Case Report
An 11-year old male presented after injuring his left tibia and had an
abnormality on X-ray which prompted a follow-up MRI. MRI demonstrated a
left tibial bony lesion, suspicious for a malignancy. Patient underwent
core needle biopsy of his left tibia and pathology revealed a low grade
osteosarcoma. Patient underwent surgical excision of his left tibia with
allograft reconstruction. Pathology now confirmed the presence of a
high-grade osteosarcoma. Patient received chemotherapy per Children’s
Oncology Group’s AOST0331 protocol9. He completed the
planned therapy regimen without any major complications.
He was followed up regularly every 3 months for physical exam,
surveillance labs, and imaging studies that did not demonstrate any
acute disease. Several months after completing therapy, his younger
brother was diagnosed with high grade osteosarcoma of left ilium. Our
patient was then evaluated via genetic testing that revealed a TP53
mutation, specifically TP53, c.818G>A (p.Arg273His),
consistent with LFS. His mother, younger brother, and another
half-brother tested positive for the same TP53 mutation. Patient
underwent surveillance as per LFS Education and Early Detection Program
(LEAD)10 . The program included annual brain and whole
body MRI’s, annual blood and urine tests to evaluate adrenal gland
function, tumor markers for common LFS associated tumors, and physical
exams every 6 months10. The inclusion of whole body
MRI and brain MRI is particularly essential as LFS has a high incidence
of asymptomatic tumors11. Following LEAD guidelines,
our patient was evaluated with MRI of brain and whole Body which showed
no evidence of new tumors or other abnormalities.
He underwent a brain MRI as part of his surveillance scans (13 month
interval since previous surveillance scan) that showed a
well-circumscribed mass in the left lateral cerebellum measuring 1.5 X
1.1 X 0.6 cm (Fig. 1). He was clinically asymptomatic, had no
abnormalities on physical exam, and had no evidence of lesions at other
body sites. The patient underwent surgical resection of his cerebellar
lesion. Neuropathological evaluation showed densely cellular highly
mitotic neoplasm with large pleomorphic nuclei and apoptotic cells
without the presence of any cerebellar tissue (Fig. 2). Next Generation
Sequencing identified the following genomic alterations; SMO copy number
loss, DDX3X copy number loss, TP53 mutation p.R273H, TP53 copy number
loss, and MYCYN copy number gain. Testing revealed that the tumor was
positive for YAP-1 and GAB-1. These results are consistent with Sonic
Hedgehog (SHH)-activated large cell anaplastic medulloblastoma arising
in a patient with germline TP53 mutation. Patient’s medulloblastoma was
located in the lateral cerebellum and most SHH tumors are known to be
mainly located in the cerebellar periphery12.
Medulloblastomas identification is enhanced via diffusion MR because
they are hypercellular tumors that result in decreased Apparent
Diffusion Coefficient (ADC) values13. Overall,
SHH-activated and TP53-mutant medulloblastomas are rare and associated
with a dismal prognosis14.
Patient and his mother decided to forego any systemic chemotherapy due
to the poor prognosis of secondary anaplastic medulloblastoma. Repeat
MRI of brain 3 months post craniotomy showed evidence of recurrent
neoplasm along the superior aspect of the left cerebellar hemisphere
that measured 3.2 X 3.4 X 1.3 cm. Patient was placed on hospice as the
family decided to forego any further intervention and he died at home on
July 23, 2018.
Shortly after, his mother died from recurrent high grade pleomorphic
sarcoma of pelvis. Patient’s younger brother, who was diagnosed with
osteosarcoma developed recurrent pulmonary metastatic disease of his
osteosarcoma. He succumbed to his illness while under Hospice care at
home. Patient’s half-brother is undergoing serial evaluations according
to LEAD program and remains cancer-free.