Poorly Differentiated Thyroid Carcinoma Research Articles

Utility of monoclonal PAX8 antibody for distinguishing intrathyroid thymic carcinoma from follicular cell-derived thyroid carcinoma.

Follicular cell-derived thyroid carcinomas, including thyroid squamous cell carcinomas (SCCs) and anaplastic carcinomas, are immunoreactive for paired-box gene 8 (PAX8), while non-follicular cell-derived thyroid carcinomas stain negative for the PAX8 antibody. Intrathyroid thymic carcinoma (ITTC) arising from the intrathyroidal ectopic thymus exhibits moderate-to-strong nuclear reactivity for polyclonal PAX8. This is difficult to understand given that PAX8 is not associated with embryonic thymic development. We aimed to determine the diagnostic significance of monoclonal PAX8 antibody in distinguishing ITTCs from follicular cell-derived thyroid carcinomas. Ten ITTCs, 14 poorly differentiated thyroid carcinomas (PDTCs), 14 thyroid SCCs, 7 thymic tissue specimens, 7 thymomas, and 1 thymic carcinoma were analyzed using antibodies against polyclonal and monoclonal PAX8, thyroid transcription factor-1, p63, and CD5. Four ITTCs (40.0%) stained positive for polyclonal PAX8; none stained positive for monoclonal PAX8. All PDTCs and 92.9% of SCCs were immunoreactive for both polyclonal and monoclonal PAX8. All PDTCs, 46.2% of SCCs, and none of the ITTCs were immunoreactive for thyroid transcription factor-1. Eight ITTCs (80.0%), but none of the PDTCs and SCCs, were immunoreactive for CD5. We are the first to show that ITTCs stain negative for monoclonal PAX8. Monoclonal PAX8 is a more reliable marker than polyclonal PAX8 for determining follicular cell origin. We conclude that monoclonal PAX8 is a useful marker for distinguishing ITTCs from PDTCs and SCCs. Monoclonal PAX8 negativity is additional evidence in support of ITTCs not being follicular cell-derived thyroid carcinomas, but having a thymic origin.

BRAF status in the variants of papillary thyroid carcinoma

Aim: The aim was to study the BRAF status by immunohistochemistry (IHC) in the variants of papillary carcinoma thyroid and compare it with the clinicopathological parameters. Materials and Methods: All the thyroid carcinomas diagnosed during the period of January 2015–June 2018 were reviewed and classified according to the WHO 2017 criteria. The demographic and clinicopathological features were noted. Microarrays were prepared on 27 cases, including classic and variants of papillary thyroid carcinoma (PTC), poorly differentiated thyroid carcinoma (PDTC), and medullary thyroid carcinoma (MTC). IHC was performed with BRAF V600E by automated staining. The BRAF status was correlated with known prognostic markers. Results: There were 23 PTC, 3 PDTC, and one MTC. The PTC included seven classic, three solid, two each of microcarcinoma, infiltrative and encapsulated follicular variant, tall-cell variant (TCV), oncocytic and one each of diffuse sclerosing, nodular fasciitis-like stroma, and Warthin-like variants. BRAF positivity was seen in 44.44%, including 11 PTC and one PDTC. The positivity was 85.71% in classic and 31.25% in variants. The age (>45 vs. Conclusion: BRAF status did not show correlation with known prognostic variables in classic as well as variants of PTC.

Targeted next-generation sequencing of cancer genes in poorly differentiated thyroid cancer.

Poorly differentiated thyroid carcinoma (PDTC) is a rare malignancy with higher mortality than well-differentiated thyroid carcinoma. The histological diagnosis can be difficult as well as the therapy. Improved diagnosis and new targeted therapies require knowledge of DNA sequence changes in cancer-relevant genes. The TruSeq Amplicon Cancer Panel was used to screen cancer genomes from 25 PDTC patients for somatic single-nucleotide variants in 48 genes known to represent mutational hotspots. A total of 4490 variants were found in 23 tissue samples of PDTC. Ninety-eight percent (4392) of these variants did not meet the inclusion criteria, while 98 potentially pathogenic or pathogenic variants remained after filtering. These variants were distributed over 33 genes and were all present in a heterozygous state. Five tissue samples harboured not a single variant. Predominantly, variants in P53 (43% of tissue samples) were identified, while less frequently, variants in APC, ERBB4, FLT3, KIT, SMAD4 and BRAF (each in 17% of tissue samples) as well as ATM, EGFR and FBXW7 (each in 13% of tissue samples) were observed. This study identified new potential genetic targets for further research in PDTC. Of particular interest are four observed ERBB4 (alias HER4) variants, which have not been connected to this type of thyroid carcinoma so far. In addition, APC and SMAD4 mutations have not been reported in this subtype of cancer either. In contrast to other reports, we did not find CTNNB1 variants.

FNA diagnosis of poorly differentiated thyroid carcinoma. A review of the recent literature.

Poorly differentiated thyroid carcinoma (PDTC) is a follicular cell-derived tumour that was recognised as a distinct entity by the World Health Organisation in 2004. The natural history and pathological features of PDTC are reported to be intermediate between those of well-differentiated and undifferentiated (anaplastic) thyroid carcinomas. Preoperative identification of PDTC could facilitate better initial patient management in many cases, namely more extensive surgery, without any delay. However, according to some experts, a diagnosis of PDTC can only be rendered on histologic specimens based on criteria recommended in the Turin proposal. Although high-grade features (namely necrosis and mitoses) can be recognised in FNA material, other cytomorphological features have limited value for the preoperative diagnosis of PDTC and specific features for a definitive diagnosis of PDTC have not yet been clearly defined. Here, we review the current status and future prospects for cytological recognition of PDTC; we emphasise the features that should raise suspicion of this rare condition in FNA cytology and provide an update on molecular features and management of PDTC. Despite proposed histological criteria for the diagnosis of PDTC, its recognition on routine thyroid cytology presents a notable challenge. Current and future advances in molecular testing could contribute to the cytological diagnosis of PDTC.

An algorithmic approach to overcome diagnostic challenges in FNAC in large-cell poorly differentiated thyroid carcinomas

Poorly differentiated thyroid carcinoma (PDTC) is a distinct entity and a rare carcinoma of thyroid follicular origin with an intermediate prognosis. It is defined by the Turin criteria set in 2007. Although this entity is well known, with widely available literature on histological features, specific studies describing the cytological features of PDTC (especially the large cell type) are lacking. In this study, wedescribe the cytological and clinical features of PDTC showing large cells (PDTC-LC) with abundant cytoplasm. Twelve cases of PDTC showing abundant cytoplasm between 2007 and 2016 were retrieved from the departmental archives and studied. The cases occurred predominantly in women with a mean age of 54.3 years. The mean tumor size was 4.3 cm. Fine-needle aspiration cytology (FNAC) smears showed singly scattered large cells with abundance of cytoplasm admixed with microfollicular and insular pattern. Lymph node metastasis was noted in 7 cases and distant metastasis to bone and visceral organs were also seen in 7 cases. Microfollicular pattern may lead to these cases being misinterpreted as a differentiated follicular neoplasm on FNAC, and the dissociated large cells may mimic Hürthle cell neoplasm. Immunocytochemistry is not helpful in this scenario, although it does resolve the diagnostic dilemma when the differential diagnoses include medullary thyroid carcinoma and metastatic tumors. It is important to identify these tumors on FNAC as this facilitates proper management.

Nonanaplastic follicular cell-derived thyroid carcinoma: mitosis and necrosis in long-term follow-up

Nonanaplastic follicular cell-derived thyroid carcinoma (NAFCTC) includes differentiated- (DTC) and poorly differentiated thyroid carcinoma (PDTC). DTC has an excellent prognosis, while PDTC is situated between DTC and anaplastic carcinomas. Short-term studies suggest that PDTC patients diagnosed only on tumor necrosis and/or mitosis have a prognosis similar to those diagnosed according to the TURIN proposal. The purpose of this study was to evaluate prognosis for NAFCTC based on long-term follow-up illuminating the significance of tumor necrosis and mitosis. A cohort of 225 patients with NAFCTC was followed more than 20 years. Age, sex, distant metastasis, histology, tumor size, extrathyroidal invasion, lymph node metastasis, tumor necrosis and mitosis were examined as possible prognostic factors. Median follow-up time for patients alive was 28 years (range 20–43 years). Age, distant metastasis, extrathyroidal invasion, tumor size, tumor necrosis and mitosis were independent prognostic factors in multivariate analysis for overall survival (OS). In disease specific survival (DSS) age was not significant. Using only necrosis and/or mitosis as criteria for PDTC the 5-, 10- and 20-year OS for DTC was 87, 79 and 69%, respectively. In DSS it was 95, 92 and 90%. For PDTC the 5-, 10- and 20-year OS was 57, 40 and 25%, respectively. In DSS it was 71, 55 and 48%. Tumor necrosis and mitosis are highly significant prognostic indicators in analysis of long time survival of nonanaplastic follicular cell-derived thyroid carcinoma indicating that a simplification of the actually used criteria for poorly differentiated carcinomas may be justified.

Hobnail variant of papillary thyroid carcinoma: molecular profiling and comparison to classical papillary thyroid carcinoma, poorly differentiated thyroid carcinoma and anaplastic thyroid carcinoma.

BackgroundAs a rare but aggressive papillary thyroid carcinoma (PTC) variant, the genetic changes of hobnail variant of PTC (HVPTC) are still unclear.ResultsThe prevalence of HVPTC was 1.69% (18/1062) of all PTC diagnosed in our cohort. 73 samples from 55 patients (17 HVPTC, 26 CPTC, 7 PDTC and 5 ATC) were successfully analyzed using targeted NGS with an 18-gene panel. Thirty-seven mutation variant types were identified among 11 genes. BRAF V600E mutation was the most common mutation, which is present in almost all HVPTC samples (16/17, 94%), most CPTC samples (20/26, 77%), and none of the ATC and PDTC samples. TERT promoter mutation (C228T) was identified in 2 ATC and one HVPTC patient. RAS and TP53 mutation are almost exclusively present among ATC and PDTC samples although TP53 mutation was also observed in 3 HVPTC patients. Six different GNAS mutations were identified among 8 CPTC patients (31%) and none of the HVPTC patients. The only patient who died of disease progression harbored concomitant TERT C228T mutation, BRAF V600E mutation and TP53 mutation.MethodsHVPTC cases were identified from a group of 1062 consecutive surgical specimens diagnosed as PTC between 2000 and 2010. Targeted next-generation sequencing (NGS) was applied to investigate the mutation spectrum of HVPTC, compared to classical PTC (CPTC), poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC).ConclusionAs an aggressive variant of PTC, HVPTC has relatively specific molecular features, which is somewhat different from both CPTC and ATC/PDTC and may underlie its relatively aggressive behavior.

Poorly differentiated thyroid carcinoma: A hospital-based clinicopathological study and review of literature.

Poorly differentiated thyroid carcinoma (PDTC) is a rare aggressive malignancy of thyroid follicular cells and has unique features in morphology and behavior. This study was aimed to describe the experience of a tertiary medical center with PDTC within a 10-year period. This is a descriptive retrospective study of eight cases of PDTC among 418 various thyroid carcinomas. All cases of PDTC were retrieved along with the clinicopathological information. Only eight cases (1.9%) of PDTC were diagnosed among 418 thyroid carcinomas. Mean age was 48.12 with 3:5 (male:female) and tumor size ranged 3-12 cm. PDTC were diagnosed coexisting with one or more other pathologies; nodular hyperplasia (four cases), papillary carcinoma (one case), follicular carcinoma (three cases), and Hashimoto thyroiditis (two cases); with ≥60% PDTC component. Six cases associated with high-grade features died within 3 years after diagnosis. Mean age in this study was younger including a 20-year-old girl. Younger age was associated with better prognosis. Most of the cases had underlying benign thyroid lesions and differentiated thyroid carcinoma. Most of the PDTC had poor prognosis associated with PDTC component ≥60%, tumor necrosis, high mitotic count, lymph node involvement, vascular invasion and distant metastasis; and these cases died within 3 years after diagnosis. Although treatment of PDTC remains surgery followed by radioiodine therapy, correct histopathological diagnosis is important for clinicians and oncologists to predict the prognosis. All thyroid carcinoma should be sampled thoroughly not to miss small foci of PDTC component.

Poorly Differentiated Thyroid Carcinoma: 10-Year Experience in a Southeast Asian Population.

BackgroundNo previous studies have been published on poorly differentiated thyroid carcinoma (PDTC) in Southeast Asia.MethodsWe included all adult PDTC patients diagnosed using the Turin criteria at the Philippine General Hospital from 2006 to 2015. The data collected included demographics, clinical presentation, histopathology, treatment, and outcomes. Tests of association were employed to compare these data with foreign studies on PDTC, as well as with local studies on well differentiated thyroid carcinoma (WDTC) and anaplastic thyroid carcinoma (ATC).ResultsEighteen PDTC cases were identified. The median age was 62 years old, with the majority being females. All patients had goiter on presentation, and most were stage IV at the time of diagnosis. In terms of PDTC subtype, insular and trabecular patterns were equally common. Extrathyroidal extension was documented in eight patients, while five patients each had nodal and distant metastasis. All but one patient underwent surgery; however, less than half received adjuvant radioiodine therapy. The 5-year survival rate was 83%. Three patients (16.7%) died at a median of 12 months after diagnosis. Nine (50%) are still alive with persistent and/or recurrent disease at a median of 39 months after diagnosis.ConclusionThe behavior of PDTC in this Southeast Asian population was found to be similar to patterns observed in other regions, and exhibited intermediate features between WDTC and ATC. Appropriate surgery provided excellent 5-year survival rates, but the role of adjuvant therapy remains unclear. Larger studies are needed to identify prognostic factors in this population.

EXPRESSION OF MENIN IN THE HUMAN THYROID GLAND.

The expression of menin in the thyroid gland has long been debated. Animal models with targeted inactivation of menin in the thyroid gland have shown that its inactivation might play a role in the progression to a more aggressive type of cancer. Human studies are conflicting, some have identified mutations in the MEN1 gene in a sub-type of oncocytic thyroid carcinomas, while others have not identified a higher prevalence of thyroid cancer in MEN1 patients. To analyze the immunohistochemical expression of menin in different types of thyroid carcinomas. 48 thyroid tumours (12 papillary thyroid carcinomas (PTC), 6 anaplastic thyroid carcinomas (ATC), 12 poorly differentiated thyroid carcinomas (PDTC), 5 medullary thyroid carcinomas (MTC), 5 oncocytic follicular carcinomas (OC), 3 oncocytic adenomas (OA) and 5 goiters (G)) were tested for nuclear expression of menin using an anti-menin antibody. The expression was considered positive, negative or decreased. The expression of menin was positive, identical to normal tissue, in 39 cases (81.25%). The expression was decreased (n=8) or absent (n=1) in 9 tumours (18.75% - 2 PTC, 5 PDTC, 2 OC) accounting for 42% (5/12) of the PDTC and 40% (2/5) of the OC. Our results show that the expression of menin is generally preserved in human thyroid carcinomas, but it can be decreased or absent in certain types of thyroid cancer. Further molecular studies are needed to evaluate to potential of menin protein in tumorigenesis.

Unilateral Exophthalmos Due To Metastasis Of Poorly Differentiated Thyroid Carcinoma To The Left Sphenoid Wing With Intra-Orbital Extension

ABSTRACT Objective: In contrast to well-differentiated and anaplastic thyroid carcinomas, metastasis patterns are not well-known for poorly differentiated thyroid carcinoma (PDTC). We report an unusual case of PDTC initially presenting as unilateral exophthalmos. Methods: Clinical, laboratory, imaging, and pathology data are presented. Results: A 55-year-old woman without significant medical history presented to an outside hospital complaining of a “bulging” left eye for several weeks. Computerized tomography–guided excisional biopsy of a left orbital mass revealed poorly differentiated insular thyroid carcinoma (positive for cytokeratins, thyroid transcription factor-1, and thyroglobulin; negative for monoclonal carcinoembryonic antigen, S100, chromogranin, and synaptophysin) with a Ki-67 index of 5 to 10%. In the midst of outpatient management, including treatment with dexamethasone, she presented to our tertiary center in diabetic ketoacidosis. Physical examination demonstrated unilateral left-sided ex...

Advances in studies of the genes related to thyroid carcinoma

Thyroid carcinoma (TC) is the most common endocrine cancer and its incidence has been increasing globally over the past decades. With the development of the genetic technology, more and more evidences showed that many genes affect the biological behaviors of TC, making sense to early diagnosis, predicting the prognosis and targeted therapy for TC. BRAF mutation is specific to papillary thyroid carcinoma (PTC). It can not only predict the prognosis, but also have diagnosis value. RET rearrangements are identified as a specific genetic event in PTC. Though the preoperative detection of RET/PTC rearrangements has not proven useful in choosing the appropriate surgical management, new medications which are capable of inhibiting RET protein kinase activity may help to therapy the PTCs. RET mutation has specific meaning for detecting familial medullar thyroid carcinoma. Though RAS mutation can be discovered in follicular thyroid carcinoma (FTC), follicular variant of papillary thyroid carcinoma (FvPTC), poorly differentiated thyroid carcinoma (PDTC) and undifferentiated thyroid carcinoma (UTC), the relationship between RAS mutation and prognosis remains controversial. P53 can be detected in more invasive variants of PTC, PDTC and UTC. P53 can be used as a prognosis-predictor. Rescuing the function of mutant p53 (mutp53) protein is an attractive anticancer therapeutic strategy. 30%-35% FTC and 37.5% FvPTC have PAX8-PPARγ rearrangement, which can distinguish carcinomas from adenomas in follicular neoplasms of the thyroid. Pioglitazone may have therapeutic efficacy in patients with PPFP-positive TCs. FTC and PTC have TERT promoter mutation, usually predicting poor prognosis. Other genes also influence on the biological behavior of TC, having diagnosis value and prognostic significance. Though the gene study about TC develops rapidly, many problems remain unclear. Further studies on TC-related genes are needed.

Application of intensity-modulated radiotherapy in unresectable poorly differentiated thyroid carcinoma.

Poorly differentiated thyroid carcinoma (PDTC) is a rare and aggressive malignancy with high rates of invasion and distant metastasis. This study was to explore the ability of intensity-modulated radiotherapy (IMRT) combined with chemotherapy to manage unresectable PDTC. Between February 2011 and April 2012, 5 patients with unresectable PDTC were treated by IMRT at our institution and were included in this analysis. The median radiotherapy dose to the gross tumor volume (GTV) was 66 Gy/33 fractions/6.4 weeks. All patients received chemotherapy, and one patient with tumor compression symptoms had a tracheotomy before treatment. The mean survival time of the 5 patients was 41.6 months. The direct causes of death were distant metastases (40%) and progression of the locoregional disease (20%). In conclusion, IMRT combined with chemotherapy for unresectable PDTC might be beneficial to improve locoregional control. Further new therapies are needed to control metastases.

TRAP1 regulates cell cycle and apoptosis in thyroid carcinoma cells.

Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a heat shock protein 90 (HSP90) molecular chaperone upregulated in several human malignancies and involved in protection from apoptosis and drug resistance, cell cycle progression, cell metabolism and quality control of specific client proteins. TRAP1 role in thyroid carcinoma (TC), still unaddressed at present, was investigated by analyzing its expression in a cohort of 86 human TCs and evaluating its involvement in cancer cell survival and proliferation in vitro Indeed, TRAP1 levels progressively increased from normal peritumoral thyroid gland, to papillary TCs (PTCs), follicular variants of PTCs (FV-PTCs) and poorly differentiated TCs (PDTCs). By contrast, anaplastic thyroid tumors exhibited a dual pattern, the majority being characterized by high TRAP1 levels, while a small subgroup completely negative. Consistently with a potential involvement of TRAP1 in thyroid carcinogenesis, TRAP1 silencing resulted in increased sensitivity to paclitaxel-induced apoptosis, inhibition of cell cycle progression and attenuation of ERK signaling. Noteworthy, the inhibition of TRAP1 ATPase activity by pharmacological agents resulted in attenuation of cell proliferation, inhibition of ERK signaling and reversion of drug resistance. These data suggest that TRAP1 inhibition may be regarded as potential strategy to target specific features of human TCs, i.e., cell proliferation and resistance to apoptosis.

Genomic Landscape of poorly Differentiated and Anaplastic Thyroid Carcinoma.

Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) are aggressive thyroid tumors associated with a high mortality rate of 38-57% and almost 100% respectively. Several recent studies utilizing next generation sequencing techniques have shed lights on the molecular pathogenesis of these tumors, providing evidence to support a stepwise tumoral progression from well-differentiated to poorly differentiated, and finally to anaplastic thyroid carcinomas. While BRAF (V600E) and RAS mutations remain the main drivers in aggressive thyroid carcinoma, PDTC and ATC gains additional mutations, e.g., TERT promoter mutation, TP53 mutation, as well as frequent alterations in PIK3CA-PTEN-AKT-mTOR pathway, SWI-SNF complex, histomethyltransferases, and mismatch repair genes. RAS-mutated PDTCs are commonly associated with a histologic phenotype defined by Turin proposal, high frequency of distant metastasis, high thyroid differentiation score, and a RAS-like gene expression profile, whereas BRAF-mutated PDTCs are usually defined solely by the Memorial Sloan Kettering Cancer Center (MSKCC) criteria with a propensity for nodal metastasis and are less differentiated with a BRAF-like expression signature. Such demarcation is largely lost in ATC which is characterized by genomic complexity, heavy mutation burden, and profound undifferentiation. Additionally, several molecular events, e.g., EIF1AX mutation, mutation burden, and chromosome 1q gain in PDTCs, as well as EIF1AX mutation, chromosome 13q loss, and 20q gains in ATCs, may serve as adverse prognostic markers predicting poor clinical outcome.

Identification of CHEK1, SLC26A4, c-KIT, TPO and TG as new biomarkers for human follicular thyroid carcinoma.

The search for preoperative biomarkers for thyroid malignancies, in particular for follicular thyroid carcinoma (FTC) diagnostics, is of utmost clinical importance. We thus aimed at screening for potential biomarker candidates for FTC. To evaluate dynamic alterations in molecular patterns as a function of thyroid malignancy progression, a comparative analysis was conducted in clinically distinct subgroups of FTC and poorly differentiated thyroid carcinoma (PDTC) nodules. NanoString analysis of FFPE samples was performed in 22 follicular adenomas, 56 FTC and 25 PDTC nodules, including oncocytic and non-oncocytic subgroups. The expression levels of CHEK1, c-KIT, SLC26A4, TG and TPO were significantly altered in all types of thyroid carcinomas. Based on collective changes of these biomarkers which correlating among each other, a predictive score has been established, allowing for discrimination between benign and FTC samples with high sensitivity and specificity. Additional transcripts related to thyroid function, cell cycle, circadian clock, and apoptosis regulation were altered in the more aggressive oncocytic subgroups only, with expression levels correlating with disease progression. Distinct molecular patterns were observed for oncocytic and non-oncocytic FTCs and PDTCs. A predictive score correlation coefficient based on collective alterations of identified here biomarkers might help to improve the preoperative diagnosis of FTC nodules.

Remarkable response in 2 cases of Advanced Poorly Differentiated Thyroid Carcinoma with liposomal doxorubicin plus cisplatin

ABSTRACTBackground: Poorly Differentiated Thyroid Carcinoma (PDTC), especially advanced PDTC, is an aggressive disease and displays a much poorer prognosis compared with well differentiated thyroid carcinoma. Surgery is the recommended treatment in the early stage of PDTC, however, no effective treatment modalities are currently available for advanced PDTCMethods: Two advanced PDTC patients with no radioiodine uptake adopted a cytotoxic chemotherapy with liposomal doxorubicin (35 mg/m2, day 1) plus cisplatin (75 mg/m2, day1–3) every 3 weeks. Computer tomography (CT) was performed after 6 cycles (case 1) or 5 cycles (case 2) of chemotherapyResults: Our patients achieved remarkable response with one a Complete Remission (CR) and the other a very good Partial Remission (PR)Conclusion: Our findings indicate that liposomal doxorubicin-based chemotherapy regimens might produce response in PDTC patients, and improve their overall survival and quality of life. Hence we believe this result is very important for oncologists in treating PDTC.

Comparison of Clinical and Ultrasonographic Features of Poorly Differentiated Thyroid Carcinoma and Papillary Thyroid Carcinoma.

Background:The clinical behavior and management of poorly differentiated thyroid carcinoma (PDTC) are very different from papillary thyroid carcinoma (PTC). By comparing the clinical and ultrasonographic features between the two tumors, we proposed to provide more possibilities for recognizing PDTC before treatment.Methods:The data of 13 PDTCs and 39 age- and gender-matched PTCs in Peking Union Medical College Hospital between December 2003 and September 2013 were retrospectively reviewed. The clinical and ultrasonic features between the two groups were compared.Results:The frequencies of family history of carcinoma, complication with other thyroid lesions, lymph node metastases, recurrent laryngeal nerve injuries, and distant metastases were higher in PDTCs (30.8%, 61.6%, 69.2%, 23.1%, and 46.2%, respectively) than those in PTCs (2.6%, 23.1%, 25.6%, 2.6%, and 2.6%, respectively) (P < 0.05). The mortality rate of PDTCs was greatly higher than PTCs (P < 0.01). Conventional ultrasound showed that the size of PDTCs was larger than that of PTCs (3.1 ± 1.9 cm vs. 1.7 ± 1.0 cm). Clear margins and rich and/or irregular blood flow were found in 92.3% of PDTCs, which differed substantially from PTCs (51.7% and 53.8%, respectively) (P < 0.05).Conclusions:PDTC is more aggressive and its mortality rate is higher than PTCs. Accordingly, more attention should be given to suspicious thyroid cancer nodules that show large size, regular shape, and rich blood flow signals on ultrasound to exclude the possibility of PDTCs.

Fine needle aspiration cytology features of poorly differentiated thyroid carcinoma

Poorly differentiated thyroid carcinoma (PDTC) is an uncommon thyroid malignancy with biological behaviour intermediate between well-differentiated and undifferentiated thyroid carcinoma. The cytological diagnosis of PDTC is often difficult as a result of a lack of well-established cytomorphological features and a considerable degree of morphological overlap with other commoner thyroid neoplasms. To review the cytomorphological features of PDTC with the aim of highlighting salient diagnostic morphological features and differential diagnostic problems. Seven cases of histologically proven PDTC with available aspiration cytology smears were reviewed for the presence of distinguishing cytomorphological features. The architectural arrangement of tumour cells was the most important diagnostic parameter. Cellular nests, three-dimensional clusters dyscohesive aggregates and singly dispersed cells in the background were present in all cases. A unique 'garlanded appearance', owing to the peripheral orientation of nuclei within the tumour cell clusters, was noted (71.4%) along with the presence of basement membrane-like material (71.4%). Transgressing vessels (85.7%) and endothelial wrapping of cell clusters (71.4%) were also noted. Interestingly, most cases lacked necrosis and mitotic activity that are included in the histological diagnostic criteria for PDTC. Although PDTC has considerable cytomorphological overlap with well-differentiated thyroid tumours, this present study highlights certain cytomorphological features that may suggest the correct pre-operative diagnosis, important for the appropriate management.

BRAF(V600E) mutation is highly prevalent in thyroid carcinomas in the young population in Fukushima: a different oncogenic profile from Chernobyl.

After the accident at the Fukushima Daiichi Nuclear Power Plant, the thyroid ultrasound screening program for children aged 0–18 at the time of the accident was started from October 2011. The prevalence of thyroid carcinomas in that population has appeared to be very high (84 cases per 296,253). To clarify the pathogenesis, we investigated the presence of driver mutations in these tumours. 61 classic papillary thyroid carcinomas (PTCs), two follicular variant PTCs, four cribriform-morular variant PTCs and one poorly-differentiated thyroid carcinoma were analysed. We detected BRAFV600E in 43 cases (63.2%), RET/PTC1 in six (8.8%), RET/PTC3 in one (1.5%) and ETV6/NTRK3 in four (5.9%). Among classic and follicular variant PTCs, BRAFV600E was significantly associated with the smaller size. The genetic pattern was completely different from post-Chernobyl PTCs, suggesting non-radiogenic etiology of these cancers. This is the first study demonstrating the oncogene profile in the thyroid cancers discovered by large mass screening, which probably reflects genetic status of all sporadic and latent tumours in the young Japanese population. It is assumed that BRAFV600E may not confer growth advantage on paediatric PTCs, and many of these cases grow slowly, suggesting that additional factors may be important for tumour progression in paediatric PTCs.