FINAL DIAGNOSIS: INTRAVASCULAR MALIGNANT LYMPHOMATOSIS
The intravascular malignant lymphomatosis (IML), also known as angiotropic large cell lymphoma, represents only 3% of the non-Hodgkin lymphomas and affects middle-aged and elderly patients (median 61 years) with a cerebral manifestation in 74% of the individuals. Signs of dementia or disorientation are reported in the literature in 53% and seizures in 25% of patients (1,3). An important point of view in this report are the symmetrical findings in the temporal lobes in combination with involvement of the cingulate gyrus which initially were misdiagnosed as limbic encephalitis. The prognosis of IML is poor with a median survival time of only 6 months after symptom onset. Temporary remission to a maximum of a few weeks is described in patients who received corticoids or cytostatic drugs (3).
The key microscopic feature of IML is the filling of lumina of small and medium-sized vessels with large atypical lymphoid cells. These cells possess predominantly round nuclei, vesicular chromatin and prominent nucleoli. Mitotic figures are common. Immunohistochemically, these cells are positive for leukocyte common antigen and usually B cell markers, but a few cases of T cell origin have been described. The blood vessels are closed and sometimes thrombosed by tumor cells leading to circulation disturbances resulting in multiple, ischemic microinfarctions as well as small parenchymal hemorrhages. Endothelial proliferation may be present (4). Migration out of the vascular spaces is rarely seen and this is likely due to the lack of surface expression of leukocyte adhesion molecule CD11a/CD18 by the tumor cells (2). Securing the diagnosis by brain biopsy is controversial, however, brain biopsy confirmed the diagnosis in 50% of individuals with brain involvement. While skin biopsy is more convenient, dermal involvement is sufficiently low to miss the diagnosis in 2/3 of all patients (3). Consequently, brain biopsy is recommended as the preferable way to establish this diagnosis.
In conclusion, in a case of dementia, seizures and infarct-like lesions by MRI, the diagnosis of an intravascular malignant lymphomatosis should be considered.
Contributed by Contributed by: Michael Friese, Michael A. Kern, Ursula Wengler-Becker, Jobst Rudolf, Roland Schröder