Case Report:
A two-month-old African American male presented with leukocoria and was diagnosed with group B (IIRC) bilateral retinoblastoma harboring a germline intronic RB1 mutation (Table 1A). He received 6 cycles of systemic chemotherapy on the Children’s Oncology Group (COG) ARET0331 protocol with carboplatin, vincristine, and focal laser therapy. Due to disease progression, his right eye was enucleated at the age of 12 months. The histopathology of the enucleated eye did not show high-risk features (e.g. choroid, anterior chamber, optic nerve or scleral involvement). He did not receive additional therapy post enucleation.
He remained in remission until 9 years of age when he presented with vague wrist pain. His physical exam demonstrated minimal soft tissue swelling of the wrist. His complete blood count (CBC) was normal and a lactate dehydrogenase (LDH) level was 271 U/L. He was evaluated by rheumatology, diagnosed with idiopathic arthritis and started on naproxen therapy with pain relief.
Three months later, he developed worsening leg pain waking him from sleep. His physical exam showed a 2 cm left axillary lymph. His hemoglobin was 10.9 gm/dL, platelets 136,000/mm3, LDH > 6000 U/L (undiluted) and uric acid 7.4 mg/dL (Figure 1A). Bone marrow evaluation demonstrated diffuse tumor infiltration by metastatic retinoblastoma confirmed by immunophenotyping and synatophysin staining. Cytogenetics demonstrated a complex abnormal karyotype including gains of chromosome 1q, 2p, 6p, and 13q32-34.
A PET/CT scan demonstrated diffuse bony FDG uptake as well as uptake in the liver, left axillary and infraclavicular regions (Figure 1D). A brain/orbits MRI did not show evidence of CNS disease. He was reclassified as stage 4A disease.
He began treatment per the COG ARET0321 protocol for metastatic retinoblastoma (Figure 1B) with the intention to ultimately proceed to stem cell transplant. His first treatment cycle was complicated by tumor lysis syndrome leading to acute renal failure requiring hemodialysis.
Tumor surveillance after the first cycle, demonstrated no evidence of bone marrow disease and a PET/CT showed no abnormal FDG uptake except for mild uptake in the left axillary node. His LDH which had peaked at 22,331 U/L, normalized to 275 U/L (Figure 1A). Following the third cycle of chemotherapy, he continued to have no evidence of residual tumor. Stem cell transplantation was postponed due to the development of cisplatin-induced thrombotic microangiopathy (TMA).
Eight months following his initial relapse, he developed left eye deviation. A MRI (Figure 1F) demonstrated a right cerebellar mass (confirmed to be retinoblastoma following a gross total resection) with spinal metastasis. Metastatic disease restaging did not demonstrate evidence of tumor outside of the CNS.
He received craniospinal proton radiation therapy (40 Gy) with daily carboplatin and weekly vincristine (Figure 1B) Due to worsening TMA, further systemic chemotherapy was stopped. He then received intra-Ommaya topotecan, intrathecal topotecan and metronomic chemotherapy with vinblastine and oral cyclophosphamide. After four weeks, he expired due to progressive disease. At autopsy, CNS involvement by retinoblastoma was confirmed without evidence of systemic or bone marrow disease.