of FNMTC of the first and second generations were objectively analyzed. Some data quoted from the literature were also used for the analysis. The median age at diagnosis of all the 66 FNMTC patients was 44 years, and 57 (86.4%) were females. Moreover, 71.2% (47 patients, 23 pedigrees) of the FNMTC patients exhibited a sibling relationship, and 28.8% (19 patients, 9 pedigrees) of the FNMTC patients exhibited a parent-offspring relationship, and 9 cases in the first generation and 10 cases in the second generation. There were significant differences between the FNMTC group and SPTC group in terms of tumor multicentricity, tumor bilaterality, lymph node metastasis, central lymph node metastasis, concomitant chronic thyroiditis and recurrence (P < 0.05). Compared with SPTC, sibling FNMTC presented a higher rate of central lymph node metastasis, while parent-offspring FNMTC showed frequent tumor bilaterality and a higher rate of recurrence (P < 0.05). Besides, patients in the second generation were diagnosed at an earlier age and had a higher male rate, the tumors were more frequently multifocal and bilateral, and had a higher rate of lymph node metastasis. FNMTC may be more aggressive than SPTC and patients in the second generation may exhibit the "anticipation" phenomenon. It's necessary to make sufficient detailed interrogation and long-term follow-up of the patients and their family for providing individual recommendations for clinical management.

Multifocal papillary thyroid carcinoma—a consensus report of the European Society of Endocrine Surgeons (ESES)

Multifocal papillary thyroid carcinoma (MPTC) has been reported in literature in 18-87% of cases. This paper aims to review controversies in the molecular pathogenesis, prognosis, and management of MPTC. A review of English-language literature focusing on MPTC was carried out, and analyzed in an evidence-based perspective. Results were discussed at the 2013 Workshop of the European Society of Endocrine Surgeons devoted to surgery of thyroid carcinoma. Literature reports no prospective randomized studies; thus, a relatively low level of evidence may be achieved. MPTC could be the result of either true multicentricity or intrathyroidal metastasis from a single malignant focus. Radiation and familial nonmedullary thyroid carcinoma are conditions at risk of MPTC development. The prognostic importance of multifocal tumor growth in PTC remains controversial. Prognosis might be impaired in clinical MPTC but less or none in MPTC <1cm. MPTC can be diagnosed preoperatively by FNAB and US, with low sensitivity for MPTC <1cm. Total or near-total thyroidectomy is indicated to reduce the risk of local recurrence. Prophylactic central node dissection should be considered in patients with total tumor diameter >1cm, or in cases with high number of cancer foci. Completion thyroidectomy might be necessary when MPTC is diagnosed after less than near-total thyroidectomy. Radioactive iodine ablation should be considered in selected patients with MPTC at increased risk of recurrence or metastatic spread.

The FOXE1 locus is a major genetic determinant for familial nonmedullary thyroid carcinoma

Thyroid cancer is the most common endocrine malignancy and nonmedullary thyroid carcinoma (NMTC) represents 90% of all cases. NMTC risk in first-degree relatives of affected cases is elevated fivefold to ninefold. Familial NMTC (FNMTC) accounts for about 3-7% of all thyroid tumors and is a more aggressive clinical entity than its sporadic counterparts. Linkage analysis on high-risk families performed a decade ago mapped several susceptibility loci, but did not lead to the identification of high-penetrance causal germline mutations. More recently, a genome-wide association study (GWAS) identified common single nucleotide polymorphisms (SNPs) affecting the risk of sporadic NMTC. We sought to verify if the newly identified genetic risk factors for NMTC are relevant for FNMTC as well. We genotyped 23 SNPs at 11 candidate loci in 672 subjects belonging to 133 pedigrees with at least two NMTC cases. Statistical analysis was performed using family-based association tests, modified quasi-likelihood score and logistic-normal models. SNPs at 9q22.33 near FOXE1 showed convincing evidence of association with NMTC risk in these high-risk families. The other tested loci resulted negative. These findings confirm the importance of the SNPs identified by recent GWAS on sporadic NMTC on FNMTC as well. However, the proposed FOXE1 causal variants do not show the strongest association signal. Moreover, mutation screening of the FOXE1 coding sequence in the FNMTC cases did not identify rarer causal variants, suggesting that other yet unidentified variants at this locus are involved in FNMTC etiology.

Coincidence of Primary Hyperparathyroidism and Nonmedullary Thyroid Carcinoma

The incidence of primary hyperparathyroidism (pHPT) combined with nonmedullary thyroid carcinoma (NMTC) has been reported between 2-13%. To date, it remains controversial whether these 2 pathologies occur coincidental or are caused by specific risk factors or genetic changes. The aim of this study was to evaluate the clinical and histological characteristics of NMTC associated with pHPT. We reviewed prospective database records of 1 464 unselected, consecutive patients who were treated for pHPT in our institution between 1986 and 2012 and identified 41 NMTC (2.8%). The collective consisted of 35 papillary (PTC) and 6 follicular (FTC) thyroid carcinomas. Our collective of 41 NMTC including 34 single adenomas and 7 multiglandular diseases consisted of 33 females and 8 males. Patients with FTC demonstrated significant lower preoperative PTH levels compared to PTC. Interestingly, NMTC were predominantly located on the right side. FTC had significant larger tumors as well as demonstrated increased extrathyroidal growth and lymph node metastases. In 71% pHPT and NMTC were diagnosed synchronously. The comorbidity of pHPT and NMTC occurs in about 3%. As pHPT is often operated by a focal minimally invasive approach, we advocate a mandatory preoperative thyroid ultrasound for all patients with pHPT to be able to identify synchronous thyroid disease.

Ultra-Rare Mutation in Long-Range Enhancer Predisposes to Thyroid Carcinoma with High Penetrance

Thyroid cancer shows high heritability but causative genes remain largely unknown. According to a common hypothesis the genetic predisposition to thyroid cancer is highly heterogeneous; being in part due to many different rare alleles. Here we used linkage analysis and targeted deep sequencing to detect a novel single-nucleotide mutation in chromosome 4q32 (4q32A>C) in a large pedigree displaying non-medullary thyroid carcinoma (NMTC). This mutation is generally ultra-rare; it was not found in 38 NMTC families, in 2676 sporadic NMTC cases or 2470 controls. The mutation is located in a long-range enhancer element whose ability to bind the transcription factors POU2F and YY1 is significantly impaired, with decreased activity in the presence of the C- allele compared with the wild type A-allele. An enhancer RNA (eRNA) is transcribed in thyroid tissue from this region and is greatly downregulated in NMTC tumors. We suggest that this is an example of an ultra-rare mutation predisposing to thyroid cancer with high penetrance.

High level of distress in long-term survivors of thyroid carcinoma: Results of rapid screening using the distress thermometer

Context. Cancer patients are at increased risk for distress. The Distress Thermometer (DT) and problem list (PL) are short-tools validated and recommended for distress screening in cancer patients. Objective. To investigate the level of distress and problems experienced by survivors of differentiated non-medullary thyroid carcinoma (DTC), using the DT and PL and whether this correlates with clinical and demographical variables. Participants, design and setting. All 205 DTC patients, under follow-up at the outpatient clinic of our university hospital, were asked to fill in the DT and PL, hospital anxiety and depression scale (HADS), illness cognition questionnaire (ICQ) and an ad hoc questionnaire. Receiver Operator Characteristic analysis (ROC) was used to establish the optimal DT cut-off score according to HADS. Correlations of questionnaires scores with data on diagnosis, treatment and follow-up collected from medical records were analyzed. Results. Of the 159 respondents, 145 agreed to participate [118 in remission, median follow-up 7.2 years (range 3 months–41 years)]. Of these, 34.3% rated their distress score ≥5, indicating clinically relevant distress according to ROC analysis. Patients reported physical (86%) over emotional problems (76%) as sources of distress. DT scores correlated with HADS scores and ICQ subscales. No significant correlations were found between DT scores and clinical or demographical characteristics except for employment status. Conclusion. Prevalence of distress is high among patients with DTC even after long-term remission and cannot be predicted by clinical and demographical characteristics. DT and PL are useful screening instruments for distress in DTC patients and could easily be incorporated into daily practice.

Somatostatin receptor expression in non-medullary thyroid carcinomas

Peptide receptor radionuclide therapy (PRRT) is dependent upon binding of radiolabelled peptides to their respective receptor expressing cells. The main objective of this study was to characterize the expression of somatostatin receptor (SSTR) subtypes in non-medullary thyroid cancers in order to be able to recommend the use of PRRT as a treatment option in patients with progressive local or metastatic disease. We constructed tissue microarrays from paraffin blocks prepared from 47 cases of non-medullary thyroid carcinomas and related normal thyroid tissue. Immunohistochemical staining was performed with five different polyclonal SSTR antibodies. SSTR subtypes sst2 and sst3 were expressed in all non-medullary thyroid carcinomas, sst1 and sst5 in 75%, and sst4 in 38%. Coexpression of more than three subtypes was detected in 36 of the 47 cases. The expression of SSTR subtypes in normal thyroid tissue was low or absent. Non-medullary thyroid carcinomas frequently express all SSTR subtypes. This expression provides a basis for further studies with the aim of exploring PRRT as a possible new treatment for iodine-131 refractory metastatic non-medullary thyroid carcinomas.

Genome Haploidisation with Chromosome 7 Retention in Oncocytic Follicular Thyroid Carcinoma

BackgroundRecurrent non-medullary thyroid carcinoma (NMTC) is a rare disease. We initially characterized 27 recurrent NMTC: 13 papillary thyroid cancers (PTC), 10 oncocytic follicular carcinomas (FTC-OV), and 4 non-oncocytic follicular carcinomas (FTC). A validation cohort composed of benign and malignant (both recurrent and non-recurrent) thyroid tumours was subsequently analysed (n = 20).MethodsData from genome-wide SNP arrays and flow cytometry were combined to determine the chromosomal dosage (allelic state) in these tumours, including mutation analysis of components of PIK3CA/AKT and MAPK pathways.ResultsAll FTC-OVs showed a very distinct pattern of genomic alterations. Ten out of 10 FTC-OV cases showed near-haploidisation with or without subsequent genome endoreduplication. Near-haploidisation was seen in 5/10 as extensive chromosome-wide monosomy (allelic state [A]) with near-haploid DNA indices and retention of especially chromosome 7 (seen as a heterozygous allelic state [AB]). In the remaining 5/10 chromosomal allelic states AA with near diploid DNA indices were seen with allelic state AABB of chromosome 7, suggesting endoreduplication after preceding haploidisation. The latter was supported by the presence of both near-haploid and endoreduplicated tumour fractions in some of the cases. Results were confirmed using FISH analysis. Relatively to FTC-OV limited numbers of genomic alterations were identified in other types of recurrent NMTC studied, except for chromosome 22q which showed alterations in 6 of 13 PTCs. Only two HRAS, but no mutations of EGFR or BRAF were found in FTC-OV. The validation cohort showed two additional tumours with the distinct pattern of genomic alterations (both with oncocytic features and recurrent).ConclusionsWe demonstrate that recurrent FTC-OV is frequently characterised by genome-wide DNA haploidisation, heterozygous retention of chromosome 7, and endoreduplication of a near-haploid genome. Whether normal gene dosage on especially chromosome 7 (containing EGFR, BRAF, cMET) is crucial for FTC-OV tumour survival is an important topic for future research.MicroarraysData are made available at GEO (GSE31828).

PTEN mutations: help spot thyroid cancer before it occurs

ATA: American Thyroid Association; FHx: Family history; FNA: Fine-needle aspiration; NMTC: Non-medullary or epithelial thyroid carcinoma; US: Ultrasound.The thyroid is the largest of the endocrine ...

The Long-Term Outcomes of the Second Generation of Familial Nonmedullary Thyroid Carcinoma Are More Aggressive than Sporadic Cases

Familial nonmedullary thyroid carcinoma (FNMTC) is frequently detected, but the prevalence or the aggressiveness of FNMTC is still unclear. We aimed to investigate the prevalence, clinical characteristics, and prognosis of FNMTC. This study included 3056 nonmedullary thyroid carcinoma (NMTC) patients who were pathologically confirmed to exhibit differentiated thyroid carcinoma from January 1962 through March 2010. The duration of follow-up was 6.2±6.2 years. The prevalence of FNMTC was 9.6%; 37.9% of the FNMTC patients exhibited a parent-offspring relationship, and 62.1% exhibited a sibling relationship. FNMTC was smaller in tumor size (1.2±0.9 vs. 1.4±1.1 cm) and more multifocal (33.6% vs. 27.0%) than sporadic cases. FNMTC presented higher recurrence rates (29.5% vs. 19.8%) and shorter recurrence-free survival than sporadic NMTC (p=0.046). When we compared sporadic NMTC with parent-offspring or sibling FNMTC separately, parent-offspring FNMTC was more multifocal (39.3% vs. 27.0%), while sibling FNMTC was more prevalent in female patients (89.6% vs. 82.5%) and presented smaller tumors (1.2±0.8 vs. 1.4±1.1 cm) than sporadic NMTC. The recurrence rate was higher than that of sporadic NMTC in parent-offspring FNMTC (35.6% vs. 19.8%) but not in sibling FNMTC. Among the 123 parent-offspring FNMTC cases, the second generation exhibited an earlier age at the diagnosis (38±11 vs. 57±11 years), more extrathyroidal invasion (57.8% vs. 29.4%), a higher recurrence rate (50.0% vs. 19.0%), and shorter recurrence-free survival (p=0.015) than the first generation. FNMTC was found to have a very high prevalence in our population. Parent-offspring FNMTC demonstrated higher recurrence than sporadic NMTC; specifically, the second generation of parent-offspring FNMTC cases exhibited more aggressive clinical characteristics than the first generation.

Familial Follicular Cell-Derived Thyroid Carcinoma

Follicular cell-derived well-differentiated thyroid cancer, papillary (PTC) and follicular thyroid carcinomas comprise 95% of all thyroid malignancies. Familial follicular cell-derived well-differentiated thyroid cancers contribute 5% of cases. Such familial follicular cell-derived carcinomas or non-medullary thyroid carcinomas (NMTC) are divided into two clinical–pathological groups. The syndromic-associated group is composed of predominately non-thyroidal tumors and includes Pendred syndrome, Warner syndrome, Carney complex (CNC) type 1, PTEN-hamartoma tumor syndrome (PHTS; Cowden disease), and familial adenomatous polyposis (FAP)/Gardner syndrome. Other conditions with less established links to the development of follicular cell-derived tumors include ataxia–telangiectasia syndrome, McCune Albright syndrome, and Peutz–Jeghers syndrome. The final group encompasses syndromes typified by NMTC, as well as pure familial (f) PTC with or without oxyphilia, fPTC with multinodular goiter, and fPTC with papillary renal cell carcinoma. This heterogeneous group of diseases does not have the established genotype–phenotype correlations known as in the familial C-cell-derived tumors or medullary thyroid carcinomas (MTC). Clinicians should have the knowledge to identify the likelihood of a patient presenting with thyroid cancer having an additional underlying familial syndrome stemming from characteristics by examining morphological findings that would alert pathologists to recommend that patients undergo molecular genetic evaluation. This review discusses the clinical and pathological findings of patients with familial PTC, such as FAP, CNC, Werner syndrome, and Pendred syndrome, and the heterogeneous group of familial PTC.

New Perspectives on Diagnostics, Prognosis, and Therapy in Aggressive Endocrine Tumours

New Perspectives on Diagnostics, Prognosis, and Therapy in Aggressive Endocrine Tumours