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An Official Publication of the Indian Association of Oral and Maxillofacial Pathologists

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Year : 2023  |  Volume : 27  |  Issue : 5  |  Page : 98-103

Adult-onset Langerhans cell histiocytosis – A Trojan horse of oral cavity: A case report with rare clinical presentation

1 Department of Oral Medicine and Radiology, JSS Dental College and Hospital, JSS Academy of Higher Education and Research (JSSAHE&R), Mysuru, Karnataka, India
2 Department of Oral and Maxillofacial Pathology, JSS Dental College and Hospital, JSS Academy of Higher Education and Research (JSSAHE&R), Mysuru, Karnataka, India

Date of Submission18-Mar-2022
Date of Decision12-May-2022
Date of Acceptance19-May-2022
Date of Web Publication04-Feb-2023

Correspondence Address:
Karthikeya Patil
Department of Oral Medicine and Radiology, JSS Dental College and Hospital, JSS Academy of Higher Education and Research, Mysore - 570 015, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jomfp.jomfp_131_22

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Langerhans cell histiocytosis (LCH), earlier recognised as histiocytosis X, is a rare haematological illness involving infants and young children. LCH is caused by unrestrained stimulation and proliferation of usual antigen presenting cells, Langerhans cells (LCs) and the disease demonstrates extensive clinical and radiographic features involving multiple sites. Since the incidence is relatively low limited data is available regarding the epidemiology of LCH, with approximation of 2–5 cases per million populations per year. LCH has male predilection with jaws involved in 10–20% cases and only 1% of the cases affecting maxilla, masquerading as periodontal or periapical pathology. We report a case of 48-year-old female with LCH involving posterior maxilla. This is a unique presentation corresponding to age, gender, location and severity. Dental clinicians should be aware of this and consider it to be a part of their differential diagnosis pertaining to unresolved periodontal pathology as it mimics clinically and radiographically.

Keywords: Adult onset, eosinophilic granuloma, Langerhans cell histiocytosis, posterior maxilla, scooped out radiolucency

How to cite this article:
Sanjay C J, Patil K, Hegde U, Panda R. Adult-onset Langerhans cell histiocytosis – A Trojan horse of oral cavity: A case report with rare clinical presentation. J Oral Maxillofac Pathol 2023;27, Suppl S1:98-103

How to cite this URL:
Sanjay C J, Patil K, Hegde U, Panda R. Adult-onset Langerhans cell histiocytosis – A Trojan horse of oral cavity: A case report with rare clinical presentation. J Oral Maxillofac Pathol [serial online] 2023 [cited 2023 Mar 24];27, Suppl S1:98-103. Available from: https://www.jomfp.in/text.asp?2023/27/5/98/369165

   Introduction Top

Langerhans cell histiocytosis (LCH) is a generalised term given to group of haematological disorders characterised by uncoordinated stimulation and proliferation of LCs and mature eosinophils with controversial etiologic origin. The data available regarding the epidemiology is limited because of its rarity in incidence and prevalence with an estimation of 2–5 cases per million populations per year.[1] The disease usually affects children and with female predilection causing destruction of bone and soft tissues involving multiple sites and tissues.[2] Oral manifestations are normally the first indicator in LCH but the initial signs and symptoms are mostly nonspecific, leading to misdiagnoses.[3] The most common clinical demonstrations seen in the majority of cases involves single or multiple bone lesions, with skull being a most frequently involved site along with ribs, vertebrae and jaws.[4] In the jaws posterior mandible is more commonly involved especially the region distal to canine.[5] However, the diagnosis of LCH is exclusively based on microscopic examination and the disease is broadly categorised into three disorders based on the clinical presentations, each of which is staged clinically according to Greenberg et al.[6] clinical staging system. Here we report case of low grade LCH with solitary monostotic bone lesion in posterior maxilla masquerading as periodontal pathology in a 48-year-old female which was diagnosed based on histopathology and immunohistochemistry. Also highlights the diverse rare presentations of disease and advocating the importance of early diagnosis by a dental surgeons and management of the same. This could be the first among the very few cases of LCH documented in English literature with minimal signs and symptoms to be reported in an adult female involving posterior maxilla.

   Case History Top

A 48-year-old female reported to our Outpatient Department (OPD) with a chief complaint of pain in the upper right back tooth region for the past 1 month which was mild, constant, dull aching associated with difficulty in chewing food. There was no history of numbness/paresthesia reported. History of exfoliation of a tooth reported six months back with no history of complete healing of socket was reported. Also, mobility of the remaining teeth in that region for 3 months was reported. No history of any significant systemic illness, positive family history and trauma were reported. On general physical examination patient was moderately built and nourished with no extraoral signs of swelling or asymmetry noted. Intraoral examination revealed poor oral hygiene, multiple missing teeth, generalised tooth mobility and periodontal pockets with halitosis. In the upper right posterior maxilla 16, 17 were missing with presence of raw granulation tissue and inflamed gingiva extending to the adjacent teeth region suggestive of chronic non-healing lesion [Figure 1]. Mobility and periodontal pockets were noted in respect to 14, 15, 18. The erythematous areas were tender on palpation with no signs of bleeding or active pus discharge on manipulation. Right submandibular lymph node was palpable, tender, mobile with firm consistency. Orthopantomography (OPG) [Figure 2] revealed scooped out radiolucency in the region of 16, 17, extending up to the floor of maxillary sinus without any breach. Advanced bone loss was noted with respect to 15, with visibility of upper and middle third of the root giving a floating tooth appearance. Considering the history of recent exfoliation, clinical and radiographic features differential diagnosis of advanced periodontitis, Wegener's granulomatosis, carcinoma alveolus/gingiva were given.
Figure 1: Intraoral picture of the lesion involving the maxillary right posterior region

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Figure 2: Orthopantomogram showing scooped out radiolucency in the right posterior maxilla

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Patient's routine complete blood examination parameters prior to incisional biopsy found to be in normal limits. Up on regular H and E staining, histopathology revealed presence of ulcerated squamous epithelium with masses of histiocytic cells in the underlying tissue along with many histiocytes [Figure 3]. LCs are found in the oral mucosa, but they are present 5 times more in the inflamed gingiva than healthy gingiva. Studies have shown that LC's are responsible for accumulation of the biofilms and they also play an important role in the antigen presentation during the phases of periodontitis. For definitive diagnosis, immunohistochemical staining was carried out and the result was positive for CD1a [Figure 4] and S100 markers [Figure 5]. Strong expression of the CD1a was the diagnostic marker of LCH in this case. Further radiographic survey for the complete skeleton was conducted to rule out multiple lesions or multiorgan involvement anywhere else in the body. Skull radiographs and radiographs of long bones did not show any bony lesions [Figure 6].
Figure 3: 40 X H and E staining showing connective tissue stroma with masses of histiocytic cells and few blood vessels.

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Figure 4: 100 X CD1a Immunohistochemistry showing membrane positivity

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Figure 5: Cells positively reacting to S-100 protein on Immunohistochemistry

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Figure 6: True lateral view of skull showing no changes

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Considering all the above findings the final diagnosis was given as eosinophilic granuloma. With regard to recent classification, single organ system LCH with clinical staging of 1a (Greenberger's criteria)[6] was given. Management of the condition was done with bone curettage of the localised lesion and the patient is still under follow-up with no new lesions identified up to 1 and half years until write up of this manuscript.

   Discussion Top

The LCs are dendritic mononuclear cells basically involved in the normal process of antigen presentation to T lymphocytes and are seen in the epidermis, mucosa, lymph nodes and bone marrow.[1] LCH is collective term given to group of disorders with diverse clinicopathological manifestations and histologically characterised by monoclonal proliferation of histiocyte-like cells associated with variable numbers of eosinophils, lymphocytes, plasma cells and multinucleate giant cells. The histiocytes existing in these disorders are identified as LCs and their proliferation is involved in the destruction of bone and soft tissues.[7] Previously, the LCH was considered to be a reactive disorder of immunological regulation but the current evidence shows it to be of neoplastic lesion with monoclonal proliferation of lesional cells.[8],[9]

LCH classification with various terms and designations such as Eosinophilic Granuloma, Hand–Schuller–Christian disease, Letterer–Siwe disease, Hashimoto-Prizker syndrome, are still used frequently by clinicians for mentioning the clinical features of LCH.[10] In real the margin between different disease entities is not stringent and despite the heterogeneous demonstrations of the disease, it is still relevant to contemplate LCH as a unique disease with various extensions and various outcomes. Greenberg et al.[6] in 1981 [Table 1] proposed a clinical staging involving all the cases of LCH into five stages based on the clinical manifestation, age of patient at the time of diagnosis and with number of bone lesions.
Table 1: The clinical staging proposed by Greenberg et al.[6]

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The current classification distinguishes LCH into single-system disease LCH (SS-LCH) involving one organ or system such as unifocal bone (single bone), multifocal bone (more than one bone), skin, lymph node (not the draining lymph node of another LCH lesion), lungs, hypothalamic-pituitary/central nervous system (CNS) or others such as thyroid or thymus. The multisystem LCH (MS-LCH) involves two or more systems that may include 'risk organs' (hematopoietic system, spleen and/or liver) or not (for example, skin and bone, or skin and pituitary).[11] Again multisystem/multiorgan is further divided into high risk or low risk depending on the organ dysfunction (High-risk organs includes lung, liver, spleen, bone marrow low risk includes skin, bone, lymph nodes and/or pituitary gland). Considering all of the above criteria and classifications the present case was categorised, our present case as eosinophilic granuloma with low-risk single organ system LCH and stage 1a lesion.

The epidemiology data shows that the LCH is normally seen in early age (range 1–15 years) with peak incidence at 2–4 yrs of age with male predilection (male to female ratio 3.7:1) and incidence of 5 cases per 1 million per year.[12],[13] Most frequently affected organ is bone followed by skin, lymph nodes, liver, spleen, oral mucosa, lung and CNS. Commonly involved bone lesions include skull, femoral lesions in children below 10-year-old and rib, shoulder girdle, mandibular lesions in those older than 20 years.[14] Other oral manifestations include halitosis, gingival hypertrophy/inflammation, mobility of teeth with alveolar expansion, jaw pain, facial swelling, mental nerve anaesthesia and failure of extracted tooth sockets to heal.[15]

The present case is unique corresponding to age, gender and location which involves 48-year-old which could be the first reported case involving maxilla in an adult female patient. The patient here presented with a pain and periodontal pathology in the right posterior maxilla 16, 17, region which is uncommon as compared to the mandibular lesions [Table 2].[15],[16],[17],[18],[19],[20],[21],[22],[23] shows list of documented cases of LCH involving maxillary bone which are very few in number.[20]
Table 2: List of documented cases of LCH involving maxillary bone

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Among the 17 cases of LCH mentioned in the literature, only 2 of them occurred as solitary lesions in maxilla. The present case could probably be 18th case in the English literature involving maxilla and 3rd case as solitary lesion in maxilla which shows the rarity of the location.

Radiographically LCH presents with varied presentation, the commonest being the punched-out lesions frequently seen in pathology of all forms. The term punched out lesions is used to define lesions in bones other than jaws. In jaws, LCH presents as solitary intraosseous lesions (outside alveolar process), multiplicity of “alveolar bone” lesions, well-defined periphery (uncorticated), scooped out shape, bone sclerosis, periosteal new bone formation, root resorption (very rare).[24] The present case was resembling a scooped-out shaped [Figure 7][24] bone loss (nonsclerotic borders) with intact maxillary sinus in the region of 16, 17 and advanced periodontitis of the adjacent teeth. This specific appearance ensues owing to bone destruction which starts under the alveolar crest and usually a slice of the superior aspect of crest of the alveolar bone is preserved at the mesial and distal margins of the destruction and produces a scooped-out appearance. With progression of the destruction, it is possible that the bone that persisted at the superior aspect of the crest is destroyed and this appearance is lost. This form of bone destruction has not been observed in periodontal disease and thus may be useful in the differentiation of lesions with LCH.
Figure 7: Diagram used as a guide to classify shape of alveolar lesions: Fig-C represents the scooped-out appearance

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In the present case, as there was no characteristic clinical and radiographic features presented, the diagnosis of LCH was considered only after histopathological and immunohistochemistry tests were done. The biopsy should be done from the most accessible area for histopathological and for immune-phenotypic examinations of the lesional tissue. The main diagnostic feature is the morphological identification of the characteristic LCH cells but according to Histocyte Society Writing Group positive staining of lesional cells with CD1a and/or Langerin (CD207) and also S100 is required for a definitive diagnosis. In the present case, strong expression of CD1a and S-100 was considered as the diagnostic marker of LCH.[25] Electron microscopy is no longer recommended since it has been shown that the expression of Langerin which was previously one of the criteria required for definitive diagnosis fully resembles with the presence of Birbeck granules. There are very few exceptions; however, in organs such as the liver, Birbeck granules are not present and CD1a and/or Langerin may be negative.[11],[26]

The treatment and the prognosis of LCH depends on staging, risk involved (high/low risk), whether its single organ system or multiple organ system. The prognosis is favourable for low grade single organ system LCH and survival rate is considered greater than 99%. The prognosis is unfavourable if the lesions involve high-risk multiorgan organ lesions with survival rate of 35%.[13] In bone, lesions of maxilla or mandible when the access is favourable then treatment involves bone curettage and intralesional steroid injection.[27] In other inaccessible lesions with multiorgan the radiotherapy/chemotherapy is preferred. In the present case, bone curettage was carried out with complete resolution of the lesion and patient still under follow-up with no new lesions identified.[28],[29] Because of the rarity in presentation and extensions, the standard treatment protocol in not still established.

   Conclusion Top

Our case adds an additional report of diversity of LCH to the English literature with unique presentation with respect to age, gender and location with uncommon location of maxilla involving adult female (first to be reported). There was no sign of added lesion anywhere in the jaws or other parts of the body and diagnosed only on the basis of histopathological and immunohistochemical examination. In conclusion, one should consider the possibility of LCH in the routine periodontal lesions. Dental clinicians should be aware of such lesions of low grade LCH and consider this to be part of their differential diagnosis of periodontal pathology in patients seeking treatment for the same since it mimics clinically and radiographically. Complete evaluation with full work up of signs and symptoms has to be done to rule out possibility of LCH in adult.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given his consent for his 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.

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Conflicts of interest

There are no conflicts of interest.

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]

  [Table 1], [Table 2]


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