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American Journal of Translational... 2023Adult granulosa cell tumor (AGCT) is a rare ovarian sex-cord malignancy notorious for late recurrences and metastases. The cytologic features of AGCT at the metastatic...
INTRODUCTION
Adult granulosa cell tumor (AGCT) is a rare ovarian sex-cord malignancy notorious for late recurrences and metastases. The cytologic features of AGCT at the metastatic sites have been documented sporadically. Hence, knowledge of the characteristic cytomorphologic features is essential for an accurate diagnosis and distinguishing it from its pathologic mimics, especially at the metastatic sites.
MATERIALS AND METHODS
This was a retrospective study conducted over six years. The cytopathology electronic database was searched for the fine needle aspirates (FNA) reported as metastatic AGCT. A detailed cytomorphologic assessment was done for multiple cytologic features, including overall cellularity, cellular arrangement of the tumor cells, cell size, cell shape, nuclear pleomorphism, nuclear grooving, chromatin pattern, nucleolar prominence, mitotic figures, amount and character of cytoplasm, and the extracellular background.
RESULTS
There were 6 cases reported as metastatic AGCT on aspiration cytology. The smears in all the cases were cellular, with tumor cells arranged in loose aggregates, three-dimensional clusters, perivascular papillary fronds, and scattered singly. The most consistent cytologic features included microfollicular arrangement of monomorphic tumor cells with round-oval nuclei, fine chromatin, longitudinal nuclear grooving, and scant cytoplasm. Typical and metachromatically stained extracellular hyaline material were noted sporadically. None of the smears showed anaplasia, prominent macronucleoli, atypical mitoses, or necrosis.
CONCLUSIONS
The current study not only outlines the distinct cytologic attributes of AGCTs across various metastatic locations but also highlights its prevalent cytologic mimics. Additionally, it outlines key clinicopathologic traits that can aid in distinguishing and precisely diagnosing these tumors through cytological analysis.
PubMed: 37854236
DOI: No ID Found -
Neuropathology : Official Journal of... Apr 2024We report a case of pediatric glioma with uncommon imaging, morphological, and genetic features. A one-year-old boy incidentally presented with a tumor in the fourth...
We report a case of pediatric glioma with uncommon imaging, morphological, and genetic features. A one-year-old boy incidentally presented with a tumor in the fourth ventricle. The tumor was completely resected surgically and investigated pathologically. The mostly circumscribed tumor had piloid features but primitive and anaplastic histology, such as increasing cellularity and mitosis. The Ki-67 staining index was 25% at the hotspot. KIAA1549::BRAF fusion and KIAA1549 partial deletions were detected by direct PCR, supported by Sanger sequencing. To the best of our knowledge, this is the first report of a glioma with both deletion of KIAA1549 p.P1771_P1899 and fusion of KIAA1549::BRAF. The tumor could not be classified using DNA methylome analysis. The present tumor fell into the category of pilocytic astrocytoma with histological features of anaplasia (aPA). Further studies are needed to establish pediatric aPA.
Topics: Male; Humans; Child; Infant; Brain Neoplasms; Anaplasia; Proto-Oncogene Proteins B-raf; Astrocytoma; Glioma
PubMed: 37779355
DOI: 10.1111/neup.12946 -
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%.
Topics: Humans; Carcinoma, Mucoepidermoid; Male; Female; Salivary Gland Neoplasms; Middle Aged; Retrospective Studies; Adult; Aged; Neoplasm Grading; Young Adult; Adolescent; Lymphatic Metastasis; Aged, 80 and over; Child; Predictive Value of Tests; Risk Factors; Time Factors; Neoplasm Staging
PubMed: 37694548
DOI: 10.1097/PAS.0000000000002120 -
Cancers Sep 2023In meningiomas, TERT promotor mutations are rare but qualify the diagnosis of anaplasia, directly impacting adjuvant therapy. Effective screening for patients at risk...
PURPOSE
In meningiomas, TERT promotor mutations are rare but qualify the diagnosis of anaplasia, directly impacting adjuvant therapy. Effective screening for patients at risk for promotor mutations could enable more targeted molecular analyses and improve diagnosis and treatment.
METHODS
Semiautomatic segmentation of intracranial grade 2/3 meningiomas was performed on preoperative magnetic resonance imaging. Discriminatory power to predict TERT promoter mutations was analyzed using a random forest algorithm with an increasing number of radiomic features. Two final models with five and eight features with both fixed and differing radiomics features were developed and adjusted to eliminate random effects and to avoid overfitting.
RESULTS
A total of 117 image sets including training ( = 94) and test data ( = 23) were analyzed. To eliminate random effects and demonstrate the robustness of our approach, data partitioning and subsequent model development and testing were repeated a total of 100 times (each time with repartitioned training and independent test data). The established five- and eight-feature models with both fixed and different radiomics features enabled the prediction of TERT with similar but excellent performance. The five-feature (different/fixed) model predicted TERT promotor mutation status with a mean AUC of 91.8%/94.3%, mean accuracy of 85.5%/88.9%, mean sensitivity of 88.6%/91.4%, mean specificity of 83.2%/87.0%, and a mean Cohen's Kappa of 71.0%/77.7%. The eight-feature (different/fixed) model predicted TERT promotor mutation status with a mean AUC of 92.7%/94.6%, mean accuracy of 87.3%/88.9%, mean sensitivity of 89.6%/90.6%, mean specificity of 85.5%/87.5%, and a mean Cohen's Kappa of 74.4%/77.6%. Of note, the addition of further features of up to = 8 only slightly increased the performance.
CONCLUSIONS
Radiomics-based machine learning enables prediction of TERT promotor mutation status in meningiomas with excellent discriminatory performance. Future analyses in larger cohorts should include grade 1 lesions as well as additional molecular alterations.
PubMed: 37686690
DOI: 10.3390/cancers15174415 -
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 -
Japanese Journal of Clinical Oncology Dec 2023Wilms tumor is the most common cancer of the kidney that occurs during childhood, and histologically, it mimics renal embryogenesis. With the development and improvement...
BACKGROUND
Wilms tumor is the most common cancer of the kidney that occurs during childhood, and histologically, it mimics renal embryogenesis. With the development and improvement of up-to-date treatment protocols, the survival rates of Wilms tumor have increased. However, metastases or local relapses are still observed in 15% of patients. The search for reliable biomarkers to identify at-risk patients is ongoing to predict the variability in treatment success. Currently, the evaluation of clinical, histopathological and genetic features are common diagnostic methods; however, epigenetic features can be examined with microRNA expression analyses and might allow us to comment on the behavior of the tumor and treatment response.
METHODS
In this study, we aimed to evaluate the relationship between microRNA-204 and microRNA-483-5p expression with clinicopathological data and the effect on Wilms tumor survival. For this purpose, the expression levels of RNU6B, microRNA-204 and microRNA-483-5p were evaluated in tumor and normal tissue by qreal time-polymerase chain reaction. We also investigated the relationship between microRNA expression levels with the clinicopathological and histological features of Wilms tumor.
RESULTS AND CONCLUSION
The results of our study indicate that the relative expression levels of microRNA-204 in Wilms tumor tissues were significantly lower than that in adjacent normal tissues. By contrast, tumor tissue had a higher microRNA-483-5p expression than the corresponding normal tissues. A statistically significant difference between microRNA-204 expression level with age and the presence of anaplasia was observed. The upregulation of microRNA-483-5p was found to have a significant correlation with patients after preoperative chemotherapy and complete tumor necrosis. Taken together, our data suggest that microRNA-204 could play a critical role as a tumor suppressor, whereas microRNA-483-5p acts as an oncogene in Wilms tumor progression. More importantly, microRNA-204 might be a novel predictive biomarker for anaplastic histology and could be useful for developing therapeutic interventions targeting this marker.
Topics: Humans; Neoplasm Recurrence, Local; MicroRNAs; Wilms Tumor; Up-Regulation; Kidney Neoplasms; Gene Expression Regulation, Neoplastic; Cell Proliferation
PubMed: 37647636
DOI: 10.1093/jjco/hyad113 -
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 -
American Journal of Clinical Pathology Dec 2023Multinucleated tumor cells (MTCs) in clear cell renal cell carcinoma (ccRCC) are not well understood.
OBJECTIVES
Multinucleated tumor cells (MTCs) in clear cell renal cell carcinoma (ccRCC) are not well understood.
METHODS
Our study included ccRCC cases in a single institution between 2010 and 2019. We classified MTC as MTC with degenerative atypia (MTCD), MTC with no anaplasia (MTCNA), and MTC with anaplasia (MTCA). Clinicopathologic characteristics and outcomes were compared between MTC groups.
RESULTS
In all, 92 of 256 people (36%) with ccRCC had MTC. People with ccRCC with MTCD and those with ccRCC but no MTC had similar clinicopathologic characteristics and outcomes. Also, MTCNA and MTCA were associated with larger tumor size, advanced pathologic tumor stage, higher World Health Organization/International Society of Urologic Pathologists nuclear grade, and higher metastatic potential (P < .001 for each parameter). Overall, MTCA was associated with an increased rate of recurrence (P = .004), higher metastatic potential (P < .001), and shorter time to metastasis (P = .033), regardless of tumor stage. Univariate Cox regression revealed MTCNA as a significant predictor of metastasis at 5 years (hazard ratio [HR], 4.171; 95% CI, 1.934-8.998); moreover, MTCA was a significant predictor of recurrence (HR, 5.723; 95% CI, 2.495-13.124), metastasis (HR, 12.024; 5.966-24.232), and death (HR, 5.661; 95% CI, 2.688-11.924) at 5 years.
CONCLUSIONS
Although MTCD may not be relevant in tumor grading, MTCNA and MTCA are associated with adverse outcomes.
Topics: Humans; Carcinoma, Renal Cell; Kidney Neoplasms; Neoplasm Grading; World Health Organization; Prognosis
PubMed: 37555895
DOI: 10.1093/ajcp/aqad096 -
Journal of the Egyptian National Cancer... Jul 2023Immunohistochemical expression of P53 protein is so closely related to status of mutation of P53 gene which is tightly linked with pathogenesis of nephroblastoma or...
OBJECTIVE
Immunohistochemical expression of P53 protein is so closely related to status of mutation of P53 gene which is tightly linked with pathogenesis of nephroblastoma or Wilms tumor. This study aims to determine the immunohistochemical expression of P53 protein and its predictors in formalin-fixed paraffin-embedded tissue blocks of patients with nephroblastoma.
MATERIALS AND METHODS
A series of 83 histologically diagnosed cases of nephroblastoma from formalin-fixed paraffin-embedded tissue blocks archived at the Department of Pathology, Makerere University, in Kampala, Uganda, were analyzed. Monoclonal anti-p53 antibody (DO-7, DAKO) was used to assess the expression of P53 protein expression. Multivariable logistic regression analysis was performed to determine the predictors of P53 protein immunohistochemical expression, and statistical significance was considered when p-value was less than 0.05.
RESULTS
Most (42.2%, n = 35) of the cases were in advanced tumor stages (III-V), and almost one-quarter (21.7%, n = 18) of the cases were in high-risk group. The immunohistochemical expression of P53 protein was (8.4%, n = 7), and there were more (83.3%, n = 5) positive anaplastic cases for P53 protein compared with (2.6%, n = 2) of P53 expression for non-anaplastic cases. High risk (AOR = 3.42, 95% CI = 7.91-12.55, p = 0.037) and anaplasia (AOR = 1.41, 95% CI = 13.85-4.46, p = 0.001) were potential predictors of immunohistochemical expression of P53 protein.
CONCLUSION
Most of patients with nephroblastoma in resources-limited settings are diagnosed with advanced clinical stages. Association of P53 protein with anaplasia found in this study indicates the possibility of having novel target therapy for treatment of patients with anaplastic form of nephroblastoma with a focus of identifying molecules that lead to its suppression in such subpopulations of patients with nephroblastoma.
Topics: Humans; Anaplasia; Formaldehyde; Immunohistochemistry; Kidney Neoplasms; Prognosis; Tumor Suppressor Protein p53; Uganda; Wilms Tumor
PubMed: 37518096
DOI: 10.1186/s43046-023-00183-2