Neurosurgical Pathology of the Posterior Fossa

Marjorie Fowler

Diverse types of pathology occur in the posterior fossa. The specific pathologic lesion is diagnosed based on the location of the lesion; the age of the patient; the associated clinical history, including signs, symptoms, and duration; and the imaging studies. The most common types of lesions, besides trauma, that the neurosurgeon will encounter in the posterior fossa include neoplasms, both metastatic and primary; vascular lesions; and infections that present as masses. For the purposes of this discussion, this chapter divides the pathology into that associated with (1) parenchyma and leptomeninges, (2) cranial nerves, and (3) bone and dura mater. The discussion is limited to the most common lesions, and it focuses on gross pathology. The chapter also discusses some of the newer techniques that are emerging to aid neurosurgeons in the management of their patients.

♦ Parenchymal and Leptomeningeal Lesions Neoplasms

One major type of lesion that neurosurgeons encounter in the posterior fossa is the neoplasm. The type of neoplasm is highly affected by the age of the patient. Most childhood nervous system neoplasms arise in the posterior fossa.¹ In adults, although neoplasms certainly do occur in the posterior fossa, they more commonly present in the cerebral hemispheres.

The three most common posterior fossa neoplasms encountered in children are pilocytic astrocytomas, ependymomas, and medulloblastomas. All of these neoplasms tend to be well circumscribed and well demarcated from the parenchyma. The least likely of these to be well demarcated is the medulloblastoma, which may extend into and seed the subarachnoid space. Cerebellar pilocytic astrocytomas classically grow as cystic masses with mural nodules. In the brainstem, they are usually dorsal, exophytic, and not usually within the parenchyma. Both medulloblastomas and ependymomas tend to grow into and fill the fourth ventricle, presenting with symptoms of hydrocephalus. A gross clue to the cell type in these intraventricular neoplasms is the more common origin of medulloblastomas from the roof of the fourth ventricle and the origin of ependymomas from the floor.² Growth within the subarachnoid space would lead one to suspect medulloblastoma, which has a strong tendency to grow and spread via the cerebrospinal fluid. It is more unusual for astrocytic neoplasms and ependymomas to spread in this manner.

Ependymomas, pilocytic astrocytomas, and medulloblastomas are generally soft, granular, and gray-pink.^1,3 Primary nervous system tumors, in general, have a consistency that varies with their cellularity; the more cellular the neoplasm, the softer the consistency. Thus, medulloblastomas are generally the softest of these three, followed by ependymomas and then the mural nodule of the pilocytic astrocytomas. The less common childhood diffuse astrocytoma is usually firm and ill-defined, as it is in adults.³ As the grade of astrocytomas increases, they are generally softer, grayer, and may develop frank areas of hemorrhage and necrosis. Although high-grade astrocytomas may appear grossly to be more demarcated than their low-grade counterparts, when examined microscopically the tumor is generally found well beyond the apparent margins of the lesion. Glioblastomas, although not as common in the posterior fossa as in the cerebral hemispheres, do occur.

With older patients, the expected type of neoplasm changes, with an increase in the incidence of hemangioblastomas and diffuse astrocytomas and a decrease in the incidence of medulloblastomas and ependymomas. Also, as the patient ages, epidermoid cysts, choroid plexus papillomas, lymphomas, and metastatic neoplasms are more commonly encountered. Hemangioblastomas are typically very red, spongy, and resilient,2 due to the large numbers of small blood vessels. They are characteristically well defined and frequently present as a mural nodule within a cyst. It is important when taking a biopsy from one of these slow-growing cystic lesions to be sure to send the mural nodules, rather than the cyst wall, to the pathology laboratory for frozen section. The often-florid gliotic tissue in the cyst walls frequently contains numerous Rosenthal fibers, which may lead to a mistaken diagnosis of pilocytic astrocytoma, if the pathologist is unaware that the biopsy is from the cyst wall rather than the mural nodule.

Epidermoid cysts characteristically have a thin cyst wall, appear somewhat translucent, and contain large amounts of pearly keratinous material. Hair is not usually seen within the cyst, but if it is seen, it would indicate that the diagnosis is more likely to be a teratoma. Teratomas and other germ cell tumors must always be considered when the tumor presents in the midline.

Choroid plexus papillomas of the fourth ventricle grossly appear to be papillary lesions that arise from the native choroid plexus of the fourth ventricle. Although they mostly grow as intraventricular neoplasms, they can rarely present as a mass at the cerebellopontine angle.

Primary lymphoma that is most commonly seen in the setting of immune suppression may present as multiple or single lesions. When associated with systemic lymphoma, it usually involves the leptomeninges rather than the parenchyma.⁴ Primary lymphoma more frequently involves the white matter than the gray matter.¹ It generally is slightly gray, opaque, and duller than the surrounding white matter.

Metastatic neoplasms are one of the most common types of neoplasms encountered, especially in adults. The appearance of metastatic neoplasms is highly variable. They are generally sharply circumscribed and multiple. However, they may be soft or firm. If they have significant necrosis, they may appear cystic and mimic an abscess. They may be hemorrhagic, mucinous, or granular appearing.

♦ Vascular and Miscellaneous Lesions

Vascular malformations are mostly cavernous angiomas and arteriovenous malformations, and they compose another group of lesions that, when seen in the posterior fossa, are most likely to be present in the cerebellum. Rupture of the vessels within these lesions leads to a hematoma of the parenchyma that may rupture into the subarachnoid space or the ventricle. Larger bleeds may destroy the lesion in the process. These vascular malformations are usually well circumscribed and may be surrounded by firm brown, yellow, or green discolored parenchyma, representing areas of old hemorrhage with gliotic repair.¹ Other vascular lesions such as aneurysms, although less common than those in the anterior circle of Willis, may occur in the posterior fossa.

Arachnoid cysts occur in the leptomeninges of the posterior fossa. They are frequently asymptomatic, but may result in a mass effect if they are large. These cysts are generally very thin walled, contain clear colorless fluid, and rupture easily during surgery. They push the adjacent parenchyma to the side. In infants and small children, they may deform and enlarge the adjacent skull if they continue to grow.

♦ Inflammatory Lesions

Inflammatory lesions may present as mass lesions of the parenchyma or the leptomeninges. Within the parenchyma, abscesses are the most common type of inflammatory lesion encountered. The earliest lesions present as areas containing soft loculated purulent material surrounded by red, wet, congested, edematous parenchyma. As the abscess matures, it forms a firm fibrous wall surrounded by parenchyma that is at first edematous and later gliotic and firm. The center remains soft, at first containing purulent material, and then later it becomes cystic, containing thinner fluid as it matures.

Granulomatous disease can affect either the parenchyma or the meninges and may be related to infectious organisms (e.g., fungi or mycobacteria) or sarcoidosis. Individual small granulomas are generally very firm, white, and discrete. As the granulomatous process evolves, the granulomas may become confluent, and, depending on the organism, may become centrally necrotic and soft. It is important to culture all lesions that have a possibility of being infections. If the lesion appears granulomatous, fungal and mycobacterial cultures are in order. Cultures done in the surgical suite are much preferred to those done in the frozen section rooms where contamination is much more possible. When the patient is immune suppressed, the neurosurgeon should also consider culturing for unusual viral agents.

Small early infarcts may also masquerade as tumors and require diagnostic biopsies. The earliest lesions are hyperemic because of dilated blood vessels. As the lesion evolves, it becomes edematous and then softens as it becomes necrotic. The eventual cystic infarct is generally not a problem to diagnose clinically, and thus is unlikely to result in neurosurgical biopsy.

♦ Cranial Nerve Lesions

The main cranial nerve lesion that is encountered is the schwannoma, which most commonly arises from sensory nerves. It may be difficult to determine whether a lesion is arising from a nerve or from the dura, especially at the cerebellopontine angle. Schwannomas are well-circumscribed lesions that generally grow to the side of the nerve of origin. They can vary from white to yellow to red-brown, and frequently contain cystic areas and areas of hemorrhage. Although the original lesion is generally firm, the lesion may become softer as it develops areas of hemorrhage or cysts. The occurrence of schwannomas at a young age or in a bilateral location should prompt the suspicion of a genetic abnormality such a von Recklinghausen’s neurofibromatosis.

♦ Bone and Dural Lesions of the Posterior Fossa

Neoplasms

Meningioma is the most common lesion arising from the dura mater. These lesions are usually firm nodular masses that indent and do not invade the brain. Because they are usually slow-growing tumors, they may grow to substantial size before presenting clinically. As in the case of schwannomas, they may also vary in color and consistency, although they are less likely to become cystic or to contain hemorrhage. The softer tumors are generally composed mostly of epithelioid-appearing meningothelial cells, and the firmer are tumors composed of spindle-shaped fibroblastic-appearing cells. They are usually shades of off-white but can have yellow or reddish areas. Meningiomas may penetrate into or through the bone and frequently cause an osteoblastic response with thickening of the bone.1 Locally aggressive hemangiopericytomas in the nervous system generally arise from the dura. Like meningiomas, these lesions are nodular and tend to push the adjacent brain to the side. They tend to be redder than the usual meningioma because of the dense vascularity, and thus will bleed more profusely.

Bony lesions may also involve the posterior fossa. Chordoma classically is seen in adults. The posterior fossa lesions most frequently involve the clivus, although they may grow predominantly on one side or the other or anteriorly into the sphenoid sinus. They are usually soft, lobulated, sometimes mucinous appearing, gray lesions that expand the bone and if growing into a space are covered by a fibrous capsule.¹ Occasional chordomas contain fragments of firm cartilaginous tissue or in some cases are composed almost entirely of cartilaginous tissue.

Chondrosarcoma occurs most frequently in patients in the fifth to seventh decades of life,⁵ and those arising in the posterior fossa are more common in females. In the skull base, the most common location is the temporo-occipital junction followed by the clivus and the sphenoethmoid complex. These tumors usually present with nervous system complaints, including headache, gait disturbances, and cranial nerve problems. Grossly, chondrosarcomas are infiltrative and nodular tumors that expand the bone.⁶ Calcification may be present within the tumor, making it sometimes difficult to differentiate grossly from osteosarcoma.

Multiple myeloma or solitary plasmacytomas are more common in older men. These are generally multiple, soft gray, well-circumscribed lesions of the bone. When the lesion ruptures through the bone, it more commonly grows into the soft tissues but may grow through the bone into the cranial vault.

Inflammatory Lesions

Lesions resulting from infections uncommonly involve the pachymeninges. When they do, they are almost always the result of infections of adjacent structures such as the middle ear, mastoid, or sinuses. Subdural empyemas are easily recognized by the purulent material within the space. Mucuscontaining mucoceles usually arise and extend from the sinuses, and cholesterol granulomas penetrate through the petrous bone and are composed of rubbery brown or tan fibrous tissue.

Frozen Section Cautions (or How to Get the Best Pathologic Diagnoses)

Precise neuropathologic diagnosis in most cases requires a combination of the gross and microscopic pathology, the imaging studies, and the clinical history.² Without all three components, the neurosurgeon risks making mistakes in diagnosis. When sending tissue for frozen section, it is essential that the neurosurgeon include the precise location of the lesion and the apparent tissue of origin, representative imaging studies, and an adequate history. The imaging characteristics of the lesion and adequate knowledge of the clinical symptoms, the progression of these symptoms, and other related history aid the pathologist in the diagnosis in the same way that they aid the neurosurgeon. Neither the pathologist nor the neurosurgeon can do his or her best job without this information.

♦ New Advances in Neuropathology

In addition to the now usual diagnostic immunohistochemical stains, there are two more recently developed types of testing that are beginning to play a very important role in neuropathology. The first of these are quantitative methods for estimating the rates of growth of tumors. The most widely used are those directed against the Ki-67 antigen.⁷ Semi-quantitative or quantitative estimation of the proliferative index using a computerized automated image analysis system is a useful adjunct to histologic grade of the tumor when determining the best treatment for patients, especially if the lesions have borderline histology.

The second group of tests that are beginning to influence treatment and occasionally diagnosis of neoplasms are molecular methods such as fluorescent in-situ hybridization, loss of heterozygosity, and microarray technologies used to map gene expression in tumors.⁸^–¹⁰ Findings such as the loss or deletions of chromosomal regions on 1p and 19q in oligodendrogliomas that indicate a tumor that is particularly responsive to chemotherapy are likely to influence the treatment decisions made by the neurosurgeon. Newly emerging microarray technologies that make it possible to test for the expression of thousands of genes with one test promise new advances in tumor diagnosis and treatment in the near future.¹¹