DIAGNOSIS: Angiotropic (intravascular) lymphoma and cerebrovascular beta-amyloidosis
Angiotropic lymphoma (AL), also known as intravascular lymphoma, is a rare, generally fatal disease often involving several organs such as brain and skin, whereas spleen, lymph nodes and bone marrow are generally spared (11, 12). AL is characterized by multifocal proliferation of neoplastic lymphocytes within small and medium sized vessels. Brain and spinal cord are involved in more than 30% of cases (6). Generally, AL occurs in adults, but to date, no distinctive epidemiological features have been identified, owing to the small number of cases that have been reported in the literature (3).
Clinical symptoms are frequently nonspecific, including neuropsychiatric changes and fever. Some patients may also present with myopathy and peripheral neuropathy (5). Cerebral imaging often shows no characteristic features, but occlusive infarcts of multiple ages usually can be found. In some instances the disease may mimic vasculitis (8). As a result of the nonspecific and somewhat variable phenotypic presentation, the clinical diagnosis often is uncertain, and definitive diagnosis can be made only at autopsy.
Macroscopically, the brain may show features of hemorrhage, thrombosis and necrosis. However, the infiltrating tumor cells themselves may be invisible to the naked eye. Microscopically, the large tumor cells are localized in the lumina of small vessels and are characterized by vesicular nuclei and prominent nucleoli. Mitotic figures are frequently recognized. Malignant cells can only rarely be observed in the cerebrospinal fluid and the peripheral blood. Immunohistochemically, tumor cells usually express B-cell-associated antigens, such as CD19, CD20, CD22 and CD79a. Some cases have shown a coexpression of CD5. A T-cell phenotype of AL is reported in rare cases (3).
Angiotropic lymphoma was first described as malignant angioendotheliomatosis (2, 7), and only later was the lymphoid nature of the tumor cells confirmed (1, 10). To date, AL is regarded by the WHO as a rare subset of diffuse large B-cell lymphoma (DLBCL) (3).
The present case demonstrated a typical clinical history and pathology of AL with involvement of the CNS. Presumably, due to low autopsy rate a larger part of AL is not diagnosed. However, this rare disorder is being seen with increasing frequency in the context of a rising incidence of cerebral lymphomas, and therefore should be included in differential diagnostic considerations.
Surprisingly, we also found cerebrovascular beta-amyloidosis with small, parenchymal bleeds that might have contributed to the clinical course in this case. While some subtypes of lymphomas, such as plasma cell myeloma, are known to be accompanied by the pathological production of amyloid (4), this has not been reported in DLBCL, especially in AL. Therefore, it is likely that the present lymphoma and cerebrovascular amyloidosis are coincidental findings without a specific pathogenetic connection. However, given the elevated susceptibility of amyloidotic blood vessels to rupture (9), the presence of cerebral amyloid angiopathy in patients with AL could increase the incidence of parenchymal microhemorrhage and thereby exacerbate and complicate the neurological manifestations of AL.
Contributed by Silke Vogelgesang, Andre Hippe, Christof Kessler, Rolf W. Warzok