**9. Investigation work ups**

A variety of diagnostic studies are used to confirm the clinical diagnosis of medulloblastoma and to localize the tumor exactly. The first-line diagnostic test for medulloblastoma is brain imaging.

Up until introduction of CT scan in 1971, air studies (pneumoencephalography and ventriculography) were most reliable and almost accurate in the diagnosis of medulloblastoma in all age groups. Angiography also yielded useful results regardless of age. With advent of MRI, CT scan has become an adjunct to that. Skull x-ray studies, once useful for the detection of brain tumors, is now rarely of value. Nucleotide brain scans and bone scans, myelographic examination, CSF cytology were also helpful in diagnosing a moderate number of cases [6, 8, 9, 67, 68].

#### **9.1. Computerized tomography (CT)**

CT is often used as the first-line diagnostic imaging because of its readily availability, fastness in imaging and comparatively cheaper price [8]. This is a good tool for early diagnosis with state of hydrocephalus, serial evaluation of tumor, postoperative assessment of extent of tumor removal, detection of residual and recurrent tumor, and tumor deposits in the CSF pathways as well as convenient follow-up studies [4, 15, 42]. Medulloblastomas appear typically hyperdense and sharply demarcated lesion near the fourth ventricle in the plain CT scan with a surrounding hypodense zone of edema which show better delineation with contrast enhancement showing moderate to marked increase in density (**Figure 2**). Cystic components may also be seen. Leptomeningeal tumor deposits appear as areas of increased density in the subarachnoid space. Calcification may be seen in about 10–20% of medulloblastomas [5, 62].

**Figure 2.** Plain axial CT scan (A) showing hyperdense and sharply demarcated lesion near the fourth ventricle with surrounding hypodense area of edema which with contrast enhancement (B) is well demarcated by increased density.

#### **9.2. Magnetic resonance imaging (MRI)**

headache, nausea, vomiting, irritability, lethargy, behavior alteration, personality change and impaired memory or attention, etc. Raised ICP occasionally gives rise to possibility of having seizure and 6th nerve palsy. Respiratory and cardiac manifestations may be evident, resulting from compromise of the respiratory and cardiac centers in the brainstem. Alteration of level of consciousness, starting from disorientation to deep coma, may result either from raised ICP or from compression on the brainstem. Papilledema or even visual impairment from raised ICP

Medulloblastoma is a very rapidly growing tumor and tends to follow a rapid progression in a very short period of time. The median time between onset of symptom until diagnosis (symptom interval) is 3.3 months (65 days) [65]. Rarely, patients may have symptoms for up to 6 months before diagnosis and younger patients have significantly longer interval to diagnosis while more

The Accurate diagnosis of pediatric tumors is essential to ensure balance between achieving a long-term cure and avoiding treatment related disability in survivors. The tentative diagnosis of medulloblastoma is relatively straight cut one from the age of the patient, history and neurological examination findings. Nonetheless, there are other maladies that are to be kept in mind. The two commonest differential diagnosis of a posterior fossa mass in children are pilocytic astrocytoma and ependymoma. Other lesions to be considered are atypical teratoid/rhabdoid tumors, exophytic brainstem glioma and choroid plexus papilloma as well as teratoma in infants and hemangioblastoma in patients with Von Hippel-Lindau syndrome. Metastasis is the first to be thought in adults as that is the most frequently encountered posterior fossa lesion [6, 10].

A variety of diagnostic studies are used to confirm the clinical diagnosis of medulloblastoma and to localize the tumor exactly. The first-line diagnostic test for medulloblastoma is brain imaging. Up until introduction of CT scan in 1971, air studies (pneumoencephalography and ventriculography) were most reliable and almost accurate in the diagnosis of medulloblastoma in all age groups. Angiography also yielded useful results regardless of age. With advent of MRI, CT scan has become an adjunct to that. Skull x-ray studies, once useful for the detection of brain tumors, is now rarely of value. Nucleotide brain scans and bone scans, myelographic examination, CSF cytology were also helpful in diagnosing a moderate number of cases [6, 8, 9, 67, 68].

CT is often used as the first-line diagnostic imaging because of its readily availability, fastness in imaging and comparatively cheaper price [8]. This is a good tool for early diagnosis with state of hydrocephalus, serial evaluation of tumor, postoperative assessment of extent

aggressive subgroups of medulloblastoma have a shorter pre-diagnostic interval [66].

is not very uncommon, especially when presented in late stage.

**8. Diagnosis and differentials**

144 Brain Tumors - An Update

**9. Investigation work ups**

**9.1. Computerized tomography (CT)**

The relationship between the tumor and the surrounding brain structures can be vividly demonstrated in MRI with and without gadolinium. Screening MRI of the whole spinal axis is capable of displaying and evaluating tumor dissemination, when present and pre-operative whole spine MRI is preferred [20, 21].

Different sequences of MRI can provide different information to help in diagnosis and treatment planning. Medulloblastomas are hypointense to gray matter on T1-weighted imaging (T1WI) with heterogeneous gadolinium enhancement in 90% of cases, while they are generally iso to hyperintense to gray matter on T2-weighted imaging (T2WI). The heterogeneity in T1WI and T2WI results from cyst formation, calcification or necrosis. Diffusion-weighted imaging (DWI) shows restricted diffusion and in fluid-attenuated inversion recovery (FLAIR) imaging, medulloblastomas are generally hyperintense to surrounding brain (**Figure 3**). MR spectroscopy (MRS) shows elevated choline peaks and decreased creatine and N-acetyl acetate peaks, with occasional elevation in lactic acid and lipid peaks [62].

**9.3. Molecular diagnosis**

**10. Treatment**

**10.1. General**

in nearly all neuropathological laboratories.

chemotherapy [20, 22–24, 26, 69].

over or under-treatment. [30, 34].

**10.2. Surgery and surgical techniques**

Molecular diagnosis is of immense importance and an integral part of the management protocol as it is invaluable in prediction of outcome and in formulation of dose of therapy, especially in cases of selection of agents for targeted therapy. As these state of the art assays are accessible merely in few laboratories of the first-world neuropathological institutions, it is often very difficult to come to an integrated diagnosis for most of the centers in the world. Nonetheless, molecular antibodies specifically targeting mutated proteins should be available

Medulloblastoma

147

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

Treatment strategies for medulloblastomas have advanced slowly over the past 5 decades. Generally based on the histology and clinical factors, especially, disease dissemination at presentation and residual tumor after surgical resection, management of medulloblastoma has evolved to maximal safe surgical resection followed by radiation therapy and adjuvant

Adjuvant chemotherapy is recommended for all patients as this improves outcomes significantly. Following surgery, risks of recurrence and of neurocognitive effects of radiation therapy, doses of radiation and the type of chemotherapy protocol vary depending on extent

Though the medulloblastoma subgroups (Wnt, Shh, Groups 3 and 4) have distinct molecular and clinical profile, current adjuvant chemotherapy that are in practice are for the nontargated ones. However, significant improvements, approximately 70% 5-year survival rate with these combined therapies are achieved at the high cost of the quality of life, resulting mostly from the effects of radiotherapy and nonspecific, antimitotic agents on the developing brains of young medulloblastoma patients [27–31]. A general approach carries significant risk of

In March 1925, Cushing first succeeded in gross total removal of a medulloblastoma [1, 2]. Since then, the first-line treatment for medulloblastoma is surgery with the aim of maximal safe resection, along with treatment of any concomitant hydrocephalus [8]. But Cushing also cautioned that "the temptation will always be present for the surgeon to attempt an enucle-

The basic principles of surgery for medulloblastoma have changed little in the modern era, but technological revolutions in surgical technique and supportive care have made surgery safer. Development of surgical skill and other facilities has dramatically reduced the perioperative

of disease and age of the patient as well as institutional preferences [20, 29].

ation, a conservative attitude in this respect is the course of wisdom" [1, 8].

**Figure 3.** Medulloblastomas in T2-weighted imaging (T2WI), T1-weighted imaging (T1WI), with gadolinium enhancement (CONT), fluid-attenuated inversion recovery (FLAIR) (D) and diffusion-weighted imaging (DWI) in axial planes.

#### **9.3. Molecular diagnosis**

Molecular diagnosis is of immense importance and an integral part of the management protocol as it is invaluable in prediction of outcome and in formulation of dose of therapy, especially in cases of selection of agents for targeted therapy. As these state of the art assays are accessible merely in few laboratories of the first-world neuropathological institutions, it is often very difficult to come to an integrated diagnosis for most of the centers in the world. Nonetheless, molecular antibodies specifically targeting mutated proteins should be available in nearly all neuropathological laboratories.
