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Cancers Mar 2022Increased mRNA is associated with disease relapse in favorable histology Wilms tumor (WT). This study sought to understand the mechanism of increased expression by...
Increased mRNA is associated with disease relapse in favorable histology Wilms tumor (WT). This study sought to understand the mechanism of increased expression by determining the association between and WT1 and N-MYC, two proteins important in Wilms tumor pathogenesis that have been shown to regulate expression. Three out of 45 (6.7%) WTs and the corresponding patient-derived xenografts harbored canonical gain-of-function mutations in the promoter. This study identified near ubiquitous hypermethylation of the promoter region in WT compared to normal kidney. WTs with biallelic inactivating mutations in (7/45, 15.6%) were found to have lower expression by RNA-seq and qRT-PCR and lower telomerase activity determined by the telomerase repeat amplification protocol. Anaplastic histology and increased percentage of blastema were positively correlated with higher expression and telomerase activity. In vitro shRNA knockdown of resulted in decreased expression of , reduced colony formation, and decreased proliferation of WiT49, an anaplastic WT cell line with wild-type . CRISPR-Cas9-mediated knockout of resulted in decreased expression of telomere-related gene pathways. However, an inducible -knockout mouse model showed no relationship between knockout and expression in normal murine nephrogenesis, suggesting that WT1 and TERT are coupled in transformed cells but not in normal kidney tissues. N-MYC overexpression resulted in increased promoter activity and transcription. Thus, multiple mechanisms of activation are involved in WT and are associated with anaplastic histology and increased blastema. This study is novel because it identifies potential mechanisms of activation in Wilms tumor that could be of therapeutic interests.
PubMed: 35406427
DOI: 10.3390/cancers14071655 -
Cancer Jul 2022An objective of the Children's Oncology Group AREN0534 Study was to improve the survival of patients with bilateral Wilms tumors (BWT) by using preoperative chemotherapy...
BACKGROUND
An objective of the Children's Oncology Group AREN0534 Study was to improve the survival of patients with bilateral Wilms tumors (BWT) by using preoperative chemotherapy of limited duration and tailoring postoperative therapy based on histopathologic response. The authors report outcomes based on postoperative histopathologic responses.
METHODS
Patients with BWT received treatment with vincristine, dactinomycin, and doxorubicin for 6 or 12 weeks followed by surgery. Postoperative therapy was prescribed based on the highest risk tumor according to the International Society of Pediatric Oncology classification and the Children's Oncology Group staging system.
RESULTS
Analyses were performed on data from 180 evaluable children. The 4-year event-free survival (EFS) and overall survival (OS) rates were 81% (95% CI, 74%-87%) and 95% (95% CI, 91%-99%), respectively. Seven patients who had completely necrotic tumors had a 4-year EFS rate of 100%. Of 118 patients who had tumors with intermediate-risk histopathology, the 4-year EFS and OS rates were 82% (95% CI, 74%-90%) and 97% (95% CI, 94%-100%), respectively. Fourteen patients who had blastemal-type tumors had 4-year EFS and OS rates of 79% (95% CI, 56%-100%) and 93% (95% CI, 79%-100%), respectively. Eighteen patients who had diffuse anaplasia had 4-year EFS and OS rates of 61% (95% CI, 35%-88%) and 72% (95% CI, 47%-97%), respectively; and the 4-year EFS and OS rates of 7 patients who had focal anaplasia were 71% (95% CI, 38%-100%) and 100%, respectively. There was no difference in the outcomes of patients who had different histopathologic subtypes within the intermediate-risk group (P = .54).
CONCLUSIONS
A risk-adapted treatment approach for BWT results in excellent outcomes. This approach was not successful in improving the outcome of patients who had diffuse anaplasia.
Topics: Anaplasia; Antineoplastic Combined Chemotherapy Protocols; Child; Humans; Infant; Kidney Neoplasms; Neoplasm Staging; Nephrectomy; Prospective Studies; Vincristine; Wilms Tumor
PubMed: 35383900
DOI: 10.1002/cncr.34219 -
Journal of Cancer Research and... 2022Pediatric renal tumours are the second most common solid tumours in children. The most common in this group is Wilms tumour with mesoblastic nephroma being the 2 most... (Observational Study)
Observational Study
CONTEXT OR BACKGROUND
Pediatric renal tumours are the second most common solid tumours in children. The most common in this group is Wilms tumour with mesoblastic nephroma being the 2 most common tumour in children, younger than 3 months.
AIMS AND OBJECTIVES
The present study was conducted to study the epidemiological occurrence of pediatric renal tumours at a tertiary care hospital and to study the diagnostic efficacy of WT1 immunostaining in distinguishing Wilms tumour from other types of renal tumours.
MATERIALS AND METHODS
It was a single institution-based prospective and observational study conducted for 2 years (from October 2013 to September 2015) in the department of pathology in our hospital. A total of 50 cases were enrolled in this study all were below 15 years of age.
RESULTS
Nephroblastoma or Wilms tumour was found to be the most common type, occurring in 66% cases. Fourteen out of 33 cases of Wilms tumour showed triphasic components (blastemal, epithelial, and stromal) with Blastemal type Wilms being the second most common (11 cases). WT1 immunostaining was positive in 93.9% cases of nephroblastoma. The highest amount of nuclear positivity noted in blastemal cells followed by epithelial cells. Rhabdomyoblastic differentiation and regressive variant showed nonspecific cytoplasmic staining. Cystic partially differentiated nephroblastoma and diffuse anaplasia type Wilms tumour showed nuclear staining in blastemal cells.
CONCLUSION
The expression of WT1 immunostain was found to be diagnostically significant in differentiating Wilms tumour from other renal tumours.
Topics: Child; Humans; Kidney; Kidney Neoplasms; Prospective Studies; Tertiary Care Centers; WT1 Proteins; Wilms Tumor
PubMed: 35381785
DOI: 10.4103/jcrt.JCRT_436_19 -
Pakistan Journal of Medical Sciences Jan 2022The assessment of histopathological risk factors (HRFs) in retinoblastoma in upfront enucleated eyes is important in deciding treatment protocols. Limited data is...
BACKGROUND & OBJECTIVES
The assessment of histopathological risk factors (HRFs) in retinoblastoma in upfront enucleated eyes is important in deciding treatment protocols. Limited data is available from the developing countries as very few studies were conducted on retinoblastoma. The study aims to report this data from Pakistan.
METHODS
This cross-sectional study included treatment naïve retinoblastoma patients who underwent upfront enucleation between 2017 to 2021. Various tumor characteristics i.e. laterality, size, histologic grade, anaplasia grade, growth pattern, extent and length of optic nerve invasion, pathologic staging, tumor involvement of ocular structures were assessed. High-risk factors such as involvement of anterior chamber, choroidal, scleral, extrascleral, and optic nerve were also noted.
RESULTS
A total number of 54 patients were enrolled, out of which 53.7% were females while remaining were males. Median age at presentation was 24 months. Unilateral tumor was seen in 92.6% cases. Most frequent histologic grade was G2 (64.7%) and moderate anaplasia was observed in 59.2% cases. Vitreous involvement was seen in (86.5%). Pathologic staging of most of the tumors was pT1 (39.2%). Assessment of high-risk factors revealed that optic nerve involvement (35.1%) was the most common finding with retrolaminar tumor invasion seen in 75% cases. Choroidal invasion (≤3mm) was seen in 55.6% of patients. Limited involvement of anterior chamber (3.8%), sclera (7.4%), and extrascleral (3.8%) tissue was also observed.
CONCLUSION
The presence of high risk histopathological factors in enucleated eyes diagnosed with retinoblastoma are known to have a profound impact on the risk stratification as well as decision of future treatment plan.
PubMed: 35310794
DOI: 10.12669/pjms.38.ICON-2022.5787 -
Brain Sciences Feb 2022p27 and p57 are tumor suppressors that are dysregulated in many cancers. We investigated the immunohistochemical expression of p27 and p57 in ependymoma, with a...
p27 and p57 are tumor suppressors that are dysregulated in many cancers. We investigated the immunohistochemical expression of p27 and p57 in ependymoma, with a secondary emphasis on cyclin D1, nestin, and Ki-67. Sixty-five patients diagnosed with ependymoma were included. Clinical and tumoral data were retrieved, and the expression of p27, p57, cyclin D1, nestin, and Ki-67 was measured. Pearson's test was used to measure associations and the Kaplan-Meier method was used for survival analysis. p27 underexpression was significantly associated with pseudopalisading necrosis in tumors with foci of necrosis ( = 0.004). Cyclin D1 overexpression was associated with intracranial ( = 0.044), recurrent ( = 0.022) and grade 3 tumors ( = 0.016); nestin overexpression was associated with supratentorial ( = 0.025), mitotically active ( < 0.001), and grade 3 tumors ( = 0.004); Ki-67 overexpression was associated with supratentorial ( = 0.044) and grade 3 tumors ( < 0.001) and the 3 main features of anaplasia. None of the markers were intercorrelated or predictive of overall survival. In conclusion, p27 underexpression in tumors with foci of necrosis signals a pseudopalisading pattern. Cyclin D1, nestin, and Ki-67 are useful markers in ependymoma, but evidence-based cutoff values are required to standardize this interpretation.
PubMed: 35204045
DOI: 10.3390/brainsci12020282 -
Cancer Apr 2022Since the International Society of Paediatric Oncology Wilms' Tumour 2001 (SIOP-WT-2001) study, focal anaplastic Wilms tumors (FAWTs) have been treated as...
BACKGROUND
Since the International Society of Paediatric Oncology Wilms' Tumour 2001 (SIOP-WT-2001) study, focal anaplastic Wilms tumors (FAWTs) have been treated as intermediate-risk Wilms tumors (WTs), and diffuse anaplastic Wilms tumors (DAWTs) have been treated as high-risk tumors.
METHODS
The authors performed a retrospective analysis of preoperatively treated patients with FAWT or DAWT recruited in 2 consecutive UK Children's Cancer and Leukaemia Group WT studies.
RESULTS
One hundred twenty-one of 1237 patients (10%) had an anaplastic WT confirmed by central pathology review (CPR): 93 (77%) had DAWT, and 28 (23%) had FAWT. The 4-year event-free survival (EFS) was 51% (95% confidence interval [CI], 41%-63%) for DAWT, 88% (95% CI, 76%-100%) for FAWT, and 84% (95% CI, 82%-87%) for intermediate-risk nonanaplastic Wilms tumor (IR-non-AWT). Overall survival (OS) was 58% (95% CI, 48%-70%) for DAWT, 95% (95% CI, 86%-100%) for FAWT, and 95% (95% CI, 93%-96%) for IR-non-AWT. In a multivariate analysis, the presence of DAWT was a significant prognostic factor for both EFS and OS in stages II, III, and IV. In a multivariate analysis of unilateral DAWT, stages III and IV remained the only significant prognostic factors for both EFS and OS. In 28% of the cases, there were discrepancies affecting the recognition of anaplasia, classification (DAWT vs FAWT), or the local pathologic stage.
CONCLUSIONS
Preoperatively treated patients with FAWT had excellent outcomes in comparison with those with identically treated IR-non-AWT, whereas patients with DAWT showed significantly worse outcomes. All patients with stage I disease had comparable good outcomes, regardless of the presence/absence of anaplasia. In contrast, the presence of DAWT was associated with significantly worse outcomes for patients with stage II to V disease. Finally, significant diagnostic discrepancies emphasize the value of CPR.
LAY SUMMARY
Anaplasia is an unfavorable feature in Wilms tumor (WT), and it is classified as focal (focal anaplastic Wilms tumor [FAWT]) or diffuse (diffuse anaplastic Wilms tumor [DAWT]). This study reports the outcomes of patients with FAWT and DAWT who were, for the first time, treated differently. Patients with FAWT received less intensive treatment, and their outcomes were comparable to the outcomes of patients with identically treated nonanaplastic WT. Patients with stage I DAWT also had good outcomes when they were treated without radiotherapy, whereas patients with stage II to V DAWT had poor outcomes despite more intensive treatment.
Topics: Child; Humans; Infant; Kidney Neoplasms; Neoplasm Staging; Prognosis; Retrospective Studies; United Kingdom; Wilms Tumor
PubMed: 35119702
DOI: 10.1002/cncr.34107 -
Veterinary and Comparative Oncology Jun 2022The human grading system is currently applied to canine meningioma, although it has not been validated in dogs. The present study focused on standardising the human...
The human grading system is currently applied to canine meningioma, although it has not been validated in dogs. The present study focused on standardising the human grading system applied to canine meningioma. Four veterinary neuropathologists graded 186 canine meningiomas as follows: Grade I tumour, with <4 mitoses/2.37 mm ; Grade II tumour, with ≥4 mitoses/2.37 mm , brain invasion or at least three of the following criteria: sheeting architecture, hypercellularity, small cells, macronucleoli, necrosis; Grade III tumour, with ≥20 mitoses/2.37 mm or anaplasia. Slides with grading disagreement were reviewed to define a consensus diagnosis and to assess reproducible criteria. Concordance between histologic grade and the consensus diagnosis, as well as intra- and inter-observer agreements for each criterion, were statistically analysed. Concordance between histologic grade and consensus diagnosis ranged from 59% to 100%, with lower concordance for Grade I and II tumours. The lowest inter-observer agreement was recorded for macronucleoli, small cells, hypercellularity and sheeting architecture. Tumour invasion and necrosis displayed fair agreement, while moderate agreement was reached for mitotic grade and anaplasia. The following recommendations were issued to improve the reproducibility of canine meningioma grading: (1) Assess mitotic grade in consecutive HPFs within the most mitotically active area; (2) Define invasion as neoplastic protrusions within central nervous tissue without pial lining; (3) Report spontaneous necrosis; (4) Report prominent nucleoli when visible at ×100; (5) Report pattern loss when visible at ×100 in >50% of the tumour; (6) Report necrosis, small cells, hypercellularity and macronucleoli, even when focal; (7) Report anaplasia if multifocal.
Topics: Anaplasia; Animals; Dog Diseases; Dogs; Humans; Meningeal Neoplasms; Meningioma; Necrosis; Neoplasm Grading; Observer Variation; Reproducibility of Results
PubMed: 35066998
DOI: 10.1111/vco.12802 -
The American Journal of Surgical... Jul 2022Acinic cell carcinoma (AciCC) is traditionally considered as a low-grade salivary gland carcinoma. However, a subset demonstrates high-grade features with a higher...
Acinic cell carcinoma (AciCC) is traditionally considered as a low-grade salivary gland carcinoma. However, a subset demonstrates high-grade features with a higher mortality rate and distant metastasis. In this large retrospective study of 117 cases, we aimed to establish a histologic grading scheme for AciCC. Adverse independent prognostic factors identified on the multivariate analysis included older age, tumor necrosis, nuclear anaplasia, lymphovascular invasion, absence of tumor-associated lymphoid stroma, and high American Joint Committee on Cancer (AJCC) pT and pN stages. A 3-tiered grading scheme using 4 pathologic parameters (mitotic index, necrosis, tumor border, and fibrosis at the frankly invasive front) was subsequently applied. Compared with low/intermediate-grade, high-grade AciCC defined as a mitotic index ≥5/10 HPFs and/or necrosis was an independently adverse prognostic factor. The 5-year overall survival was 50% in high-grade AciCCs, and 100% in low-grade or intermediate-grade AciCCs. Compared with low-grade or intermediate-grade AciCC, high-grade tumors were associated with older age, larger tumor size, focal rather than diffuse zymogen granules, solid architecture, infiltrative tumor border, fibrosis at the frankly invasive front, lymphovascular invasion, perineural invasion, positive margin, high pT, and pN stages. NR4A3 was a highly sensitive and specific immunohistochemical stain for diagnosing AciCC with a sensitivity and specificity of 96% and 93%, respectively. In conclusion, although we proposed a 2-tiered grading system for AciCC with high-grade tumors defined by a mitotic count ≥5/10 HPFs and/or necrosis, more studies are needed to assess the prognostic value of intermediate grade. NR4A3 immunohistochemical stain is a useful diagnostic marker for AciCC.
Topics: Carcinoma; Carcinoma, Acinar Cell; DNA-Binding Proteins; Fibrosis; Humans; Immunohistochemistry; Necrosis; Receptors, Steroid; Receptors, Thyroid Hormone; Retrospective Studies
PubMed: 35034042
DOI: 10.1097/PAS.0000000000001867 -
Frontiers in Medicine 2021Ovarian mucinous cystic tumors may be associated with various types of mural nodules, which can be classified as benign or malignant (anaplastic carcinoma, sarcoma,...
Ovarian mucinous cystic tumors may be associated with various types of mural nodules, which can be classified as benign or malignant (anaplastic carcinoma, sarcoma, carcinosarcoma). However, anaplastic malignant nodules have rarely been reported. Here, we present a case of a 35-year-old woman who presented with abdominal discomfort. Ultrasonography showed a large cystic mass in the pelvic and abdominal cavities measuring 337 × 242 mm. Abdominal computed tomography revealed upper anterior and posterior uterine pelvic cystic lesions based on multiple nodule partition walls and classes. During hospitalization, the patient underwent exploratory laparotomy, which revealed a poorly differentiated ovarian malignant tumor, and subsequent surgical excision was performed. The pathological analysis of the surgical samples of the right ovary revealed a mucinous ovarian tumor, while the mural nodules were classified as anaplastic carcinoma. After surgery, the patient started receiving chemotherapy. Unfortunately, the patient died 6 months later. Mucinous tumor occurring with an anaplastic carcinoma is rare, and the current diagnostic methods are not sufficient in providing an early and accurate diagnosis. Most patients are already in the advanced stage upon diagnosis and combined with poorly differentiated pathological features, the prognosis is extremely poor. Clinicians need to improve the clinical evaluation before surgery and conduct preoperative preparation and communication to improve the prognosis of patients as much as possible.
PubMed: 34970558
DOI: 10.3389/fmed.2021.753904 -
JAMA Ophthalmology Jan 2022High-risk histopathologic features of retinoblastoma are useful to assess the risk of systemic metastasis. In this era of globe salvage treatments for retinoblastoma,...
IMPORTANCE
High-risk histopathologic features of retinoblastoma are useful to assess the risk of systemic metastasis. In this era of globe salvage treatments for retinoblastoma, the definition of high-risk retinoblastoma is evolving.
OBJECTIVE
To evaluate variations in the definition of high-risk histopathologic features for metastasis of retinoblastoma in different ocular oncology practices around the world.
DESIGN, SETTING, AND PARTICIPANTS
An electronic web-based, nonvalidated 10-question survey was sent in December 2020 to 52 oncologists and pathologists treating retinoblastoma at referral retinoblastoma centers.
INTERVENTION
Anonymized survey about the definition of high-risk histopathologic features for metastasis of retinoblastoma.
MAIN OUTCOMES AND MEASURES
High-risk histopathologic features that determine further treatment with adjuvant systemic chemotherapy to prevent metastasis.
RESULTS
Among the 52 survey recipients, the results are based on the responses from 27 individuals (52%) from 24 different retinoblastoma practices across 16 countries in 6 continents. The following were considered to be high-risk features: postlaminar optic nerve infiltration (27 [100%]), involvement of optic nerve transection (27 [100%]), extrascleral tissue infiltration (27 [100%]), massive (≥3 mm) choroidal invasion (25 [93%]), microscopic scleral infiltration (23 [85%]), ciliary body infiltration (20 [74%]), trabecular meshwork invasion (18 [67%]), iris infiltration (17 [63%]), anterior chamber seeds (14 [52%]), laminar optic nerve infiltration (13 [48%]), combination of prelaminar and laminar optic nerve infiltration and minor choroidal invasion (11 [41%]), minor (<3 mm) choroidal invasion (5 [19%]), and prelaminar optic nerve infiltration (2 [7%]). The other histopathologic features considered high risk included Schlemm canal invasion (4 [15%]) and severe anaplasia (1 [4%]). Four respondents (15%) said that the presence of more than 1 high-risk feature, especially a combination of massive peripapillary choroidal invasion and postlaminar optic nerve infiltration, should be considered very high risk for metastasis.
CONCLUSIONS AND RELEVANCE
Responses to this nonvalidated survey conducted in 2020-2021 showed little uniformity in the definition of high-risk retinoblastoma. Postlaminar optic nerve infiltration, involvement of optic nerve transection, and extrascleral tumor extension were the only features uniformly considered as high risk for metastasis across all oncology practices. These findings suggest that the relevance about their value in the current scenario with advanced disease being treated conservatively needs further evaluation; there is also a need to arrive at consensus definitions and conduct prospective multicenter studies to understand their relevance.
Topics: Eye Enucleation; Humans; Infant; Neoplasm Invasiveness; Optic Nerve Injuries; Prospective Studies; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Risk Factors; Surveys and Questionnaires
PubMed: 34762098
DOI: 10.1001/jamaophthalmol.2021.4732