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Journal of Neurosurgery. Case Lessons Mar 2022Primary intramedullary spinal cord (IMSC) pilocytic astrocytoma (PA) with anaplasia is extremely rare.
BACKGROUND
Primary intramedullary spinal cord (IMSC) pilocytic astrocytoma (PA) with anaplasia is extremely rare.
OBSERVATIONS
A 50-year-old man presented to our hospital with numbness of the left posterior rib region, back, and bilateral lower limbs. Contrast-enhanced T1-weighted magnetic resonance imaging (MRI) revealed an intramedullary lesion at T2-T3 with no contrast enhancement. The patient opted for conservative treatment. Eighteen months after the first consultation, the patient presented with slowly progressive numbness of the bilateral upper limbs, paraparesis, and dysuria, with rapid deterioration over the following 3 months. T1- and T2-weighted MRI revealed expansion of the intramedullary lesion, which extended from C7 to T5, and syringomyelia at C5-C6. Contrast-enhanced T1-weighted MRI revealed an enhancing intramedullary lesion at C7-T5. Open biopsy and C5-T5 laminectomy were performed for diagnosis and decompression. PA with anaplasia was diagnosed based on pathological and immunohistochemical findings. The patient received postoperative radiotherapy and chemotherapy.
LESSONS
Rapidly progressive IMSC PA with a change in contrast enhancement is extremely rare in adults. PA may undergo a spontaneous malignant transformation during its natural clinical course. In this case, the change in contrast enhancement may have been associated with the malignant transformation of the PA.
PubMed: 36273864
DOI: 10.3171/CASE21702 -
Brain Pathology (Zurich, Switzerland) Jan 2019Myxopapillary ependymomas (MPE) are considered benign (World Health Organization (WHO) grade I) neoplasms with favorable prognosis. However, malignant behavior occurs in...
Myxopapillary ependymomas (MPE) are considered benign (World Health Organization (WHO) grade I) neoplasms with favorable prognosis. However, malignant behavior occurs in a small subset. To our knowledge, only five anaplastic MPEs have been reported without consensus on diagnostic criteria. We retrieved 14 anaplastic MPEs from the pathology archives of six institutions. Each tumor included at least two of the following features: ≥5 mitoses per 10 high power fields, Ki-67 labeling index (LI) ≥10%, microvascular proliferation (MVP) and spontaneous necrosis. These features were typically encountered in the foci of hypercellularity and reduced mucin. There were eight male and six female patients (age range 6-57 years, median = 16.5). Ten tumors displayed anaplasia at initial resection, and 4 were anaplastic at a second surgery for recurrence (ranging from 9 months to 14 years following initial resection). The Ki-67 LI ranged between 8% and 40% in the anaplastic foci and <3% in the foci of classic MPE. There was documented cerebrospinal fluid (CSF) dissemination in seven cases, recurrence following an anaplastic diagnosis in three cases and bone or soft tissue invasion in two cases. One patient suffered lung metastases. Two cases evaluated by targeted next-generation sequencing and one evaluated by fluorescence in situ hybridization (FISH) showed nonspecific chromosomal gains. We conclude that although rare, anaplastic MPE occurs in both pediatric and adult patients, similar to other ependymomas. At a minimum, closer follow-up is recommended, given the concern for aggressive biologic potential. Further study is needed to determine WHO grading criteria and genetic indicators of tumor progression.
Topics: Adolescent; Adult; Antigens, Nuclear; Child; Ependymoma; Female; Humans; In Situ Hybridization, Fluorescence; Ki-67 Antigen; Male; Middle Aged; Neoplasm Recurrence, Local; Spinal Cord Neoplasms
PubMed: 30417460
DOI: 10.1111/bpa.12673 -
Modern Pathology : An Official Journal... Jan 2020DICER1 syndrome is a hereditary cancer predisposition syndrome caused by deleterious germline DICER1 mutations. Characteristic "hotspot" somatic mutations of DICER1 have...
DICER1 syndrome is a hereditary cancer predisposition syndrome caused by deleterious germline DICER1 mutations. Characteristic "hotspot" somatic mutations of DICER1 have been identified in DICER1-associated tumors. With the exception of genitourinary embryonal rhabdomyosarcoma and anaplastic sarcoma of the kidney, sarcomas are rarely reported in DICER1 syndrome. Herein, we report the clinical, histopathologic, and molecular findings of a germline DICER1-associated ovarian sarcoma in a 5-year-old female, a somatic DICER1-associated metastatic peritoneal sarcoma in a 16-year-old female, and a somatic DICER1-associated primary intracranial sarcoma in a 4-year-old male. A comprehensive review of the literature, including 83 DICER1-associated sarcomas, illustrates an unequivocal histologic pattern mimicking pleuropulmonary blastoma, regardless of the site of origin. The features include undifferentiated small round blue cells, poorly differentiated spindle cells, and large bizarre pleomorphic cells (anaplasia), often with rhabdomyoblastic and/or chondroid differentiation, and rare bone/osteoid formation. This unique heterogeneous histologic pattern should raise suspicion for pathogenic DICER1 mutation(s) warranting a detailed review of the family history and DICER1 mutation analysis. In addition to expanding the phenotypic spectrum of DICER1-associated conditions, identification of pathogenic DICER1 variants facilitates optimized genetic counseling, caregiver education and judicious imaging-based surveillance.
Topics: Adolescent; Brain Neoplasms; Child, Preschool; DEAD-box RNA Helicases; Female; Genetic Predisposition to Disease; Humans; Male; Mutation; Ovarian Neoplasms; Peritoneal Neoplasms; Ribonuclease III; Sarcoma
PubMed: 31537896
DOI: 10.1038/s41379-019-0366-x -
Frontiers in Pediatrics 2020Wilms tumor (WT) is the most frequently diagnosed malignant renal tumor in children. With current treatments, ~90% of children diagnosed with WT survive and generally...
Wilms tumor (WT) is the most frequently diagnosed malignant renal tumor in children. With current treatments, ~90% of children diagnosed with WT survive and generally present with tumors characterized by favorable histology (FHWT), whereas prognosis is poor for the remaining 10% of cases where the tumors are characterized by cellular diffuse anaplasia (DAWT). Relatively few studies have investigated microRNA-related epigenetic regulation and its relationship with altered gene expression in WT. Here, we aim to identify microRNAs differentially expressed in WT and describe their expression in terms of cellular anaplasia, metastasis, and association with the main genetic alterations in WT to identify potential prognostic biomarkers. Expression profiling using TaqMan low-density array was performed in a discovery cohort consisting of four DAWT and eight FHWT samples. Relative quantification resulted in the identification of 109 (48.7%) microRNAs differentially expressed in both WT types. Of these, miR-10a-5p, miR-29a-3p, miR-181a-5p, miR-200b-3p, and miR-218-5p were selected and tested by RT-qPCR on a validation cohort of 53 patient samples. MiR-29a and miR-218 showed significant differences in FHWT with low ( = 0.0018) and high ( = 0.0131) expression, respectively. To discriminate between miRNA expression FHWTs and healthy controls, the receiver operating characteristic (ROC) curves were obtained; miR-29a AUC was 0.7843. Furthermore, low expression levels of miR-29a and miR-200b ( = 0.0027 and = 0.0248) were observed in metastatic tumors. ROC curves for miR-29a discriminated metastatic patients (AUC = 0.8529) and miR-200b (AUC = 0.7757). To confirm the differences between cases with poor prognosis, we performed hybridization for three microRNAs in five DAWT and 17 FHWT samples, and only significant differences between adjacent tissues and FHWT tumors were found for miR-181a, miR-200b, and miR-218, in both total pixels and nuclear analyses. Analysis of copy number variation in genes showed that the most prevalent alterations were (47%), (21%), 1q (36%) gain, 1p36 (16%), and deletion/1q duplicate (26%). The five microRNAs evaluated are involved in the Hippo signaling pathway and participate in Wilms tumor development through their effects on differentiation, proliferation, angiogenesis, and metastasis.
PubMed: 32766179
DOI: 10.3389/fped.2020.00337 -
Diagnostic Cytopathology Feb 2024Pleuropulmonary blastoma (PPB) is a rare, aggressive, primary intrathoracic malignancy typically seen in infancy and early childhood. Accurate distinction from... (Review)
Review
INTRODUCTION
Pleuropulmonary blastoma (PPB) is a rare, aggressive, primary intrathoracic malignancy typically seen in infancy and early childhood. Accurate distinction from congenital cystic lung lesions is crucial due to significant prognostic and therapeutic differences. Cytologic features have rarely been described. Establishing a cytodiagnosis is challenging owing to its rarity, lack of awareness, and multiple morphologic mimics.
MATERIALS AND METHODS
This was a retrospective study conducted over 8 years. The histopathology and cytopathology databases were searched for all pediatric PPB cases. The corresponding cytologic samples were reviewed to identify characteristic features that can help distinguish PPB from its mimics.
RESULTS
There was a total of six cases of pediatric PPB reported during the study period. Of these, four (66.7%) presented as intrathoracic, and two (33.3%) as pleural-based masses. Cytology smears showed discretely scattered and perivascular arrangements of round-oval tumor cells with background eosinophilic stromal material. The tumor cells were mildly pleomorphic (n = 3) with round nuclei, fine chromatin, inconspicuous nucleoli, and scanty cytoplasm; however, three cases showed marked anaplasia, and one each showed necrosis and rhabdoid differentiation. On immunocytochemistry (4/6), these were positive for vimentin and desmin and negative for WT1, chromogranin, SALL4, cytokeratin, CD45, and CD99. FISH (1/6) did not show N-Myc amplification.
CONCLUSIONS
Knowledge of the characteristic cytomorphological and immunocytochemical features of PPB is vital to establish a prompt and accurate cytodiagnosis with appropriate clinicoradiologic correlation.
Topics: Humans; Child; Child, Preschool; Lung Neoplasms; Retrospective Studies; Pleural Neoplasms; Pulmonary Blastoma
PubMed: 37964698
DOI: 10.1002/dc.25254 -
Modern Pathology : An Official Journal... Jul 2020We describe a morphologically distinct pattern of tumor infarction and associated sarcoma-like changes, mimicking focal anaplasia, in otherwise WHO grade I meningiomas....
We describe a morphologically distinct pattern of tumor infarction and associated sarcoma-like changes, mimicking focal anaplasia, in otherwise WHO grade I meningiomas. The described cases (n = 9) all demonstrated a discrete spindle-cell (pseudosarcomatous) component with brisk mitotic activity (12-14 mitoses/10 HPF), elevated Ki-67 (mean 75.5 ± 25.0%, quantified), absence of PR, SSTR2A, or EMA expression, and potential SMA expression (50%). Despite these high-grade features, all nine patients remained free of progression or recurrence post resection (follow-up mean: 49.8 months). In contrast, among a comparison (control) cohort of consecutive WHO grade II and III meningiomas (n = 16), as expected, progression rate was high (68.8%, P = 0.002, Fisher's exact, average time to progression = 25 months, follow-up mean: 39.8 months). While necrosis was a frequent feature among atypical/anaplastic meningiomas (12/16, 75%), and elevated mitoses and proliferative index were present consistent with histologic grade, a well-defined zonal pattern with pseudosarcomatous component was not present among these tumors. DNA methylation-based analysis readily distinguished meningiomas by copy number profiles and DNA-based methylation meningioma random forest classification analysis (meningioma v2.4 classifier developed at University of Heidelberg); all pseudosarcomatous cases analyzed (4/9) matched with high level calibrated classifier score to "MC benign-1", with isolated loss of chromosome 22q identified as the sole copy number alteration. In contrast, multiple chromosomal losses were detected among the comparison cohort and classifier results demonstrated good concordance with histologic grade. Our findings suggest that pseudosarcomatous alterations represent reactive changes to central meningioma infarction, rather than focal anaplasia, and further support the use of DNA methylation-based analysis as a useful adjunct for predicting meningioma behavior. These indolent tumors should be distinguished from their atypical and anaplastic counterparts.
Topics: Aged; Anaplasia; Biomarkers, Tumor; DNA Methylation; Female; Humans; Infarction; Male; Meningeal Neoplasms; Meningioma; Middle Aged
PubMed: 32047229
DOI: 10.1038/s41379-020-0491-6 -
International Journal of Molecular... Jun 2017Ulcerative colitis (UC) is defined as an idiopathic inflammatory disorder primarily involving the mucosa and submucosa of the colon. UC-associated colon cancers (also... (Review)
Review
Ulcerative colitis (UC) is defined as an idiopathic inflammatory disorder primarily involving the mucosa and submucosa of the colon. UC-associated colon cancers (also known as colitic cancers) develop through the inflammation-dysplasia sequence, which is a major problem affecting the prognosis of patients with UC. It is therefore very important to detect malignancy from UC at an early stage. As precancerous lesions arising in UC, there are pathological adenomatous changes, basal cell changes, in situ anaplasia, clear cell changes, and pan-cellular change. It is considered that the mutation of the p53 gene plays a crucial role, and the protein expression of p53 in dysplastic crypts may serve as a good biomarker in the early stages of UC-associated colon carcinogenesis. Immunohistochemistry for p53 is a very valuable diagnostic tool in UC-associated colon cancers. However, protein expression of p53 is not always universal, and additional methods may be required to assess p53 status in UC-associated colon cancers.
Topics: Animals; Colitis, Ulcerative; Colon; Colonic Neoplasms; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Mutation; Tumor Suppressor Protein p53
PubMed: 28621756
DOI: 10.3390/ijms18061284 -
World Neurosurgery Nov 2019Anaplastic meningiomas are rare tumors with a poor prognosis, even after complete surgical resection and radiotherapy. There has been limited evidence with respect to...
BACKGROUND
Anaplastic meningiomas are rare tumors with a poor prognosis, even after complete surgical resection and radiotherapy. There has been limited evidence with respect to the clinical factors and their effects on the course of the disease. Various retrospective studies have not been able to provide clear evidence of standardized treatment, usually presenting contradictory results. The aim of this study was to evaluate the prognostic factors influencing the progression-free survival (PFS) and overall survival (OS) of anaplastic meningiomas, with a particular focus on the roles of the extent of resection and postoperative adjuvant radiotherapy.
METHODS
Between October 2001 and March 2016, 36 patients with anaplastic meningiomas were treated in our Department of Neurosurgery, of whom 11 underwent gross total resection (GTR) and 18 subtotal resection. Twenty-one patients received postoperative adjuvant radiotherapy, and 8 were treated with surgery alone. GTR (Simpson grades I and II) was associated with significantly improved PFS (P = 0.01) and OS (P = 0.004). Furthermore, adjuvant radiotherapy showed an improvement in PFS (P = 0.01) but not in OS (P = 0.16).
CONCLUSIONS
The extent of resection in anaplastic meningiomas is correlated with a better outcome. However, resection alone is not sufficient for the long-term control of anaplastic meningiomas. Adjuvant radiotherapy is an essential component in the adjuvant treatment of anaplastic meningiomas, including for patients undergoing GTR. Further investigations through which to improve adjuvant therapy options are necessary to improve meningioma therapy.
Topics: Aged; Anaplasia; Combined Modality Therapy; Female; Humans; Male; Meningeal Neoplasms; Meningioma; Middle Aged; Neoplasm Grading; Neoplasm Recurrence, Local; Neurosurgical Procedures; Prognosis; Progression-Free Survival; Proportional Hazards Models; Radiotherapy, Adjuvant; Retrospective Studies; Survival Rate
PubMed: 31356972
DOI: 10.1016/j.wneu.2019.07.148 -
Journal of the Egyptian National Cancer... Feb 2021Medulloblastoma (MB) is a heterogeneous disease, displaying distinct genetic profiles with specific molecular subgroups. This study aimed to validate MB molecular...
BACKGROUND
Medulloblastoma (MB) is a heterogeneous disease, displaying distinct genetic profiles with specific molecular subgroups. This study aimed to validate MB molecular subgrouping using surrogate immunohistochemistry and associate molecular subgroups, histopathological types, and available clinicopathological parameters with overall survival (OS) and progression-free survival (PFS) of MB patients. This study included 40 MBs; immunohistochemical staining, using β-catenin and GRB2-Associated Binding Protein 1 (GAB1) antibodies, was used to classify MB cases into wingless signaling activated (WNT), sonic hedgehog (SHH), and non-WNT/SHH molecular subgroups. Nuclear morphometric analysis (for assessment of degree of anaplasia) and Kaplan-Meier survival curves were done.
RESULTS
MB cases were classified into WNT (10%), SHH (30%), and non-WNT/SHH (60%) subgroups. Histopathological types differed significantly according to tumor location (p< 0.001), degree of anaplasia (p = 0.014), molecular subgroups (p < 0.001), and risk stratification (p = 0.008). Molecular subgroups differed significantly in age distribution (p = 0.031), tumor location (p< 0.001), histopathological variants (p < 0.001), and risk stratification (p < 0.001). OS was 77.5% and 50% after 1 and 2 years, while PFS was 65% and 27.5% after 1 and 2 years, respectively. OS and PFS were associated significantly with histopathological variants (p < 0.001 and 0.001), molecular subgroups (p = 0.012 and 0.005), and risk stratification (p < 0.001 and < 0.001), respectively.
CONCLUSIONS
Medulloblastoma classification based on molecular subgroups, together with clinicopathological indicators, mainly histopathological types; accurately risk stratifies MB patients and predicts their survival.
Topics: Cerebellar Neoplasms; Hedgehog Proteins; Humans; Medulloblastoma; Risk Assessment; Survival Analysis
PubMed: 33555447
DOI: 10.1186/s43046-021-00060-w -
Urologic Oncology Oct 2016The Gleason grading system measures architectural differentiation and disregards nuclear atypia and the cell proliferation index. Several studies have reported that...
OBJECTIVES
The Gleason grading system measures architectural differentiation and disregards nuclear atypia and the cell proliferation index. Several studies have reported that nuclear grade and mitotic index (MI) are prognostically useful.
PATIENTS AND METHODS
This study included 232 radical prostatectomy specimens. Nuclear anaplasia (NA) was determined on the basis of nucleomegali (at least 20µm); vesicular chromatin; eosinophilic macronucleoli, nuclear lobulation, and irregular thickened nuclear membranei. The proportion of area of NA was recorded in each tumor in 10% increments. The MI was defined as the number of mitotic figures in 10 consecutive high-power fields (HPF).
RESULTS
In univariate analysis, significant differences included associations between biochemical prostate-specific antigen recurrence (BCR) and Gleason score, extraprostatic extension, positive surgical margin, the presence of high-pathologic stage, NA≥10% of tumor area, MI≥3/10 HPF, and preoperative prostate-specific antigen. In a stepwise Cox regression model, a positive surgical margin, the presence of a NA≥10% of tumor area, and a MI of≥3/10 HPF were independent predictors of BCR after radical prostatectomy. NA≥10% of tumor area appeared to have a stronger association with outcome than MI≥3/10 HPF, as still associated with BCR when Gleason score was in the model.
CONCLUSIONS
The results of our study showed that, in addition to the conventional Gleason grading system, NA, and MI are useful prognostic parameters while evaluating long-term prognosis in prostatic adenocarcinoma.
Topics: Adenocarcinoma; Anaplasia; Area Under Curve; Cell Nucleus; Humans; Male; Margins of Excision; Mitotic Index; Neoplasm Grading; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasm, Residual; Prognosis; Proportional Hazards Models; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; ROC Curve
PubMed: 27264167
DOI: 10.1016/j.urolonc.2016.04.017