International Journal of Pediatric Otorhinolaryngology Extra
Volume 3, Issue 2 , Pages 61-65, March 2008

Case study: Langerhans’ cell histiocytosis (LCH)

  • Nico Jonas

      Affiliations

    • Division of Otolaryngology, University of Cape Town Medical School, South Africa
    • Corresponding Author InformationCorresponding author at: Division of Otolaryngology, University of Cape Town Medical School, H53 Old Main Building, Groote Schuur Hospital, Observatory, Cape Town 7925, South Africa. Tel.: +27 21 4066420; fax: +27 21 4488865.
    • ,
  • Wakisa Mulwafu

      Affiliations

    • Division of Otolaryngology, University of Cape Town Medical School, South Africa
    • ,
  • Sally-Anne Khosa

      Affiliations

    • Department of Anatomical Pathology, Red Cross Children's Hospital, South Africa
    • ,
  • Marc Hendricks

      Affiliations

    • Haematology/Oncology Service, Red Cross Children's Hospital, South Africa

Received 30 May 2007; accepted 4 October 2007. published online 22 November 2007.

Article Outline

Summary 

The clinical spectrum of Langerhans cell histiocytosis (LCH) can be very diverse. Pathology can range from a single bony lesion to systemic disease with multi-organ dysfunction. Up to 61% of patients with LCH have otologic involvement and in 5–25% it might be the initial form of presentation [A.J. Goldsmith, D. Myssiorek, E. Valderrama, M. Patel, Unifocal Langerhans’ cell histiocytosis (eosinophilic granuloma) of the petrous apex, Arch. Otolaryngol. Head Neck Surg. 119 (1993) 113–116; R. Hermans, B. De Foer, M.H. Smet, J. Leysen, Eosinophilic granuloma of the head and neck: CT and MRI features in three cases, Pediatr. Radiol. 24 (1994) 33–36; T.V. McCaffrey, T.J. McDonald, Histiocytosis X of the ear and temporal bone: review of 22 cases, Laryngoscope 89 (1979) 1735–1742]. The otologic findings of LCH are similar to otomastoiditis and therefore LCH should be considered as a possible differential diagnosis in very young patients presenting with signs and symptoms suggestive of chronic otitis media.

Keywords: Langerhans cell histiocytosis (LCH), Eosinophilic granuloma, Temporal bone

 

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1. Case study 

A 2-year-old boy presented to our ENT clinic with a discharging right ear for 1 month. There was no history of previous ear infections or hearing loss. Apart from suffering from recurrent atopic eczema he had no significant medical history.

A complete ENT examination was performed. Examination of his right ear revealed a purulent discharge with a polyp in the deep part of the external ear canal, obscuring the tympanic membrane. He also had a small lymph node in the right postauricular area. Examination of his left ear was normal.

A diagnosis of otitis media was made and he was treated with oral Co-amoxiclav and aminoglycoside eardrops.

A week later, the ear canal polyp was still present and an inflamed fluctuant swelling was present in the postauricular area. The patient was apyrexial and he had no neurological deficits. A diagnosis of acute mastoiditis was made and a mastoidectomy was performed.

Intraoperative findings revealed an eroded bony external ear canal and mastoid bone giving the picture of an ‘automastoidectomy’. The deep part of the external ear canal, middle ear and mastoid cavity were filled with friable soft tissue and no tympanic membrane or ossicles could be identified. There was no evidence of cholesteatoma. Biopsies of the soft tissue were taken and sent for histology.

The histology result showed fragments of granulation tissue lined by focally ulcerated squamous epithelium. There was marked congestion of stromal blood vessels and the tissue was infiltrated by numerous eosinophils and histiocytic cells. Stains for fungi and bacteria were negative. The histiocytic cells stained positive for S100, CD68 and CD1a (Fig. 1, Fig. 2, Fig. 3, Fig. 4).

  • View full-size image.
  • Fig. 2. 

    Histiocytes, some of which are multinucleate, are also present in the background and these are highlighted well on the CD 68 stain (upper left-hand corner), high-power view.

A diagnosis of eosinophilic granuloma was made and the child was referred to the oncology service.

The patient was assessed by the oncologist. The child did not have polyuria or polydipsia (posterior pituitary involvement). Furthermore there was no history of anorexia, hyperphagia, changes in temperature control or sleep patterns (hypothalamic involvement) and he had normal anthropometry (anterior pituitary involvement). On examination he was well grown and had no focal neurology. This in-depth history is important because children with lytic lesions involving the temporal bone are at risk of developing CNS disease, in particular diabetes insipidus. The diabetes insipidus is classically unresponsive to systemic therapy and irreversible.

Complete systemic investigation including a temporal bone CT scan revealed this to be an isolated temporal bone lesion (Fig. 5). He was reviewed by the dermatologists to exclude cutaneous involvement by LCH. The skin disease was felt to be chronic atopic eczema rather than cutaneous LCH.

Due to the fact that children with eosinophilic granulomas of the skull are at increased risk of central nervous system disease and complete clearance of disease during mastoidectomy was not achieved, the decision was made to treat this patient systemically.

The patient was commenced on oral Prednisone 40mg in two divided doses daily for 4 weeks, tapering over 2 weeks, with weekly Vinblastine injections for 6 weeks. Continuation therapy followed, consisting of oral Prednisone 40mg in two divided doses for 5 days per week and weekly Vinblastine injections for 16 weeks.

A repeat CT scan of his head 1 year later showed bone remodelling in the temporal bone with no evidence of recurrence (Fig. 6). A skeletal survey revealed no disease recurrence at any other site.

The patient remains in remission. Subsequent admissions to hospital have been related to cellulitis of the legs as a complication of impetigenised eczema.

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2. Discussion 

The classification for histiocytic disorders has undergone a number of changes over the last two decades. In 1987, the Writing Group of the Histiocyte Society recommended a division of the histiocytic disorders into three classes: Langerhans cell histiocytosis (LCH) (class I); non-Langerhans cell histiocytosis (class II); malignant histiocytic disorders (class III) [1]. A minor revision of this classification has more recently been proposed, and the three major groups are now termed (1) dendritic cell-related disorders (of which LCH is by far the most common), (2) macrophage-related disorders, and (3) malignant disorders [2]. LCH includes the disorders formerly known as histiocytosis X (eosinophilic granuloma, Hand-Schüller-Christian disease, and Letterer-Siwe disease) [3].

In children other variations include an exclusive nodal presentation, a pulmonary syndrome (usually seen in adolescents) and a cutaneous form. Rarely patients present with subcutaneous nodules (Hashimoto-Pritzker syndrome).

Langerhans cells are bone marrow derived cells from the monocyte-macrophage line. These cells migrate to the epidermis and function as potent antigen presenting cells.

Langerhans cell histiocytosis is a disorder in which cells having the phenotypic markers of epidermal Langerhans cells are found in skin and other organs where they cause damage by excessive production of cytokines and prostaglandins. The lesions can be varied, ranging from a single bony lesion to systemic disease with multi-organ dysfunction [4], [5], [6].

The etiology and pathogenesis are still unknown. Most studies suggest that it is a reactive disease caused by abnormal immune regulation [7]. This is controversial and there are arguments to the contrary, suggesting that LCH is a clonal proliferation, i.e. neoplastic disorder [8]. Although several studies have failed to define a role for viruses in the pathogenesis, the possibility remains [9], [10]. The possibility of a super-antigen has been postulated and is still under investigation [11].

The disease may present at any age, but young children are most often affected [12]. LCH can affect many systems/organs including skeleton, skin, reticulo-endothelial, pulmonary, central nervous system, gastro-intestinal tract and the ear, nose and throat. The skeleton is involved in 80% of cases, with the skull the most common site (49%) [13].

Fifteen to sixty-one percent of patients with LCH have otologic involvement [4], [5], [6]. In 5–25% it might be the initial form of presentation [4], [5]. Outer ear involvement can present with mastoid swelling, aural polyps, otorrhoea and erosion of the bony canal wall with sagging of canal wall skin [4], [6], [14]. Involvement of the middle ear can present with involvement of the ossicular chain and conductive hearing loss [4], [15]. The inner ear is fairly resistant, but involvement of the bony labyrinth (vertigo and sensorineural hearing loss) and the facial and vestibule-cochlear nerve has been described [4].

The diagnosis should be made histologically with the demonstration of Birbeck granules on electron microscopy, or the presence of special markers (anti CD1a, S100, D mannosidase, Peanut agglutinin, Surface ATP-ase).

Computed tomography is the best radiological investigation for demonstrating disease in the temporal bone. This usually demonstrates destruction of the temporal bone, including the mastoid, with associated enhanced soft tissue masses [15], [16]. MRI is probably better for diagnosing pituitary disease and other central nervous system involvement.

Isolated small temporal bone lesions are usually treated with surgical curettage of the lesions followed by radiotherapy, or local injection of steroids. Extensive or multiple bone lesions or multi-system disease is treated with immunomodulatory therapy which includes systemic glucocorticoids (prednisone), chemotherapeutics (like the vinca alkaloids), the folate antagonists (methotrexate) and the purine analogues (6-mercaptopurine) [17].

The prognosis is unpredictable. Universally accepted poor prognostic factors are age less than 2 years and patients with certain organ involvement, i.e. bone marrow, liver, spleen or lung. The estimated 10-year survival for single organ disease has been reported as high as 100% while the survival for multi-organ disease is 77% [12]. Temporal bone disease has a good long-term prognosis. These lesions usually re-ossify and remodel well [3].

In conclusion, because the otologic findings of LCH are similar to otomastoiditis, the diagnosis is often delayed [14], [16]. Chronic otitis media or cholesteatoma should only be diagnosed after careful consideration in children younger than 3 years, especially when the ESR is elevated [14].

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Conflict of interest 

None.

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References 

  1. Histiocytosis Syndromes in Children, Writing Group of the Histiocyte Society, Lancet 1 (8526) (1987) 208–209.
  2. Favara BE, Feller AC, Pauli M, et al. Contemporary classification of histiocytic disorders. The WHO Committee On Histiocytic/Reticulum Cell Proliferations, Reclassification Working Group of the Histiocyte Society. Med. Pediatr. Oncol. 1997;29(3):157–166
  3. Fernandez-Latorre F, Menor-Serrano F, Alonso-Charterina S. Langerhans’ cell histiocytosis of the temporal bone in paediatric patients. AJR. 2000;174:217–221
  4. Goldsmith AJ, Myssiorek D, Valderrama E, Patel M. Unifocal Langerhans’ cell histiocytosis (eosinophilic granuloma) of the petrous apex. Arch. Otolaryngol. Head Neck Surg. 1993;119:113–116
  5. Hermans R, De Foer B, Smet MH, Leysen J. Eosinophilic granuloma of the head and neck: CT and MRI features in three cases. Pediatr. Radiol. 1994;24:33–36
  6. McCaffrey TV, McDonald TJ. Histiocytosis X of the ear and temporal bone: review of 22 cases. Laryngoscope. 1979;89:1735–1742
  7. Irving RM, Broadbent V, Jones NS. Langerhans’ cell histiocytosis in childhood: management of head and neck manifestations. Laryngoscope. 1994;104:64–70
  8. McClain KL, Natkunam Y, Swerdlow SH. Atypical cellular disorders. Hematol. Am. Soc. Hematol. Educ. Program. 2004;283–296
  9. McClain K, Weiss RA. Viruses and Langerhans’ cell histiocytosis: is there a link?. Br. J. Cancer. 1994;70(Suppl. 23):S34–S36
  10. Leahy MA, Krejci SM, Friednash M, et al. Human Herpesvirus 6 is present in lesions of Langerhans’ cell histiocytosis. J. Invest. Dermatol. 1993;101:642–645
  11. Kannourakis GK, Abbas A. The role of cytokines in the pathogenesis of Langerhans’ cell histiocytosis. Br. J. Cancer. 1994;70(Suppl. 13):S37–S40
  12. Bernstrand C, Sandstedt B, Ahstrom L, Henter JI. Long-term follow-up of Langerhans cell histiocytosis: 39 years’ experience of a single centre. Acta Paediatr. 2005;94(8):1073–1084
  13. Broadbent V, Egeler RM, Nesbit ME. Langerhans’ cell histiocytosis: clinical and epidemiological aspects. Br. J. Cancer. 1994;70(Suppl. XXIII):S11–S16
  14. Anonsen CK, Donaldson S. Langerhans’ cell histiocytosis of the head and neck. Laryngoscope. 1987;97:537–541
  15. Hadjigeorgi C, Parpounas C, Zarmakoupis P, Lafoyianni S. Eosinophilic granuloma of the temporal bone: radiological approach in the pediatric patient. Pediatr. Radiol. 1990;20:546–549
  16. Cunningham MJ, Curtin HD, Butkiewicz BL. Histiocytosis X of the temporal bone: CT findings. J. Comput. Assist. Tomogr. 1988;12:70–74
  17. The French Langerhans’ Cell Study Group . A multicentre retrospective survey of Langerhans’ cell histiocytosis: 348 cases observed between 1983 and 1993. Arch. Dis. Child. 1996;75:17–24

PII: S1871-4048(07)00081-0

doi:10.1016/j.pedex.2007.10.004

International Journal of Pediatric Otorhinolaryngology Extra
Volume 3, Issue 2 , Pages 61-65, March 2008

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