In this report, we presented a case series of three female pediatric patients, each with distinct clinical behaviors and treated in different ways, reflecting the heterogenicity of the tumor and lack of a consensus on proper therapeutic and management plans.
The radiological findings of PTPR in our case series mostly match those reported in the literature. However, our cases showed a heterogeneous signal intensity on T2WI with diffusion restriction and heterogeneous enhancement.
Although case #2 showed multiple large areas of high signal intensity on T1WI, the other cases mostly presented with isosignal intensity on T1WI, but along the periphery of the lesion, we observed hyperintensity. Most of the high T1 signal intensity in our cases is attributed to hemorrhage, as the high signal on T1WI was decreased in the follow-up studies with a greater susceptibility effect, but other areas were unchanged and did not show any susceptibility and were not suppressed in fat saturated sequences, indicating proteinaceous content.
In a study by Chang et al.,7 the authors found a high T1WI signal intensity and intrinsic T1 hyperintensity within the PTPR lesion of an adult patient after confirming the absence of fat, hemorrhage, melanin, or calcification in a mass of the posterior commissure or pineal region.7
Similarly, a case report study on a 17-year-old patient found a T1 hyperintensity within the lesion after the authors excluded fat content, melanin, calcification and extracellular methemoglobin A; they concluded that the glycopeptide content was likely the cause for this T1 hyperintensity.8
Interestingly, images in our young pediatric patients showed a diminished appearance on T1WI relative to that reported for older patients, which might indicate a thus far unexplored intrinsic difference in PTPR tumors dependent on the patient's age.
The clinical behavior, prognosis, and appropriate treatment of PTPR in pediatric patients have yet to be fully defined due to the rarity of these tumors and the limited numbers of reported cases in the literature. PTPR in adults has a high recurrence rate of up to 67–73%, with a reported 5-year progression-free survival rate of only 27%, while a lower recurrence rate of 47% has been reported in children.3
Surgery is the primary therapy for PTPR, and the extent of surgical resection is the only clinical factor significantly associated with better overall survival. Incomplete surgical resection and tumors with higher mitotic and proliferative activity (as measured by Ki-67 expression) are associated with a poor prognosis.4 Focal adjuvant radiotherapy plays an important role in controlling subsequent tumor recurrence.
There is no proven benefit of chemotherapy, and different chemotherapy regimens have been reported in recurrent refractory cases, including procarbazine, lomustine, vincristine and temozolomide.9
At the molecular signaling level, mTOR kinase inhibitors such as everolimus have been reported to be effective in controlling recurrent PTPR tumors with chromosome 10 deletions and specifically with inactivating mutations in the PTEN (phosphatase and tensin-like protein) tumor suppressor gene on chromosome 10, which is involved in the PI3K/Akt/mTOR signaling pathway. PTEN and its downstream targets may respond to everolimus with or without temozolomide.10
Based on the DNA methylation patterns, we could discriminate two separate clinical behaviors. First case The DNA methylation class was PTPR Group B. The patient presented with spinal leptomeningeal dissemination, which is rarely reported in PTPR. Tumor control with CSI radiation therapy alone was excellent, with further tumor volume reduction continuing over time posttreatment.
The second case The DNA methylation class was PTPR Group A, but the patient had an aggressive course with recurrent local tumor growth despite radiation therapy and repeated surgical resections without spinal seeding metastasis. Interestingly, this patient responded well to Pineoblastoma-like intensive chemotherapy, indicating that there are instances where chemotherapy is indicated in the treatment of PTPR.
The third patient The DNA methylation class was PTPR Group B. The patient also had local recurrence with microscopic CSF spinal dissemination, and was treated with CSI radiation therapy.
Currently, the clinical behavior of PTPRs can be compared to that of ependymoma, with gross total resection as a mainstay of treatment, followed by surveillance neuroimaging. Adjuvant therapies such as radiation with or without chemotherapy should be considered when complete surgical resection is not feasible.
Based on our case series, we recommend using the DNA methylation patterns to detect PTPR Group B, which has been reported to have a more aggressive course and was present in our patients with spinal metastasis that needs to be controlled with CSI radiation therapy.
Future therapeutic strategies will undoubtedly benefit from further molecular and mechanistic insights into the effects of the chromosomal changes associated with individual PTPR tumors. This might open the door to individualized medicine approaches that allow therapeutic targeting of specific signaling pathways or molecular mechanisms that play critical roles in the development of an individual's PTPR tumor.