Keywords Langerhans cell histiocytosis - mandible - periostitis
Introduction
Langerhans cell histiocytosis (LCH) is an uncommon hematological disorder affecting
infants and young children.[1 ] LCH, previously termed as histiocytosis X, is characterized by an uncontrolled stimulation
and proliferation of normal antigen presenting cells, Langerhans cells, and mature
eosinophils.[2 ] The term histiocytosis refers to the proliferation of histiocytes and other inflammatory
cells, and “X” was added to denote the unknown cause of the disease. The accumulation
of the pathological Langerhans cells causes infiltration and destruction of the local
tissues.[3 ] The incidence of LCH is relatively low with an estimation of 2–5 cases per million
per year.[1 ]
LCH mainly comprises of three morphologically similar lesions, namely eosinophilic
granuloma, Hand–Schuller–Christian syndrome, and Letterer–Siwe syndrome classified
by Lichtenstein in the year 1953.[3 ]
[4 ] The cause of this disease is not clearly known; however, there is evidence that
the disorder is a presentation of an immunological variation.[5 ] In this article, we report a case of LCH involving the mandible with an overt swelling
of one side of the face which was diagnosed with the help of imaging modalities and
histopathological investigation.
Case Report
A 5-year-old girl reported to the department of oral medicine and radiology with a
chief complaint of swelling in the left side of the face since 1 and ½ months. The
patient complained of pain in the same region during mouth opening and on chewing.
The patient’s parents gave a history of consulting local doctor for the same where
antibiotics and analgesics were prescribed. Swelling persisted even after medications.
On extraoral examination, a solitary diffuse swelling was noticed on the left side
of the face measuring around 6 cm × 5 cm in size extending superoinferiorly from the
ala-tragal line to the inferior border of the mandible, mediolaterally from the left
commissure of the mouth to the preauricular area [Figure 1a ]. Swelling was firm in consistency and tender on palpation. Local rise in temperature
was present. Solitary right and left submandibular lymph nodes were palpable, firm
in consistency, mobile, and nontender. On intraoral examination, obliteration of the
buccal vestibule was noted in the left posterior mandibular region [Figure 1b ]. On palpation, tenderness was present in the distal aspect of the deciduous left
mandibular second molar region and ascending body of the ramus region. Expansion and
perforation was present in the medial and lateral aspect of the ascending body of
the ramus of the mandible. Laboratory investigation was within normal limits.
Figure 1: (a) Extraoral swelling on the middle and lower one-third of the face right
side. (b) Intraoral obliteration of the buccal vestibule was noted in the left posterior
mandibular region
Panoramic imaging showed an ill-defined osteolytic lesion extending from the distal
aspect of tooth bud of mandibular left permanent second molar till the coronoid process
and sigmoid notch of the mandible [Figure 2 ]. Computed tomography (CT) scan of the patient showed areas of ill-defined destruction
and pathologic fracture of the ramus of the mandible. Aggressive periosteal reaction
was noted giving a sun ray-like appearance [Figure 3 ].
Figure 2: Panoramic imaging showed an ill-defined osteolytic lesion extending from
the distal aspect of tooth bud of mandibular left permanent second molar till the
coronoid process and sigmoid notch of the mandible
Figure 3: (a) Axial, (b) Sagittal and (c) Coronal sections of computed tomography
scan showing areas of ill-defined destruction and pathologic fracture of the ramus
of the mandible. Also aggressive periosteal reaction can be noted giving a sun ray-like
appearance
Based on the age, rapidly aggressive nature, clinical presentation, and radiological
features, a differential diagnosis of LCH, Ewing’s sarcoma, and nonsuppurative osteomyelitis
was considered.
Histopathological examination of incisional biopsy specimen showed extensive proliferation
of histiocytes with indistinct cytoplasmic borders and rounded vesicular nuclei with
interspersed eosinophils suggestive of LCH [Figure 4a ]. Immunohistochemistry showed positivity for CD68, CD1a, and S-100 confirming the
diagnosis [Figure 4b ] and [c ]. Positron emission tomography revealed no active lesion elsewhere in the body.
Figure 4: (a) Histopathological picture showing extensive proliferation of histiocytes
with indistinct cytoplasmic borders and rounded vesicular nuclei with interspersed
eosinophils suggestive of Langerhans cell histiocytosis . (b and c) Immunohistochemistry
showed positivity for CD68, CD1a, and S-100 confirming the diagnosis
The patient was treated with surgical corticotomy under general anesthesia of the
affected side with extraction of the left mandibular second and third molar tooth
buds. The patient is currently under periodic follow-up.
Discussion
Histiocytosis is a term that refers to a group of rare disorders of the reticuloendothelial
system. LCH is associated with proliferation of specialized bone marrow-derived antigen
presenting dendritic cells, namely the Langerhans cells and mature eosinophils.[2 ] Since the proliferating histiocytes involved in LCH are phenotypically similar to
that of the Langerhans cells found in the normal mucosa and skin, the condition was
named as LCH.[3 ]
[6 ]
Various hypotheses have been proposed explaining the etiology of LCH. The presence
of inclusion bodies resembling the Birbeck granules of Langerhans cells classifies
LCH as a proliferative disorder of the Langerhans cells or their marrow derivatives.[4 ] Studies have also shown that LCH is a reactive disease that may result from environmental
or other triggering factors, which leads to the aberrant reaction between Langerhans
cell and T-lymphocytes.[7 ]
LCH is more frequent in males than in females with a ratio ranging from 1.1:1 to 4:1.[4 ] It predominantly affects children and young adults.[4 ]
[5 ]
[6 ] The present case was reported in a 5-year-old girl.
Eosinophilic granuloma of the monostatic and multifocal form is a type of LCH which
affects children and young adults and manifests as solitary or multiple skeletal lesions
without extraskeletal involvement. The chronic and disseminated form of LCH termed
as the Hand–Schuller–Christian syndrome consists of skeletal and extraskeletal lesions
usually affecting children below 3 years of age. The Letterer–Siwe syndrome is a disseminated
acute or subacute form of LCH, that is, most often fatal because of extensive skeletal
and extraskeletal lesions; this form usually affects infants and children below 3
years of age.[3 ]
[4 ] The present case represents monostotic eosinophilic granuloma of the mandible.
The relative incidence of organ system involvement in LCH is as follows: bone in 80%
of the cases; skin 60% of the cases; liver, spleen, and lymph nodes 33%; lungs and
orbit in around 25% of the cases; and maxillofacial in around 25% of the cases.[1 ] Skeletal involvement can involve any bone, but the most common are pelvis, ribs,
skull, long bones, vertebra, and facial bones.[4 ] In the skull, frontal and parietal bones are commonly involved followed by the jaws.[7 ]
[8 ] Mandible is more commonly involved when compared to the maxilla.[2 ] In the present case, only the posterior aspect of the mandible was involved.
A literature search for case reports consisting of the following words “’Langerhans
cell histiocytosis of the jaw” and “eosinophilic granuloma of the jaw” for the past
10 years was carried out in PubMed database which reported 38 cases of LCH of the
jaw. It consisted of 12 cases below the age of 10 years, 6 cases between the age groups
of 11–20 years, and 13 cases above the age group of 20 years. Out of the 38 cases,
information regarding the age for 7 cases were unavailable. Only mandible was involved
in 25 [68%] cases, maxilla alone was involved in 6 (15.7%) cases, and both maxilla
and mandible were involved in 4 (10.52%) cases, and in 3 cases, the site involved
was not specified [Table 1 ].
Table 1
Clinical characteristics (age and site) of cases of LCH of jaw reported in PubMed
in the last 10 years
Author name
Number of cases reported
Age
Site
*Details could not be accessed or were not available
Varsha et al. 2016[9 ]
1
Child aged 4 year
Hard palate
Vargas et al. 2016[10 ]
1
Adolescent aged 16 years
Maxilla
Fiorini et al. 2016[11 ]
1
*
Mandible
Xian et al. 2015[12 ]
1
Adult patient
Mandibular condyle
Emmanouil et al. 2015[13 ]
1
Child aged 8 years
Hand-Schuller-Christian syndrome
Vennamaneni et al. 2015[14 ]
1
Adult aged 29 years
Mandible
Sherwani et al. 2014[15 ]
1
Child aged 4 years
Mandible
Liu et al. 2014[16 ]
1
Infant aged 21 months
Hard palate
Zajko 2013[17 ]
1
Adult aged 45 years
Mandible
Felstead et al. 2013[18 ]
1
*
Mandible
Alshadwi et al. 2013[19 ]
1
Infant
Mandible
Terada et al. 2013[20 ]
1
Adult aged 46 years
Maxilla and mandible
Lee and Yoon 2012[21 ]
1
*
Two cases reported in mandible
Ge et al. 2012[22 ]
1
Adult aged 34 years
Mandible
Yepes et al. 2012[23 ]
1
Adult aged 23 years
Mandibular condyle
Lajolo et al. 2012[24 ]
2
a. Adult aged 71 years
a. Mandible
b. Adult aged 77 years
b. Hard palate
Shetty et al. 2012[25 ]
1
Child aged 14 years
Bilateral maxilla
Aydin et al. 2012[26 ]
1
Adult aged 45 years
Mandible
Anastasilakis et al. 2012[27 ]
1
Adult aged 21 years
Mandible
Martin et al. 2011[28 ]
1
Infant aged 4 months
Mandible
Murray et al. 2011[29 ]
1
Infant aged 22 months
Maxilla, mandible, and hard palate
Bas et al. 2011[30 ]
1
Child aged 7 years
Mandible
Dholam et al. 2011[31 ]
1
Child aged 12 years
Mandible
Alloh Amichia et al. 2010[32 ]
1
*
Jaw
Muramatsu et al. 2010[33 ]
1
Infant aged 13 months
Mandible
Park and Chung 2010[34 ]
1
Child aged 1 year
Mandibular condyle
Gaundong Mbéthé et al. 2010[35 ]
2
*
Jaw
Altug et al. 2010[36 ]
1
Adult aged 20 years
Mandible
Esen et al. 2010[37 ]
1
*
Mandible
Bouw and Nout 2009[38 ]
1
Infant aged 6 months
Maxilla
Rees and Paterson 2009[39 ]
1
Adult aged 31 years
Jaw
Helbling-sieder et al. 2009[40 ]
1
Adult aged 27 years
Mandible
Guiglia et al. 2009[41 ]
1
Child aged 13 years
Mandible
Orzechowska-Wylegala et al. 2008[42 ]
2
a. Adult aged 28 years
a. Mandible
b. Child aged 2 years
b. Maxilla, mandible
In a review of 1120 patients, oral involvement was reported in around 10% of the cases.[43 ] Intraorally, it usually appears as a soft-tissue swelling or ulceration of the gingiva.[44 ] The most common site is the mandibular molar area, followed by the ramus region.[2 ] In the present case, obliteration of the buccal vestibule with no surface ulceration,
discharge, or bony exposure was noticed.
Destruction of the lamina dura, floating teeth appearance indicative of destruction
of alveolar bone is evident on radiographs.[2 ] Other radiographic features include localized, punched-out radiolucencies with no
evidence of calcification and sclerosis.[4 ] Mandibular lesions are ill-defined with single or multiple punched-out radiolucencies
without corticated rimming suggestive of active disease.[1 ] Radiographically, eosinophilic granuloma typically presents as punched-out osteolytic
lesions with or without periosteal reaction.[45 ] These radiological features are present due to the destruction caused by the Langerhans
cells which may cause pathological fracture of the bone.[1 ] In the present case, it manifested as an osteolytic ill-defined lesion with pathological
fracture and periosteal reaction.
Based on the age, rapidly aggressive nature, clinical presentation, and radiological
features, a differential diagnosis of Ewing’s sarcoma, LCH, and nonsuppurative osteomyelitis
was considered. Both Ewing’s sarcoma and LCH show similar radiological appearance.
Ewing’s sarcoma usually affects long bone and very rarely affects the mandible. The
other possible diagnosis is nonsuppurative osteomyelitis based on the history of trauma,
nature of the lesion, and moth-eaten appearance of the mandibular ramus area noticed
in the CT scan.
Histopathologically, LCH presents as a diffuse infiltration of pale-staining mononuclear
cells that resemble histiocytes with indistinct cytoplasmic borders and rounded vesicular
nuclei. Multiple eosinophils can be seen typically interspersed among the histiocytes,
plasma cells, lymphocytes, and multinucleated giant cells.[46 ] In the present case, similar histopathological features were noticed.
On immunohistochemistry, LCH is positive for S-100 and anti-CD-1a, which was also
seen in the present case.[6 ] LCH is characterized by antigen Ki-67 that selectively binds to a nuclear antigen
which is only expressed by proliferating cells.[6 ]
Treatment modalities available for LCH depend on the site of the lesion, its extent,
and the number of lesions present. Depending on this either surgical curettage, radiotherapy
or chemotherapy can be used alone or in combination.[47 ]
[48 ] In the present case, as the lesion was unifocal and involved only mandible, surgical
curettage was carried out. However, if there are multifocal involvement and associated
systemic disease, chemotherapy should be considered. Recurrence rates around 1.6%
to 25% are noticed, and a close and regular follow-up for a long period is advised.[4 ]
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.
