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\begin{document}

\title{Temporal Findings of Erdheim-Chester Disease A Case Report and Review of
the Literature}



\author[1]{Jie Tang}%
\author[1]{* Wang，Tao}%
\author[1]{* Tang，FengZhu}%
\author[1]{ShenHong Qu}%
\affil[1]{People's Hospital of Guangxi Zhuang Autonomous Region}%


\vspace{-1em}



  
  \date{June 13, 2024}


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\selectlanguage{english}
\begin{abstract}
Introduction: Erdheim-Chester Disease (ECD) is a rare non-Langerhans
cell histiocytic disorder, first described in 1930. Its diverse
manifestations range from asymptomatic bone lesions to severe systemic
involvement. Herein, we report a novel case of ECD presenting with
temporal bone pain, a symptom not previously described in the
literature. Methods: We observed and analyzed the symptoms, clinical
history, and imaging manifestations of a patient presenting with
significant temporal bone pain. The diagnosis was confirmed via a
biopsy. We also investigated the presence of the BRAFV600E mutation,
which is known to be present in over half of ECD cases. Results: The
patient presented with significant temporal bone pain on pressure but
exhibited no clinical signs of urinary collapse or neurological
symptoms. Imaging studies showed typical signs of ECD, and a biopsy
confirmed the diagnosis. Genetic testing revealed the presence of the
BRAFV600E mutation. Conclusion: This case extends our understanding of
the clinical manifestations of ECD and highlights the potential for
variable symptomatology. Temporal bone pain may be a novel presentation
of ECD, emphasizing the need for a high index of suspicion and thorough
evaluation in patients presenting with unexplained bone pain. The
confirmation of the BRAFV600E mutation in this patient underlines its
potential as a therapeutic target in ECD. Future research is necessary
to fully elucidate the clinical significance and treatment implications
of this novel presentation.%
\end{abstract}%



\sloppy


Temporal Findings of Erdheim-Chester Disease A Case Report and Review of
the Literature

All authors agreed to submit this article to your journal, and there is
no conflict of interest in this manuscript.

Conflicts of interest: None.

Funding: None.

Abstract

Introduction: Erdheim-Chester Disease (ECD) is a rare non-Langerhans
cell histiocytic disorder, first described in 1930. Its diverse
manifestations range from asymptomatic bone lesions to severe systemic
involvement. Herein, we report a novel case of ECD presenting with
temporal bone pain, a symptom not previously described in the
literature.

Methods: We observed and analyzed the symptoms, clinical history, and
imaging manifestations of a patient presenting with significant temporal
bone pain. The diagnosis was confirmed via a biopsy. We also
investigated the presence of the BRAFV600E mutation, which is known to
be present in over half of ECD cases.

Results: The patient presented with significant temporal bone pain on
pressure but exhibited no clinical signs of urinary collapse or
neurological symptoms. Imaging studies showed typical signs of ECD, and
a biopsy confirmed the diagnosis. Genetic testing revealed the presence
of the BRAFV600E mutation.

Conclusion: This case extends our understanding of the clinical
manifestations of ECD and highlights the potential for variable
symptomatology. Temporal bone pain may be a novel presentation of ECD,
emphasizing the need for a high index of suspicion and thorough
evaluation in patients presenting with unexplained bone pain. The
confirmation of the BRAFV600E mutation in this patient underlines its
potential as a therapeutic target in ECD. Future research is necessary
to fully elucidate the clinical significance and treatment implications
of this novel presentation.

A short informative title:\textbf{Temporal Bone Pain as a Novel
Manifestation in Erdheim-Chester Disease: A Case Report}

Keywords:Erdheim-Chester Disease,Temporal Bone Pain,Histiocytic
Disorders,BRAFV600E Mutation,Rare Diseases,Systemic Involvement,Case
Report

\textbf{key points}

1. Temporal Bone Pain:This case presents a novel manifestation of
Erdheim-Chester Disease (ECD) with significant temporal bone pain, a
symptom not previously reported in the literature.

2. ECD's Diverse Manifestations:ECD is characterized by multi-organ
involvement, often with various clinical manifestations, from
asymptomatic bone lesions to serious systemic conditions.

3. Importance of Comprehensive Assessment:The diagnostic process for ECD
relies on an extensive evaluation that includes understanding patient's
clinical history, observing presenting symptoms, and performing imaging
studies and biopsies.

4. Role of Genetic Testing:The identification of the BRAFV600E mutation
in this ECD patient underlines its common occurrence in ECD and
potential as a therapeutic target, emphasizing the importance of genetic
testing in ECD management.

5. Further Research Needed:This case extends the understanding of ECD's
clinical manifestations, underscoring the need for more research to
fully elucidate the clinical significance and treatment implications of
such novel presentations.

Main text

Introduction

A female patient aged 26 years was admitted into the hospital. The
patient had recurrent left retroauricular pain with no apparent cause
two years ago, with intermittent pinprick-like pain that was tolerable.
More than three months ago, swelling behind the left ear was found, with
a raised skin surface and persistent postauricular pain. The pain was
persistent and needle-like, radiating to the occipital region and neck,
making it difficult to sleep at night. The patient was admitted to our
hospital on September 1, 2021 for further consultation and treatment.
Specialized examination revealed a 3*3 cm swelling with pressure pain
behind the left ear; the surface skin did not show any redness,
swelling, or rupture.Laboratory tests revealed no abnormality in the
five sex hormones, triiodothyronine 0.51 nmol/L, albumin 35.5 g/L, and
no abnormality in the rest of the laboratory tests. The patient's CT
enhancement of the temporal bone suggested that her left mastoid area
was occupied with eosinophilic granuloma. The mastoid MRI enhancement
suggested an abnormal signal in the left mastoid region, possible
eosinophilic granuloma; no inner-ear vestibule or cochlea invasion was
seen (Figure 2). None of the bone ECT scans revealed any evidence of
large bone involvement (Figure 3).

Methods and Results

On September 6, 2021, the patient was treated received microscopic
excision of the left skull base tumor, partial resection of the temporal
bone, and excision and grafting of the tipped myocutaneous flap.
Intraoperatively, the left temporal mass was seen to be protruding and
destroying the bone, with an incomplete mass envelope and a yellowish
flesh-like appearance, adhering to the surrounding tissue but peelable
(Figure 4). The damaged temporal bone was abraded by electric drill to
the dural surface, and the white fish-like swelling tissue was seen to
be adherent to the dural surface and was peeled off. Intraoperative
frozen pathological examination suggested it was a benign tumor. Routine
pathological examination was performed postoperatively.
Immunohistochemistry suggested foamy cells CD68 (+); CD1a (-); Langerin
(-) S-100 (-); CD30 (I); CD34 (I); Desmin (-); Fascin (few cells +);
Ki-67 (positivity rate of about 10\%); SMA (-). Molecular pathology
testing indicated negative for BRAFV600E gene mutation (Figure 1). After
hospital discussion, Erdheim-chester disease (ECD) was diagnosed by
combining imaging, pathology, and genetic testing results.

Discussion and Conclusion

Erdheim-chester disease (ECD) is a rare non-Langerhans cell histiocytic
hyperplasia (LCH) first described by Jakob Erdheim and William Chester
in 1930 as a lipodystrophic granulomatous disease(Calandra et al.,
2017). However, to date, no reports of this disease in the ear-temporal
region have been published. The disease is characterized by histiocytic
infiltration of multiple organ systems, including the skeleton, central
nervous system, cardiovascular system, lungs, and kidneys. When the
skeleton is involved, the clinical presentation may be asymptomatic or
may present with mild bone pain, depending on the distribution and
severity of the lesion, ranging from asymptomatic bone lesions to
life-threatening conditions, with osteosclerosis seen in more than 80\%
of cases; cranial, rib, facial, and vertebral involvement has also been
reported,(Goyal et al., 2020) with temporal bone pain being the main
manifestation in this case. When the respiratory system is involved, it
is mainly foam cells infiltrating the lobular septum or pleura, which is
mostly asymptomatic clinically, and a few may also present with dyspnea
after exertion(Sorenson and Emam, 2021). Almost all patients with ECD
involve the bones, with the femur and tibia showing symmetrical
osteosclerosis of the backbone on imaging(Ozkaya et al., 2018), and
infiltration of the kidneys, retroperitoneum, lungs, and heart can lead
to dysfunction of the involved organ systems.The disease occurs as a
rare lesion in the temporal region of the skull. The patient in this
case had significant temporal bone pain on pressure but did not show
clinical signs of urinary collapse or neurological symptoms.The
diagnosis of ECD relies on a suggestive clinical history and imaging
manifestations, relying on biopsy for confirmation. Haroche(Haroche et
al., 2017) et al. published a complete review of histiocytic enzymes,
discussing their tumorigenic nature; more than half of the patients had
BRAFV600E mutations.

This is a rare case because of the atypical clinical presentation and
the absence of large, long bone involvement. She mentioned a painful
pinprick-like mass behind the left ear, radiating to the occiput and
neck, with ``buzzing'' tinnitus. No evidence of large bone involvement
was found on plain film and bone ECT scan. The diagnosis of ECD can be
difficult due to the diverse presentation and multisystem involvement.
Other conditions of the temporal bone, including osteochondrodysplasia,
osteochondroma, eosinophilic granuloma, carcinoma of the external
auditory canal, and osteoma are often difficult to differentiate based
on the clinical presentation included in the differential
diagnosis(Vallejo Herrera et al., 2022).

Reference

Calandra, C. R., et al. (2017). `Erdheim-Chester disease: atypical
presentation of a rare disease', BMJ Case Rep, 2017. doi:
10.1136/bcr-2017-220827.

Goyal, G., et al. (2020). `Erdheim-Chester disease: consensus
recommendations for evaluation, diagnosis, and treatment in the
molecular era', Blood, 135 (22), pp. 1929-1945. doi:
10.1182/blood.2019003507.

Haroche, J., et al. (2017). `Histiocytoses: emerging neoplasia behind
inflammation', Lancet Oncol, 18 (2), pp. e113-e125. doi:
10.1016/S1470-2045(17)30031-1.

Ozkaya, N., et al. (2018). `The histopathology of Erdheim-Chester
disease: a comprehensive review of a molecularly characterized cohort',
Mod Pathol, 31 (4), pp. 581-597. doi: 10.1038/modpathol.2017.160.

Sorenson, A. D. and Emam, H. A. (2021). `Oral Findings of
Erdheim-Chester Disease: A Case Report and Review of the Literature', J
Oral Maxillofac Surg, 79 (6), pp. 1287-1291. doi:
10.1016/j.joms.2021.01.009.

Vallejo Herrera, M. J., et al. (2022). `Erdheim-Chester disease:
Diagnosis in endocrinology', Endocrinol Diabetes Nutr (Engl Ed), 69 (6),
pp. 444-446. doi: 10.1016/j.endien.2022.06.004.

Fig 1 pathological:Molecular pathology testing indicated negative for
BRAFV600E gene mutation\selectlanguage{english}
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Fig 2 MRI preoperatively; No inner-ear vestibule or cochlea invasion
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Fig3 Whole body bone ECT examination:None of the bone ECT scans
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Fig 4 Tumor resection,with an incomplete mass envelope and a yellowish
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