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Modern Pathology : An Official Journal... Jan 2022The literature is highly conflicted on what percentage of pancreatic ductal adenocarcinomas (PDACs) arise in association with intraductal papillary mucinous neoplasms... (Comparative Study)
Comparative Study
Pancreatic ductal adenocarcinomas associated with intraductal papillary mucinous neoplasms (IPMNs) versus pseudo-IPMNs: relative frequency, clinicopathologic characteristics and differential diagnosis.
The literature is highly conflicted on what percentage of pancreatic ductal adenocarcinomas (PDACs) arise in association with intraductal papillary mucinous neoplasms (IPMNs). Some studies have claimed that even small (Sendai-negative) IPMNs frequently lead to PDAC. Recently, more refined pathologic definitions for mucin-lined cysts were provided in consensus manuscripts, but so far there is no systematic analysis regarding the frequency and clinicopathologic characteristics of IPMN-mimickers, i.e., pseudo-IPMNs. In this study, as the first step in establishing frequency, we performed a systematic review of the pathologic findings in 501 consecutive ordinary PDACs, which disclosed that 10% of PDACs had associated cysts ≥1 cm. While 31 (6.2%) of these were IPMN or mucinous cystic neoplasm (MCN), 19 (3.8%) were other cyst types that mimicked IPMN (pseudo-IPMNs) per recent WHO/consensus criteria. As the second step of the study, we performed a comparative clinicopathologic analysis by also including our entire surgical pathology/consultation databases that was comprised of 60 IPMN-associated PDACs, 30 MCN-associated PDACs and 40 pseudo-IPMN-associated PDACs. We found that 84% of true IPMNs were pre-operatively recognized, whereas IPMN was considered in differential diagnosis of 33% of pseudo-IPMNs. Of the 40 pseudo-IPMNs, there were 15 secondary duct ectasias; 6 large-duct-type PDACs; 5 pseudocysts; 5 cystic tumor necrosis; 4 simple mucinous cysts; 3 groove pancreatitis-associated paraduodenal wall cysts; and 2 congenital cysts. Microscopically, pseudo-IPMNs had at least partial mucinous-lining mimicking IPMN but had smaller cystic (mean = 1.9 cm) and larger PDAC (mean = 3.8 cm) components compared to true IPMNs (cyst = 5.7 cm; PDAC = 2.0 cm). In summary, in this pathologically verified analysis that utilized refined criteria, 10% of PDACs were discovered to have cysts ≥1 cm, about two-thirds of which were IPMN/MCN but about one-third were pseudo-IPMNs. True IPMNs underlying the PDACs are often large and are already diagnosed pre-operatively as having an IPMN component, whereas only a third of the pseudo-IPMNs receive IPMN diagnosis by imaging and their cysts are smaller. At the histopathologic level, pseudo-IPMNs are highly prone to misdiagnosis as IPMN, which presumably accounts for much higher association of IPMNs with PDAC as reported in some studies. The subtle but salient characteristics of pseudo-IPMNs elucidated in this study should be combined with careful radiological/clinical correlation in order to exclude pseudo-IPMNs.
Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Bile Duct Neoplasms; Carcinoma, Pancreatic Ductal; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Pancreatic Intraductal Neoplasms; Pancreatic Neoplasms
PubMed: 34518632
DOI: 10.1038/s41379-021-00902-x -
Diagnostic Pathology Oct 2015Nodular follicular lesions of thyroid gland comprise benign and malignant neoplasms, as well as some forms of hyperplasia. "Follicular" refers to origin of cells and in...
BACKGROUND
Nodular follicular lesions of thyroid gland comprise benign and malignant neoplasms, as well as some forms of hyperplasia. "Follicular" refers to origin of cells and in the same time to growth pattern - building follicles. Nodular follicular thyroid lesions have in common many morphological features, therefore attempts were made to define additional criteria for distinction between follicular adenoma, follicular carcinoma and follicular variant of papillary carcinoma. Increasing number of immunohistochemical markers is in the continual process of evaluation.
METHODS
Tissue microarrays incorporating, total 201 cases, out of which 122 malignant and 79 benign follicular lesions, including neoplastic and non-neoplastic, were constructed and immunostained with antibodies to CD56, CK19, Galectin-3, HBME-1. Tissue cores were exclusively being acquired from tumour/lesion on interface with normal thyroid tissue. A systematic review of literature was done for period from the year 2001 to present time.
RESULTS
All analysed markers may make a difference between benign lesions/tumours from differentiated thyroid carcinomas (p = <0.01, for all markers). Expression of all markers is significantly higher in papillary carcinoma than in follicular adenoma (p < 0.01). Statistically significant difference in expression of Galectin-3 and CD56 between follicular carcinoma and follicular adenoma was registered (p = 0.043; p = 0.028, respectively). The only marker which expression showed statistically significant difference between adenoma and carcinoma of Hurthle cells was Galectin 3 (p = 0.041). CK19 and HBME-1 were significantly expressed more in papillary carcinoma as compared to follicular carcinoma.
CONCLUSION
Galectin 3 is most sensitive marker for malignancy, while loss of expression of CD56 is very specific for malignancy. Expected co-expression for combination of markers in diagnosis of follicular lesions decreases sensitivity and increases specificity for malignancy.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Adenocarcinoma, Follicular; Biomarkers, Tumor; Carcinoma, Papillary; CD56 Antigen; Galectin 3; Keratin-19; Thyroid Neoplasms
PubMed: 26503236
DOI: 10.1186/s13000-015-0428-4 -
European Journal of Surgical Oncology :... Dec 2020Implementing high-quality randomized controlled trials is difficult for patients with 1-4 cm low-risk differentiated thyroid carcinoma (DTC). Controversy exists...
Implementing high-quality randomized controlled trials is difficult for patients with 1-4 cm low-risk differentiated thyroid carcinoma (DTC). Controversy exists regarding whether lobectomy (LT) or total thyroidectomy (TT) is the optimal surgical approach over the short term and long term. Inconsistent recommendations have led to confusion amongst surgeons. Consequently, the outcomes of patients may be influenced. A great deal of new literature is published monthly, and there have been numerous studies supporting both LT and TT. Surgeons must spend considerable time and energy clarifying why controversy exists and which studies should be used as references. We selected 19 recent guidelines/consensuses for surgical approach in treating of 1-4 cm DTC. This study presents various topics relevant to the present debate, including disease-specific survival (DSS), persistence/recurrence, and complications between LT and TT, in patients with 1-4 cm low-risk DTC. This review includes a discussion of the background of those recommendations with regard to various medical, cultural and geographic environments. Additionally, recent technologies and future directions for current issues in risk identification were integrated into the review to provide a reference for individualized decision-making for patients with 1-4 cm low-risk DTC. Given different national conditions, there are different points of emphasis amongst the guidelines. Consideration of surgical approach should consider the character of both surgeons and patients. We should balance the relative benefits, risks and resulting quality of life in order to perform individualized surgical decision-making, and to make reasonable decisions in employing either TT or LT.
Topics: Adenocarcinoma, Follicular; Clinical Decision-Making; Consensus; Disease-Free Survival; Humans; Neoplasm Grading; Neoplasm Recurrence, Local; Practice Guidelines as Topic; Quality of Life; Risk Assessment; Survival Rate; Thyroid Cancer, Papillary; Thyroid Neoplasms; Thyroidectomy; Tumor Burden
PubMed: 32933805
DOI: 10.1016/j.ejso.2020.08.014 -
Endocrine Journal Feb 2020Thyroglobulin measurement in the needle washout after fine-needle aspiration (FNA-Tg) served as an important measurement for suspicious recurrent or metastatic lesions.... (Meta-Analysis)
Meta-Analysis
Thyroglobulin measurement in the needle washout after fine-needle aspiration (FNA-Tg) served as an important measurement for suspicious recurrent or metastatic lesions. We conducted a pooled analysis to evaluate the diagnostic accuracy of FNA-Tg and searched electronic databases for original articles in English from 1993 through 2017. Finally, a total of 22 studies containing 2,670 lymph nodes (LNs) that enrolled participants with suspicious neck LNs during thyroid nodule workup or papillary thyroid cancer (PTC) follow-up were included. In our analysis, the overall pooled sensitivity for FNA-Tg was 0.91 (95%CI: 0.87-0.93), specificity was 0.94 (95% CI: 0.91-0.96). Meta regression revealed that the cutoff value and status of serum Tg were sources of heterogeneity for sensitivity, and the cutoff value was source of heterogeneity for specificity. Additionally, the cutoff value and status of serum Tg were sources of heterogeneity in the joint model. Subgroup analysis about cut-off value showed that the choice of 1 ng/mL had highest sensitivity, 40 ng/mL had highest specificity. At last, we arrived at the conclusion that FNA-Tg measurement had high specificity and sensitivity in the early detection of LNs metastases from PTC by our meta-analysis. The technique was simple and could be recommended to apply in any FNA facility, especially when LN were small-sized. Significantly, a better standardization of criteria for FNA-Tg detection and cutoff value was required to provide useful data and to improve management of PTC patients in the future.
Topics: Biopsy, Fine-Needle; Humans; Lymph Nodes; Lymphatic Metastasis; Neck; Sensitivity and Specificity; Thyroglobulin; Thyroid Cancer, Papillary; Thyroid Neoplasms; Ultrasonography
PubMed: 31723088
DOI: 10.1507/endocrj.EJ18-0558 -
Head and Neck Pathology Dec 2020The evaluation of surgically resected papillary thyroid carcinomas (PTC) by immunohistochemistry (IHC) for BRAF mutation has diagnostic, prognostic and therapeutic... (Comparative Study)
Comparative Study Meta-Analysis
The evaluation of surgically resected papillary thyroid carcinomas (PTC) by immunohistochemistry (IHC) for BRAF mutation has diagnostic, prognostic and therapeutic implications. The goal of this meta-analysis was to perform a systematic review of studies using the VE1 clone (specific for detection of the BRAF V600E mutation) on formalin-fixed paraffin embedded (FFPE) thyroid surgical resection specimens for primary papillary thyroid carcinoma. The authors' molecular techniques, immunohistochemistry protocols, and scoring methods for VE1 immunostaining were also evaluated. This study included 4079 PTCs representing data from 23 studies. The results extracted from each study were split into two different groups, direct sequencing group or PCR group, based on the molecular "gold standard" method used to compare VE1 IHC staining. In the direct sequencing group, the IHC sensitivity was 100% (95% CI 0.97-1.00) and specificity 84% (95% 0.72-0.91). In the PCR group the sensitivity was 98% (95% CI 0.96-0.99) and specificity 89% (95% CI 0.82-0.94). Although immunohistochemical procedures varied by author, the overall performance of the VE1 clone shows that it is highly sensitive and relatively specific for detecting the BRAF V600E mutation in surgical resection specimens. However, standardization of immunohistochemical procedural method and scoring/interpretation criteria may improve the reliability and reproducibility for the use of VE1 clone for future practice.
Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Genetic Techniques; Humans; Immunohistochemistry; Mutation; Proto-Oncogene Proteins B-raf; Thyroid Cancer, Papillary; Thyroid Neoplasms
PubMed: 32358715
DOI: 10.1007/s12105-020-01166-8 -
BMC Surgery Apr 2019Papillary thyroid carcinoma is a slow-growing cancer with a generally good prognosis that sometimes have an aggressive behaviour. Metastases to neck lymph nodes is the...
Papillary thyroid carcinoma is a slow-growing cancer with a generally good prognosis that sometimes have an aggressive behaviour. Metastases to neck lymph nodes is the first step of the diffusion. The central neck compartment is involved most commonly. The ipsilateral lateral neck compartments are usually involved afterwards, and the involvement of the contralateral one is considered a quite rare occurrence. In more rare cases, metastases to lateral neck compartment without central lymph node metastasis (so called "skip metastases") could be observed. Aim of this literature review study is to analyse the average incidence, pattern and risk factors of this occurrence.This study was performed according to PRISMA criteria. A final selection of 13 articles published in English language from 1997 to 2017 was performed. Any research article, review or meta-analysis was taken into consideration. Research was expanded considering the related references of articles.The incidence of skip metastases ranged from 1.6 to 21.8%. Risk factors such as age > 45 years, size < 5 mm and tumor located in the upper pole or isthmus of thyroid gland were found.Due to the frequency of skip metastases in thyroid cancer, a careful preoperative examination of lateral lymph nodes should be necessary.
Topics: Humans; Incidence; Lymph Nodes; Lymphatic Metastasis; Neck; Risk Factors; Thyroid Cancer, Papillary; Thyroid Neoplasms
PubMed: 31074393
DOI: 10.1186/s12893-018-0435-y -
Medicine Aug 2021Papillary thyroid carcinoma (PTC) incidence has been increasing worldwide. Obesity, that is, having a high body mass index, is associated with the incidence of several... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Papillary thyroid carcinoma (PTC) incidence has been increasing worldwide. Obesity, that is, having a high body mass index, is associated with the incidence of several cancers including colon, breast, esophageal, and kidney cancer. However, the association between obesity and the clinical features of PTC is still unknown. This study aimed to determine the impact of obesity on the clinical features of PTC.
METHOD
A database search was conducted for articles published up to 2020 on obesity and clinical features of PTC. Data were extracted from articles that met the meta-analysis inclusion criteria.
RESULTS
A total of 11 retrospective cohorts and 11,729 patients were included. Obesity was associated with the following variables in PTC patients: older age (difference in means = 1.95, 95% confidence interval [CI] 0.16-3.74, P = .03), male sex (odds ratio [OR] = 3.13, 95%CI 2.24-4.38, P < .00001), tumor size ≥1 cm (OR = 1.34, 95%CI 1.11-1.61, P < .002), multifocality (OR = 1.54, 95%CI 1.27-1.88, P < .0001), extrathyroidal extension (OR = 1.78, 95%CI 1.22-2.59, P = .003) and advanced tumor, node, metastasis stage (OR = 1.68, 95%CI 1.44-1.96, P < .00001). Preoperative serum thyroid-stimulating hormone level (difference in means = 0.09, 95%CI 0.35-0.52, P = .70), Vascular invasion (OR = 0.84, 95%CI 0.56-1.26, P = .41), lymph node metastasis (OR = 1.07, 95%CI 0.87-1.32, P = .50), distant metastasis (OR = 1.14, 95%CI 0.64-2.04, P = .66), and recurrence (OR = 1.45, 95%CI 0.97-2.15, P = .07) were not associated with obesity.
CONCLUSION
Obesity was associated with several poor clinicopathologic prognostic features: older age, male gender, tumor size ≥1 cm, extrathyroidal extension, multifocality, and advanced tumor/node/metastasis stage. However, thyroid-stimulating hormone level, vascular invasion, lymph node metastasis, distant metastasis, and recurrence were not associated with obesity in PTC.
Topics: Body Mass Index; Causality; Disease Progression; Humans; Obesity; Prognosis; Risk Assessment; Thyroid Cancer, Papillary; Thyroid Neoplasms
PubMed: 34397906
DOI: 10.1097/MD.0000000000026882 -
Endocrinology and Metabolism (Seoul,... Feb 2024Active surveillance (AS) has been introduced as a management strategy for low-risk papillary thyroid carcinoma (PTC) due to its typically indolent nature. Despite this,...
BACKGRUOUND
Active surveillance (AS) has been introduced as a management strategy for low-risk papillary thyroid carcinoma (PTC) due to its typically indolent nature. Despite this, the widespread adoption of AS has encountered several challenges. The aim of this systematic review was to evaluate the safety of AS related to disease progression and its benefits compared with immediate surgery (IS).
METHODS
Studies related to AS in patients with low-risk PTC were searched through the Ovid MEDLINE, Embase, Cochrane Library, and KoreaMed databases. Studies on disease progression, surgical complication, quality of life (QoL), and cost-effectiveness were separately analyzed and narratively synthesized.
RESULTS
In the evaluation of disease progression, the proportions of cases with tumor growth ≥3 mm and a volume increase >50% were 2.2%-10.8% and 16.0%-25.5%, respectively. Newly detected lymph node metastasis was identified in 0.0%-1.4% of patients. No significant difference was found between IS and delayed surgery in surgical complications, including vocal cord paralysis and postoperative hypoparathyroidism. AS was associated with better QoL than IS. Studies on the cost-effectiveness of AS reported inconsistent data, but AS was more cost-effective when quality-adjusted life years were considered.
CONCLUSION
AS is an acceptable management option for patients with low-risk PTC based on the low rate of disease progression and the absence of an increased mortality risk. AS has additional benefits, including improved QoL and greater QoL-based cost-effectiveness.
Topics: Humans; Thyroid Cancer, Papillary; Thyroid Neoplasms; Quality of Life; Thyroidectomy; Watchful Waiting; Disease Progression
PubMed: 38417830
DOI: 10.3803/EnM.2023.1794 -
Frontiers in Endocrinology 2023To investigate the effect and clinical significance of Delphian lymph nodes (DLN) on the factors influencing papillary thyroid cancer (PTC) to provide individualized... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To investigate the effect and clinical significance of Delphian lymph nodes (DLN) on the factors influencing papillary thyroid cancer (PTC) to provide individualized guidance for the surgical treatment of thyroid cancer.
METHODS
Relevant studies from PubMed, Web of Science, the Cochrane Library, Embase, and China National Knowledge Infrastructure databases were searched until February 13, 2023. Stringent selection parameters were used to obtain included data and homogeneous articles. Analyses were performed using Revman 5.4 and SPSS software. A -value of < 0.05 was considered statistically significant.
RESULTS
Five studies were finally included in this study. The results revealed a higher risk of DLN metastasis (DLNM) in patients with tumor size >1cm, multifocality, and extrathyroidal extension (ETE) of the thyroid. The risk of central lymph node metastasis (CLNM) was 11.25 times higher in DLN-positive patients with PTC than in DLN-negative (OR = 11.25, 95% CI: 8.64-14.64, < 0.05) patients. The risk of LLNM was 5.57 times higher in DLN-positive patients with PTC than in DLN-negative (OR = 5.57, 95% CI: 4.57-6.78, < 0.001) patients. The risk of postoperative recurrence in DLN-positive patients with PTC was 3.49 times higher (OR = 3.49, 95% CI: 1.91-6.38, < 0.001) than in DLN-negative patients with PTC.
CONCLUSION
Patients with tumor size >1 cm in diameter, multifocality, and ETE have an increased risk for DLN development. DLN-positive patients with central and lateral cervical lymph node metastasis and postoperative recurrence are at higher risk than DLN-negative patients.
Topics: Humans; Thyroid Cancer, Papillary; Lymphatic Metastasis; Clinical Relevance; Carcinoma, Papillary; Thyroid Neoplasms
PubMed: 38313842
DOI: 10.3389/fendo.2023.1295548 -
Diagnostic Cytopathology Sep 2019This study was designed to explore whether ultrasound of thyroid nodules facilitates the interpretation of the malignant risk of Bethesda III/IV thyroid nodules to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This study was designed to explore whether ultrasound of thyroid nodules facilitates the interpretation of the malignant risk of Bethesda III/IV thyroid nodules to inform further therapies.
METHODS
We reviewed patient records in which the results of ultrasound-guided fine-needle aspiration (US-FNA) were classified by the Bethesda III/IV in our institution between January 2016 and June 2018. Studies were retrieved from PubMed, Cochrane Central Register of Controlled Trials, ISI Web of Science, Science Direct, Wiley Online Library, EMBASE, China National Knowledge Infrastructure, WanFang, and Chinese VIP. The odds ratio (OR) was used to measure associations between risk factors and thyroid nodule malignancy.
RESULTS
Fifty-nine cases of Bethesda III/IV with corresponding surgeries were included, and the malignancy risk was 54.2%. Meta-analysis revealed irregular borders, solitary nodules, hypoechogenicity, microcalcifications, and being taller than wide, all of which increased the malignancy risk of thyroid nodules. Combined ORs for these factors were 4.08 (95% CI: 2.34-7.14, P < .001), 2.18 (95% CI: 1.39-3.42, P = .001), 2.02 (95% CI: 1.35-3.01, P = .001), 3.21 (95% CI: 2.26-4.56, P < .001), and 4.35 (95% CI: 3.07-6.15, P < .001), respectively.
CONCLUSION
As the risk of malignancy for papillary thyroid carcinoma (PTC) is high, when any one of the five ultrasound features of malignancy were confirmed, repeated FNA is recommended to confirm PTC-type malignancy, even though nodules were Bethesda III/IV classification. However, repeated FNA should be avoided when none of these ultrasound features are identified because repeated FNA does not contribute to identifying non-PTC type malignancies, such as follicular thyroid carcinoma and poorly differentiated thyroid carcinoma.
Topics: Adenocarcinoma, Follicular; Adult; Biopsy, Fine-Needle; Diagnosis, Differential; Female; Humans; Image-Guided Biopsy; Male; Middle Aged; Thyroid Cancer, Papillary; Thyroid Nodule; Ultrasonography
PubMed: 31211509
DOI: 10.1002/dc.24248