Recurrent switch 2 domain RAC2 mutations in intravascular large B-cell lymphoma.
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ABSTRACT:
SUBMITTER: Kodgule R
PROVIDER: S-EPMC9706525 | biostudies-literature | 2022 Dec
REPOSITORIES: biostudies-literature
Publications
Recurrent switch 2 domain RAC2 mutations in intravascular large B-cell lymphoma.
Kodgule Rohan R Chen Jie J Khonde Pooja P Robinson Joshua J D'Albora Amy A Cook Lisa L Fronick Catrina C CC Fulton Robert R Srivatsan Sridhar Nonavinkere SN Cimino Patrick J PJ Duncavage Eric J EJ
Blood advances 20221201 23
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Project description:IntroductionRenal intravascular large B-cell lymphoma (IVLBCL) is a rare, aggressive B-cell lymphoma with neoplastic cells occupying the vascular lumina with only 53 patients reported to date. Here, we present the largest case series to characterize this rare disease.MethodsWe performed a multi-institutional, retrospective review of kidney biopsies and autopsies with a diagnosis of kidney IVLBCL and report our findings.ResultsWe identified 20 patients with an average age of 65.7 ± 7.8 years (55% males) with IVLBCL on kidney biopsy. The most common clinical presentation was fever and anemia. Acute kidney injury (AKI) was noted in 70% to 90%, proteinuria in 70% to 84.1%, hematuria in 45%, and nephrotic-range proteinuria in 10% to 26.1% of cases. The median (interquartile range) of serum creatinine was 1.75 (1.14, 3.3) mg/dl. Neoplastic lymphoid cells were present in glomeruli, peritubular capillaries, and arteries or veins. Of the patients, 44.3% showed extrarenal infiltration into bone marrow, liver, spleen, central vervous system, lung and skin. Neoplastic cells express CD20, CD79a, PAX-5, and MUM1+, and were CD10-negative. Available follow-up data showed a median survival of 21 months after diagnosis. Extrarenal involvement is a significant and independent predictor of mortality with a hazard ratio of 4.975 (95% confidence interval:1.38, 17.88) after controlling for age and gender. Serum creatinine, age, sex, and infiltration of intrarenal arteries or veins did not affect survival.ConclusionKidney IVLBCL is a rare disease that is unexpectedly diagnosed by kidney biopsy, presenting with fever, anemia, mild AKI, and proteinuria. Median survival is 21 months and extrarenal involvement is associated with worse outcome.
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Project description:IVL is characterized by a propensity for intravascular tumor cell proliferation. Premortem diagnosis of IVL is difficult because of its nonspecific clinical, laboratory, and imaging manifestations. This study examined cerebral MR imaging patterns of IVL and their changes with and without chemotherapy. Nine of 11 patients studied presented with abnormal findings. We define 5 patterns of abnormal MR imaging findings: 1) infarctlike lesions, 2) nonspecific white matter lesions, 3) meningeal enhancement, 4) masslike lesions, and 5) hyperintense lesions in the pons on T2WI. Seven patients presented with only 1 pattern, while 2 patients presented with multiple patterns. Lesions in 7 treated patients responded to chemotherapy. Pathologic specimens revealed intravascular tumor cell infiltration with associated infarctions, necrosis, congestion, demyelination, vasculitis, and tumor cell extravasation. We conclude that MR imaging patterns can be possible manifestations of intravascular-dominant infiltration by tumor cells with associated occlusion or inflammation, depending on the level of affected vessels.
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Project description:IVLBCL is a rare distinct disease entity of extranodal large B-cell lymphoma . The disease is characterized by selective growth of tumor cells in the lumina of small vessels and by the absence of remarkable lymphadenopathy. We have developed patient derived xenograft IVLBCL mouse models from primary patient bone marrow samples. This dataset includes the array CGH analysis of IVLBCL tumor cells from the mouse xenograft models.
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