Pediatric Considerations for Pineal Tumor Management

Pineal tumors are relatively rare central nervous system lesions with a predilection for the pediatric population. For the vast majority of these lesions, surgical resection is a critical step in effective treatment. This article discusses current strategies for preoperative evaluation, operative management, and postoperative care of the pediatric patient with a newly diagnosed pineal region tumor.

Pineal region tumors are rare, accounting for 0.4% of tumors found in the central nervous system (CNS). Pineal region tumors are nearly 10 times more common in the pediatric population than in adults, accounting for 2.8% to 9% of all childhood CNS malignancies. There are 3 main categories of pediatric pineal region tumors based on histology and cell origin: germ cell tumors (GCTs), pineal parenchymal tumors, and others, which include tumors of glial cell origin and rare metastases. Of these, GCTs are the most common, representing 50% to 75% of all pediatric pineal region tumors, depending on the study. Pineal parenchymal tumors are the second most common, representing 15% to 30%, and other tumors, such as astrocytoma, ependymoma, lymphoma, and atypical teratoid rhabdoid tumors, are less common.

Demographics of the affected pediatric population vary depending on histologic diagnosis. Pineal region GCTs occur almost exclusively in boys aged 10 to 19 years and have a marked increased prevalence in the Asian population, notably in Japan and Korea. GCTs may be associated with Klinefelter syndrome. Pineal parenchymal tumors occur with equal frequency in both genders, with one study citing a mean age of 12 years.

Several studies have looked at the histologic breakdown of pineal tumors within the pediatric population ( Table 1 ). Among GCTs, about 60% are pure germinomas, and the remainder are nongerminomatous GCTs (NGGCTs), including yolk sac tumor (endodermal sinus tumor), choriocarcinoma, embryonal carcinoma, and mixed malignant GCTs (comprising germinoma or teratoma with additional malignant elements). Pineal parenchymal tumors include pineocytoma, a benign lesion, and pineoblastoma, a World Health Organization grade IV malignant primitive neuroectodermal tumor (PNET).

Table 1

The predominance of GCTs among pineal region tumors. In all 3 studies shown, GCTs comprise more than one-third, and in most cases more than two-thirds of all pineal region tumors in children

Study	N	Age Range (y)	Histologic Breakdown, n (%)
Al-Hussaini et al	355	0–18	GCT, 237 (67)
			PPT, 96 (27)
			Glioma, 9 (2)
			AT/RT, 2 (<1)
			Other, 11 (3)
Yazici et al	24	0.5–15.1	Germinoma, 5 (21)
			NGGCT, 4 (17)
			PPT, 10 (42)
			Glioma, 1 (4)
			Other, 4 (17)
Cho et al	35	0–20	Germinoma, 10 (28.5)
			NGGCT, 19 (54)
			PPT, 8 (22.8)
			Glioma, 3 (8.6)

Abbreviations: AT/RT, atypical rhabdoid/teratoid tumor; NGGCT, nongerminomatous GCT; PPT, pineal parenchymal tumor.

Overall treatment strategies for these tumors vary significantly depending on histologic diagnosis and continue to evolve as new techniques become available. Treatment of malignant pineal tumors generally involves surgical resection or biopsy, radiation therapy, and chemotherapy. For symptomatic benign tumors, such as pineocytomas, pineal cysts, pilocytic astrocytomas, and mature teratomas, surgical resection is the definitive therapy. Surgery generally plays a role in the management of nearly all these patients because of the need for tissue diagnosis and management of hydrocephalus. In addition, there is growing evidence to support aggressive debulking of malignant lesions to improve efficacy of adjuvant therapies.

This article discusses current strategies for preoperative evaluation, operative management, and postoperative care of the pediatric patient with a newly diagnosed pineal region tumor.

Preoperative assessment

There are 3 main mechanisms by which pineal tumors become symptomatic: elevated intracranial pressure from obstructive hydrocephalus, direct compression of the brainstem or cerebellum, and neuroendocrine dysfunction. The most common presenting symptoms seen in patients with pineal lesions are related to hydrocephalus. Symptoms reported include headache, Parinaud syndrome, decreased visual acuity, ataxia, and diabetes insipidus. Less-frequent symptoms include precocious puberty and hypogonadism. In 2 studies by Mandera and colleagues and Cho, the mean duration of symptoms was between 5 and 10 months, respectively. Symptoms often correlate with the degree of hydrocephalus, and in the study by Cho, 29 of 48 patients had moderate to severe hydrocephalus on imaging that warranted immediate cerebrospinal fluid (CSF) diversion.

Head computed tomography (CT) or brain magnetic resonance imaging (MRI) typically demonstrate a lesion within the posterior portion of the third ventricle, protruding anteroinferiorly to the tectal plate. It is difficult to differentiate between GCTs and pineal parenchymal tumors based on imaging alone. Pineal gland calcification is commonly seen in all types of pineal tumors and cannot typically aid in diagnosis. Findings on CT are generally isodense to hyperdense lesions that are contrast enhancing. On MRI, lesions may be isointense to hypointense on T1-weighted imaging and may vary from isointense to hyperintense on T2-weighted imaging. The tumors are most often heterogeneously enhancing ( Figs. 1 and 2 ). Because of possible synchronous lesions, total neuroaxis imaging is recommended. Disease dissemination may occur intracranially, most commonly in the pituitary region or thalamus, and is most frequently associated with GCTs ( Fig. 3 ). One study estimated that one-third of patients show spinal dissemination at the time of diagnosis, with other study estimates ranging from 10% to 57%.

In all patients presenting with a newly diagnosed pineal region tumor, appropriate initial workup includes MRI of the brain and total spine with and without contrast, evaluation of serum markers for α-fetoprotein, β-human chorionic gonadotropin (β-hCG), routine laboratory tests to rule out metabolic abnormalities or infection, evaluation for endocrine dysfunction, and CSF diversion with either placement of an external ventricular drain or an endoscopic third ventriculostomy (ETV) if hydrocephalus is present. CSF should additionally be tested for germ cell markers as well as cytology. Preoperative CSF sampling is a critical part of the workup because CSF has greater sensitivity than serum and may be diagnostic. Elevation of CSF α-fetoprotein levels above 10 ng/mL and/or β-hCG above 50 mIU/mL is diagnostic of NGGCT; isolated lesser elevation of β-hCG levels may occur in pure germinoma. In addition to diagnostic purposes, lumbar CSF is also important in determining postoperative chemotherapy protocol eligibility. Except for patients in whom elevated serum or CSF marker levels are diagnostic for endodermal sinus tumor or choriocarcinoma, histopathologic diagnosis must be made by tissue biopsy.

Surgical treatment

In patients with obstructive hydrocephalus, CSF diversion is frequently planned before resection of tumor. Options for CSF diversion include placement of external ventricular drain, ventriculoperitoneal shunt, and ETV. However, ETV is generally the preferred choice in patients requiring treatment for hydrocephalus before tumor resection. Reasons for this include higher risks of infection, increased tumor dissemination, shunt failure, overshunting, and subdural hematoma associated with ventriculoperitoneal shunt placement.

When the decision is made to perform an initial biopsy, the biopsy may be performed via an endoscopic, stereotactic, or open approach. Biopsy enables tissue diagnosis for the planning of adjuvant therapy without open resection. In addition, biopsy guides the surgeon in the decision to perform radical tumor resection. Several recent studies have advocated the use of endoscopy for biopsy over the stereotactic approach and report a histologic diagnosis in 75% to 94% of tumors biopsied. These results are comparable with biopsy yields previously reported for stereotactic biopsy of between 87% and 97%, and endoscopic approach offers the additional benefit of simultaneous ETV as well as visualization of the lesion at the time of biopsy. Wong and colleagues advocate the use of endoscopy to simultaneously perform ETV and tumor biopsy in patients with obstructive hydrocephalus before performing radical resection. In their study, histologic diagnosis was achieved in 21 of 25 (84%) patients who underwent endoscopic tumor biopsy. Endoscopy also does not need to be limited to patients with ventriculomegaly. A recent study by Naftel and colleagues describes successful biopsy of tumors in patients with small ventricles with low morbidity and high diagnostic yield. In this report, a brain navigation system was used for initial trajectory into the ventricle. A 1.1-mm endoscope (NeuroPEN, Medtronic) was used inside a 1.7-mm ventricular catheter, and 10 to 20 mL of lactated Ringer solution was insufflated into the ventricle to improve visualization. Postoperatively, an external ventricular drain was left in case of need for emergent CSF diversion, although no patient from this group ultimately required additional CSF diversion procedures. Bruce and colleagues have described the role of stereotactic biopsy in determining the need for total resection. This approach is particularly appropriate if CSF diversion has already been established or in patients without hydrocephalus. Stereotactic biopsy does not confer the same opportunity to perform simultaneous ETV, but it is equally safe and likely to yield diagnostic tissue.

A third option for obtaining tissue is open resection. Because aggressive surgical resection of benign pineal region tumors as well as many malignant lesions affords the best outcome for the patient, open biopsy is the approach favored at the authors’ institution for patients with negative CSF and serum markers. In addition, because there is often significant heterogeneity seen in germ cell histology, open biopsy is more likely to yield accurate histologic diagnosis ( Fig. 4 ). General indications for surgery include symptomatic benign lesions for which surgery is curative, cytoreduction of tumor for chemotherapy/radiotherapy of malignant lesions, and removal of residual tumor after chemotherapy. Whenever possible, if the patient is going to undergo biopsy, we perform an open biopsy with a plan to resect the lesion after frozen tissue is obtained. Once frozen specimen is obtained, surgical resection can be performed, unless the frozen specimen yields a diagnosis of germinoma, in which case no further surgery is indicated. For patients undergoing planned surgical resection of a pineal region tumor, operative approaches include the supracerebellar-infratentorial (SCIT) approach, the occipital-transtentorial (OTT) approach, and the transcallosal-interhemispheric approach. In the pediatric population, the SCIT and OTT approaches may be performed in modified prone, park bench, or sitting position. The authors favor the sitting position and have successfully used this position in children as young as 2 years ( Fig. 5 ). When planning a surgical resection, it is important to consider the anatomic relationship of the tumor with the third ventricle, tentorium, falx, and vein of Galen. Preoperative MRI can usually provide this information.