**4. Pathology**

#### **4.1. General**

The World Health Organization (WHO) defines medulloblastoma as "a malignant, invasive embryonal tumor of the cerebellum with preferential manifestation in children, predominantly neuronal differentiation and an inherent tendency to metastasize via cerebrospinal (CSF) pathways" [30]. Although it is generally agreed that cerebellar medulloblastoma is an embryonic tumor, its origin is still a matter of speculation [9].

#### **4.2. Macroscopic pathology**

Macroscopically these midline globular, soft tumors are fairly well demarcated, and are apparently encapsulated. The marked vascularity gives them a dark, dirty brownish-red hue and occasionally they have extensive areas of necrosis. Consistency may vary from suckable to rubbery or to even firm sometimes. Calcifications are seen occasionally while hemorrhage in medulloblastoma is an extremely rare occurrence. Often marked edema of a wide zone of the neighboring tissue is also seen. They overlie the fourth ventricle as they develop in the midline in the roof of the fourth ventricle to occupy it, but most of the floors of the fourth ventricle in the great majority of cases are typically free. They usually block the aqueduct of Sylvius, with significant dilatation. These have a tendency to invade the meninges. Commonly they grow downward through the foramen magnum from the primary location between the tonsils of the cerebellum [1–3, 9]. CSF dissemination into the subarachnoid spaces often lead to local or widespread leptomeningeal metastases in the spinal axis or over the surface of the cerebral hemispheres or cerebellum and this also may cause characteristic pearly gray sheets of tumor in the meninges. Furthermore, widespread implantation of tumor can be found throughout the ventricles [9, 31].

mutations in signal pathways that regulate their functions; these mutations modify normal development pathways and may result in the development of distinct variants of medul-

Medulloblastoma

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http://dx.doi.org/10.5772/intechopen.76783

From the very beginning of history of this special type of tumor, these has been tried to be classified in different ways. With the advent and development of molecular biology and incorporation of that with genetic profiling has taken the classification beyond the level of mere histological classification. The molecular subgroupings are helpful in prediction of course of the disease and outcome as well as choosing therapeutic options. Recently the treatment plan is devised in accordance with the classification that integrates both histological and the molecular subgroupings to have the best possible outcome on the basis of a personalized

Histopathological classification of medulloblastoma has evolved with time. Rubinstein and Northfield [34] initially identified three variants of medulloblastoma: pigmented papillary medulloblastoma, medullomyoblastoma, and desmoplastic medulloblastoma. With newer technologies, newer histological types were being introduced. To alleviate the confusions, the World Health Organization (WHO) in 1976 developed a common classification of brain tumors in an effort to combine the various systems in use till then and the WHO publication "Histological Typing of Tumours of the Central Nervous System" in 1979 outlined and illustrated the new classification system [30, 35, 36]. Since then modifications, additions and characterization of classification of medulloblastoma has evolved a lot throughout the newer classifications of medulloblastoma of the WHO editions of classifications gradually in 1993 [35], 2000 [37, 38] and 2007 [30]. The present histological classification that is in practice has

**1. Classic medulloblastoma:** Most common histologic subtype (66%). Composed of sheets of densely packed, small to medium-sized, round to oval-shaped, blue cells (basophilic) with a high nuclear to cytoplasmic ratio and high mitotic and apoptotic activity. Reticulin

**2. Large cell/anaplastic medulloblastoma**: Large cell medulloblastomas have monomorphic cells with large, round, prominent nuclei, high mitotic activity, and frequent apoptosis, while the anaplastic medulloblastoma are characterized by hallmarks of anaplasia. Large cell and anaplastic medulloblastomas have a significant degree of cytologic overlap and

**3. Desmoplastic/nodular medulloblastoma**: Widespread desmoplasia, characterized by presence of nodular, reticulin-poor "pale islands" of neurocytic differentiation surrounded by densely packed, mitotically active cells having pleomorphic and hyperchromatic nuclei.

loblastoma [33].

**5. Classification**

treatment for individual patients.

**5.1. Histological classification**

the following types:

staining shows a lack of nodular desmoplasia.

are differentiated only by the degree of anaplasia.

Reticulin staining highlights internodular desmoplasia.

#### **4.3. Microscopic pathology**

Generally medulloblastomas are categorized as small blue-cell tumors, based on presence of their deeply basophilic nuclei [25]. Histologically, these tumors comprise of densely packed rounded or pear-shaped or sometimes spindle-shaped cells having large ovoid nuclei containing plentiful network of chromatin with scanty cytoplasm and for the most part consisting of numerous embryonic glia fibrillae [1, 3, 8]. These are highly cellular tumors forming uniform sheets of cells, interposed with occasional thin-walled blood vessels. Low magnification reveals that the cells appear as a loose structureless mass, but the nuclei sometimes may form pseudo-rosettes or may show a palisade arrangement. Extensive areas of necrosis, numerous hemorrhagic foci and great vascularity often come across too [1, 3, 9]. Thin-walled blood vessels with delicate connective tissue confined to their walls can be demonstrated by special staining with Perdrau's stain [9].

#### **4.4. Electron microscopic examination**

The electron microscopic picture is a mosaic of cells, processes, and fibers. The tumor cells are arranged in a tightly packed mass as also seen in light microscopy. Both the glial and neuronal cells can be recognized on electron microscopic analysis [9].

#### **4.5. Immunohistochemistry**

Immunohistochemistry can help in diagnosis of medulloblastoma and can provide information augmenting the plan for further management. Mitosis is seen in up to 80% of tumors, as assessed by positive staining with the Ki-67/MIB1 antibody. Medulloblastomas are frequently positive for vimentin and synaptophysin staining [32].

#### **4.6. Genetic aspects**

With the advent of genetic profiling and molecular analysis, evolving evidences point to the fact that the different precursor cell populations that form the cerebellum are vulnerable to mutations in signal pathways that regulate their functions; these mutations modify normal development pathways and may result in the development of distinct variants of medulloblastoma [33].
