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.