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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 -
Indian Journal of Pathology &... 2022Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Anaplasia is a rare phenomenon seen in childhood RMS. The most common histologic subtype was...
BACKGROUND
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Anaplasia is a rare phenomenon seen in childhood RMS. The most common histologic subtype was Embryonal followed by Alveolar and spindle subtype.
DESIGN
A total of 11 cases of pediatric RMS were selected from January 2017 to June 2019 presenting at various sites. Out of 11 cases, 2 were further diagnosed as Embryonal, 2 as Alveolar, 2 as Pleomorphic, 1 as Spindle subtype and rest 4 as RMS-NOS based on morphology. All cases were positive for Desmin. The presence of cells with lobated, hyperchromatic nuclei at least three times larger than the tumor cell (anaplastic cells) was selected as the main criterion to diagnose Anaplasia.
RESULTS
Out of the total 11 cases, anaplasia was seen in 7 cases. Out of these seven, five cases showed Focal Anaplasia (FA) (71.4%) and 2 cases showed Diffuse Anaplasia (DA) (28.6%). Out of 2 cases of Embryonal RMS one exhibited focal anaplasia (50%). One case of Spindle RMS showed diffuse anaplasia, 2 cases of pleomorphic RMS showed focal anaplasia. Out of 3 cases of RMS- NOS, 2 exhibited focal anaplaisa and one displayed Diffuse anaplasia. Both Alveolar RMS had no features of anaplasia.
CONCLUSION
Presence of Anaplasia is a frequent observation in pediatric RMS. Anaplasia is often under reported in pediatric RMS. Pathologist should be more aware of this rare phenomenon.
Topics: Child; Humans; Anaplasia; Rhabdomyosarcoma; Sarcoma; Soft Tissue Neoplasms; Rhabdomyosarcoma, Alveolar
PubMed: 36308195
DOI: 10.4103/ijpm.ijpm_178_21 -
Brain Pathology (Zurich, Switzerland) Jul 2003The variable clinical outcomes of medulloblastoma patients have prompted a search for markers with which to tailor therapies to individuals. In this review, we discuss... (Review)
Review
The variable clinical outcomes of medulloblastoma patients have prompted a search for markers with which to tailor therapies to individuals. In this review, we discuss clinical, histological and molecular features that can be used in such treatment customization, focusing on how histopathological grading can impact both patient care and research on the molecular basis of CNS embryonal tumors. Medulloblastomas span a histological spectrum ending in overtly malignant large cell/anaplastic lesions characterized by increased nuclear size, marked cytological anaplasia, and increased mitotic and apoptotic rates. These "high-grade" lesions make up approximately one quarter of medulloblastomas, and recur and metastasize more frequently than tumors lacking anaplasia. We believe anaplastic change represents a type of malignant progression common to many medulloblastoma subtypes and to other CNS embryonal lesions as well. Correlation of these histological changes with the accumulation of genetic events suggests a model for the histological and molecular progression of medulloblastoma.
Topics: Anaplasia; Carcinoma, Large Cell; Cerebellar Neoplasms; Disease Progression; Gene Expression Profiling; Humans; Medulloblastoma; Neoplasm Metastasis; Neoplasms, Germ Cell and Embryonal
PubMed: 12946027
DOI: 10.1111/j.1750-3639.2003.tb00037.x -
Pediatric Blood & Cancer Jan 2023
Review
Topics: Humans; Infant; Ganglioglioma; Anaplasia; Age of Onset; Brain Neoplasms; Magnetic Resonance Imaging
PubMed: 35670752
DOI: 10.1002/pbc.29808 -
Brain Tumor Pathology Apr 2019Many breakthroughs have been made in the past decade regarding our knowledge of the biological basis of the diffuse gliomas, the most common primary central nervous... (Review)
Review
Many breakthroughs have been made in the past decade regarding our knowledge of the biological basis of the diffuse gliomas, the most common primary central nervous system (CNS) tumors. These tumors as a group are aggressive, associated with high mortality, and have a predilection for adults. However, a subset of CNS glial and glioneuronal tumors are characterized by a more circumscribed pattern of growth and occur more commonly in children and young adults. They tend to be indolent, but our understanding of anaplastic changes in these tumors continues to improve as diagnostic classifications evolve in the era of molecular pathology and more integrated and easily accessible clinical databases. The presence of anaplasia in pleomorphic xanthoastrocytomas and gangliogliomas is assigned a WHO grade III under the current classification, while the significance of anaplasia in pilocytic astrocytomas remains controversial. Recent data highlight the association of the latter with aggressive clinical behavior, as well as the presence of molecular genetic features of both pilocytic and diffuse gliomas, with the recognition that the precise terminology remains to be defined. We review the current concepts and advances regarding histopathology and molecular understanding of pilocytic astrocytomas, pleomorphic xanthoastrocytomas, and gangliogliomas, with a focus on their anaplastic counterparts.
Topics: Anaplasia; Astrocytoma; Brain Neoplasms; Carcinoma; Central Nervous System Neoplasms; Ganglioglioma; Glioma; Humans; Neuroglia; Proto-Oncogene Proteins B-raf
PubMed: 30859342
DOI: 10.1007/s10014-019-00336-z -
Annals of Internal Medicine Jul 1977Anaplasia refers to the apparent retrogression toward an embryonic state that occurs in some human and animal tumors, the consequence, presumably, of a derepression of...
Anaplasia refers to the apparent retrogression toward an embryonic state that occurs in some human and animal tumors, the consequence, presumably, of a derepression of genes that would normally have been switched off in the course of development. The fetal substances newly formed in tumors are identified immunologically and are therefore referred to as "antigens." Some such antigens, for example, carcinoembryonic antigen and alpha-fetoprotein, and blood-group precursor substances have great promise diagnostically but play no known part in resistance to malignant growth. The reawakened fetal antigens that are of special interest and importance are those that are capable of arousing cell-mediated immunity and thus may contribute to antitumor immunity. Modern research, therefore, rehabilitates an etiologc notion earlier thought to have been discredited.
Topics: Anaplasia; Animals; Antigens, Neoplasm; Carcinoembryonic Antigen; Female; HLA Antigens; Humans; Immunity, Cellular; Lymphocytes; Neoplasms, Experimental; Oncogenic Viruses; Pregnancy; alpha-Fetoproteins
PubMed: 69414
DOI: 10.7326/0003-4819-87-1-100 -
Journal of the American Society of... 2022The presence of tumor cell anaplasia and multinucleation (A/M) in oropharyngeal squamous cell carcinoma (OPSCC) has recently been found to be associated with increased...
INTRODUCTION
The presence of tumor cell anaplasia and multinucleation (A/M) in oropharyngeal squamous cell carcinoma (OPSCC) has recently been found to be associated with increased disease recurrence and poorer disease-specific survival, regardless of human papillomavirus status. We studied the detection of A/M in cytology specimens.
MATERIALS AND METHODS
We performed a comprehensive data search for all patients with OPSCC diagnosed and treated at Northwestern Memorial Hospital between January 2013 and April 2020. All cytology and histopathologic slides were reviewed for the presence of A/M in patients with both surgical resection or biopsy specimens and fine needle aspiration cytology of a metastatic site.
RESULTS
A total of 87 patients were identified with both surgical and cytology specimens available for review. A/M was identified in 21 cytology specimens and 14 surgical specimens. Cytologic A/M was seen in 11 of the 14 patients (78.5%) with corresponding histologic A/M and in 10 of the 73 patients (13.7%) without histologic A/M. Disease-specific survival was significantly worse for the patients with cytologic A/M regardless of the presence of histologic A/M (P = 0.0064) and for the patients with cytologic A/M only (P = 0.0271). In patients with p16-positive/human papillomavirus-associated carcinoma, disease-specific survival was significantly worse for the patients with both histologic and cytologic A/M (P = 0.0305).
CONCLUSIONS
A/M can be reliably identified in cytology specimens among all the various stains and preparations, irrespective of the primary tumor histologic type. Identification of A/M on cytology specimens could indicate more aggressive clinical behavior and help guide patient management.
Topics: Alphapapillomavirus; Anaplasia; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Squamous Cell Carcinoma of Head and Neck
PubMed: 35474265
DOI: 10.1016/j.jasc.2022.03.004 -
The American Journal of Surgical... Aug 1996Anaplasia, defined by the presence of extreme nuclear and mitotic atypia, is a potent marker of adverse prognosis in Wilms tumor (WT). Anaplastic WT cells apparently... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial Review
Anaplasia, defined by the presence of extreme nuclear and mitotic atypia, is a potent marker of adverse prognosis in Wilms tumor (WT). Anaplastic WT cells apparently have increased resistance to therapy rather than increased aggressiveness. The distribution of anaplasia should therefore have critical prognostic relevance. The original definitions for focal anaplasia (FA) and diffuse anaplasia (DA) were based on quantitative rather than topographical criteria and lacked prognostic significance. A new definition was developed based on the distribution of anaplastic changes within the tumor: FA applies only to tumors with anaplasia confined to one or a few discrete loci within the primary tumor, with no anaplasia or marked nuclear atypia elsewhere. This revised definition was evaluated in 165 cases with anaplastic WT entered on the third and fourth National Wilms Tumor Study. Only three relapses and one death occurred among 39 cases with FA, regardless of tumor stage, a result comparable to that for nonanaplastic WT. Eight children with metastases at diagnosis and FA in the primary tumor were alive and free of relapse; 22 of 23 children with stage IV DA WT died of tumor. This new definition reinforces the importance of carefully documenting the exact site from which each tumor section is obtained.
Topics: Anaplasia; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Image Processing, Computer-Assisted; Infant; Kidney Neoplasms; Male; Prognosis; Wilms Tumor
PubMed: 8712292
DOI: 10.1097/00000478-199608000-00001 -
European Journal of Cancer (Oxford,... Jan 2021Established prognostic indicators in rhabdomyosarcoma (RMS), the most common childhood soft tissue sarcoma, include several clinicopathologic features. Among pathologic...
BACKGROUND
Established prognostic indicators in rhabdomyosarcoma (RMS), the most common childhood soft tissue sarcoma, include several clinicopathologic features. Among pathologic features, anaplasia has been suggested as a potential prognostic indicator, but the clinical significance of anaplasia remains unclear.
METHODS
Patients enrolled on one of five recent Children's Oncology Group clinical trials for RMS (D9602, n = 357; D9802, n = 80; D9803, n = 462; ARST0331, n = 335; and ARST0531, n = 414) with prospective central pathology review were included in this study. Clinicopathologic variables including demographic information, risk group, histologic subtype, and anaplasia were recorded along with overall survival (OS) and failure-free survival (FFS) with failure defined by recurrence, progression, or death. The log-rank test was used to compare OS and FFS.
RESULTS
Anaplasia was more common in embryonal RMS (27% of all embryonal RMS) than other subtypes of RMS (11% for alveolar RMS, 7% for botryoid RMS, 11% for spindle cell RMS). On multivariate analyses, anaplasia was not an independent prognostic factor in RMS (OS:hazard ratio (HR) = 1.12, p = 0.43; FFS:HR = 1.07, p = 0.56) across all subtypes or within embryonal RMS only (OS:HR = 1.41, p = 0.078; FFS:HR = 1.25, p = 0.16). Among tumors with TP53 mutations, 69% had anaplasia, while only 24% of tumors with anaplasia had a tumoral TP53 mutation.
CONCLUSIONS
Anaplasia is not an independent indicator of adverse outcomes in RMS. Emerging information on the prognostic significance of TP53 mutations raises the possibility that anaplasia may be a surrogate marker of TP53 mutations in some cases. Tumoral TP53 mutation status may be investigated as a prognostic indicator in future studies.
Topics: Anaplasia; Child; Child, Preschool; Female; Humans; Infant; Male; Prognosis; Rhabdomyosarcoma; Risk Factors; Survival Analysis
PubMed: 33302115
DOI: 10.1016/j.ejca.2020.10.018 -
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