Hobnail variant of papillary thyroid carcinoma: a systematic review and meta-analysis.
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ABSTRACT: Objective
The hobnail variant of papillary thyroid carcinoma (HVPTC) has emerged as a rare and aggressive variant of papillary thyroid carcinoma (PTC). We aim to determine the prevalence and clinicopathologic factors of HVPTC.Methods
A systematic review of the literature for studies examining HVPTC was performed. Four databases (PubMed, Scopus, OVID, Cochrane library) were queried from inception of databases through March 20th, 2020.Results
Sixteen studies with 124 cases of HVPTC were included. The mean age for all patients was 52.3 years. HVPTC had a prevalence of 1.08% out of all PTC cases, with a mean tumor size of 3.1 cm. In 62% and 50% of cases, lymphovascular invasion and extrathyroidal extension were present, respectively. Follow-up data, with a mean of 49.9 months, revealed a 66% rate of lymph node metastasis and 23% rate of distant metastasis. Tumors with ≥30% hobnail morphology had a 2.6-fold increased odds of developing lymph node metastasis compared with <30% hobnail morphology, however did not differ in rates of distant metastasis. Patients ≥55 years old had a 4.5-fold increased odds of distant metastasis and a 4.7-fold increased odds of lymphovascular invasion over patients <55.Conclusions
High rates of locoregional and distant disease as well as high-risk pathological factors reveal the aggressive nature of HVPTC. Diagnostic criteria regarding percentage of hobnail morphology requires further refinement. Further studies are warranted in order to better understand how recognition of this high-risk variant impacts clinical treatment.
SUBMITTER: Donaldson LB
PROVIDER: S-EPMC8111367 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Purpose: To explore the risk factors that may predict the lymph node metastasis potential of these lesions and new prevention strategies in papillary thyroid carcinoma patients. Materials and Methods: In total, 9,369 papillary thyroid carcinoma patients with 37.17% lymph node metastasis were analyzed (Revman 5.3 software) in this study. The PubMed and Embase databases were used for searching works systematically that were published through to January 22, 2020. Results: Several factors were related to the increased risk of lymph node metastasis in patients with papillary thyroid carcinoma: age <45 years (pooled OR = 1.52, 95% CI = 1.14-2.01, p <0.00001); gender = male (pooled OR = 1.68, 95% CI = 1.51-1.87, p <0.00001); multifocality (pooled OR = 2.05, 95% CI = 1.45-2.89, p <0.0001); tumor size ?1.0 cm (pooled OR = 3.53, 95% CI = 2.62-4.76, p <0.00001); tumor location at the upper pole 1/3 (pooled OR =1.46, 95% CI = 1.04-2.04, p = 0.03); capsular invasion + (pooled OR = 3.48, 95% CI = 1.69-7.54, p = 0.002); and extrathyroidal extension + (pooled OR = 2.03, 95% CI= 1.78-2.31, p <0.00001). However, tumor bilaterality (pooled OR = 0.85, 95% CI = 0.54-1.34, p = 0.49) and Hashimoto's thyroditis (pooled OR = 1.08, 95% CI = 0.79-1.49, p = 0.62) showed no correlation with lymph node metastasis in papillary thyroid carcinoma patients. Conclusion: The systematic review and meta-analysis defined several significant risk factors of lymph node metastasis in papillary thyroid cancer patients: age (<45 years), gender (male), multifocality, tumor size (>1 cm), tumor location (1/3 upper), capsular invasion, and extra thyroidal extension. Bilateral tumors and Hashimoto's thyroiditis were unrelated to lymph node metastasis in patients with papillary thyroid cancer.
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Project description:BackgroundCentral lymph node metastasis (CLNM) is common in papillary thyroid carcinoma (PTC). Prophylactic central lymph node dissection (PCLND) for patients with clinically negative central compartment lymph nodes (CN0) remains controversial. The phrase "clinically negative" is used to indicate that patients exhibited no clinical evidence of CLNM by ultrasonography (US) or computerized tomography (CT) preoperatively. In this study, we analyze the risk factors for CLNM in CN0 patients.MethodsThe PUBMED and SCIE databases were systematically searched for works published through January 31, 2015. All of the patients included in this study underwent thyroidectomy+PCLND. Revman 5.3 software was used to analyze the data.ResultsTwenty studies and 9084 patients were included in this meta-analysis. The following variables were associated with an increased risk of CLNM in CN0 patients: age < 45 years (OR = 1.59, 95% CI = 1.42-1.78, p<0.00001), male sex (OR = 1.95, 95% CI = 1.63-2.32, p<0.00001), multifocality (OR = 1.43, 95% CI = 1.22-1.67, p<0.00001), tumor size > 2 cm for PTC patients (OR = 2.98, 95% CI 2.08-4.28, p<0.00001) or tumor size > 0.5 cm for papillary thyroid microcarcinoma (PTMC) patients (OR = 2.30, 95% CI = 1.71-3.09, p<0.00001), location of the primary tumor in the central area and low pole (OR = 1.86, 95% CI = 1.48-2.33, p<0.00001), lymphovascular invasion (OR = 4.35, 95% CI = 2.24-8.46, p<0.0001), extrathyroidal extension (OR = 2.27, 95% CI = 1.76-2.94, p<0.00001), and capsular invasion (OR = 1.72, 95% CI = 1.39-2.41, p<0.00001). PTC (tumor size > 1 cm) exhibited a higher risk factor associated with CLNM than PTMC (tumor size < 1 cm) (OR = 2.83, 95% CI = 2.15-3.72, p<0.00001). Bilateral tumors (OR = 1.21, 95% CI = 0.92-1.58, p = 0.17) and lymphocytic thyroiditis (OR = 0.88, 95% CI = 0.71-1.09, p = 0.25) had no association with CLNM in CN0 patients.ConclusionsOur systematic review identified several clinical features associated with CLNM in CN0 patients, including age, sex, multifocality, size, location, lymphovascular invasion, capsular invasion, and extrathyroidal extension. These factors should guide the application of PCLND in CN0 patients.
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Project description:The main nonmedullary form of thyroid cancer is papillary thyroid carcinoma (PTC) that accounts for 80-90% of all thyroid malignancies. Only 3-10% of PTC patients have a positive family history of PTC yet the familiality is one of the highest of all cancers as measured by case control studies. A handful of genes have been implicated accounting for a small fraction of this genetic predisposition. It was therefore of considerable interest that a mutation in the HABP2 gene was recently implicated in familial PTC. The present work was undertaken to examine the extent of HABP2 variant involvement in PTC. The HABP2 G534E variant (rs7080536) was genotyped in blood DNA from 179 PTC families (one affected individual per family), 1160 sporadic PTC cases and 1395 controls. RNA expression of HABP2 was tested by qPCR in RNA extracted from tumor and normal thyroid tissue from individuals that are homozygous wild-type or heterozygous for the variant. The variant was found to be present in 6.1% familial cases, 8.0% sporadic cases (2 individuals were homozygous for the variant) and 8.7% controls. The variant did not segregate with PTC in one large and 6 smaller families in which it occurred. In keeping with data from the literature and databases the expression of HABP2 was highest in the liver, much lower in 3 other tested tissues (breast, kidney, brain) but not found in thyroid. Given these results showing lack of any involvement we suggest that the putative role of variant HABP2 in PTC should be carefully scrutinized.
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Project description:ObjectivePapillary thyroid cancer (PTC) is the most common endocrine malignancy with a steadily increasing incidence. Researches have reported that tumor multifocality occurs in an extensive number of cases. Nevertheless, the clinical characteristics and prognostic value remained controversial. This study was performed to investigate the relationship between multifocal PTC and adverse clinicopathologic features and the prognosis.MethodsA systematic review and meta-analysis were conducted based on three electronic databases up to December 31, 2021. Parameters of interest included five clinical features (extrathyroidal extension, lymphovascular invasion, central lymph node metastasis, lateral lymph node metastasis, distant metastasis) and were pooled into risk ratios (RRs). Time-to-event data (recurrence-free survival and all-cause mortality) were evaluated using hazard ratios (HRs). Publication bias was examined using funnel plots and Egger's test.ResultsA total of 23 articles were included according to the inclusion criteria; all of the studies were retrospective cohorts. In comparison with unifocality, multifocality showed an increased risk of extrathyroidal extension (RR 1.38, 95% CI 1.25-1.53), lymphovascular invasion (RR 1.27, 95% CI 1.04-1.55), central lymph node metastasis (RR 1.21, 95% CI 1.12-1.30), lateral lymph node metastasis (RR 1.86, 95% CI 1.62-2.14), and distant metastasis (RR 1.35, 95% CI 1.03-1.76). Multifocal patients were predisposed to postoperative recurrence (HR 1.76, 95% CI 1.50-2.07). The rate of all-cause mortality did not reach a statistical difference.Level of evidence2.ConclusionMultifocal PTC is more aggressive in contrast to unifocal PTC and is accompanied by an increased risk of recurrence. They were usually diagnosed in higher grades and stages. To achieve the maximal benefit, we recommend personalized therapy and close follow-up for multifocal PTC patients. Further prospective studies will clarify the best-fitted treatment plans.
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Project description: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.
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Project description:BackgroundThe association between adiposity and papillary thyroid carcinoma (PTC) has been reported in several studies, but its association with aggressive clinicopathologic features is not well-recognized. Our aim is to systematically review the literature to identify whether adiposity, expressed through Body Mass Index (BMI), is related to aggressive clinicopathologic features such as tumor-node-metastasis (TNM) stage, extrathyroidal extension (ETE), lymph node (LN) metastasis and multifocality in patients with PTC.MethodsA systematic search for articles was performed using the PubMed, EBSCO, and Cochrane Library for all articles published in English until December 2020. Specific keywords such as "papillary thyroid carcinoma", "Body Mass Index", "clinicopathologic features" were used in the search strategy. Two independent reviewers screened all retrieved articles based on predefined inclusion and exclusion criteria. Meta-analysis was performed in the studies that reported crude and adjusted odds ratios (OR). The methodological quality was assessed using the Newcastle-Ottawa Scale.ResultsA total of 11 retrospective cohort studies involving 26,196 participants included. Our findings showed that elevated BMI was significantly associated with ETE in both overweight (OR 1.26, 95% CI: 1.09-1.44) and obesity group (OR 1.45, 95% CI:1.26-1.64). Elevated BMI was also significantly associated with multifocality in overweight patients (OR 1.17, 95% CI:1.10-1.24) and obese patients (OR 1.45, 95% CI:1.29-1.62). Also, obesity was significantly associated with increased tumor size (OR 1.77, 95% CI:1.52-2.03) and with LN metastasis (OR 1.28, 95% CI: 1.12-1.44), whereas being overweight was significantly associated with advanced TNM stage (OR 1.55, 95% CI:1.27-1.83).ConclusionOur results provide strong evidence for the association between higher BMI and ETE, multifocality, and tumor size. Further studies with a larger number of participants are required to elucidate further the association of increased BMI with advanced TNM stage and LN metastasis.
| S-EPMC8279812 | biostudies-literature
Project description:BackgroundWhile papillary thyroid carcinoma (PTC) is associated with high occult central neck metastasis (CNM) rates, prophylactic central neck dissection (pCND) is controversial. This meta-analysis aims to look at the occult CNM rate according to tumor size.MethodsA literature search was conducted in PubMed from inception to April 2023. Inclusion criteria were primary studies that determined occult CNM rates in cN0 PTC by tumor size. Heterogeneity, influential case diagnostics, and proportion data were evaluated with Cochran's Q-test, Baujat plots and Forest plots, respectively.ResultsFifty-two studies were included in this meta-analysis. The findings demonstrated an occult CNM rate of 30.3% for tumors ≤ 5 mm, 32.7% for tumors ≤ 1 cm, 46.0% for tumors between 1 and 2 cm, 43.1% for tumors between 2 and 4 cm, and 61.2% for tumors > 4 cm. The heterogeneity of each study group was high, though no publication bias was noted. While there was a trend towards increased occult CNM rates with larger tumors, comparisons between different size cutoffs varied in significance.ConclusionThis comprehensive review affirms that occult CNM is high and that an ipsilateral pCND can be justified in all PTC patients for accurate differentiation between Stage I and Stage II disease and its clinical implications.
| S-EPMC10453273 | biostudies-literature
Project description:ImportanceActive surveillance is sometimes considered as a disease management option for individuals with small, low-risk papillary thyroid carcinoma.ObjectiveTo assess whether patient age is associated with progression of low-risk papillary thyroid carcinoma (tumor growth or incident metastatic disease) in adults under active surveillance.Evidence reviewEight electronic databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Emcare, PsycINFO, Web of Science, and ClincalTrials.gov) were searched from inception to March 2019, supplemented with a hand search. Two investigators independently screened citations, reviewed full-text articles, and abstracted data. Additional data were sought from authors. Random-effects meta-analyses were performed using incidence data (statistically adjusted for confounders and crude rates).FindingsA total of 1658 unique citations were screened, and 62 full-text articles were reviewed, including 5 studies. Three studies included exclusively microcarcinomas and 2 included tumors up to 2 cm in maximal diameter. The mean age of participants was 51.0 to 55.2 years in 4 studies reporting this value. The mean or median follow-up was 5 years or more in 3 studies and approximately 2 years in 2 studies. The pooled risk ratio for tumor growth of 3 mm or more in maximal diameter in individuals aged 40 to 50 years compared with younger individuals was 0.51 when adjusted for confounders (95% CI, 0.29-0.89; 1619 patients, 2 studies), and the unadjusted risk ratio of this outcome for individuals 40 years or older was 0.55 (95% CI, 0.36-0.82; 2097 patients, 4 studies). In adults aged 40 to 45 years, the unadjusted risk ratio for any tumor volume increase compared with younger individuals was 0.65 (95% CI, 0.51-0.83; 1232 patients, 4 studies). The pooled risk ratio for incident nodal metastases in individuals 40 years or older was 0.22 (95% CI, 0.10-0.47; 1806 patients, 3 studies); however, in a secondary analysis, the risk difference was not significantly different. There was no statistically significant heterogeneity in any of the meta-analyses. There were no thyroid cancer-related deaths nor incident distant metastases.Conclusions and relevanceThis study suggests that older age may be associated with a reduced risk of primary papillary thyroid carcinoma tumor growth under active surveillance. Incident metastatic disease is uncommon during active surveillance.
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Project description:Background and aimsFor most patients with follicular variant of papillary thyroid carcinoma (FVPTC), surgery is required, while the surgical management remains controversial. We aim to further understanding of treatment of FVPTC and to determine whether specific features could be identified for the decision of surgical strategy.Materials and methodsData were obtained from the Surveillance, Epidemiology, and End Results (SEER) Program database during 2003 and 2013. 26700 patients were eligible and stratified by tumor size or extension. Survival rates were compared using multivariate Cox proportional hazard regressions.ResultsOf the total death of 1041, 136 patients died from thyroid cancer. Most patients (79.1%) underwent total thyroidectomy while only a little part of patients (8.2%) underwent lobectomy. Patients receiving radioisotopes had significantly better overall survival (OS) (HR = 0.659, P < 0.001), but showed no differences on disease-specific survival (DSS). No statistical difference was found between total thyroidectomy and lobectomy in multivariate analysis when controlling for tumor size. While for tumor > 2 cm with extrathyroidal extension, lobectomy had significantly worse OS (aHR = 3.364, P = 0.010) and DSS (aHR = 5.494, P = 0.032) compared to total thyroidectomy. Multivariate analysis demonstrated that advanced age, male, higher grade, extrathyroidal extension, lymph nodes metastases and distant metastases had negative effects on OS and DSS controlling for the remaining variables (each P < 0.05).ConclusionsThe results of our study revealed total thyroidectomy could benefit the survival for patients whose tumors > 2 cm with extrathyroidal extension, total thyroidectomy should be recommended for those patients. Lots of factors should be taken into consideration on the decision of surgical treatment.
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