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Pancreatology : Official Journal of the... Jul 2019The clinicopathological features and biological behaviors of cystic pancreatic neuroendocrine tumors (pNETs) are unclear and controversial. Here we performed a... (Meta-Analysis)
Meta-Analysis
BACKGROUND/OBJECTIVES
The clinicopathological features and biological behaviors of cystic pancreatic neuroendocrine tumors (pNETs) are unclear and controversial. Here we performed a systematic review and meta-analysis to investigate the unique characteristics of cystic pNETs, to determine whether they represent a distinct clinical entity.
METHODS
We selected comparative studies published since January 2000 that explore the differences between clinicopathological features of cystic and solid pNETs. Demographic information, pathological characteristics, and survival information were analyzed.
RESULT
The 12 selected studies comprised 355 and 1530 patients diagnosed with cystic and solid pNETs, respectively. Compared with solid pNETs, cystic pNETs were less likely to be functional (odds ratio, OR = 0.31, 95% confidence interval (CI) 0.19-0.50, p < 0.00001), more likely to affect males (OR = 1.56, 95% CI 1.22-2.00, p = 0.0005), and significantly associated with multiple endocrine neoplasia type 1 (OR = 2.71). Cystic pNETs were more likely to present with G1 and G2 rather than G3 (OR = 1.66). Cystic pNETs were associated with less frequent distant organs and lymph node metastasis, microvascular invasion, perineural invasion, and a low Ki-67 index and mitotic count. There were no significant differences between 5- and 10-year overall survival. However, the 5-year disease-free survival (DFS) and 10-year DFS rate of patients with cystic pNETs was significantly higher compared with those with solid pNETs (94.6% vs 83.5%, OR = 3.00; 92.7% vs 63.6%, OR = 5.92, respectively).
CONCLUSIONS
Cystic pNETs represent a distinct subgroup of pNETs that present with an indolent biological behavior, and patients experience better DFS. Observation and surveillance should be considered in some selected cases.
Topics: Humans; Neuroendocrine Tumors; Pancreatic Neoplasms; Prognosis
PubMed: 31160191
DOI: 10.1016/j.pan.2019.05.462 -
Annals of Diagnostic Pathology Oct 2022To describe the clinicopathological features and differential diagnoses of 15 cases of superficial myofibroblastoma, a rare mesenchymal tumor involving the lower female...
OBJECTIVE
To describe the clinicopathological features and differential diagnoses of 15 cases of superficial myofibroblastoma, a rare mesenchymal tumor involving the lower female genital tract.
METHODS
The clinicopathological data and immunohistochemical findings were retrospectively analyzed in 15 cases of superficial myofibroblastoma. Meanwhile, a systematic literature review was conducted.
RESULTS
The age of patients ranged from 34 to 73 years (median, 49 years). Most patients presented with nodular or polypoid masses ranging in size from 0.4 cm to 6.5 cm. Twelve tumors were located in the vagina, two in the vulva, and one in the cervix. Microscopically, the tumor was located in the subepithelial tissue, with a clear boundary and without capsule on the surface. The tumor cells were spindle, oval, stellate or wavy, and arranged in various architectural patterns of reticular, fascicular, wavy and disorderly patterns. There were no obvious cellular atypia and mitotic figures. Thin collagen fibers and thin-walled vessels could be observed in all cases. Most cases were diffusely and strongly reactive to Vimentin (12/12), Desmin (14/15), ER (15/15) and PR (13/14). Variable immunoreactivity for CD34 (8/15), Caldesmon (2/8), SMA (4/14) and CD99 (4/5) were observed. The tumors showed a low Ki67 proliferative index (≤5 %). Follow-up information was available in 10 patients and there was no evidence of recurrence or metastasis.
CONCLUSIONS
Superficial myofibroblastoma is a rare benign tumor that originates from the hormone-sensitive, subepithelial mesenchymal tissue of the lower female genital tract, and should be differentiated from other mesenchymal tumors.
Topics: Adult; Aged; Biomarkers, Tumor; Calmodulin-Binding Proteins; Collagen; Desmin; Female; Hormones; Humans; Ki-67 Antigen; Middle Aged; Neoplasms, Muscle Tissue; Retrospective Studies; Vagina; Vimentin
PubMed: 35907316
DOI: 10.1016/j.anndiagpath.2022.152010 -
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 -
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 -
Pathology, Research and Practice Apr 2020Granular cell tumor (GCT) remains a diagnostic clinicopathologic problem because the exact frequency of its detailed morphological and clinical characteristics is...
BACKGROUND
Granular cell tumor (GCT) remains a diagnostic clinicopathologic problem because the exact frequency of its detailed morphological and clinical characteristics is unknown as most observations are collected from small series or isolated cases. Herein, our aim is to highlight the frequency of all clinicopathological characteristics of this rare tumor based in our series and the available medical (PubMed) literature.
MATERIAL AND METHODS
42 cases were evaluated for: tissue layers involved by the tumor (in skin and mucosae), growth pattern, nuclear pleomorphism, mitotic index, necrosis, spindling, calcification, hyalinization, and pustule-ovoid bodies of Milian, as well as perineural and vascular invasion, and the presence of adjacent epithelium changes, and lymphocytes and eosinophils infiltration., Follow-up was analyzed. The tumors were subclassified into benign, atypical and malignant according to Fanburg-Smith criteria and into benign or GCT of uncertain malignant potential according to Nasser criteria. The same characteristics were analyzed for 1499 cases reviewed according to PRISMA guidelines.
RESULTS
In the current series, the mean age at diagnosis was 45.8 years (range 6-69 years). Most patients were females (60 %) and the involved organs were by descending frequency: skin and subcutaneous tissue, bronchus, esophagus, breast, tongue, larynx, pharynx, gingiva, trachea, right colon, vulva, and hypopharynx. No recurrence or progression was seen, despite 32 cases were incompletely excised, with the exception of one malignant tumor. The growth pattern was either infiltrative (85.71 %) or well limited (7.14 %). Sixteen tumors had vesicular nuclei. Mitotic activity was found in two tumors. Lymphocytic infiltration was found in 14 tumors. Eosinophils were present in 6 cases. One GCT of the right colon showed extensive calcification and hyalinization. Perineural invasion was noted in 6 lesions. No vascular invasion was found. One tumor was clinically malignant and the patient died 2 years after diagnosis. Medical literature review showed similar results in terms of frequency of the reported clinical and morphological features. Among cases with available follow up, almost 20 % showed positive margins and of those 20 % developed local recurrence. According to the Fanburg-Smith criteria, 72 % would be benign, 17 % atypical and 11 % malignant tumors, while according to those of Nasser, 93 % would be benign and 7% of uncertain malignant potential. However, true malignancy, as affirmed by metastasis of GCT is found in almost 2.5 % of the cases.
CONCLUSION
GCT is a usually benign tumor, affecting any anatomic location. Necrosis and mitotic activity seem to be the most effective histologic criteria for detecting aggressive tumors, but the presence of metastasis (2.5 % of the cases) remains the most accepted definitive criterion for diagnosis of malignant GCT.
Topics: Adolescent; Adult; Aged; Child; Female; Granular Cell Tumor; Humans; Male; Middle Aged; Young Adult
PubMed: 32089415
DOI: 10.1016/j.prp.2020.152865 -
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 -
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 -
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 -
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 -
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