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Diagnostics (Basel, Switzerland) Sep 2023Hepatic inflammatory pseudotumors (IPTs) are defined as benign, non-malignant, non-metastasizing tumors characterized by the presence of myofibroblastic spindle cells,... (Review)
Review
Hepatic inflammatory pseudotumors (IPTs) are defined as benign, non-malignant, non-metastasizing tumors characterized by the presence of myofibroblastic spindle cells, hetorogenous populations of inflammatory cells, particularly plasma cells, lymphocytes and macrophages, as well as locations of fibrosis and necrosis without cellular anaplasia or atypical mitoses. Despite subsequent reports in the references, hepatic IPT remains difficult to diagnose; while posing major issues specifically for its differential diagnosis compared with that of other various benign diseases and malignant hepatic tumors. Histopathological findings are always a requisite for confirming the diagnosis, particularly given that the pathogenesis of IPT remains ambiguous to date. Hepatic IPT is a heterogeneous entity in terms of its clinical features, pathological findings, and pathogenesis. Once the diagnosis is confirmed, however, needless surgery such as wedge resection and lobectomy should be avoided. Here, we discuss the heterogeneity of hepatic IPT, its clinical features, pathological findings, and pathogenesis, and describe its differential diagnosis.
PubMed: 37685395
DOI: 10.3390/diagnostics13172857 -
Pediatric Blood & Cancer Jul 2024Anaplasia in Wilms tumor is recognized as the most important prognostically unfavorable histological feature. It is subtyped as focal anaplastic Wilms tumor (FAWT) and... (Review)
Review
Anaplasia in Wilms tumor is recognized as the most important prognostically unfavorable histological feature. It is subtyped as focal anaplastic Wilms tumor (FAWT) and diffuse anaplastic Wilms tumor (DAWT). Outcomes of patients with DAWT remain poor in patients with stage III and IV tumors. Important issues relevant to anaplasia in Wilms tumor, including prevalence, treatment, outcomes, biomarkers, anaplasia, and chemotherapy, and the concept of tumor aggressiveness, are reviewed and discussed here. We also consider the differences in clinical approaches to anaplasia in Wilms tumor between the two major renal tumor clinical research groups: the International Society of Paediatric Oncology (SIOP) Renal Tumour Study Group and the Children's Oncology Group (COG) Renal Tumor Group. We emphasize the importance and implications of recognizing FAWT and DAWT as separate clinico-pathological entities.
Topics: Wilms Tumor; Humans; Kidney Neoplasms; Anaplasia; Prognosis
PubMed: 38605554
DOI: 10.1002/pbc.31000 -
Pathology Mar 2024Characterisation of histological, immunohistochemical and molecular prognostic and predictive biomarkers has contributed significantly to precision medicine and better... (Review)
Review
Characterisation of histological, immunohistochemical and molecular prognostic and predictive biomarkers has contributed significantly to precision medicine and better outcomes in the management of paediatric solid tumours. Prognostic biomarkers allow predictions to be made regarding a tumour's aggressiveness and clinical course, whereas predictive biomarkers help determine responses to a specific treatment. This review summarises prognostic biomarkers currently used in the more common paediatric solid tumours, with a brief commentary on the most relevant less common predictive biomarkers. MYCN amplification is the most important genetic alteration in neuroblastoma prognosis, and the histological classification devised by Shimada in 1999 is still used in routine diagnosis. Moreover, a new subgrouping of unfavourable histology neuroblastoma enables immunohistochemical characterisation of tumours with markedly different genetic features and prognosis. The predominant histology and commonly observed cytogenetic abnormalities are recognised outcome predictors in Wilms tumour. Evaluation for anaplasia, which is tightly associated with TP53 gene mutations and poor outcomes, is central in both the International Society of Paediatric Oncology and the Children's Oncology Group approaches to disease classification. Characterisation of distinct genotype-phenotype subclasses and critical mutations has expanded overall understanding of hepatoblastoma outcomes. The C1 subclass hepatoblastoma and CTNNB1 mutations are associated with good prognosis. In contrast, the C2 subclass, NFE2L2 mutations, TERT promoter mutations and high expression of oncofetal proteins and stem cell markers are associated with poor outcomes. Risk stratification in sarcomas is highly variable depending on the entity. The prognosis of rhabdomyosarcoma, for example, primarily depends on histological and molecular characteristics. Advances in our understanding of clinically significant biomarkers will translate into more precise diagnoses, improved risk stratification and more effective and less toxic treatment in this challenging group of patients.
Topics: Child; Humans; Prognosis; Hepatoblastoma; Neuroblastoma; Biomarkers, Tumor; Liver Neoplasms
PubMed: 38216399
DOI: 10.1016/j.pathol.2023.11.007 -
Clinical Cancer Research : An Official... Jul 2023While patients with intermediate-risk (IR) Wilms tumors now have an overall survival (OS) rate of almost 90%, those affected by high-stage tumors with diffuse anaplasia...
PURPOSE
While patients with intermediate-risk (IR) Wilms tumors now have an overall survival (OS) rate of almost 90%, those affected by high-stage tumors with diffuse anaplasia have an OS of only around 50%. We here identify key events in the pathogenesis of diffuse anaplasia by mapping cancer cell evolution over anatomic space in Wilms tumors.
EXPERIMENTAL DESIGN
We spatially mapped subclonal landscapes in a retrospective cohort of 20 Wilms tumors using high-resolution copy-number profiling and TP53 mutation analysis followed by clonal deconvolution and phylogenetic reconstruction. Tumor whole-mount sections (WMS) were utilized to characterize the distribution of subclones across anatomically distinct tumor compartments.
RESULTS
Compared with non-diffuse anaplasia Wilms tumors, tumors with diffuse anaplasia showed a significantly higher number of genetically distinct tumor cell subpopulations and more complex phylogenetic trees, including high levels of phylogenetic species richness, divergence, and irregularity. All regions with classical anaplasia showed TP53 alterations. TP53 mutations were frequently followed by saltatory evolution and parallel loss of the remaining wild-type (WT) allele in different regions. Morphologic features of anaplasia increased with copy-number aberration (CNA) burden and regressive features. Compartments demarcated by fibrous septae or necrosis/regression were frequently (73%) associated with the emergence of new clonal CNAs, although clonal sweeps were rare within these compartments.
CONCLUSIONS
Wilms tumors with diffuse anaplasia display significantly more complex phylogenies compared with non-diffuse anaplasia Wilms tumors, including features of saltatory and parallel evolution. The subclonal landscape of individual tumors was constrained by anatomic compartments, which should be considered when sampling tissue for precision diagnostics.
Topics: Humans; Kidney Neoplasms; Anaplasia; Retrospective Studies; Phylogeny; Wilms Tumor
PubMed: 37140929
DOI: 10.1158/1078-0432.CCR-23-0311 -
Modern Pathology : An Official Journal... Jan 2024Patients with Wilms tumor (WT) in general have excellent survival, but the prognosis of patients belonging to the subgroup of WT with diffuse anaplasia (DA) is poor due...
Patients with Wilms tumor (WT) in general have excellent survival, but the prognosis of patients belonging to the subgroup of WT with diffuse anaplasia (DA) is poor due to frequent resistance to chemotherapy. We hypothesized that DA WT cells might undergo changes, such as acquiring a persistent tolerance to DNA damage and copy number aberrations (CNAs), which could eventually lead to their resistance to chemotherapy treatment. Tissue sections from chemotherapy-treated DA WTs (n = 12) were compared with chemotherapy-treated nonanaplastic WTs (n = 15) in a tissue microarray system, enabling analysis of 769 tumor regions. All regions were scored for anaplastic features and immunohistochemistry was used to quantify p53 expression, proliferation index (Ki67), and DNA double-strand breaks (γH2AX). CNAs were assessed by array-based genotyping and TP53 mutations using targeted sequencing. Proliferation index and the frequency of DNA double-strand breaks (γH2AX dot expression) increased with higher anaplasia scores. Almost all (95.6%) areas with full-scale anaplasia had TP53 mutations or loss of heterozygosity, along with an increased amount of CNAs. Interestingly, areas with wild-type TP53 with loss of heterozygosity and only one feature of anaplasia (anaplasia score 1) also had significantly higher proliferation indices, more DNA double-strand breaks, and more CNAs than regions without any anaplastic features (score 0); such areas may be preanaplastic cell populations under selective pressure for TP53 mutations. In conclusion, we suggest that chemoresistance of DA WTs may be partly explained by a high proliferative capability of anaplastic cells, which also have a high burden of double-stranded DNA breaks and CNAs, and that there is a gradual emergence of anaplasia in WT.
Topics: Humans; Kidney Neoplasms; Anaplasia; Wilms Tumor; Mutation; Prognosis; DNA
PubMed: 37951357
DOI: 10.1016/j.modpat.2023.100382 -
Frontiers in Oncology 2023Treatment of children with medulloblastoma (MB) includes surgery, radiation therapy (RT) and chemotherapy (CT). Several treatment protocols and clinical trials have been...
INTRODUCTION
Treatment of children with medulloblastoma (MB) includes surgery, radiation therapy (RT) and chemotherapy (CT). Several treatment protocols and clinical trials have been developed over the time to maximize survival and minimize side effects.
METHODS
We performed a systematic literature search in May 2023 using PubMed. We selected all clinical trials articles and multicenter studies focusing on MB. We excluded studies focusing exclusively on infants, adults, supratentorial PNETs or refractory/relapsed tumors, studies involving different tumors or different types of PNETs without differentiating survival, studies including <10 cases of MB, solely retrospective studies and those without reference to outcome and/or side effects after a defined treatment.
RESULTS
1. The main poor-prognosis factors are: metastatic disease, anaplasia, MYC amplification, age younger than 36 months and some molecular subgroups. The postoperative residual tumor size is controversial.2. MB is a collection of diseases.3. MB is a curable disease at diagnosis, but survival is scarce upon relapse.4. Children should be treated by experienced neurosurgeons and in advanced centers.5. RT is an essential treatment for MB. It should be administered craniospinal, early and without interruptions.6. Craniospinal RT dose could be lowered in some low-risk patients, but these reductions should be done with caution to avoid relapses.7. Irradiation of the tumor area instead of the entire posterior fossa is safe enough.8. Hyperfractionated RT is not superior to conventional RT9. Both photon and proton RT are effective.10. CT increases survival, especially in high-risk patients.11. There are multiple drugs effective in MB. The combination of different drugs is appropriate management.12. CT should be administered after RT.13. The specific benefit of concomitant CT to RT is unknown.14. Intensified CT with stem cell rescue has no benefit compared to standard CT regimens.15. The efficacy of intraventricular/intrathecal CT is controversial.16. We should start to think about incorporating targeted therapies in front-line treatment.17. Survivors of MB still have significant side effects.
CONCLUSION
Survival rates of MB improved greatly from 1940-1970, but since then the improvement has been smaller. We should consider introducing targeted therapy as front-line therapy.
PubMed: 37456257
DOI: 10.3389/fonc.2023.1229853 -
Veterinary and Comparative Oncology Dec 2023Canine meningiomas are currently graded using the human grading system. Recently published guidelines have adapted the human grading system for use in dogs. The goal of...
Canine meningiomas are currently graded using the human grading system. Recently published guidelines have adapted the human grading system for use in dogs. The goal of this study was to validate the new guidelines for canine meningiomas. To evaluate the inter-observer agreement, 5 veterinary surgical pathologists graded 158 canine meningiomas following the human grading system alone or with the new guidelines. The inter-observer agreement for histologic grade and each of the grading criteria (mitotic grade, invasion, spontaneous necrosis, macronucleoli, small cells, hypercellularity, pattern loss and anaplasia) was evaluated using the Fleiss kappa index. The diagnostic accuracy (sensitivity and specificity) was assessed by comparing the diagnoses obtained with the 2 grading systems with a consensus grade (considered the reference classification). The consensus histologic grade was obtained by agreement between 4 experienced veterinary neuropathologists following the guidelines. Compared with the human grading alone, the canine-specific guidelines increased the inter-observer agreement for: histologic grade (κ = 0.52); invasion (κ = 0.67); necrosis (κ = 0.62); small cells (κ = 0.36); pattern loss (κ = 0.49) and anaplasia (κ = 0.55). Mitotic grade agreement remained substantial (κ = 0.63). The guidelines improved the sensitivity in identifying grade 1 (95.6%) and the specificity in identifying grade 2 (96.2%) meningiomas. In conclusion, the new grading guidelines for canine meningiomas are associated with an overall improvement in the inter-observer agreement and higher diagnostic accuracy in diagnosing grade 1 and grade 2 meningiomas.
Topics: Humans; Dogs; Animals; Meningioma; Anaplasia; Dog Diseases; Meningeal Neoplasms; Necrosis; Reference Standards; Neoplasm Grading
PubMed: 37635372
DOI: 10.1111/vco.12932 -
Radiologia 2023Meningiomas are tumors that originate in the arachnoid villi and are the most common non-glial neoplasm in the central nervous system. The clinical manifestations...
Meningiomas are tumors that originate in the arachnoid villi and are the most common non-glial neoplasm in the central nervous system. The clinical manifestations associated with meningioma depend, fundamentally, on its location. The location in the cerebral convexity is the most frequent, especially in the frontal lobes, manifesting with headache, motor disturbances, seizures and even neurocognitive disorders. There are 15 histologic subtypes of meningioma and three histologic grades. Within these, grades two and three have a worse prognosis and a higher rate of recurrence, as well as a radiological behavior that is generally more aggressive. Although there are some imaging features that can suggest a specific subtype, the definitive diagnosis will always require histological/molecular confirmation.
Topics: Humans; Meningioma; Diagnostic Imaging; Radiography; Prognosis; Meningeal Neoplasms
PubMed: 37758336
DOI: 10.1016/j.rxeng.2023.09.002 -
The American Journal of Surgical... Nov 2023Multiple 3-tiered grading systems exist for mucoepidermoid carcinoma (MEC), leading to controversial results on the frequency and prognostic values of each grade. We...
Multiple 3-tiered grading systems exist for mucoepidermoid carcinoma (MEC), leading to controversial results on the frequency and prognostic values of each grade. We aimed to identify prognostic histologic factors and to evaluate grading schemes in this retrospective study of 262 resected primary head and neck MECs. The rate of nodal metastasis was 8.4%. Large tumor size, tumor fibrosis, infiltrative border, lymphovascular invasion, perineural invasion, atypical mitosis, mitotic index (MI) ≥4/2 mm 2 (4/10 HPFs), necrosis, and pT4 stage were associated with increased risk of nodal metastasis. The 5-year recurrence-free survival (RFS) was 95%. Significant prognostic factors for RFS included infiltrative border, tumor-associated lymphoid stroma, architectural patterns (macrocystic, microcystic, and noncystic), anaplasia, atypical mitosis, MI, necrosis, lymphovascular invasion, margin, pT stage, and tumor size. Nuclear anaplasia, high mitotic rate, and ≥25% microcystic component were significant independent prognostic factors on multivariate survival analysis. There was no significant difference between low-grade (LG) and intermediate-grade (IG) MECs in terms of risk of nodal metastasis and outcomes using all 4 known grading systems. Rather, high-grade MEC was consistently associated with an increased risk of nodal metastasis at presentation and decreased RFS and distant metastasis-free survival (DMFS) compared with the LG/IG MECs. We therefore recommend simplifying MEC grading to a 2-tiered grading scheme using MI and/or tumor necrosis. Using a 2-tiered grading, high-grade histology independently predict RFS, and is associated with a 25% risk of nodal metastasis, a 5-year RFS of 76%, and a 5-year DMFS of 76%, whereas LG MEC has a nodal metastasis rate of 7.0%, 5-year RFS of 97% and 5-year DMFS of 99%.
PubMed: 37694548
DOI: 10.1097/PAS.0000000000002120