Intravascular large B-cell lymphoma (IVLBCL) is a rare extra-nodal B-cell lymphoma that proliferates within small/intermediate blood vessels and capillaries while sparing large blood vessels and organ parenchyma. Clinical presentation is highly variable and may include B symptoms, neurological deficits, and/or cutaneous findings. The diagnosis of IVLBCL is difficult due to multiorgan involvement and nonspecific symptoms. We describe the case of a 68-year-old male who presented with progressive weakness, confusion, and falls. He had a past medical history of liver cirrhosis secondary to Wilson’s disease. Physical exam and laboratory results revealed a lethargic man with jaundice, hepatic encephalopathy, and abnormal liver/kidney function tests. He expired after a short hospital course in the setting of hepatic and renal failure. Postmortem examination revealed large neoplastic lymphoid cells involving multiple organ blood vessels; however skin and neurologic involvement was absent. The neoplastic cells demonstrated B-cells positive for CD5, rendering a diagnosis of IVLBCL. Our case represents the occurrence of IVLBCL with CD5-positivity in a patient with Wilson’s disease, diagnosed at autopsy demonstrating the challenging nature of diagnosing IVLBCL.
Intravascular large B-cell lymphoma (IVLBCL) is a rare B-cell lymphoma involving and proliferating within small blood vessels and capillaries with sparing of large blood vessels [
A 68-year-old male presented to the emergency department with progressive weakness, intermittent confusion, and falls. Past medical history was significant for coronary artery disease, peripheral vascular disease, hypertension, diabetes mellitus, and liver cirrhosis secondary to Wilson’s disease. Physical exam revealed a lethargic but oriented patient with jaundice, superficial skin abrasions on arms, bilaterally diminished breath sounds, grade 2/6 systolic murmur, and lower extremity edema.
The patient was admitted for management of acute renal failure and hepatic encephalopathy. Complete metabolic profile revealed elevated ammonia of 186
The patient was placed on hemodialysis and lactulose with serial monitoring of ammonia levels. His clinical status improved slightly after dialysis but showed no sustained clinical improvement. On the
At autopsy, the patient had jaundice, bipedal edema, hepatomegaly (weight = 2219 grams) with diffuse micronodular cirrhosis, and splenomegaly (weight = 907 grams), consistent with liver failure. He had moderate cardiomegaly (weight = 533 grams) with marked concentric left ventricular hypertrophy and bilateral nephrosclerosis, consistent with long-standing hypertensive cardiovascular disease. Upon microscopic examination, numerous large atypical lymphoid cells were found within the lumen of several small blood vessels of the thyroid gland (Figures
H&E. Large neoplastic lymphoid cells with hyperchromatic nuclei and coarse chromatin are present within the small blood vessels in thyroid ((a), 10X; (b), 40X), lung ((c), 10X), omentum ((d), 20X), and gall bladder ((e), 10X).
Immunohistochemical studies performed on thyroid gland revealed that the neoplastic lymphoid cells are positive for CD20 ((a), 20X), dim CD79a ((b), 20X), MUM1 ((c), 20X), and CD5 ((d), 20X); negative for CD10 ((e), 20X), HHV8 ((f), 10X), EBER ((g), 10X), c-MYC, BCL6, and cyclin D1 (not shown).
CD20
CD79a
MUM1
CD5
CD10
HHV8
EBER
IVLBCL is a rare type of extranodal large B-cell lymphoma first described in 1959 by Pfleger and Tappeiner [
Clinical manifestations are very heterogeneous and include nonspecific B symptoms while laboratory abnormalities may show anemia and elevated lactate dehydrogenase levels [
Our case presented with nonspecific neurological symptoms (loss of consciousness and balance difficulties), found to have acute renal failure and hepatic encephalopathy which was attributed to liver cirrhosis due to Wilson’s disease. The abnormal laboratory findings of liver and kidney failure as well as deranged hematological parameters did not raise suspicion of lymphoma as these abnormalities can present in both diseases. Together with the negative brain imaging, the overall clinical findings kept clinical suspicion of any lymphomatous process very low. Detecting IVLBCL in such patients with active comorbidities is a real challenge. The antemortem diagnosis of CNS IVLBCL is especially difficult in elderly patients due to the overlapping stroke-like symptoms and nonenhancement of IVLBCL on MRI [
Histopathology is still the standard for the diagnosis of IVLBCL. Immunohistochemically, IVLBCL is positive for B-cell markers with variable aberrant expression of CD5. CD10 is found in low frequency [
Our case is unique in that the immunophenotype showed nongerminal center phenotype with CD5 positivity (more often seen in the Asian variant); however, bone marrow and peripheral blood involvement was not found. Additionally, our patient did not have hemophagocytosis or skin/CNS involvement, thus not fitting into either Asian variant (also referred to as “IVL associated with hemophagocytic syndrome”) or Western variant [
IVLBCL is an aggressive rare B-cell lymphoma with a high mortality rate. Our case demonstrates the difficulty in the diagnosis of IVLBCL, especially in the setting of neurologic symptoms and underlying liver disease due to the highly variable tissue involvement and potentially nonspecific clinical presentation. Some useful features might include neurological symptoms with negative radiological findings of a lesion or mass effect with or without skin eruptions accompanied by laboratory evidence of deranged organ function. Making an antemortem diagnosis of IVLBCL is very important given the impact of early treatment on the clinical course and prognosis of this disease. This case also illustrates the importance of careful postmortem examination and collaboration with the hematopathology team to identify and work up any atypical cells seen within the vessels, as such findings can easily go unrecognized.
The authors declare that there are no conflicts of interest regarding the publication of this article.