Pineoblastoma is a malignant

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

of the

pineal gland The pineal gland (also known as the pineal body or epiphysis cerebri) is a small endocrine gland in the brain of most vertebrates. It produces melatonin, a serotonin-derived hormone, which modulates sleep, sleep patterns following the diurnal c ...

. A pineoblastoma is a supratentorial midline

primitive neuroectodermal tumor Primitive neuroectodermal tumor is a malignant (cancerous) neural crest tumor. It is a rare tumor, usually occurring in children and young adults under 25 years of age. The overall 5 year survival rate is about 53%. It gets its name because the ...

. Pineoblastoma can present at any age, but is most common in young children. They account for 0.001% of all primary CNS neoplasms.

Epidemiology

Pineoblastomas typically occur at very young ages. One study found the average age of presentation to be 4.3 years, with peaks at age 3 and 8. Another cites cases to more commonly occur in patients under 2 years of age. Rates of occurrence for males and females are similar, but may be slightly more common in females. One study found incidence of pineoblastoma to be increased in black patients compared to white patients by around 71%. This difference was most apparent in patients aged 5 to 9 years old.

Pathophysiology

The

is a small organ in the center of the brain that is responsible for controlling

melatonin Melatonin, an indoleamine, is a natural compound produced by various organisms, including bacteria and eukaryotes. Its discovery in 1958 by Aaron B. Lerner and colleagues stemmed from the isolation of a substance from the pineal gland of cow ...

secretion. Several tumors can occur in the area of the pineal gland, with the most aggressive being pineoblastoma. Pineoblastomas arise from embryonal cells in the pineal gland and are rapidly growing. They are considered grade 4 tumors, meaning they are

malignant Malignancy () is the tendency of a medical condition to become progressively worse; the term is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous benign tumor, ''benign'' tumor in that a malig ...

and may

metastasize Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...

. Due to the pineal gland's location at the center of the brain and the rapidly growing nature of this disease, obstruction of CNS fluid is a common symptom. The exact cause of pineoblastoma is unknown.

MicroRNA Micro ribonucleic acid (microRNA, miRNA, μRNA) are small, single-stranded, non-coding RNA molecules containing 21–23 nucleotides. Found in plants, animals, and even some viruses, miRNAs are involved in RNA silencing and post-transcr ...

dysregulation has been found to be associated with many cases of pineoblastoma, specifically, mutations in

DICER1 Dicer, also known as endoribonuclease Dicer or helicase with RNase motif, is an enzyme that in humans is encoded by the gene. Being part of the RNase III family, Dicer cleaves double-stranded RNA (dsRNA) and pre-microRNA (pre-miRNA) into short ...

and

DROSHA Drosha is a Class 2 ribonuclease III enzyme that in humans is encoded by the ''DROSHA'' (formerly ''RNASEN'') gene. It is the primary nuclease that executes the initiation step of miRNA processing in the nucleus. It works closely with DGCR8 and ...

genes. DICER1

germline mutation A germline mutation, or germinal mutation, is any detectable variation within germ cells (cells that, when fully developed, become sperm and Egg cell, ova). Mutations in these cells are the only mutations that can be passed on to offspring, when e ...

s cause a tumor predisposition syndrome, and should be considered in patients with pineoblastoma. Pineoblastoma may occur in patients with hereditary uni- or bilateral

retinoblastoma Retinoblastoma (Rb) is a rare form of cancer that rapidly develops from the immature cells of a retina, the light-detecting tissue of the eye. It is the most common primary malignant intraocular cancer in children, and 80% of retinoblastoma cas ...

. When retinoblastoma patients present with pineoblastoma this is characterized as " trilateral retinoblastoma". Up to 5% of patients with hereditary retinoblastoma are at risk of developing trilateral retinoblastoma. This tumor combination is more aggressive than an isolated pineoblastoma. Prognosis of patients with trilateral retinoblastoma is dismal, only a few patients have survived more than 5 years after diagnosis; all survivors were diagnosed with small tumors in a subclinical stage. Recent advances in (high-dose) chemotherapy treatment regimens and early detection have improved survival of patients with trilateral retinoblastoma to up to 50%. Additionally, various mutations or deletions in chromosomes 1, 9, 13, 16 and 22 have been associated with pineoblastoma incidence.

Clinical features

The most common symptoms to occur with pineoblastoma are headache, behavior changes, and cognitive disturbances. These masses also often cause

obstructive hydrocephalus Hydrocephalus is a condition in which cerebrospinal fluid (CSF) builds up within the brain, which can cause pressure to increase in the skull. Symptoms may vary according to age. Headaches and double vision are common. Elderly adults with no ...

, leading to increased intracranial pressure. This can result in vision changes and Parinaud's syndrome. Due to the aggressive nature of the disease, tumor spread at the time of diagnosis is common. Pineoblastomas often invades locally, with spread to the head and spine seen in 25–41% of patients. While CNS spread is relatively common, these tumors rarely cause distant metastases.

Diagnosis

Several imaging methods can be used to diagnose pineoblastoma. Initially, urgent CTs are recommended, followed by MR imaging. CT will show large, multilobulated masses with heterogenous

contrast enhancement A contrast agent (or contrast medium) is a substance used to increase the contrast of structures or fluids within the body in medical imaging. Contrast agents absorb or alter external electromagnetism or ultrasound, which is different from radioph ...

and peripheral calcification of the pineal gland. On MRI, pineoblastomas again appear as masses with heterogenous enhancement. They often appear hypo- to isointense on T1 and slightly hyperintense on T2-weighted images. Some areas of necrosis or hemorrhage may be seen as well. PET-CT has also been used in diagnosis, and shows increased uptake of fludeoxyglucose with pineoblastomas compared to other pineal masses. Diagnosis also requires CSF sampling via lumbar puncture to assess for cytology and tumor markers. Biopsy is required for diagnosis. Pineoblastomas appear as high grade, highly cellular, small blue cells histologically. Features of aggressive malignancies can be seen, like high nucleus-to-cytoplasm ration, poorly differentiated cells, high mitotic activity, and necrosis. Homer Wright, or neuroblastic, and Flexner-Wintersteiner, or retinoblastic, rosettes can also be seen. In contrast to other masses of the pineal gland, pineocytomatous rosettes are not present.

Immunohistochemistry Immunohistochemistry is a form of immunostaining. It involves the process of selectively identifying antigens in cells and tissue, by exploiting the principle of Antibody, antibodies binding specifically to antigens in biological tissues. Alber ...

staining will reveal

neuronal A neuron (American English), neurone (British English), or nerve cell, is an excitable cell that fires electric signals called action potentials across a neural network in the nervous system. They are located in the nervous system and help to ...

glial Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cell (biology), cells in the central nervous system (the brain and the spinal cord) and in the peripheral nervous system that do not produce Action potential, electrical ...

, and photoreceptor marker positivity. This includes

synaptophysin Synaptophysin, also known as the major synaptic vesicle protein p38, is a protein that in humans is encoded by the ''SYP'' gene. Gene The gene is located on the short arm of X chromosome (Xp11.23-p11.22). It is 12,406 bases in length and li ...

neurofilament Neurofilaments (NF) are classed as Intermediate filament#Type IV, type IV intermediate filaments found in the cytoplasm of neurons. They are protein polymers measuring 10 nm in diameter and many micrometers in length. Together with mic ...

protein, and CRX, a specific pineal or

retinal Retinal (also known as retinaldehyde) is a polyene chromophore. Retinal, bound to proteins called opsins, is the chemical basis of visual phototransduction, the light-detection stage of visual perception (vision). Some microorganisms use ret ...

marker, positive staining. Four methylation-based subtypes of pineoblastoma with clinical relevance is now recognized.

Treatment

Initial treatment for pineoblastoma often includes a shunting procedure to redirect accumulated cerebrospinal fluid secondary to obstructive hydrocephalus. This shunt can help manage increased intracranial pressure and relieve some symptoms. Surgery to remove the tumor is associated with better outcomes, however, this is not always possible due to the proximity of the pineal gland to neurovascular structures. Complete tumor resection is only seen in about 30% of cases. Following surgery,

radiation therapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a therapy, treatment using ionizing radiation, generally provided as part of treatment of cancer, cancer therapy to either kill or control the growth of malignancy, malignant cell (biology), ...

to the brain and spinal cord can increase survival. However, radiation can only safely be used in patients over 3 years old due to the risk of significant neurological impairment.

Chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

treatment can also be used, either before or after surgery; its optimal use is still under investigation.

Prognosis

Pineoblastomas are very aggressive tumors. 5-year survival for patients with pineoblastomas is around 58%. Prognosis for patients under 5 years old is lower, between 15 and 40%. Disseminated disease at diagnosis is also associated with worse outcomes. When pineoblastomas occur with retinoblastomas, the prognosis is typically worse, and these patients require more aggressive treatment. When stratified by molecular subtype, localized, microRNA-altered pineoblastomas are in contrast associated with superior outcome when treated with radiation and chemotherapy. Complete gross tumor resection is associated with improved prognosis, but is difficult and rare to achieve. Radiation therapy after surgery is also linked to improved survival.

References

External links

{{Endocrine gland neoplasia Endocrine neoplasia Brain tumor