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CASE REPORT
Year : 2022 | Volume
: 28
| Issue : 3 | Page : 242-245
Atypical presentation of langerhans cell histiocytosis of temporal bone in a toddler
Eng Siang Lee1, Jeyasakthy Saniasiaya1, Jeyanthi Kulasegarah1, Wai Leong Kok2, Seow Fun Chew3
1 Department of Otorhinolaryngology, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
2 Department of Otorhinolaryngology, Hospital Putrajaya, Jalan P9, Presint 7, 62250 Putrajaya, Malaysia
3 Department of Pathology, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
Correspondence Address:
Dr. Jeyasakthy Saniasiaya
Department of Otorhinolaryngology, Faculty of Medicine, Universiti Malaya, Jalan Universiti, 50603 Kuala Lumpur, 50603 Wilayah Persekutuan Kuala Lumpur
Malaysia
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/indianjotol.indianjotol_44_22
Ever since Langerhans cell histiocytosis (LCH) was first described in 1865, mystery revolving around its cause and pathogenesis remains, although most agree that LCH is either a reactive or neoplastic process. We aim to highlight the importance of careful investigations of common presentation, which may lead to the diagnosis and treatment in a toddler. We report a case of LCH of the temporal bone with an atypical presentation in a toddler, which led to delayed diagnosis. The patient presented with a vague preauricular swelling and aural polyp. Imaging and histopathological examination of the biopsy revealed temporal bone LCH, and the child was referred to the pediatric oncology unit and successfully treated. This case clearly demonstrates the highly diversified clinical manifestation of LCH and the high level of suspicion required to diagnose it. We describe the challenge faced in managing this rare entity.
Keywords: Children, children tumor, Langerhans cell histiocytosis, temporal bone
Langerhans cell histiocytosis (LCH) is an idiopathic condition characterized by the presence of proliferation and dissemination of pathological histiocytic cells.[1] Conventionally, approximately 60% of patients with LCH present with head-and-neck manifestations, while approximately 20% of patients will eventually develop lesions within the head-and-neck region during the course of the disease.[2] LCH predominately afflicts children albeit adults' cases with LCH have been reported,[3],[4] with an average age at onset between 1 and 3 years of age, and a higher prevalence in males has been reported.[5] The clinical manifestation and course of LCH vary considerably, from solitary, self-healing lesions to fatal multiorgan disease, oftentimes resulting in the delayed diagnosis of LCH.
Case ReportA previously healthy 1-year 3-month-old-boy presented with a 2-month history of slow-growing left preauricular swelling. According to the mother, she initially noticed a vague left preauricular swelling which subsequently increased in size. The swelling was not tender, and the child fed as usual. In addition, 2 weeks before the outpatient clinic, the mother noticed scanty left-sided otorrhea which she described as not foul-smelling with no otorrhagia. The child remained active, tolerating feeding well with no facial asymmetry or fever. There was no history of sick contact or similar complaints among other family members. The child completed multiple courses of antibiotics as treatment for otitis externa given by the general practitioner over the past 2 months which was in vain. In addition, the child had a left ear tissue biopsy in another which revealed granulation tissue.
Upon review, the child was active and not in respiratory distress. A left preauricular mass measuring 3 cm × 3 cm, nontender but firm, with no inflammation of the skin was noted. No obvious facial asymmetry was present. Otoscopic examination revealed an aural polyp occupying the entire left ear canal, whereas right ear examination was unremarkable. Nasal and intraoral examination was normal. Flexible nasopharyngolaryngoscopy performed was normal.
Blood investigation taken showed no evidence of infection and a normal lactate dehydrogenase level. A peripheral blood film study confirmed microcytic hypochromic anemia. Diagnostic auditory brainstem response test showed normal hearing at least at high frequencies bilaterally.
Computed tomography (CT) scan showed enhancing soft-tissue density with epicenter at the left preauricular and temporomastoid region, infiltrating the left ear canal with bony erosion involving the zygomatic process, mastoid, and squamous portion of the left temporal bone.
Magnetic resonance imaging (MRI) showed minimal intracranial extension of the lesion with no clear plane with dura [Figure 1]. A CT of the neck, thorax, abdomen, and pelvis showed bilateral cervical and axillary lymph nodes, pelvic nodes, and lung nodules.
Figure 1: Coronal MRI showing soft tissue lesion occupying left temporal lobeExamination under general anesthesia revealed left ear granulation tissue arising from the posterosuperior part of the external auditory canal (EAC), filling the entire EAC. Multiple deep biopsies were taken. Histopathological report showed dense subepithelial infiltrates of LCHs in clusters, associated with prominent eosinophil and neutrophil infiltrates. The Langerhans cells have kidney-shaped nuclei, occasional nuclear groove, fine granular chromatin, and abundant eosinophilic cytoplasm. No overt mitosis or anaplasia is detected. The Langerhans cells are strongly positive for CD1a [Figure 2] and CD68.
A multidisciplinary team meeting involving pediatric oncologist, radiologist, pathologist, and otorhinolaryngologist was conducted to discuss the treatment plan for the child. The child was subjected to chemotherapy and had since completed six cycles of LCH IV protocol Stratum 1 Group 1 initial course 1 (prednisone, vinblastine, and mercaptopurine), with good clinical response. He is on regular follow-up whereby the initial left preauricular swelling is no longer palpable, and otoscopic examination shows a normal ear canal with intact tympanic membrane. At 4 months postchemotherapy treatment follow-up, the child was thriving, and repeated CT scan showed a smaller left preauricular lesion with unchanged bony erosion. The scan also showed that the cervical lymphadenopathy has reduced in size and resolution of both the pelvic nodes and lung nodules. He has since been scheduled to continue the chemotherapy protocol with LCH IV protocol Stratum 1 Group 1 initial course 2.
DiscussionLCH is an entity characterized by the presence of proliferation and dissemination of pathological histiocytic cells.[4] Recent studies revealed the characterization of LCH as a neoplastic disorder. This was ensuing the studies which reported that approximately 60% of cases express somatic mutation which produces the oncogenic BRAF V600E variant.[1] In the same vein, LCH samples reveal evidence of activation of the MAP kinase pathway.[1],[2] LCH predominantly affects children, although it can be diagnosed in any age group,[5],[6] with an average age at onset ranging between 1 and 3 years of age. In addition, a higher prevalence in males has been reported.[7]
LCH does not have any pathognomonic or specific presentation as it expresses various clinical manifestations depending on the sites of involvement. In clinical settings, LCH can present as either a single system (or organ) disease or a multisystem disease involving two or more organs. The external and middle ear is commonly involved in LCH, but it is often misdiagnosed as the clinical presentation often mimics more common conditions, such as mastoiditis, otitis media, recurrent otitis externa or otitis media, and cholesteatoma. The most frequent ear symptoms are aural discharge, postauricular swelling, hearing impairment, otalgia, and sometimes vertigo or facial nerve paralysis. Temporal bone lesions and ear involvement usually are associated with a multifocal disease reported in up to 93% of cases.[8] Series on pediatric LCH showed that bony skull lesion was the most frequent presenting symptom, followed by neck swellings, skin lesions, and a discharging ear.[9],[10] In our patient, the child presented with preauricular swelling and ear polyps, which is not a common presentation of LCH. Parallel to that, as reported in cases with temporal bone involvement, our child had multifocal disease involving the cervical nodes, pelvic nodes, and lung nodules.
Imaging is of paramount importance as it aids in the diagnosis and management of LCH as well as to monitor treatment outcome. CT scan is able to demonstrate bony destruction, the presence of soft-tissue masses, and the presence of lung nodules. CT scan typically demonstrates “punched-out” radiolucent defects, differentiating LCH from other osteolytic lesions of the temporal bone such as cholesteatoma, solitary bone cyst, surgical defects, or chronic infections.[10] A study on imaging presentation of LCH showed that erosion of otic capsule occurs in about 18.4% while the ossicular chain usually remains intact.[11] MRI on the other hand can better delineate the soft-tissue lesion, its extension as well as its relationship to the adjacent structure, especially for parenchymal brain and pituitary lesions. The LCH mass traditionally appears iso- to hypointense on T1-weighted images with marked enhancement ensuing contrast, and hyperintense on T2-weighted with no evidence of peripheral edema.[12] Full-body CT scans that include the liver, spleen, and thorax are useful to rule out multisystem involvement of the disease.[13] In our case, both CT and MRI performed revealed typical radiological findings of LCH.
As for blood investigations, no specific blood tests for LCH exist, however, routine blood investigations such as full blood count and kidney function and liver function tests serve as indicators of disease extension as well as a baseline before commencing treatment.
The definitive diagnosis of LCH is based upon pathological and immunohistochemical findings, which requires tissue samples. Microscopically, LCH lesion is composed of mixed infiltrate of macrophages, lymphocytes, eosinophils, and Langerhans cells, with the hallmark feature being the presence of Langerhans cells. Nonetheless, multiple markers can be used to confirm the diagnosis including CD1a, CD68, CD207, and S100 protein. The presence of Birbeck granules on electron microscopic examination is also diagnostic.[5]
Any case with suspicion of LCH will require a tissue biopsy. However, biopsies must be taken carefully to avoid superficial specimens which may not be representative and may lead to false-negative result such as granulation tissue. This is experienced in our case as well, where the first biopsy specimen only yielded inflamed granulation tissue. Similar to full-body scans, bone marrow aspiration, liver and lung biopsies, and immunologic studies are reserved for specific patients to dismiss a multisystemic involvement.[13],[14]
Treatment modality of LCH reported ranges from close observation, steroid therapy, chemotherapy, surgery, local steroid injections, and even radiations, either single-modality or combined modality approach.[7] Surgical removal is advocated, especially when the lesion is single and localized. Chemotherapy is the treatment of choice in a multifocal disease or when the lesion is deemed inaccessible surgically, whereas radiotherapy is no longer recommended following the morbidity which ensues.[9] The current chemotherapy regimen follows the ongoing LCH-IV and previous prospective trial LCH-III as a standard regimen for multisystemic LCH in patients with and without risk of organ involvement. The LCH-IV study aims to tailor treatment based on features at presentation and on response to treatment, leading to seven strata, due to the complexity of the disease presentations and outcomes.[15] The detection of BRAF and MAP2K1 mutations has led to targeted therapies acting upon the RAS/RAF/MEK/ERK pathway, such as BRAF inhibitor, vemurafenib.[16] However, these studies are small series or anecdotal case report which lacks sufficient data on the safety, optimal duration, and cost-effectiveness of these therapies. The patient described in our case received a course of chemotherapy in view of multisystem involvement and has shown good clinical and radiological response. The course of treatment in our case is in accordance with the latest LCH-III regimen.
Prognosis appears to be affected by age, location, and extent of disease. LCH outcome appears to worsen according to age. Earlier age on onset is a negative prognostic factor. The presence of cervical lymph nodes and scalp involvement points toward a higher rate of recurrence.[9] LCH which affects only the temporal bone showed a good long-term prognosis and the lesions characteristically reossify and remodel. In single-system form of LCH, prognosis is usually satisfactory, while multisystemic form shows more frequent recurrences. Studies have shown multisystemic LCH carries up to 7 times higher risk of disease reactivation.[13],[17],[18] The child in our study has multisystemic involvement including cervical, axillary, and pelvic nodes with lung nodules. He will require long-term follow-up to detect any recurrences. All patients should be followed up at least 5 years after the end of therapy; or 5 years after the last recurrence, in those who did not receive systemic therapy; or until final growth and pubertal development.[19]
ConclusionClinical manifestation and course of LCH vary considerably, from solitary, self-healing lesions to fatal multiorgan disease, often leading to delayed diagnosis of LCH. Atypical clinical presentations in our case were preauricular swelling and ear canal mass. Furthermore, this case was initially misdiagnosed as an inflammatory process due to the short history at presentation and negative biopsy, which resulted in an unnecessary delay in initiation of chemotherapy. The purpose of this report is to alert clinicians about the varied clinical presentations of LCH, which will lead to early diagnosis of the disease and treatment.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
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