Clinicopathological Study of Pediatric Posterior Fossa Tumors

Abstract

Context:

Brain tumor is one of the most devastating forms of human illness, especially when occurring in the posterior fossa and involving the brainstem. Tumors in the posterior fossa are considered some of the most critical brain lesions. This is primarily due to the limited space within the posterior fossa, as well as the potential involvement of the vital brainstem nuclei.

Aims:

The aim of this study is to analyze the incidence, clinical features, surgical outcome, complications, and prognosis in a series of 37 pediatric patients with posterior fossa tumors who underwent surgery between September 2012 and January 2015 from the Department of Neurosurgery, King George Hospital, Visakhapatnam (both prospective and retrospective study).

Materials and Methods:

A series of 37 cases were treated by the Department of Neurosurgery, King George Hospital, between August 2012 and January 2015.

Results:

Posterior fossa tumors are predominantly seen in children with a peak incidence in the first decade. The most common presenting symptoms are raised intracranial pressure with headache and vomiting. Majority of the tumors are medulloblastomas, ependymomas, and cerebellar astrocytomas. The most common location is the cerebellar vermis, followed by the cerebellar hemispheres, followed by the forth ventricle and then the brainstem.

INTRODUCTION

Brain tumor is one of the most devastating forms of human illness, especially when occurring in the posterior fossa and involving the brainstem. Cushing probably was the first to report a large series of posterior fossa tumors.[1] He published information about 61 patients with cerebellar medulloblastoma (MB) with mostly fatal outcome. Now, the outcome is improving because of advances in the discovery of anesthesia, asepsis, neurological localization, and technique of tumor removal. Tumors in the posterior fossa are considered some of the most critical brain lesions. This is primarily due to the limited space within the posterior fossa, as well as the potential involvement of the vital brainstem nuclei. Some patients should undergo operation on an emergency basis, especially if they present with acute symptoms of brainstem involvement or herniation.

Frequency

Tumors of the central nervous system are the second most common childhood tumors (20%) after leukemia (37%) and are the most common solid pediatric tumors comprising 40%–50% of all tumors.[2,3] Posterior fossa (infrateritorial) tumors comprise between 54% and 70% of childhood brain tumors compared to 15%–20% in the adult population.[4] The estimated incidence of brain tumors in children is 2–3.5 per 100,000.[5] Common posterior fossa brain tumors in children include juvenile pilocytic astrocytoma, MB, ependymoma, and brainstem glioma. Less frequently, atypical rhabdoid/teratoid tumor, hemangioblastoma, dermoids, schwannoma of the VIII^th cranial nerve, cerebellar gangliocytoma, meningioma, high-grade glioma, and metastatic lesions are encountered.

Aims and objectives

The aim of this study is to analyze the incidence, clinical features, surgical outcome, complications, and prognosis in a series of 37 pediatric patients with posterior fossa tumors who underwent excision between September 2012 and January 2015 from the Department of Neuro Surgery, King George Hospital, Visakhapatnam (both prospective and retrospective study).

MATERIALS AND METHODS

A series of 37 cases were treated by the Department of Neurosurgery, King George Hospital, between August 2012 and January 2015. Patients with age ranging from neonate to 15 years were included in the study. Of the 37 patients, 24 were females and 13 were males giving a male:female of 1:1.8. In our series, 50% of pediatric posterior fossa tumors were in children <5 years with 30% in the 0–3 year age group, while 15% was in older children (11–15 years). The duration of symptoms ranged between 1 month and 2½ years. Cerebellar symptoms were the most common mode of presentation followed by headaches and vomiting. Blindness was found in seven (20%) of our patients probably due to late presentation. Neck stiffness was described in only three of our patients. All patients underwent computed tomography (CT) and magnetic resonance imaging (MRI). All patients underwent posterior craniectomy with excision of tumor. Few of the patients needed ventriculoperitoneal shunt (in the case of obstructive hydrocephalus and raised intra-cranial pressure features) preoperatively or some postoperatively to the definitive tumor removal procedure. Some even did not need VP shunt procedure.

RESULTS

Common signs and symptoms

The clinical presentation depends on the site of the tumor, biological behavior, and aggressiveness of the tumor. Symptoms may be caused by focal compression of the cerebellum or brainstem and due to increased intracranial pressure.

Recurrence

Of the 37 patients, only two patients had recurrence after a follow-up period of 2 years.

1. Ependymoma

2. Brainstem glioma.

According to Winston and Gilles, the 5-year survival rate exceeds 60% for all patients and 80% for certain good – risk individual with posterior fossa tumors.[6] In cases of pilocytic cerebellar astrocytoma, the 25-year survival rate exceeds 94%.[7]

Patients with MB are classified into good, risk, and bad risk categories based on the following:

• Age of presentation

• Extent of surgical resection

• Leptomeningeal dissemination or metastasis.

Prognosis in MB is worse for children younger than 2 years (Albright, 1986),[8] for patients with subtotal resection (80%),[9] and for those with subarachnoid metastasis or positive results on cerebrospinal fluid (CSF) cytology more than 2 weeks after surgery. In patients with ependymomas, the 5-year survival rate is 20%.[10] In ependymoblastoma, the 5-year survival rate is only 6%. Choroid plexus papilloma has an excellent prognosis, as high as 100% survival rate. Choroid plexus carcinoma has a poor prognosis.

DISCUSSION

Brain tumors are the most common solid tumors of the children and occur at a rate of 2.4/1.00,000 children at risk per year. Approximately half of the brain tumors of childhood arrive from the posterior fossa.

Age incidence

In the literature, the case which is youngest is 6 weeks old (Rorke, 1989).[11] In our series, the youngest was 1 year and 6 months old. Posterior fossa tumors are predominant between 1 and 9 years of age. In our series, 81% of cases are seen below 10 years [Table 1]. According to Albright, most of the posterior fossa tumors occur in the age group between 1 and 10 years.[12]

Table 1.

Age incidence

Sex incidence

In a series of literature, slight male predominance was seen.[13] In our series, male participants are 22 (60%) in number and female participants are 15 (44%) in number. The male predominance may be due to increased number of male patients being investigated, which is a social feature in Indian society [Table 2].

Table 2.

Sex incidence

Clinical presentation

Headache is the predominant symptom in most of the series with 80%–92% of cases,[14] followed by vomiting in 60% and gait disturbances. In our series also, predominant symptoms are being headache and vomiting with a mean frequency of 20 and 17 followed by cerebellar symptoms (gait disturbances). In our series, ten patients presented with seizures. The predominant signs in our study are ataxia and papilledema. Seventeen patients (46%) presented with cranial nerve palsies [Table 3].

Table 3.

Clinical presentation – Common signs and symptoms

Sites [Figure 1]

Figure 1.

Anatomical distribution

In our series, cerebellum is the predominant site in 59% cases, the fourth ventricle in 27% cases, in 9% cases the tumours were extrinsic, and in 5% they were brainstem in location [Table 4].

Table 4.

Anatomical location

Pathology

According to data from the Children's Hospital, Philadelphia, MBs range about 36%, cerebellar astrocytoma in 28%, brainstem glioma 9%, and ependymoma in 4%.[14]

In a study from the Hospital foe Sick Cjildren in Toronto, MB range about 27%, astrocytomas 23%, brainstem glioma in 9%, and ependymoma in 8% of cases.

In our series, the MB form about 34%, astrocytomas 27%, ependymoma 18%, tuberculomas 10%, brainstem glioma 5%, meningiomas in 2%, and choroid plexus papilloma 2% were observed [Table 5].

Table 5.

Histopathology

Recurrence

Although long survival period is generally reported, a surprisingly high incidence of recurrence ranging from 5% to 17% is evident in many series (Austin, 1984), (Geissenger, 1971).[15]

The extent of surgical resection is the most common important factor bearing on recurrence. The recurrence is common after subtotal removal and recurrence is rare after total removal. Recurrence can occur after total excision, but paradoxically cure is reported even after partial excision. Other factors that can be associated with tumors tendency to recur are grossly solid tumors. According to some authors, the diffuse histological variant has a worse prognosis than the juvenile one but is not predictive of recurrence.[16]

Qwallner et al.[17] found that pilocytic astrocytomas are associated with improved survival. Bruce et al.[18] reported 5.6% of recurrence.

In the present series, two patients had recurrence (ependymoma and brainstem glioma) after 2 year follow-up. Complete surgical resection is an important prognostic factor in relation to the tumor recurrence and the patients’ survival.[19]

Pencalet et al.[20] also showed that it is a sole independent factor that significantly detects the tumor recurrence. Total resection influences surgical outcome and quality of life. Brainstem infiltration and nonpilocytic variant of astrocytomas were associated with recurrence. The incidence of recurrence is also less after total excision of tumor. In our series, all the cases of ependymomas were subjected to the radiotherapy. Radiotherapy improves the survival in cases of ependymomas Salazar et al.[21]

All the children with MB received the chemotherapy as adjuvant chemotherapy improves survival.[22]

Patients with focal intrinsic brainstem gliomas should be treated with both chemotherapy and focal radiotherapy after surgical excision of tumor.[23] High-dose chemotherapy with autologous bone marrow rescue was advocated for children with diffuse pontine tumors after the biopsy.[24]

Follow-up

• Maximum period - 2 years

• Minimum period - 2 months.

Long-term survival of different types of pediatric posterior fossa tumors

Medulloblastoma

Long-term follow-up imaging has become the standard of care for MB patients, with most receiving repeat brain and spine MRI every 3–6 months in the first 2 years following treatment. Collin's law states that tumor relapse should occur within a period equal to the patient's age at diagnosis plus 9 months. This usually holds true for MB in spite of several exceptions. The most common site of recurrent disease is the primary tumor site. However, up to 60% of patients will display evidence of disseminated disease at relapse. Metastasis outside the nervous system is uncommon. Bone lesions are the most common, and lymph nodes are the second most common site. Early detection of recurrence offers the opportunity to test novel therapies in the setting of minimal disease burden. However, there is a controversy to the proven benefit because of the high percentage of dissemination at recurrence.

Cerebellar astrocytomas

Long-term prognosis is dependent on the extent of resection, the presence of brainstem invasion, and histological features of malignancy. Total resection is associated with considerably better outcome than is subtotal or partial resection.

Total resection overall carries a 5-year survival of 90% compared to subtotal resection with 48.5%. There is no difference between diffuse and pilocytic astrocytoma in outcome for totally resected tumors. The diffuse type has been considered more prone to recurrence, but the histologic type is not as definitive as a predictor of recurrence as it is extent of removal.

Brainstem involvement is a significant adverse prognostic factor for cerebellar astrocytoma, and the poor prognosis of solid tumors is related to the increased likelihood of brainstem involvement. There is a tendency for some tumors to invade the subarachnoid space and grow along the surface of the cerebellum, but this is not ominous and does not usually portend a negative prognosis. However, patients with malignant pathology will have poor clinical courses.

Ependymoma

Surgical resection is the best prognostic factor. A number of studies have shown that complete surgical resection offers the best hope of cure. Surgery and radiation therapies yield 5-year progression-free survival ranging from 60% to 87% after complete resection to 0%–33% after incomplete surgical resection. Postoperative imaging is essential. In patients where postoperative imaging shows residual disease that is surgically accessible, there may be a role for early second look surgery or perhaps delayed surgery for resection of residual disease after chemotherapy and radiation. These tumors are relatively well demarcated and distinct from adjacent brain parenchyma. However, depending on location, tumors arising from the roof of the fourth ventricle are the easiest to remove totally. Lateral tumors with a large cerebellopontine angle component are the most difficult to totally remove as they are often adherent to cranial nerves and vascular structures. Morbidity remains high secondary to brainstem and cranial nerve injury. The complete removal rates of the mid-floor type (origin of the fourth ventricular floor), lateral type (extension to cerebellopontine angle), and roof type (origin of the fourth ventricular roof) tumors are approximately 23%, 0%, and 100%, respectively.

The incidence of dissemination of ependymoma is only 11%–17%. Nonetheless, it is important to demonstrate its presence or absence because disseminated disease is a strong adverse prognostic factor. Perioperative disease staging with craniospinal MRI and CSF cytology is recommended. Thus, the overall prognosis in ependymomas is determined by a matrix of variables comprising age, location, completeness of surgical resection, and histological type and grade.

Brainstem glioma

Two radiographic features provide the most useful prognostic information: epicenter of the tumor and diffuseness. In a large series of patients with brain stem gliomas, the 5-year survival rate was 75% and 65% for patients with lesions in the midbrain and medulla, respectively, versus an 18% survival rate for patients with diffuse pontine lesions. Focal tumors had a 5-year survival rate of 70, whereas patients with diffuse tumors had just a 22% rate. Other studies have reported even lower 3-year survival rates of 10%.

Role of radiotherapy

Radiotherapy is routinely given to the patients with medulloblastoma, ependymoma, and brainstem glioma. After the surgery, radiotherapy is given as an adjuvant treatment. Radiotherapy is not advocated for children to the children who are under the age of 3. Radiotherapy improves the survival as well as the quality of life in patients with ependymomas, brainstem gliomas, and medulloblastoma (Healey, 1991). Routine conventional radiation dose includes 5500 rads at the frequency of 1000 rads at weekly intervals. Craniospinal irradiation is advocated for patients with poor risk MBs and ependymomas. Focal high-frequency radiotherapy is advocated in brainstem gliomas (7000 rads).

Role of the chemotherapy

Chemotherapy is used as an adjuvant treatment for children below 3 years after the definitive surgery. According to the studies by children hospital, Philadelphia, aggressive surgical resection followed by radiotherapy and chemotherapy improves the survival rates. Chemotherapy regimen includes CCNU, vincristine (1.5 mg/m²), and prednisolone (8 cycles).

Chemotherapy of recurrent tumors has produced regressions but no cures. The most active agents identified to date in the treatment of recurrent posterior fossa tumors include cisplatinum, cyclophosphamide, and methotrexate.

Vincristine (Oncovin) plant-derived vinca alkaloid acts as a mitotic inhibitor by binding tubulin, inhibits microtubule formation in the mitotic spindle causing metaphase arrest.

Cisplatin (plastinol) is a heavy metal coordination complex that exerts its cytotoxic effect by platination of DNS, a mechanism analogous to alkylation. This leads to interstrand and intrastrand DNA crosslinks and inhibition of DNA replication.

Cyclophosphamide (Cytoxan) exerts its cytotoxic effect by alkylation of DNA, leading to interstrand and intrastrand DNA crosslinks, DNA-protein crosslinks, and inhibition of DNA replication.

CONCLUSIONS

• Posterior fossa tumors are predominantly seen in children with peak incidence in the first decade

• The most common presenting symptom is raised intracranial pressure with headache and vomiting

• Majority of the tumors are MBs, ependymomas, and cerebellar astrocytomas

• Majority of the tumors are hypodense on CT scan enhancing with contrast

• The most common locations are the cerebellar vermis, lobe followed by the fourth ventricle and then the brainstem.

• Recurrence rates are very low after gross total excision

• Prognosis is good in patients with total excision. This drives the surgeon to go for total excision.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.