Question 2 of 26

(demo test)

The vignette and the histology point the same way. A cystic posterior fossa mass with an enhancing mural nodule in an adult is the classic radiologic signature of hemangioblastoma, and the micrograph described shows the corresponding histology: a dense network of thin-walled capillary channels with intervening stromal cells, no mitotic figures and no necrosis. The stromal cells are the neoplastic element and their lipid-laden and glycogen-laden cytoplasm gives them the vacuolated, clear appearance seen on routine staining. Bradley records that hemangioblastoma usually presents as a cyst with an enhancing mural nodule in the cerebellum and is the most common primary cerebellar neoplasm in adults, which is exactly the clinical picture here.

Hemangioblastoma is a WHO grade 1 vascular tumor of uncertain histogenesis, peaking around age 40 and slightly more common in men. The stromal cells stain for inhibin-alpha, S100 protein, neuron-specific enolase and brachyury, and alpha-inhibin and D2-40 help separate hemangioblastoma from its main mimic, metastatic clear cell renal cell carcinoma, a distinction that matters greatly because both occur in von Hippel-Lindau disease. The VHL gene at chromosome 3p25-26 is a classic tumor suppressor: patients with the syndrome carry one germline defective allele and lose the second somatically, while sporadic tumors acquire two somatic hits. Loss of VHL protein stabilizes hypoxia-inducible factor and drives vascular endothelial growth factor expression, which explains the extreme vascularity, the associated cysts and occasional erythropoietin-mediated polycythemia. About ten percent of hemangioblastomas occur in von Hippel-Lindau disease, so a new diagnosis warrants germline testing, and in the syndrome the lesions are often multiple, arise in the cerebellum, brainstem and spinal cord, and require lifelong surveillance imaging.

The transferable principle is that in the posterior fossa the combination of age and imaging morphology narrows the differential before any tissue is obtained. Cystic lesions with a mural nodule in an adult suggest hemangioblastoma or metastasis; midline fourth ventricular tumors in children suggest medulloblastoma or ependymoma; and dural-based enhancing masses suggest meningioma. Recognizing hemangioblastoma and the obligation to test for von Hippel-Lindau disease sits at the Core level of RITE content, because it is a common posterior fossa lesion whose diagnosis triggers genetic counselling and multisystem screening for the whole family.

Incorrect Answers

• A. Ependymoma arises from ependymal lining, is far more common in children than adults, and typically fills and conforms to the fourth ventricle rather than forming a cyst with a mural nodule. Choose this if the histology showed perivascular pseudorosettes and true ependymal rosettes with a fibrillary background.
• B. Glioblastoma is a WHO grade 4 astrocytoma that is uncommon in the cerebellum and would show marked nuclear atypia, brisk mitotic activity, microvascular proliferation and pseudopalisading necrosis, none of which is present. Choose this if the imaging had shown an irregular ring-enhancing mass with central necrosis and infiltrating margins.
• D. Medulloblastoma is an embryonal tumor of the cerebellum that overwhelmingly affects children and adolescents, and its histology is sheets of small round blue cells with high nuclear to cytoplasmic ratio, frequent mitoses and Homer Wright rosettes. Choose this if the vignette described a young child with a midline vermian mass and leptomeningeal drop metastases on spinal imaging.
• E. Meningioma is a dural-based extra-axial tumor with a dural tail, and its histology shows meningothelial whorls and psammoma bodies rather than capillary channels with clear stromal cells. Choose this if the imaging had shown a broad dural attachment along the tentorium or petrous ridge with homogeneous enhancement.

Testing Pearls

• A cystic cerebellar mass with an enhancing mural nodule in an adult is hemangioblastoma until proven otherwise; in a child the same picture suggests pilocytic astrocytoma.
• Hemangioblastoma is WHO grade 1; the neoplastic element is the lipid-laden stromal cell, not the abundant capillary network.
• Roughly ten percent of hemangioblastomas occur in von Hippel-Lindau disease, so every new diagnosis warrants germline VHL testing.
• VHL loss stabilizes hypoxia-inducible factor and raises vascular endothelial growth factor, explaining tumor vascularity, cyst formation and occasional polycythemia.
• The main histologic mimic is metastatic clear cell renal cell carcinoma, which also occurs in von Hippel-Lindau disease; inhibin-alpha and D2-40 staining separate them.

References

1. Jankovic J, Mazziotta JC, Newman NJ, Pomeroy SL, editors. Bradley and Daroff's Neurology in Clinical Practice. 8th ed. Philadelphia, PA: Elsevier; 2022. p. 1097.
2. Dornbos D, Kim HJ, Butman JA, Lonser RR. Review of the neurological implications of von Hippel-Lindau disease. JAMA Neurol. 2018;75(5):620-627.
3. Chittiboina P, Lonser RR. Von Hippel-Lindau disease. Handb Clin Neurol. 2015;132:139-56.