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Surgery Apr 2019Pancreatic neuroendocrine neoplasms are a heterogenous group of rare tumors whose natural history remains poorly defined. Accurate prognostication of pancreatic...
BACKGROUND
Pancreatic neuroendocrine neoplasms are a heterogenous group of rare tumors whose natural history remains poorly defined. Accurate prognostication of pancreatic neuroendocrine neoplasms is essential for guiding clinical decisions. This paper aims to summarize all the commonly utilized and recently proposed prognostication systems for pancreatic neuroendocrine neoplasms published in the literature to date.
METHODS
A systematic review of Pubmed, Scopus, and Embase databases, of the period from January 1, 2000-November 29, 2016, was conducted to identify all published articles reporting on prognostication systems of pancreatic neuroendocrine neoplasms.
RESULTS
A total of 23 articles were included in our review, and a total of 25 classification systems were identified. There were 2 modifications of the World Health Organization 2004 criteria, 4 modifications of the World Health Organization 2010 criteria, 2 modifications of the American Joint Committee on Cancer 2010 staging system, 3 modifications of the European Neuroendocrine Tumor Society 2006 tumor, node, metastasis staging system, 7 novel categorial classification systems, and 2 novel proposed continuous classifications. The most commonly included variables included age, size of tumor, presence of distant and lymph node metastases, Ki-67 index, and mitotic count.
CONCLUSION
Numerous prognostication systems have been proposed for pancreatic neuroendocrine neoplasms, of which the most commonly used systems presently include the World Health Organization 2010 criteria and the two tumor, node, metastasis staging systems by the European Neuroendocrine Tumor Society and the American Joint Commission on Cancer. However, prognostication systems for pancreatic neuroendocrine neoplasms continue to evolve with time as more prognostication factors are identified. More validation and comparative studies are needed to identify the most effective prognostication system.
Topics: Humans; Ki-67 Antigen; Neoplasm Staging; Neuroendocrine Tumors; Pancreatic Neoplasms; Prognosis
PubMed: 30558808
DOI: 10.1016/j.surg.2018.10.031 -
Veterinary Pathology Mar 2024One of the most relevant prognostic indices for tumors is cellular proliferation, which is most commonly measured by the mitotic activity in routine tumor sections. The...
One of the most relevant prognostic indices for tumors is cellular proliferation, which is most commonly measured by the mitotic activity in routine tumor sections. The goal of this systematic review was to analyze the methods and prognostic relevance of histologically measuring mitotic activity that have been reported for canine tumors in the literature. A total of 137 articles that correlated the mitotic activity in canine tumors with patient outcome were identified through a systematic (PubMed and Scopus) and nonsystematic (Google Scholar) literature search and eligibility screening process. Mitotic activity methods encompassed the mitotic count (MC, number of mitotic figures per tumor area) in 126 studies, presumably the MC (method not specified) in 6 studies, and the mitotic index (MI, number of mitotic figures per number of tumor cells) in 5 studies. A particularly high risk of bias was identified based on the available details of the MC methods and statistical analyses, which often did not quantify the prognostic discriminative ability of the MC and only reported values. A significant association of the MC with survival was found in 72 of 109 (66%) studies. However, survival was evaluated by at least 3 studies in only 7 tumor types/groups, of which a prognostic relevance is apparent for mast cell tumors of the skin, cutaneous melanoma, and soft tissue tumor of the skin and subcutis. None of the studies using the MI found a prognostic relevance. This review highlights the need for more studies with standardized methods and appropriate analysis of the discriminative ability to prove the prognostic value of the MC and MI in various tumor types. Future studies are needed to evaluate the influence of the performance of individual pathologists on the appropriateness of prognostic thresholds and investigate methods to improve interobserver reproducibility.
PubMed: 38533804
DOI: 10.1177/03009858241239565 -
Translational Cancer Research Aug 2023Neuroendocrine neoplasm (NEN) is a group of rare tumors. Among which, gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) is the most common group. The World Health...
BACKGROUND
Neuroendocrine neoplasm (NEN) is a group of rare tumors. Among which, gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) is the most common group. The World Health Organization (WHO) classified these tumors into three different grades (G1, G2, and G3) based on Ki-67 and mitotic rate, and updated the classification in 2019. Several previous studies proved that Ki-67 was related to tumor prognosis, but others still reported that Ki-67 had no predictive value for tumor prognosis. There are different conclusions between studies regarding the correlation between Ki-67 and tumor prognosis, and there is a lack of studies about this correlation of GEP-NENs. Further analysis is still needed to evaluate the prognostic value of Ki-67 in GEP-NENs, to provide reference for clinical decisions.
METHODS
A total of 303 studies were retrieved that included Ki-67, GEP-NENs, prognosis, survival, and other subject terms and keywords. We excluded studies that did not show complete Ki-67 index, number of patients and 5-year survival data available for meta-analysis, non-cohort studies, articles published before 2000 or not published in English. Fifteen studies were finally included to assess the value of Ki-67 in the prognosis of patients with GEP-NENs using a random-effects model.
RESULTS
The cumulative 5-year survival rate for GEP-NEN G1 (Ki-67 ≤2%), G2 (Ki-67 2-20%) and G3 (Ki-67 >20%) was 86%, 65%, 25% respectively. The 5-year survival rate of GEP-NEN G1 (Ki-67 <3%, first revised in WHO classification 2017, redefined WHO classification 2019) and G1 (Ki-67 ≤2%, WHO classification 2010) was 97% and 84% respectively.
CONCLUSIONS
The overall prognosis of GEP-NENs patients showed a decreasing trend with the increase of Ki-67, which confirmed the significance of Ki-67 index as a prognostic marker for the prognosis of GEP-NENs. Increasing the cut-off value of Ki-67 index for G1 grade from ≤2% to <3% according to WHO classification 2019 did not significantly decrease the 5-year survival rate.
PubMed: 37701110
DOI: 10.21037/tcr-23-248 -
Genes, Chromosomes & Cancer Dec 2018Tumors characterized by co-expression of S100 and CD34, in the absence of SOX10, remain difficult to classify. Triggered by a few index cases with monomorphic...
Tumors characterized by co-expression of S100 and CD34, in the absence of SOX10, remain difficult to classify. Triggered by a few index cases with monomorphic cytomorphology and distinctive stromal and perivascular hyalinization, immunopositivity for S100 and CD34, and RAF1 and NTRK1 fusions, the authors undertook a systematic review of tumors with similar features. Most of the cases selected were previously diagnosed as low-grade malignant peripheral nerve sheath tumors, while others were deemed unclassified. The tumors were studied with targeted RNA sequencing and/or FISH. A total of 25 cases (15 adults and 10 children) with kinase fusions were identified, including 8 cases involving RAF1, 2 BRAF, 14 NTRK1, and 1 NTRK2 gene rearrangements. Most tumors showed a monomorphic spindle cell proliferation with stromal and perivascular keloidal collagen, in a patternless architecture, with only occasional scattered pleomorphic or multinucleated cells. Most cases showed low cellularity, a low mitotic count, and absence of necrosis. Although a subset showed overlap with lipofibromatosis-like neural tumors, the study group showed distinctive hyalinization and overt malignant features, such as highly cellular fascicular growth and primitive appearance. All tumors showed co-expression of S100 and CD34, ranging from focal to diffuse. SOX10 was negative in all cases. NTRK1 immunohistochemistry showed high levels of expression in all tumors with NTRK1 gene rearrangements. H3K27me3 expression performed in a subset of cases was retained. These findings together with the recurrent gene fusions in RAF1, BRAF, and NTRK1/2 kinases suggest a distinct molecular tumor subtype with consistent S100 and CD34 immunoreactivity.
Topics: Adolescent; Adult; Child; Child, Preschool; Gene Fusion; Gene Rearrangement; Genes, Neoplasm; Humans; Male; Membrane Glycoproteins; Middle Aged; Nerve Sheath Neoplasms; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins c-raf; Receptor, trkA; Receptor, trkB; Receptors, Complement 3b; S100 Proteins; SOXE Transcription Factors; Sarcoma; Soft Tissue Neoplasms; Young Adult
PubMed: 30276917
DOI: 10.1002/gcc.22671 -
The performance of digital microscopy for primary diagnosis in human pathology: a systematic review.Virchows Archiv : An International... Mar 2019Validation studies of whole slide imaging (WSI) systems produce evidence regarding digital microscopy (DM). This systematic review aimed to provide information about the...
Validation studies of whole slide imaging (WSI) systems produce evidence regarding digital microscopy (DM). This systematic review aimed to provide information about the performance of WSI devices by evaluating intraobserver agreement reported in previously published studies as the best evidence to elucidate whether DM is reliable for primary diagnostic purposes. In addition, this review delineates the reasons for the occurrence of discordant diagnoses. Scopus, MEDLINE/PubMed, and Embase were searched electronically. A total of 13 articles were included. The total sample of 2145 had a majority of 695 (32.4%) cases from dermatopathology, followed by 200 (9.3%) cases from gastrointestinal pathology. Intraobserver agreements showed an excellent concordance, with values ranging from 87% to 98.3% (κ coefficient range 0.8-0.98). Ten studies (77%) reported a total of 128 disagreements. The remaining three studies (23%) did not report the exact number and nature of disagreements. Borderline/challenging cases were the most frequently reported reason for disagreements (53.8%). Six authors reported limitations of the equipment and/or limited image resolution as reasons for the discordant diagnoses. Within these articles, the reported pitfalls were as follows: difficulties in the identification of eosinophilic granular bodies in brain biopsies; eosinophils and nucleated red blood cells; and mitotic figures, nuclear details, and chromatin patterns in neuropathology specimens. The lack of image clarity was reported to be associated with difficulties in the identification of microorganisms (e.g., Candida albicans, Helicobacter pylori, and Giardia lamblia). However, authors stated that the intraobserver variances do not derive from technical limitations of WSI. A lack of clinical information was reported by four authors as a source for disagreements. Two studies (15.4%) reported poor quality of the biopsies, specifically small size of the biopsy material or inadequate routine laboratory processes as reasons for disagreements. One author (7.7%) indicated the lack of immunohistochemistry and special stains as a source for discordance. Furthermore, nine studies (69.2%) did not consider the performance of the digital method-limitations of the equipment, insufficient magnification/limited image resolution-as reasons for disagreements. To summarize the pitfalls of digital pathology practice and better address the root cause of the diagnostic discordance, we suggest a Categorization for Digital Pathology Discrepancies to be used in further validations studies. Among 99 discordances, only 37 (37.3%) had preferred diagnosis rendered by means of WSI. The risk of bias and applicability concerns were judged with the QUADAS-2. Two studies (15.4%) presented an unclear risk of bias in the sample selection domain and 2 (15.4%) presented a high risk of bias in the index test domain. Regarding applicability, all studies included were classified as a low concern in all domains. The included studies were optimally designed to validate WSI for general clinical use, providing evidence with confidence. In general, this systematic review showed a high concordance between diagnoses achieved by using WSI and conventional light microscope (CLM), summarizes difficulties related to specific findings of certain areas of pathology-including dermatopathology, pediatric pathology, neuropathology, and gastrointestinal pathology-and demonstrated that WSI can be used to render primary diagnoses in several subspecialties of human pathology.
Topics: Biopsy; Humans; Image Interpretation, Computer-Assisted; Microscopy; Observer Variation; Pathology; Predictive Value of Tests; Reproducibility of Results
PubMed: 30685784
DOI: 10.1007/s00428-018-02519-z -
Dermatologic Surgery : Official... Sep 2014The seventh edition of the American Joint Committee on Cancer guidelines recognize mitotic rate (MR) as a component of the staging criteria for cutaneous melanomas with... (Review)
Review
BACKGROUND
The seventh edition of the American Joint Committee on Cancer guidelines recognize mitotic rate (MR) as a component of the staging criteria for cutaneous melanomas with a Breslow depth ≤1 mm.
OBJECTIVE
This review discusses the evidence behind the threshold of 1 mitosis per square millimeter as a prognostic variable in thin melanomas, particularly because it relates to the decision to pursue a sentinel lymph node biopsy (SLNB).
MATERIALS AND METHODS
We performed a systematic review using the PubMed database to identify articles that contain prognostic information for thin melanomas based on MR and sentinel lymph node (SLN) status.
RESULTS
Although the threshold of a single mitosis correlates with a statistically significant decrease in survival rates for patients with thin melanomas, the clinical relevance remains questionable particularly because it relates to the decision to pursue an SLNB.
CONCLUSION
A single mitosis in thin melanomas does not increase the risk of a positive SLN so much that SLN biopsy should be routinely performed for this cohort.
Topics: Humans; Lymphatic Metastasis; Melanoma; Mitotic Index; Patient Selection; Prognosis; Sentinel Lymph Node Biopsy; Skin Neoplasms
PubMed: 25072127
DOI: 10.1097/01.DSS.0000452619.94264.ff -
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 -
Radiotherapy and Oncology : Journal of... Nov 2019Myoepithelial carcinoma (MEC) is an extremely rare low grade salivary gland neoplasm [1-4]. A surgical resection is considered as corner stone of therapy. Role of...
INTRODUCTION
Myoepithelial carcinoma (MEC) is an extremely rare low grade salivary gland neoplasm [1-4]. A surgical resection is considered as corner stone of therapy. Role of adjuvant therapy is not clear.
METHODOLOGY
We performed systematic review and individual patient data analysis of 691 patients to look into the impact of adjuvant therapy and different prognostic variable for MEC.
RESULTS
Data of 691 individual patients were retrieved from 340 publications. Median age of presentation was 56 years (Range: 0-103 years) with a trend of increasing incidence for increase in age. Major salivary glands (36.4%) were the commonest sub-site followed by minor salivary glands, skin and soft tissue, and breast. Median PFS and OS of entire cohort was 48 months (95% CI: 30-65 months) and 167 months (95% CI: 82-251 months). In univariate analysis A R0 resection was associated with significantly better PFS and OS. Median PFS and OS were significantly worse for patients with tumour size >5 cm compared to smaller tumours and for patients with a mitotic index >10/10 high power field (hpf) compared to lower mitotic index. Adjuvant radiation was found to reduce loco-regional recurrence. Adjuvant radiation and chemotherapy both were associated with negative impact on survival in univariate analysis. This negative impact on survival was lost in multivariate analysis.
CONCLUSION
MEC appears to be a low grade malignancy with good survival outcome. A R0 resection should be the standard of care. Adjuvant radiation should be considered for patients with adverse risk features to improve loco-regional disease control.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Cohort Studies; Combined Modality Therapy; Data Analysis; Humans; Infant; Infant, Newborn; Middle Aged; Myoepithelioma; Salivary Gland Neoplasms; Young Adult
PubMed: 31276988
DOI: 10.1016/j.radonc.2019.06.017 -
APMIS : Acta Pathologica,... Apr 2021We aimed to assess whether the presence of atypical mitotic figures (AMF) in smooth muscle tumors of uncertain malignant potential (STUMP) of the uterus and uterine...
We aimed to assess whether the presence of atypical mitotic figures (AMF) in smooth muscle tumors of uncertain malignant potential (STUMP) of the uterus and uterine adnexa is associated with increased risk of recurrence, and the association of AMF with the Stanford criteria, that is, significant cytologic atypia, mitotic index ≥ 10/10HPF, and coagulative tumor cell necrosis (CTCN). A systematic review was performed to identify all studies reporting the presence of AMF and oncologic outcomes in STUMP series. Fisher's exact test was used to assess the association of AMF with the three Stanford parameters. Kaplan-Meier and Cox regression survival analyses with hazard ratio (HR) calculation were performed to assess the association between AMF and STUMP recurrence. A p-value < 0.05 was considered significant. Five studies with 80 STUMPs were included, out of which 23.8% had AMF. AMF were significantly associated with the presence of significant atypia (p = 0.023), but not with the presence of a mitotic index ≥ 10/10HPF (p = 0.769), CTCN (p = 1), or more than one Stanford parameter (p = 0.171). AMF was not significantly associated with the risk of STUMP recurrence at both univariate (HR = 0.366; p = 0.188) and multivariate analyses (HR = 0.528; p = 0.463). In STUMP of the uterus and uterine adnexa, AMF are more common in the case of significant cytologic atypia, but do not seem to increase the risk of recurrence. Further studies are necessary in this regard.
Topics: Adnexal Diseases; Female; Humans; Leiomyoma; Mitosis; Prognosis; Uterine Neoplasms
PubMed: 33445214
DOI: 10.1111/apm.13114