Expanded analysis of high-grade astrocytoma with piloid features identifies an epigenetically and clinically distinct subtype associated with neurofibromatosis type 1.

High-grade astrocytoma with piloid features (HGAP) is a recently recognized glioma type whose classification is dependent on its global epigenetic signature. HGAP is characterized by alterations in the mitogen-activated protein kinase (MAPK) pathway, often co-occurring with CDKN2A/B homozygous deletion and/or ATRX mutation. Experience with HGAP is limited and to better understand this tumor type, we evaluated an expanded cohort of patients (n = 144) with these tumors, as defined by DNA methylation array testing, with a subset additionally evaluated by next-generation sequencing (NGS). Among evaluable cases, we confirmed the high prevalence CDKN2A/B homozygous deletion, and/or ATRX mutations/loss in this tumor type, along with a subset showing NF1 alterations. Five of 93 (5.4%) cases sequenced harbored TP53 mutations and RNA fusion analysis identified a single tumor containing an NTRK2 gene fusion, neither of which have been previously reported in HGAP. Clustering analysis revealed the presence of three distinct HGAP subtypes (or groups = g) based on whole-genome DNA methylation patterns, which we provisionally designated as gNF1 (n = 18), g1 (n = 72), and g2 (n = 54) (median ages 43.5 years, 47 years, and 32 years, respectively). Subtype gNF1 is notable for enrichment with patients with Neurofibromatosis Type 1 (33.3%, p = 0.0008), confinement to the posterior fossa, hypermethylation in the NF1 enhancer region, a trend towards decreased progression-free survival (p = 0.0579), RNA processing pathway dysregulation, and elevated non-neoplastic glia and neuron cell content (p < 0.0001 and p < 0.0001, respectively). Overall, our expanded cohort broadens the genetic, epigenetic, and clinical phenotype of HGAP and provides evidence for distinct epigenetic subtypes in this tumor type.

Pleomorphic xanthoastrocytoma: report of two cases with unconventional clinical presentations.

AIMS: Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic neoplasm with a relative circumscribed architecture that typically arises superficially in the cerebral hemispheres of teenagers and young adults. Our aim is to highlight unconventional clinical presentations of this distinct neoplasm. MATERIALS AND METHODS: We report two cases of PXA with unconventional clinical features, including clinical, pathologic, and immunohistochemical features. RESULTS: The first case developed in the left frontal lobe of a 20-year-old female with neurofibromatosis type 1 (NF1). Focal anaplastic features were present. The neoplastic cells were immunoreactive for GFAP, S-100 protein and focally for synaptophysin, with a MIB-1/Ki-67 proliferative labelling index of 16%. The second case developed in a 39-year-old female as a suprasellar neoplasm. The neoplastic cells expressed GFAP, S-100 protein and focally CD34. The adenohypophysis was positive for synaptophysin and pituicytes for TTF1. Molecular studies were negative for BRAF (V600E) mutation in both cases. CONCLUSION: PXA is a distinct circumscribed neoplasm that may present in unexpected locations or clinical backgrounds. Neuropathologists must be aware of these unconventional presentations in order to provide a precise diagnosis leading to appropriate treatment.

Sarcomatous Meningioma: Diagnostic Pitfalls and the Utility of Molecular Testing.

Anaplastic meningiomas can have a sarcomatous appearance on histology but true sarcomatous (metaplastic) differentiation is rare. These tumors follow an aggressive clinical course with recurrence and poor clinical outcomes. Due to significant overlap in morphology and immunohistochemical profiles, distinguishing between sarcomatous transformation of a meningioma and a true sarcoma can be challenging. Here, we outline potential diagnostic pitfalls and the utility of ancillary molecular testing in 3 patients diagnosed with sarcomatous meningiomas. We report loss of typical meningothelial markers in sarcomatous meningiomas. Ancillary molecular testing can support the diagnosis of sarcomatous meningioma when a molecular signature consistent with meningioma is seen, such as inactivation of the NF2 gene. Recognition of this rare transformation in meningioma can prevent a misdiagnosis of a primary sarcoma, whether sporadic or radiation-induced from prior treatment of a more classic meningioma.

Successful treatment of recurrent primary sclerosing cholangitis after orthotopic liver transplantation with oral vancomycin.

Primary sclerosing cholangitis (PSC) is a progressive, cholestatic disease of the liver that is marked by inflammation of the bile ducts and damage to the hepatic biliary tree. Approximately 60-70% of patients also have inflammatory bowel disease and progression of PSC can lead to ulcerative colitis and cirrhosis of the liver. Due to limited understanding of the etiology and mechanism of PSC, the only existing treatment option is orthotopic liver transplantation (OLT); however, recurrence of PSC, after OLT is estimated to be between 5% and 35%. We discuss the successful treatment of a pediatric patient, with recurrent PSC, after OLT with oral Vancomycin.

Intramedullary papillary ependymoma with choroid plexus differentiation and cerebrospinal fluid dissemination to the brain.

This 8-year-old girl presented with a papillary ependymoma in the thoracic spinal cord. Resection was followed by recurrence at the primary site and later in the lumbosacral thecal sac, followed by cerebrospinal fluid dissemination to the brain approximately 5 years after her initial presentation. The tumor showed cytological and immunohistochemical features overlapping those of classic ependymomas and choroid plexus tumors similar to those seen in uncommon supratentorial papillary ependymomas, also known as papillary tumors of the pineal region. The histopathological and clinical courses of this rare spinal papillary ependymoma exhibiting mixed ependymal and choroid plexus-like differentiation are discussed.