Primary oral manifestation of Langerhans cell histiocytosis refractory to conventional therapy but susceptible to BRAF-specific treatment: a case report and review of the literature

Abstract

Langerhans cell histiocytosis (LCH) is a diagnostic and therapeutic challenge. We report on a rare case of its primary oral manifestation that was treated successfully with the BRAF-specific agent, vemurafenib, after insufficient standard LCH treatment. This case underlines the importance of proper diagnosis and the evaluation of targeted therapy as a valuable tool in LCH treatment. Furthermore, the close collaboration of surgeons, oncologists, and dentists is mandatory to ensure adequate treatment, restore the stomatognathic system in debilitating post-treatment situations, improve quality of life, and ensure effective disease control in infants and young patients.

Primary Oro-Facial Manifestations of Langerhans Cell Histiocytosis in Pediatric Age: A Bi-Institutional Retrospective Study on 45 Cases

“…The histological features of LCH have been well described and defined throughout the years. Electron microscopy was used in the past to detect X bodies and so as to confirm the diagnosis, but is nowadays no longer necessary [ 2 , 3 ]. The diagnosis of LCH is determined by conventional histology along with the immunohistochemical staining for CD1a and Langerin (CD207); the latter is the most recent introduced monoclonal antibody for LCH diagnosis, as highly specific and sensitive protein needed for formation of the Birbeck–Broadbent granules [ 1 , 2 , 3 , 5 ].…”

“…Langerhans Cell Histiocytosis (LCH), previously known as Histiocytosis X, is a rare hematologic disorder usually affecting children [ 1 , 2 , 3 ]. LCH is characterized by an abnormal proliferation of bone-marrow derived histocytes (dendritic cells resembling Langerhans cells of the epidermis) that may infiltrate and consequently damage single or multiple organs and tissues, especially the bones [ 1 , 4 , 5 ].…”

“…LCH signs and symptoms can greatly differ according to the unifocal or multifocal clinical occurrence [ 2 , 7 , 8 ]. LCH affects fewer than five people per million with a rate of 0.2 to 0.5 cases per 100,000 children per year, with a peak of incidence between 3–4 years of age and with a male predilection of 1.6–1.7 increased occurrence than female [ 2 , 3 , 7 , 8 ]. LCH predominantly involves the skeleton, followed by the skin and the pituitary gland, while organs/systems commonly related to a higher risk of severe progression, such as bone marrow, liver, spleen and lungs, are less frequently involved.…”

“…Notably, 55% to 80% of cases of disseminated LCH may manifest lesions in the head and neck, especially of the skull (mostly of the temporal bone), lymph nodes, skin and orbit, while only 7–10% have oral lesions (mostly jaw lesions); moreover, primary manifestations in the oral cavity are rare [ 2 , 3 , 4 , 9 , 10 , 11 ]. Clinically, localized or multiple gingival swellings with edema/inflammation or ulceration (rarely), periodontal involvement with teeth mobility/dislocation, often associated to destroying bone lesions (especially of the posterior mandible) with the conventional appearance of “floating teeth” or “floating in air” teeth on radiograms, are common primary findings in not yet diagnosed cases [ 2 , 3 , 7 , 12 ].…”

“…Notably, 55% to 80% of cases of disseminated LCH may manifest lesions in the head and neck, especially of the skull (mostly of the temporal bone), lymph nodes, skin and orbit, while only 7–10% have oral lesions (mostly jaw lesions); moreover, primary manifestations in the oral cavity are rare [ 2 , 3 , 4 , 9 , 10 , 11 ]. Clinically, localized or multiple gingival swellings with edema/inflammation or ulceration (rarely), periodontal involvement with teeth mobility/dislocation, often associated to destroying bone lesions (especially of the posterior mandible) with the conventional appearance of “floating teeth” or “floating in air” teeth on radiograms, are common primary findings in not yet diagnosed cases [ 2 , 3 , 7 , 12 ]. Even less frequent is the primary onset of a single bone lesion (especially in the maxilla) with periosteal reaction, punch-out radiolucent appearance, absence of cortical bone or diffuse periodontal involvement, mimicking on radiograms aggressive and diffuse periodontal disease, as well as mucosal infiltration (almost exclusively of the palate) with slight proliferation, erythema and strawberry appearance [ 2 , 3 , 7 , 13 , 14 ].…”