A unique case of hybrid SEF-LGFMS with EWSR1-CREB3L1 Fusion and
robotic-assisted bronchoscopy in an 11-year-old
To the editor,
Primary lung malignancies in the pediatric population are rare at 0.049
per 100,000 individuals, with a histological distribution unique to the
pediatric population (1, 2). Here we present a novel case of a child who
presented with hemoptysis that safely underwent robotic assisted
flexible bronchoscopy and was diagnosed with a tumor not previously
reported in the literature with the lung as primary site: a hybrid
sclerosing epithelioid fibrosarcoma (SEF)-low grade fibromyxoid sarcoma
(LGFMS), with Ewing sarcoma breakpoint region 1 (EWSR1)/cAMP-responsive
element binding protein 3-like 1 (CREB3L1) fusion mutation.
EWSR1/CREB3L1 are the most frequent fusion mutations in SEF, composing
80-90% of cases, while FUS/CREB3L1 and FUS/CREB3L2 gene fusions are
more common in hybrid or LGFMS (8). EWSR1 is an RNA binding protein that
functions in maintenance of genomic integrity and CREB3L1 is a
transcription factor implicated in cancer cell migration and invasion
(3, 4). EWSR1 belongs to the same family of RNA binding proteins as
Fused in Sarcoma (FUS) gene, and mutations in both drive soft tissue
tumors, though mutation frequency varies by sarcoma type (3). SEF is
associated with a more aggressive clinical course than LGFMS, though
differences in clinical presentation between patients with EWSR1-CREB3L1
fusions and FUS-CREB3L1 fusions remain an active area of research. SEF,
LGFMS, and hybrid tumors are all rare in the pediatric population (5).
An 11-year-old female with no significant medical history presented to
the emergency department with cough, shortness of breath and 3 episodes
of bright red hemoptysis for 1 day. A chest x-ray showed a round,
well-demarcated 4.1 cm mass in the right lower lung (Figure 1). A
computed tomography (CT) chest revealed a 4.9 x 3.0 cm mass in the right
lower lobe with coarse calcification (Figure 2), suggestive of a
pulmonary hamartoma.
The patient underwent flexible bronchoscopy with transbronchial needle
aspiration guided by radial ultrasound. Rapid on-site evaluation (ROSE)
did not show adequate specimens. The case was converted to
robotic-guided bronchoscopy; transbronchial needle aspiration and
transbronchial biopsies of the right lower lobe (RLL) mass were
successfully obtained. Surgical pathology showed fragments of
fibromyxoid stroma possibly consistent with hamartoma but not
conclusive. Patient then underwent a RLL lobectomy and pathology
revealed a hybrid SEF-LGFMS, with genetic sequencing [Sema4 whole
exome sequencing (WES)/ whole transcriptome sequencing (WTS)]
demonstrating an EWSR1-CREB3L1 fusion gene. Background lung demonstrated
emphysema and hemorrhage; bronchial and vascular markers were negative
for tumor.
The patient underwent staging scans, negative for metastasis. Pulmonary
function testing demonstrated low diffusing capacity for carbon monoxide
(DLCO), yet normal DLCO/alveolar volume (VA) and total lung capacity.
After surgical resection, the patient has been in complete remission for
12 months.