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Neoplasma Sep 2022Tumor budding is a significant independent prognostic factor in colorectal cancer. Routine reporting of tumor budding is now advocated for in the colorectal cancer...
Tumor budding is a significant independent prognostic factor in colorectal cancer. Routine reporting of tumor budding is now advocated for in the colorectal cancer standard approach recommended by the International Tumor Budding Consensus Conference guidelines. However, the current tumor budding assessment system only emphasizes tumor budding quantity and ignores other features. Therefore, this study aimed to further determine the prognostic value of tumor budding based on a more comprehensive feature analysis. To this end, we conducted a retrospective pathology review of the different characteristics of tumor budding (that is quantity, structure, cell atypia, location, stromal reaction, and immunohistochemical phenotype) in 224 specimens of stage II colorectal cancer at our institution between 2009 and 2015. The mean age of the patients was 60.3±9.2 years (range, 39-84 years). Among various features of tumor budding, single-cell budding, anaplasia-like cell atypia, myxoid stroma, high tumor budding quantity, and loss of CDX2 expression were independent predictors of recurrence and mortality in patients with stage II colorectal cancer. Based on these results, we suggest that in addition to tumor-budding quantity, other tumor budding features play important biological roles in the development of colorectal cancer. Our findings provide prognostic information that could help with guiding clinical management and oncology care models for patients with stage II colorectal cancer.
Topics: Colorectal Neoplasms; Humans; Neoplasm Staging; Prognosis; Retrospective Studies
PubMed: 36004649
DOI: 10.4149/neo_2022_220525N557 -
Oral Surgery, Oral Medicine, Oral... Oct 2022Adrenocortical carcinoma (ACC) is an uncommon primary cancer in the adrenal gland. Its incidence of showing metastasis in the head and neck region is very rare. Herein,...
Adrenocortical carcinoma (ACC) is an uncommon primary cancer in the adrenal gland. Its incidence of showing metastasis in the head and neck region is very rare. Herein, we present a case of a 46-year-old man who presented with complaints of pain and numbness on the left side of the lower face for 4 months. Radiographic examination revealed an osteolytic lesion with an ill-defined border in the left body region of the mandible. Histopathologic examination revealed a tumor composed of sheets of oval to polygon-shaped tumor cells predominantly displaying abundant eosinophilic granular cytoplasm. These tumor cells showed features of a high degree of anaplasia. On immunohistochemical examination, tumor cells were focally positive for synaptophysin, inhibin, vimentin, pancytokeratin (pan-CK), cytokeratin (CK)5/6, CD68, and CK8/18 and immunonegative for CK7, chromogranin, melan-A, S100, SMA, and SATB2. The Ki-67 proliferation index was approximately 20%. To the best of our knowledge, this is the first case of metastatic oncocytic ACC to the oral cavity region.
Topics: Adrenal Cortex Neoplasms; Adrenocortical Carcinoma; Biomarkers, Tumor; Chromogranins; Humans; Inhibins; Keratins; Ki-67 Antigen; MART-1 Antigen; Male; Mandible; Middle Aged; Synaptophysin; Vimentin
PubMed: 35989231
DOI: 10.1016/j.oooo.2022.01.022 -
The American Journal of Surgical... Nov 2022Embryonal rhabdomyosarcoma of the uterine cervix (cERMS) is rare and frequently associated with DICER1 mutations. We report 94 tumors that arose in patients aged 7 to 59...
Embryonal rhabdomyosarcoma of the uterine cervix (cERMS) is rare and frequently associated with DICER1 mutations. We report 94 tumors that arose in patients aged 7 to 59 (median=23) years and presented with vaginal bleeding (52), protruding vaginal mass (17), cervical polyp (8), or expelled tumor fragments per vagina (5). Nine had DICER1 syndrome, 8 of whom had other syndromic manifestations including ovarian Sertoli-Leydig cell tumor (7), multinodular goiter (3), pleuropulmonary blastoma (2), pineoblastoma (1), and osteosarcoma (1). Syndromic patients were younger than nonsyndromic patients (16 vs. 24 y). Tumor size ranged from 2 to 24 (median=4.5) cm. Ninety-two tumors were polypoid, most being grape-like (77 of 92). They were characterized by aggregates of primitive cells, almost always exhibiting a cambium layer, within a variably myxoedematous stroma and were hypocellular (63), moderately cellular (22), or hypercellular (9). Entrapped glands, typically scant, were present in 84 tumors. Primitive hyperchromatic ovoid to spindled cells with minimal cytoplasm predominated but differentiated rhabdomyoblasts with abundant eosinophilic cytoplasm (having cross-striations in 30) were seen in 83 tumors; they were often sparse but predominated in three. Nine tumors showed areas of intersecting fascicles and 4 zones with densely cellular (solid) growth. Cartilage was present in 38. Anaplasia was seen in 15 tumors, as was necrosis. Mitotic activity ranged from 1 to 58/10 high-power fields (median=8). The varied microscopic features resulted in a spectrum of differential diagnostic considerations, mainly typical and cellular forms of fibroepithelial polyps, Mullerian adenosarcoma, and other sarcomas. Follow-up was available for 79 patients ranging from 6 to 492 (median=90) months. Treatment information was available in 62 and included polypectomy in 6 patients (2 also received chemotherapy), limited resection in 26 (14 also received chemotherapy), hysterectomy in 29 (15 with adjuvant chemotherapy), and biopsies only in 1 (with chemotherapy). Staging was possible in 56 tumors; according to the "uterine sarcoma" system (tumor size and extent) they were: stage I (10/56; could not be further subclassified as size not available), IA (22/56), IB (18/56), IIA (2/56), IIB 3/56), IIIC (1/56). According to the "adenosarcoma" system (depth of invasion and extent) they were: stage IA (26/56), IB (14/56), IC (10/56), IIA (2/56), IIB (3/56), IIIC (1/56). Eight patients had local recurrence following incomplete excision (10%). Eleven of 79 patients had extrauterine recurrences (14%) and 9 died of disease (11%). Older age was associated with extrauterine recurrence (median 44 vs. 22; P =0.002) and decreased disease-specific survival (median 44 vs. 22; P =0.02). For patients with tumors initially confined to the cervix, the adenosarcoma staging system was superior to the uterine sarcoma staging system for predicting survival ( P =0.02). Three patients with DICER1 syndrome who underwent fertility-preserving surgery developed a second primary cERMS 7, 7, and 12 years after their primary tumor. All 9 patients with DICER1 syndrome had tumors confined to the cervix and none died of disease. This study highlights the intriguing clinical aspects of cERMS including its long-known tendency to occur in the young but also more recently appreciated association with DICER1 syndrome. Establishing the diagnosis may still be difficult because of the hazard of sampling a neoplasm which in areas may appear remarkably bland and also because of its potential confusion with other neoplasms. This study indicates that this tumor has a good prognosis at this site and in selected cases a conservative surgical approach is a realistic consideration.
Topics: Adenosarcoma; Cervix Uteri; DEAD-box RNA Helicases; Diagnosis, Differential; Female; Humans; Neoplastic Syndromes, Hereditary; Prognosis; Rhabdomyosarcoma, Embryonal; Ribonuclease III; Uterine Cervical Neoplasms; Uterine Neoplasms
PubMed: 35941719
DOI: 10.1097/PAS.0000000000001933 -
Arab Journal of Urology 2022To evaluate whether p53, cyclin A and ki67 immunohistochemical (IHC) assay can be used as predictors for Wilms' tumor (WT) unfavorable outcomes.
OBJECTIVE
To evaluate whether p53, cyclin A and ki67 immunohistochemical (IHC) assay can be used as predictors for Wilms' tumor (WT) unfavorable outcomes.
METHODS
It is a non-concurrent cohort study including patients who underwent nephrectomy for WT from January 2000 to December 2015 in a tertiary referral center. Over a 5- year follow-up, unfavorable events, including relapse and cancer-specific mortality (CSM), were recorded. P53, cyclin A, and ki67 IHC assay were carried out for formalin-fixed paraffin-embedded WT samples.
RESULTS
After excluding those who did not meet the inclusion criteria, 75 patients were enrolled. Of the patients, 15/75 (20%) experienced WT relapse while 11/75 (14.6%) died of WT over five years. Unfavorable histology (UFH), including prominent blastemal components and anaplasia, was found in 15/75 (20%) children.Cyclin A immunopositivity was associated with high rates of relapse and CSM. P53 and ki67 positive IHC assay did not show any statistically significant association with unfavorable outcomes. Other risk factors e.g. advanced staging, UFH, extracapsular extension, tumor rupture, lymphadenopathy, and venous thrombosis were not associated with poor prognosis. However, the presence of residual tumors was accompanied by lower survival rates.
CONCLUSION
Cyclin A IHC assay can be used as a predictor of WT recurrence and CSM. Further studies with prospective patterns and a larger sample size are needed. WT: Wilms' tumor, UFH: unfavorable histology, IHC: immunohistochemical, PI: proliferation index, RFS: relapse-free survival, CSS: cancer-specific survival, FH: favorable histology, CSM: cancer-specific mortality, CDK: cyclin-dependent kinase.
PubMed: 35935912
DOI: 10.1080/2090598X.2022.2058240 -
Neurologia May 2023No formal indication currently exists for seizure prophylaxis in neurosurgical oncology patients. Neither have specific recommendations been made on the use of... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
No formal indication currently exists for seizure prophylaxis in neurosurgical oncology patients. Neither have specific recommendations been made on the use of antiepileptic drugs (AED) in seizure-free patients with meningiomas scheduled for surgery. AEDs are generally prescribed on a discretionary basis, taking into consideration a range of clinical and radiological risk factors. We present a systematic review and meta-analysis exploring the effectiveness of antiepileptic prophylaxis in patients with meningioma and no history of seizures.
METHODS
We performed a systematic review of the PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Embase, and clinicaltrials.gov databases. Of a total of 4368 studies initially identified, 12 were selected for extraction of data and qualitative analysis. Based on the clinical data presented, we were only able to include 6 studies in the meta-analysis. We performed heterogeneity studies, calculated a combined odds ratio, evaluated publication bias, and conducted a sensitivity analysis.
RESULTS
AED prophylaxis in patients with meningioma and no history of seizures did not significantly reduce the incidence of post-operative seizures in comparison to controls (Mantel-Haenszel combined odds ratio, random effects model: 1.26 [95% confidence interval, 0.60-2.78]; 2041 patients). However, we are unable to establish a robust recommendation against this treatment due to the lack of prospective studies, the presence of selection bias in the studies reviewed, the likelihood of underestimation of seizure frequency during follow-up, and the strong influence of one study on the overall effect.
CONCLUSIONS
Despite the limitations of this review, the results of the meta-analysis do not support the routine use of seizure prophylaxis in patients with meningioma and no history of seizures.
Topics: Humans; Meningioma; Phenytoin; Anticonvulsants; Incidence; Meningeal Neoplasms
PubMed: 35781420
DOI: 10.1016/j.nrleng.2022.03.002 -
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 -
Biomedicines Apr 2022This research aimed to investigate the interrelationship of carbohydrate metabolism parameters and immunohistochemical characteristics of glial tumors. Tumor tissue,...
This research aimed to investigate the interrelationship of carbohydrate metabolism parameters and immunohistochemical characteristics of glial tumors. Tumor tissue, peritumoral area, and adjacent noncancerous tissue fragments of 20 patients with gliomas of varying degrees of anaplasia were analyzed. The greatest differences in the carbohydrate metabolism compared to adjacent noncancerous tissues were identified in the tumor tissue: reduction in the levels of lactate and glycogen synthase kinase-3β. Significant differences with adjacent noncancerous tissues for the peritumoral zone were not found. The activity of the carbohydrate metabolism enzymes was different depending on the immunohistochemical glioma profile, especially from Ki 67 level. Bioinformatic analysis of the interactions of immunohistochemical markers of gliomas and carbohydrate metabolism enzymes using the databases of STRING, BioGrid, and Signor revealed the presence of biologically significant interactions with glycogen synthase kinase 3β, hexokinase, glucose-6-phosphate dehydrogenase, and transketolase. The established interconnection of glycolysis with methylation of the promoter of O-6-methylguanine-DNA-methyltransferase (MGMT) of gliomas can be used to increase chemotherapy efficiency.
PubMed: 35625744
DOI: 10.3390/biomedicines10051007 -
World Neurosurgery Aug 2022The prevalence of BRAFV600E mutations in pleomorphic xanthoastrocytoma (PXA) World Health Organization (WHO) Grade 2 and PXA WHO Grade 3 reported varies from 60% to 80%,... (Review)
Review
BACKGROUND
The prevalence of BRAFV600E mutations in pleomorphic xanthoastrocytoma (PXA) World Health Organization (WHO) Grade 2 and PXA WHO Grade 3 reported varies from 60% to 80%, yet the prognostic implications remain unclear.
METHODS
We reviewed the demographic and clinicoradiologic data of 20 PXAs WHO Grade 2 and 13 PXAs WHO Grade 3, operated between 2007 and 2020, to ascertain extent of excision, recurrence, progression-free survival (PFS), and overall survival (OS). PXAs WHO Grade 3 were defined by the presence of >5 mitoses/high-power field. PXAs WHO Grade 3 received adjuvant radiation therapy and chemotherapy whereas PXAs received radiation therapy if subtotally excised. All samples were analyzed for the presence of BRAFV600E mutation using DNA obtained from paraffin blocks using droplet-digital polymerase chain reaction.
RESULTS
The median patient age at diagnosis was 22 years with a male preponderance. BRAFV600E mutations were noted in 30% of tumors; 8 PXAs WHO Grade 2 and 2 PXAs WHO Grade 3. Recurrence occurred in 6 of 13 PXA WHO Grade 3 (55%) and 1 of 20 PXAs WHO Grade 2 (5%). At median follow-up of 45 months, the OS was 54 months and 33 months in the PXA WHO Grade 2 and PXA WHO Grade 3 groups, respectively (P = 0.02). OS and PFS did not differ between BRAF-mutated and BRAF-negative tumors.
CONCLUSIONS
BRAFV600E mutations are less frequent in our population than reported in the literature. The BRAF mutation does not significantly impact OS and PFS. PXAs WHO Grade 3 are a distinct clinical entity, associated with worse PFS and OS than PXAs WHO Grade 2.
Topics: Astrocytoma; Brain Neoplasms; Humans; Male; Mutation; Prevalence; Prognosis; Proto-Oncogene Proteins B-raf
PubMed: 35618235
DOI: 10.1016/j.wneu.2022.05.066 -
Biochemical and Biophysical Research... Jul 2022This study aimed to screen anaplasia-related genes that influence the progression of retinoblastoma (RB) and to identify immune cells associated with the poor prognosis.
OBJECTIVE
This study aimed to screen anaplasia-related genes that influence the progression of retinoblastoma (RB) and to identify immune cells associated with the poor prognosis.
METHODS
Differentially expressed genes (DEGs) between retina and RB samples were acquired from gene expression omnibus (GEO) database. Candidate hub genes were screened by taking intersections among the co-expressed genes, the hub nodes, and DEGs of the validation set. The hub genes were identified by receiver operating characteristic (ROC) and quantitative real-time PCR (qPCR). Immune infiltration levels of RB tissues were estimated using single-sample gene set enrichment analysis (ssGSEA). The functions of RB cells were detected by CCK8, EDU and flow cytometry assays.
RESULTS
665 DEGs involved in the genesis and progression of RB were acquired from GEO database. 29 candidate hub genes were screened by examining 43 co-expressed genes and 63 hub nodes. 9 hub genes (CHEK1, EXO1, FANCI, GTSE1, MELK, MKI67, NCAPH, PRC1, and UBE2T) strongly related to the anaplastic grades were validated by ROC curve analysis (AUC >0.8). Based on the ssGSEA scores, the immune infiltration levels of Th2 cells were positively associated with anaplastic grade. qPCR assay showed that 9 hub genes were upregulated in RB cells, and UBE2T expressed remarkably high. CCK 8, EDU, and flow cytometry assays revealed that UBE2T silencing inhibited the proliferation of RB cells and incited apoptosis.
CONCLUSIONS
The increased infiltration of Th2 cells and upregulated expression of 9 hub genes predict a poor prognosis of RB. UBE2T can be a therapeutic target for RB treatment.
Topics: Biomarkers; Cell Cycle Proteins; Computational Biology; Gene Regulatory Networks; Humans; Microtubule-Associated Proteins; Nuclear Proteins; Prognosis; Protein Serine-Threonine Kinases; Retinal Neoplasms; Retinoblastoma; Th2 Cells; Ubiquitin-Conjugating Enzymes
PubMed: 35594577
DOI: 10.1016/j.bbrc.2022.04.096 -
Journal of Hepatology Oct 2022Hepatoblastoma (HB) and hepatocellular carcinoma (HCC) are the predominant liver cancers in children, though their respective treatment options and associated outcomes...
BACKGROUND & AIMS
Hepatoblastoma (HB) and hepatocellular carcinoma (HCC) are the predominant liver cancers in children, though their respective treatment options and associated outcomes differ dramatically. Risk stratification using a combination of clinical, histological, and molecular parameters can improve treatment selection, but it is particularly challenging for tumors with mixed histological features, including those in the recently created hepatocellular neoplasm not otherwise specified (HCN NOS) provisional category. We aimed to perform the first molecular characterization of clinically annotated cases of HCN NOS.
METHODS
We tested whether these histological features are associated with genetic alterations, cancer gene dysregulation, and outcomes. Namely, we compared the molecular features of HCN NOS, including copy number alterations, mutations, and gene expression profiles, with those in other pediatric hepatocellular neoplasms, including HBs and HCCs, as well as HBs demonstrating focal atypia or pleomorphism (HB FPAs), and HBs diagnosed in older children (>8).
RESULTS
Molecular profiles of HCN NOS and HB FPAs revealed common underlying biological features that were previously observed in HCCs. Consequently, we designated these tumor types collectively as HBs with HCC features (HBCs). These tumors were associated with high mutation rates (∼3 somatic mutations/Mb) and were enriched with mutations and alterations in key cancer genes and pathways. In addition, recurrent large-scale chromosomal gains, including gains of chromosomal arms 2q (80%), 6p (70%), and 20p (70%), were observed. Overall, HBCs were associated with poor clinical outcomes.
CONCLUSIONS
Our study indicates that histological features seen in HBCs are associated with combined molecular features of HB and HCC, that HBCs are associated with poor outcomes irrespective of patient age, and that transplanted patients are more likely to have good outcomes than those treated with chemotherapy and surgery alone. These findings highlight the importance of molecular testing and early therapeutic intervention for aggressive childhood hepatocellular neoplasms.
LAY SUMMARY
We molecularly characterized a class of histologically aggressive childhood liver cancers and showed that these tumors are clinically aggressive and that their observed histological features are associated with underlying recurrent molecular features. We proposed a diagnostic algorithm to identify these cancers using a combination of histological and molecular features, and our analysis suggested that these cancers may benefit from specialized treatment strategies that may differ from treatment guidelines for other childhood liver cancers.
Topics: Carcinoma, Hepatocellular; Child; Chromosome Aberrations; Hepatoblastoma; Humans; Liver Neoplasms; Mutation; Young Adult
PubMed: 35577029
DOI: 10.1016/j.jhep.2022.04.035