Langerhans Cell Histiocytosis in Sphenoid Sinus: Uncommon Bone Involvement

Introduction

Langerhans cell histiocytosis (LHC) is a rare and uncontrolled proliferation of dendritic cells of myeloid origin [1,2]. The incidence of LHC was estimated at 5 cases per million children. This neoplasm presents a very rare involvement of the skull base [3,4]. This tumor is most common in bones (77%), mainly the jaw, vertebra, pelvis, and extremities [5]. Two-thirds of affected children have involvement of a single system, most commonly in the bones, but also lymph nodes or the skin. In one-third of the remaining cases, the disease with multisystem involvement can present a mortality rate of 20% [6]. We present a case with an unusual bone involvement of cranial base and challenging diagnosis. The patient was a boy with rare bone involvement from LCH and atypical clinical presentation, but who had a satisfactory outcome. Earlier diagnosis of this rare tumor in a child was essential to establish an effective treatment without sequelae.

Case Report

A 6-year-old boy was admitted to for intense daily holocranial headache, worse in the frontal region and refractory to anal-gesia for 10 days, evolving strabismus, homonymous diplopia, and right palpebral ptosis. There were no reports of rhinorrhea, epistaxis, nasal itching, fever, or sneezing. His parents reported that he had not had any previous symptoms, comorbidities, surgeries, or long-term use of medication. Anterior rhinoscopy and endoscopy did not show any alteration. Computed tomography revealed an expansive lesion in the right sphenoid sinus, which caused cortical rupture in its posterior wall and extended to the intracranial compartment next to the right cavernous sinus. The size of the lesion was 1.5×1.2 cm (Figure 1). Nuclear magnetic resonance imaging (MRI) showed a solid expansive and infiltrative lesion in the body of the sphenoid on the right side of the midline, occupying a large part of the sphenoid sinus, and bone erosions on the posterior, lateral and superior walls. There was also extension to the right cavernous sinus involving about 180° of the cavernous segments of the right internal carotid artery, and this artery was narrowed. There was erosion of the sella turcica floor and contact with the hypophysis, and foramen rotundum involvement in the V2 pathway (Figure 2). Technetium-99m bone scintillography showed increased osteogenic activity in the sphenoid bone on the right side of the mid-line, corresponding to bone lesions disseminated by contiguity, and there were no secondary implants (Figure 3). A joint surgical approach by Otorhinolaryngology and Neurosurgery was performed by nasal endoscopic access to the skull base. The steps of surgery were right medial turbinectomy (for the access) and right sphenoid opening, septectomy and opening of the left sphenoid to be able to work with 4 hands and, after the resection of lesion, to work inside the sphenoid. There was no neuronavigation system available. All the macroscopically visible lesions appeared to have been removed. The anatomo-pathology exam indicated a poorly differentiated neoplasia of indeterminate histogenesis analysis on stored preparations stained with hematoxylin-eosin (Figure 4). Immunohistochemistry (IHC) was compatible with Langerhans cell histiocytosis (positive markers were anti-macrophages CD68, CD163, Ki67, CD1A, and S-100 protein) (Figure 5). Subsequently, the patient underwent 12 sessions of Vinblastine adjuvant chemotherapy. There was complete resolution of headache and diplopia on the thirtieth postoperative day. Follow-up was carried out for 2 years following the surgery, with biannual bone scintigraphy, videonasoscopy, and MRI, without evidence of any recurrence or sequelae. The patient is still being followed up.

Discussion

Histiocytosis is identified by abnormal proliferation of cells of the dendritic lineage monocytes and lymphocytes, differentiated from myeloid progenitor cells [7]. These neoplasms are classified as Langerhans cell-related, non-Langerhans cell-related, or malignant. LHC is derived from an immature myeloid progenitor and can occur in all age groups, but is most frequent in children aged 1–3 years [8]. This differs from our patient, who presented clinical symptoms at age 6 years. It is more common in White and male children. The male-to-female ratio is about 2.5: 1 [9]. It affects about 3–5 per million children aged 0–15 years [10]. Although there are silent cases, signs and symptoms vary according to the location and extent of the disease. The most frequent symptom is localized pain. It is limited to a single organ system – eg, skin, lymph nodes, thymus, lungs, spleen, liver, bone marrow, or central nervous system (CNS) – in about half of patients, and in children, in up to two-thirds of cases [11]. Bone involvement occurs in most cases, and it can involve any bone tissue in the body. Cutaneous involvement occurs in up to 40% of cases, and was not observed in our patient. Significant risk factors for LCH can include maternal urinary tract infection during pregnancy, feeding problems or blood transfusions during infancy, Hispanic ethnicity, crowding, low education level, neonatal infections, solvent exposure, family history of thyroid disease, and in vitro fertilization [12], but our patient did not have any of these. Protective factors appear to be Black race, childhood vaccinations, and supplemental vitamins [13]. Our patient had all vaccines on the Brazilian public health system calendar up to date and he was supplemented with vitamins A and D until he was 2 years old. Imaging exams demonstrate lytic areas and erosions, as well as a possible adjacent soft-tissue mass. The most sensitive diagnostic test is high-resolution CT, which can demonstrate cysts and nodules characteristic of LCH, and it was the initial exam performed in this case. MRI was important in the anatomical study and delimitation of the lesion for surgical programming [14]. The risk of affecting the CNS varies according to bone involvement. Injuries to facial bones and the anterior and middle cranial fossa present a higher risk, affecting almost 25%. The most common symptoms of CNS involvement are diabetes insipidus, ataxia, and cognitive dysfunction. LCH is diagnosed from the pathological evaluation, interpreted in association with the clinical context [15].

The possible differential diagnosis is benign tumors of the anterior skull base, which can originate from intracranial, cranial, or extracranial sites, as well as fibro-osseous lesions like osteoma, ossifying fibroma, and fibrous dysplasia. The most common extracranial neoplasms that can extend to the cranial base include inverted papilloma and angiofibroma. The diagnosis is often delayed because symptoms are nonspecific. Small asymptomatic tumors (eg, meningioma, osteoma) may be only observed, while others must be treated due to potential for malignancy (eg, inverted papilloma) or continued destructive growth (eg, angiofibromas) [16]. More rare differential diagnoses include epithelial adenomatoid hamartomas and schwannoma of the anterior skull base [17,18].

Biopsy of the osteolytic bone or cutaneous lesion is preferred when possible. Langerhans cell histiocytes may be suspected based on morphologic criteria. Their identity should be confirmed by positive immunohistochemical staining for CD1a and CD207 or identification of Biberck granules by electron microscopy [19]. LHC can be challenging to diagnose due to its rarity and the possibility of affecting many systems, with a wide range of symptoms. Histological and immunophenotypic differentiation from other histiocytic diseases, such as dendritic cell diseases, lymphohistiocytic and macrophage hemophagocytic activation syndromes, and solid metastatic or hematopoietic neoplasms is required [18,19]. The prognosis of the single-system form is better than the form affecting multiple systems, with a 5-year survival of close to 100%. The 5-year recurrence rate is under 20%. Bone involvement usually occurs in the same location as the primary involvement [19]. In this case, there was no recurrence in 2 years of follow-up. Despite the possibility of spontaneous remission in the bone lesion within 3 months, the recommended treatment was surgical resection due to its location next to important and delicate structures. Although the surgery was risky, our patient had a very satisfactory outcome, without evidence of any recurrence or sequelae.

Conclusions

We report a case of LCH involving the sphenoid sinus, internal carotid artery, and sella turcica, making contact with the pituitary gland. CT and MR images, particularly with contrast, were helpful in defining extent before treatment. LCH should be considered in the differential diagnosis of lesions in this location in the pediatric age group. Despite the possibility of spontaneous remission, in bone lesions within 3 months, the recommended treatment was surgical resection due to its location next to important and delicate structures. Although the surgery was risky, our patient had a very satisfactory outcome, without evidence of any recurrence or sequelae.