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   Table of Contents    
CASE REPORT
Year : 2021  |  Volume : 25  |  Issue : 2  |  Page : 166-170  

Adult multifocal Langerhan's cell histiocytosis involving periodontal tissues


Department of Periodontology, Narayana Dental College and Hospital, Nellore, Andhra Pradesh, India

Date of Submission11-Jan-2020
Date of Decision11-Oct-2020
Date of Acceptance12-Oct-2020
Date of Web Publication01-Mar-2021

Correspondence Address:
Vijay Kumar Chava
Department of Periodontology, Narayana Dental College and Hospital, Nellore, Andhra Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jisp.jisp_22_20

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   Abstract 


Langerhans cell histiocytosis (LCH) is a rare inflammatory neoplasia characterized by uncontrolled stimulation and abnormal proliferation of Langerhans cells (LCs). It can present as unifocal or multifocal with local and systemic manifestations which involves various internal organs and mucosal tissues. The clinical course varies among individuals, ranges from spontaneous resolution to life-threatening conditions with multisystem involvement. Prognosis relies on the involvement of risk organs (liver, spleen, and bone marrow) at diagnosis, mainly on organ dysfunction, and response to initial therapy. The diagnosis is based on histological study of tissues samples and shows tissue infiltration with LCs and the tumor cells immunopositive for s100/CD1a/Langerin/CD68 focal). In the oral cavity, LCH affects the alveolar or cortical bone and causes ulcerated lesions involving various mucosal and periodontal tissues. This article reports a case of adult multifocal LCH involving periodontal tissues with 1½ year posttreatment follow-up showing regression of the lesion.

Keywords: Gingiva, jaws, Langerhans cell histiocytosis, oral lesions, periodontitis


How to cite this article:
Chava VK, Bhanu VU. Adult multifocal Langerhan's cell histiocytosis involving periodontal tissues. J Indian Soc Periodontol 2021;25:166-70

How to cite this URL:
Chava VK, Bhanu VU. Adult multifocal Langerhan's cell histiocytosis involving periodontal tissues. J Indian Soc Periodontol [serial online] 2021 [cited 2021 May 12];25:166-70. Available from: https://www.jisponline.com/text.asp?2021/25/2/166/310571




   Introduction Top


Langerhans cell histiocytosis (LCH) is a unique disorder of reticuloendothelial system characterized by marked, aberrant proliferation and infiltration of pathological Langerhans cells (LCs) and other inflammatory cells in one or more organs system.[1] In 1953, based on cytoplasmic bodies, Lichtenstein proposed three clinical forms of LCH, that include eosinophilic granuloma (localized chronic form), hand Schuller Christian disease disseminated chronic form), and Letterer siwe syndrome (subacute or acute disseminated form)[2] with an incidence of 1 in 20,000 per year in childhood, and in adults as they are treated by various specialists, the epidemiologic data are scarce.[3] The etiology of LCH remains unknown. Various proposed hypothesis regarding the pathogenesis includes the altered immune responses, hypersensitivity reaction to an unknown antigen, and structural changes of the thymus, which ultimately leads to activation and proliferation of histiocyte macrophage system. However, a well satisfactory explanation was still lacking for the proliferation of LCs.[4],[5] Recently, the exploration of recurrent mutations in the mitogen-activated protein kinase pathway (i.e., BRAF and MAP2K1 mutations) indicates the possibility as a neoplastic disease.[6],[7]

The International Registry of Histiocyte Society proposed criteria for the diagnosis and clinical evaluation of LCH. The presence of Birbeck granules in the site of lesion/CD1a antigen determination on the surface of lesional cells confirms the definitive diagnosis of LCH.[8]

In oral cavity, LCH may manifest as single or multiple lesions and can be painful lesion affecting the alveolar or cortical bone and produce ulcerated mucosa lesions, lymphadenopathies, and periodontal lesions such as gingival inflammation, bleeding, recession, necrosis, dental mobility, and premature loss of teeth.[5] In this context, the role of a dental professional is critical in diagnosing such cases. The diagnosis of LCH is differentiated from periodontitis clinically by variation in the aggressiveness of disease presentation, correlation of gingival, and periodontal findings with local factors, gingival manifestations, radiographically by severity of bone loss, and floating teeth appearance.[9]

The course and predilection of untreated LCH vary from progressive to self-limiting lesion or fatal. The most commonly affected areas include bones (jaws), lungs, skin, mucous membranes, and other tissues.[1],[4] Salivary gland involvement by LCH is extremely rare, and only a few cases of LCH involving parotid gland were reported in literature.

We are here with report a classic case of LCH of periodontal tissues in an adult with multisystem involvement (lungs and sublingual glands).


   Case Report Top


A 31-year-old male patient, who is a software engineer by profession, reported to the outpatient department of periodontology, with a chief complaint of bleeding and pain in gums, along with burning sensation for 4 years. Medical history reveals no past exposure to any surgical interventions. No signs of pallor, icterus, clubbing, cyanosis, and edema were observed. No facial asymmetry or temporomandibular joint abnormalities were detected. The patient gave the history of smoking 3–5 packets of cigarettes per day for 15 years and was an occasional alcoholic. The patient provides the past history of visits to multiple private dental clinics and also underwent extraction of mandibular posterior teeth (35, 36, 37, 44, 45, 46) due to periodontal problems 2 years back. Later on, he presented with the loosening of adjacent teeth that aids in difficulty in chewing foods.

Clinical examination

Intraoral examination

Upon examination, oral hygiene was poor with hard deposits in the mandibular and left maxillary regions. On the labial aspect, gingiva was a fiery red with streaks evident on the mandibular buccal aspect extending from 34, 33, 32, 31, 41, 42, 43, 44. Keratinization and stippling were lost in those areas. There was a loss of interdental papillae in relation to 41, 42 and abscess in relation to 33, 34, 31, and 41 [Figure 1].
Figure 1: Ulcerated gingival in mandibular labial surface

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On the palatal aspect, ulcerated fiery red gingiva covered with pseudomembranous slough with exudation was evident on 26, 27, 28. There was a bilateral loss of mandibular posterior teeth. Multiple ulcerated areas were noticed in relation to 34, 33, 32, 31, 41, 42, 43, 44, 26, 27, and 28 with bleeding on provocation [Figure 2].
Figure 2: Fiery red gingiva with multiple ulcerations covered with pseudomembranous slough in maxillary left palatal surface

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On palpation, the affected areas were painful, with pus discharge 26–28, 34, 33, 32, 31, 41, 42, 43, 44. The periodontal examination showed deep pocketing (7–10 mm) in the left maxillary sextant 26, 27, and 28 and the mandible 31–34, 33, 32, 31, 41, 42, 43, 44. Gingival recession was seen in relation to 41, 42, 26, 27, and 28 with denudation of root surface. Segmental mobility was associated in the mandibular anterior region from 34, 33, 32, 31, 41, 42, 43, 44/along with Grade-II mobility in relation to 26, 27, and 28.

Radiographic examination

On radiographic examination, generalized bone loss in the mandibular region was evident from 34, 33, 32, 31, 41, 42, 43, 44, 46, 47, 26, 27, 28 with ill-defined margins and surrounded by areas of hyperdensity in mandibular posterior aspect. Apical resorption was noticed in relation to 34 [Figure 3].
Figure 3: Orthopantogram with generalized bone loss in mandible and left maxilla showing floating teeth bilaterally in mandibular premolar region

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Cone-beam computed tomography (CT) showed bone loss and resorption in the right and left mandible up to the level of the inferior alveolar nerve [Figure 4].
Figure 4: Cone-beam computed tomography reconstructed panoramic view showing bone loss in the right and left mandible up to the level of the inferior alveolar nerve

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Hematological and biochemical investigation reports showed the results within the normal range. (Hemoglobin% was 15.4 g/dl with normal total and differential count. Thyroid function and liver function were within normal limits. HIV, herpes simplex virus, and hepatitis C virus were nonreactive.

At the initial visit, scaling and root planing was performed; oral hygiene instructions were given (use of 3% hydrogen peroxide mouthwash). As the gingival findings were not consistent with periodontal findings, an incisional biopsy was performed under local anesthesia (lidocaine HCL 2% and epinephrine 1:100,000) in 34 region and subjected for histologic examination. A provisional diagnosis of necrotizing ulcerative periodontitis was made. In the 4 week recall evaluation, the patient reported with a reduction in the burning sensation, and there was no significant improvement in the periodontal status.

Histopathological findings

The biopsy specimen revealed malignant polyhedral cells with eosinophilic cytoplasm, hyperchromatic nuclei, and mitotic figures. Cells with clear cytoplasm and plasmacytoid features and occasional binucleated forms were evident. The surrounding fibrocellular and vascular connective tissue showed intense chronic inflammatory changes such as few perivascular plasma cells, eosinophils, and other inflammatory cells subepithelially. Overlying ulcerated epithelium exhibited mild dysplastic changes in focal areas. LCs characterized by abundant eosinophilic cytoplasm with cleaved, small reniform nuclei or with grooved, coffee bean nuclei were evident [Figure 5]. Immunohistochemical (IHC) analysis showed positivity for S-100 and CD 1A antigen and langerin [Figure 6].
Figure 5: H and E image showing inflammatory area with cluster of mononuclear and histiocytes (H and E, ×50)

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Figure 6: Immunohistochemical staining showing reactivity for (a) S-100; (b) Langerin; (c) CD 1A antigen with infiltrated Langerhans cells

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Based on the histological and IHC analysis, the diagnosis of LCH was confirmed.

Findings on positron emission tomography/computed tomography

F-fluoro-D-deoxyglucose positron emission tomography/CT revealed ill-defined soft-tissue thickening adjacent to the lower canine on the left side. Multiple cysts of varying sizes and few fibronodular densities were observed in the lungs. Hypertrophy of bilateral sublingual glands was noted which was suggestive of involvement and metabolic activity [Figure 7]. Further, the patient was referred to an oncologist for management and supportive care. With the history, clinical findings, and investigation, the diagnosis of LCH was confirmed. Under the medical oncology department, chemotherapy was started with initial treatment of corticosteroids – prednisone (40 mg.kg) repeated every 3 weeks. Vinblastine (VBL) 6 mg/m intravenous on day 1 repeated every 3 weeks (VBL/methotrexate [MTX]/6MP/Pred). Cycle 1/chemotherapy – injection-VBL 10 mg/day tablet prednisone 40 mg twice daily. A total of 16 cycles of chemotherapy was completed. The patient responded well and is presently under 1½ year follow-up with uneventful healing [Figure 8].
Figure 7: Positron emission tomography-computed tomography scan images Follow-up image showing regression of lesion on palatal aspect showing (a) multiple cysts of varying sizes and few fibronodular densities in both lungs; (b) hypertrophy of bilateral sublingual glands noted showing metabolic activity

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Figure 8: Follow-up image showing regression of lesion on palatal aspect

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   Discussion Top


LCH is mainly characterized by clonal proliferation of LCs, which are autologous to the cells present in the epidermis. LCs are derived from bone marrow and are located in suprabasal layers and the middle portion of the stratum spinosum of stratified squamous epithelium. This is indicated by the expression of CDla and S-100 and the ultrastructural presence of Birbeck granules in the LCH cells. The course of untreated LCH varies from self-limiting lesion to progressive or fatal outcome. The most commonly affected areas include bones (jaws), lungs, skin, mucous membranes, and other tissues.[1],[4] Pulmonary LCH is entitled separately in the classification, as it is mostly associated with cigarette smoking, a form of interstitial lung disease predominantly in adults.[10]

The diagnosis of LCH is difficult, and it is reported to be misdiagnosed, especially in the adult population. The possible differential diagnosis includes leukemia (acute myeloid leukemia) neutropenia, osteonecrosis of jaws, deep mycotic infections, hypophosphatasia, and necrotizing sialometaplasia. Acute myeloid leukemia presents with gingival hypertrophy and simulates as LCH. As the hematological findings on complete hemogram are within normal range, suspicion of leukemia was not considered. Whereas among neutropenic disorders, gingivitis and periodontal problems are common manifestations that are attributed to defective functioning of neutrophils which normally migrate to gingival crypts where bacteria tends to proliferate.[11]

Based on the histological and immunohistochemistry findings, the present case was diagnosed as adult LCH-X with multisystem involvement (lungs and sublingual glands).

The treatment of LCH is dependent on the site, size, degree of involvement, and whether it is unifocal or multifocal. Therapy includes surgery, radiation, and chemotherapy; either individually or in combination, is most indicated. For more disseminated cases, chemotherapy (MTX and VBL with prednisone) is usually recommended.[12] As in the present case, there was multifocal and systemic involvement chemotherapy was instituted to the patient after referral to the higher center (medical oncologist).

With progression in the systemic involvement of organs, there will be a limited treatment response and the prognosis becomes worse. The present case has responded well to chemotherapy, with a regression of oral lesions with a reduction in tooth mobility. There was a complete regression in soft-tissue thickening in the oral site. Multiple cysts with interstitial thickening in both lungs remain static. Significant metabolic and morphologic regression was noticed in sublingual glands. The patient was advised to refrain from smoking and alcohol consumption. The patient was under observation and supportive care for further dental treatment.

In the present case, LCH was unrecognized and overlooked over the course of a few years with impact on patient's psychological and social consequences, resulting in functional impairment. Adversely, there was a rapid progression of the periodontal disease, leading to the loss of dentition and further systemic involvement. Periodic supervision of the oral manifestations of disease possibly allowed early detection of LCH.


   Conclusion Top


LCH is a diagnostic challenge for a periodontist because its features could simulate periodontal disease. Therefore, recognition of the clinical features of LCH is essential to avoid misdiagnosis and to render a correct multidisciplinary approach in the diagnosis and clinical management of this rare entity.

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.

Acknowledgement

We would like to acknowledge Dr. Vandana Raghunath Prof and HOD Department of oral pathology and Dr.Vindya Vasini (Oncolgist).

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

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2.
Annibali S, Cristalli MP, Solidani M, Ciavarella D, La Monaca G, Suriano MM, et al. Langerhans cell histiocytosis: Oral/periodontal involvement in adult patients. Oral Dis 2009;15:596-601.  Back to cited text no. 2
    
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Krooks J, Minkov M, Weatherall AG. Langerhans cell histiocytosis in children: History, classification, pathobiology, clinical manifestations, and prognosis. J Am Acad Dermatol 2018;78:1035-44.  Back to cited text no. 3
    
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Muzzi L, Pini Prato GP, Ficarrat G. Langerhans' cell histiocytosis diagnosed through periodontal lesions: A case report. J Periodontol 2002;73:1528-33.  Back to cited text no. 4
    
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Neves-Silva R, Fernandes DT, Fonseca FP, Rebelo Pontes HA, Brasileiro BF, Santos-Silva AR, et al. Oral manifestations of Langerhans cell histiocytosis: A case series. Spec Care Dentist 2018;38:426-33.  Back to cited text no. 5
    
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Abla O, Rollins B, Ladisch S. Langerhans cell histiocytosis: Progress and controversies. Br J Haematol 2019;187:559-62.  Back to cited text no. 6
    
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Brown NA, Furtado LV, Betz BL, Kiel MJ, Weigelin HC, Lim MS, et al. High prevalence of somatic MAP2K1 mutations in BRAF V600E-negative Langerhans cell histiocytosis. Blood 2014;124:1655-8.  Back to cited text no. 7
    
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Aricò M, Girschikofsky M, Généreau T, Klersy C, McClain K, Grois N, et al. Langerhans cell histiocytosis in adults. Report from the International Registry of the Histiocyte Society. Eur J Cancer 2003;39:2341-8.  Back to cited text no. 8
    
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Zaveri J, La Q, Yarmish G, Neuman J. More than just Langerhans cell histiocytosis: A radiologic review of histiocytic disorders. Radiographics 2014;34:2008-24.  Back to cited text no. 9
    
10.
Radzikowska E. Pulmonary Langerhans' cell histiocytosis in adults. Adv Respir Med 2017;85:277-89.  Back to cited text no. 10
    
11.
Emile JF, Abla O, Fraitag S, Horne A, Haroche J, Donadieu J, et al. Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages. Blood 2016;127:2672-81.  Back to cited text no. 11
    
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Monsereenusorn C, Rodriguez-Galindo C. Clinical characteristics and treatment of Langerhans cell histiocytosis. Hematol Oncol Clin North Am 2015;29:853-73.  Back to cited text no. 12
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]



 

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