Logo American Journal of Case Reports

Call: 1.631.629.4328
Mon-Fri 10 am - 2 pm EST

Contact Us

Logo American Journal of Case Reports Logo American Journal of Case Reports Logo American Journal of Case Reports

24 November 2020: Articles  Saudi Arabia

Incidental Diagnosis on Orthopantomography of Langerhans Cell Histiocytosis with Multifocal Jaw Involvement: A Case Report of Single-System Disease

Unusual clinical course, Challenging differential diagnosis

Amr S. Bugshan1ABCD, Mohammed A. Alsaati2BDE, Faiyaz A. Syed1CEF, Khalid S. Almulhim3EFG*, Adel I. Abdulhady1CDE

DOI: 10.12659/AJCR.928307

Am J Case Rep 2020; 21:e928307

0 Comments

Abstract

BACKGROUND: Langerhans cell histiocytosis (LCH) is a relatively rare neoplasm with a strong inflammatory component. It has diverse clinical manifestations, which range from a single lesion or multiple bony lesions to severe multisystem involvement. Approximately 10% to 20% of cases of LCH occur in the jaw, with the posterior mandible being the site most frequently involved.

CASE REPORT: We report on the case of a 42-year-old man who presented with bilateral osteolytic lesions in the posterior mandible that were incidentally discovered during routine radiographic screening. Histological examination of the specimen confirmed the diagnosis of LCH.

CONCLUSIONS: This case illustrates the importance of orthopantomography (OPG) as a screening tool in new patients to perform an overall evaluation of the teeth and surrounding structures, such as the bone, temporomandibular joint, and sinuses. Moreover, OPG can be used to screen for the presence of asymptomatic lesions that are often diagnosed incidentally on radiographs.

Keywords: Diagnosis, Oral, Histiocytosis, Jaw Diseases, Langerhans cells, Osteolysis, Adult, Histiocytosis, Langerhans-Cell, Mass Screening, Radiography, Panoramic

Background

Langerhans cells (LCs) are inflammatory dendritic cells that are derived from the bone marrow, migrate through the bloodstream to the epidermis of the skin and the epithelium of oral mucosa, and play an important role in development of local immune response [1]. These cells belong to the antigen-presenting cell family, which processes and presents foreign bodies (antigens) to T-cell lymphocytes and initiates adaptive immune response [1].

In the oral cavity, improper function or abnormal proliferation of LCs is associated with the initiation or development of various oral diseases, such as periodontitis, candidiasis, lichen planus, squamous cell carcinoma, and Langerhans cell histiocytosis (LCH) [2].

LCH is characterized by abnormal proliferation of LCs. Clinically, its presentation can range from affecting only a single system such as the skin or bone to a life-threatening multisystem disease that involves other organs, including the lungs, spleen, bone marrow, and liver [3]. The incidence of LCH in adults ranges from 1 to 2 cases per million, with a male predilection and a mean age at diagnosis of 35 years [4].

There is much debate about whether LCH represents a reactive process or a neoplasm. The monoclonal proliferation of LCs in addition to the somatic mutations in mitogen-activated protein kinase genes, such as BRAF V600E and MAP2K1, support an underlying neoplastic process [5,6].

LCH in the oral cavity may be the first presenting sign before the disease becomes apparent elsewhere in the body [7]. The posterior mandible is the site most commonly affected [8]. Advanced jaw lesions may perforate the bone and present as either ulcerative lesions or as gingival masses [9].

Radiographically, LCH presents as non-corticated, well-defined radiolucent areas around the teeth, resulting in a “floating-inair” appearance. Histopathological examination is essential to confirm the diagnosis [8].

Treatment depends on the extent of the lesions. Accessible jaw lesions are conventionally treated with curettage, whereas low-dose radiation can be considered for inaccessible lesions [9]. Intralesional steroid injection is also effective in some cases [10].

In this paper, we report on a case of oral LCH, emphasizing the radiographic and histopathological findings and differential diagnoses of the disease.

Case Report

HISTORY AND CLINICAL EXAMINATION:

A 42-year-old man presented with a chief complaint of missing teeth, which he wanted to restore. The patient’s medical history was not significant, and he denied taking any medications. Extraoral findings were unremarkable. Intraoral examination revealed multiple missing teeth, multiple remaining roots, and generalized moderate gingival inflammation with grade III mobility of the mandibular posterior teeth bilaterally. The patient denied tooth sensitivity or pain.

RADIOGRAPHIC FINDINGS: An orthopantomogram (OPG) showed bilateral, well-demarcated radiolucent (geographic pattern) lesions eroding the mandibular bodies in the premolar/molar areas with complete loss of alveolar supporting bone around the mandibular posterior teeth. One lesion epicenter was at the mid-root level. Another radiolucent lesion was noted on the right maxilla distal to the canine. There was no clear evidence of root resorption or displacement or of septation of calcifications (Figure 1A). Only multiple small, periapical odontogenic lesions in the mandibular left premolars and right molar were observed, compared with an OPG taken 2 years earlier (Figure 1B).

A multi-detector computed tomography (CT) scan performed with bone window settings showed multiple non-expansible osteolytic (scooped-out shape) lesions associated with multiple floating teeth on the right anterior maxilla and bilaterally on the mandible. There was no evidence of calcification or septation (Figure 2A). The adjacent labial and buccal soft tissue and fat planes were preserved with no evidence of fat stranding or drainable collection. A CT scan performed after injection of iodine) showed no evidence of abnormal intralesional enhancement. There was no clear evidence of periosteal bone reaction. A whole-body (planar) CT scan and limited field of view, single-photon emission CT (SPECT-CT) scan were performed. The whole-body image showed increased up-take in both mandibular bodies, extending to the angle of the mandible (Figure 2B). There was no other uptake in the rest of the body. The SPECT-CT scan showed intense localized osseous uptake in the same areas in the right anterior maxilla and the mandible bilaterally, indicating a high level of metabolic activity (Figure 2C).

DIFFERENTIAL DIAGNOSIS: Given the location of these lesions within the jaws (mid-root epicenter), punched-out radiolucent density, and the radio-graphic “floating- in-air” appearance of the teeth, LCH was considered the most likely diagnosis [8]. Other conditions were included n the differential diagnosis because of radio-graphic appearances.

Primary intraosseous squamous cell carcinoma of the jaws was considered because of the rapid and aggressive bone destruction and the radiographic presentation of ill-defined radiolucent lesions [11]. The radiographic appearance of lytic radiolucent lesions with ill-defined margins raised the suspicion of malignancy [12]. Leukemia and lymphoma can present as multifocal intraosseous radiolucent lesions that tend to grow within the periodontal ligament spaces [13]. Ewing sarcoma can appear as aggressive intraosseous lesions with poor demarcated borders in posterior areas of both jaws [8]. Because calculus deposits were absent on radiography and the epicenters of the lesions were at the mid-root level, aggressive periodontal disease was considered the least likely diagnosis.

LABORATORY INVESTIGATIONS:

A complete blood count was performed as well as testing for levels of triiodothyronine, thyroid stimulating hormone, free thyroxine, immunoglobulin (Ig) A, IgG, IgE, and alkaline phosphatase; erythrocyte sedimentation rate; minerals (sodium, potassium, and chloride); and renal and liver function. None of the results were significant for any underlying medical conditions.

HISTOPATHOLOGICAL FINDINGS: Microscopic examination revealed a diffuse infiltrate of large cells with pale, eosinophilic cytoplasm intermixed with inflammatory cells that were predominantly composed of eosinophils. Immunohistochemical staining showed numerous large cells that exhibited immunoreactivity to CD1a, CD68, and S-100 antibodies (Figure 3).

DIAGNOSIS:

The clinical, radiographic, and microscopic findings confirmed the diagnosis of single-system LCH with multifocal jaw involvement. The patient was referred to an oncology center to start appropriate treatment.

Discussion

LCH (previously known as histiocytosis X) can present in 3 different clinical forms, the most common (70%) and least aggressive of which is eosinophilic granuloma. Hand-Schüller-Christian disease is the chronic recurring form of multifocal LCH, with a triad that consists of diabetes insipidus, skull lesions, and exophthalmos. Letterer-Siwe disease, the most severe form of LCH, constitutes approximately 10% of cases and patients with it have multifocal, multisystem involvement [14].

Faber and Green observed that the different clinical forms of LCH had similar features on radiographic and histologic examination [15]. In 1953, Lichenstein and Jeffe grouped the different clinical forms under the term histiocytosis X, with the X denoting the uncertainty about the cell of origin [16]. The development of electron microscopy made it possible to identify intracytoplasmic rod- or tennis racquet-shaped organelles, called Birbeck granules. These were found specifically in normal epidermal LCs and were a pathognomonic feature of histiocytosis X lesions, thus establishing a histogenic relationship between the 2. Accordingly, histiocytosis X was renamed LCH [17].

In a retrospective study, the radiographic features of the disease in the jaws were reviewed in 29 patients diagnosed with histiocytosis X. The authors reported 7 characteristics that may be helpful in histiocytosis X identification: unifocal “intraosseous” lesions, multifocal “alveolar bone” lesions, the “scooped-out” appearance in the alveolar process, well-defined radiolucency, prelesional sclerosis in the alveolar bone, new bone formation of the periosteum, and root resorption [18]. Hartman et al. retrospectively investigated 114 patients with histiocytosis X who had oral involvement. They found that jaw swelling and a palpable mass were the most common soft tissue manifestations. Other presenting symptoms were mobility of adjacent teeth and pain [19].

In our case, there were no signs of aggressive alveolar bone destruction on either the right or left side of the mandible in the radiograph that had been taken 2 years earlier, nor was there bone loss distal to the right maxillary canine. Repeating the OPG revealed geographic bony destruction of the maxilla and both sides of the mandible, with the teeth appearing to float. This shows that taking dental radiographs serves to not only evaluate general dental health but also as a baseline record with which to monitor the development, progress, and aggressiveness of bony lesions of the jaw. Our patient is undergoing intralesional steroid injections, which have produced positive outcomes in several cases of mandibular LCH [20].

Lesions of the gingiva, jawbones, and teeth are seen as the first manifestation or a complication of LCH [21]; therefore, dentists can play an important role in the early detection and treatment of the disease, which would lead to better management.

According to the International Histiocyte Society Registry, 68% of adults with LCH had involvement in more than 1 system. Thus, dentists have a responsibility to refer patients with symptoms of LCH to a physician for a thorough systemic evaluation for possible multiorgan involvement [4].

Conclusions

Although rare, LCH should be considered in the differential diagnosis when an OPG shows “floating teeth.” In such cases, full-body imaging must be performed to check for lesions in other organs. Therefore, treating a patient without taking a current dental radiograph that includes OPG can lead to mis-diagnosis, delayed diagnosis, and mismanagement. Early diagnosis of LCH will not only prevent the progression of the disease but also avert further complications.

References:

1.. Jaitley S, Saraswathi T, Pathophysiology of Langerhans cells: J Oral Maxillofac Pathol, 2012; 16(2); 239-44

2.. Lombardi T, Hauser C, Budtz-Jorgensen E, Langerhans cells: Structure, function and role in oral pathological conditions: J Oral Pathol Med, 1993; 22(5); 193-202

3.. Simko SJ, Garmezy B, Abhyankar H, Differentiating skin-limited and multisystem Langerhans cell histiocytosis: J Pediatr, 2014; 165(5); 990-96

4.. Arico M, Girschikofsky M, Genereau T, Langerhans cell histiocytosis in adults. Report from the International Registry of the Histiocyte Society: Eur J Cancer, 2003; 39(16); 2341-48

5.. Roden AC, Hu X, Kip S, BRAF V600E expression in Langerhans cell histiocytosis: clinical and immunohistochemical study on 25 pulmonary and 54 extrapulmonary cases: Am J Surg Pathol, 2014; 38(4); 548-51

6.. Allen CE, Merad M, McClain KL, Langerhans-cell histiocytosis: N Engl J Med, 2018; 379(9); 856-68

7.. Altay MA, Sindel A, Ozalp O, Langerhans cell histiocytosis: A diagnostic challenge in the oral cavity: Case Rep Pathol, 2017; 2017; 1691403

8.. Mallya SM, Lam EWN: White and Pharoah’s oral radiology: Principles and interpretation, 2018; ix; 659

9.. Neville BW, Damm DD, Allen CM, Chi AC: Oral and maxillofacial pathology, 2016, St. Louis, Missouri, Elsevier https://www.clinicalkey.com/dura/browse/bookChapter/3-s2.0-C20110077025

10.. Putters TF, de Visscher JG, van Veen A, Spijkervet FK, Intralesional infiltration of corticosteroids in the treatment of localised langerhans’ cell histiocytosis of the mandible Report of known cases and three new cases: Int J Oral Maxillofac Surg, 2005; 34(5); 571-75

11.. Huang JW, Luo HY, Li Q, Li TJ, Primary intraosseous squamous cell carcinoma of the jaws. Clinicopathologic presentation and prognostic factors: Arch Pathol Lab Med, 2009; 133(11); 1834-40

12.. Hirshberg A, Berger R, Allon I, Kaplan I, Metastatic tumors to the jaws and mouth: Head Neck Pathol, 2014; 8(4); 463-74

13.. Damante JH, Casati Alvares L, Montenegro Chinellato LE, Eosinophilic granuloma of mandible. Report of a case with a 7-year follow-up: Oral Surg Oral Med Oral Pathol, 1981; 51(4); 456-59

14.. Naik M, Mehta A, Mehrotra N, Solanki A, Isolated Langerhans cell histiocytosis of orbit: A case report and review of the literature: Case Rep Ophthalmol Med, 2018; 2018; 1529281

15.. Green W, Farber S, Eosinophilic or solitary granuloma of bone: J Bone Joint Surg, 1942; 499-526

16.. Lichtenstein L, Jeffe HL, Eosinophilic granuloma of bone: With report of a case: Am J Pathol, 1940; 16(5); 595-604

17.. Nezelof C, Basset F, Rousseau MF, Histiocytosis X histogenetic arguments for a Langerhans cell origin: Biomedicine, 1973; 18(5); 365-71

18.. Dagenais M, Pharoah MJ, Sikorski PA, The radiographic characteristics of histiocytosis X. A study of 29 cases that involve the jaws: Oral Surg Oral Med Oral Pathol, 1992; 74(2); 230-36

19.. Hartman KS, Histiocytosis X, A review of 114 cases with oral involvement: Oral Surg Oral Med Oral Pathol, 1980; 49(1); 38-54

20.. Almuzayyen A, Elhassan W, Alabbadi M, Intralesional triamcinolone for treating mandibular langerhans cell histiocytosis: A case report and literature review: Saudi J Med Med Sci, 2019; 7(1); 47-50

21.. Sigala JL, Silverman S, Brody HA, Kushner JH, Dental involvement in histiocytosis: Oral Surg Oral Med Oral Pathol, 1972; 33(1); 42-48

SARS-CoV-2/COVID-19

30 June 2022 : Editorial  USA

Editorial: World Health Organization (WHO) Variants of Concern Lineages Under Monitoring (VOC-LUM) in Respo...

Med Sci Monit In Press; DOI: 10.12659/MSM.937676  

29 June 2022 : Case report  USA

A Clinical Case of COVID-19 Vaccine-Associated Guillain-Barré Syndrome

Am J Case Rep In Press; DOI: 10.12659/AJCR.936896  

16 June 2022 : Case report  Ecuador

Multidrug-Resistant Klebsiella pneumoniae in a Patient with SARS-Cov-2 Pneumonia in an Intensive Care Unit ...

Am J Case Rep In Press; DOI: 10.12659/AJCR.936498  

13 June 2022 : Case report  Japan

Stenotrophomonas maltophilia Infection Associated with COVID-19: A Case Series and Literature Review

Am J Case Rep In Press; DOI: 10.12659/AJCR.936889  

In Press

30 Jun 2022 : Case report  Philippines

Erasmus Syndrome: A Case Report and Literature Review

Am J Case Rep In Press; DOI: 10.12659/AJCR.937061  

30 Jun 2022 : Case report  USA

A Clinical Case of COVID-19 Vaccine-Associated Guillain-Barré Syndrome

Am J Case Rep In Press; DOI: 10.12659/AJCR.936896  

30 Jun 2022 : Case report  China (mainland)

Septic Shock Induced by Acute Pyelonephritis Resulting from Kidney Stones Treated by Double-J Ureteral Sten...

Am J Case Rep In Press; DOI: 10.12659/AJCR.936967  

29 Jun 2022 : Case report  Kuwait

A Challenging Case of Jejunal Dieulafoy’s Lesion: A Rare Cause of Refractory Lower-Gastrointestinal Bleeding

Am J Case Rep In Press; DOI: 10.12659/AJCR.936313  

Most Viewed Current Articles

23 Feb 2022 : Case report  USA

Penile Necrosis Associated with Local Intravenous Injection of Cocaine

DOI :10.12659/AJCR.935250

Am J Case Rep 2022; 23:e935250

17 Feb 2022 : Case report  Oman

Myocarditis, Pulmonary Hemorrhage, and Extensive Myositis with Rhabdomyolysis 12 Days After First Dose of P...

DOI :10.12659/AJCR.934399

Am J Case Rep 2022; 23:e934399

06 Dec 2021 : Case report  Brazil

Lipedema Can Be Treated Non-Surgically: A Report of 5 Cases

DOI :10.12659/AJCR.934406

Am J Case Rep 2021; 22:e934406

09 Feb 2022 : Case report  Saudi Arabia

Extensive Cerebral Venous Sinus Thrombosis (CVST) After the First Dose of Pfizer-BioNTech BNT162b2 mRNA COV...

DOI :10.12659/AJCR.934744

Am J Case Rep 2022; 23:e934744

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

American Journal of Case Reports eISSN: 1941-5923
American Journal of Case Reports eISSN: 1941-5923