FINAL DIAGNOSIS: CALCIFYING PSEUDONEOPLASM OF THE NEURAXIS IN ASSOCIATION WITH A GANGLIOGLIOMA.
Calcifying pseudoneoplasm of the neuraxis or fibroosseous lesion of the central nervous system (CNS) is a rare entity first described by Rhodes and Davis in 1978(1). It is described as a fibrocalcific reactive lesion whose origin is poorly understood but believed to originate from arachnoid cells or fibroblasts (1, 2). It can occur at all ages with a mean age of 12 to 83 years as reported in one study (3) .CNS localization ranges from intracranial (extraaxial/intraxial), intraspinal and dural based. Radiologically its appearance is nonspecific, even with advanced studies like Magnetic Resonance Imaging (MRI). There have been at least 27 cases reported in the literature (3). Clinical presentation includes headaches, seizures, paralysis as well as sensory loss.
Histologically they are fibro-"osseous" in nature with a lobular to focal nodular pattern. The pathognomonic characteristic is the faintly eosinophilic to amphophilic acellular chondromyxoid matrix surrounded by palisading spindle to polygonal epitheloid cells. Coarse fibrillar material in linear or anastomosing patterns, are typically seen within the central amphophilic area giving a "chicken footprint" appearance. The palisading spindle or round to polygonal cells are variably positive for vimentin and EMA (3, 4). There is absence of atypia, mitoses or necrosis. Intraaxial lesions can be seen in association with reactive to atypical astrocytes, Rosenthal fibers and sometimes neurofibrillary degeneration. In our case, there were associated reactive astrocytes together with a ganglioglioma. Occasional to prominent multinucleated giant cells can sometimes be seen at the periphery of the matrix giving an appearance of a granuloma. Bone formation, which may be either mature lamellar or woven, is seen in many cases, but to a variable degree. The bone and most commonly seems to arise in the fibrous stroma (3). Electron microscopy shows the central amorphous area of the matrix material seen at light microscopy to consist of masses of electron-dense amorphous material. Many of these masses contain a central accumulation of collagen fibers (2) or spherical nodules consisting of a central core of collagen fibers and nonperiodic fibrils, an intermediate zone of scattered fibrils, and a peripheral zone similar to the central locus (1).
Since many conditions in the CNS are associated with some form of calcification, which can be intrinsic, neoplastic, metastatic or non-neoplastic it is very important to recognize this rare entity, which is slow growing and has a good prognosis. Tumors of the CNS, which tend to be associated with calcification, include astrocytomas, oligodendrogliomas, meningiomas, craniopharyngiomas and choroid plexus papillomas. Non-neoplastic tumors that show calcification are usually those of longstanding including parasitic lesions, tuberculomas, intracerebral hematomas, aneurysms and vascular malformations (4). Cases of metastatic tumors associated with calcification are rare but should be excluded (5-6). Also included in the differential diagnoses are chordoma, chondroid chordoma, chondroblastoma and chondrosarcoma. Treatment is in the form of simple wide local excision with a known excellent prognosis.
Ganglioglioma is a slow growing neuroepithelial tumor composed of neoplastic mature ganglion cells in combination with neoplastic glial cells. By WHO criteria it is a grade I or II.Gangliogliomas with anaplastic features in their glial component are considered WHO grade III. The age ranges from 2 month to 80 years with a mean of 8 to 25 years (7). This tumor can occur any where in the CNS but majority are supratentorial and involve the temporal lobe. A significant clinical feature is chronic seizures. It forms a well-circumscribed lesion, which on MRI shows as a T1 weighted hypointense and a T2-weighted hyperintense mass. The lesion is sometimes associated with calcification but rarely necrosis or hemorrhage. The key characteristic histological features of this tumor are a highly variable mixture of glia and neurons. The glial component is most often astrocytic but may be predominantly oligodendrocytic or mixed and may show variable anaplasia. Mitotic activity is rare. Other features include perivascular lymphocytic infiltrates, cyst formation and calcification .The neurons of ganglioglioma are haphazardly oriented in a fibrillary matrix. They have a highly variable size and shape with frequent multinucleation and large bizarre forms. The neuronal component is often irregularly clustered and may be lobulated by bundles of reticulin. Immunohistochemistry demonstrates neuronal expression of neuron specific enolase, neuralfilament synaptophysin, microtubule associated proteins, class III beta tubulin and chromogranin. Staining for GFAP demonstrates the astrocytes that usually form the neoplastic component of the ganglioglioma. Total resection is the treatment of choice with adjuvant therapy (radiation) reserved for anaplastic examples.
This case of a combined calcifying pseudoneoplasm of the neuraxis in combination with a ganglioglioma represents to the best of our knowledge the first example of such a combination.
In lieu of these benign entities, accurate histological diagnosis is extremely important for both the pathologist and the neurosurgeon in order to provide appropriate treatment in the form of wide local excision and prevent unwarranted radical therapies.
Contributed by Akosua B. Domfeh, MBchB and Geoffrey Murdoch, MD