A 42‐YEAR‐OLD MAN WITH A DENSELY VASCULAR SPINAL MASS

CLINICAL HISTORY

A 42‐year‐old man was admitted to the neurosurgery department because of paraparesis and sensory deficits of both feet. The CT scan and MRI examination revealed a solitary intramedullary lesion bulging dorsally from the thoracic spine (T4 level) (Figure 1). Spinal angiography revealed the dense vascularity of the lesion, the presence of feeding and draining vessels, as well as intra‐lesional shunting. A gross total resection was performed.

Figure 1.

MICROSCOPIC DESCRIPTION

Examined at low power, the lesion was a densely cellular, highly vascularized tumor (Figure 2A). Malformative vessels of different calibers were conspicuous; some were dilated with thickened sclerotic walls (Figure 2B). In addition, vessel walls were encrusted with more or less abundant deep‐blue dot‐like or laminated material (Figure 2C); some larger accumulations of it were easily recognizable as “tombstones” of obliterated vessels (Figure 2D). Areas separating these vascular channels were dominated by sheets of immature‐looking mostly round or vaguely spindled cells with indistinct cell borders (Figure 3A,B). Larger ones with irregular nuclei, course chromatin, and more abundant eosinophilic cytoplasm were easily found (Figure 3A), as were mitoses. So were mitoses (Figure 3A) and foci of necrosis (Figure 3B). At closer look, a second minor population was identified consisting of large, oval cells with central nuclei, large nucleoli, and cytoplasm in which fine pale granulations were present (Figure 3C); few of these cells were bi‐nucleated (Figure 3D). Focally, these large cells were embedded in a more prominent fiber background created by spindle cells with coarse eosinophilic processes (Figure 3C).

Figure 2.

Figure 3.

By immunohistochemical examination, most cells were immunopositive for GFAP (Figure 4A). Cells of the second type, as well as some of the smaller nondescript cells, showed in their majority a granular perimembranous synaptophysin staining. Rare cell were unequivocally immunopositive for CD34 (Figure 4B), chromogranin A, and neurofilament (Figure 4C). Most of these labelings highlighted the tendency of these cells to cluster in a perivascular position. The highest MIB1 proliferation index was 25% (Figure 4D).

Figure 4.

DIAGNOSIS

De novo malignant ganglioglioma (GG) of the spinal cord with unusually prominent dysplastic vessels (“malignant angio‐ganglioglioma”)

DISCUSSION

We present a detailed description of a rare de novo malignant spinal GG in an adult patient. Despite broad excision and radiotherapy at diagnosis, the tumor disseminated 12 months later to give rise to multiple spinal and cerebral predominantly periventricular deposits, and lead to a rapidly fatal outcome.

While there is general agreement that spinal GGs in adults are rare tumors, their true incidence is not known. The highest reported estimates of 6% of all spinal tumors of adulthood (9) are considered unacceptably high by some authors (12). Only eight cases were listed in an exhaustive review of the older literature (4), two case reports appear to have been published ever since (11, 13), a large series of 326 GGs seemingly includes less than 10 adult cases (1). Our own search of the literature produced five more (3, 5, 6). It has been argued that over‐diagnosis of GG in some series may have been due to misleading expression of synaptophysin by normal neurons overrun by an astrocytoma, a phenomenon reportedly prone to occur in the spine quite often (12). While this anatomical peculiarity may indeed be vexing in some specimens, it is clear that insufficiently representative biopsies are the main obstacle to establish the correct diagnosis. Spinal tumors, not always easily accessible, often yield small biopsies (9). The useful synaptophysin immunostaining should always be backed up by immunopositivities for other markers of neuronal cells. Interestingly, CD34 was recently shown to be expressed by the majority of GG (1), and is thus helpful to make the diagnosis.

Most GG in children as well as in adults are benign (9). Malignant transformation is rare, and when it occurs, it is almost invariably through a protracted evolution of the astrocytic component to a high‐grade tumor (1, 2). In an extensive review of older and more recent reports, McLendon et al (2) cited 12 cases of de novo GG/malignant astrocytoma (grade III‐IV); none of them was spinal. In their large series, Blümcke & Wiestler (1) reported 17 de novo anaplastic GGs. Four of these tumors were spinal, and, to our knowledge, this is the sole report to have documented anaplastic GGs at this location.

In our case, endothelial proliferation was inconspicuous, but the presence of vast areas of ischemic necrosis and of many highly atypical and immature GFAP positive cells, were most compatible with a grade IV astrocytoma.

Angioglioma is a descriptive term long applied to composite lesions of tumoral or reactive glial proliferations associated to vessel proliferations (8). As indicated in a detailed study, this term, devoid of prognostic connotations, should probably best be retained for some excessively vascularized low‐grade astrocytomas, commonly of the pilocytic type (8). The vessels are likely malformative, and older theories of causal relationships between vascular and glial tumors or common viral etiology of both lesions, although stimulating, are probably overambitious (8). The importance of this pattern is that angiogliomas may simulate a vascular tumor or malformation. In our case, this exophytic tumor evoked in the first place a hemangioblastoma both clinically and angiographically. Spinal cord hemangioblastomas, rare benign tumors that commonly arise in a dorsal and median position in the thoracic spine of middle aged men, are densely vascular, and produce a typical angiographic image (10). Rarely, vessels in GGs are malformative, in line with the presumed dysontogenetic origin of these tumors (1). Exceptionally, they may be conspicuous enough to engender the diagnosis of a mixed lesion as exemplified by a remarkable childhood case of a bihemispheric GG (7).

CASE OF THE MONTH: ABSTRACTS

July 2006. Metastatic melanoma to a pituitary oncocytoma is a very rare condition. A 76‐year‐old man was presented with progressive visual disturbance and falling down with initial loss of consciousness 2 days before admission. He had a subungual acral lentiginous melanoma (T3N1M0) with gangrenous change of left big toe, treated by amputation 15 months ago. Computed tomography and MR imaging demonstrated masses involving inguina, mediastinum and left renal hilum and a dumb‐bell shaped hyperdense mass, approximately 6.2 × 3.7 mm, that involved pituitary fossa and suprasellar region with adjacent bony destruction. He underwent surgical resection of the tumor. Microscopically, the tumor revealed an admixture of pituitary adenoma and invasive metastatic melanoma with fragments containing both populations in juxtaposition. The adenoma was negative for melanoma markers and pituitary hormone markers. The melanoma was positive for S‐100 protein and HMB‐45. Ultrastructure of the adenoma revealed abundant mitochondria and sparse secretory granules. The diagnosis was metastatic melanoma to a pituitary oncocytoma. The current literature on metastatic tumors to pituitary adenoma is reviewed.

August 2006. In a 64‐year‐old woman presenting with rapidly progressive dementia, brain magnetic resonance imaging revealed a diffuse leukoencephalopathy without gadolinium enhancement, and the 14.3.3 protein was found to be positive in the cerebrospinal fluid. An electroencephalogram showed diffused slow waves and epileptic seizures without periodic paroxysmal activity. The patient died 3 months after onset of symptoms, and an autopsy restricted to the brain was performed. Gross examination was not informative, and only microscopic examination permitted identification of scattered lymphomatous cells on all sections from the brain hemispheres, brain stem and cerebellum. Immunopositivity of these tumor cells for CD20 attested their B phenotype. This observation illustrates “lymphomatosis cerebri”, a recently described entity, which has to be considered in the differential diagnosis of rapidly progressive dementia in adults.

September 2006. A 42‐year‐old man was admitted to the neurosurgery department because of paraparesis and sensory deficits of both feet. A solitary exophytic lesion of the thoracic spine was seen on MRI, and angiography further revealed the presence of feeding and draining vessels and intra‐lesional shunting. The preoperative diagnosis was spinal hemangioblastoma. A gross total resection was performed. By histological examination, the lesion was a tumor composed of neoplastic astrocytes and cells immunopositive for neuronal markers and CD34. The neuronal subpopulation was quite polymorphous and consisted of large anaplastic neurons including binucleate forms and smaller immature looking cells. Vessels were abundant and showed dysplastic changes such as sclerosis, calcium incrustations and extreme dilatation. Because of necrosis and marked proliferative activity, the tumor was considered a de novo malignant ganglioglioma (GG). In conformity with the diagnosis of malignancy, the tumor gave rise to extensive cerebrospinal deposits in the intracranial and spinal compartments 12 months post‐diagnosis. De novo malignant GG of the spine are very rare tumors of which few cases are on record. Interestingly, in our case the rich malformative vasculature and the corresponding angiographic image were most compatible with descriptions of “mixed” angiogliomas. The diagnosis of spinal GGs should rely on both histologic hallmarks and unequivocal immunopositivity for several neuronal markers because of reported aberrant expression of synaptophysin by non‐neoplastic spinal neurons.