Tatevossian R, Nanduri V, Salotti J Adults with LCH – orphans with an orphan disease. Clin Med. 2006; 6:404-408
Chu T. Langerhans cell histiocytosis. Aust J Dermatol. 2001; 42:237-242
Zuendel MT, Bowers DF, Kramer RN. Recurrent histiocytosis X with mandibular lesions. Oral Surg Oral Med Oral Pathol. 1984; 58:420-423
McElligott J, McMichael A, Sangueza OP, Anthony E, Rose D, McLean TW. Spontaneous regression of Langerhans cell histiocytosis in a neonate with multiple bony lesions. J Pediatr Hematol Oncol. 2008; 30:85-86
Moralis A, Kunkel M, Kleinsasser N, Muller-Richter U, Reichert TE, Driemel O. Intralesional corticosteroid therapy for mandibular Langerhans cell histiocytosis preserving the intralesional tooth germ. Oral Maxillofac Surg. 2008; 12:105-111
Eckardt A, Schultze A. Maxillofacial manifestations of Langerhans cell histiocytosis: a clinical and therapeutic analysis of 10 patients. Oral Oncol. 2003; 39:687-694
Langerhans cell histiocytosis: a diagnostic dilemma Paul L Ryan Kim M Piper Francis J Hughes Dental Update 2024 39:10, 707-709.
Authors
Paul LRyan
BDS, MFDS RCS(Eng), MClinDent
Academic Clinical Fellow (Specialist Registrar) in Restorative Dentistry, Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Turner Street, London
Langerhans cell histiocytosis (LCH) is a rare clonal neoplastic disorder of unknown aetiology which can present with a diverse range of clinical presentations. It encompasses a diverse number of idiopathic conditions which can involve multiple body systems and is characterized by bone marrow-derived Langerhans cell proliferation. The disease can affect multiple body systems and lesions can be solitary or widespread. We present a case of a multifocal eosinophilic granuloma (LCH) in a young adult female with clinical signs and symptoms similar to aggressive periodontitis.
Clinical Relevance: Langerhans cell histiocytosis is a rare disease which can have a similar clinical presentation to aggressive periodontitis.
Article
Langerhans cell histiocytosis encompasses a diverse number of idiopathic conditions which can involve multiple body systems.1 It is characterized by bone marrow-derived Langerhans cell proliferation and can affect many body systems, including: bone, lung, skin, mucous membranes, lymph nodes and the liver. The lesions can be solitary or widespread.
LCH includes a group of disorders which are classically described as being of one of three forms with distinct clinical presentations. The eosinophilic granuloma normally presents as a solitary slowly progressing lesion in the bone, lungs or stomach, often found as an incidental radiographic finding typically in young adults. It tends to be more benign in nature and solitary, responding well to conservative local treatment. Letterer-Siwe disease, in contrast, is a multi-system rapidly progressing form of the condition in very young children, which is treated with chemotherapy, but has a very poor survival rate. The final condition which makes up the disease triad is Hand-Schüller-Christian disease which is a multifocal eosinophilic granuloma with multiple bony lesions, exophthalmos and diabetes insipidus. This typically affects young children, on average between 2–5 years, and lies somewhere intermediate to the other forms of LCH in terms of prognosis and severity. Disease onset can occur several years before symptoms and signs lead to a diagnosis.
Histologically, LCH is characterized by the presence of multi-nucleated Langerhans cells which can be identified using immunoperoxidase CD1a staining. This is often surrounded by a dense mixed inflammatory and endothelial rich tissue infiltrate. Classically, electron microscopy reveals the presence of Birbeck granules.
Treatment of solitary bone lesions is usually by local surgical excision and curettage of the bone or with local steroid injections. This conservative approach tends to lead to elimination of the lesion, although recurrence can occur.2 Multi-focal lesions tend to be treated with chemotherapeutic agents or radiotherapy to control the activity of the condition. LCH lesions also sometimes undergo spontaneous regression, particularly within the oral cavity, which is not typical of a neoplastic disease and an observation that confuses the disease pathogenesis.3
We present a case of multifocal eosinophilic granuloma (LCH) affecting the mandible bilaterally which presented with similar signs to localized aggressive periodontitis.
Case report
A 26-year old female was referred to the periodontal department at Barts and The London NHS Trust regarding a painful gingival swelling localized to her two-rooted lower left canine and lateral incisor, with associated deep pocketing around these teeth (Figure 1). Her dentist had observed rapid and progressive localized horizontal bone loss from 30% to 90% over a six-month period (Figure 2 a–e).
Figure 1.
(a, b) Pre-operative clinical pictures showing buccal and lingual localized gingival inflammation between lower left canine and lateral incisor.Figure 2. Periapical of left lower canine and lateral incisor: (a) revealing 40% horizontal bone loss (February 2007); (b) revealing 90% horizontal bone loss (October 2007); (c) revealing 90% horizontal bone loss (March 2008); (d) revealing 90% bone loss around mesial of lateral incisor following the extraction of lower left canine (October 2008); (e) DPT revealing localized advanced bone loss between lower left canine and lateral incisor (December 2007).
Initial biopsy and curettage of the lesion down to bone revealed a mixed inflammatory infiltrate and the site initially healed well post surgery (Figure 3).
Figure 3.
(a, b) Non-surgical maintenance of the site with resolution of gingival inflammation and marked labial and lingual recession (maximum probing depth of 4 mm).
The site was maintained with non-surgical periodontal treatment for a further eight months before further bone destruction and tooth mobility around the canine tooth occurred, leading to its extraction (Figure 4a).
(a) Extraction of the two-rooted lower left canine. (b) Compromised healing of socket post-extraction.
Failure of the socket to heal prompted a second biopsy of the lesion (Figure 4b), with CD1a staining revealing the presence of Langerhans cells and leading to a diagnosis of LCH (Figure 5). Radiographic and CT imaging revealed the presence of a second mandibular lesion associated with an unerupted and impacted lower third molar (Figure 6). The patient is currently being treated with a three month course of oral azathioprine by a consultant dermatologist with a special interest in LCH.
Figure 5. CD1a positive immuno-staining of Langerhans cells.Figure 6. Significant bone loss associated with unerupted and impacted lower third molar (January 2009).
Discussion
The clinical and radiographical presentation of LCH can mimic periodontitis and, in view of its low incidence, reportedly approximately 1 in 560,000 in adults,1 the diagnosis can often be overlooked or delayed. The non-specific inflammatory tissue identified histologically in the initial biopsy, and the presence of the two-root lower canine at the affected site, initally reinforced the clinical diagnosis of bone loss due to localized periodontal disease. Similarly, the recurrent gingival inflammation around the lower right third molar was found eventually not to be due to recurrent periodontitis, as initially diagnosed, but a second LCH lesion.
Diagnosis of LCH must be with positive histopathology, however, as shown in this case, a single biopsy may not always reveal a diagnosis.2 The case also highlights the value of a detailed clinical history in aiding the histopathologist in diagnosis as well as the importance of full body CT scans or scintigraphy to ensure there are no other affected sites.
The classical radiological appearance of LCH is the ‘floating teeth’ sign, where alveolar bone is gradually replaced by a Langerhans cell lesion, which is seen radiographically in this case. There is a variable radiographical appearance which is dependent on the site and progression/extent of the disease. It varies from poorly defined lesions with lamellated periosteal reaction in early lesions, to well defined lesions with sclerotic margins in more established lesions.3
There has been much speculation and debate over the likely pathogenesis of LCH. It is considered by some to be a cancer or pre-cancerous condition and by others a reactive lesion.4 However, a viral aetiology has also been considered as a likely disease trigger.5
The prognosis of solitary LCH lesions is generally good and local curettage of these lesions is all that is usually required for treatment. As demonstrated in this case, LCH can show improvement following non-surgical periodontal treatment but this will rarely be curative.6 In fact, there are some reports of spontaneous regression,7 as well as conservative treatment with intra-lesional steroid injections.8
If lesions are multiple or not easily accessible for surgical access, then adjunctive treatments, including radiotherapy, chemotherapy and steroids, can be used to manage the disease. Immunosuppressive drugs such as azathioprine and methotrexate, as well as cytotoxic chemotherapy, such as etoposide, have been used to treat the disease successfully. This is why dermatologists who have experience in prescribing these types of medications may be best placed to manage LCH patients.5
The prognosis of eosinophilic granuloma is generally good, however, there is a need for close follow-up after treatment, as recurrence and other new lesions can occur.9
