Pineoblastoma – Brief information

Author:  Maria Yiallouros, Editor:  Maria Yiallouros, Reviewer:  Dr. med. Martin Mynarek, English Translation:  Dr. med. Gesche Riabowol (geb. Tallen), Last modification: 2025/03/06 https://kinderkrebsinfo.de/doi/e279751

General information on the disease

A pineoblastoma is a malignant brain tumour‎. It arises from cells of the pineal gland‎ (Glandula pinealis), a small endocrine organ in the diencephalon‎, which is located in the centre of the brain. Since pineoblastoma directly originate from the central nervous system‎ (CNS), they are also called primary CNS tumour‎s, thereby differentiating them from malignant tumours of other organs that have spread (metastasised) to the CNS.

Pineoblastoma originate from extremely immature (undifferentiated‎, embryonal‎) cells of the central nervous system, which divide at a high rate. Therefore, these tumours grow very fast. Due to their aggressive growth behaviour, they are defined as high-grade malignant tumours.

Pineoblastoma may spread from the area of the pineal gland into other regions of the brain and spinal cord‎ as well. Metastasis outside the CNS, for instance to bones, bone marrow‎, lung, or lymph nodes‎, is rare.

In the past, many authors considered pineoblastomas and embryonal, non-rhabdoid CNS tumours – due to their rarity and similarity regarding the course of the disease – as one group. Today, however, it is well-known that a pineoblastoma differs substantially from other embryonal CNS tumour on the molecular‎ level and, therefore, needs to be dealt with as an independent tumour type.

Incidence

Pineoblastomas are very rare: with about three or four newly diagnosed patients under 18 years of age per year, they account for less than 1 % of all CNS tumours in childhood and adolescence in Germany. Pineoblastoma is mostly diagnosed in children and young adults. The patients‘ average age at diagnosis is approximately 18 years.

Causes

A pineoblastoma is caused by a malignant transformation of nerve tissue‎ cells. The reasons for tumour development have not been completely found out yet. It is well-known, though, that radiotherapy‎ of the brain, for example as received by children with certain forms of leukaemia‎ or with eye cancer (retinoblastoma‎), leads to an increased risk of developing a CNS tumour later in life.

In addition, it has been shown that pineoblastoma are sometimes associated with certain genetic‎ and chromosomal‎ abnormalities in the tumour cells. The resulting impairments of cell development and cell communication may be contributing factors promoting the transformation of a healthy into a cancer cell. However, since pineoblastomas are rare, only a few molecular‎ abnormalities that might be responsible for causing the disease have been identified yet.

Good to know: rarely, pineoblastoma can be associated with hereditary retinoblastoma and thus genetic alterations of the retinoblastoma gene‎ (so-called trilateral retinoblastoma). More information on trilateral retinoblastoma can be found in our Retinoblastoma chapter.

Symptoms

Due to the uncontrolled and aggressive growth pattern of pineoblastoma, symptom‎s typically develop and deteriorate fast. The presenting symptoms of this tumour (like other tumours of the central nervous system‎) primarily depend on the patient’s age, the site and size of the tumour as well as its pattern of spread within the CNS. The following general (nonspecific) and local (specific) symptoms can occur:

General (nonspecific) symptoms

Unspecific general symptoms occur independently of the tumour’s location. They may be similar to and therefore mimic other, non-CNS diseases. General symptoms of a child or adolescent with a CNS tumour may include headaches and/or back pain, dizziness, loss of appetite, nausea and vomiting (particularly after getting up in the morning), weight loss, increasing fatigue, inability to concentrate, school problems, mood swings, and character changes as well as developmental delay, to name a few.

Major reason for these symptoms is the slowly but continuously increasing intracranial pressure (ICP). An elevated intracranial pressure may be caused by the growing, thus more and more space-occupying tumour within the bony skull. It may as well be due to the tumour blocking the regular flow of the cerebrospinal fluid‎, thereby forming hydrocephalus‎. In babies or small children with soft spots (open fontanelle‎s), elevated intracranial pressure and hydrocephalus typically present with a bulging fontanelle or a larger than expected head circumference (macrocephalus‎), respectively.

Local (specific) symptoms

Local symptoms may indicate the tumour location and, thus, which functional regions of the CNS might be affected. Pineoblastoma, for example, can cause trouble with eye movements, in particular limitations of upgaze. This vision impairment results from the tumour’s specific location in the diencephalon‎ and is also known as Parinaud syndrome. Furthermore, a tumour in the diencephalon or in the hemispheres of the cerebrum‎ can be associated with seizures‎ and/or motor deficits. Also, vision impairments, speech disorders, behavioural and sleep problems, as well as moodiness and altered appetite regulation may, although to a lesser extent, be indicative of tumour location.

Good to know: Not all patients presenting with one or more of the symptoms mentioned above do have a pineoblastoma or another type of brain tumour. Many of these symptoms may also occur with other, harmless diseases that are not associated with a brain tumour at all. However, if certain symptoms persist or get worse (for example repetitive headaches or rapid increase of head circumference in a young child), a doctor should be seen to find the underlying reason. In case it is a brain tu-mour, treatment should be started as soon as possible.

Diagnosis

If the paediatrician thinks that the young patient’s history (anamnesis‎) and physical examination‎ are suspicious of a tumour of the central nervous system (CNS), the child should immediately be referred to a hospital with a childhood cancer program (paediatric oncology unit), where further diagnostics can be initiated and performed by childhood cancer professionals. Very close collaboration between various specialists (such as paediatric oncologist‎s, paediatric neurosurgeons, paediatric radiologist‎s, to name a few) is required, both to find out, whether the patient really suffers from a malignant CNS tumour and, if so, to determine the tumour type and the extension of the disease. Knowing these details is absolutely essential for optimal treatment and prognosis‎.

Tests to secure diagnosis

The initial diagnostic procedures for a young patient presenting with a suspected CNS tumour at a childhood cancer centre include another assessment of the patient’s history, a thorough physical/neurological‎ exam and imaging‎ diagnostics, such as magnetic resonance imaging‎ (MRI) or (less often) computed tomography‎ (CT). These tests help find out exactly whether the patient has a tumour of the central nervous system. Also, localisation and extent of the tumor, its demarcation regarding adjacent tissue as well as a potential hydrocephalus‎ can be diagnosed by these imaging techniques very well.

In order to validate the final diagnosis, histological‎ and molecular‎ analysis of surgically obtained tumour tissue (biopsy‎) is required. Usually, this is done using the tissue obtained during surgical tumour removal.

The extent of histological and, especially, molecular genetic‎ workup has been substantially increased over the past years. Today’s option of using modern lab techniques makes it possible to identify molecular tissue characteristics that do not only help finalize the diagnosis, but can also provide information on what to expect regarding the course of the disease (such as growth behaviour).

Tests to assess spread of disease

Once the diagnosis of a pineoblastoma has been confirmed, additional tests are required to assess the extent of the disease within the central nervous system (CNS). Apart from MRI‎ scans of the complete CNS (brain and spine) for macroscopic metastases, these tests also include microscopic checking of the cerebrospinal fluid‎ (CSF) for tumour cells in the spinal cord‎ (which are not visible by MRI scan). Cerebrospinal fluid is mostly obtained from the spine in the lower back (lumbar puncture‎), since the risk of the puncture needle damaging the spinal cord is lowest at the lower back level.

Tests before treatment begins

In preparation for the intensive treatment of the brain tumour, further investigations are performed, such as electrocardiography‎ (ECG) and echocardiography‎ to check cardio function. Furthermore, additional blood tests are needed to assess the patient’s general health condition and to check whether the function of certain organs (such as liver and kidneys) is affected by the disease and whether there are any metabolic disorders to be considered prior or during therapy.

The condition and function of the hormonal glands will be checked in order to detect and manage potential tumour- and/or treatment-associated endocrinological impairments as early as possible. For the same reason, neuropsychological testing [see neuropsychology‎‎] might be done prior to cancer treatment. Any changes occurring during the course of treatment can be assessed and managed better based on the results of those initial tests, which thus help to keep the risk of certain treatment-related side effects as low as possible.

Also, the patient’s blood group‎ needs to be determined in case a blood transfusion‎ is required during treatment. In sexually mature females (which means after they have experienced their first menstruation), a pregnancy test is recommended prior to treatment as well.

Good to know: Not every patient needs the complete check-up. On the other hand, tests might be added that haven't been mentioned here, depending on the individual situation of the patient. Your caregivers will inform you and your child, which diagnostic procedures are individually required in your child’s situation and why.

Treatment planning

Once the diagnosis and extent of a CNS tumour has been confirmed, treat-ment planning starts. In order to provide the patient with the best possible individual and risk-adapted therapy, the treatment team considers specific factors that are known to have an impact on the prognosis‎ (so-called prognostic factors).

Important prognostic factors‎ in case of a pineoblastoma are the type, localization, extent and spread of the tumour. Also, the biological (molecular) features of a tumour increasingly impact the choice of optimal treatment. In addition, the patient’s age and overall physical condition play an important role. Age at diagnosis, above all, determines whether the patient may receive radiotherapy or not. All these factors are included in treatment planning in order to achieve the best outcome possible for each patient.

Classification of tumours of the pinealis region

Pineoblastoma belongs to the group of so-called pineal tumours. Various types of tumour can arise in the pineal gland‎, which differ from each other both in terms of their appearance under the microscope‎ (i.e. histological‎ly) and in terms of their molecular‎ tissue properties. Sometimes they are also associated with different prognosis‎ for patients. Pineoblastoma, the most frequent tumour of the pineal region, is defined as a high-grade malignant tumour by the World Health Organization (WHO‎).

According to the current WHO classification‎ for tumours of the central nervous system (WHO classification 2021), pineal tumours are differentiated as follows:

• Pineoblastoma (CNS WHO grade 4)
• Papillary tumour of the pineal region (PTPR) (CNS WHO grade 2 or 3)
• Pineal parenchymal tumour of intermediate differentiation (CNS WHO grade 2 or 3)

Pineal tumours other than pineoblastoma are less malignant (CNS WHO grade 2 or 3), but very rare in childhood and adolescence.

Treatment

Treatment of children and adolescents with pineoblastoma should take place in a children's hospital with a paediatric oncology program. Only in such a childhood cancer centre, highly experienced and qualified staff (doctors, nurses and many more) is guaranteed, since they are specialized and focus on the diagnostics and treatment of children and teenagers with cancer according to the most advanced treatment concepts. The doctors in these centres collaborate closely with each other. Together, they treat their patients according to treatment plans (protocols) that are continuously optimised. The goal of the treatment is to achieve higher cure rates while avoiding side effects as much as possible.

Current treatment concepts involve neurosurgical tumour removal, chemotherapy and, depending on the patient’s age, radiotherapy. In selected patients, high-dose chemotherapy followed by autologous stem cell transplantation may also be an option.

Pineoblastomas are very rare diseases and their therapies are constantly being further developed. The treatment options presented below are based on recommendations from the study/registry centre, however, these must be discussed individually in each case. They do not claim to be exhaustive at this point. The exact course of treatment for individual patients will be decided by the attending physician in consultation with the patient or their relatives.

Surgery

The first step in treating a pineoblastoma is surgery‎. Goal of surgery is gross (microsurgical) total tumour removal. This means that at the end of the surgical procedure, no tumour tissue can be identified through the surgical microscope. Frequently, however, total tumour resection cannot be achieved due to the localization of these tumours.

In most patients, neurosurgical intervention results in normalising the flow of cerebrospinal fluid‎ (CSF). Patients initially presenting with hydrocephalus‎ may need a transient hydrocephalus drainage‎ prior to tumour removal or, sometimes, even a permanent drainage system later.

Additional, non-surgical treatment

Since pineoblastomas tend to infiltrate adjacent tissue and, furthermore, often spread into other parts of the central nervous system via the cerebrovascular fluid (CSF), treating the tumour locally only is not sufficient. Therefore, surgery is followed by additional non-surgical treatment, comprising radiotherapy‎ and/or chemotherapy‎.

Chemotherapy uses drugs (so-called cytostatic agents or cytostatics‎) that can kill fast-dividing cells, such as cancer cells, or inhibit their growth, respectively. In order to eliminate as many of the cancer cells as possible, a combination of several cytostatics is usually applied. Frequently-used agents are, for example, carboplatin, etoposide, methotrexate, vincristine, cyclophosphamide, lomustine, cisplatin and/or temozolomide.

Radiotherapy is done using energy-rich, electromagnetic‎ radiation, given through the skin to the tumour region. Radiation causes DNA‎ damage in tumour cells, thereby leading to cell death. Modern techniques, such as intensity-modulated radiotherapy‎ (IMRT), help minimise radiation damages in healthy tissue. Instead of conventional radiotherapy with photon‎s, particle-radiation with proton‎s (proton therapy‎) can be an option in suitable cases as well. This type of radiotherapy allows to reduce the effects of radiation in healthy tissue even better and is, therefore, gaining an increasing importance in the treatment of children and teenagers with solid tumour‎s.

Decision upon which therapy is to be applied (treatment modalities, intensity of chemo-/radiotherapy) is based on the patient’s age, the histological and molecular subtype of the tumour, certain biological risk factors, as well as on the extent of both metastases and surgical tumour removal (see chapter “Therapy planning”).

Possible treatment strategies are as described below.

Treatment options for pineoblastoma patients

After maximal possible tumour removal, patients with non-metastasised pineoblastoma, who are older than four years of age, will receive radiation‎ of the complete central nervous system (craniospinal radiotherapy), followed by an additional boost to the tumour site. Radiotherapy is followed by a so-called maintenance chemotherapy‎, which includes multiple cytostatic agents. In cases of metastasis‎, treatment will be intensified, for example by giving higher doses of radiotherapy combined with a preceding chemotherapy (induction chemotherapy).

In children under four years of age, radiotherapy should be avoided or delayed in order to minimize the risk of serious late effects. Instead of radiotherapy after surgery, patients will receive chemotherapy with multiple agents. In some patients, radiotherapy may be an option later on. Some patients are also eligible for high-dose chemotherapy‎ followed by autologous stem cell transplantation‎ to increase the chances of survival.

There are no standard therapies for patients who develop a papillary tumour of the pineal region or a pineal parenchymal tumour with intermediate differentiation in childhood and adolescence (see chapter "Treatment planning – Classification"). These tumour types are extremely rare diseases. Therapeutic strategies must be confirmed on an individual basis.

Important to know: The details of how an individual patient is treated will be discussed between the responsible physician, the patient and the family.

Therapy optimising trials and registries

In Germany, children and adolescents with pineoblastoma and relapses (recurrence‎) of this tumour are generally treated individually and monitored in the framework of registry studies. Where available, participation in therapy optimising trial‎s or early phase studies (phase I/II studies, in cooperation with the pharmaceutical industry) is considered together with the patients and/or their relatives. There are various early phase networks in Germany for finding suitable early phase studies.

Therapy optimising trials are standardised and controlled clinical trials that aim at steadily developing and improving treatment concepts for sick patients based on the current scientific knowledge.

Patients who cannot participate in any study, for example because none is available or open for them at that time or since they do not meet the required inclusion criteria, respectively, are often included in a so-called registry. One goal of a registry is to collect treatment data for research questions. Furthermore, the registry centre supports the doctors at site with (non-commital) treatment recommendations based on the most recent data on best treatment options, in order to provide the patient with optimal therapy even without the framework of a clinical study.

The following registries are available at the moment:

• I-HIT-MED Registry: Patients with pineoblastoma can be enrolled the International HIT-MED Registry, regardless of the treatment given. These patients will receive treatment as per individually designed treatment plans. The goal of the registry is not to assess the feasibility of an ongoing trial, safety or efficacy of a certain treatment. It rather aims at collecting individual patient data for future analysis. The headquarters of the registry are located in the Children’s Cancer Centre at the University of Hamburg, Germany. The head of the registry is Prof. Dr. med. Stefan Rutkowski.

Prognosis

The cure rates for children and adolescents with pineoblastoma are about 60–70 % (5-year-survival rate). However, in individual patients, prognosis‎ is dependent on various factors. In particular, the stage of the disease and the patient’s age play a significant role. Hence, children and adolescents with metastasized disease have generally a more unfavourable prognosis than patients with localized disease. In young patients who cannot receive radiotherapy‎ as part of their treatment, the prognosis is significantly worse, while cure rates of over 80 % have been described in older children with non-metastasised disease.

Note: The survival rates mentioned in the text above are statistical values. Therefore, they only provide information on the total cohort of patients with childhood Medulloblastoma. They do not predict individual outcomes.

In the context of cancer, the term "cure“ should rather be referred to as „free of cancer“, for even if current treatment regimens may help remove the tumour, the the tumour’s growth may have caused irrepairable damage to the brain or the treatment may be associated with late effects. Early detection and appropriate management of these long-term secondary effects typically require intensive rehabilitation‎ and thorough long-term follow-up care.

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04/03/2025