Intravascular Large B-cell Lymphoma



Intravascular Large B-cell Lymphoma


Francisco Vega, MD, PhD





Key Facts


Terminology



  • Rare large B-cell lymphoma characterized by selective intravascular growth


Clinical Issues



  • Absence of marked lymphadenopathy


  • Middle-aged or elderly patients


  • Predominant neurologic and dermatologic manifestations (Western countries)


  • Patients from Asia (mainly Japan) preferentially show hemophagocytic syndrome (Asian variant)


Microscopic Pathology



  • IVLBCL cells are large, with vesicular nuclear chromatin, distinct nucleoli, and frequent mitoses


  • Lymphoma cells are mainly located in lumina of small vessels


  • Sinusoidal involvement of liver, spleen, and bone marrow


Ancillary Tests



  • Pan-B-cell markers(+), Bcl-2(+), MUM1(+)


  • CD5([+] 30%); other T-cell markers(−)


  • Ki-67 high


Top Differential Diagnoses



  • Peripheral T- or NK-cell lymphomas with intravascular pattern


  • Hepatosplenic T-cell lymphoma


  • T-cell large granular lymphocytic leukemia


  • Aggressive NK-cell leukemia/lymphoma


  • Splenic B-cell marginal zone lymphoma


  • Diffuse large B-cell lymphoma







Intravascular large B-cell lymphoma (IVLBCL) in nephrectomy specimen of a patient with renal clear cell carcinoma. Large atypical lymphoid cells are seen inside of small sinusoid-like vessels image.






The intravascular large cells are CD20(+) and negative for T-cell antigens (not shown), which supports a B-cell lineage and the diagnosis of IVLBCL.


TERMINOLOGY


Abbreviations



  • Intravascular large B-cell lymphoma (IVLBCL)


Synonyms



  • Angiotropic large cell lymphoma


  • Angioendotheliotropic (intravascular) lymphoma


  • Intravascular lymphomatosis


Definitions



  • Large B-cell lymphoma characterized by selective intravascular growth


  • Preferential intravascular growth is a conditio sine qua non for diagnosing IVLBCL



    • Concomitant and minimal extravascular location of neoplastic cells, usually surrounding involved vessels, can be seen


CLINICAL ISSUES


Site



  • Selective tumor growth within lumina of small blood vessels, particularly capillaries


  • Widely disseminated


  • Any organ can be involved


  • Absence of marked lymphadenopathy


  • Mechanisms responsible for selective growth of neoplastic cells within blood vessel lumina are unknown


  • Possible explanations include



    • Chemokine-chemokine receptor interactions



      • e.g., CXCL9 (expressed in endothelium) and CXCR3 (expressed in IVLBCL)


    • Decreased expression of adhesion molecules on surface of IVLBCL cells



      • e.g., CD29 and CD54


Presentation



  • Middle-aged or elderly patients; median: 67 years


  • M:F ratio = 1.3:1


  • IVLBCL can involve any organ with heterogeneous, often nonspecific symptoms



    • Fever of unknown origin


    • General fatigue


    • Deterioration in performance status


  • Diagnosis can be clinically difficult and some cases are diagnosed postmortem


  • 2 major patterns of clinical presentation



    • Western IVLBCL



      • Predominant neurologic and dermatologic manifestations


      • Central nervous system is involved in most patients


    • Asian IVLBCL



      • Hemophagocytic syndrome


      • Fever and B symptoms


      • Pancytopenia and bone marrow infiltration


      • Skin and central nervous system involvement are uncommon


  • Skin lesions



    • Heterogeneous clinical presentation: Plaques, telangiectatic patches, cellulitis, ulcerated nodules


    • Skin involvement is sometimes detected by random skin biopsy of grossly unremarkable skin


    • Cutaneous variant



      • Most frequent in females


      • Younger than other IVLBCL patients


      • Better prognosis


  • Kidney



    • Increased creatinine


    • Proteinuria


    • Renal insufficiency


  • Liver



    • Hepatomegaly


    • Increased bilirubin and liver enzymes


  • Central nervous system




    • Alteration of consciousness


    • Motor and sensory deficits


    • Seizure


    • Dementia


  • Lungs



    • Dyspnea and hypoxia


  • Hematopoietic system



    • Splenomegaly


    • Hemophagocytosis


    • Anemia, thrombocytopenia, and leukopenia


  • Other



    • Increased LDH


    • Ascites


    • Endocrine dysfunction (hypopituitarism)


    • Multiorgan failure


Treatment



  • Rituximab-containing chemotherapy plus central nervous system-oriented therapy



    • R-CHOP plus high-dose methotrexate


Prognosis



  • Aggressive behavior and often fatal course


  • Predictive factors that are useful for risk-stratification are not established


MICROSCOPIC PATHOLOGY


Histologic Features



  • Lymphoma cells are mainly located in lumina of small vessels


  • Minimal extravascular location of tumor cells can be seen



    • Usually surrounding involved vessels


    • Extravascular masses can be detected at autopsy in some patients


  • Sinusoidal involvement of liver, spleen, and bone marrow


  • Spleen: Red pulp involvement


  • Kidney: Neoplastic cells within glomerular capillaries and peritubular capillaries


  • Brain: Neoplastic cells within small vessels


  • Circulating lymphoma cells can be occasionally seen in peripheral blood


  • Fibrin thrombi, hemorrhage, and necrosis


Cytologic Features



  • Usually tumor cells are large, with vesicular nuclear chromatin with distinct nucleoli


  • In some cases, tumor cells have coarse nuclear chromatin and irregular or indented nuclei


  • Mitoses are frequent


  • IVLBCL cell size may be smaller than usual in some cases

Tags:
Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Intravascular Large B-cell Lymphoma

Full access? Get Clinical Tree
Get Clinical Tree app for offline access