686

(22-47A) Coronal bone CT in a 36y woman shows a partially ossified destructive mass in the upper nasal vault, anterior cranial fossa .

(22-47B) Axial T2 FS demonstrates that the lobulated mass is hypointense compared with the brain.

(22-47C) T1 C+ FS shows the strongly enhancing mass . Malignant phosphaturic mesenchymal tumor was diagnosed on histopathology.

Contrast enhancement is marked but heterogeneous. Nonenhancing necrotic foci are common. A "dural tail" sign is absent.

Angiography. HPCs may invade and occlude dural sinuses, so CTV or MRV are helpful noninvasive techniques for delineating patency.

DSA shows HPCs as hypervascular masses with prominent vascularity, "early draining" veins, and intense prolonged tumor "staining" (22-46D). HPCs usually recruit blood supply from both dural and pial vessels.

Differential Diagnosis

The major differential diagnosis of low-grade SFT is typical (WHO grade I) meningioma. The major differential of HPC is a highly vascular aggressive meningioma, particularly an atypical or malignant meningioma. HPCs rarely calcify or cause hyperostosis, and a "dural tail" sign is typically absent.

Dural metastases with skull invasion can be indistinguishable from HPC. Rare neoplasms that can resemble HPC include gliosarcoma and malignant mesenchymal tumors.

Rarely, an intracranial SFT/HPC or malignant mesenchymal tumor can cause severe hypophosphatemia and metabolic bone disease not explained by any other metabolic or hereditary disease. These osteomalacia-inducing tumors (OITs) can be confused with aggressive meningioma (22-47). OITs secrete fibroblast growth factor 23, resulting in a paraneoplastic syndrome of hypophosphatemic osteomalacia. The most common intracranial OITs are phosphaturic mesenchymal tumors and SFT/HPCs. Most are preferentially located within the anterior cranial fossa.

Primary Melanocytic Lesions

Primary melanocytic tumors of the CNS are very rare with an estimated incidence of 0.9 per 10 million. Focal melanotic masses span a morphologic spectrum from low-grade melanocytoma to malignant melanoma. By far the most frequent melanocytic CNS lesions are metastases from extracranial malignant melanomas.

Primary CNS melanomas are thought to originate from leptomeningeal melanocytes, which are preferentially located at the base of the brain, ventral medulla, and along the upper cervical spinal cord. They can present as focal nodular masses or diffuse leptomeningeal infiltrates. Diffuse leptomeningeal melanotic infiltrates also occur in meningeal melanocytosis/melanomatosis (neurocutaneous melanosis) (22-48).

Melanocytoma and Melanoma

Melanocytomas account for less than 0.1% of all CNS neoplasms. Recent studies have shown that melanocytomas carry GNAQ/GNA11 mutations and present with copy number variants in chromosomes 3 and 6.

Melanocytomas are solitary, darkly pigmented, low-grade tumors that do not invade adjacent brain. Preferred sites are the posterior fossa (skull base, cerebellopontine angle), temporal lobe, Meckel cave (with nevus of Ota), and spinal cord/nerve roots. Melanocytomas rarely undergo malignant transformation.

Melanomas frequently demonstrate TERT promoter mutations and frequently harbor additional oncogene mutations. Prognosis is variable for melanocytic tumors of intermediate differentiation and poor for melanoma.

Melanotic lesions are hyperdense on NECT and enhance strongly on CECT. The paramagnetic properties of melanin cause T1 shortening, so

hyperintensity on T1WI and hypointensity (22-49) on T2WI are characteristic.

The major differential diagnosis for primary melanocytic lesions of the brain is metastatic malignant melanoma.

Diffuse Meningeal

Melanocytosis/Melanomatosis

Diffuse leptomeningeal melanocytosis and melanomatosis are usually features of neurocutaneous melanosis (NCM), a rare neurocutaneous syndrome of childhood. Most patients present with numerous congenital melanotic nevi of the skin.

Diffuse melanocytic lesions appear as dense, thick, black confluent aggregates that fill the subarachnoid spaces and coat the pia.

Bilateral T1 hyperintense foci in the amygdala is an early sign of NCM (22-49A). Diffuse leptomeningeal enhancement and

Tumors of the Meninges

687

extension into the brain parenchyma via the perivascular spaces can occur and usually indicate malignant transformation with poor prognosis (22-49B).

Melanotic Neuroectodermal Tumor

of Infancy

Also known as melanotic progonoma or retinal anlage tumor, melanotic neuroectodermal tumor of infancy (MNTI) is a rare tumor that usually arises from the maxilla, mandible, or cranial vault. Most patients present within the first year of life.

MNTIs are neural crest tumors that exhibit biphasic histology with melanin-containing and neuroblast-like cells. They are generally considered benign but can grow rapidly and be locally aggressive with intracranial extension, mimicking solitary fibrous tumor/hemangiopericytoma or sarcoma (2250). Malignant degeneration occurs but is uncommon.

(22-48A) Autopsy specimen shows diffuse leptomeningeal melanosis with gray-black discoloration of the entire brain surface. (Courtesy R. Hewlett, MD.) (22-48B) Axial section from the same specimen shows that the gyri are enlarged, studded with innumerable tiny black nodules representing tumor extension via perivascular spaces. This is diffuse primary leptomeningeal malignant melanocytosis. (Courtesy R. Hewlett, MD.)

(22-49A) T1WI in a patient with neurocutaneous melanosis shows characteristic ovoid hyperintensities in the amygdala of both temporal lobes . Another focus of melanotic deposition with T1 shortening is seen along the midbrain. (Courtesy S. Blaser, MD.) (22-49B) T1 C+ scan in the same patient shows diffuse, thick leptomeningeal enhancement. (Courtesy S. Blaser, MD.)

(22-50A) Axial T2WI in a 3m infant with a "bump" on the left side of the head shows an aggressive-appearing mass centered on the left occipital bone. Note intracranial extradural extension .

Other Related Neoplasms

Hemangioblastoma

Terminology

Hemangioblastoma (HGBL) is also known as capillary hemangioma. Although the term "blastoma" suggests malignant, highly aggressive lesions, HGBLs are benign, slowgrowing, relatively indolent vascular neoplasms. HGBL occurs in both sporadic and multiple forms.

Multiple HGBLs are almost always associated with the autosomal-dominant inherited cancer syndrome von HippelLindau disease (VHL). A rare non-VHL form of multiple disseminated HGBLs is termed leptomeningeal hemangioblastomatosis.

Etiology

The precise etiology of HGBLs remains unknown. VHL gene mutations (losses or inactivations) are present in 20-50% of sporadic HGBLs. Multiple key angiogenic pathways (including VEGF/VEGFR2 and Notch/DII4) are massively activated in HGBL and contribute synergistically to the tumor's abundant vascularization.

Pathology

Location. HGBLs can occur in any part of the CNS, although the vast majority (90-95%) of intracranial HGBLs are located in the posterior fossa. The cerebellum is by far the most common site (80%) followed by the vermis (15%). Approximately 5% occur in the brainstem, usually the medulla.

(22-50B) T1 C+ FS shows that the intra- , extracranial components of the calvarial mass enhance intensely. This is melanotic progonoma (melanotic neuroectodermal tumor of infancy). (Courtesy T. Poussaint, MD.)

The nodule of an HGBL is superficially located and typically abuts a pial surface (22-51).

Supratentorial tumors are rare, accounting for 5-10% of all HGBLs. Most are clustered around the optic pathways and occur in the setting of VHL.

Size and Number. Hemangiomas vary in size from tiny to large, especially when associated with a cyst. Unless they are syndromic, HGBLs are solitary lesions. If more than one HGBL is present, the patient by definition has VHL. A positive family history or presence of other VHL markers (such as visceral cysts, retinal angioma, renal cell carcinoma) should prompt genetic screening.

Gross Pathology. The common appearance is that of a beefy red, vascular-appearing nodule that abuts a pial surface (2252). A variably sized cyst is present in 50-60% of cases. Cyst fluid is typically yellowish, and the cyst wall is usually smooth. Approximately 40% of HGBLs are solid tumors.

Microscopic Features. HGBLs contain two different cell types, stromal and vascular cells. Generally it is the stromal (not the vascular) cells that are the neoplastic element of an HGBL.

The cyst wall of most HGBLs is nonneoplastic, composed of compressed brain with fibrillary neuroglia devoid of tumor cells. The intratumoral cyst fluid shares a proteomic fingerprint with normal serum and has no proteins in common with HGBL tumor tissue. Cyst formation in HGBLs is therefore a result of vascular leakage from tumor vessels, not tumor liquefaction or active secretion.

Mitoses in HGBLs are few or absent, so proliferation rates are low, too (usually MIB-1 less than 1). HGBL is a WHO grade I neoplasm. There is no recognized atypical or anaplastic variant.

HEMANGIOBLASTOMA: PATHOLOGY AND CLINICAL ISSUES

Pathology

•Posterior fossa (90-95%)

○Cerebellum most common site

•Cyst + nodule (60%), solid (40%)

Clinical Issues

•Epidemiology/demographics

○Uncommon (1.0-2.5% of primary brain tumors)

○7% of all adult primary posterior fossa tumors

○Peak age = 30-65 years (younger with VHL), rare < 15 years

•Presentation/natural history

○May cause hydrocephalus

○Dysmetria, ataxia

○5% have secondary polycythemia

○Slow, "stuttering" growth

○Metastasis rare

Clinical Issues

Epidemiology. HGBL accounts for 1.0-2.5% of primary CNS neoplasms and approximately 7% of all primary posterior fossa tumors in adults. It is the second most common infratentorial parenchymal mass in adults (after metastasis).

Between 25-40% of HGBLs are associated with VHL.

Demographics. HGBL is generally a tumor of adults between the ages of 30 and 65 years. Pediatric HGBLs are rare. VHL-associated HGBLs tend to present at a significantly younger age but are still relatively rare in children under the age of 15. There is a slight male predominance.

Presentation. Most symptoms in patients with the cystic form of HGBL are caused by the cyst, not the neoplastic nodule. Headache is the presenting symptom in 85% of cases. HGBLs produce erythropoietin, which causes secondary polycythemia in approximately 5% of patients.

Natural History and Treatment Options. Because HGBLs exhibit a "stuttering" growth pattern, they frequently are stable lesions that can remain asymptomatic for long intervals. Imaging progression alone is not an indication for treatment although tumor/cyst growth rates can be used to predict symptom formation and future need for treatment.

Although HGBLs show no intrinsic tendency to metastasize, there are sporadic reports of intraspinal dissemination. Complete en bloc resection is the procedure of choice. Total resection eliminates tumor recurrence although new HGBLs may develop in the setting of VHL.

Imaging

General Features. HGBLs have four basic imaging patterns: (1) solid HGBLs without associated cysts, (2) HGBLs with intratumoral cysts, (3) HGBLs with peritumoral cysts (nonneoplastic cyst with solid tumor nodule), and (4)

HGBLs associated with both periand intratumoral cysts (nonneoplastic cyst with cysts in the tumor nodule). A nonneoplastic peritumoral cyst with solid nodule is the most common pattern, seen in 50-65% of cases. The second most common pattern is the solid form, seen in about 40% of cases.

689

(22-51) Graphic depicts typical HGBL with cyst wall composed of compressed cerebellum. Vascular tumor nodule abuts pial surface.

(22-52A) Autopsy specimen shows superficial nodule abutting the pia , hemorrhagic cyst of a typical HGBL. (Courtesy E. Ross, MD.)

(22-52B) Sagittal section in the same case shows the hemorrhagic cyst . The tumor nodule is not visible. (Courtesy E. Ross, MD.)

690

HEMANGIOBLASTOMA: IMAGING

General Features

•"Cyst + nodule" (60%)

○Nodule abuts pial surface

•Solid (40%)

CT

•Low-density cyst

•Strongly enhancing nodule

MR

•Cyst

○Fluid slightly hyperintense to CSF

○Wall usually nonneoplastic

•Nodule

○Isointense to brain

○"Flow voids" common

○Enhances intensely

(22-53A) Axial T1WI in a

70y woman with ataxia shows a cystic cerebellar mass with a mural nodule . (22-53B) Axial T2 FS MR in the same case shows that the cyst fluidis very hyperintense, while the nodule is mostly isointense with adjacent brain.

(22-53C) FLAIR shows that the fluid does not suppress, and the mural nodule is hyperintense to brain parenchyma. (2253D) T1 C+ MR shows that the mural nodule enhances intensely , while the cyst wall does not exhibit any contrast enhancement . This is solitary hemangioblastoma, WHO grade I.

CT Findings. The most common appearance is a welldelineated isoto slightly hyperdense nodule associated with a hypodense cyst. Calcification and gross hemorrhage are absent. The nodule enhances strongly and uniformly following contrast administration.

MR Findings. An isointense nodule with prominent "flow voids" is seen on T1WI. If an associated peritumoral cyst is present, it is typically hypointense to parenchyma on T1WI but hyperintense compared with CSF (22-53).

Compared with brain parenchyma, the tumor nodule of an HGBL is moderately hyperintense on T2WI and FLAIR. Intratumoral cysts and prominent "flow voids" are common. The cyst fluid is very hyperintense on both T2WI and FLAIR

(22-53).

Occasionally an HGBL hemorrhages. If present, blood products "bloom" on T2*.

Intense enhancement of the nodule—but not the cyst itself—is typical (22-53D). Cyst wall enhancement should raise the possibility of tumor involvement, as compressed, nonneoplastic brain does not enhance.

Noncystic HGBLs enhance strongly but often heterogeneously (22-54). Multiple HGBLs are seen in VHL and vary from tiny punctate to large solid tumors (see Chapter 40).

Supratentorial HGBLs are rare. Most occur around the optic nerves or chiasm. HGBL occasionally occurs as a hemispheric mass with a "cyst + nodule" appearance (22-56).

Angiography. The most common appearance is that of an intensely vascular tumor nodule that shows a prolonged vascular "blush" (22-55). "Early draining" veins are common. If a tumor-associated cyst is present, vessels appear displaced and "draped" around an avascular mass.

Tumors of the Meninges

691

Differential Diagnosis

The differential diagnosis of HGBL varies with age. In a middleaged or older adult, the statistically most common cause of an enhancing posterior fossa intraaxial (parenchymal) mass is metastasis, not HGBL! DWI and DSC-PWI are helpful in the characterization and differentiation of HGBL from brain metastases. HGBL has higher minimum ADC values and relative ADC ratios compared with metastases.

A cerebellar mass with "cyst + nodule" in a child or young adult is most likely a pilocytic astrocytoma, not HGBL or metastasis. Occasionally a cavernous malformation can mimic an HGBL with hemorrhage.