T-Cell Acute Lymphoblastic Leukemia-associated Membranous Nephropathy in an Adult Patient - A Case Report - Abstract
Background: Patients with membranous nephropathy (MN) may have an associated malignancy, commonly solid tumors. Here we present a case of T-cell acute lymphoblasti leukemia (T-ALL) and concurrent MN; the clinical course indicated there was a causal link between the two disorders.
Case presentation: A 58-year-old Caucasian woman was admitted because of weakness, leukocytosis, anemia, thrombocytopenia, symptoms of the nephrotic syndrome, and renal failure. The hematological workup diagnosed Philadelphia chromosome-positive T-ALL. The UKALL60+ protocol then induced the complete remission of leukemia; the renal function returned to normal, and proteinuria almost ceased. A molecular relapse of leukemia was detected in the third month of chemotherapy, followed by the recurrence of the ephrotic syndrome and renal failure. The renal biopsy workup revealed MN stage 1-2, glomerular leukocytosis, and acute tubular injury. The deposits, distributed incomplete globally, were stained brightly for polytypic IgG, IgG1, IgG4, and C3. The staining for PLA2R antigen revealed a segmental distribution and weak positivity in deposits. The IgG2, IgG3, C1q, THSD7A and NELL1 staining were negative. The leukemic lymphoblasts expressed CD10 (CALLA/NEP) immunohistochemically; no change was observed in the CD10 expression of podocytes. An indirect immunofluorescence assay for autoantibodies against PLA2R, THSD7A or NEP revealed an anti-PLA2R titer of 1:40. Despite complex therapy, she remained on hemodialysis and passed.
Conclusions: The remission of heavy proteinuria with successful treatment of leukemia followed by relapse soon after the molecular recurrence of leukemia indicated T-ALLassociated MN. The pathological phenotype was characterized by an incomplete global distribution of IgG1-IgG4 codominant deposits, segmental and weak staining for PLA2R in the deposits, and glomerular leukocytosis. Taking into consideration the low serum anti-PLAR antibody titer, MN was probably mediated by a dual autoimmune response; namely a robust one for a hidden tumor antigen, and a weak one for PLA2R.