Mycobacterial spindle cell pseudotumour of the brain in a patient with sarcoidosis

Abstract

Mycobacterial spindle cell pseudotumours (MSP) are benign lesions characterised by local proliferation of spindle-shaped histiocytes caused by mycobacterial infections. Cerebral MSP due to Mycobacterium avium intracellulare (MAI) infection is rare, and is often misdiagnosed clinically and radiologically as a brain tumour. We present a case with underlying sarcoidosis and known pulmonary MAI infection presenting with partial seizures and headaches. Imaging of the brain revealed a solitary extra axial tumour within the right temporal area. Biopsy of the tumour showed evidence of MPS due to MAI infection. Prolonged treatment with antituberculous therapy showed complete resolution of the cerebral lesion.

Background

Mycobacterial spindle cell pseudotumours (MSP) are rare benign lesions characterised by local proliferation of spindle-shaped histiocytes containing acid fast bacilli.¹ MSP can be caused by tuberculous as well as non-tuberculous mycobacteria (NTM). Spindle cell pseudotumours due to Mycobacterium avium intracellulare (MAI) infection usually present with pulmonary disease in immunosuppressed patients,² particularly those with AIDS. Other organs affected include the lymph nodes,^{1 3–5} skin,⁶ spleen⁷ and bone marrow.⁸ We present a case of cerebral MSP secondary to MAI infection in an HIV negative patient presenting radiologically as a solitary right extra-axial temporal tumour. Spindle cell pseudotumours are often confused with malignant lesions and, usually, only biopsy of these lesions confirms the diagnosis.

Case presentation

A 69-year-old Caucasian man, a retired maintenance engineer, was referred to our respiratory clinic in 2009 for treatment as his sputum was repeatedly culture positive for MAI. He had a persistent cough and was reporting of dyspnoea and significant fatigue. He was originally diagnosed to have sarcoidosis in 1983, based on radiology appearance of bilateral hilar lymphadenopathy and a transbronchial biopsy that showed granulomatous changes. He was diagnosed to have asthma as a child and used combination inhalers of fluticasone and salmeterol. In 2005, he was found to have bronchiectasis, and 2 years later presented with two episodes of haemoptysis, which were managed conservatively with antibiotics after bronchoscopy failed to show a bleeding source. He required treatment for his sarcoidosis in 2007, and was maintained on a dose of 5–15 mg of prednisolone for 2 years until his presentation to our clinic. CT of the chest was consistent with features of chronic sarcoidosis and widespread bronchiectasis. His lymphocyte count was persistently low (0.43–0.46×10⁹/L, normal 1.50–4.00×10⁹/L). HIV test was negative and the ACE levels were normal.

In 2008, the patient presented to the neurosurgeons with a 9-month history of headaches and partial seizures. A CT and MRI of the brain scan showed a contrast enhancing solitary extra axial tumour within the right temporal area (figure 1). He underwent a craniotomy and complete macroscopic excision of the dural-based tumour. Intraoperatively, the tumour was noted to be firm, rubbery and adherent to the dura. Histologically, the tumour showed cellular nodules composed of interlacing bundles of plump spindle cells with oval or elongated nuclei, an open chromatin pattern and bipolar fibrillar cytoplasmic processes, arranged in a vague storiform pattern. Relatively uniform infiltrates of small lymphocytes and occasional neutrophils were interspersed. A few mitoses were present (figure 2). Immunostaining of the specimen showed that the spindle cells were strongly CD68 (KP-1) and vimentin positive, weakly leucocyte common antigen and smooth muscle actin positive. Stains for epithelial membrane antigen (EMA), desmin, CD1, S-100 protein, cytokeratins, glial fibrillar acidic protein (GFAP) and CD34 were all negative.

Figure 1.

MRI at presentation.

Figure 2.

H&E stain shows a spindle cell lesion with a storiform pattern and scattered lymphocytes.

Investigations

The patient's initial diagnosis was of a low grade tumour (meningioma), radiologically, but since he persistently cultured MAI in his sputum, a retrospective analysis of his brain mass by electron microscopy was undertaken (figure 3), which revealed the presence of numerous intracellular bacteria. This prompted staining for organisms on light microscopy, and Ziehl-Neelsen positive intracellular bacilli were identified (figure 4). PCR of the brain biopsy was positive for MAI.

Figure 3.

Electron microscopy shows intracellular bacteria.

Figure 4.

Numerous intracellular Ziehl-Neelsen positive bacilli.

Differential diagnosis

Other differential diagnoses for spindle cell tumours include malignant fibrous histocytomas, sarcomas and schwannomas. More rare forms are pleomorphic spindle cell tumours including spindle carcinomas, lymphomas and melanomas, as well as pleomorphic sarcoma. Immunostaining helps to differentiate between the tumours.

Treatment

The patient had prolonged treatment with ethambutol, rifampicin and moxifloxcain, as his sputum showed clarithromycin resistance.⁹ He was gradually weaned off prednisolone and, once stopped, his sputum became culture negative.

Outcome and follow-up

The patient successfully completed 2 years of treatment with the last positive culture for MAI 16 months before the end of treatment. Since the radiological and histological findings were initially interpreted as consistent with a low-grade meningioma, the tumour was excised. However, repeat imaging by MRI scan revealed a residual contrast enhancing nodule. Only after 2 years of antituberculous treatment was there complete resolution of the previous pseudotumour, with minimal dural enhancement.

Discussion

NTM are low grade pathogens that usually affect immunodeficient patients or those with underlying lung disease. In keeping with previous reports, this patient's intracranial MAI infection was associated with sarcoidosis, secondary bronchiectasis and long-term use of steroids. Morrison et al¹⁰ described a similar case of cerebral MSP in an HIV negative patient with sarcoidosis on steroids but with an idiopathic low CD4 count. Our patient had a persistently low lymphocyte count and this may have been a risk factor for him to develop cerebral MAI infection through a haematogenous spread since NTM disease is known to be associated with CD4 T cell lymphopaenia.¹⁰ Interestingly, Ho et al¹¹ found that a subset of CD4 T-cells (CD1d-restricted natural killer cells) was significantly reduced in patients with sarcoidosis. The authors postulated that this deficiency was implicated in the pathogenesis of the disease in sarcoidosis rather than a contributing factor for acquiring relatively low-virulent organisms such as NTM. There is growing evidence that mycobacterial antigens may be implicated in the pathogenesis of sarcoidosis,¹² however, it is not clear if patients with sarcoidosis develop NTM infections due to underlying disease, associated lymphocytopenia or immunosuppressant therapy.¹³

MSP of the skin has been described with the use of prednisolone and azathioprine in a systemic lupus erythematosus patient,¹⁴ and immunosuppressive therapy in a scleroderma case, but due to Mycobacterium chelonae.¹⁵ An intracranial MAI infection presenting as a meningioma on imaging has also been previously documented.¹⁶ Other differential diagnoses for spindle cell tumours include histocytomas, sarcomas and schwannomas. Immunostaining helps to differentiate between the tumours. Immunostaining in spindle cell meningiomas has at least focal membranous positivity for EMA, positivity for vimentin, negativity for cytokeratin and weak or negative staining for S100 protein.^{3 17} With schwannomas, S100 is strongly expressed by most cells and these can also express Vimentin and myelin basic protein.^{3 17 18} Malignant fibrous histocytomas stain positive for vimentin, lysozyme, α-1-antitrypsin, α-1-chymotrypsin and reticulin, but negative for GFAP and S-100 protein.¹⁹

Learning points.

• Spindle cell pseudotumours caused by Mycobacterium avium intracellulare (MAI) infection are extremely rare in immunocompetent patients.

• However, patients on steroids and chemotherapy, and those post-transplantation, are at risk of developing intracranial MAI infections.

• Spindle cell pseudotumours should be considered as a differential diagnosis in patients presenting with lesions in the central nervous system.