The differential diagnosis of pilocytic astrocytoma with atypical features and malignant glioma: an analysis of 16 cases with emphasis on distinguishing molecular features.

Rare pilocytic astrocytomas (PA) have atypical histologic and clinicoradiologic features that raise the differential diagnosis of glioblastoma. Whether ancillary studies can supplement histopathologic examination in placing these cases accurately on the spectrum of WHO Grade I PA to higher-grade glioma is not always clear, partly because these cases are not common. Here, ten PAs with atypical clinicoradiologic and histologic features and six pediatric glioblastoma multiforme (pGBMs) were analyzed for BRAF V600E, IDH1, IDH2, and TP53 mutations. Ki-67, p53, and p16 protein expression were also examined by immunohistochemistry. BRAF-KIAA1549 fusion status was assessed in the PA subgroup. The rate of BRAF-KIAA1549 fusion was high in these PAs (5/7 tumors) including four extracerebellar examples. A single BRAF V600E mutation was identified in the fusion-negative extracerebellar PA of a very young child who succumbed to the disease. TP53 mutations were present only in malignant gliomas, including three pGBMs and one case designated as PA with anaplastic features (with consultation opinion of pGBM). IDH1 and IDH2 were wild type in all cases, consistent with earlier findings that IDH mutations are not typical in high-grade gliomas of patients ≤14 years of age. Immunohistochemical studies showed substantial overlap in Ki-67 labeling indices, an imperfect correlation between p53 labeling and TP53 mutation status, and complete p16 loss in only two pGBMs but in no PAs. These results suggest that (a) BRAF-KIAA1549 fusion may be common in PAs with atypical clinicoradiologic and histologic features, including those at extracerebellar sites, (b) BRAF V600E mutation is uncommon in extracerebellar PAs, and (c) TP53 mutation analysis remains a valuable tool in identifying childhood gliomas that will likely behave in a malignant fashion.

Papillary tumor of the pineal region: ultrastructural study of a case.

Papillary tumor of the pineal region (PTPR) is a recently classified neuroepithelial tumor for which there has been little comprehensive ultrastructural study. Here, we describe the radiographic, intraoperative, histologic, immunohistochemical, and in-depth ultrastructural findings in a case of PTPR. This study corroborates that PTPR has concomitant ependymal, neuroendocrine, and secretory features, and details novel ultrastructural as well as immunohistochemical features that further this argument. Discrepancies with prior descriptions of PTPR are described, as these differences may reflect phenotypic variability in this rare tumor, and the ultrastructural features that relate to the putative ependymal origin of the entity are emphasized.

Chordoma in the lateral medullary cistern in a patient with tuberous sclerosis: A case report and review of the literature.

BACKGROUND: Chordomas are rare intracranial tumors. There are several reported cases of these tumors arising in patients with tuberous sclerosis (TSC), a neurocutaneous disorder inherited in autosomal dominant fashion that predisposes patients to hamartomatous and neoplastic lesions. CASE DESCRIPTION: A 38-year-old man with the diagnosis of TSC presented with the complaint of dizziness and near syncope. Imaging revealed a mass in the lateral medullary cistern that was found at the time of surgery to be a chordoma. The patient underwent a left far lateral approach for removal of the tumor. Upon opening of the dura, the tumor could be seen under the arachnoid. The tumor was carefully debulked within the limits of safety. The patient did well postoperatively and was referred to the radiation oncology department at our institution for follow-up radiotherapy of the tumor bed. CONCLUSION: This study presents an unusual presentation and location for a chordoma and contributes to the growing literature associating chordomas with TSC.

Involvement of skeletal muscle in dialysis-associated systemic fibrosis (nephrogenic fibrosing dermopathy).

Nephrogenic fibrosing dermopathy (NFD), a newly recognized scleroderma-like disease, was originally described as a purely cutaneous disorder. More widespread involvement, including fibrosis of pulmonary and cardiac tissues, has been documented only recently, and it has been suggested that a more appropriate designation is dialysis-associated systemic fibrosis. We report five cases of this novel disorder, spanning a spectrum of primarily skin to primarily muscle involvement. Clinical, radiological, electrophysiological, and pathological studies revealed moderate to severe fibrosis of striated muscles. All patients had end-stage renal failure on chronic dialysis, subacute to chronic hardening of the skin and muscles, restriction of limb movements with joint contractures, but normal to only mildly weak muscle strength. Limitation of movements was caused predominantly by skin tightness and induration, and by joint contractures rather than muscle weakness. Computerized tomography showed fibrosis of the fascia and muscles in the most severely affected patients, and electromyography showed mild to severe myopathic changes. Histopathology of affected muscles revealed a spectrum of mild to severe fibrosis, degenerating fibers, and chronic inflammatory cells. These results further support the contention that NFD is not a purely cutaneous disease, but is part of a larger systemic fibrotic process that may involve muscles.

Hagfish intestinal antimicrobial peptides are ancient cathelicidins.

Three potent broad-spectrum antimicrobial peptides (HFIAP-1, -2, and -3) isolated from intestinal tissues of Myxine glutinosa (Atlantic hagfish) are identified as ancient members of the cathelicidin family of antimicrobial peptides, hitherto known only from mammals. In situ hybridization reveals that HFIAPs are produced in nests of myeloid cells within the loose connective tissue of the gut wall, a tissue reminiscent of both gut-associated lymphoid tissue (GALT) and vertebrate spleen. We suggest that this tissue organization provides local defense of the hagfish gastrointestinal tract via innate immunity and possibly served as the architectural plan upon which the adaptive immune system evolved.