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Neuro-oncology Practice Aug 2018Ependymomas are rare primary central nervous system (CNS) tumors in adults. They occur most commonly in the spinal cord, and have classically been graded histologically... (Review)
Review
Ependymomas are rare primary central nervous system (CNS) tumors in adults. They occur most commonly in the spinal cord, and have classically been graded histologically into World Health Organization (WHO) grades I, II, or III based on the level of anaplasia. Recent data are showing that genetic heterogeneity occurs within the same histological subgroup and that ependymomas arising from different CNS locations have different molecular signatures. This has renewed interest in developing targeting therapies based on molecular profiles especially given the variable outcomes with radiation and the poor results with cytotoxic agents. In this paper, we present the case of a 46-year-old woman with a classic presentation of spinal cord ependymoma and discuss the current histopathological and molecular classification for ependymomas as well as current guidelines for patient management.
PubMed: 31386035
DOI: 10.1093/nop/npy026 -
European Journal of Cancer (Oxford,... Sep 2019In the fifth National Wilms Tumor Study (NWTS-5), the 4-year event-free survival (EFS) and overall survival (OS) estimates for 29 patients with stage I focal (n = 10)... (Comparative Study)
Comparative Study
BACKGROUND
In the fifth National Wilms Tumor Study (NWTS-5), the 4-year event-free survival (EFS) and overall survival (OS) estimates for 29 patients with stage I focal (n = 10) or diffuse (n = 19) anaplastic Wilms' tumour (AWT) treated with vincristine and dactinomycin without flank radiation were 69.5% and 82.6%, respectively. The Children's Oncology Group AREN0321 study evaluated whether adding doxorubicin and flank radiation improves survival for these patients.
PATIENTS AND METHODS
Tumour histology and stage were confirmed by real-time central pathology, surgery and radiology review. The patients received 25 weeks of vincristine, dactinomycin and doxorubicin (cumulative dose 150 mg/m) with flank radiation (1080 cGy). We retrospectively analysed outcomes of all patients with stage I AWT enrolled in NWTSs 1-5 and AREN0321 with respect to treatment regimens.
RESULTS
Eighteen patients with stage I AWT (8 focal and 10 diffuse) were enrolled on AREN0321. With a median follow-up of 4.6 years, the 4-year EFS and OS were 100%. One patient with diffuse AWT had pulmonary relapse 4.12 years after diagnosis. In the 112 patients with stage I AWT treated in NWTSs 1-5 and AREN0321, the EFS was significantly improved with doxorubicin treatment (p = 0.01; 4-year EFS: 97.2% [95% confidence interval {CI}: 91.3-100] vs. 77.5% [95% CI: 67.6-87.4]) but not by flank radiation (p = 0.15).
CONCLUSIONS
Treatment of stage I AWT with vincristine, dactinomycin, doxorubicin and flank radiation in AREN0321 yielded excellent survival outcomes. Retrospective analysis of AREN0321 and NWTS patients suggests that doxorubicin had a greater contribution to the excellent outcomes than radiation.
Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Child; Child, Preschool; Dactinomycin; Disease Progression; Doxorubicin; Female; Humans; Infant; Kidney Neoplasms; Male; Neoplasm Staging; Nephrectomy; Progression-Free Survival; Radiotherapy, Adjuvant; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; United States; Vincristine; Wilms Tumor
PubMed: 31325873
DOI: 10.1016/j.ejca.2019.05.033 -
Journal of Current Ophthalmology Jun 2019To present a rare anaplastic form of retinal pleomorphic xanthoastrocytoma (PXA) unassociated with phakomatosis.
PURPOSE
To present a rare anaplastic form of retinal pleomorphic xanthoastrocytoma (PXA) unassociated with phakomatosis.
METHODS
A 9-year-old girl, presented with a rapidly growing unilateral intraocular white mass unresponsive to intra-arterial chemotherapy, underwent enucleation with the clinical suspicion of retinoblastoma versus malignant astrocytoma.
RESULTS
Histopathology revealed pleomorphic cells with rosenthal fibers, mitosis, and necrosis. Immunohistochemistry confirmed the diagnosis of anaplastic pleomorphic xanthoastrocytoma (aPXA). The patient had no signs of phakomatosis.
CONCLUSION
Retinal PXA may occur in patients without phakomatosis and rarely progress toward malignant transformation.
PubMed: 31317107
DOI: 10.1016/j.joco.2018.09.005 -
Cancer Cytopathology Jul 2019Certain carcinomas of the thyroid gland behave aggressively resulting in increased patient morbidity and poor patient prognosis. The diagnosis of these aggressive... (Review)
Review
Certain carcinomas of the thyroid gland behave aggressively resulting in increased patient morbidity and poor patient prognosis. The diagnosis of these aggressive thyroid cancer subtypes is sometimes challenging and subject to increased interobserver variability. This review deals with the cytological features of such tumors including aggressive variants of papillary thyroid carcinoma, poorly differentiated thyroid carcinoma, and anaplastic thyroid carcinoma. These malignancies fall into 2 groups based on their cytomorphology: those that exhibit distinct microscopic features (eg, nuclear findings typical of classical papillary thyroid carcinoma or marked anaplasia) and those that present with more subtle cytologic features (eg, nuclear pseudostratification, "soap bubble" nuclei, supranuclear or subnuclear cytoplasmic vacuoles, rosette-like structures, hobnail cells). We review the literature regarding these aggressive thyroid cancers and highlight important phenotypic characteristics that can be useful for their diagnosis based on fine needle aspiration.
Topics: Adenocarcinoma, Follicular; Biopsy, Fine-Needle; Diagnosis, Differential; Humans; Prognosis; Thyroid Cancer, Papillary; Thyroid Carcinoma, Anaplastic; Thyroid Gland; Thyroid Neoplasms
PubMed: 31150164
DOI: 10.1002/cncy.22136 -
Case Reports in Oncology 2019Benign metastasizing leiomyomas (BML) represent a rare phenomenon consisting of the extra-uterine spread of smooth muscle cells with similar histological, immunological,...
Benign metastasizing leiomyomas (BML) represent a rare phenomenon consisting of the extra-uterine spread of smooth muscle cells with similar histological, immunological, and molecular patterns to those of benign uterine leiomyomas. They are considered benign based off their low mitotic activity, lack of anaplasia or necrosis, and limited vascularization. This condition represents an interesting diagnostic and treatment challenge based on their rarity and indolent nature. Our case represents a unique finding of BML in the thoracic spine in a postmenopausal woman many years after hysterectomy and partial oophorectomy. There are currently no standard guidelines for treatment of BML, given the rare nature of this condition, with most patients treated with a combination of surgical resection and radiotherapy, followed by hormonal treatment and radiological surveillance serving as the primary backbone of current management plans. Given that these patients present a unique clinical challenge in terms of diagnosis and management, it is important to delineate and further examine these rare entities.
PubMed: 31011319
DOI: 10.1159/000496333 -
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 -
International Journal of Applied &... 2019Sertoli-Leydig cell tumor (SLCT) of the ovary is an extremely uncommon neoplasm accounting for <0.5% of all primary ovarian neoplasms. These tumors belong to the...
Sertoli-Leydig cell tumor (SLCT) of the ovary is an extremely uncommon neoplasm accounting for <0.5% of all primary ovarian neoplasms. These tumors belong to the category of sex cord-stromal tumors. The tumor has variable clinical and histopathological presentations complicating the diagnosis and therefore the treatment. The presence of heterologous elements is seen in one-fifth of these already rare neoplasms. Herein, we report a case of a 28-year-old female presenting with irregular menses, features of virilization, and abdominal pain. Histopathological examination revealed marked focal anaplasia in this tumor of, otherwise, intermediate differentiation along with the presence of heterologous elements. Reporting of such elements is imperative for adequate treatment and deciding follow-up.
PubMed: 30820423
DOI: 10.4103/ijabmr.IJABMR_84_18 -
International Journal of... Oct 2018Pleomorphic xanthoastrocytoma is a rare tumour of children and young adults, particularly for those with features of anaplasia. This retrospective study comprises...
Pleomorphic xanthoastrocytoma is a rare tumour of children and young adults, particularly for those with features of anaplasia. This retrospective study comprises five cases of anaplastic pleomorphic xanthoastrocytomas diagnosed over a period of 4 years in a tertiary care institute. A detailed clinicopathological and immunohistochemical profile of the tumours were noted from the hospital database. Five cases of anaplastic pleomorphic xanthoastrocytomas were evaluated for their clinicoradiological, histomorphological as well as immunohistochemical findings, which included 3 females and 2 males, with age range of 11-40 years and a mean age at presentation of 22 years. Histologically a solid cystic biphasic tumour with moderate to high cellularity, spindled pleomorphic astrocytes, hyperchromatic nuclei showing moderate to marked atypia, intranuclear inclusions, ≥5 mitoses per 10 high power fields, with evidence of necrosis and atypical mitoses was noted. One of the cases showed transformation into glioblastoma with evidence of spinal metastasis on follow-up. The tumours expressed both glial as well as neuronal markers with expression of CD34 with increased Ki 67 ranging between 5-20%. It was concluded that PXA, a low-grade glioneuronal tumour, can show odd site presentation, marked pleomorphism, increased mitosis, atypical mitoses and increased Ki 67 when associated with features of anaplasia. An appropriate panel of immunohistochemical markers in conjunction with a detailed evaluation of histomorphological features and clinicoradiological information are useful for its diagnosis.
PubMed: 30774826
DOI: No ID Found -
PloS One 2019Malignant transformation is associated with loss of cell differentiation, anaplasia. Transcription factors gli, required for embryonic development, may be involved in...
Malignant transformation is associated with loss of cell differentiation, anaplasia. Transcription factors gli, required for embryonic development, may be involved in this process. We studied the activity of transcription factors gli in high-grade gliomas and their role in maintenance of stem cell state and glioma cell survival. 20 glioma cell lines and a sample of a normal adult brain tissue were used in the present study. We found the expression of gli target genes, including GLI1 and FOXM1, in all tested glioma cell lines, but not in the normal tissue. Interestingly, the expression of gli target genes in some glioma cell lines was observed together with a high level of their transcriptional repressor, Gli3R. Knockdown of GLI3 in one of these lines resulted in decrease of gli target gene expression. These data suggest that Gli3R does not prevent the gli target genes transcription, and gli3 acts in glioma cells more as an activator, than a repressor of transcription. We observed that gli regulated the expression of such genes, as SOX2 or OCT4 that maintain stem cell state, and TET1, involving in DNA demethylation. Treatment with GANT61 or siRNA against GLI1, GLI2, or GLI3 could result in complete glioma cell death, while cyclopamine had a weaker and line-specific effect on glioma cell survival. Thus, the gli transcription factors are abnormally active in high-grade gliomas, regulate expression of genes, maintaining the stem cell state, and contribute to glioma cell survival.
Topics: Brain Neoplasms; Cell Line, Tumor; Cell Survival; Forkhead Box Protein M1; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Glioma; HeLa Cells; Humans; Neoplastic Stem Cells; Nerve Tissue Proteins; Nuclear Proteins; Pyridines; Pyrimidines; Repressor Proteins; Zinc Finger Protein GLI1; Zinc Finger Protein Gli2; Zinc Finger Protein Gli3
PubMed: 30730955
DOI: 10.1371/journal.pone.0211980 -
PeerJ 2019Cyclin A overexpression is found in a variety of human tumors and correlates with unfavorable outcome. We analyzed immunohistochemical expression of cyclin A in Wilms...
BACKGROUND
Cyclin A overexpression is found in a variety of human tumors and correlates with unfavorable outcome. We analyzed immunohistochemical expression of cyclin A in Wilms tumor (WT) in relation to clinicopathological characteristics, preoperative chemotherapy (PrOpChTh), and overall survival (OS).
METHODS
This retrospective study involved 43 patients who underwent nephrectomy from January 1996 to October 2010. Tumor stage and histological subtype were determined by revised Societé International d'Oncologie Pediatrique protocol, based on histological components/alterations caused by PrOpChTh, within the prognostic group of low, intermediate and high risk, and with criteria for anaplasia. The regressive/necrotic changes in total tumor mass of primary tumor and the proportion of epithelial, blastemal, and stromal components in the remaining viable tumor tissue were also determined. Cyclin A expression was evaluated by immunohistochemistry using a polyclonal rabbit, antihuman antibody (H-432).
RESULTS
Cyclin A overexpression was found in 34.3% of WTs, with higher frequency in tumors with epithelial (31.3%) and blastemal (37.1%) components than those with stromal component (17.7%). Regarding histological type, cyclin A overexpression was found most often in focal anaplasia (100%), stromal (60%), and diffuse anaplastic (66.7) WTs. The overexpression was also more frequent in stages 3 and 4 (77.8% and 66.7%, respectively) compared to tumors in stages 1 and 2 (13.3% and 12.5%, respectively; = 0.004) in all components, as well as in blastemal component in stages 3 and 4 (77.8% and 66.7%, respectively) vs. stages 1 and 2 (13.3% and 25%, respectively, = 0.009). Cyclin A overexpression in all components was 66.7% in WTs with metastasis and 31.3% in WTs without metastasis ( = 0.265, Fisher test). Log-rank testing revealed differences of OS regarding stage ( = 0.000), prognostic groups ( = 0.001), and cyclin A expression in blastemal component ( = 0.025). After univariate analysis, tumor stage ( = 0.001), prognostic group ( = 0.004), and cyclin A expression in blastemal component ( = 0.042) were significant prognostic factors for OS; however, after multivariate analysis, none of these factors were confirmed as independent predictors of survival.
DISCUSSION
This study showed that cyclin A overexpression might be associated with the development and progression of WT with anaplasia. Also, cyclin A overexpression was more often observed in advanced stages (3 and 4) of WT, in the group of high-risk WTs, and in focal and diffuse anaplasia WTs. There was no relation of cyclin A overexpression and metastatic ability of WT. Although this study has not confirmed the prognostic value of cyclin A overexpression, its association with unfavorable prognosis should be further evaluated.
PubMed: 30648000
DOI: 10.7717/peerj.6212