Unveiling the Clinical and Imaging Signatures of Intravascular Lymphoma of the Central Nervous System: A Multicentric Cohort Study

Abstract

ObjectiveIntravascular lymphoma is a rare subtype of B‐cell lymphoma characterized by a clonal proliferation restricted to the lumen of small vessels. Over 50% of patients exhibit central nervous system (CNS) involvement, but diagnosis is often delayed due to the lack of distinctive features. We aimed to identify key phenotypic features for early diagnosis of intravascular lymphoma with CNS involvement through an in‐depth cohort study.MethodsWe built up a multicenter retrospective cohort of 17 patients recruited in collaboration with the French Expert Network for Oculo‐Cerebral Lymphomas (LOC network), and retrospectively analyzed data from medical records.ResultsIn this cohort, 15 of 17 (88%) patients developed focal neurological episodes, often fluctuating and/or recurrent, with a sudden onset in 68% of episodes, suggesting a vascular origin. Rapid cognitive deterioration occurred in 15 of 17 (88%) patients, psychiatric manifestations in 8 of 17 (47%), and “B signs” in 14 of 17 (82%). Brain MRI showed polymorphic FLAIR hyperintensities in 14 of 16 (87%) patients, and DWI‐positive lesions in 13 of 16 (81%) of patients, which accumulated over time and had unusual characteristics for ischemic lesions (progressive growth, persistent DWI‐hyperintensity over 1 month, surrounded by a wider FLAIR hyperintensity). Early‐onset inflammatory syndrome, and elevated lactate dehydrogenase (LDH) levels were observed in over 90% of cases. Mild and inconsistent meningitis contrasted with a nearly‐constant hyperproteinorachia. An increased interleukin 10/6 ratio over 0,7 was found in 4 of 7 (57%) patients, and skin biopsy led to a pathological diagnosis in 3 of 6 (50%) patients.InterpretationThe results of this study highlight “red flags” that could help accelerate the diagnosis of intravascular lymphoma involving the CNS. ANN NEUROL 2024

Intravascular Large B-Cell Lymphoma Diagnosed After Recurrent Stroke: Case Report and Literature Review

“…Currently, there is no noninvasive method to confirm IVLBCL without a biopsy; however, potential markers that can raise suspicion about the disease are being identified [ 9 ]. Potential blood markers for IVLBCL include elevated levels of CRP, ferritin, fibrinogen, LDH, and β2-microglobulin, as well as cytopenia affecting at least one cell line, which may manifest as anemia, lymphopenia, or thrombopenia, which have been noted in most cases.…”

“…Potential blood markers for IVLBCL include elevated levels of CRP, ferritin, fibrinogen, LDH, and β2-microglobulin, as well as cytopenia affecting at least one cell line, which may manifest as anemia, lymphopenia, or thrombopenia, which have been noted in most cases. In some instances, liver function tests have revealed cholestasis and elevated transaminases, along with mild hyponatremia and renal failure [ 9 ]. CSF abnormalities have also been noted, with increased protein levels observed in 94% of cases and pleocytosis in 71%, although tumor cells have not been detected in cytology.…”

“…CSF abnormalities have also been noted, with increased protein levels observed in 94% of cases and pleocytosis in 71%, although tumor cells have not been detected in cytology. Additionally, some patients may present with elevated levels of CSF LDH, IL-6, IL-10, IL-10/IL-6 ratios, and β2 microglobulin [ 9 , 10 ]. A biopsy is essential for a definitive diagnosis of IVLBCL, as it allows for the identification of tumor cells within the small blood vessels of the tissue [ 7 ].…”

Intravascular Large B-Cell Lymphoma Diagnosed After Recurrent Stroke: Case Report and Literature Review

“…Currently, there is no noninvasive method to confirm IVLBCL without a biopsy; however, potential markers that can raise suspicion about the disease are being identified [ 9 ]. Potential blood markers for IVLBCL include elevated levels of CRP, ferritin, fibrinogen, LDH, and β2-microglobulin, as well as cytopenia affecting at least one cell line, which may manifest as anemia, lymphopenia, or thrombopenia, which have been noted in most cases.…”

“…Potential blood markers for IVLBCL include elevated levels of CRP, ferritin, fibrinogen, LDH, and β2-microglobulin, as well as cytopenia affecting at least one cell line, which may manifest as anemia, lymphopenia, or thrombopenia, which have been noted in most cases. In some instances, liver function tests have revealed cholestasis and elevated transaminases, along with mild hyponatremia and renal failure [ 9 ]. CSF abnormalities have also been noted, with increased protein levels observed in 94% of cases and pleocytosis in 71%, although tumor cells have not been detected in cytology.…”

“…CSF abnormalities have also been noted, with increased protein levels observed in 94% of cases and pleocytosis in 71%, although tumor cells have not been detected in cytology. Additionally, some patients may present with elevated levels of CSF LDH, IL-6, IL-10, IL-10/IL-6 ratios, and β2 microglobulin [ 9 , 10 ]. A biopsy is essential for a definitive diagnosis of IVLBCL, as it allows for the identification of tumor cells within the small blood vessels of the tissue [ 7 ].…”

A 13‐Year Review of Non‐Diffuse Large B Cell Lymphomas of the Central Nervous System at a Tertiary Hospital: A Case Series Study

“…The second case was diagnosed at post-mortem examination of an individual with a history of CLL and Parkinsonism; many leptomeningeal and intraparenchymal vessels were distended and filled with enlarged atypical B cells which had resulted in several recent infarcts (Figure 4). ILBCL is a rare entity with a high incidence of skin and CNS involvement with a heterogeneous nonspecific clinical presentation and variable imaging sometimes suggestive of vasculitis [16,17].…”

Intravascular Lymphoma: A Unique Pattern Underlying a Protean Disease

“…IVLBCL is a rare neoplasm mostly affecting elderly individuals, with an incidence below 1/1.000.000 person/year, a median age at diagnosis of 67 years (range: 23–92) and an approximately equal male-to-female ratio [ 2 , 3 ].…”

Intravascular Large B-Cell Lymphoma Diagnosed After Recurrent Stroke: Case Report and Literature Review

“…Currently, there is no noninvasive method to confirm IVLBCL without a biopsy; however, potential markers that can raise suspicion about the disease are being identified [ 9 ]. Potential blood markers for IVLBCL include elevated levels of CRP, ferritin, fibrinogen, LDH, and β2-microglobulin, as well as cytopenia affecting at least one cell line, which may manifest as anemia, lymphopenia, or thrombopenia, which have been noted in most cases.…”

“…Potential blood markers for IVLBCL include elevated levels of CRP, ferritin, fibrinogen, LDH, and β2-microglobulin, as well as cytopenia affecting at least one cell line, which may manifest as anemia, lymphopenia, or thrombopenia, which have been noted in most cases. In some instances, liver function tests have revealed cholestasis and elevated transaminases, along with mild hyponatremia and renal failure [ 9 ]. CSF abnormalities have also been noted, with increased protein levels observed in 94% of cases and pleocytosis in 71%, although tumor cells have not been detected in cytology.…”

“…CSF abnormalities have also been noted, with increased protein levels observed in 94% of cases and pleocytosis in 71%, although tumor cells have not been detected in cytology. Additionally, some patients may present with elevated levels of CSF LDH, IL-6, IL-10, IL-10/IL-6 ratios, and β2 microglobulin [ 9 , 10 ]. A biopsy is essential for a definitive diagnosis of IVLBCL, as it allows for the identification of tumor cells within the small blood vessels of the tissue [ 7 ].…”

A 13‐Year Review of Non‐Diffuse Large B Cell Lymphomas of the Central Nervous System at a Tertiary Hospital: A Case Series Study

“…The second case was diagnosed at post-mortem examination of an individual with a history of CLL and Parkinsonism; many leptomeningeal and intraparenchymal vessels were distended and filled with enlarged atypical B cells which had resulted in several recent infarcts (Figure 4). ILBCL is a rare entity with a high incidence of skin and CNS involvement with a heterogeneous nonspecific clinical presentation and variable imaging sometimes suggestive of vasculitis [16,17].…”

Intravascular Lymphoma: A Unique Pattern Underlying a Protean Disease

“…IVLBCL is a rare neoplasm mostly affecting elderly individuals, with an incidence below 1/1.000.000 person/year, a median age at diagnosis of 67 years (range: 23–92) and an approximately equal male-to-female ratio [ 2 , 3 ].…”

Intravascular Large B-Cell Lymphoma Diagnosed After Recurrent Stroke: Case Report and Literature Review

“…Currently, there is no noninvasive method to confirm IVLBCL without a biopsy; however, potential markers that can raise suspicion about the disease are being identified [ 9 ]. Potential blood markers for IVLBCL include elevated levels of CRP, ferritin, fibrinogen, LDH, and β2-microglobulin, as well as cytopenia affecting at least one cell line, which may manifest as anemia, lymphopenia, or thrombopenia, which have been noted in most cases.…”

“…Potential blood markers for IVLBCL include elevated levels of CRP, ferritin, fibrinogen, LDH, and β2-microglobulin, as well as cytopenia affecting at least one cell line, which may manifest as anemia, lymphopenia, or thrombopenia, which have been noted in most cases. In some instances, liver function tests have revealed cholestasis and elevated transaminases, along with mild hyponatremia and renal failure [ 9 ]. CSF abnormalities have also been noted, with increased protein levels observed in 94% of cases and pleocytosis in 71%, although tumor cells have not been detected in cytology.…”

“…CSF abnormalities have also been noted, with increased protein levels observed in 94% of cases and pleocytosis in 71%, although tumor cells have not been detected in cytology. Additionally, some patients may present with elevated levels of CSF LDH, IL-6, IL-10, IL-10/IL-6 ratios, and β2 microglobulin [ 9 , 10 ]. A biopsy is essential for a definitive diagnosis of IVLBCL, as it allows for the identification of tumor cells within the small blood vessels of the tissue [ 7 ].…”

A 13‐Year Review of Non‐Diffuse Large B Cell Lymphomas of the Central Nervous System at a Tertiary Hospital: A Case Series Study

“…The second case was diagnosed at post-mortem examination of an individual with a history of CLL and Parkinsonism; many leptomeningeal and intraparenchymal vessels were distended and filled with enlarged atypical B cells which had resulted in several recent infarcts (Figure 4). ILBCL is a rare entity with a high incidence of skin and CNS involvement with a heterogeneous nonspecific clinical presentation and variable imaging sometimes suggestive of vasculitis [16,17].…”

Intravascular Lymphoma: A Unique Pattern Underlying a Protean Disease

“…IVLBCL is a rare neoplasm mostly affecting elderly individuals, with an incidence below 1/1.000.000 person/year, a median age at diagnosis of 67 years (range: 23–92) and an approximately equal male-to-female ratio [ 2 , 3 ].…”