Embryonal Tumor with Multilayered Rosettes (ETMR) is a rare and aggressive form of brain cancer that primarily affects very young children. This tumor presents a significant challenge due to its rapid growth and location within the central nervous system. Understanding ETMR requires recognizing its unique biological characteristics and specialized management approaches.
What is ETMR Cancer
Embryonal Tumor with Multilayered Rosettes is classified as a central nervous system (CNS) embryonal tumor, meaning it originates from primitive, undeveloped cells in the brain or spinal cord. The World Health Organization (WHO) classifies ETMR as a Grade 4 tumor. It unifies tumors previously known as embryonal tumor with abundant neuropil and true rosettes (ETANTR) and ependymoblastoma, due to shared molecular features.
A defining feature of ETMR is its characteristic histological appearance under a microscope, which includes “multilayered rosettes.” These are distinct cellular structures formed by the tumor cells, often appearing alongside areas of neuropil, which is a network of nerve fibers and cells. Beyond its microscopic appearance, ETMR is most notably identified by a specific genetic alteration: the amplification of the C19MC microRNA cluster on chromosome 19q13.42. This C19MC amplification is present in approximately 90% of ETMR cases and is considered a genetic hallmark that drives the tumor’s development.
The tumor affects infants and very young children. While the exact cause remains unclear, the C19MC amplification is believed to play a significant role in its development and aggressive progression.
Symptoms and Diagnosis of ETMR
Symptoms of ETMR can be non-specific in infants and often relate to increased pressure within the skull or the tumor’s location. Common signs may include a rapidly increasing head circumference, persistent vomiting, lethargy, and irritability. Some children might also experience developmental regression, where they lose previously acquired skills, or develop seizures. Dizziness, trouble walking or talking, or vision issues like seeing double can also occur.
The diagnostic process for ETMR begins with imaging techniques, primarily Magnetic Resonance Imaging (MRI) of the brain and spine. MRI scans help visualize the tumor’s size, location, and extent, and can show areas of calcification, a frequent finding in ETMRs. However, ETMRs can resemble other brain tumors on imaging, necessitating further steps for an accurate diagnosis.
A definitive diagnosis requires a tissue sample obtained through a biopsy, which involves the surgical removal of a small piece of the tumor. This tissue is then examined under a microscope for characteristic multilayered rosettes. Molecular testing is then performed on the biopsy sample to confirm the diagnosis, involving techniques to detect the C19MC amplification. DNA methylation profiling, which analyzes patterns of gene activity, has also become an important tool for definitive diagnosis, helping to classify ETMR and distinguish it from other brain tumors.
Treatment Options for ETMR
Treatment for ETMR involves a multidisciplinary approach, combining several therapeutic modalities due to the tumor’s aggressive nature. The initial step involves surgery, aiming for maximal safe resection, which means removing as much of the tumor as possible without causing significant neurological damage. Complete removal of the tumor, when feasible, has been associated with improved outcomes.
Following surgery, intensive, multi-agent chemotherapy regimens are a standard part of treatment. These regimens often involve high-dose chemotherapy, which is more potent and aims to kill remaining cancer cells. Due to the intensity of these treatments, high-dose chemotherapy is frequently followed by stem cell rescue, a procedure that replenishes the patient’s blood-forming cells damaged by the chemotherapy.
Radiation therapy is another component of treatment, though its use is carefully considered, especially in very young children. Radiation can have long-term neurocognitive side effects on a developing brain. Therefore, for very young children, radiation might be delayed or used in specific cases. When radiation is used, careful planning and delivery are implemented to minimize damage to healthy brain tissue.
Ongoing research explores targeted therapies and enrollment in clinical trials, which represent a frontier in ETMR treatment. These newer therapies aim to specifically target the genetic mutations or molecular pathways unique to ETMR, such as the C19MC amplification. Clinical trials provide access to innovative treatments and and contribute to the understanding of ETMR biology, offering potential new avenues for managing this challenging disease.
Outlook and Support for ETMR
The prognosis for ETMR has historically been poor due to its aggressive nature and tendency to recur. Despite intensive multimodal treatments, the median survival has been reported to be around 12 to 14 months, with low 5-year overall survival rates. However, recent advancements in treatment protocols, particularly intensive chemotherapy regimens, have shown promising improvements, with some studies reporting 5-year survival rates closer to 47%.
Given the challenging outlook, comprehensive supportive care is an ongoing and important aspect of managing ETMR. This includes neurorehabilitation to help children regain lost developmental skills and manage any neurological deficits resulting from the tumor or its treatment. Psychosocial support is provided to both the child and their family, addressing the emotional and psychological burdens of dealing with a rare and aggressive cancer.
Palliative care also plays a role, focusing on improving the quality of life by managing symptoms and providing comfort throughout the illness. Long-term follow-up is also necessary to monitor for any signs of tumor recurrence and to manage potential late effects of the intensive treatments received during early childhood.