Solitary langerhans cell histiocytosis in an adult: case report and literature review

Histiocytosis comprises a diverse group of proliferative disorders characterized by
the infiltration and accumulation of histiocytes and other immune effector cells within
various tissues 2]. Historically, the nomenclature regarding this entity has been confused. The disease
had been subcategorized based upon different clinical manifestations, such as Histiocytosis
X, Letterer-Siwe disease, Hand-Schuller-Christian syndrome and Eosinophilic Granuloma
of bone. The Histiocyte Society proposed the reclassification of histiocytosis based
upon the predominant cell type within the infiltrate. The classification system includes
four divisions: dendritic disorders (including LCH), macrophage-related disorders,
malignant histiocytic disorders and dendritic cell or macrophage-related histiocytic
sarcoma 2], 3]. The LCH etiology has been discussed for many years and its reactive nature is suggested.
Clonal proliferation has been reported with the presence of BRAF V600E oncogenic mutation
in more than half of patients with LCH, which suggests a neoplasm 4], 6]. LCH is a rare disease with a wide variety of clinical presentations. Its course
may damage different tissues, including the periodontal bone and gingiva. In addition,
one of the types of LCH can lead to death 4], 5]. In our specific case, the patient had a lesion that mimicked periodontal disease
associated with an oral squamous cell carcinoma or carcinomatous lesion.

LCH in adults has been reported at an incidence of 1:1,000,000 and a mean age of presentation
of 34 years and is usually a multisystem disease. Childhood LCH has a reported incidence
of 1:200,000, peaking between ages 1–4 years 3], 6]. In children, an association between high concentrations of salivary IL-1 ? and PGE(2)
and advanced stages of LCH have been observed, suggesting that the abnormal amount
of these factors in the saliva may be a risk marker for disease progression 7].

Our case was distinct to most reported cases in the literature, since the patient
was a 63-year-old man who did not show any bone or organ involvement other than the
maxilla. Despite the strong possibility of pulmonary manifestation, due to the duration
time of time that he had been a smoker, there was no evidence of pulmonary involvement.
The chest x-ray confirmed this fact. However, experimental studies have shown that
cigarette exposure is associated with pulmonary inflammation 8]. Interestingly, most LCH bone lesions that have been described in the literature
were present in the skull, spine, or mandible 9]. In our case, the lesion was located only in the maxilla. Bone scintigraphy was determinant
to show the unique bony involvement.

Diabetes insipidus (DI) is the most common endocrine abnormality, reported in 5–50 %
of patients with LCH. DI is a result of the destruction of more than 80 % of the paraventricular-supraoptic
neurons 10], 11]. Despite the high frequency of DI reported in prior literature, in our case, all
hematological and biochemical parameters, liver function tests, urine osmolarity and
endocrine evaluations were within the normal limits.

It is essential to note that the clinical and radiographic presentation of LCH could
mimic an acute or chronic periodontal or periapical lesion, radicular cysts, osteomyelitis
and malignancies. The lesions often appear as sharply punched-out radiolucent images,
and the teeth appear to be “floating” when extensive alveolar involvement occurs 12]. Professionals should consider LCH as a possible diagnosis in different situations:
periodontal lesions recurrent after conventional treatment, the presence of systemic
symptoms previously mentioned and associated with periodontal lesions and after rapid,
severe and localized periodontal bone loss. In this specific case, the lesion resembled
a periodontal lesion associated with a carcinomatous lesion; however, the histological
findings did not show any evidence of neoplastic cells.

The presence of pale histiocytes was fundamental to decide to do an immunohistochemical
panel to investigate the nature of these cells. Monoclonal antibodies for S-100 (Fig. 3a), CD1a pan-cytokeratin, CD-68, melanoma marker (HMB45) and melanoma A protein were
included in this panel. Positive staining for S-100, CD1a, and CD-68 established the
final diagnosis in our case. The CD1a marker is essential for distinguishing Langerhans
cells from other dentritic cells and histiocytes 13]. In our case, this additional examination by immunohistochemical techniques was critical
for the establishment of the correct diagnosis of LCH and treatment planning for the
patient.

The first step for the treatment of LCH should be to determine the number of organ
systems involved. Then patients who have single-system disease should be subcategorized
based on the number of sites involved. The presence or absence of organ dysfunction
is a subcategory for patients who have multi-organ disease 14]–18]. Curettage is generally sufficient for patients with localized bone lesions. However,
it also possible to employ intralesional steroids or low-dose radiation. Treatment
of multiorgan disease is controversial. Some state that high-dose prednisone should
be the first-line therapy, whereas others suggest the use of single-agent chemotherapy
3], 14]–17]. A combination of vinblastine and prednisone is an effective therapy used as the
standard regimen for multisystem LCH in children and should be further explored in
adult patients 18]. Other treatments, such as targeted therapy with BRAF inhibitors, has been used in
select patients with encouraging results 18]. Another model indicates both BRAF mutation and IL-1 loop regulation as potential
LCH therapeutic targets 19].

In our case, the patient underwent surgical extraction of all superior teeth, due
to their periodontal involvement; curettage of the bone lesion; local radiation and
corticoid therapies and prosthesis. The prognosis of LCH depends on the number of
organs involved, as well as the presence of organ dysfunction and, in minors, on the
age of the patient at the disease onset 4], 14]–18]. In this specific case reported, the prognosis was favorable, due to single bone
involvement, early diagnosis and proper treatment. Moreover, the patient had no signs
of recurrence after 8 years of follow-up.