| 1. |
- Asa, Sylvia L., et al.
(author)
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Pituitary neuroendocrine tumors : a model for neuroendocrine tumor classification
- 2021
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In: Modern Pathology. - : Springer Nature. - 0893-3952 .- 1530-0285. ; 34:9, s. 1634-1650
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Research review (peer-reviewed)abstract
- The classification of adenohypophysial neoplasms as "pituitary neuroendocrine tumors" (PitNETs) was proposed in 2017 to reflect their characteristics as epithelial neuroendocrine neoplasms with a spectrum of clinical behaviors ranging from small indolent lesions to large, locally invasive, unresectable tumors. Tumor growth and hormone hypersecretion cause significant morbidity and mortality in a subset of patients. The proposal was endorsed by a WHO working group that sought to provide a unified approach to neuroendocrine neoplasia in all body sites. We review the features that are characteristic of neuroendocrine cells, the epidemiology and prognosis of these tumors, as well as further refinements in terms used for other pituitary tumors to ensure consistency with the WHO framework. The intense study of PitNETs has provided information about the importance of cellular differentiation in tumor prognosis as a model for neuroendocrine tumors in different locations.
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| 3. |
- Dahlin, Lars B., et al.
(author)
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Intraneural glomus tumor of "uncertain malignant potential" and with BRAF mutation in the median nerve - an unusual case
- 2017
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In: Clinical Neuropathology. - 0722-5091. ; 36:7, s. 164-170
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Journal article (peer-reviewed)abstract
- A glomus tumor of uncertain malignant potential is defined as a glomus tumor with some, but not all, criteria for malignancy and without a known metastasis. Here, we present a rare example presenting in the median nerve in a 40-year-old woman with a long history of severely impaired left median nerve function. A large panel of immunohistochemical stains excluded other diagnoses, and the designation of a "uncertain malignant potential" was based on the high proliferative activity, the tumor size and location, and the lack of WHO malignancy criteria such as marked nuclear atypia, necrosis, or atypical mitoses. A BRAF mutation was found in the tumor. Although extremely rare, both benign and malignant glomus tumors may present in large peripheral nerves and should therefore be considered in the differential diagnosis.
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| 4. |
- Keck, Michaela Kristina, et al.
(author)
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Amplification of the PLAG-family genes—PLAGL1 and PLAGL2—is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplification
- 2023
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In: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 145:1, s. 49-69
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Journal article (peer-reviewed)abstract
- Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0–14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal high-level amplification and resultant overexpression of either PLAGL1 or PLAGL2, and an absence of recurrent genetic alterations characteristic of other pediatric CNS tumor types. Both genes act as transcription factors for a regulatory subset of imprinted genes (IGs), components of the Wnt/β-Catenin pathway, and the potential drug targets RET and CYP2W1, which are also specifically overexpressed in this tumor type. A derived PLAGL-specific gene expression signature indicates dysregulation of imprinting control and differentiation/development. These tumors occurred throughout the neuroaxis including the cerebral hemispheres, cerebellum, and brainstem, and were predominantly composed of primitive embryonal-like cells lacking robust expression of markers of glial or neuronal differentiation (e.g., GFAP, OLIG2, and synaptophysin). Tumors with PLAGL1 amplification were typically diagnosed during adolescence (median age 10.5 years), whereas those with PLAGL2 amplification were diagnosed during early childhood (median age 2 years). The 10-year overall survival was 66% for PLAGL1-amplified tumors, 25% for PLAGL2-amplified tumors, 18% for male patients, and 82% for female patients. In summary, we describe a new type of biologically distinct CNS tumor characterized by PLAGL1/2 amplification that occurs predominantly in infants and toddlers (PLAGL2) or adolescents (PLAGL1) which we consider best classified as a CNS embryonal tumor and which is associated with intermediate survival. The cell of origin and optimal treatment strategies remain to be defined.
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| 5. |
- Swartling, Fredrik J., et al.
(author)
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Distinct Neural Stem Cell Populations Give Rise to Disparate Brain Tumors in Response to N-MYC
- 2012
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In: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 21:5, s. 601-613
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Journal article (peer-reviewed)abstract
- The proto-oncogene MYCN is mis-expressed in various types of human brain tumors. To clarify how developmental and regional differences influence transformation, we transduced wild-type or mutationally stabilized murine N-myc(T58A) into neural stem cells (NSCs) from perinatal murine cerebellum, brain stem, and forebrain. Transplantation of N-myc(WT) NSCs was insufficient for tumor formation. N-myc(T58A) cerebellar and brain stem NSCs generated medulloblastoma/primitive neuroectodermal tumors, whereas forebrain NSCs developed diffuse glioma. Expression analyses distinguished tumors generated from these different regions, with tumors from embryonic versus postnatal cerebellar NSCs demonstrating Sonic Hedgehog (SHH) dependence and SHH independence, respectively. These differences were regulated in part by the transcription factor SOX9, activated in the SHH subclass of human medulloblastoma. Our results demonstrate context-dependent transformation of NSCs in response to a common oncogenic signal.
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