Liman AD

Introduction: Monoclonal gammopathy of renal significance (MGRS) is a recently recognized disorder from pathologic M protein causing renal disease and minimal hematologic disease burden. Failure to treat leads to poor outcomes from progression to advanced monoclonal gammopathies and end stage renal disease (ESRD). We present a case of MGRS with immunotactoid glomerulopathy.

Case Report: A 66-year-old female presented in December 2015 with mild granulocytopenia and anemia. Workup revealed serum 0.28 mg/dL IgM kappa monoclonal M-protein and kappa/lambda ratio of 2.23. She underwent surveillance for MGUS. Due to acute kidney injury, peripheral edema and hypertension, nephrology workup was obtained in December 2017. She had nephrotic range proteinuria and hematuria. Urine studies suggested paraproteinemia. Renal biopsy demonstrated immunotactoid glomerulopathy with membranoproliferative glomerulonephritis pattern. Immunofluorescence showed kappa light chain in mesangial and capillary loop, and heavy IgM and moderate C3 staining. Electron microscopy revealed numerous immunotactoid deposits beneath the glomerular basement membrane and mesangium. M-protein burden remained stable. Her bone marrow biopsy was nondiagnostic, however peripheral flow cytometry identified a small CD20+, CD5-, CD10-, CD23-, B-cell population with kappa light chain restriction. Diagnosis was reclassified as MGRS and she was treated with rituximab weekly for four doses. Follow-up demonstrated stability of M-protein and light chains, improvement of AKI and hypertension, but persistent nephrotic range proteinuria. We are planning an additional eight-week course of weekly rituximab. Treatment outcome and further studies are pending.

Discussion: MGRS is a rare monoclonal gammopathy that was formerly subclassified under MGUS. Patients were undertreated due to under-recognition of the disorder and its renal sequalae. Treatment with regimens targeting a plasma cell or B-cell clone can reduce the clone and improve renal outcomes. Our patient experienced a partial response to clone directed therapy with rituximab. Further treatment is pending.

Conclusion: Clinicians should be aware of MGRS. Collaboration with nephrology is key for proper diagnosis and prognosis. Consider treating more aggressively than MGUS to improve renal and hematologic outcomes. Prospective interventional studies are needed.

Introduction: Monoclonal gammopathy of renal significance (MGRS) is a recently recognized disorder from pathologic M protein causing renal disease and minimal hematologic disease burden. Failure to treat leads to poor outcomes from progression to advanced monoclonal gammopathies and end stage renal disease (ESRD). We present a case of MGRS with immunotactoid glomerulopathy.

Case Report: A 66-year-old female presented in December 2015 with mild granulocytopenia and anemia. Workup revealed serum 0.28 mg/dL IgM kappa monoclonal M-protein and kappa/lambda ratio of 2.23. She underwent surveillance for MGUS. Due to acute kidney injury, peripheral edema and hypertension, nephrology workup was obtained in December 2017. She had nephrotic range proteinuria and hematuria. Urine studies suggested paraproteinemia. Renal biopsy demonstrated immunotactoid glomerulopathy with membranoproliferative glomerulonephritis pattern. Immunofluorescence showed kappa light chain in mesangial and capillary loop, and heavy IgM and moderate C3 staining. Electron microscopy revealed numerous immunotactoid deposits beneath the glomerular basement membrane and mesangium. M-protein burden remained stable. Her bone marrow biopsy was nondiagnostic, however peripheral flow cytometry identified a small CD20+, CD5-, CD10-, CD23-, B-cell population with kappa light chain restriction. Diagnosis was reclassified as MGRS and she was treated with rituximab weekly for four doses. Follow-up demonstrated stability of M-protein and light chains, improvement of AKI and hypertension, but persistent nephrotic range proteinuria. We are planning an additional eight-week course of weekly rituximab. Treatment outcome and further studies are pending.

Discussion: MGRS is a rare monoclonal gammopathy that was formerly subclassified under MGUS. Patients were undertreated due to under-recognition of the disorder and its renal sequalae. Treatment with regimens targeting a plasma cell or B-cell clone can reduce the clone and improve renal outcomes. Our patient experienced a partial response to clone directed therapy with rituximab. Further treatment is pending.

Conclusion: Clinicians should be aware of MGRS. Collaboration with nephrology is key for proper diagnosis and prognosis. Consider treating more aggressively than MGUS to improve renal and hematologic outcomes. Prospective interventional studies are needed.

Introduction: Monoclonal gammopathy of renal significance (MGRS) is a recently recognized disorder from pathologic M protein causing renal disease and minimal hematologic disease burden. Failure to treat leads to poor outcomes from progression to advanced monoclonal gammopathies and end stage renal disease (ESRD). We present a case of MGRS with immunotactoid glomerulopathy.

Case Report: A 66-year-old female presented in December 2015 with mild granulocytopenia and anemia. Workup revealed serum 0.28 mg/dL IgM kappa monoclonal M-protein and kappa/lambda ratio of 2.23. She underwent surveillance for MGUS. Due to acute kidney injury, peripheral edema and hypertension, nephrology workup was obtained in December 2017. She had nephrotic range proteinuria and hematuria. Urine studies suggested paraproteinemia. Renal biopsy demonstrated immunotactoid glomerulopathy with membranoproliferative glomerulonephritis pattern. Immunofluorescence showed kappa light chain in mesangial and capillary loop, and heavy IgM and moderate C3 staining. Electron microscopy revealed numerous immunotactoid deposits beneath the glomerular basement membrane and mesangium. M-protein burden remained stable. Her bone marrow biopsy was nondiagnostic, however peripheral flow cytometry identified a small CD20+, CD5-, CD10-, CD23-, B-cell population with kappa light chain restriction. Diagnosis was reclassified as MGRS and she was treated with rituximab weekly for four doses. Follow-up demonstrated stability of M-protein and light chains, improvement of AKI and hypertension, but persistent nephrotic range proteinuria. We are planning an additional eight-week course of weekly rituximab. Treatment outcome and further studies are pending.

Discussion: MGRS is a rare monoclonal gammopathy that was formerly subclassified under MGUS. Patients were undertreated due to under-recognition of the disorder and its renal sequalae. Treatment with regimens targeting a plasma cell or B-cell clone can reduce the clone and improve renal outcomes. Our patient experienced a partial response to clone directed therapy with rituximab. Further treatment is pending.

Conclusion: Clinicians should be aware of MGRS. Collaboration with nephrology is key for proper diagnosis and prognosis. Consider treating more aggressively than MGUS to improve renal and hematologic outcomes. Prospective interventional studies are needed.

Introduction: Systemic mastocytosis (SM) is a rare myeloid neoplasm that is caused by accumulation of abnormal mast cells in the bone marrow, liver, spleen, and skin. The KIT D816V mutation encodes a constitutively activated receptor tyrosine kinase that drives disease pathogenesis. We present a case of systemic mastocytosis with associated clonal hematological non-mast cell disease (SM-AHNMD).

Background: A 71-year-old man presented with anemia, thrombocytopenia, absolute monocyte count of 2,000-4,000 and weight loss in August 2016. A CT showed splenomegaly and lymphadenopathy. Bone marrow biopsy revealed positive CD117 mast cells, CD34 myeloblasts and reticulin fibrosis consistent with SM. Immunohistochemistry confirmed the neoplastic cells were positive for CD25, but negative for CD2. PCR analysis revealed KIT D816V point mutation. Serum tryptase was 295 ug/L (normal 2.2-13.2). He was started on imatinib mesylate. However, his anemia, thrombocytopenia and splenomegaly worsened. He developed bilateral femoral neck fractures in April 2017. Imatinib was discontinued. He underwent bilateral hip hemiarthroplasty. Histology was consistent with SM (positive CD25 and CD117) with dysplastic megakaryocytes and increased monocytosis. By WHO classification he has SM-AHNMD with chronic myelomonocytic leukemia. He was started on cladribine for 4 cycles with good response in splenomegaly, anemia and thrombocytopenia, but he developed leukocytosis. Serum tryptase initially decreased to 141 but then rose to 243. Midostaurin 100 mg orally twice a day was initiated in December 2017. His cytopenia and splenomegaly improved. In March 2018 he was admitted for sigmoid colon obstruction due to inflammation or mass and underwent diverting loop ileostomy. Biopsy could not be performed. His serum tryptase decreased to 178 but increased to 275 in June 2018. He continues on midostaurin.

Discussion: SM-AHNMD constitutes approximately 40% of all SM with poor prognosis. SM is resistance to imatinib because of KIT D816V mutation. Cladribine has some activity. Midostaurin inhibits non-mutant and mutant KIT D816V with 58% response rate and median overall survival of 20 months. Our patient has a good response to both drugs.

Conclusions: Clinicians should be able to diagnose and treat SM. Cladribine and midostaurin are active drugs for SM.

Introduction: Systemic mastocytosis (SM) is a rare myeloid neoplasm that is caused by accumulation of abnormal mast cells in the bone marrow, liver, spleen, and skin. The KIT D816V mutation encodes a constitutively activated receptor tyrosine kinase that drives disease pathogenesis. We present a case of systemic mastocytosis with associated clonal hematological non-mast cell disease (SM-AHNMD).

Background: A 71-year-old man presented with anemia, thrombocytopenia, absolute monocyte count of 2,000-4,000 and weight loss in August 2016. A CT showed splenomegaly and lymphadenopathy. Bone marrow biopsy revealed positive CD117 mast cells, CD34 myeloblasts and reticulin fibrosis consistent with SM. Immunohistochemistry confirmed the neoplastic cells were positive for CD25, but negative for CD2. PCR analysis revealed KIT D816V point mutation. Serum tryptase was 295 ug/L (normal 2.2-13.2). He was started on imatinib mesylate. However, his anemia, thrombocytopenia and splenomegaly worsened. He developed bilateral femoral neck fractures in April 2017. Imatinib was discontinued. He underwent bilateral hip hemiarthroplasty. Histology was consistent with SM (positive CD25 and CD117) with dysplastic megakaryocytes and increased monocytosis. By WHO classification he has SM-AHNMD with chronic myelomonocytic leukemia. He was started on cladribine for 4 cycles with good response in splenomegaly, anemia and thrombocytopenia, but he developed leukocytosis. Serum tryptase initially decreased to 141 but then rose to 243. Midostaurin 100 mg orally twice a day was initiated in December 2017. His cytopenia and splenomegaly improved. In March 2018 he was admitted for sigmoid colon obstruction due to inflammation or mass and underwent diverting loop ileostomy. Biopsy could not be performed. His serum tryptase decreased to 178 but increased to 275 in June 2018. He continues on midostaurin.

Discussion: SM-AHNMD constitutes approximately 40% of all SM with poor prognosis. SM is resistance to imatinib because of KIT D816V mutation. Cladribine has some activity. Midostaurin inhibits non-mutant and mutant KIT D816V with 58% response rate and median overall survival of 20 months. Our patient has a good response to both drugs.

Conclusions: Clinicians should be able to diagnose and treat SM. Cladribine and midostaurin are active drugs for SM.

Introduction: Systemic mastocytosis (SM) is a rare myeloid neoplasm that is caused by accumulation of abnormal mast cells in the bone marrow, liver, spleen, and skin. The KIT D816V mutation encodes a constitutively activated receptor tyrosine kinase that drives disease pathogenesis. We present a case of systemic mastocytosis with associated clonal hematological non-mast cell disease (SM-AHNMD).

Background: A 71-year-old man presented with anemia, thrombocytopenia, absolute monocyte count of 2,000-4,000 and weight loss in August 2016. A CT showed splenomegaly and lymphadenopathy. Bone marrow biopsy revealed positive CD117 mast cells, CD34 myeloblasts and reticulin fibrosis consistent with SM. Immunohistochemistry confirmed the neoplastic cells were positive for CD25, but negative for CD2. PCR analysis revealed KIT D816V point mutation. Serum tryptase was 295 ug/L (normal 2.2-13.2). He was started on imatinib mesylate. However, his anemia, thrombocytopenia and splenomegaly worsened. He developed bilateral femoral neck fractures in April 2017. Imatinib was discontinued. He underwent bilateral hip hemiarthroplasty. Histology was consistent with SM (positive CD25 and CD117) with dysplastic megakaryocytes and increased monocytosis. By WHO classification he has SM-AHNMD with chronic myelomonocytic leukemia. He was started on cladribine for 4 cycles with good response in splenomegaly, anemia and thrombocytopenia, but he developed leukocytosis. Serum tryptase initially decreased to 141 but then rose to 243. Midostaurin 100 mg orally twice a day was initiated in December 2017. His cytopenia and splenomegaly improved. In March 2018 he was admitted for sigmoid colon obstruction due to inflammation or mass and underwent diverting loop ileostomy. Biopsy could not be performed. His serum tryptase decreased to 178 but increased to 275 in June 2018. He continues on midostaurin.

Discussion: SM-AHNMD constitutes approximately 40% of all SM with poor prognosis. SM is resistance to imatinib because of KIT D816V mutation. Cladribine has some activity. Midostaurin inhibits non-mutant and mutant KIT D816V with 58% response rate and median overall survival of 20 months. Our patient has a good response to both drugs.

Conclusions: Clinicians should be able to diagnose and treat SM. Cladribine and midostaurin are active drugs for SM.