Aggressive Lung Adenocarcinoma in a Multiple Sclerosis Patient Treated with Natalizumab
Cases of natalizumab-treated MS patient developing malignancies have been rare and most have been lymphomas. Even more rare are solid tumors in this setting.
To describe a case of lung adenocarcinoma in a 68 y.o. non-smoker male MS patient treated with natalizumab, discuss possible causative association, and review the literature.
Methods: Case report.
A 68 y.o man with active RRMS, based on sustaining a major relapse with severe paraparesis while on INF-beta 1b three years earlier, was switched to natalizumab. The patient remained relapse-free for the duration of the 27 total natalizumab infusions period. He presented with new headaches 6 months before diagnosis of lung ca and death. A brain and cervical MRIs with gadolinium were negative for parenchymal or meningeal process other than MS lesions at presentation with headache. Despite symptomatic treatment the headaches worsened and repeat brain MRI showed dural enhancement and unchanged MS lesions. A LP showed normal cell count and glucose, mild CSF protein elevation. PCRs were negative for HVS and VZV. A full course of acyclovir was given. Subsequently the patient developed subdural fluid collections, extensive thoracic vertebral lesions suggestive of metastases and a lung lesion on CXR suspicious for carcinoma or infection. The patient could not be resuscitated after sustaining cardiac arrest.
Autopsy showed lung adenocarcinoma of the left lung along with diffuse tumor micro-embolization of myocardium and lung tissue, as well as with solid tumor infiltration of heart, regional lymph nodes, vertebrae and other organs. A small solitary cerebellar metastasis, diffuse tumor infiltration of the dura without involving the leptomeninges, and a subacute infarct in the right anterior cerebral artery distribution were found in the brain.
To out knowledge this is the first case of lung adenocarcinoma in a patient treated with natalizumab. Possible association of natalizumab treatment with: 1. malignancy development, 2. aggressive dissemination of carcinoma via an uncommon tumor microembolization spread will be discussed, including mechanisms involving VLA-4 modulation in tumor cells.