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Diagnostic Pathology May 2020Most sporadic gastrointestinal stromal tumors (GISTs) occur as solitary tumors, while multiple sporadic GISTs are extremely rare and often misdiagnosed as metastatic... (Review)
Review
Clinicopathologic characteristics, diagnostic clues, and prognoses of patients with multiple sporadic gastrointestinal stromal tumors: a case series and review of the literature.
BACKGROUND
Most sporadic gastrointestinal stromal tumors (GISTs) occur as solitary tumors, while multiple sporadic GISTs are extremely rare and often misdiagnosed as metastatic GISTs, leading to inappropriate treatment. This study aimed to investigate the clinicopathological characteristics, diagnostic clues, and prognoses of multiple sporadic GISTs.
METHODS
Twenty-seven patients with multiple sporadic GISTs and 11 patients with metastatic GISTs mimicking sporadic GISTs were analyzed. The clinicopathological characteristics, genetic mutation types, and prognoses were summarized. In addition, 1066 cases of primary GISTs with a single lesion diagnosed at the same hospital were included as controls.
RESULTS
Compared with 1066 cases of primary GIST with a single lesion, multiple sporadic GISTs occurred at an older age, were more common in women than in men, and were located mainly in the stomach. They were generally small in size, had a low mitotic index and were more often rated as very low risk/low risk. Mutation analysis of all available lesions revealed different KIT/PDGFRA mutation patterns among tumors from the same patients. No patient relapsed during the follow-up period. Among 11 patients with metastatic GISTs that mimicked multiple sporadic GISTs, multiple lesions from the same patient always had concordant pathological and mutational characteristics; namely, they carried an identical KIT/PDGFRA mutation, and the mitotic index was usually high.
CONCLUSIONS
The prognoses of patients with multiple sporadic GISTs were not worse than those of patients with a single lesion of the same risk under the same treatment. When it was difficult to distinguish multiple sporadic GISTs from metastatic GISTs, multiple lesions in the same patient carried different KIT/PDGFRA mutation patterns, which supported tumor multiplicity, while the concordant hypermitotic phase in multiple lesions of GISTs suggested that the tumor was metastatic.
Topics: Aged; Female; Gastrointestinal Stromal Tumors; Humans; Male; Middle Aged; Mutation; Prognosis; Proto-Oncogene Proteins c-kit; Receptor, Platelet-Derived Growth Factor alpha; Retrospective Studies
PubMed: 32408889
DOI: 10.1186/s13000-020-00939-7 -
Journal of Clinical Medicine Feb 2021Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors and have some malignant potential. Mitotic count is important for predicting the malignant potential of...
BACKGROUND
Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors and have some malignant potential. Mitotic count is important for predicting the malignant potential of GISTs. Proper treatment of GISTs requires accurate pathological diagnosis. In general, endoscopic ultrasound-guided fine-needle aspiration and deep biopsy are used for pathological diagnosis of GIST before making decisions about surgery. This study sought to evaluate the pathological uniformity of gastric GISTs for mitotic index of the center and periphery of the GIST.
METHODS
We retrospectively reviewed the data of 37 gastric GIST patients who underwent wedge resection at Hanyang University Hospital. We used Armed Forces Institute of Pathology criteria to classify gastric GISTs. To determine the pathological uniformity of gastric GISTs, we compared GIST risk stratification between the center and periphery of GISTs.
RESULTS
The mean size of GISTs was 3.56 ± 2.10 cm. Three lesions were located in the antrum, 11 in the fundus, 9 in the cardia, and 14 in the body. The mean age of patients was 58.65 ± 9.44 years; 18 patients were male and 19 were female. Thirty-five patients (94.6%) showed the same level of risk stratification between the center and periphery of gastric GISTs, while two patients (5.4%) presented different levels of risk between the two sites. No significant difference in mitotic count was observed between the two sites (kappa value = 0.863; = 0.001).
CONCLUSIONS
Mitotic index category (either more than five mitoses per high-power field or five or fewer mitoses per high-power field) of GISTs showed good concurrence between the center and periphery.
PubMed: 33578901
DOI: 10.3390/jcm10040687 -
The British Journal of Surgery Jul 2015This study evaluated the clinical characteristics, surgical procedures and prognosis of duodenal gastrointestinal stromal tumours (GISTs).
BACKGROUND
This study evaluated the clinical characteristics, surgical procedures and prognosis of duodenal gastrointestinal stromal tumours (GISTs).
METHODS
Patients with a diagnosis of primary duodenal GIST treated between January 2000 and December 2012 were analysed. Patients with gastric and small intestinal GISTs were chosen as control groups according to the following parameters: age, tumour size, mitotic index and adjuvant imatinib therapy. Operative procedures for patients with duodenal GIST included pancreaticoduodenectomy or limited resection. Disease-free survival (DFS) was calculated using Kaplan-Meier analysis.
RESULTS
Some 71 patients with duodenal, 71 with gastric and 70 with small intestinal GISTs were included in the study. DFS of patients with duodenal GIST was shorter than that of patients with gastric GIST (3-year DFS 84 versus 94 per cent; hazard ratio (HR) 3.67, 95 per cent c.i. 1.21 to 11.16; P = 0.014), but was similar to that of patients with small intestinal GIST (3-year DFS 84 versus 81 per cent; HR 0.75, 0.37 to 1.51; P = 0.491). Patients who underwent pancreaticoduodenectomy were older, and had larger tumours and a higher mitotic index than patients who had limited resection. The 3-year DFS was 93 per cent among patients who had limited resection compared with 64 per cent for those who underwent PD (HR 0.18, 0.06 to 0.59; P = 0.001).
CONCLUSION
The prognosis of duodenal GISTs is similar to that of small intestinal GISTs.
Topics: Adult; Aged; Aged, 80 and over; Disease-Free Survival; Duodenal Neoplasms; Female; Gastrointestinal Stromal Tumors; Humans; Intestinal Neoplasms; Intestine, Small; Male; Middle Aged; Pancreaticoduodenectomy; Prognosis; Stomach Neoplasms; Survival Analysis
PubMed: 25980461
DOI: 10.1002/bjs.9831 -
Interactive Cardiovascular and Thoracic... May 2021Atypical carcinoids are neuroendocrine neoplasms of intermediate degree and low frequency. The aim of this study is to analyse their clinical characteristics and the...
OBJECTIVES
Atypical carcinoids are neuroendocrine neoplasms of intermediate degree and low frequency. The aim of this study is to analyse their clinical characteristics and the importance of different histopathological factors in their prognosis.
METHODS
Multicentre cooperative group EMETNE prospectively reviewed 153 patients operated on between 1998 and 2016 with diagnosis of atypical carcinoids. Clinical variables and histopathological features were assessed.
RESULTS
Mean age was 54.36 years, similar for both genders. Concerning pathological study, mean tumour size was 31.7 mm. Rosettes were presented in 17% of the cases and tumoural necrosis in 23.3%. The cell proliferation factor Ki-67 index was 10.7%. The 2- and 5-year overall survival rates were 95.8% and 88.9%, respectively. In the univariate study, statistically significant differences in survival were found for each of the categories of T, N and M factors. Mitotic index and quantification of expression of Ki-67 showed influence in overall survival, although without statistical significance. In the multivariate analysis, factors N, M and mitotic index behaved as independent prognostic factors related to survival. Median disease-free interval in the series was 163.35 months. In cases with loco-regional recurrence, 53% had positive hiliar or mediastinal nodal involvement at the time of the surgery. In the univariate analysis, we observed statistically significant differences in disease-free interval in patients with nodal involvement (P = 0.024) and non-anatomical resections (P = 0.04). Histological characteristics showed no statistically significant differences in disease-free interval.
CONCLUSIONS
Lymph node involvement, the development of distant metastasis and mitotic index, more than Ki-67 determination, were shown as independent prognostic factors related to survival of these patients.
Topics: Carcinoid Tumor; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Prognosis; Retrospective Studies
PubMed: 33580683
DOI: 10.1093/icvts/ivab026 -
Biochimica Et Biophysica Acta May 2015Cancer cells with defective DNA decatenation checkpoint can be selectively targeted by the catalytic inhibitors of DNA topoisomerase IIα (topo IIα) enzyme. Upon...
Cancer cells with defective DNA decatenation checkpoint can be selectively targeted by the catalytic inhibitors of DNA topoisomerase IIα (topo IIα) enzyme. Upon treatment with catalytic topo IIα inhibitors, cells with defective decatenation checkpoint fail to arrest their cell cycle in G2 phase and enter into M phase with catenated and under-condensed chromosomes resulting into impaired mitosis and eventually cell death. In the present work we analyzed decatenation checkpoint in five different colon cancer cell lines (HCT116, HT-29, Caco2, COLO 205 and SW480) and in one non-cancerous cell line (HEK293T). Four out of the five colon cancer cell lines i.e. HCT116, HT-29, Caco2, and COLO 205 were found to be compromised for the decatenation checkpoint function at different extents, whereas SW480 and HEK293T cell lines were found to be proficient for the checkpoint function. Upon treatment with ICRF193, decatenation checkpoint defective cell lines failed to arrest the cell cycle in G2 phase and entered into M phase without proper chromosomal decatenation, resulting into the formation of tangled mass of catenated and under-condensed chromosomes. Such cells underwent mitotic catastrophe and rapid apoptosis like cell death and showed higher sensitivity for ICRF193. Our study suggests that catalytic inhibitors of topoisomerase IIα are promising therapeutic agents for the treatment of colon cancers with defective DNA decatenation checkpoint.
Topics: Biocatalysis; Cell Cycle Checkpoints; Cell Death; Cell Line, Tumor; Cell Survival; Chromosomes, Human; Colonic Neoplasms; Diketopiperazines; Etoposide; G2 Phase; HEK293 Cells; Humans; Mitosis; Mitotic Index; Piperazines; Topoisomerase II Inhibitors; Tumor Stem Cell Assay
PubMed: 25746763
DOI: 10.1016/j.bbamcr.2015.02.021 -
Frontiers in Surgery 2024Solitary fibrous tumor (SFT) is a rare soft tissue tumor found at any site of the body. The treatment of choice is surgical resection, though 10%-30% of patients... (Review)
Review
INTRODUCTION
Solitary fibrous tumor (SFT) is a rare soft tissue tumor found at any site of the body. The treatment of choice is surgical resection, though 10%-30% of patients experience recurrent disease. Multiple risk factors and risk stratification systems have been investigated to predict which patients are at risk of recurrence. The main goal of this systematic review is to create an up-to-date systematic overview of risk factors and risk stratification systems predicting recurrence for patients with surgically resected SFT within torso and extremities.
METHOD
We prepared the review following the updated Prisma guidelines for systematic reviews (PRISMA-P). Pubmed, Embase, Cochrane Library, WHO international trial registry platform and ClinicalTrials.gov were systematically searched up to December 2022. All English studies describing risk factors for recurrence after resected SFT were included. We excluded SFT in the central nervous system and the oto-rhino-laryngology region.
RESULTS
Eighty-one retrospective studies were identified. Different risk factors including age, symptoms, sex, resection margins, anatomic location, mitotic index, pleomorphism, hypercellularity, necrosis, size, dedifferentiation, CD-34 expression, Ki67 index and -expression, APAF1-inactivation, TERT promoter mutation and fusion variants were investigated in a narrative manner. We found that high mitotic index, Ki67 index and presence of necrosis increased the risk of recurrence after surgically resected SFT, whereas other factors had more varying prognostic value. We also summarized the currently available different risk stratification systems, and found eight different systems with a varying degree of ability to stratify patients into low, intermediate or high recurrence risk.
CONCLUSION
Mitotic index, necrosis and Ki67 index are the most solid risk factors for recurrence. TERT promoter mutation seems a promising component in future risk stratification models. The Demicco risk stratification system is the most validated and widely used, however the G-score model may appear to be superior due to longer follow-up time.
SYSTEMATIC REVIEW REGISTRATION
CRD42023421358.
PubMed: 38357190
DOI: 10.3389/fsurg.2024.1332421 -
Asian Pacific Journal of Cancer... Mar 2022Breast cancer is one of the most frequently diagnosed malignancy among women. Turmeric is isolated from Curcuma longa. Curcumin is main curcuminoid of the turmeric which...
OBJECTIVE
Breast cancer is one of the most frequently diagnosed malignancy among women. Turmeric is isolated from Curcuma longa. Curcumin is main curcuminoid of the turmeric which is a member of Zingiberaceae. In this current study antiproliferative effects of curcumin were investigated in luminal A breast cancer cell line MCF-7 and triple negative breast cancer cell line MDA-MB-231.
METHODS
For this purpose cell viability, cell index values by xCELLigence Real-Time Cell Analysis DP instrument, mitotic index and apoptotic index analysis were used.
RESULTS
Cell viability and cell index values showed that 75 µM concentration of curcumin was IC50 concentration. When IC50 concentration was applied to both cell lines, a significant decrease was observed in the mitotic index values, while a significant increase was observed in the apoptotic index values (p<0.05).
CONCLUSION
Curcumin, which has antiproliferative effects on breast cancer cells, is thought to be effective in cancer treatment.
Topics: Cell Survival; Curcumin; Female; Humans; Mitotic Index; Triple Negative Breast Neoplasms
PubMed: 35345363
DOI: 10.31557/APJCP.2022.23.3.911 -
Histopathology Feb 2023Mitotic count in breast cancer is an important prognostic marker. Unfortunately, substantial inter- and intraobserver variation exists when pathologists manually count...
Improving mitotic cell counting accuracy and efficiency using phosphohistone-H3 (PHH3) antibody counterstained with haematoxylin and eosin as part of breast cancer grading.
BACKGROUND
Mitotic count in breast cancer is an important prognostic marker. Unfortunately, substantial inter- and intraobserver variation exists when pathologists manually count mitotic figures. To alleviate this problem, we developed a new technique incorporating both haematoxylin and eosin (H&E) and phosphorylated histone H3 (PHH3), a marker highly specific to mitotic figures, and compared it to visual scoring of mitotic figures using H&E only.
METHODS
Two full-face sections from 97 cases were cut, one stained with H&E only, and the other was stained with PHH3 and counterstained with H&E (PHH3-H&E). Counting mitoses using PHH3-H&E was compared to traditional mitoses scoring using H&E in terms of reproducibility, scoring time, and the ability to detect mitosis hotspots. We assessed the agreement between manual and image analysis-assisted scoring of mitotic figures using H&E and PHH3-H&E-stained cells. The diagnostic performance of PHH3 in detecting mitotic figures in terms of sensitivity and specificity was measured. Finally, PHH3 replaced the mitosis score in a multivariate analysis to assess its significance.
RESULTS
Pathologists detected significantly higher mitotic figures using the PHH3-H&E (median ± SD, 20 ± 33) compared with H&E alone (median ± SD, 16 ± 25), P < 0.001. The concordance between pathologists in identifying mitotic figures was highest when using the dual PHH3-H&E technique; in addition, it highlighted mitotic figures at low power, allowing better agreement on choosing the hotspot area (k = 0.842) in comparison with standard H&E (k = 0.625). A better agreement between image analysis-assisted software and the human eye was observed for PHH3-stained mitotic figures. When the mitosis score was replaced with PHH3 in a Cox regression model with other grade components, PHH3 was an independent predictor of survival (hazard ratio [HR] 5.66, 95% confidence interval [CI] 1.92-16.69; P = 0.002), and even showed a more significant association with breast cancer-specific survival (BCSS) than mitosis (HR 3.63, 95% CI 1.49-8.86; P = 0.005) and Ki67 (P = 0.27).
CONCLUSION
Using PHH3-H&E-stained slides can reliably be used in routine scoring of mitotic figures and integrating both techniques will compensate for each other's limitations and improve diagnostic accuracy, quality, and precision.
Topics: Humans; Female; Eosine Yellowish-(YS); Mitotic Index; Breast Neoplasms; Hematoxylin; Reproducibility of Results; Biomarkers, Tumor; Immunohistochemistry; Mitosis; Antibodies; Phosphorylation
PubMed: 36349500
DOI: 10.1111/his.14837 -
The American Journal of Surgical... Jul 2022Acinic cell carcinoma (AciCC) is traditionally considered as a low-grade salivary gland carcinoma. However, a subset demonstrates high-grade features with a higher...
Acinic cell carcinoma (AciCC) is traditionally considered as a low-grade salivary gland carcinoma. However, a subset demonstrates high-grade features with a higher mortality rate and distant metastasis. In this large retrospective study of 117 cases, we aimed to establish a histologic grading scheme for AciCC. Adverse independent prognostic factors identified on the multivariate analysis included older age, tumor necrosis, nuclear anaplasia, lymphovascular invasion, absence of tumor-associated lymphoid stroma, and high American Joint Committee on Cancer (AJCC) pT and pN stages. A 3-tiered grading scheme using 4 pathologic parameters (mitotic index, necrosis, tumor border, and fibrosis at the frankly invasive front) was subsequently applied. Compared with low/intermediate-grade, high-grade AciCC defined as a mitotic index ≥5/10 HPFs and/or necrosis was an independently adverse prognostic factor. The 5-year overall survival was 50% in high-grade AciCCs, and 100% in low-grade or intermediate-grade AciCCs. Compared with low-grade or intermediate-grade AciCC, high-grade tumors were associated with older age, larger tumor size, focal rather than diffuse zymogen granules, solid architecture, infiltrative tumor border, fibrosis at the frankly invasive front, lymphovascular invasion, perineural invasion, positive margin, high pT, and pN stages. NR4A3 was a highly sensitive and specific immunohistochemical stain for diagnosing AciCC with a sensitivity and specificity of 96% and 93%, respectively. In conclusion, although we proposed a 2-tiered grading system for AciCC with high-grade tumors defined by a mitotic count ≥5/10 HPFs and/or necrosis, more studies are needed to assess the prognostic value of intermediate grade. NR4A3 immunohistochemical stain is a useful diagnostic marker for AciCC.
Topics: Carcinoma; Carcinoma, Acinar Cell; DNA-Binding Proteins; Fibrosis; Humans; Immunohistochemistry; Necrosis; Receptors, Steroid; Receptors, Thyroid Hormone; Retrospective Studies
PubMed: 35034042
DOI: 10.1097/PAS.0000000000001867 -
PloS One 2021In this research, eight local mung bean (Vigna radiata) varieties were analyzed for their performance against two levels of CdCl2 solution (0.3 and 0.5 mM) alone and...
In this research, eight local mung bean (Vigna radiata) varieties were analyzed for their performance against two levels of CdCl2 solution (0.3 and 0.5 mM) alone and priming with gibberellic acid (GA3) (100 μM), salicylic acid (SA) (50 μM) and proline (5 mM) solution prior to Cd exposure. Mung bean seedlings were analyzed for disturbance in cytological, morphological, biochemical and enzymatic parameters under cadmium stress. For cytological studies, 48 h grown mung bean seedlings root tips were used to prepare slides and studied for percent mitotic index (MI%) and to calculate percent C-mitosis, laggard, sticky and fragmented chromosomes, pictures were captured by a Nikon camera (DS-Fi 1 Japan) attached with a microscope. One-week grown mung seedlings were studied for growth traits, malondialdehyde (MDA), protein, proline and antioxidant enzymes. ANOVA and DMR test of this research revealed that all the tested mung bean varieties and treatments were significantly different regarding mitotic index and number of chromosomal aberrations. Both the Cd treatments exhibited increased total chromosomal aberrations with different types and a maximum decrease in MI%. In pretreated samples, GA3, SA and proline serve as mitigating agents that reduce mutagenic effects of Cd in mung bean by increasing MI% and decreasing chromosomal aberrations as compared to non-pretreated samples. Both the Cd treatments showed a decrease in all growth traits. Total proteins were also found to be significantly reduced in a dose-dependent manner in all genotypes. Cd treatment increased the activities of all antioxidant enzymes tested. Cd caused oxidative damage as indicated by elevated levels of MDA content in treated samples in comparison to control. Proline content levels were also high in Cd treated seedlings indicating stress. Results demonstrated that pretreatment with phytohormones and proline before Cd were found to improve all morphological parameters, by altering antioxidant enzymes activities along with a decrease in MDA and proline contents as well. It was further noticed that the performance of GA3 was better at 0.3 mM Cd treatment while SA was found to be a good mitigating agent at 0.5 mM Cd stress in all tested mung bean varieties. This research concluded less deleterious effects of Cd on AZRI-2006 while more sensitivity to NM-51 towards Cd. Priming with phytohormones and proline is a user-friendly, economical, and simple mitigation strategy to reduce Cd toxicity in plants and get better yield from contaminated lands.
Topics: Acclimatization; Cadmium Chloride; DNA, Plant; Malondialdehyde; Mitotic Index; Oxidative Stress; Plant Growth Regulators; Plant Roots; Proline; Salicylic Acid; Seedlings; Vigna
PubMed: 34587203
DOI: 10.1371/journal.pone.0257924