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Human Pathology Feb 2024Differentiated high-grade thyroid carcinomas (DHGTCs) are a new diagnostic entity most recently defined in the 2022 World Health Organization's (WHO) Classification of...
BACKGROUND
Differentiated high-grade thyroid carcinomas (DHGTCs) are a new diagnostic entity most recently defined in the 2022 World Health Organization's (WHO) Classification of Endocrine and Neuroendocrine Tumors. This new entity has been minimally described in the literature, and additional cases classified as such are missing.
MATERIALS AND METHODS
Cases of DHGTCs diagnosed at our institution from 2012 to 2022 were identified, and the following were reviewed: cytologic and histologic diagnoses, ancillary testing, immunohistochemical staining, treatments, and patient outcomes. Immunohistochemical staining for Ki67 was performed on selected cases lacking this immunostain. A systematic literature review of the English literature on DHGTCs from 2013 to 2023 was performed using PubMed and Embase.
RESULTS
Case cohort included 32 cases of DHGTCs, with an average age of 52.6 years (range 17-84 years) and a male:female ratio of 1.3:1. All cases underwent fine needle aspiration (FNA) and were categorized by The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) as follows: 14 cases as malignant (43.8 %), 10 as follicular neoplasm (31.3 %), 5 as atypia of undetermined significance (15.6 %), 2 as suspicious for malignancy (6.2 %), and 1 as non-diagnostic (3.1 %). The average tumor size was 5.15 cm, and most were papillary thyroid carcinoma (28, 87.5 %), with classic subtype being the most common. Twenty-one cases revealed tumor necrosis and the mitotic activity in lesions without necrosis averaged to 5.5 mitoses per 2 mm (range 0-7). The average Ki67 proliferative index was 5.6 %. Extrathyroidal extension was seen in 17, angioinvasion in 21, lymphatic invasion in 7, and perineural invasion in 1 case. Foci of solid or trabecular growth were identified in five cases. Lymph node metastases at the time of diagnosis were noted in 10 cases and 7 demonstrated distant metastases or locoregional recurrence. To date, 25 patients are alive, and one has died from disease.
CONCLUSIONS
Our institutional experience demonstrates that DHGTC is a rare, but aggressive thyroid tumor subtype that requires consideration in the setting of a well-differentiated thyroid neoplasm to appropriately assess for possible disease recurrence and determination of patient prognosis.
Topics: Humans; Male; Female; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Ki-67 Antigen; Thyroid Neoplasms; Thyroid Cancer, Papillary; Necrosis; Adenocarcinoma, Follicular; Retrospective Studies
PubMed: 38244615
DOI: 10.1016/j.humpath.2024.01.002 -
BMC Surgery Aug 2019By comparing the long-term prognostic outcomes after pancreaticoduodenectomy (PD) and limited resection (LR), this study aimed to investigate the optimal surgical... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
By comparing the long-term prognostic outcomes after pancreaticoduodenectomy (PD) and limited resection (LR), this study aimed to investigate the optimal surgical modality for duodenal gastrointestinal stromal tumors (GISTs).
METHODS
Two authors independently searched PubMed, Web of Science, Embase, and the Cochrane Library for published articles comparing the long-term prognostic and clinicopathological factors of duodenal GIST patients undergoing PD versus LR. Relevant information was extracted and analyzed.
RESULTS
After screening, 10 items comprising 623 cases were eventually included. This meta-analysis explicitly indicated that PD treatment was associated with worse long-term prognosis (hazard ratio = 1.93; 95% confidence interval [CI], 1.39-2.69; p < 0.001; I = 0) and more complications (odds ratio [OR] = 2.90; 95% CI, 1.90-4.42; p < 0.001; I = 10%) than LR treatment. Nevertheless, for duodenal GISTs, PD was related to the following clinicopathological features: invasion of the second part of the duodenum (OR = 3.39; 95% CI, 1.69-6.79; p < 0.001; I = 50%), high-degree tumor mitosis (> 5/50 high-power fields; OR = 2.24; 95% CI, 1.42-3.52; p < 0.001; I = 0), and high-risk classification (OR = 3.17; 95% CI; 2.13-4.71; p < 0.001; I = 0).
CONCLUSIONS
Since PD is associated with worse long-term prognosis and more complications, its safety and efficacy should be ascertained. Our findings recommend the use of LR to obtain negative incision margins when conditions permit it.
Topics: Duodenal Neoplasms; Duodenum; Gastrointestinal Stromal Tumors; Humans; Margins of Excision; Middle Aged; Pancreaticoduodenectomy; Prognosis
PubMed: 31455328
DOI: 10.1186/s12893-019-0587-4 -
Human Reproduction Update 2016ICSI is currently the most commonly used assisted reproductive technology, accounting for 70-80% of the cycles performed. This extensive use, even excessive, is partly... (Review)
Review
BACKGROUND
ICSI is currently the most commonly used assisted reproductive technology, accounting for 70-80% of the cycles performed. This extensive use, even excessive, is partly due to the high level of standardization reached by the procedure. There are, however, some aspects that deserve attention and can still be ameliorated. The aim of this systematic review was to evaluate the results of available publications dealing with the management of specific situations during ICSI in order to support embryologists in trying to offer the best laboratory individualized treatment.
METHODS
This systematic review is based on material obtained by searching PUBMED between January 1996 and March 2015. We included peer-reviewed, English-language journal articles that have evaluated ICSI outcomes in the case of (i) immature oocytes, (ii) oocyte degeneration, (iii) timing of the various phases, (iv) polar body position during injection, (v) zona-free oocytes, (vi) fertilization deficiency, (vii) round-headed sperm, (viii) immotile sperm and (ix) semen samples with high DNA fragmentation.
RESULTS
More than 1770 articles were obtained, from which only 90 were specifically related to the issues developed for female gametes and 55 for the issues developed for male gametes. The studies selected for this review were organized in order to provide a guide to overcome roadblocks. According to these studies, the injection of rescue metaphase I oocytes should be discouraged due to poor clinical outcomes and a high aneuploidy rates; laser-assisted ICSI represents an efficient method to solve the high oocyte degeneration rate; the optimal ICSI timing and the best polar body position during the injection have not been clarified; injected zona-free oocytes, if handled carefully, can develop up to blastocyst stage and implant; efficient options can be offered to patients who suffered fertilization failure in previous conventional ICSI cycles. Most controversial and inconclusive are data on the best method to select a viable spermatozoa when only immotile spermatozoa are available for ICSI and, to date, there is no reliable approach to completely filter out spermatozoa with fragmented DNA from an ejaculate. However, most of the studies do not report essential clinical outcomes, such as live birth, miscarriage and fetal abnormality rate, which are essential to establish the safety of a procedure.
CONCLUSIONS
This review provides the current knowledge on some controversial technical aspects of the ICSI procedures in order to improve its efficacy in specific contexts. Notwithstanding that embryologists might benefit from the approaches presented herein in order to improve ICSI outcomes, this area of expertise still demands a greater number of well-designed studies, especially in order to solve open issues about the safety of these procedures.
Topics: Asthenozoospermia; DNA Fragmentation; Female; Fertilization; Humans; Male; Metaphase; Microinjections; Oocytes; Pregnancy; Sperm Injections, Intracytoplasmic; Spermatozoa
PubMed: 26586241
DOI: 10.1093/humupd/dmv050 -
Veterinary Pathology Mar 2024Increased proliferation is a driver of tumorigenesis, and quantification of mitotic activity is a standard task for prognostication. This systematic review is an...
Increased proliferation is a driver of tumorigenesis, and quantification of mitotic activity is a standard task for prognostication. This systematic review is an analysis of all available references on mitotic activity in feline tumors to provide an overview of the assessment methods and prognostic value. A systematic literature search in PubMed and Scopus and a nonsystematic search in Google Scholar were conducted. All articles on feline tumors that correlated mitotic activity with patient outcome were identified. Data analysis revealed that of the 42 eligible articles, mitotic count (MC, mitotic figures/tumor area) was evaluated in 39 studies, and mitotic index (MI, mitotic figures/tumor cells) in 3 studies. The risk of bias was considered high for most studies (26/42, 62%) based on small study populations, insufficient details of the MC/MI methods, and lack of statistical measures for diagnostic accuracy or effect on outcome. The MC/MI methods varied between studies. A significant association of MC with survival was determined in 20 of 28 (71%) studies (10 studies evaluated other outcome metrics or provided individual patient data), while 1 study found an inverse effect. Three tumor types had at least 4 studies, and a prognostic association with survival was found in 5 of 6 studies on mast cell tumors, 5 of 5 on mammary tumors, and 3 of 4 on soft-tissue sarcomas. MI was shown to correlate with survival for mammary tumors by 2 research groups; however, comparisons to MC were not conducted. Further studies with standardized mitotic activity methods and appropriate statistical analysis for discriminant ability of patient outcome are needed to infer the prognostic value of MC and MI.
PubMed: 38533803
DOI: 10.1177/03009858241239566 -
European Journal of Surgical Oncology :... Jul 2017The identification of small (<2 cm) gastrointestinal stromal tumors (GISTs) is increasingly recognized. The malignancy potential is not absent. However, data on risk is... (Review)
Review
INTRODUCTION
The identification of small (<2 cm) gastrointestinal stromal tumors (GISTs) is increasingly recognized. The malignancy potential is not absent. However, data on risk is scarce. The aim was to review the existing data on perceived risk of small GISTs in population-based studies.
METHODS
A combined review of small GISTs (<2 cm) in a population-based dataset compared with a systematic review of available population-based studies.
RESULTS
About one in every four (27%) patient has a small GIST, of which 79% were incidental in presentation, and all had a low-risk mitoses index (<5/hpf). The small GISTs had C-KIT mutations in exon 11 or 9 (66%), none had mutation in PDGFRA, and 33% were non-KIT/PDGFRA. The rate of small GISTs increased for each advancing age group. None of the small GISTs had a recurrence nor were there any GIST-specific deaths during follow-up. A "small GIST" rate at one-fourth of all GISTs reported was corroborated in other population-based studies from Norway, Iceland and Korea. Common to studies reporting mitosis index were an almost universal finding of very low-risk in small GISTs, with very few recurrences and an excellent long-term survival reported to 95-100% in several series.
DISCUSSION
One in every four GIST diagnosed is a small GIST (<2 cm). Small GISTs are increasingly found with advanced age and have an overall excellent prognosis. Defining true risk-features for proper surveillance and treatment strategy is needed in order to avoid over- and under-treatment.
Topics: Age Factors; Aged; Cell Transformation, Neoplastic; Gastrointestinal Neoplasms; Gastrointestinal Stromal Tumors; Humans; Middle Aged; Mitotic Index; Neoplasm Recurrence, Local; Norway; Proto-Oncogene Proteins c-kit; Receptor, Platelet-Derived Growth Factor alpha; Survival Rate; Tumor Burden
PubMed: 28222971
DOI: 10.1016/j.ejso.2017.01.240 -
Tumori Oct 2020Primary cervical leiomyosarcomas (CLMS) constitute 21% of all cervical sarcomas. Because of their rarity, to our knowledge, fewer than 40 cases have been reported. The... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Primary cervical leiomyosarcomas (CLMS) constitute 21% of all cervical sarcomas. Because of their rarity, to our knowledge, fewer than 40 cases have been reported. The aim of this study is to evaluate the clinical and surgical-pathological features, prognosis, treatment options, and survival of primary CLMS.
METHODS
A systematic review of the medical literature was conducted to evaluate articles about primary CLMS. The literature was searched between 1959 and May 2019. On final evaluation, there were 29 articles (one consisted of 8 cases; one consisted of 3 cases) and 42 cases with the addition of our 4 cases.
RESULTS
Age (⩾48 versus ⩽47 years) (hazard ratio.HR], 4.528; 95% confidence interval.CI], 1.550-13.227; =0.006) and mitoses count (<10/10 high-power field [HPF] versus ⩾10/10 HPF) (HR, 3.865; 95% CI, 1.046-14.278; =0.043) are independent prognostic factors for recurrence and age (HR, 5.318; 95% CI, 1.671-16.920; =0.005) and hysterectomy (performed versus not performed) (HR, 4.377; 95% CI, 1.341-14.283; =0.014) are independent prognostic factors for death because of disease on multivariate analysis.
CONCLUSIONS
Information on primary CLMS is sparse and obtained from rare case reports and case series. Hysterectomy must be the first choice of treatment in these patients according to our results on multivariate analysis. The type of hysterectomy does not have an effect on oncologic outcome. Radical hysterectomy is not obligatory and more data are needed to make more accurate conclusions.
Topics: Adult; Cervix Uteri; Chemotherapy, Adjuvant; Female; Humans; Hysterectomy; Leiomyosarcoma; Middle Aged; Neoplasm Recurrence, Local; Prognosis; Radiotherapy, Adjuvant; Uterine Cervical Neoplasms
PubMed: 32403994
DOI: 10.1177/0300891620919161 -
Frontiers in Oncology 2022Digital pathology with whole-slide imaging (WSI) has many potential clinical and non-clinical applications. In the past two decades, despite significant advances in WSI...
OBJECTIVE
Digital pathology with whole-slide imaging (WSI) has many potential clinical and non-clinical applications. In the past two decades, despite significant advances in WSI technology adoption remains slow for primary diagnosis. The aim of this study was to identify common pitfalls of WSI reported in validation studies and offer measures to overcome these challenges.
METHODS
A systematic search was conducted in the electronic databases Pubmed-MEDLINE and Embase. Inclusion criteria were all validation studies designed to evaluate the feasibility of WSI for diagnostic clinical use in pathology. Technical and diagnostic problems encountered with WSI in these studies were recorded.
RESULTS
A total of 45 studies were identified in which technical issues were reported in 15 (33%), diagnostic issues in 8 (18%), and 22 (49%) reported both. Key technical problems encompassed slide scan failure, prolonged time for pathologists to review cases, and a need for higher image resolution. Diagnostic challenges encountered were concerned with grading dysplasia, reliable assessment of mitoses, identification of microorganisms, and clearly defining the invasive front of tumors.
CONCLUSION
Despite technical advances with WSI technology, some critical concerns remain that need to be addressed to ensure trustworthy clinical diagnostic use. More focus on the quality of the pre-scanning phase and training of pathologists could help reduce the negative impact of WSI technical difficulties. WSI also seems to exacerbate specific diagnostic tasks that are already challenging among pathologists even when examining glass slides with conventional light microscopy.
PubMed: 35785212
DOI: 10.3389/fonc.2022.918580 -
Asian Journal of Andrology 2020Peripheral nerve damage, such as that found after surgery or trauma, is a substantial clinical challenge. Much research continues in attempts to improve outcomes after...
Peripheral nerve damage, such as that found after surgery or trauma, is a substantial clinical challenge. Much research continues in attempts to improve outcomes after peripheral nerve damage and to promote nerve repair after injury. In recent years, low-intensity pulsed ultrasound (LIPUS) has been studied as a potential method of stimulating peripheral nerve regeneration. In this review, the physiology of peripheral nerve regeneration is reviewed, and the experiments employing LIPUS to improve peripheral nerve regeneration are discussed. Application of LIPUS following nerve surgery may promote nerve regeneration and improve functional outcomes through a variety of proposed mechanisms. These include an increase of neurotrophic factors, Schwann cell (SC) activation, cellular signaling activations, and induction of mitosis. We searched PubMed for articles related to these topics in both in vitro and in vivo animal research models. We found numerous studies, suggesting that LIPUS following nerve surgery promotes nerve regeneration and improves functional outcomes. Based on these findings, LIPUS could be a novel and valuable treatment for nerve injury-induced erectile dysfunction.
Topics: Animals; Cell Proliferation; Cell Survival; Erectile Dysfunction; Humans; Male; Mitosis; Nerve Growth Factors; Nerve Regeneration; Penis; Peripheral Nerve Injuries; Pudendal Nerve; Schwann Cells; Signal Transduction; Ultrasonic Therapy; Ultrasonic Waves
PubMed: 31535626
DOI: 10.4103/aja.aja_95_19 -
Asian Pacific Journal of Cancer... 2012The vascular endothelial growth factor (VEGF) mediates vasculogenesis and angiogenesis through promoting endothelial cell growth, migration and mitosis, and has... (Review)
Review
BACKGROUND
The vascular endothelial growth factor (VEGF) mediates vasculogenesis and angiogenesis through promoting endothelial cell growth, migration and mitosis, and has involvement in cancer pathogenesis, progression and metastasis. However, the prognostic value of VEGF in patients with prostate cancer remains controversial.
OBJECTIVES
The aim of our study was to evaluate the prognostic value of VEGF in prostate cancer, and summarise the results of related research on VEGF.
METHODS
In accordance with an established search strategy, 11 studies with 1,529 patients were included in our meta-analysis. The correlation of VEGF-expression with overall survival and progression-free survival was evaluated by hazard ratio, either given or calculated.
RESULTS
The studies were categorized by introduction of the author, demographic data in each study, prostate cancer-relatived information, VEGF cut-off value, VEGF subtype, methods of hazard ratio (HR) estimation and its 95% confidence interval (CI). High VEGF-expression in prostate cancer is a poor prognostic factor with statistical significance for OS (HR=2.32, 95%CI: 1.40-3.24). However, high VEGF-expression showed no effect on poor PFS (HR=1.30, 95%CI: 0.88-1.72). Using Begg's, Egger's test and funnel plots, we confirmed lack of publication bias in our analysis.
CONCLUSION
VEGF might be regarded as a prognostic maker for prostate cancer, as supported by our meta-analysis. To achieve a more definitive conclusion enabling the clinical use of VEGF in prostate cancer, we need more high-quality interventional original studies following agreed research approaches or standards.
Topics: Biomarkers, Tumor; Clinical Trials as Topic; Humans; Male; Meta-Analysis as Topic; Prognosis; Prostatic Neoplasms; Vascular Endothelial Growth Factor A
PubMed: 23317235
DOI: 10.7314/apjcp.2012.13.11.5665 -
Journal Der Deutschen Dermatologischen... Sep 2011TNM classifications are the basis for diagnostic and therapeutic procedures in oncology. Histopathological reports have to enable a proper indexing of tumor specific...
Histopathological diagnostics of malignant melanoma in accordance with the recent AJCC classification 2009: Review of the literature and recommendations for general practice.
BACKGROUND
TNM classifications are the basis for diagnostic and therapeutic procedures in oncology. Histopathological reports have to enable a proper indexing of tumor specific findings into recent classifications.
METHODS
A systematic review of the literature was performed to identify reports dealing with the assessment of mitotic rate and the processing and evaluation of sentinel node biopsies in malignant melanoma. On the basis of this review an expert panel of dermatopathologists and general pathologists discussed and agreed recommendations for general practice.
RESULTS
Following recommendations were agreed with a broad consensus (93-100 % agreement): The determination of the mitotic rate in primary melanoma is performed on HE slides. The evaluation of an area of 1 mm(2) is sufficient. Only dermal mitoses are considered. The counted number of mitoses is provided as an integer value. The mitotic rate shall be determined in primary melanomas of ≤1.00 mm vertical tumor thickness according to the hot-spot method and provided as an integer value in relation to an area of 1 mm(2) . The determination of the mitotic rate in the case of thicker primary melanomas is desirable. In general, for the evaluation of each sentinel lymph node, 4 slides should be prepared. For diagnostic purposes, immunohistochemistry (preferably with antibodies against S100ß, Melan A and HMB-45) should be performed in addition to HE staining. The pathology report should provide information about micro-metastases and their longest extension (one-tenth of a millimeter).
CONCLUSIONS
These recommendations are suitable for standardizing the histopathological diagnosis of malignant melanoma and for providing a common basis for clinical decisions and scientific research.
Topics: Biomarkers, Tumor; Germany; Humans; Lymphatic Metastasis; Melanoma; Mitotic Index; Neoplasm Invasiveness; Neoplasm Micrometastasis; Neoplasm Staging; Sentinel Lymph Node Biopsy; Skin; Skin Neoplasms; United States
PubMed: 21651721
DOI: 10.1111/j.1610-0387.2011.07714.x