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Tumor Discovery CRMO presenting as multifocal bone LCH

regulation, with increases in pro-inflammatory cytokines suspicion of LCH from January 2020 to November 2022.
such as interleukin (IL)-1β, IL-6, tumor necrosis factor- Out of the total 25 children identified, the data of those
alpha (TNF-α), and chemokines. There are also decreased with a final diagnosis of CRMO were analyzed. Clinical
levels of the immune regulatory cytokine IL-10 and its features, radiological evaluations, and pathological
homolog IL-19, due to impaired activation of mitogen- characteristics were retrieved from the files. Our institute,
activated protein kinases. Recently, the upregulation of being a standalone cancer center with limited expertise in
the NOD-, LRR-, and pyrin domain-containing protein treating rheumatological disorders, referred all children
3 (NLRP3) inflammasome, a cytoplasmic multi-protein diagnosed with CRMO to a dedicated rheumatological
complex that assembles in response to “danger signals,” center for management and follow-up. Telephonic
has also been implicated in the pathogenesis of this consultations were conducted to obtain the current status
condition. Thus, an imbalance in cytokines is central to the of the children for analysis.
development of CRMO. 2 The analysis revealed that three children from the
In the past, several single gene defects (LPIN2, PSTPIP2, cohort suspected of having LCH had a final diagnosis of
and IL1RN) were implicated in genetic susceptibility to CRMO.
CRMO. However, as CRMO is a complex genetic disorder, 2.1. Case 1
many genes have been discovered in recent years that cause
abnormal regulation of the IL-1β axis, with a potential An 11-year-old girl presented with complaints of pain and
implication of the NLRP3 inflammasome. A variant in swelling over the right forearm, persisting for 8 months.
the filamin-binding domain of the FBLIM1 gene has been Clinical examination revealed no lymphadenopathy or
discovered in familial CRMO. It is postulated that IL10 hepatosplenomegaly. There was minimal swelling and
3
promotor haplotypes, in association with the FBLIM1 tenderness over the lower end of the right ulna. A plain
gene, might contribute to the pathogenesis. 4 X-ray demonstrated a lytic lesion in the distal end of the
right ulna. Whole-body magnetic resonance imaging
The clinical presentation varies from mild, self-limiting (MRI) scan revealed lesions in the right ulnar, metacarpal,
unifocal bone inflammation, which is more common, to mandibular, and acetabular regions with marrow
multifocal recurrent disease. The clinical features are not infiltration. The inflammatory marker (erythrocyte
specific to CRMO, and the most common presenting feature sedimentation rate) was 36 mm/hr. Whole-body positron
is insidious onset chronic bone pain, which significantly emission tomography-computed tomography (PET-CT)
affects the quality of life of school-aged children. Physical scan showed low-grade fluorodeoxyglucose (FDG) uptake
examination is usually inconclusive, with only a minority (SUVmax: 2.3) in a lytic lesion with cortical break and
of children showing features of inflammation, such as minimal intramedullary and extracortical soft tissue in the
tenderness or warmth over the affected sites. The majority distal aspect of the right ulna (Figure 1). Low-grade FDG
of children are misdiagnosed as having “growing pains” uptake (SUVmax: 2.4) was also noticed in the shaft of the
until the symptoms become debilitating. The clavicle, right third metacarpal. Biopsy from the right ulna and
vertebrae, mandible, long bones, and pelvic bony structures right third metacarpal showed chronic inflammatory
are the classical sites affected by CRMO. cells, predominantly small lymphocytes with a small
CRMO is a diagnosis of exclusion, with the main cluster of histiocytes. Immunohistochemistry (IHC) was
differential diagnosis including benign and malignant bone negative for CD1a, resulting in a final diagnosis of chronic
disease, Langerhans cell histiocytosis (LCH), infectious inflammatory osteomyelitis. She has been on follow-up
causes, lymphoma, and metabolic bone disease. 5 with a rheumatologist for the past 22 months. Treatment
with non-steroidal anti-inflammatory drugs (NSAIDs) was
We conducted a retrospective analysis to describe a initiated, and she remained asymptomatic at follow-up.
case series of children who were referred to our center
with a diagnosis of LCH but were ultimately diagnosed 2.2. Case 2
with CRMO. A 10-year-old boy presented with difficulty in neck

2. Case presentations movements, persisting for 2 months. Clinical examination
revealed stiffness of the cervical spine with restriction of
A retrospective data collection was conducted from the movement. There were no lymph node enlargements or
electronic medical records of children under 18 years of other relevant clinical examination findings. A radiograph
age who had been referred to the Department of Paediatric of the cervical spine showed loss of cervical curvature
Hematology, Oncology, and Bone Marrow Transplantation with no definite lesions identified. Whole-body MRI
at the MVR Cancer Centre and Research Institute with revealed lesions in the base of the skull, multiple cervical

Volume 3 Issue 3 (2024) 2 doi: 10.36922/td.3102