We describe a 14 month old female with episodic agitation upon awakening followed by a very intense episode of agitation with associated respiratory compromise. She was transported to a local hospital where CT imaging demonstrated a large hemorrhagic lesion in the right frontal lobe extending into the right lateral ventricle (see Fig. a). A gross total resection of this hemorrhagic lesion was completed as demonstrated by CT imaging (see Fig. b). Microscopic evaluation showed an atypical neurocytic tumor (see Fig. a–d). The histology was that of a mildly pleomorphic round cell tumor with diffuse, strong immunolabeling for synaptophysin. The tumor cells were negative for glial fibrillary acidic protein (GFAP). Atypical features were noted including the presence of mitoses, glomeruloid vascular proliferation, and necrosis. The Ki-67 labeling index was 10% overall though focally was higher. A decision to avoid consolidative radiation therapy was made secondary to her young age.
Fig. 1 a Preoperative post contrast coronal CT images demonstrating a hemorrhagic lesion in the right frontal lobe extending into the right lateral ventricle. b Postoperative post contrast coronal CT images demonstrating a gross total resection of the right (more ...)
Fig. 2 a Microscopic evaluation showed an atypical neurocytic tumor composed of cells with round to oval nuclei. (H&E 400×). b Diffuse, strong immunolabeling for synaptophysin was demonstrated. (400×). c Atypical features were noted including (more ...)
Two months after her resection she developed a recurrence with obstructive hydrocephalus and midline shift requiring placement of a ventriculo-peritoneal shunt. Imaging demonstrated diffuse meningeal enhancement as well as interval development of an area of local enhancement concerning for recurrence (see Fig. ). Her CSF was negative for evidence of malignant cells. She subsequently received 3 cylces of chemotherapy including vincristine (0.05 mg/kg/dose, Days 1 & 8), cisplatin (3.5 mg/kg/dose, Day 2), and etoposide (2.5 mg/kg/dose, Days 1–3). This was followed by GCSF beginning on day 3. Imaging demonstrated a partial response with decreased leptomeningeal and local enhancement in the resection cavity. She was then given 2 cycles of temodar for (Days 1–5).
Post contrast coronal and axial T1-weighted images show nodular enhancement (black arrow) along the margin of the right posterior frontal resection cavity, suggesting recurrent tumor
At 24 months she was noted to have development of a cystic lesion in the resection cavity and increased leptomeningeal enhancement. As a result, she then received 2 cycles of cytoxan (55 mg/kg/dose, Days 1–2) and MESNA; however, the second cycle was complicated by hyponatremia and seizures. She was then placed back on the chemotherapy regimen consisting of vincristine, cisplatin, and etoposide. Repeat imaging demonstrated stable disease.
At 28 months of age prior to the completion of additional chemotherapy she underwent GCSF mobilized peripheral blood stem cell collection. A total of 12 × 106 CD34+ cells/kg were collected in anticipation of high dose chemotherapy and autologous stem cell rescue. Additional chemotherapy was provided with 3 cycles of ifosfamide (1800 mg/m2/dose Days 1–5), carboplatin (400 mg/m2/dose Days 1–2), and etoposide (100 mg/m2/dose Days 1–5). Repeat imaging was completed demonstrating stable disease.
Due to a lack of significant clinical response and nephrotoxicity (hypomagnesaemia, hypokalemia, and academia) she was then treated with cytoxan and topotecan per Pediatric Oncology Group Protocol 9464. She received one cycle of therapy followed by imaging demonstrating interval progression of her leptomeningeal disease.
At 34 months of age, high dose chemotherapy per the consolidation phase of Children’s Cancer Group Protocol 99703 was started. This chemotherapy regimen consisted of carboplatin (17 mg/kg, Days 0–1) and thiotepa (10 mg/kg, Days 0–1). This was followed by a day of rest, stem cell infusion, and then GCSF. This phase was repeated every 4 weeks for 3 cycles with the infusion of 2.4 × 106 CD34+ cells/kg, 3.68 × 106 CD34+ cells/kg, and 3.86 × 106 CD34+ cells/kg, respectively. Toxicity included fever and neutropenia.
At 40 months of age she was disease free by imaging criteria and was started on isotretinoin (8 mg/kg/day, 14 days/month) and oral etoposide (3 mg/kg/day, 21 days/month) for 8 months until the development of neutropenia. Unfortunately, 6 months later abnormal enhancement in the cervical, thoracic, or lumbar spine was noted on MRI, suggesting recurrent disease (see Fig. ). Surgical biopsy confirmed the diagnosis. Following her most recent relapse, a decision was made to begin therapy with temodar (5 days per week every 2 weeks) and irinotecan (every 2 weeks). She is tolerating this therapy without complications and is currently waiting for re-imaging.
Post contrast sagittal T1 and axial T1-weighted images show enhancement of the surface of the cord (white arrow), suggesting recurrent disease