57 research outputs found
Magnetic resonance imaging of a temporal lobe cerebral amyloidoma
Amyloidomas are focal solitary amyloid masses without systemic involvement that have been observed to occur in various body locations. When presenting intracranially, they pose a challenging diagnostic and therapeutic course given their location and rarity. We report a case of a 62-year-old man with a 4-year history of seizure and headaches. Magnetic resonance imaging was initially inconclusive but revealed an ill-defined right temporal lobe lesion. Biopsy later confirmed a cerebral amyloidoma. We also review the current literature on the pathogenesis, imaging findings, prognosis, and treatment of cerebral amyloidomas
BRAF activating mutations involving the ÎČ3-αC loop in V600E-negative anaplastic pleomorphic xanthoastrocytoma
https://deepblue.lib.umich.edu/bitstream/2027.42/142789/1/40478_2018_Article_525.pd
The Role of CD 133+ Cells in a Recurrent Embryonal Tumor with Abundant Neuropil and True Rosettes ( ETANTR )
Embryonal tumor with abundant neuropil and true rosettes ( ETANTR ) is a recently described embryonal neoplasm of the central nervous system, consisting of a wellâcircumscribed embryonal tumor of infancy with mixed features of ependymoblastoma (multilayer ependymoblastic rosettes and pseudorosettes) and neuroblastoma (neuroblastic rosettes) in the presence of neuropilâlike islands. We present the case of a young child with a very aggressive tumor that rapidly recurred after gross total resection, chemotherapy and radiation. Prominent vascular sclerosis and circumscribed tumor led to the diagnosis of malignant astroblastoma; however, rapid recurrence and progression of this large tumor after gross total resection prompted review of the original pathology. ETANTR is histologically distinct with focal glial fibrillary acid protein ( GFAP ) and synaptophysin expression in the presence of neuronal and ependymoblastic rosettes with focal neuropil islands. These architectural features, combined with unique chromosome 19q13.42 amplification, confirmed the diagnosis. In this report, we describe tumor stem cell ( TSC ) marker CD 133, CD 15 and nestin alterations in ETANTR before and after chemotherapy. We found that TSC marker CD 133 was richly expressed after chemotherapy in recurrent ETANTR , while CD 15 is depleted compared with that expressed in the original tumor, suggesting that CD 133+ cells likely survived initial treatment, further contributing to formation of the recurrent tumor.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102077/1/bpa12079.pd
Amyloid Myopathy as an Inclusion Body Myositis Mimic
Introduction: Amyloid myopathy is a rare presentation of systemic amyloidosis. Amyloid myopathy can be initially misdiagnosed as sporadic inclusion body myositis (IBM).
Methods: We report 4 cases of amyloid myopathy clinically mimicking inclusion body myositis and initially thought to be phenotypically IBM by neuromuscular experts.
Results: Case 1 is an 81-year-old woman who presented with distal arm and proximal leg asymmetric weakness (myopathy pattern 4). Case 2 is a 76-year-old man with primary systemic amyloidosis who presented with myopathy pattern 4 and progressive dysphagia for four years. Case 3 is an 82-year-old man with progressive myopathy pattern 4 weakness and swallowing difficulty. Case 4 is a 62-year-old man with progressive bilateral finger flexor weakness. Muscle biopsies in all 4 cases showed perivascular amyloid deposits
Discussion: Amyloid myopathy may be clinically indistinguishable from IBM. Muscle biopsy is of critical importance in the evaluation of patients suspected to have IBM
Potential association of LMNA-associated generalized lipodystrophy with juvenile dermatomyositis
Abstract
Background
Juvenile dermatomyositis (JDM) is an auto-immune muscle disease which presents with skin manifestations and muscle weakness. At least 10% of the patients with JDM present with acquired lipodystrophy. Laminopathies are caused by mutations in the lamin genes and cover a wide spectrum of diseases including muscular dystrophies and lipodystrophy. The p.T10I LMNA variant is associated with a phenotype of generalized lipodystrophy that has also been called atypical progeroid syndrome.
Case presentation
A previously healthy female presented with bilateral proximal lower extremity muscle weakness at age 4. She was diagnosed with JDM based on her clinical presentation, laboratory tests and magnetic resonance imaging (MRI). She had subcutaneous fat loss which started in her extremities and progressed to her whole body. At age 7, she had diabetes, hypertriglyceridemia, low leptin levels and low body fat on dual energy X-ray absorptiometry (DEXA) scan, and was diagnosed with acquired generalized lipodystrophy (AGL). Whole exome sequencing (WES) revealed a heterozygous c.29Câ>âT; p.T10I missense pathogenic variant in LMNA, which encodes lamins A and C. Muscle biopsy confirmed JDM rather than muscular dystrophy, showing perifascicular atrophy and perivascular mononuclear cell infiltration. Immunofluroscence of skin fibroblasts confirmed nuclear atypia and fragmentation.
Conclusions
This is a unique case with p.T10I LMNA variant displaying concurrent JDM and AGL. This co-occurrence raises the intriguing possibility that LMNA, and possibly p.T10I, may have a pathogenic role in not only the occurrence of generalized lipodystrophy, but also juvenile dermatomyositis. Careful phenotypic characterization of additional patients with laminopathies as well as individuals with JDM is warranted.https://deepblue.lib.umich.edu/bitstream/2027.42/142870/1/40842_2018_Article_58.pd
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Rapid, Label-Free Detection of Brain Tumors with Stimulated Raman Scattering Microscopy
Surgery is an essential component in the treatment of brain tumors. However, delineating tumor from normal brain remains a major challenge. We describe the use of stimulated Raman scattering (SRS) microscopy for differentiating healthy human and mouse brain tissue from tumor-infiltrated brain based on histoarchitectural and biochemical differences. Unlike traditional histopathology, SRS is a label-free technique that can be rapidly performed in situ. SRS microscopy was able to differentiate tumor from nonneoplastic tissue in an infiltrative human glioblastoma xenograft mouse model based on their different Raman spectra. We further demonstrated a correlation between SRS and hematoxylin and eosin microscopy for detection of glioma infiltration (Îș = 0.98). Finally, we applied SRS microscopy in vivo in mice during surgery to reveal tumor margins that were undetectable under standard operative conditions. By providing rapid intraoperative assessment of brain tissue, SRS microscopy may ultimately improve the safety and accuracy of surgeries where tumor boundaries are visually indistinct.Chemistry and Chemical Biolog
Opposing Tumor-Promoting and -Suppressive Functions of Rictor/mTORC2 Signaling in Adult Glioma and Pediatric SHH Medulloblastoma.
Most human cancers arise from stem and progenitor cells by the sequential accumulation of genetic and epigenetic alterations, while cancer modeling typically requires simultaneous multiple oncogenic events. Here, we show that a single p53 mutation, despite causing no defect in the mouse brain, promoted neural stem and progenitor cells to spontaneously accumulate oncogenic alterations, including loss of multiple chromosomal (chr) regions syntenic to human chr10 containing Pten, forming malignant gliomas with PI3K/Akt activation. Rictor/mTORC2 loss inhibited Akt signaling, greatly delaying and reducing glioma formation by suppressing glioma precursors within the subventricular zone stem cell niche. Rictor/mTORC2 loss delayed timely differentiation of granule cell precursors (GCPs) during cerebellar development, promoting sustained GCP proliferation and medulloblastoma formation, which recapitulated critical features of TP53 mutant sonic hedgehog (SHH) medulloblastomas with GLI2 and/or N-MYC amplification. Our study demonstrates that Rictor/mTORC2 has opposing functions in neural stem cells and GCPs in the adult and the developing brain, promoting malignant gliomas and suppressing SHH-medulloblastoma formation, respectively
Alternative lengthening of telomeres, ATRX loss and H3Ăą K27M mutations in histologically defined pilocytic astrocytoma with anaplasia
Anaplasia may be identified in a subset of tumors with a presumed pilocytic astrocytoma (PA) component or piloid features, which may be associated with aggressive behavior, but the biologic basis of this change remains unclear. FiftyĂą seven resections from 36 patients (23 M, 13 F, mean age 32 years, range 3Ăą 75) were included. A clinical diagnosis of NF1 was present in 8 (22%). Alternative lengthening of telomeres (ALT) was assessed by telomereĂą specific FISH and/or CISH. A combination of immunohistochemistry, DNA sequencing and FISH were used to study BRAF, ATRX, CDKN2A/p16, mutant IDH1 p.R132H and H3Ăą K27M proteins. ALT was present in 25 (69%) cases and ATRX loss in 20 (57%), mostly in the expected association of ALT+/ATRXĂą (20/24, 83%) or ALTĂą /ATRX+ (11/11, 100%). BRAF duplication was present in 8 (of 26) (31%). H3Ăą K27M was present in 5 of 32 (16%) cases, all with concurrent ATRX loss and ALT. ALT was also present in 9 (of 11) cases in the benign PA precursor, 7 of which also had ATRX loss in both the precursor and the anaplastic tumor. In a single pediatric case, ALT and ATRX loss developed in the anaplastic component only, and in another adult case, ALT was present in the PAĂą A component only, but ATRX was not tested. Features associated with worse prognosis included subtotal resection, adult vs. pediatric, presence of a PA precursor preceding a diagnosis of anaplasia, necrosis, presence of ALT and ATRX expression loss. ALT and ATRX loss, as well as alterations involving the MAPK pathway, are frequent in PA with anaplasia at the time of development of anaplasia or in their precursors. Additionally, a small subset of PA with anaplasia have H3Ăą K27M mutations. These findings further support the concept that PA with anaplasia is a neoplasm with heterogeneous genetic features and alterations typical of both PA and diffuse gliomas.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147190/1/bpa12646_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147190/2/bpa12646.pd
Plasmacytoid urothelial carcinoma: a rapid autopsy case report with unique clinicopathologic and genomic profile
Abstract
Background
Rapid (âwarmâ) autopsies of patients with advanced metastatic cancer provide important insight into the natural history, pathobiology and histomorphology of disease in treatment-resistant tumors. Plasmacytoid urothelial carcinoma (PUC) is a rare variant of urothelial carcinoma characterized by neoplastic cells morphologically resembling plasma cells. PUC is typically aggressive, high-stage at presentation, and associated with poor outcomes. Recurrence is common in PUC, with the majority of recurrences occurring in the peritoneum.
Case presentation
Here, we report rapid autopsy findings from a patient with recurrent PUC. The patient had persistent pain after cystoprostatectomy, although initial post-operative imaging showed no evidence of disease. Imaging obtained shortly before his death showed only subtle growth along vascular tissue planes; however, extensive disease was seen on autopsy. Plasmacytoid tumor cells formed sheets involving many serosal surfaces. Molecular interrogation confirmed a mutation in CDH1 exon 12 leading to early truncation of the CDH1 protein in the tumor cells.
Conclusions
The sheet-like growth pattern of PUC makes early phases of disease spread much more difficult to capture on cross-sectional imaging. Alternative forms of surveillance may be required for detection of recurrent PUC, and providers may need to treat based on symptoms and clinical suspicion.https://deepblue.lib.umich.edu/bitstream/2027.42/152229/1/13000_2019_Article_896.pd
Artificial-intelligence-based molecular classification of diffuse gliomas using rapid, label-free optical imaging
Molecular classification has transformed the management of brain tumors by
enabling more accurate prognostication and personalized treatment. However,
timely molecular diagnostic testing for patients with brain tumors is limited,
complicating surgical and adjuvant treatment and obstructing clinical trial
enrollment. In this study, we developed DeepGlioma, a rapid ( seconds),
artificial-intelligence-based diagnostic screening system to streamline the
molecular diagnosis of diffuse gliomas. DeepGlioma is trained using a
multimodal dataset that includes stimulated Raman histology (SRH); a rapid,
label-free, non-consumptive, optical imaging method; and large-scale, public
genomic data. In a prospective, multicenter, international testing cohort of
patients with diffuse glioma () who underwent real-time SRH imaging, we
demonstrate that DeepGlioma can predict the molecular alterations used by the
World Health Organization to define the adult-type diffuse glioma taxonomy (IDH
mutation, 1p19q co-deletion and ATRX mutation), achieving a mean molecular
classification accuracy of . Our results represent how
artificial intelligence and optical histology can be used to provide a rapid
and scalable adjunct to wet lab methods for the molecular screening of patients
with diffuse glioma.Comment: Paper published in Nature Medicin
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