• There were only very rare cases arising in malignant transformation of benign schwannoma or sympathetic ganglion tumors.⁴ Large and medium-sized nerves are more often involved than small nerves. Common sites of origin include the sciatic nerve, brachial plexus, and upper arm. MPNSTs affect young to middle-aged adults, with a slight female predominance.

• Neurofibromatosis type 1 (NF-1) predisposes to the development of MPNSTs. About 50–60% of MPNSTs occur in patients with NF-1.^2,³ In addition to hereditary factors, exposure to ionizing radiation also may play a role in the development of MPNSTs.

HISTOLOGY

• The malignant nerve sheath tumors are confined to the cells intrinsic to the peripheral nerve sheath, including the perineurium and endoneurium. These tumors are generally regarded as being of Schwann cell origin because most of them usually exhibit some evidence of Schwann cell differentiation and the small minority have the features of fibroblast or perineurial cells.

• Histologically, MPNSTs are usually more hypercellular with spindle cell proliferation. The tumor cells often show hyperchromatic nuclei and are mitotically active.⁴

• Microscopically, the tumor shows fasciculated growth of tightly packed, hyperchromatic spindle cells (Fig. 6-1). The fibrosarcoma-like fascicles are focally alternating with hypocellular myxoid zones, creating a marbleized appearance. Focal, subtle nuclear palisading and waving nuclei are present. Moderate cellular atypism, high mitotic activity, and foci of necrosis are also noted (Fig. 6-2).

• In the immunohistochemical studies, the tumor cells are positive for S100 and negative for cytokeratin, desmin, and CD34. Positive p53 immunoreactivity is noted in 10% of tumor cells.

Fig. 6-1 Low-power photomicrograph of malignant peripheral nerve sheath tumor shows spindle to ovoid tumor cells with fascicular arrangement (hematoxylin–eosin stain, ×40).

Fig. 6-2 High-power photomicrograph of MPNST shows buckle-like irregular nuclear shape (hematoxylin–eosin stain, ×400).

RADIOLOGY

• Imaging findings with MPNST are not specific and can mimic metastatic lesions to the vertebrae.

• On plain radiographs, nerve sheath tumors typically appear as sharply marginated, round, elliptical, or lobulated paraspinal masses. Intervertebral foramen widening is seen and erosion of the ribs and vertebral bodies sometimes is evident ⁵ (Fig. 6-3).

• On computed tomography (CT) scan, schwannoma has been shown to have a mixed attenuation, attributable to a confluent area of hypocellularity adjacent to dense cellularity, or xanthomatous change, or regions of cystic degeneration. Variable enhancement of the tumor may be seen after contrast infusion. Calcification (about 5–10%) may be present with either benign or malignant tumors but is not a reliable sign of benign character.

• On magnetic resonance imaging (MRI), MPNSTs typically have iso-signal intensity as muscle on T1-weighted images (T1WI) and markedly increased signal intensity on T2-weighted images (T2WI) or contrast-enhanced images, although often in an inhomogeneous fashion (Figs. 6-4 to 6-7).

Fig. 6-3 Plain radiography (left) and CT scan (right) of MPNST. Compression fracture of T7 and T8 and mild scoliotic deformity are seen on plain radiography. On CT scan, an osteolytic lesion invades the vertebral body and epidural mass formation is observed. On the margin of the tumor mass, an osteosclerotic bony margin is formed (right).

Fig. 6-4 MRI sagittal view of MPNST. On T2WI, a mixed high signal intensity mass is seen in the T7, T8 vertebral body and epidural space. The spinal cord is compressed from the posterior side (left). Diffuse low signal change of the T7, T8 vertebral body is observed on T1WI (middle). An epidural mass is easily delineated from the epidural fat. With gadolinium use, a homogeneous enhancement pattern is shown (right).

Fig. 6-5 Axial MRI of MPNST at T7. Tumor mass surrounds the spinal cord and constricts the entire dura. Epidural mass is connected with an intraosseous mass at T7.

Fig. 6-6 Another case of the MPNST at T10. On the sagittal view of MRI, the signal of the mass is mixed (T2WI; left), diffuse low (T1WI; middle), and dense enhancement pattern (right). On T1WI, the T10 vertebral body shows no signal change. The mass abuts the posterior cortex of the vertebral body. The tumor does not infiltrate the vertebral body.

Fig. 6-7 Axial view of T10 MPNST. The location of the tumor mass is purely extradural. The mass grows into posterior back muscle, but the lamina is not destroyed. The signal of the mass is the same as that in the sagittal view. The posterior cortex of the vertebral body is slightly displaced and eroded but not destroyed.

HEMANGIOPERICYTOMA

EPIDEMIOLOGY

• Hemangiopericytomas are thought to arise from the pericyte, a modified smooth muscle cell that normally surrounds reticular sheath capillaries and postcapillary venules.⁶

• Hemangiopericytomas are soft tissue tumors that rarely occur within the CNS.

• A recent review of 94 CNS hemangiopericytomas reported a 60% local recurrence rate and a 23% rate of metastasis.⁷

DISTRIBUTION

Only 39 cases of primary hemangiopericytoma have been reported in the spinal column, and only five have been intradural.⁷

HISTOLOGY

• The microscopic examination reveals a richly vascular tumor with thin-walled blood vessels (Fig. 6-8). With reticulin staining, an individual tumor cell is surrounded by fine reticular fibers.

• The vessels vary in size and show the classic “staghorn” ramification.

• The tumor cells have oval to elongated nuclei and are densely cellular between the vessels, with occasional mitoses.

• Malignant features such as increased cellularity, prominent mitoses, necrosis, and hemorrhage are commonly seen.

• On immunohistochemistry, tumor cells are positive for vimentin (a mesenchymal marker) and factor 13a.⁶

• They are negative for CD34, which stains the vascular endothelium. Epithelial membrane antigen, factor 8, Leu 7, and S100 protein are also negative.⁶

Fig. 6-8 Ovoid to spindle cell tumor with branching “stag horn” pattern of vascular spaces. This case is malignant hemangiopericytoma with hyperchromatic nuclei and frequent mitotic figures (hematoxylin–eosin stain, ×200).

RADIOLOGY

• Hemangiopericytoma is of intermediate signal on the precontrast T1-weighted sequence and of increased signal on the T2-weighted sequence (Fig. 6-9).

• After the intravenous administration of gadolinium, the lesion enhanced diffusely (Fig. 6-10).

• Extradural hemangiopericytoma often can be associated in the same patient (Fig. 6-11).

• The differential diagnoses made on the basis of the imaging findings include neurofibroma, schwannoma, meningioma, and myxopapillary ependymoma.

Fig. 6-9 Sagittal MR of intradural hemangiopericytoma. On T2WI, ventral mass of slightly high signal is seen at the C1 level (A). On T1WI the mass is slightly high signal (B). On gadolinium use, the mass becomes bright (C).

Fig. 6-10 Axial MR of intradural hemangiopericytoma. On T1WI, the mass is attached to the ventral dura and abuts the spinal cord (A). With gadolinium, the mass shows dense enhancement (B). On coronal view, the configuration of the mass is round and apart from the spinal cord (C).

Fig. 6-11 Extradural mass of metastatic hemangiopericytoma. The mass is located in the left extraforaminal space between T7 and T8. Sagittal view (A) and axial view (B).

CEREBROSPINAL FLUID DISSEMINATED METASTASIS—LEPTOMENINGEAL METASTASIS

EPIDEMIOLOGY

• The dissemination of cancer cells within the spinal subarachnoid space is a devastating complication of systemic cancer, which is a feature of advanced stages of disease.

• Leptomeningeal metastasis (LM) is a relatively common complication of cancer, occurring in 3–8% of all patients with cancer.

• The primary tumors that commonly cause leptomeningeal spread comprise primary brain tumors (particularly glioblastoma), central nervous system (CNS) lymphoma, lymphoreticular tumors (leukemia, lymphoma), breast cancer, lung cancer, and melanoma (Table 6-1).⁸

• The percentage of primary brain tumors is very high (23%). LM develops in the end stage of disease in primary brain tumor patients.

Table 6-1 Primary Tumors that Commonly Cause Leptomeningeal Metastasis ⁸

Primary Tumor	n (%)	Histology (n)
Primary brain tumors	36 (23)	Glioblastoma (20)
		Astrocytoma (4)
		Oligodendroglioma (2)
		Ependymoma (3)
		Medulloblastoma (6)
		Germinoma (1)
PCNSL	14 (9)	High-grade NHL (14)
Lymphoreticular tumors	17 (11)	Low-grade NHL (3)
Metastatic to the CNS		CLL (4)
		High-grade NHL (3)
		ALL (1)
		NHL nos (2)
		Hodgkin’s lymphoma (1)
		Langerhans’ histiocytosis (1)
		Non-Langerhans’ histiocytosis (1)
		AML (1)
Melanoma	21 (14)
Breast cancer	30 (19)
Lung cancer	20 (13)	SCLC (8)
		NSCLC (7)
		nos (5)
Others	8 (5)	Gastric cancer (2)
		Ovarian cancer (1)
		Endometrial carcinoma (1)
		Prostate cancer (1)
		Myosarcoma of the uterus (1)
		Fibrous histiocytoma (1)
		Mesothelioma (1)
CUP	9 (6)

PCNSL, primary central nervous system lymphoma; NHL, non-Hodgkin’s lymphoma; NOS, not otherwise specified; CNS, central nervous system; CLL, chronic lymphocytic leukemia; CUP, carcinoma of unknown primary; ALL, Acute lymphoblastic leukemia; AML, acute myeloblastic leukemia; SCLC, small-cell lung cancer; NSCLC, non-small lung cell cancer.