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Vol. 26. Num. 5.September - October 2015Pages 209-260
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Vol. 26. Num. 5.September - October 2015Pages 209-260
Case Report
DOI: 10.1016/j.neucir.2014.12.004
Isolated neurosarcoidosis mimicking intracranial tumours – Analysis of 3 cases
Neurosarcoidosis aislada imitando tumores intracraneales – análisis de tres casos clínicos
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Karol Wiśniewskia,
Corresponding author
karol.lek@poczta.fm

Corresponding author.
, Rafał Wójcika, Wielisław Papierzb, Agata Majosc, Dariusz J. Jaskólskia
a Department of Neurosurgery and Neurooncology, Medical University of Lodz, Barlicki University Hospital, Kopcińskiego 22, Lodz 90-153, Poland
b Department of Pathomorphology, Medical University of Lodz, Czechoslowacka 8/10, Poland
c Department of Radiology, Medical University of Lodz, WAM University Hospital Lodz, Żeromskiego 113, Poland
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Abstract

Isolated neurosarcoidosis (INS), as a disease of low prevalence, is commonly overlooked in differential diagnosis, and its discovery on histopathological examination usually comes as a surprise. Preoperative diagnosis is difficult because the clinical picture of INS is non-specific. Its symptoms depend on the location of the lesions, and the MRI results are similar to those found in meningiomas or optic nerve gliomas. Although up to 5% of all sarcoidosis patients present with neurological symptoms, those with INS are exceptionally infrequently encountered.

Three cases of INS are presented here, analysing their clinical course and radiological images, in order to determine characteristic traits that might lead to a correct diagnosis.

Keywords:
Isolated neurosarcoidosis
Neurosarcoidosis clinical manifestations
Neurosarcoidosis MRI
Brain tumour diagnosis
Meningioma
Optic nerve glioma
Resumen

La neurosarcoidosis aislada (Isolated neurosarcoidosis - INS), como enfermedad de prevalencia baja, a menudo no es tomada en consideración en el diagnóstico diferencial, entonces su descubrimiento en los estudios histológicos generalmente llega inesperadamente. El diagnóstico preoperatorio es difícil porque el cuadro clínico de la INS no es específico pues sus síntomas dependen sólo de la localización de las lesiones, mientras que los resultados de RM son parecidos a los encontrados en los meningiomas o gliomas del nervio óptico. Aunque hasta el 5% de todos los pacientes con sarcoidosis presentan síntomas neurológicos, aquellos con INS se encuentran excepcionalmente.

Presentamos tres casos de INS, analizando su curso clínico y la imagen radiológica para determinar unos síntomas típicos que podrían ayudar a realizar el diagnóstico correcto.

Palabras clave:
Neurosarcoidosis aislada
Neurosarcoidosis manifestaciones clínicas
Neurosarcoidosis RM
Diagnóstico de tumour cerebral
Meningioma
Glioma del nervio óptico
Full Text
Introduction

Sarcoidosis is a systemic disease of unknown aetiology, characterized by the presence of noncaseating granulomas. The disease usually occurs in young adults and commonly affects the lungs. Should sarcoidosis involve CNS, then the mortality rate grows and in up to 48% of the patients neurological symptoms will precede manifestation from other organs.1 However, only 1–3%2 of neurosarcoidosis cases prove to be INS, i.e. with the disease restricted to the CNS. In these instances the diagnosis is particularly challenging as neither neurological symptoms nor MRI findings are characteristic enough to warrant the correct diagnosis.

The aim of this study is to review three cases of isolated neurosarcoidosis mimicking a tuberculum sellae meningioma, falcine meningioma and glioma of the left optic nerve, in order to define their common clinical and radiological features sufficient to establish the correct diagnosis. The literature on therapeutic approach to INS is scanty and limited to case reports. All our patients were operated on; hence, the diagnosis was confirmed on histopathological examination.

Case description

Imaging findings in neurosarcoidosis can mimic astrocytoma, meningioma, intracranial metastatic disease, multiple sclerosic, central nervous system (CNS) vasculitis, other granulomatous diseases such as tuberculosis, parasitic, fungal infections, Wegener's or lymphomatous granulomatosis. Therefore we performed in all cases general exams and laboratory examination which were normal. Results of routine blood tests were normal, including erythrocyte sedimentation rate, C-reactive protein (CRP) concentration, serum angiotensin-converting enzyme (ACE) activity, anti-human immunodeficiency virus antibody and serum cryptococcal antigen. Further serologic testing disclosed no evidence of viral, bacterial, fungal or parasitic infection. A tuberculin test showed no reaction and both IGRA tests were negative. We also performed serological studies for systemic autoimmunity, including rheumatoid factor, antinuclear, anti-dsDNA, anti-SSA/SSB and antiphospholipid antibodies showed no abnormality. The cerebrospinal fluid (CSF) analysis including biochemistry, IgG index and oligoclonal band was normal. Lumbar puncture yielded clear cerebrospinal fluid (CSF). CSF analysis showed normal protein level, normal glucose concentration and normal gamma globulin concentration. Cytologic examination of CSF identified no malignant cells. Increased CSF lymphocytes CD4:CD8 ratio was not observed in our cases, because it requires large numbers of vivid lymphocytes, which are usually unavailable.

In all cases, on the systemic evaluations, there was no disease activity on other organs (brain MRI and chest X-ray – before surgery). After the surgery we performed chest CT, abdominal MRI, whole body gallium scintigraphy, muscle magnetic resonance imaging and whole body fluorodeoxyglucose positron emission tomography (PET) to search for systemic sarcoidosis but all additional examinations were normal.

Case 1

A 46-year-old female with a two-month-history of morning headaches and no other neurological symptoms. Neurological examination detected no abnormality.

The patient had been treated in an outpatient neurological clinic for retinal migraine and venous angioma in the right cerebellar hemisphere diagnosed back in 2008.

MRI revealed a focal lesion of uneven surface and irregular shape, dimensions: 19mm×23mm×6mm, situated on the convexity, right above the upper left frontal gyrus. The tumour was strongly attached to the superior sagittal sinus and the falx. As it showed a strong contrast enhancement, the image suggested a parasagittal meningioma (Fig. 1A–D).

Fig. 1.
(0.65MB).

Case 1. Preoperative MRI. T1-weighted images after administration of gadolinium shows a uniformly enhancing lesion, located parasagittally in the left hemisphere (A, B and D) and in T2-weighted image demonstrating extreme law signal of the lesion (C). E – A group of noncaseating granulomas. H+E. ×200. F – CD4+ lymphocytes are seen mainly in the periphery of inflammatory granuloma. Staining with anti CD4 antibody. ×200 (positive in all cases).

Additionally, the MRI scan revealed a venous angioma in the right cerebellar hemisphere. Chest X-ray and subsequently chest CT scan showed no abnormalities.

The patient underwent fronto-parietal parasagittal craniotomy. The tumour was totally excised. The lesion had no distinct boundaries, was heterogeneous, brittle and grey. Microscopic examination revealed chronic inflammation with tubercle-like granuloma formation with CD4+ lymphocytes in the periphery of granuloma and with no tendency to either ossification, or fibrosis, characteristic of sarcoidosis (Fig. 1E and F). However, no changes, specific to sarcoidosis, were observed during ophthalmological examination, which was performed after histopathological results had been received.

The patient was referred for further treatment to outpatient pulmonological and neurological clinics. At one-month follow-up, the pain had subsided. There were also no abnormalities on neurological examination.

Case 2

A 22-year-old male with a six-month history of progressive deterioration of vision in the left eye followed up in an ophthalmological clinic. On admission he had scotoma in the left eye.

The MRI revealed thickening of the left optic nerve stretching from roughly 4.5mm posterior to the globe to about 9mm anterior to the optic chiasm. Hence, the affected segment which showed strong contrast enhancement was 35mm long and 5.7mm thick. The image was compatible with this of an optic nerve glioma (Fig. 2A–D).

Fig. 2.
(0.34MB).

Case 2. Preoperative MRI. T2-weighted image shows thickening of the left optic nerve (A and B), more evident in coronal cross-sections of both eyes (C and D) with intense contrast enhancement (B). E – Inflammatory noncaseating granuloma with lymphocytic infiltrate in the surrounding. H+E. ×400.

Chest X-ray showed no abnormalities as did not a subsequent chest CT. The patient underwent left-side fronto-temporal craniotomy for subfrontal approach. The lesion was difficult to separate from the arachnoid, without distinct boundaries, brittle and grey. It was totally excised.

Histopathological examination revealed multiple histiocytic granulomas without necrosis, with multinucleated giant cells present in a number of granulomas (Fig. 2E). The focal concentrations of lymphocytes were also present, mostly around blood vessels. The CD4+ lymphocytes were seen in the periphery of granuloma (Fig. 1F). Microscopic image suggested sarcoidosis. The patient was referred for further treatment to outpatient pulmonological and neurological clinics. At one-month follow-up no new neurological symptoms were noted.

Case 3

A 71-year-old female with a past medical history of hypertension, ischaemic heart disease, atherosclerosis and recent six months history of progressive deterioration of vision in both eyes with bitemporal hemianopsia. Otherwise neurological examination detected no abnormality.

MRI suggested the presence of a tuberculum sellae meningioma, showing strongly enhancing, irregular mass encompassing both optic nerve canals and anterior clinoid processes (Fig. 3A–D). Chest X-ray revealed no abnormalities; the chest CT scan which followed the histopathological diagnosis was also normal.

Fig. 3.
(0.38MB).

Case 3. Preoperative MRI. T1-weighted images after administration of gadolinium shows strongly enhancing irregular mass encompassing both optic nerve canals and anterior clinoid processes (A–D). E – Some noncaseating granulomas enclosed within fibrous rims. Note a stellate inclusion (asteroid body) within giant multinucleated cell. H+E. ×400.

The patient underwent left sided fronto-temporal craniotomy and the tumour was totally excised via subfrontal approach. As there was no distinct plane of cleavage, this fragile and grey lesion was difficult to remove without minor damage to the cortex. Postoperatively, the vision remained unchanged.

Histopathological examination revealed chronic inflammation with formation of tubercle-like structures and fibrosis (Fig. 3). The CD4+ lymphocytes were seen mainly in the periphery of inflammatory granuloma (Fig. 1F).

The patient, in good general condition, with preserved left-eye vision was discharged to the department of neurology for further treatment and rehabilitation.

Discussion

Early diagnosis of neurosarcoidosis allows the introduction of immunosuppressive therapy, thus decreasing mortality rate, whilst in a case of isolated neurosarcoidosis, it reduces the risk of neurological damage.

Intracranial sarcoidosis is usually located within the meninges, especially at the base of the brain, secondarily affecting cranial nerves and impeding the flow of the cerebrospinal fluid. Basing on the literature on the subject, one can point a number of most frequent locations of INS lesions, namely: parasagittally, on the convexity or in the cerebellopontine angle.3–9 There are also single case reports which mention localization of non-caseating granulomas in the cerebellum, medulla oblongata, and very rarely, in the spinal cord.10,11

Due to various possible locations and the extend of a lesion, the clinical picture differs widely from case to case. According to case reports, the most common INS symptoms are those of cranial nerves neuropathy, particularly, of facial (35–73%) or optic nerves, both uni- or bilateral.12–14 Thus, isolated cerebral form should be considered whenever there is involvement of the abovementioned nerves.

The diagnosis in patients in whom the disease begins with neurological dysfunctions requires neurological diagnostics, MRI being the most important one. On MRI, the lesion is isointensive at T1 and hypointensive at T2 weighted images, and enhances uniformly after contrast injection. Such image resembles diseases such as meningioma, optic nerve glioma and others mentioned above. When CNS involvement is a first manifestation, all the illnesses mentioned in differential diagnosis should be excluded. This makes INS one of the great mimickers in medicine.

The literature suggests also the relationship between extremely low signal observed at T2 weighted images and the presence of noncaseating granulomas.15 This was seen only in the first case.

Intracranial sarcoidosis can also be suspected intraoperatively, basing on macroscopic appearance of the mass. Among our patients, who were operated on for INS, as a rule, the lesion was heterogenous, brittle and did not have distinct plane of cleavage.

According to the literature, we recommended to assess cerebrospinal fluid (CSF) serum angiotensin-converting enzyme (ACE) level to monitor disease activity or treatment response, because it is synthesized within the nervous system.16 It is worth to evaluate CSF lymphocytes CD4:CD8 ratio. Should the ratio prove positive it may be helpful in establishing a diagnosis, but would require large numbers of vivid lymphocytes, which are usually unavailable.17

In brief, should an intracranial tumour have an MRI characteristic of a meningioma or optic nerve glioma, and present with an involvement of a facial or optic nerve, the diagnosis of INS ought to be taken into account.

Conclusion

Isolated neurosarkoidosis is a rare disease which every neurosurgeon must nonetheless remember. If intracranial tumour has extremely low signal observed at T2 weighted images and MRI images look similar to meningioma or optic nerve glioma and facial or optic nerve is affected, INS should be taken into consideration.

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Copyright © 2014. Sociedad Española de Neurocirugía
Neurocirugía (English edition)

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