Case 1. Oligodendroglioma. Tissue infiltration, seen well in the cortex as perineuronal satellitosis, essentially identifies this lesion aseither oligodendroglioma (grade II or III)or infiltrating astrocytoma (grade II, III, or IV). Distinguishing the two is based on cell distribution (more uniform in oligodendroglioma), cytological features (round and monotonous in the oligodendroglioma), and the well known perinuculear haloes (“fried egg cells”)that, while distinctive, are non-specific. The scattered nodules with higher cellularity, seen both on macro- and microscopically in this case, are common in oligodendrogliomas, usually higher grade examples. Molecular characterization is increasingly utilized in the distinction. The requisite chromosomal loss (1p and 19q)is not an either/or situation, but deletion of both, i.e. codeletion, of 1p and 19q. Isolated loss of 19q or, less commonly, of 1p does not make the lesion oligodendroglioma, or “halfway” so. Grading depends largely on mitotic activity, although there are no consensus guidelines about a grade III threshold. Some observers assume that vascular proliferation is an index of grade III as well. The present lesion has mitoses but not in large numbers. No vascular proliferation is present.

Case 2. Hematoma.Composed of blood and macrophages, the mass is not thehigh grade glioma anticipated by the surgeon. The blood is recognizable without much effort,or overlooked as incidental, but macrophages may go undetected if the surgeon’s impression is taken at face value. A “prove-it-to-me”approach that asurgical specimen isreally a neoplasm is highly recommended. Smear preparations are helpful since macrophages are readily recognized therein. Common causes of intracranial hemorrhage likely to be approached surgically include tumor such as melanoma, vascular malformation, and amyloid (congophilic) angiopathy. The last should be suspected in hemorrhages in the elderly.

Case 3.Immature TeratomaWith Germinoma. Representatives of all germ cell layers are obviousin this complex lesion. Although matureoverall, there were areas of fetal-like brain for which the designation “immature teratoma” was appropriate.Less obviousare isolated or clustered cells with large round nuclei, prominent nucleoli, and scattered mitoses. Some have attracted lymphocytes, but not in the large numbers common in germinomas. The cytological features are highly suggestive of the entity, and confirmed by positive staining for CD117 and OCT4. Although still widely used, immunostaining for placental alkaline phosphatase has a substantial incidence of false negatives and was not employed. Although obvious here, germinoma cells in teratomas can be focal and need to be carefully sought.

Case 4. Hemangioblastoma.Hemangioblastomas can assume many guisesand, especially in small fragmented specimens, may be difficult to recognize. Awareness of the entity, which occurs in cerebellum, medulla oblongata, spinal cord, and retina, is therefore critical. The present,highly vascular lesion has a sharp tumor-brain interface, compact nested architecture with clear cells suggesting both hemangioblastoma and renal cell carcinoma, and scattered large dark, pleomorphic nuclei. The lipid content of the vacuolated extravascular, “stromal”, cells can be demonstrated by oil-red-O staining at the time of frozen section. The immunostain of choice is inhibin that is often paired with markers for renal cell carcinoma, e.g. CD10 and Pax8. RCC is less useful.Scanning of the kidneys may be advisable in ambiguous cases.

Case 5. Meningioma. The histologically non-descript lesion has a compact growth pattern and does not appear to be an infiltrative process. While there is a resemblance to meningioma, no specific features, i.e. whorls, are present. Because of an initial negative result for EMA staining, tissue set aside in glutaraldehyde wasprocessed for electron microscopy. The latter found interdigitating processes joined by desmosomestypical of meningioma and many other epithelial tumors. These complex junctions are to be distinguished from less structured and less specificadherens junctionsthat are present in many tumor types. Repeat immunostaining for EMA was positive,albeit focally, in the granular surface reaction typical of meningioma. Some tumor cells were positive for progesterone receptors. The third ventricle is an unusual site for a meningioma, which, when intraventricular, favors the lateral ventricles.

Case 6. Primary CNS Lymphoma (PCNSL). The infiltrating lesion has prominent aggregates of cells that in favorable planes of sectionsare clearly angiocentric. At higher magnification, large round nuclei, prominent nucleoli, mitoses, and abundant apoptosis are all typical of PCNSL. Immunostainingrevealed crisp membrane positivity for CD20, with small reactive lymphocytes reacting for CD3. A lesion that enhances homogeneously, i.e. without a dark central core of necrosis so common in glioblastoma and many metastases, should always raise the possibility of PCNSL. Multiple such lesions are even more suspicious. PCNSLs are often approached by stereotactic approach and specimensare therefore typically small. The distinctive cytological features of lymphomas are well seen in smear preparations. Corticosteroids used to control edemaoften have a powerful antitumor apoptotic effect and PCNSLs so treated may have few if any viable tumor cells. Steroids had been withheld in this case until the biopsy was completed.