Neuroradiology-Neuropathology Conference May, 2011 Michael Solle, MD Tom Bouldin, MD

 History  31 y/o male with 9 days headaches and nausea, and intermittent confusion.

ADC rCBV SWI

 Pathology ▪ Sections show proliferation of atypical astrocytes. Mitotic figures are identified. Microvascular proliferation is present. Foci of necrosis are also present. Histologic changes are consistent with glioblastoma. ▪ Glioblastoma, WHO grade IV

 CNS tumor classification (NCI webpage): ▪ WHO grade I includes lesions with low proliferative potential, a frequently discrete nature, and the possibility of cure following surgical resection alone. ▪ WHO grade II includes lesions that are generally infiltrating and low in mitotic activity but recur. Some tumor types tend to progress to higher grades of malignancy. ▪ WHO grade III includes lesions with histologic evidence of malignancy, generally in the form of mitotic activity, clearly expressed infiltrative capabilities, and anaplasia.  WHO grade IV includes lesions that are mitotically active, necrosis-prone, and generally associated with a rapid preoperative and postoperative evolution of disease.

 History  Patient was initially diagnosed with a posterior fossa mass presenting with headaches and vision disturbances in 6/2007.

 Pathology  Juvenile Pilocytic Astrocytoms, WHO grade I.  Sections of posterior fossa mass show moderately cellular glial proliferation with modest atypia and scattered Rosenthal fibers and eosinophilic granular bodies. Focally, there are microcytic changes within the cellular proliferation. No mitoses or necrosis are identified. ▪ Tumor cells stain positively for GFAP and negatively for synaptophysin.

 History  3 y-o male complaining of intermittent severe headache, was noted to have some gait ataxia by his mother.

 Lumbar puncture -Malignant cells present, consistent with medulloblastoma.

 Pathology  Intraoperative: ▪ Small round cell tumor consistent with medulloblastoma.  Final: ▪ Sections show a densely cellular neoplasm with small to medium sized nuclei. Some cells show nucleoli. There are mitotic figures and apoptosis. Also present are anaplastic features, including cell wrapping.  Immunohistochemical stains for synaptophysin, chromogranin, EMA, and GFAP are performed. The tumor cells are diffusely positive for synaptophysin. There are a few cells staining faintly for chromogranin. There are areas of strong staining for GFAP. There is only slight, focal, nonspecific staining for EMA. Controls immunostain appropriately. The immunohistochemical findings are consistent with medulloblastoma. ▪ Areas of this tumor show marked atypia, worrisome for anaplastic features. A stain for INI-1 was positive in tumor cells, ruling out ATRT.

Anaplastic medulloblastoma

Medulloblastoma “Classic” medulloblastoma Desmoplastic/nodular medulloblastoma Medulloblastoma with extensive nodularity Large cell medulloblastoma and anaplastic medulloblastoma (large cell/anaplastic medulloblastoma) Pathological Subtypes of Medulloblasoma

 History  … consultation for evaluation of a suprasellar mass… 41-year-old right-handed woman who has noted the onset of headaches for several years  … some confusion and memory loss  … progressive loss of vision, particularly in the periphery of her right eye since 8/2010.

Operative Findings:  1) Normal pituitary gland  2) diffusely infiltrative infundibular mass with subchiasmatic compression  3) gross total resection  4) preservation of right superior hypophyseal artery and perforators  5) visualization of third ventricle, basilar artery, posterior cerebral arteries, posterior communicating arteries, anterior communicating arteries, A2 vessels, A1 vessels, bilaterally.

 Pathology  Intraoperative: ▪ Granular cell tumor of the infundibulum  Final: ▪ Sections show a patternless proliferation of large cells with oval nuclei and large amounts of pink cytoplasm. Cytoplasm has a fine granularity. Modest nuclear pleomorphism. Sections stained with PAS-D, S-100, GFAP, synaptophysin, and CD68. Tumor cells show PAS-positive granules in cytoplasm. Tumor cells show positive immunostaining for S100 and GFAP. Tumor cells do not stain for synaptophysin. Numerous CD68- positive cells, consistent with macrophages, are scattered throughout the tumor.

PASH&E

Rare tumor arising in the sella turcica or suprasellar space. Arises from pituicytes, which are specialized astrocytes found in the posterior pituitary (neurohypophysis). Pituicytes give rise to granular cell tumors and pituicytomas, which are phenotypic variants. Granular Cell Tumor of the Infundibulum

 History  68 y-o female with multiple past cancers (lymphoma, breast, thyroid, melanoma) presenting with recently diagnosed lung and brain masses. Patient became acutely aphasic and was taken to the ED out of concern for a possible stroke.

 Pathology; Autopsy; Gross Description:  Large numbers of black, well circumscribed tumors, consistent with metastases, in all lobes of the cerebrum. Metastases are often, but not always, located at the gray/white junctions. Tumors vary from 2 mm to 2 cm in diameter.…. The deep gray matter nuclei also contain metastases.

 Pathology: Light Microscopy.  There is considerable involvement of leptomeninges by the metastatic melanoma. Tumor cells show marked pleomorphism. Some of neoplastic cells contain brown pigment. ▪ Immunohistochemical stains for S-100, Mart-1, and GFAP done on sections from brain. Many neoplastic cells show positive staining for S-100. Scattered neoplastic cells show positive staining for MART-1. The positive staining of some cells for S-100 and MART-1 and presence of brown pigment are consistent with malignant melanoma.

 40-60% of patients with melanoma have brain metastasis.  Melanoma cells are closely related to CNS cells due to their embryonic origin and neural crest cells, and they share common antigens such as MAG-1 and MAG-2.  After melanoma is detected in the brain, median survival is 3 months.  Source: eMedicine, brain metastases article. ▪