Comparative Analysis About Clinical Manifestation and Prognostic Factors of Thyroid Follicular and Hurthle Cell Carcinoma

Background and Objectives Follicular thyroid carcinoma (FTC) is the second common thyroid cancer which comprises about 10% of differentiated thyroid carcinoma. Hurthle cell carcinoma (HCC) is a relatively rare disease that has been classified as a subtype of FTC. However, there have been insufficient reports about these two similar thyroid cancers in South Korea due to low incidences. This study aims to present clinical features and evaluate prognostic factors of FTC and HCC.Subjects and Method We reviewed data of 189 FTC and 12 HCC patients who underwent surgery in our center from January 2000 to December 2020. Variables such as clinical characteristics, surgical method, pathologic result, post-operative treatment, survival rate and prognostic factors were included in our study.Results As for age, 67.2% of patients in FTC group and 33.3% of patients in HCC group were older than 55 years-old (p=0.017). The average tumor sizes of FTC and HCC were 2.98 and 3.1 cm, respectively. The 10-year overall survival rates of FTC and HCC were 96.5% and 100%, respectively. The 10-year disease free survival rates of FTC and HCC were 89.1% and 91.7%, respectively. Subclassification (widely invasive: p=0.036) and initial distant metastasis (p<0.001) were significant prognostic factors in FTC.Conclusion This study will be helpful for diagnosis and treatment of FTC and HCC, which are relatively rare.

Oncocytic Papillary Thyroid Carcinoma and Oncocytic Poorly Differentiated Thyroid Carcinoma: Clinical Features, Uptake, and Response to Radioactive Iodine Therapy, and Outcome

ObjectiveThe main objective of this study was to review the clinicopathologic characteristics and outcome of patients with oncocytic papillary thyroid carcinoma (PTC) and oncocytic poorly differentiated thyroid carcinoma (PDTC). The secondary objective was to evaluate the prevalence and outcomes of RAI use in this population.MethodsPatients with oncocytic PTC and PDTC who were treated at a quaternary cancer centre between 2002 and 2017 were retrospectively identified from an institutional database. All patients had an expert pathology review to ensure consistent reporting and definition. The cumulative incidence function was used to analyse locoregional failure (LRF) and distant metastasis (DM) rates. Univariable analysis (UVA) was used to assess clinical predictors of outcome.ResultsIn total, 263 patients were included (PTC [n=218], PDTC [n=45]) with a median follow up of 4.4 years (range: 0 = 26.7 years). Patients with oncocytic PTC had a 5/10-year incidence of LRF and DM, respectively, of 2.7%/5.6% and 3.4%/4.5%. On UVA, there was an increased risk of DM in PTC tumors with widely invasive growth (HR 17.1; p&lt;0.001), extra-thyroidal extension (HR 24.95; p&lt;0.001), angioinvasion (HR 32.58; p=0.002), focal dedifferentiation (HR 19.57, p&lt;0.001), and focal hobnail cell change (HR 8.67, p=0.042). There was additionally an increased risk of DM seen in male PTC patients (HR 5.5, p=0.03).The use of RAI was more common in patients with larger tumors, angioinvasion, and widely invasive disease. RAI was also used in the management of DM and 43% of patients with oncocytic PTC had RAI-avid metastatic disease. Patients with oncocytic PDTC had a higher rate of 5/10-year incidence of LRF and DM (21.4%/45.4%; 11.4%/40.4%, respectively). Patients with extra-thyroidal extension had an increased risk of DM (HR 5.52, p=0.023) as did those with angioinvasion. Of the patients with oncocytic PDTC who received RAI for the treatment of DM, 40% had RAI-avid disease.ConclusionWe present a large homogenous cohort of patients with oncocytic PTC and PDTC, with consistent pathologic reporting and definition. Patients with oncocytic PTC have excellent clinical outcomes and similar risk factors for recurrence as their non-oncocytic counterparts (angioinvasion, large tumor size, extra-thyroidal extension, and focal dedifferentiation). Compared with oncocytic PTCs, the adverse biology of oncocytic PDTCs is supported with increased frequency of DM and lower uptake of RAI.

Invasion in a Community Context: Genetic Variation in the Strength of Direct and Indirect Effects

Predicting invasion success requires understanding how abiotic and biotic factors in the local environment interact with the particular traits of potential invaders. Relative to studies of direct antagonistic effects, fewer studies have examined how positive species interactions, such as facilitation or mutualism, or indirect interactions in multispecies communities, can affect invasion success. We examined the effects of drought and mutualisms with rhizobia bacteria on the performance of a widely invasive legume, Medicago polymorpha. In a greenhouse experiment, we found that watering regime affected plant performance, but non-linear patterns in response to decreasing water were dependent on the specific plant genotype. In a second experiment, we found that the effects of drought on plant performance were dependent on the presence of rhizobia, particularly for genotypes collected from the invasive range. This suggests that indirect ecological effects may have important consequences for invasion success. We contextualize the strength of these direct and indirect effects by comparing this study to effect sizes in other studies of the same species. In this species, predicting invasion into a natural community context will require understanding multiple direct and indirect effects in the local environment, as well as their effects on the specific genetic composition of the invading population.

Whole-genome sequencing of follicular thyroid carcinomas reveal recurrent mutations in microRNA processing subunit DGCR8

Background The genomic and transcriptomic landscape of widely invasive follicular thyroid carcinomas (wiFTCs) and Hürthle cell carcinoma (HCC) are poorly characterized and subsets of these tumors lack information on genetic driver events. The aim of this study was to bridge this gap. Methods We performed whole-genome and RNA sequencing and subsequent bioinformatic analyses of 11 wiFTCs and 2 HCCs with a particularly poor prognosis, and matched normal tissue. Results All wiFTCs exhibited one or several mutations in established thyroid cancer genes, including TERT (n=4), NRAS (n=3), HRAS, KRAS, AKT, PTEN, PIK3CA, MUTYH, TSHR and MEN1 (n=1 each). MutSig2CV analysis revealed recurrent somatic mutations in FAM72D (n=3, in two wiFTCs and in a single HCC), TP53 (n=3, in two wiFTCs and a single HCC) and EIF1AX (n=3), with DGCR8 (n=2) as borderline significant. The DGCR8 mutations were recurrent p.E518K missense alterations, known to cause familial multinodular goiter via disruption of microRNA processing. Expression analyses showed reduced DGCR8 mRNA expression in FTCs in general, and the two DGCR8 mutants displayed a distinct miRNA profile compared to DGCR8 wildtypes. Copy number analyses revealed recurrent gains on chromosomes 4, 6 and 10, and fusiongene analyses revealed 27 high-quality events. Both HCCs displayed hyperploidy, which was fairly unusual in the FTC cohort. Based on the transcriptome data tumors amassed in two principal clusters. Conclusion We describe the genomic and transcriptomic landscape in wiFTCs and HCCs and identify novel recurrent mutations and copy number alterations with possible driver properties and lay the foundation for future studies.

Genetics, Diagnosis, and Management of Hürthle Cell Thyroid Neoplasms

Hürthle cell lesions have been a diagnostic conundrum in pathology since they were first recognized over a century ago. Controversy as to the name of the cell, the origin of the cell, and even which cells in particular may be designated as such still challenge pathologists and confound those treating patients with a diagnosis of “Hürthle cell” anything within the diagnosis, especially if that anything is a sizable mass lesion. The diagnosis of Hürthle cell adenoma (HCA) or Hürthle cell carcinoma (HCC) has typically relied on a judgement call by pathologists as to the presence or absence of capsular and/or vascular invasion of the adjacent thyroid parenchyma, easy to note in widely invasive disease and a somewhat subjective diagnosis for minimally invasive or borderline invasive disease. Diagnostic specificity, which has incorporated a sharp increase in molecular genetic studies of thyroid tumor subtypes and the integration of molecular testing into preoperative management protocols, continues to be challenged by Hürthle cell neoplasia. Here, we provide the improving yet still murky state of what is known about Hürthle cell tumor genetics, clinical management, and based upon what we are learning about the genetics of other thyroid tumors, how to manage expectations, by pathologists, clinicians, and patients, for more actionable, precise classifications of Hürthle cell tumors of the thyroid.

Echinochloa pyramidalis.

E. pyramidalis, a perennial grass, has decidedly invasive characteristics with its vigorous shoot and rhizome growth and abundant seed production. As an aquatic, it also has the potential to be very damaging to sensitive aquatic habitats. Holm et al. (1979) record it as a major weed in its native area in Nigeria, Swaziland, Sudan and Madagascar. In Guyana, after being introduced and cultivated for some years, it was noticed as a weed in sugar cane in 1982 and increased rapidly to become one of the most troublesome weeds in the aquatic system of the Guyana Sugar Corporation (Bishundial et al., 1997). In Mexico, again after introduction as a fodder grass, it has become widely invasive in wetlands, tending to reduce native wetland species (López Rosas et al., 2010). Apart from its competitive growth, Wells et al. (1986) note its tendency to obstruct water flow. For the USA it is highly ranked as a potential invasive weed of the future (Parker et al., 2007) and it has been identified as a species 'not authorized (for introduction) pending pest risk analysis' (NAPPRA) (USDA-APHIS, 2012).

Desert pumpkinseed: diet composition and breadth in a Moroccan river

The widely invasive North American pumpkinseed sunfish, Lepomis gibbosus, is currently established in desert rivers in Morocco. The success of pumpkinseed in novel ecosystems has been associated with its generalist diet, but this trait remains unevaluated in arid regions. Desert rivers are harsh environments with limited water and prey availability which may adversely constrain the diet of fish. Here we studied the diet of pumpkinseed across 4 sites in the Draa River, embracing a 450 m elevational gradient covering from extremely dry lowlands to relatively humid highlands. We described pumpkinseed diet through the analysis of stomach contents of 82 individuals, collected in the fall of 2013. Pumpkinseed diet was dominated by Chironomidae in dry lowlands, while Ephemeroptera, Heteroptera, Trichoptera and Odonata were relevant prey in more humid highlands. Population diet breadth expanded with elevation, but individual specialization in diet was low among all sites. Our results highlight considerable changes in diet composition and breadth with aridity, suggesting that feeding plasticity and use of exclusive, locally abundant prey rather than generalized feeding may be associated with the success of pumpkinseed in most arid areas in desert rivers.

Molecular profile of Hürthle cell carcinomas: recurrent mutations in the Wnt/β-catenin pathway

Objective Genomic alterations in Hürthle cell carcinomas (HCC) include chromosomal losses, mitochondrial DNA mutations, and changes in the expression profile of the PI3K-AKT-mTOR and Wnt/β-catenin pathways. This study aimed at characterizing the mutational profile of HCC. Methods Next-generation sequencing (NGS) of 40 HCC using a 102-gene panel including, among others, the MAPK, PI3K-AKT-mTOR, Wnt/β-catenin, and Notch pathways. HCC was widely invasive in 57.5%, and lymph node and distant metastases were diagnosed in 5% and 7.5% of cases. During follow-up, 10% of patients presented with persistent/recurrent disease, but there were no cancer-related deaths. Results Genetic alterations were identified in 47.5% of HCC and comprised 190 single-nucleotide variants and 5 insertions/deletions. The Wnt/β-catenin pathway was most frequently affected (30%), followed by MAPK (27.5%) and PI3K-AKT-mTOR (25%). FAT1 and APC were the most frequently mutated genes and present in 17.5%. RAS mutations were present in 12.5% but no BRAF mutation was found. There was no association between the mutational profile and clinicopathological features. Conclusions This series of HCC presents a wide range of mutations in the Wnt/β-catenin, MAPK and PI3K-AKT-mTOR pathways. The recurrent involvement of Wnt/β-catenin pathway, particularly mutations in APC and FAT1, are of particular interest. The data suggest that mutated FAT1 may represent a potential novel driver in HCC tumorigenesis and that the Wnt/β-catenin pathway plays a critical role in this distinct thyroid malignancy.