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Year : 2017  |  Volume : 6  |  Issue : 2  |  Page : 119-122

Langerhans cell histiocytosis mimicking a complicated mastoiditis: A review and case report

1 Department of ENT, Ain Al-Khaleej Hospital, Al-Ain, UAE
2 Department of Surgery, Taif University, Saudi Arabia

Date of Web Publication15-Sep-2017

Correspondence Address:
Mohiyuddin A. Q. Ali
Department of ENT, Ain Al-Khaleej Hospital, P. O. Box. 88206, Al-Ain
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/sjhs.sjhs_6_17

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Langerhans cell histiocytosis (LCH) is a rare entity of an unknown etiology, usually reported in children. It commonly involves cranial bones mimicking an otological disease. We report a case of a 22-month-old Saudi boy who was referred to our Otolaryngology Department, in the North West Armed Forces Hospital, Tabuk, Saudi Arabia, as a case of complicated mastoiditis with a fistula that was resistant to conventional treatment. The patient underwent surgical exploration, and a biopsy confirmed the diagnosis of LCH X. The case was treated accordingly. LCH of temporal bone can be misdiagnosed and mismanaged. This, however, can be minimized by a high index of suspicion, appropriate radiological and histopathological examination.

Keywords: Ear-nose-throat manifestation, histiocytosis X, Langerhans cell histiocytosis, mastoid fistula

How to cite this article:
Ali MA, Al-Kindy SA. Langerhans cell histiocytosis mimicking a complicated mastoiditis: A review and case report. Saudi J Health Sci 2017;6:119-22

How to cite this URL:
Ali MA, Al-Kindy SA. Langerhans cell histiocytosis mimicking a complicated mastoiditis: A review and case report. Saudi J Health Sci [serial online] 2017 [cited 2021 Jan 28];6:119-22. Available from: https://www.saudijhealthsci.org/text.asp?2017/6/2/119/214853

  Introduction Top

Langerhans cell histiocytosis (LCH), formerly known as histiocytosis X, is a rare group of idiopathic disease that has always caused diagnostic dilemma.[1] The disease has a spectrum of a milder form on one end, eosinophilic granuloma and an aggressive form on the other, Letterer–Siwe disease with an intermediate form in between, Hand–Schuller–Christian disease, so the patients could present with all kinds of clinical presentation.[2] Even the etiology is debatable: some argue that it is an inflammatory disorder while others advocate neoplastic origin while yet others describe immune disorder as the basis of the disease.[2],[3],[4] Histopathology is characterized by the presence of multinucleated giant cells (MNGCs) with a lot of osteoclastic activity.[5] Otolaryngologists and family physicians usually see these patients presenting to them with ear-related problems often as indolent as mimicking otitis media and sometimes as severe as mastoiditis, ear polyps, and granulations.[2],[6],[7] Hence, the diagnosis always got delayed as they do not improve or presented with recurrent symptoms.

The purpose of this case report is to demonstrate how this disease mimics common acute and chronic ear, nose, and throat (ENT) diseases so that we can suspect this disease if such diseases are refractory to usual treatment. This will avoid unnecessary delay in diagnosis, and appropriate measures for referral and treatment could be taken timely to improve the quality of life of these patients.

  Case Report Top

A 22-month-old Saudi boy presented to emergency department of our hospital with a chronic discharging ulcer of the left mastoid [Figure 1]. He was diagnosed elsewhere as a case of mastoiditis where he was treated with incision/drainage and systemic antibiotics. Seven months before his presentation, there was a history of left mastoid swelling and adjoining area of temporal bone; it was not associated with otorrhea. Clinically, the child was afebrile, there was a 15 mm × 15 mm ulcer in the left postauricular area with granulation tissue, and tympanic membrane was slightly dull. A provisional diagnosis of complicated mastoiditis was made. The patient was admitted for further investigations.
Figure 1: The lesion as it appeared before our intervention

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Computed tomography (CT) examination showed a lytic lesion of the temporal bone [Figure 2]. Exploration of the mastoid was done where the cavity was full of friable and gelatinous tissue; it was highly suspicious of Langerhans histiocytosis, which was later confirmed by H and E histopathology and immunohistochemistry studies (CD1a and S100).
Figure 2: A coronal cut through the skull computed tomography scan showing the typical lytic lesions of the vault bones

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The patient was later referred to pediatric oncology where he was classified as multistage LCH Hand–Schuller–Christian variant as he was also found to have pulmonary infiltrates with effusions and cervical lymphadenopathy, following screening by CT scan. However, bone marrow aspiration biopsy was free from disease. Over the next 50 weeks, he underwent 17 cycles of chemotherapy consisting of vinblastine 3 mg, with prednisolone (6.6 mg–7 mg TID for 5 days) and 6-mercaptopurine (25 mg PO OD 21 days). The child is currently in clinical remission [Figure 3].
Figure 3: Posttreatment during follow-up showing healed lesion

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  Discussion Top

LCH, a rare group of idiopathic disorder (incidence of 0.5–5.0/million/year in USA), is a systemic disease that may manifest and present as a primary otorhinolaryngology disease, causing a diagnostic and management dilemma. It was formerly known as “histiocytosis X” because the cellular basis of these disorders was unknown. However, with the advances, cells with morphology of Langerhans cells are present in the stroma along with other cells such as eosinophils, macrophages, and T-cells.[1] Hence, the Histiocyte Society in 1985 recommended using the term “Langerhan cell histiocytosis” instead.

The Histiocyte Society classified histiocytic disorders into three groups: dendritic cell histiocytosis, macrophage-related disorders, and malignant histiocytosis.[8] LCH is included in the first group and denotes a spectrum of diseases that includes the indolent eosinophilic granuloma on one end to the fulminant and disseminated Letterer–Siwe disease on the other end. In the middle of this clinical spectrum lies Hand–Schuller–Christian disease.[2] This latter disease may present itself as proptosis and lytic lesions of the skull bones and may sometimes mimic ENT diseases such as otitis media and mastoiditis.

The exact pathophysiology of this disease is unknown, but there are all the possible theories. There is a group that proposes inflammatory pathophysiology on the basis of the fact that there are incidences of spontaneous remissions and elaboration of cytokines by dendritic cells and T-cells.[3],[9],[10] Another group advocates the neoplastic origin as there is infiltration of organs by aberrant monoclonal cells and favorable response to treatment with anticancer drugs.[2],[3],[4],[11],[12],[13],[14] Some suggest immune dysfunction as the possible pathogenesis of LCH.[4] Histopathology of LCH shows, among other cells, MNGCs. These show osteoclastic activity and cause bone necrosis. Researchers have shown that certain cytokines such as macrophage colony stimulating factor and receptor activator of nuclear factor-κB ligand expressed by LCH cells cause fusion of normal dendritic cells into MNGCs.[5],[9] In some families, multiple incidences of LCH have been documented raising the possibility of it being a genetic disorder.[12] It is commonly seen in males in the age group of 0–15 years; however, any age group can be involved.[9] Almost 50%–70% of the children with LCH present with multiple organ involvement.[8] In contrast, most of the studies have shown that almost 70% of adults present with single organ involvement, although some recent series reported otherwise.[8] ENT manifestation usually occurs in the Hand–Schuller–Christian disease. Moreover, nodulo-ulcerative cutaneous lesions can occur in the mandible, scalp, and retroauricular areas. Multifocal bony lytic lesions can cause recurrent otitis media and aural polyps.[6] Occasionally, mastoiditis and destructive tumor in mastoids have been reported.[2],[7],[15],[16],[17],[20] Hearing impairment with or without dizziness by destroying the bones of middle ear and temporal bone has been reported, sometimes even bilaterally.[9],[18],[19] Similar lesions in the orbit can cause exophthalmos. Secondary acquired cholesteatoma has been reported to develop from previously treated LCH as a result of posterior canal wall defect.[10] This may cause a misleading diagnosis of recurrence of LCH, but in fact, it is not and may require mastoid exploration as any other cholesteatomatous ear disease. It has been reported in maxillary sinus also.[17] The diagnosis is usually clinicopathological.[8] From the diagnostic point of view, when the history seems to indicate a disease with systemic involvement and routine plain films show lytic lesions of the skull, LCH should be considered in the differential diagnosis. In such cases, pediatricians are involved for skeletal screening with plain films as well as CT scan and/or magnetic resonance imaging.[19],[20] Endocrine evaluation may reveal diabetes insipidus. Diagnosis is usually established after biopsy that is usually carried out on one of the cutaneous ulcers or masses. Microscopic examination shows typical features of a granulomatous lesion, however, the key to diagnosis is to identify the pathologic Langerhans cell that resembles a typical Langerhans cell but it is nondendritic.[13] Birbeck granules, which are intracytoplasmic inclusions, are the hallmark of a pathologic Langerhans cell. Special tests such as transmission electron microscopy might be needed to identify them.[8] Other special tests are immunohistochemical tests such as CD1a, S-100, and CD207 (langerin). Currently, demonstration of CD1a and Birbeck granule is required for the diagnosis. Moreover, CD207 has been found to be associated with Birbeck granules with a 100% concordance, and hence, immunohistochemical positivity of these two markers (CD1a and CD207) defines the disease.[8],[9]

LCH is staged by the Histiocyte Society into single-system LCH or multi-system LCH depending on the number of systems involved.[9]

The treatment depends on the stage and the severity of the disease. It ranges from simple topical application of corticosteroids or antineoplastic agents, intralesional corticosteroid injections, and surgical curettage of skin lesions to full-blown course of systemic antineoplastic agents lasting up to a year.[8],[11]

The prognosis also depends on the stage and the severity of the disease. Unifocal LCH has the best prognosis with complete remission seen in cases of solitary lymph node involvement or isolated skin lesions. The disseminated disease (Letterer–Siwe disease) has the worst prognosis among all the forms of LCH with mortality in excess of 50%. The prognosis of the multifocal variant lies in-between and is bad in patients in extremes ages and those with pulmonary involvement. The mortality rate is around 10%, and less than a third of the patients could achieve complete remission.[15] The best prognostic indicator, after analyzing many clinical trials, has been demonstrated to be the response of the patient to chemotherapy during the 6-week induction phase.[8]

  Conclusion Top

LCH is a rare disease with a diversity of clinical presentations that may involve any organ. Otorhinolaryngology manifestations may cause diagnostic difficulties; a high index of suspicious and its inclusion in the differential diagnosis are suggested.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Komp DM. Historical perspectives of Langerhans cell histiocytosis. Hematol Oncol Clin North Am 1987;1:9-21.  Back to cited text no. 1
Skoulakis CE, Drivas EI, Papadakis CE, Bizaki AJ, Stavroulaki P, Helidonis ES, et al. Langerhans cell histiocytosis presented as bilateral otitis media and mastoiditis. Turk J Pediatr 2008;50:70-3.  Back to cited text no. 2
Egeler RM, Favara BE, van Meurs M, Laman JD, Claassen E. Differential in situ cytokine profiles of Langerhans-like cells and T cells in Langerhans cell histiocytosis: Abundant expression of cytokines relevant to disease and treatment. Blood 1999;94:4195-201.  Back to cited text no. 3
Willman CL, Busque L, Griffith BB, Favara BE, McClain KL, Duncan MH, et al. Langerhans'-cell histiocytosis (histiocytosis X) – A clonal proliferative disease. N Engl J Med 1994;331:154-60.  Back to cited text no. 4
da Costa CE, Annels NE, Faaij CM, Forsyth RG, Hogendoorn PC, Egeler RM, et al. Presence of osteoclast-like multinucleated giant cells in the bone and nonostotic lesions of Langerhans cell histiocytosis. J Exp Med 2005;201:687-93.  Back to cited text no. 5
Burns P, Foster A, Moran T, Blayney A. Multifocal Langerhans' cell histiocytosis: A case report. Ir J Med Sci 2010;179:611-3.  Back to cited text no. 6
Thelen A, Weikert S, Schrom T, Sedlmaier B. Histiocytosis of langerhans cells. simultaneous manifestation in both mastoid cavities. HNO 2009;57:1029-32.  Back to cited text no. 7
Satter EK, High WA. Langerhans cell histiocytosis: A review of the current recommendations of the Histiocyte Society. Pediatr Dermatol 2008;25:291-5.  Back to cited text no. 8
Weitzman S, Egeler RM. Langerhans cell histiocytosis: Update for the pediatrician. Curr Opin Pediatr 2008;20:23-9.  Back to cited text no. 9
Roger G, Dupré M, Leboulanger N, Godey B, Thomas C, Gandemer V, et al. Cholesteatoma secondary to temporal bone involvement by Langerhans cell histiocytosis: A complication amenable to curative surgery. Otol Neurotol 2009;30:190-3.  Back to cited text no. 10
Gadner H, Grois N, Arico M, Broadbent V, Ceci A, Jakobson A, et al. A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. J Pediatr 2001;138:728-34.  Back to cited text no. 11
Aricò M, Egeler RM. Clinical aspects of Langerhans cell histiocytosis. Hematol Oncol Clin North Am 1998;12:247-58.  Back to cited text no. 12
Annels NE, Da Costa CE, Prins FA, Willemze A, Hogendoorn PC, Egeler RM, et al. Aberrant chemokine receptor expression and chemokine production by Langerhans cells underlies the pathogenesis of Langerhans cell histiocytosis. J Exp Med 2003;197:1385-90.  Back to cited text no. 13
Yu RC, Chu C, Buluwela L, Chu AC. Clonal proliferation of Langerhans cells in Langerhans cell histiocytosis. Lancet 1994;343:767-8.  Back to cited text no. 14
Lahey E. Histiocytosis X – An analysis of prognostic factors. J Pediatr 1975;87:184-9.  Back to cited text no. 15
Adib AF, Lazrak A, Boulaich M, Nazih N, Oujilal A, Kzadri M, et al. Mastoid eosinophilic granuloma: A case report. Rev Laryngol Otol Rhinol (Bord) 2005;126:37-41.  Back to cited text no. 16
Lee JH, Suh SI, Kim YS, Kim CW, Chae YS, Kim I, et al. Unusual recurrence in ureters and maxillary sinus of langerhans cell histiocytosis involving mastoid bone. Pathol Res Pract 2005;200:845-9.  Back to cited text no. 17
Kleinjung T, Woenckhaus M, Bachthaler M, Wolff JE, Wolf SR. Langerhans' cell histiocytosis with bilateral temporal bone involvement. Am J Otolaryngol 2003;24:265-70.  Back to cited text no. 18
Marioni G, De Filippis C, Stramare R, Carli M, Staffieri A. Langerhans' cell histiocytosis: Temporal bone involvement. J Laryngol Otol 2001;115:839-41.  Back to cited text no. 19
Postovsky S, Daitzchman M, Dale A, Elhasid R, Ben Arush MW. Unusual presentation of mastoid eosinophilic granuloma in a young patient. Pediatr Hematol Oncol 2001;18:283-9.  Back to cited text no. 20


  [Figure 1], [Figure 2], [Figure 3]


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