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Solitary fibrous tumor: a clinicopathological study of 110 cases and proposed risk assessment model.Modern Pathology : An Official Journal... Sep 2012Solitary fibrous tumor represents a spectrum of mesenchymal tumors, encompassing tumors previously termed hemangiopericytoma, which are classified as having intermediate...
Solitary fibrous tumor represents a spectrum of mesenchymal tumors, encompassing tumors previously termed hemangiopericytoma, which are classified as having intermediate biological potential (rarely metastasizing) in the 2002 World Health Organization classification scheme. Few series have reported on clinicopathological predictors with outcome data and formal statistical analysis in a large series of primary tumors as a single unified entity. Institutional pathology records were reviewed to identify primary solitary fibrous tumor cases, and histological sections and clinical records reviewed for canonical prognostic indicators, including patient age, tumor size, mitotic index, tumor cellularity, nuclear pleomorphism, and tumor necrosis. Patients (n=103) with resected primary solitary fibrous tumor were identified (excluding meningeal tumors). The most common sites of occurrence were abdomen and pleura; these tumors were larger than those occurring in the extremities, head and neck or trunk, but did not demonstrate significant outcome differences. Overall 5- and 10-year metastasis-free rates were 74 and 55%, respectively, while 5- and 10-year disease-specific survival rates were 89 and 73%. Patient age, tumor size, and mitotic index predicted both time to metastasis and disease-specific mortality, while necrosis predicted metastasis only. A risk stratification model based on age, size, and mitotic index clearly delineated patients at high risk for poor outcomes. While small tumors with low mitotic rates are highly unlikely to metastasize, large tumors ≥ 15 cm, which occur in patients ≥ 55 years, with mitotic figures ≥ 4/10 high-power fields require close follow-up and have a high risk of both metastasis and death.
Topics: Abdominal Neoplasms; Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Mitotic Index; Models, Biological; Pleural Neoplasms; Risk Assessment; Solitary Fibrous Tumor, Pleural; Survival Rate; Young Adult
PubMed: 22575866
DOI: 10.1038/modpathol.2012.83 -
Modern Pathology : An Official Journal... Sep 2021Mitoses are often assessed by pathologists to assist the diagnosis of cancer, and to grade malignancy, informing prognosis. Historically, this has been done by... (Review)
Review
Mitoses are often assessed by pathologists to assist the diagnosis of cancer, and to grade malignancy, informing prognosis. Historically, this has been done by expressing the number of mitoses per n high power fields (HPFs), ignoring the fact that microscope fields may differ substantially, even at the same high power (×400) magnification. Despite a requirement to define HPF size in scientific papers, many authors fail to address this issue adequately. The problem is compounded by the switch to digital pathology systems, where ×400 equivalent fields are rectangular and also vary in the area displayed. The potential for error is considerable, and at times this may affect patient care. This is easily solved by the use of standardized international (SI) units. We, therefore, recommend that features such as mitoses are always counted per mm, with an indication of the area to be counted and the method used (usually "hotspot" or "average") to obtain the results.
Topics: Humans; Microscopy; Mitotic Index; Neoplasms
PubMed: 34079071
DOI: 10.1038/s41379-021-00825-7 -
Annals of Oncology : Official Journal... Sep 2013In a retrospective study on node-negative breast cancer, a prognostic index consisting of a proliferation factor, S-phase fraction (SPF), progesterone receptor status... (Clinical Trial)
Clinical Trial
A prospective, multicenter validation study of a prognostic index composed of S-phase fraction, progesterone receptor status, and tumour size predicts survival in node-negative breast cancer patients: NNBC, the node-negative breast cancer trial.
BACKGROUND
In a retrospective study on node-negative breast cancer, a prognostic index consisting of a proliferation factor, S-phase fraction (SPF), progesterone receptor status (PR), and tumour size identified one-third of patients as high risk, with a sixfold increased risk of breast cancer death. This prospective multicenter cohort study was set up to validate the index.
PATIENTS AND METHODS
In 576 T1-2N0 patients <60 years, prospective analyses of PR and SPF were carried out. High risk was defined as ≥2 of the following: size >20 mm, PR-negativity, and high SPF (in the absence of SPF, Bloom-Richardson grade 3). Median follow-up was 17.8 years.
RESULTS
Thirty-one percent were high risk. In univariate analysis, the index was prognostic for breast cancer-specific survival after 5 years [hazard ratio (HR) = 4.7, 95% confidence interval (95% CI) 2.5-8.9], 10 years (HR = 2.2, 95% CI 1.5-3.3), and 15 years (HR = 1.7, 95% CI 1.2-2.5), and remained significant after adjustment for adjuvant medical treatment and age. In the 37% of patients with no risk factors, only one patient died of breast cancer the first 5 years.
CONCLUSIONS
This prospective study validates a prognostic index consisting of a proliferation factor, PR-status, and tumour size. The index may be helpful for prognostic considerations and for selection of patients in need of adjuvant therapy.
Topics: Biomarkers, Tumor; Breast Neoplasms; Cell Proliferation; Cohort Studies; Disease-Free Survival; Female; Humans; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Mitotic Index; Prospective Studies; Receptors, Progesterone; S Phase; Survival
PubMed: 23704202
DOI: 10.1093/annonc/mdt186 -
Journal of Comparative Pathology Nov 2021Gastrointestinal lymphomas are uncommon in dogs and little is known about their distinct subtypes or proliferation rate. The aim of this study was to stratify 33 canine...
Gastrointestinal lymphomas are uncommon in dogs and little is known about their distinct subtypes or proliferation rate. The aim of this study was to stratify 33 canine gastrointestinal lymphoma samples according to the latest World Health Organization classification and to determine the Ki67 proliferation index by manual counting, digital image analysis and visual estimation. The Ki67 index was then correlated with subtype, immunophenotype, mitotic index, grade and tumour location. The mitotic index correlated positively with the Ki67 index. A significantly higher number of Ki67-positive cells was found in enteropathy-associated T-cell lymphoma type I and in diffuse large B-cell lymphoma compared with enteropathy-associated T-cell lymphoma type II. There was also a significant difference in Ki67 immunolabelled cells between grade 1 and grade 2 lymphomas. Moderate agreement was found between the Ki67 index as obtained by manual counting and visual estimation, but there was strong agreement between manual counting and digital image analysis. The user-friendly digital imaging system used in this study could have potential for future determination of the Ki67 index in lymphoid neoplasms.
Topics: Animals; Cell Proliferation; Dog Diseases; Dogs; Gastrointestinal Neoplasms; Ki-67 Antigen; Lymphoma, Large B-Cell, Diffuse; Mitotic Index
PubMed: 34886989
DOI: 10.1016/j.jcpa.2021.10.003 -
Anticancer Research 2004The study was designed in order to evaluate the degree of correlation of mitotic index (MI), Ki67 (MIB1) score and S-phase fraction (SPF) as markers of cell...
Analysis of correlation between mitotic index, MIB1 score and S-phase fraction as proliferation markers in invasive breast carcinoma. Methodological aspects and prognostic value in a series of 257 cases.
BACKGROUND
The study was designed in order to evaluate the degree of correlation of mitotic index (MI), Ki67 (MIB1) score and S-phase fraction (SPF) as markers of cell proliferation and prognosis in breast cancer.
MATERIALS AND METHODS
The series analysed corresponded to 257 consecutive invasive breast carcinoma, treated at the Institut Curie, France, in 1995. Nottingham histological grade and MIB1 semiquantitative and quantitative score were assessed on histological sections, whereas SPF was calculated using flow cytometry analysis of fine-needle aspiration products. Proliferation indices were compared to pathological data and to overall survival (OS) and disease-free survival (DFS) (minimum follow-up: 72 months).
RESULTS
The median values for the proliferation markers were 9/10 HPF for MI, 32.4% for MIB1 and 3.7% for SPF. A high rate of correlation (r=0.96; p<0.001) was observed between semi-quantitative and quantitative MIBI evaluation. A positive correlation was found between the three markers (r ranging from 0.54 to 0.61;p<0.001). Univariate analysis of markers associated to disease outcome showed that MIB1, axillary node status (N) and progesterone receptor (PR) status were significantly associated with OS and that MIB1 and SPF were associated with DFS, together with node and hormone receptor status. In multivariate analysis, when proliferation markers were adjusted on the N and PR status, only MIB1 retained a prognostic value for OS (RR= 1.83) [1.00;3.35] and SPF for DFS (RR= 1.58) [1.02-2.44] (p=0.04).
CONCLUSION
A good level of correlation was observed between the values of the three markers of tumour cell proliferation analysed. In this series of invasive breast cancers, MIB1 immunostaining was found to be a prognostic marker of both OS and DFS. The median (32.4%) was a valuable cut-off value for prognostic assessment. Semi-quantitative and quantitative evaluations provided very similar values. MIB1 can thus be considered as a reliable prognostic maker, usable in small size tissue specimens which are inappropriate for MI or SPF analysis. The impact of MIB1 compared to that of the other proliferative markers will be further assessed in a subgroup of T1N0M0 for which the prognostic assessment is of major interest.
Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Cell Division; Disease-Free Survival; Humans; Ki-67 Antigen; Middle Aged; Mitotic Index; Neoplasm Staging; Prognosis; S Phase
PubMed: 15510624
DOI: No ID Found -
Journal of Medical Case Reports Jan 2016Atypical uterine leiomyomas show benign behavior. However, the distinction between leiomyomas and leiomyosarcomas may at times be problematic. We report a rare case of... (Review)
Review
BACKGROUND
Atypical uterine leiomyomas show benign behavior. However, the distinction between leiomyomas and leiomyosarcomas may at times be problematic. We report a rare case of atypical uterine leiomyoma. We try to investigate potential immunohistochemical parameters that could be essential to distinguish cases of malignant smooth muscle tumors and those of uncertain or borderline histology.
CASE PRESENTATION
A 56-year-old white ethnic Albanian woman from Kosovo presented with uterine bleeding because of uterine multiple leiomyomas. A hysterectomy with unilateral adnexectomy was performed. Her hysterectomy specimen contained multiple leiomyomas in submucosal, intramural and subserosal locations. The leiomyomas were well demarcated, firm and white with a whorled cut surface and one had foci of hemorrhage. Histology of most of the leiomyomas showed a whorled (fascicular) pattern of smooth muscle bundles separated by well-vascularized connective tissue. Smooth muscle cells were elongated with eosinophilic or occasional fibrillar cytoplasm and distinct cell membranes. Some of them developed areas of degeneration including hyaline change, with less than five mitotic figures per ten high power fields in most mitotically active areas, and no significant atypia. One leiomyoma was characterized by moderately to severely pleomorphic atypical tumor cells with low mitotic counts and no coagulative tumor cell necrosis. Immunohistochemistry showed strong immunoreactivity for vimentin, smooth muscle actin and desmin, while cyclin-dependent kinase inhibitor 2A (p16), and B-cell lymphoma 2 (bcl-2) showed focal immunoreactivity, estrogen and progesterone were positive, Ki-67 expressed a low proliferation index, whereas p21 and tumor suppressor gene p53 were negative.
CONCLUSIONS
The combination of evaluation of conventional morphologic criteria with cyclin-dependent kinase inhibitor 2A (p16), p21, progesterone, B-cell lymphoma 2, tumor suppressor gene p53 and Ki-67 expression may be of great value in the assessment of uterine smooth muscle tumors of uncertain or borderline histology.
Topics: Diagnosis, Differential; Female; Humans; Leiomyomatosis; Leiomyosarcoma; Middle Aged; Mitotic Index; Uterine Neoplasms
PubMed: 26801982
DOI: 10.1186/s13256-016-0800-3 -
Archives of Pathology & Laboratory... Jun 2015Neuroendocrine tumors (NETs) of the gastrointestinal tract have been recognized for more than a century. Despite histologic similarities between different sites in the... (Review)
Review
CONTEXT
Neuroendocrine tumors (NETs) of the gastrointestinal tract have been recognized for more than a century. Despite histologic similarities between different sites in the tract, behavior varies between areas. All of these tumors have malignant potential, but determination of exact risk is difficult.
OBJECTIVES
To review the diagnosis of luminal gastrointestinal NETs, including a discussion of grading. Grading by mitotic index/activity, in conjunction with tumor size/stage, has been found to be the strongest predictor of behavior.
DATA SOURCES
Literature review of luminal gastrointestinal NETs was performed and the results summarized.
CONCLUSIONS
Our understanding of these lesions is incomplete and continues to evolve.
Topics: Biomarkers, Tumor; Gastrointestinal Neoplasms; Gastrointestinal Tract; Humans; Hyperplasia; Mitotic Index; Neoplasm Grading; Neoplasm Staging; Neuroendocrine Cells; Neuroendocrine Tumors
PubMed: 26030244
DOI: 10.5858/arpa.2014-0130-RA -
Breast Cancer Research : BCR 2006Various methods are available for the measurement of proliferation rates in tumours, including mitotic counts, estimation of the fraction of cells in S-phase of the cell... (Review)
Review
Various methods are available for the measurement of proliferation rates in tumours, including mitotic counts, estimation of the fraction of cells in S-phase of the cell cycle and immunohistochemistry of proliferation-associated antigens. The evidence, advantages and disadvantages for each of these methods along with other novel approaches is reviewed in relation to breast cancer. The potential clinical applications of proliferative indices are discussed, including their use as prognostic indicators and predictors of response to systemic therapy.
Topics: Antigens, Nuclear; Breast Neoplasms; Cell Proliferation; Cyclin-Dependent Kinases; Cyclins; DNA Topoisomerases, Type II; Deuterium Oxide; Disease Progression; Female; Humans; Ki-67 Antigen; Mitotic Index; Nuclear Proteins; Positron-Emission Tomography; Proliferating Cell Nuclear Antigen; S Phase; Thymidine Kinase; Tissue Array Analysis
PubMed: 17164010
DOI: 10.1186/bcr1618 -
Neuro-oncology Aug 2023
Topics: Humans; Prognosis; Isocitrate Dehydrogenase; Mitotic Index; Homozygote; Consensus; Sequence Deletion; Astrocytoma; Brain Neoplasms; Cyclin-Dependent Kinase Inhibitor p16
PubMed: 37097042
DOI: 10.1093/neuonc/noad063 -
Breast (Edinburgh, Scotland) Aug 2008We have performed a systematic review and meta-analysis of proliferation markers (Ki-67, mitotic index (MI), proliferating cell nuclear antigen (PCNA) and thymidine or... (Meta-Analysis)
Meta-Analysis Review
We have performed a systematic review and meta-analysis of proliferation markers (Ki-67, mitotic index (MI), proliferating cell nuclear antigen (PCNA) and thymidine or bromodeoxyuridine labelling index (LI)) with respect to survival in early breast cancer. Eighty-five studies involving 32,825 patients were analysed. Ki-67 (43 studies, 15,790 patients), MI (20 studies, 7021 patients), and LI (11 studies, 7337 patients) were associated with significantly shorter overall and disease free survival, using results from univariate and multivariate analyses from the individual studies. PCNA (11 studies, 2677 patients) was associated with shorter overall survival by multivariate analysis only, because of lack of data. There was some evidence for publication bias, but all markers remained significant after allowing for this. Ki-67, MI, PCNA and LI are associated with worse survival outcomes in early breast cancer. However, whether these proliferation markers provide additional prognostic information to commonly used prognostic indices remains unclear.
Topics: Breast Neoplasms; Disease-Free Survival; Female; Humans; Ki-67 Antigen; Mitotic Index; Predictive Value of Tests; Proliferating Cell Nuclear Antigen; Survival Rate
PubMed: 18455396
DOI: 10.1016/j.breast.2008.02.002