Introduction
Ewing sarcoma (EWS) is a high-grade sarcoma described as a small round
cell tumor of bone and soft tissue.1,2 EWS is an
aggressive malignancy that accounts for approximately 2% of cases of
childhood cancer, most commonly occurring in adolescent and young adult
patients. The metastatic pattern is typically hematogenous, with lung,
bone, and bone marrow being the most common sites of metastasis. Ewing
sarcoma family of tumors (ESFT) have been rarely reported as a secondary
malignant neoplasm after treatment of childhood cancer. Friedman et al
studied subsequent neoplasms via the Childhood Cancer Survivor Study
(CCSS) data and found that secondary neoplasms occur more frequently
among females, patients older at time of cancer diagnosis, and those
treated with radiation therapy.3 With increasing
awareness of adverse long-term sequalae in survivors of childhood
cancer, the most feared complications include subsequent malignant
neoplasms.4 We describe two pediatric cases of
secondary EWS of the 9th rib that presented following
surveillance visits for diagnoses of primary precursor B-acute
lymphoblastic leukemia (pre B-ALL) and acute myeloid leukemia (AML)
within northeast Pennsylvania. Further investigation regarding these
cases of secondary EWS is warranted to identify potential risk factors
and emphasize the importance of surveillance cancer screening.
Case Descriptions
Patient 1 was a previously healthy 9-year-old female who presented to
her pediatrician with a fever and right-sided neck mass. Laboratory
evaluation revealed pancytopenia with a platelet count of 13,000/uL,
white blood count of 4,000/uL, and hemoglobin of 6.0 g/dL. Computed
tomography (CT) of the neck, chest, and abdomen revealed cervical
lymphadenopathy, right greater than left, and hepatosplenomegaly.
Subsequent bone marrow aspiration revealed lymphoblast morphology (92%
blasts) and flow cytometry consistent with pre B-ALL. Cytogenics were
notable for hyperdiploid karyotype with 56 chromosomes and trisomy 4,
10, and 17 positive. Central nervous system classification was negative.
The patient underwent treatment for standard risk pre B-ALL per the
Children’s Oncology Group (COG) protocol AALL0932 and achieved complete
remission. She received a cumulative of 75 mg/m2 of
anthracyclines. Almost 46 months after completing chemotherapy, the
patient presented with complaints of right-sided chest pain and dyspnea.
Chest x-ray was unrevealing for acute pathology. Three weeks later, she
developed increasing pain and swelling of her chest. CT chest revealed a
large lesion involving the right chest wall. The lesion was biopsied,
and pathology demonstrated a small round blue cell tumor consistent with
EWS. Flow cytometry was notable for EWSRI (22q12) gene rearrangement.
Positron emission tomography (PET) scan revealed localized EWS of the
right 9th rib with regional lymphadenopathy (Fig. 1).
The patient was treated via the COG protocol AEWS0031 (regimen
B2) with proton radiation (5580 cGy) to achieve
remission; lifetime anthracycline total was 450 mg/m2.
Fourteen months later, she endorsed right-sided chest and wrist pain.
Surveillance PET/CT revealed findings of a new metabolically active
tumor within a 7.3x8.2x7cm soft tissue mass in the central and posterior
aspects of the right lung. Her previous lesions remained stable and
there were no other areas of radiotracer uptake. Biopsy confirmed
relapsed EWS positive for EWSR1 rearrangement. Bone marrow evaluation at
time of relapse was negative. She underwent 7 cycles of individualized
salvage therapy with temozolomide and irinotecan with progression of her
right lung mass. She was subsequently enrolled in the pediatric MATCH
(Molecular Analysis for Therapy Choice) trial (COG APEC1621) with no
match identified. She had significant progression and underwent
palliative radiation with 60% decrease in tumor size. She is currently
undergoing further chemotherapy at time of writing this document.
Patient 2 was a previously healthy 14-year-old male who presented with 3
weeks of right lower rib pain associated with night sweats, fatigue, and
flu-like symptoms. Laboratory evaluation revealed leukocytosis
(29,220/uL), severe thrombocytopenia (34,000/uL), and anemia (11.1g/dL).
CT scan of the abdomen and pelvis revealed splenomegaly and no bony
lesions. Peripheral blood flow cytometry showed 58% blasts with myeloid
phenotype concerning for acute myeloid leukemia (AML). Subsequent bone
marrow aspiration exhibited myeloblast morphology (75% blasts) and flow
cytometry consistent with AML, non-M3 subtype. Cytogenetics revealed
karyotype 45,X,-Y (loss of Y chromosome) and t(8;21)(q22;q22), positive
for the RUNX1T1/RUNX1 fusion protein. Central nervous system
classification was negative. The patient underwent standard chemotherapy
per the COG AAML1031 protocol and achieved complete remission. He
received a cumulative of 492 mg/m2 of anthracyclines.
Five months after completing treatment, he developed back pain. X-ray of
the thoracic spine was unremarkable, however the pain intermittently
persisted. Three months later, he presented to the emergency room for
worsening back pain radiating to the right upper quadrant. CT scan
showed an expansile permeative lesion with periosteal reaction involving
the right posterior 9th rib. Biopsy revealed a small
round blue cell tumor and flow cytometry suspicious for a
non-hematolymphoid tumor consistent with EWS. PET/CT showed localized
disease (Fig. 2). Bilateral bone marrow aspirates were negative for
disease. The patient was started on treatment per the COG AEWS0031
protocol. He underwent wide surgical excision of a 4.7x3.0x2.0cm tumor
with negative margins, but viable tumor on the pleural margin. He was
subsequently treated with radiotherapy and consolidation chemotherapy.
He completed treatment without evidence of disease on follow-up imaging.