Patrick Farley MD (Neuroradiology) and Thomas Bouldin MD (Neuropathology), UNC, Chapel Hill

1. Patrick Farley MD (Neuroradiology) and Thomas Bouldin MD (Neuropathology), UNC, Chapel Hill

2. Case 1 • History: Middle-aged man with no significant PMH became confused and disoriented. Head CT showed a brain mass. He was transferred to UNC.

3. Imaging: • Head CT: • 2.6-cm left frontal lobe lesion with surrounding edema. • Brain MRI: • Multiple bilateral supra-and infratentorial enhancing lesions. The largest is located in the left parietal lobe causing 7 mm of midline shift. • MR Spectroscopy: • Increased choline to creatinine ratio in the region of the left parietal mass. • Diffusion tensor imaging: • Loss of anisotropy in mass and surrounding tissues.

7. Ring Enhancing Lesion Diff Dx • Metastases Parenchymal • Substantial vasogenic edema for relative size of lesion at corticomedullary junctions • Abscess • Thin T2 hypointense rim characteristic and central diffusion restriction • Multiple Sclerosis • Enhancement indicates acute demyelination, with minimal mass effect; periventricular location • Coexistence of enhancing and nonenhancing lesions due to relapsing, remitting nature of disease • Acute Disseminated Encephalomyelitis (ADEM) • Multifocal white matter and/or basal ganglia lesions • May have with punctate, ring, incomplete ring, or peripheral enhancement • Neurocysticercosis • Ring enhancement seen in colloidal vesicular & granular nodular stages

8. Less Common Ring Enhancing Diagnoses • Immunocompromised • Tuberculosis • Caseating TB granulomas often have markedly T2 hypointense centers • Infants, children, & immunocompromised are predisposed. Opportunistic Infection, AIDS • Multiple ring-enhancing lesions in HIV+ patient: • Consider toxoplasmosis, TB, pyogenic/fungal abscess, & lymphoma • Toxoplasmosis is most common opportunistic infection • Basal Ganglia & gray-white matter junctions • Asymmetric "target sign": Enhancing eccentric nodules within abscess cavity • MRS may differentiate Toxo from lymphoma; NAA & choline usually nearly absent (Toxo) • Lymphoma, Primary CNS • Ring enhancement seen in HIV+ patients with lymphoma • MRS: Elevated choline peak • Radiation necrosis may cause multiple enhancing lesions • Often difficult to differentiate from recurrent tumor • MRS: No elevated choline. MR perfusion: Hypoperfusion • Multifocal Glioblastoma Multiforme • Seen in malignant transformation of low grade glioma & spread of primary GBM • Subacute Intracerebral Hematomas • Subacute Cerebral Infarctions • Enhancement pattern is ring-like and gyriform

9. Neuropathology  Photomicrograph of brain biopsy showing necrosis (*), nuclear debris of degenerating cells (short arrow), and two tissue cysts containing bradyzoites (long arrow) typical of Toxoplasma gondii. The histologic changes are consistent with CNS toxoplasmosis.

10. Toxoplasma gondii • A protozoan and an obligate intracellular parasite • Affects ~30% of the world’s population • Sexual cycle (oocyst stage containing sporozoites) occurs within feline intestinal tract (definitive host) • Humans get infected by ingesting oocysts (fecal–oral spread) or tissue cysts (undercooked meat). • After ingesting the organisms (sporozoites in oocysts; bradyzoites in tissue cysts), the organisms invade the gut epithelium, differentiate into tachyzoites, and disseminate to body organs via the blood stream.

11. Toxoplasma gondii • Tachyzoites invade cells, especially those of CNS, eye, skeletal muscle, and heart. • When conditions are unfavorable, tachyzoites convert to bradyzoites and become encysted (tissue cyst) within cells. • Wall of tissue cyst has very low immunogenicity, so that tissue cysts can persists for very long time. • If tissue cyst ruptures, bradyzoites convert to tachyzoites and replicate within tissue until controlled by immune response. • Control of infection depends on an interferon-gamma-dependent cellular immune reaction. • CNS toxoplasmosis has a predilection for the basal ganglia and gray-white junction

12. Case 2 • Middle-aged man recently s/p left upper lobectomy for fungal infection. Resected lung specimen also found to contain a poorly differentiated spindle cell neoplasm. • Several days after surgery, patient was noted to have rhythmic jerking of his head to the left with intermittent jerking spells in his right and left arms. Imaging studies of the head were done.

13. Imaging • CT: • Multiple lesions in brain parenchyma with surrounding edema. • MRI: • Enhancing masses w/central necrosis and surrounding vasogenic edema. One lesion demonstrated blood products compatible with hemorrhage.

15. Neuropathology Left panel: Patient died from metastatic cancer. At postmortem examination, a coronal section of the formalin-fixed brain shows two well-circumscribed metastases. Note the edema surrounding each metastasis. The dark color of the metastases is due to associated hemorrhage. Right panel: Photomicrograph of one of the brain metastases shows a poorly differentiated, pleomorphic spindle cell neoplasm. Immunohistochemical stains did not reveal the histogenesis of this neoplasm.

16. Middle-aged man w/personality changes, occasional left-sided headaches, left-sided pain in teeth, and left lower extremity pain. Dentist found no cause for pain and advised him to go to hospital. A head CT was done and showed a left temporal mass. MRI of brain confirmed this finding. Case 3

17. MRI: Large enhancing mass in the left temporal lobe, with solid and cystic components and mass effect on left temporal lobe.

19. Neuropathology Neuropathology Photomicrograph of brain biopsy showing a poorly differentiated, very pleomorphic glial neoplasm. Several tumor giant cells with huge nuclei are present in this field. The histologic findings are those of a giant cell glioblastoma, WHO grade IV.

20. There are two currently recognized variants of glioblastoma— Giant cell glioblastoma and Gliosarcoma The mean age at presentation for giant cell glioblastoma is ~41 years. Giant cell glioblastoma has short clinical course, like “primary” glioblastoma, but a high frequency of TP53 mutations, like “secondary” glioblastoma. Giant cell glioblastoma is usually a circumscribed, firm tumor that may mimic a metastasis. Giant cell glioblastoma often arises in the temporal or parietal lobes. Giant cell glioblastoma and glioblastoma have a similar prognosis. Giant cell glioblastoma

21. Case 4 • History: • 7 yo boy with no PMH presents with progressively worsening HA x 2 weeks, vomiting x 1 today, and lethargy. Had a CT that showed hydrocephalus and a mass in 3rd ventricle. • MRI: • Round hypointense lesion in 3rd ventricle and suprasellar regions with peripheral enhancement and internal septations. Obstructive hydrocephalus, secondary to mass.

23. Neuropathology  Photomicrograph of biopsy of tumor showing a squamous epithelium and the formation of “wet keratin” (*). These histologic features are typical of an adamantinomatous craniopharyngioma, WHO grade I.

24. Case 5 • History: • This 23-year-old patient was involved in an altercation and had a head CT as part of the trauma workup. The CT revealed a cerebellar mass. MRI confirmed the lesion. • MRI: • Complex enhancing cerebellar mass with two components. Inferior component has thicker rim of enhancement. Superior component demonstrates numerous internal septa, fluid levels, and low T2 signal rim, suggesting possible prior hemorrhage.

26. Neuropathology Photomicrograph of biopsy showing proliferation of glial cells with mild atypia and no mitotic figures. Several microcysts are present in this field. The histologic findings are those of pilocytic astrocytoma, WHO grade I.

27. Pilocytic Astrocytoma • Cystic cerebellar mass with enhancing mural nodule • Rare in adults • Hemorrhage is rare • Other Considerations • Medulloblastoma • Hyperdense enhancing mass filling 4th ventricle • Ependymoma • Mass within the 4th ventricle • Metastasis • Hemangioblastoma

28. Case 6 • Man in is late 60s, who has felt unsteady on his feet for last three months, as though he were "drunk." He feels he needs to focus on walking and needs a wider-based gait to feel steady. • CT: Partially solid and cystic, enhancing mass lesion; intra-axial in cerebellum. • MRI: Large, partially cystic mass, with solid nodular component that demonstrates intense contrast enhancement.

30. Neuropathology Photomicrograph of biopsy showing a proliferation of “stromal cells” with oval nuclei, mild atypia, and no mitotic figures. Also prominent in the tumor are multiple blood-filled vascular channels. The histologic findings are consistent with a hemangioblastoma, WHO grade I.

31. Hemangioblastoma • Solid and cystic cerebellar tumor in an adult with enhancing mural nodule abutting the pia. • 25-40% occur in patients with Von Hippel-Lindau syndrome. • The histogenesis of the “stromal cells” is not clear.