Kidney – S001

Submitted by: Jan Klos

Case History:

65 yrs. old man with shortness of breath and increasing creatinine levels. Renal biopsy.

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Intravascular Large B-cell Lymphoma

Selective growth of lymphoma cells within lumen of predominantly capillary blood vessels with the exception of larger arteries and veins.
T-cell and NK-cell type are reported. In Asian population there is a frequent association of this lymphoma with hemophagocytic syndrome. The first describe by two German doctors Pfelger and Tappeiner in 1959. Under many years the true nature of the disease was not recognized and cases were considered to represent endothelial proliferation and described under different names: malignant angioendotheliosis, neoplastic angioendotheliosis, malignant angioendotheliomatosis, hemangioendotheliosis, angioendotheliomatosis proliferans, angiotropic lymphoma or intravascular lymphomatosis. In 2001 WHO recognized the disease and defined it as Intravascular Large B-cell Lymphoma. The most common involvement is skin (single lesion 11% and multiple lesions in 30%) and CNS (40%), liver (26%), spleen (26%) and bone marrow (32% but only 5% in peripheral blood). Kidneys are affected in 21%, endocrine glands, lung and prostate in 16%, heart and lymph nodes in 11%, gastrointestinal tract, urinary bladder and uterus in 8% each.
Immunophenotyping shows strong positivity for B-cell markers (CD20, CD79a, PAX5) and negativity for CD3. In 20-40% of cases positivity for CD5 is reported and in 10-20% the cells are positive for CD10 or Bcl6. Absolute majority of cases is positive for MUM1 (80-90%) and Bcl-2 (>90%). Proliferating fraction estimated using KI-67 staining is around 50%. Some cases of aberrant expression of MPO or PSAP are reported. The preference to vascular spaces is explained by aberrant expression of cell adhesion molecules (CD11a, CD49d) on tumour cells which make them able to home to CD54 (CD11a ligand) and CD106 (CD49d ligand) expressed on endothelial cells. A role is played by G protein-coupled receptor 9 (CXCR3) on atypical lymphocytes, and aberrant expression of its ligand, chemokine ligand 9 (CXCL9), by the endothelial cells. Lack of molecules facilitating transvascular migration on tumour cells (CD29, CD54?) prevents them from infiltrating extravascular tissues. The diagnosis of IVBCL is dependent upon obtaining biopsy from the affected

Differential diagnosis

Non-lymphomatous intravascular growth e.g. inflammatory breast carcinoma, carcinomatosis NOS.

Lymphomatous intravascular infiltration of other than IVLBCL type like large cell lymphoma of T-cell or NK-cell type, intravascular growth in otherwise typical DLBCL, intravascular growth of B-cell lymphoma of non-large cell type (persistent polyclonal B-cell lymphocytosis, B-cell chronic lymphocytic leukaemia, mantle zone lymphoma, splenic marginal zone lymphoma, splenic B-cell lymphoma/leukaemia, unclassifiable, T-cell lymphoma of non-large cell type (hepatosplenic T-cell lymphoma, T-cell large granular lymphocytic leukaemia)