3-D imaging mass spectrometry of protein distributions in mouse Neurofibromatosis 1 (NF1)-associated optic glioma.

Neurofibromatosis type 1 (NF1) is a common neurogenetic disorder, in which affected individuals develop tumors of the nervous system. Children with NF1 are particularly prone to brain tumors (gliomas) involving the optic pathway that can result in impaired vision. Since tumor formation and expansion requires a cooperative tumor microenvironment, it is important to identify the cellular and acellular components associated with glioma development and growth. In this study, we used 3-D matrix assisted laser desorption ionization imaging mass spectrometry (MALDI IMS) to measure the distributions of multiple molecular species throughout optic nerve tissue in mice with and without glioma, and to explore their spatial relationships within the 3-D volume of the optic nerve and chiasm. 3-D IMS studies often involve extensive workflows due to the high volume of sections required to generate high quality 3-D images. Herein, we present a workflow for 3-D data acquisition and volume reconstruction using mouse optic nerve tissue. The resulting 3-D IMS data yield both molecular similarities and differences between glioma-bearing and wild-type (WT) tissues, including protein distributions localizing to different anatomical subregions. BIOLOGICAL SIGNIFICANCE: The current work addresses a number of challenges in 3-D MALDI IMS, driven by the small size of the mouse optic nerve and the need to maintain consistency across multiple 2-D IMS experiments. The 3-D IMS data yield both molecular similarities and differences between glioma-bearing and wild-type (WT) tissues, including protein distributions localizing to different anatomical subregions, which could then be targeted for identification and related back to the biology observed in gliomas of the optic nerve.

Primary atypical teratoid/rhabdoid tumor of the optic nerve: a rare entity in an exceptional location.

Atypical teratoid/rhabdoid tumors are rare and highly malignant central nervous system tumors. They have no specific radiological features and often present several histological components that make a problem in differential diagnosis with medulloblastoma and primitive neuroectodermal tumors. We present the case of a newborn girl complained of a gradual proptosis of the left eye secondary to an expansive lesional process of the optic nerve. The location at the optic nerve, reported only twice in the literature, and an exclusive rhabdoid appearance on biopsy added additional differential diagnosis problems. The proptosis worsened and the infant died few days after two cycles of chemotherapy. VIRTUAL SLIDES: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2037718783145212 .

Isolated optic nerve infiltration in systemic lymphoma--a case report and review of literature.

Ocular involvement in non-Hodgkin lymphoma occurs either as primary ocular, central nervous system lymphoma or isolated intraocular lymphoma. Recurrence of systemic non-Hodgkin lymphoma in the form of CNS lymphoma has been reported. However, recurrence as an isolated optic nerve lesion without involving CNS has never been reported in the pediatric age group. We report a case of systemic diffuse large B-cell lymphoma in a 2-year-old female, which primarily occurred as suprapubic mass and later recurred in the form of isolated optic nerve infiltration, after remission of the primary disease. Early detection and prompt treatment resulted in complete reversal of the disease.

Artery, vein, neither, both?

Combined central retinal vein and central retinal artery occlusion is a rare complication of compressive or infiltrative optic nerve disease. In this case combined retinal arterial and venous occlusive disease was the presenting sign of metastatic adenocarcinoma to the optic nerve sheath. An optic nerve sheath biopsy led to the diagnosis. Clinicians should be aware that retinal vascular disease can be due to optic nerve disorders including metastatic carcinoma.

A case of neurofibromatosis 1 presenting with optic pathway glioma with an early onset and an aggressive course.

Optic pathway glioma associated with neurofibromatosis 1 has a classically indolent course. However, involvement of the optic radiations is relatively rare and is associated with a more aggressive course. A three-year-old girl presented with strabismus and loss of vision in the left eye with relative afferent pupillary defect and optic disc pallor. She had multiple cafiota au lait spots. Visually evoked potential was suggestive of an optic nerve conduction defect and magnetic resonance imaging of the brain was suggestive of an optic pathway glioma involving the optic nerves, the optic chiasma and the optic tracts. The optic radiations and the dendate nuclei had hamartomas. Optic nerve biopsy confirmed pilocytic astrocytoma. Radical radiotherapy under general anesthesia was subsequently given. This case report aims to highlight the involvement of the optic radiations and the unusually aggressive clinical course in this case.

Bilateral primary optic nerve lymphoma.

A 69-year-old man was examined for bilateral infiltrative optic neuropathy. Optic nerve biopsy confirmed a malignant B cell lymphoma. Systemic examination and investigations failed to show involvement of other sites.

Hemangiopericytoma of the optic nerve sheath.

PURPOSE: To report the clinicopathologic findings in patient with optic nerve sheath hemangiopericytoma. DESIGN: Clinicopathologic report. METHODS: The clinical, histologic, and immunohistochemical findings of a patient with optic nerve sheath hemangiopericytoma were reviewed. RESULTS: An excisional biopsy of an optic nerve sheath tumor from a 35-year-old woman showed a staghorn vascular pattern consisting of CD34-positive tumor cells. CONCLUSIONS: Hemangiopericytoma may occur rarely in the optic nerve sheath.

Systemic non-Hodgkin's lymphoma with optic nerve infiltration in a patient with AIDS.

PURPOSE: To report the clinicopathologic features of a patient with AIDS and clinically regressed systemic non-Hodgkin's lymphoma who subsequently developed lymphomatous infiltration of the optic nerve and occlusion of the central retinal vein in both eyes. METHODS: The eyes of this patient were examined ophthalmologically and by fluorescein angiography. The eyes, brain, and body were obtained after death and studied by light microscopy. RESULTS: Ophthalmic examination and fluorescein angiography revealed optic nerve swelling and central retinal vein occlusion first in the left eye and shortly thereafter in the right eye. Postmortem histopathologic examination showed dense infiltration of both optic nerves by lymphoma as well as necrotizing vasculitis involving the retinal vessels near the left optic nerve head. Examination of the brain revealed lymphomatous involvement in the paraventricular region with associated necrosis and inflammation. No bone marrow recurrence or other residual systemic lymphoma was present. CONCLUSION: This case demonstrates that infiltrative optic neuropathy may occur as the sole ocular manifestation of disease recurrence in a patient with systemic non-Hodgkin's lymphoma otherwise thought to be in clinical remission.

Gliomas of the optic nerve: histological, immunohistochemical (MIB-1 and p53), and MRI analysis.

Gliomas of the optic nerve, although typically of pilocytic (WHO grade I) histology, can present within the spectrum of astrocytic neoplasia including glioblastoma (WHO grade IV). In certain cases, histologic features alone make the distinction between pilocytic and diffuse astrocytomas difficult. We reviewed 22 cases of optic nerve gliomas, 19 of which were pilocytic astrocytomas (PA), and 3 of which were diffuse, non-pilocytic astrocytomas. The cases were evaluated for their clinical course, radiographic appearance, histologic grade, and proliferation indices as detected by MIB-1 (Ki-67) and p53 antibodies. Of the 19 PA, 14 showed no tumor growth by magnetic resonance imaging, and had Ki-67 and p53 labeling indices (LI) of < 1%. The other 5 PA exhibited aggressive behavior manifest by marked diffuse infiltrative tumor growth causing death in 2 patients, 1 of whom was diagnosed with neurofibromatosis type 1 (immunoperoxidase and radiographs not available), and marked local growth with an average time to growth of 39.3 months, a Ki-67 LI of 2-3%, and a p53 LI of < 1% in three others. Three of the five aggressive PA histologically demonstrated a finely reticulated pattern, a pattern that appears as an exaggeration or expansion of the normal neuroglia of the optic nerve, and may simulate a diffuse low-grade astrocytoma. Two demonstrated the coarsely reticulated pattern, with the biphasic and microcystic pattern typical of PA. Three diffuse astrocytomas (2 anaplastic astrocytomas and 1 glioblastoma) originated clinically and radiographically from the optic nerve, and revealed a Ki-67 LI of 2-12%, a p53 LI of 2-8%, and an average time to growth of 8 months. We conclude that the majority of PA of the optic nerve are non-aggressive, stabilize radiographically, and have Ki-67 and p53 LI < 1%. However, a subpopulation of PA has a propensity for aggressive behavior, and are identified by a Ki-67 LI of 2-3% and a p53 LI of < 1%. Diffuse astrocytomas have both Ki-67 and p53 LI > 2%. Thus, in cases of aggressive optic nerve tumors in which the histologic review of biopsy material cannot confidently confirm the diagnosis of pilocytic or diffuse fibrillary glioma, a p53 LI of > 1% appears to favor the diagnosis of diffuse astrocytoma.