Rhabdomyosarcoma (RMS) is a pediatric malignancy with a variable prognosis depending on tumor stage and genotype. There has been a significant improvement in survival rates over the past decades. ...However, aggressive variants can metastasize to locations that are difficult to treat. We report a case of prostatic alveolar rhabdomyosarcoma with metastases to the bone marrow and thoracic spine in a child. The patient was treated with a multimodal approach that included surgical resection of the epidural mass; the administration of vincristine, dactinomycin, and cyclophosphamide; and radiotherapy. Unfortunately, after six months, the patient showed disease progression and was started on secondary-line treatment. This case illustrates the difficulties in managing end-stage metastatic rhabdomyosarcoma and is the first report of prostatic rhabdomyosarcoma presenting with spinal cord compression in a child.
Patients with von Hippel–Lindau disease carry a germline mutation of the Von Hippel–Lindau (VHL) tumor-suppressor gene. We discuss the molecular consequences of loss of VHL gene function and their ...impact on the nervous system. Dysfunction of the VHL protein causes accumulation and activation of hypoxia inducible factor (HIF) which can be demonstrated in earliest stages of tumorigenesis and is followed by expression of VEGF, erythropoietin, nitric oxide synthase and glucose transporter 1 in VHL-deficient tumor cells. HIF-independent functions of VHL, epigenetic inactivation of VHL, pVHL proteostasis, and links between loss of VHL function and developmental arrest are also described. A most intriguing feature in VHL disease is the occurrence of primary hemangioblastic tumors in the nervous system, the origin of which has not yet been entirely clarified, and current hypotheses are discussed. Endolymphatic sac tumors may extend into the brain, but originally arise from proliferation of endolymphatic duct/sac epithelium; the exact nature of the proliferating epithelial cell, however, also has remained unclear, as well as the question why tumors almost consistently develop in the intraosseous portion of the endolymphatic sac/duct only. The epitheloid clear cell morphology of both advanced hemangioblastoma and renal clear cell carcinoma can make the differential diagnosis challenging, recent developments in immunohistochemical differentiation are discussed. Finally, metastasis to brain may not only be caused by renal carcinoma, but may derive from VHL disease-associated pheochromocytoma/paraganglioma, or pancreatic neuroendocrine tumor.
Delayed radiation-induced vasculitic leukoencephalopathy Rauch, Philipp J; Park, Henry S; Knisely, Jonathan P S ...
International journal of radiation oncology, biology, physics,
05/2012, Letnik:
83, Številka:
1
Journal Article
Recenzirano
Recently, single-fraction, high-dosed focused radiation therapy such as that administered by Gamma Knife radiosurgery has been used increasingly for the treatment of metastatic brain cancer. ...Radiation therapy to the brain can cause delayed leukoencephalopathy, which carries its own significant morbidity and mortality. While radiosurgery-induced leukoencephalopathy is known to be clinically different from that following fractionated radiation, pathological differences are not well characterized. In this study, we aimed to integrate novel radiographic and histopathologic observations to gain a conceptual understanding of radiosurgery-induced leukoencephalopathy.
We examined resected tissues of 10 patients treated at Yale New Haven Hospital between January 1, 2009, and June 30, 2010, for brain metastases that had been previously treated with Gamma Knife radiosurgery, who subsequently required surgical management of a symptomatic regrowing lesion. None of the patients showed pathological evidence of tumor recurrence. Clinical and magnetic resonance imaging data for each of the 10 patients were then studied retrospectively.
We provide evidence to show that radiosurgery-induced leukoencephalopathy may present as an advancing process that extends beyond the original high-dose radiation field. Neuropathologic examination of the resected tissue revealed traditionally known leukoencephalopathic changes including demyelination, coagulation necrosis, and vascular sclerosis. Unexpectedly, small and medium-sized vessels revealed transmural T-cell infiltration indicative of active vasculitis.
We propose that the presence of a vasculitic component in association with radiation-induced leukoencephalopathy may facilitate the progressive nature of the condition. It may also explain the resemblance of delayed leukoencephalopathy with recurring tumor on virtually all imaging modalities used for posttreatment follow-up.
Histological Tracking into the Third Dimension Mubarak, Mayyan; Al Gharaibeh, Nayef; Sommaruga, Samuel ...
Journal of kidney cancer and VHL,
09/2021, Letnik:
8, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Using a novel three-dimensional (3D) approach, we tracked histological changes to elucidate the earliest stages of renal clear cell neoplasia in normal kidney tissue of patients with von ...Hippel-Lindau (VHL) disease. Tissue blocks of interest were procured, serially sectioned, and 3D reconstruction of the entirety of pathologic events was performed. The results reveal an abundance of foci with aberrant clear cell proliferation that initially develop along the tubular lining, but have the potential to aggregate within individual tubules. This stage is followed by the extension of clear cell aggregates beyond the tubular basement membrane, which allows for the recruitment of angiogenesis derived from interstitial vasculature. The results suggest that the most frequent pathologic event in VHL kidneys is the presence of isolated or aggregated clear cells within the tubular epithelium, potentially developing further into a protracted process of neoplasia. The abundance of independent pathologic events in VHL kidneys confirms developmental mechanisms to precede tumor initiation. To our knowledge, this is the first report demonstrating that tracking of histologic changes in the 3rd dimension enables the confirmation of the sequence of events from the earliest pathologic change in the VHL kidney to the neoplastic stage. This approach is not only useful for visualization and quantification of pathologic changes but also for targeted sampling allowing selective analysis of the earliest stages of clear cell carcinogenesis.
OBJECTIVE Following an initial response of brain metastases to Gamma Knife radiosurgery, regrowth of the enhancing lesion as detected on MRI may represent either radiation necrosis (a ...treatment-related inflammatory change) or recurrent tumor. Differentiation of radiation necrosis from tumor is vital for management decision making but remains difficult by imaging alone. In this study, gas chromatography with time-of-flight mass spectrometry (GC-TOF) was used to identify differential metabolite profiles of the 2 tissue types obtained by surgical biopsy to find potential targets for noninvasive imaging. METHODS Specimens of pure radiation necrosis and pure tumor obtained from patient brain biopsies were flash-frozen and validated histologically. These formalin-free tissue samples were then analyzed using GC-TOF. The metabolite profiles of radiation necrosis and tumor samples were compared using multivariate and univariate statistical analysis. Statistical significance was defined as p ≤ 0.05. RESULTS For the metabolic profiling, GC-TOF was performed on 7 samples of radiation necrosis and 7 samples of tumor. Of the 141 metabolites identified, 17 (12.1%) were found to be statistically significantly different between comparison groups. Of these metabolites, 6 were increased in tumor, and 11 were increased in radiation necrosis. An unsupervised hierarchical clustering analysis found that tumor had elevated levels of metabolites associated with energy metabolism, whereas radiation necrosis had elevated levels of metabolites that were fatty acids and antioxidants/cofactors. CONCLUSIONS To the authors' knowledge, this is the first tissue-based metabolomics study of radiation necrosis and tumor. Radiation necrosis and recurrent tumor following Gamma Knife radiosurgery for brain metastases have unique metabolite profiles that may be targeted in the future to develop noninvasive metabolic imaging techniques.
•Mature teratoma with nephroblastoma is most often in mediastinum or retroperitoneum.•This case is a novel finding of CNS mature teratoma with nephroblastoma.•Development via teratoma with either ...malignant transformation or immature component.
Neonatal germ cell tumors are rare and comprise both benign and malignant neoplasms. Teratoma with nephroblastoma is a malignant subset defined pathologically by the presence of nephroblastoma and teratoma elements. Although teratoma with nephroblastoma is most often found in the kidney, 24 of 59 reported cases are associated with extrarenal locations, such as the mediastinum or retroperitoneum. To our knowledge, this is the first patient in the literature with intracranial/pineal teratoma with nephroblastoma, which was managed with staged transcranial approaches resulting in gross total resection and no adjuvant therapy (surveillance observation imaging). We further augmented the patient’s management by comprehensive genomic profiling of the tumor to better understand the molecular biology and explore options for targeted therapy.
Pediatric low-grade gliomas (LGGs) are found in approximately one to three percent of patients with childhood epilepsy. Epilepsy in these patients is often medically refractory and therefore ...represents a unique cohort with significant morbidity from concomitant pathology. Similar studies in adult patients with low-grade gliomas have identified predictors of seizure freedom including gross-total resection, preoperative seizure control on antiepileptic medication and duration of seizures of less than one year. This study aims to identify similar predictors of seizure freedom in operatively managed pediatric LGGs.
A retrospective chart review was performed for patients diagnosed with World Health Organization (WHO) Grade I and II gliomas in patients ≤18 years old at a single institution (Indiana University School of Medicine at Riley Hospital for Children in Indianapolis, IN) from 2007-2017. Infratentorial and purely intraventricular lesions were excluded. WHO classification and histologic diagnosis were based on surgical pathology. Tumor grade, location, laterality, seizure status at presentation, and AED requirements pre- and post-operatively were recorded. Chi-squared analyses for independence were performed controlling for age at presentation, resection extent, seizure type, and Engel Class for seizure freedom post-operatively.
Forty-two patients met the inclusion criteria. Preoperative seizures were observed in 23 patients (55%). Presentation with preoperative seizures was highly associated with continued seizure burden post-operatively, independent of the extent of surgical resection. Supratentorial location and the administration of prophylactic pre- and post-operative AEDs were associated with Engel Class I seizure freedom. Temporal location was not significantly associated with medically refractory epilepsy compared with extra-temporal locations.
In our cohort of pediatric LGGs, we find that patients that did not initially present with seizures and those who were treated with prophylactic pre- and post-operative AEDs, were more likely to achieve Engel Class I seizure freedom post-operatively. Tumors located in the temporal location were not significantly associated with a higher seizure burden than other supratentorial, extra-temporal tumors. Neither extent of resection nor electrocorticography-guided resection correlated with improved seizure freedom outcomes during glioma resection.
To systematically review and analyze clinical, diagnostic, and management trends in sellar and parasellar brown tumors reported in existing literature.
In this systematic review, PubMed, Ovid ...MEDLINE, Scopus, and Google Scholar databases were searched for reported cases of sellar/parasellar brown tumors. Relevant titles and abstracts were screened in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. Articles meeting inclusion criteria were subjected to data extraction, summarization, and analysis. A rare case of parasellar brown tumor was also presented.
Eight reports (including the current report) were eligible for inclusion. Mean patient age was 42.75 years. Reported symptoms included visual disturbances (n = 6), headache (n = 5), fatigue (n = 3), nausea/vomiting (n = 2), chest pain (n = 1), neck pain (n = 1), and dysphagia (n = 1). In cases where computed tomography findings were provided (n = 6), lesions were noted to be expansile and lytic. Lesions were hyperintense on T2-weighted magnetic resonance imaging (66.7%) and demonstrated contrast enhancement (83.3%). Histology unanimously showed multinucleated giant cells in a fibrovascular connective tissue stroma. Dramatic symptom resolution was noted in all patients who underwent resection of the sellar/parasellar brown tumor (n = 4; 50%).
Sellar/parasellar brown tumors are a rare, tertiary manifestation of hyperparathyroidism and can be elusive to diagnose. Diagnosis requires a high index of clinical suspicion in addition to comprehensive biochemical testing, imaging, and histopathologic analysis. Surgical extirpation is favored in cases where the lesion is causing compressive symptoms, or if it is unresponsive to management of hyperparathyroidism.
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