Unusual presentation of a skull base mass lesion in sarcoidosis mimicking malignant neoplasm: a case report

Sarcoidosis is an idiopathic granulomatous disease which commonly involves the lungs, skin, and eyes, with simultaneous or metachronous features [1, 2]. Sarcoidosis involving the central nervous system (CNS; neurosarcoidosis) occurs in approximately 5-15% of adults with systemic sarcoidosis [3, 4]. Even fewer cases of sarcoidosis have been reported in children, especially cases affecting the CNS [5]. Baumann and Robertson [6] reviewed pediatric neurosarcoidosis and concluded that childhood neurosarcoidosis differs in its presenting signs and symptoms from neurosarcoidosis in adults; children are more likely to have seizures, less likely to have cranial nerve palsies, and perhaps more likely to have a space-occupying lesion. More recently, Rao et al. [4] reviewed neurosarcoidosis in pediatric patients. They found that only 53 examples of neurosarcoidosis had been reported in the pediatric population, with nine of these cases being isolated neurosarcoidosis. The most common manifestations included cranial neuropathy (21%), papilledema or optic neuritis (15%), seizures (24.5%), and hypothalamic dysfunction (17%), with the latter two conditions being more likely in younger children.

We described here the rare clinical and radiological manifestations of 12-year-old boy with monocular vision loss who was initially thought to have a skull base tumor, but was subsequently confirmed to have neurosarcoidosis with systemic sarcoidosis. In addition, we present a small literature review of neurosarcoidosis, especially in pediatric patients.

Intracranial pseudotumors are uncommon, but it is important to recognize such lesions. They may occur in inflammatory diseases (systemic diseases, vasculitis, and demyelinating diseases), infectious diseases, vascular diseases, and radionecrosis [7]. Among such conditions, sarcoidosis is a multi-organ disease of unknown etiology, but is thought to be associated with an abnormal immune response, and develops from young people to elderly people with a peak in the fourth decade [1, 8]. The clinical symptoms at the time of onset are diverse, and the subsequent clinical course is also diverse. Sarcoidosis most commonly affects the lungs and thoracic lymph nodes; however, virtually any organ system can be involved including the eyes, skin, kidney, heart, and CNS [2, 3, 8]. Sarcoidosis may involve any of the intracranial regions including the supratentorial and infratentorial compartments as well as leptomeningeal and intraparenchymal areas, with solitary or multiple lesions, and such involvement gives rise to a broad variety clinical manifestations [1, 3, 9, 10]. Thus, a significant number of patients with neurosarcoidosis may have asymptomatic lesions or be misdiagnosed [8]. It has been reported that ¹⁸F-FDG PET/CT is a valuable tool for the diagnostic evaluation of patients suspected of sarcoidosis and is also important for other major diagnostic discrimination, including lymphoma and metastasis [11].

Although imaging studies are nonspecific, MRI is a very sensitive diagnostic tool for the finding and detection of intracranial lesions due to neurosarcoidosis [3]. Previous reports have regarded mass lesions as rare in pediatric neurosarcoidosis [12], however Baumann and Robertson reported 24% had mass lesions on imaging and it is unclear whether children have different patterns from adults [6]. The lesions are frequently reported to be isointensive on T1-weighted images and hypointensive masses on T2-weighted images, and to be uniformly enhanced after contrast medium injection [3]. Other common findings in pediatric neurosarcoidosis include periventricular high signal lesions on T2-weighted images and leptomeningeal enhancement on T1-weighted images with contrast [6]. Wiśniewski et al. [13] pointed out the relationship between the observation of extremely low signal on T2-weighted images and noncaseating granuloma in their neurosarcoidosis case. In our patient, the low signals on T2-weighted images further advanced after steroid therapy, which may indicate an inactive lesion, although we need to continue observation of the future course.

One of the typical images of neurosarcoidosis is leptomeningeal involvement which usually appears as a thickening and diffuse and/or focal enhancement [1, 4, 10]. Such an image may be readily misidentified for diseases such as glioma, meningioma, metastatic tumor, demyelinating disease, vasculitis, and other granulomatous diseases including tuberculosis, Wegener’s granulomatosis, etc. [3, 13]. Thus, even in children, we need to include the possibility of neurosarcoidosis in the differential diagnosis of intracranial lesions [3, 13, 14].

It has been reported that cranial neuropathies, which may involve one or more nerves and occur unilateral or bilaterally [8], are seen in about 60% of adult patients with neurosarcoidosis [4, 8]. Among them, facial nerve palsy is suggested to be the most commonly encountered neurologic complication [4, 6], although it could include cases related to parotitis. Carlson et al. [8], who reviewed the cranial base manifestations of neurosarcoidosis, found that the optic, trigeminal, and facial nerve(s) represented the most frequently involved neuropathies, in that order. On the other hand, Rao et al. [4], who reviewed neurosarcoidosis in pediatric patients, indicated that the prepubertal aged group most commonly presented with seizures, while postpubertal children presented similarly to adults and were more likely to have cranial neuropathy; facial nerve palsy was the most common condition, followed by acoustic neuropathy and optic nerve involvement. The mechanism of such neuropathy may not only result from nerve granuloma, but may also be due to increased intracranial pressure or granulomatous basal meningitis [4, 8].

Several studies have indicated that increased serum ACE levels may be observed in sarcoidosis, but not in all cases [6]. Furthermore, elevated ACE levels are not specific for sarcoidosis because other diseases have also revealed elevated serum ACE levels including tuberculosis, lung cancer, Hodgkin lymphoma, liver cirrhosis, etc. [4]. Thus, an elevated serum ACE does not provide a definitive diagnosis [4]. It is also controversial as to whether the level of ACE in the cerebral spinal fluid is useful for the diagnosis of neurosarcoidosis [1]. However, sequential serum ACE levels have been employed as a marker of disease progression in sarcoidosis [4].

Although criteria for the pediatric diagnosis of neurosarcoidosis have not yet been established, the most widely used criteria are those developed for adults by Zajicek et al. [4, 15]. Definitive diagnosis is based on histological evidence, which can prove non-caseating granulomas and multinucleated giant cells with surrounding lymphocytes [9], and must exclude differential diagnoses such as tuberculosis, berryliosis, and Sjögren’s syndrome which can elicit a similar histological picture. [4, 5]. It is important and necessary therefore to establish a histopathological diagnosis as far as possible, and to carry out an exclusion diagnosis adequately. Dural or leptomeningeal involvements with sarcoidosis are preferred for biopsies, because such sites require less invasive procedures as compared to brain or spinal cord biopsies [1].

The most appropriate treatment for pediatric neurosarcoidosis is remains uncertain. There is no evidence of clinical benefit from surgical removal for neurosarcoidosis [9], and the role of surgical removal may be limited to diagnostic biopsy rather than therapeutic resection. In general, corticosteroids are the most commonly used first line agents and are often effective [5, 6]. For adult patients, other agents such as immunomodulating and/or cytotoxic agents, including azathioprine, cyclophosphamide, cyclosporine A, methotrexate, etc. have been employed in combination with corticosteroids to provide better outcomes, in either severe cases, steroid-resistant cases, recurrent cases, or cases in which steroids cause side effects [1, 5, 6, 10]. 25% of the patients are refractory to steroid treatment and 20 - 40% of such refractory patients are not responsive to immunomodulating agents [10]. Although it has been indicated that adults with seizures and other intracranial lesions could be less responsive to treatment [6], our patient displayed a good response to high-dose prednisolone with slow taper treatment for 3 months including significant evidence of radiological and clinical improvement. This may be because pediatric patients can show improved lesions with corticosteroids alone [4]. The efficacy of immunomodulating and/or cytotoxic agents in children with neurosarcoidosis has not yet been fully elucidated [4]. We clearly need to undertake carefull follow-up of our patient’s future course.