PlentiPlex™ MYD88 Waldenström lymphoma qPCR assay: A highly sensitive method for detection of MYD88 L265P mutation.

INTRODUCTION: Agarose gel-based conventional and real-time allele-specific polymerase chain reaction (AS-PCR) assays are currently used for sensitive detection and quantification of MYD88 L265P mutation. Visual inspection of an agarose gel can often be ambiguous. We propose a new allele-specific quantification PCR (AS-qPCR) assay, PlentiPlex™ MYD88 Waldenström lymphoma qPCR assay, that uses Intercalating Nucleic Acid (INA®) technology for increased affinity and specificity. METHODS: This study compares PlentiPlex™ MYD88 Waldenström lymphoma qPCR assay with conventional AS-PCR. We included a total of 102 peripheral and bone marrow blood samples from 94 patients with a lymphoproliferative disorder. Droplet digital PCR (ddPCR) was used as a third method in case of discrepancy. RESULTS: A positive percent agreement of 100% (95% CI 0.92-1.0) and a negative percent agreement of 98% (95% CI 0.90-1.0) were found between the conventional AS-PCR and the AS-qPCR methods. Including the ddPCR results to validate the discrepant cases, the sensitivity and specificity of PlentiPlex™ MYD88 Waldenström lymphoma qPCR Assay were 1.0 (95% CI 0.97-1.0) and 1.0 (95% CI 0.96-1.0), respectively. CONCLUSION: Our data demonstrate that PlentiPlex™ MYD88 Waldenström lymphoma qPCR assay is a fast, highly sensitive, and specific method for the detection of MYD88 L265P compared with conventional AS-PCR.

Enzyme replacement therapy leading to improvement in myeloma indices in a patient with concomitant Gaucher disease.

Patients with Gaucher disease (GD) have been shown previously to carry an increased risk for cancer, most commonly multiple myeloma (MM). It is currently unknown whether treatment for GD has an effect on the prevention or amelioration of MM. We present the case of a 41-year-old patient simultaneously diagnosed with GD and smouldering MM. Enzyme replacement therapy with Velaglucerase-alfa significantly improved myeloma indices.

Immunoglobulin M (IgM) multiple myeloma versus Waldenström macroglobulinemia: diagnostic challenges and therapeutic options: two case reports.

BACKGROUND: Immunoglobulin M multiple myeloma and Waldenström macroglobulinemia are two different hematological diseases with the common finding of an immunoglobulin M monoclonal gammopathy of unknown significance. However, clinical characteristics of the two entities can overlap. CASE PRESENTATION: In this report, we describe two cases of immunoglobulin M neoplasm with the same histological bone marrow presentation but with different clinical behavior, cytogenetics, and biological assessment. On the basis of comprehensive diagnostic workup, these patients were considered to have different diseases and treated accordingly with different approaches. Patient 1 (Caucasian man) presented with increased serum protein and immunoglobulin M (7665 mg/L) with an M-spike electrophoresis of 4600 mg/L. His bone marrow biopsy revealed a small-cell immunoglobulin M multiple myeloma. The result of testing for the MYD88 L265P mutation was negative, while fluorescence in situ hybridization analysis showed translocation t(11,14). A diagnosis of immunoglobulin M-κ multiple myeloma was made. Patient 1 was a candidate for bortezomib plus thalidomide and dexamethasone, followed by autologous stem cell transplant consolidation. Patient 2 (Caucasian man) showed an M-spike by protein electrophoresis (300 mg/L, 4.9%), with serum immunoglobulin M level of 327 mg/L. His bone marrow biopsy revealed immunoglobulin M-κ multiple myeloma. Computed tomography showed many enlarged lymph nodes and splenomegaly. Patient 2's clinical features were suggestive of Waldenström macroglobulinemia, in contrast to the bone marrow biopsy results. The result of testing for the MYD88 L265P mutation was positive. Patient 2 was diagnosed with Waldenström macroglobulinemia and received rituximab, cyclophosphamide, and dexamethasone. CONCLUSIONS: A correct differential diagnosis between immunoglobulin M multiple myeloma and Waldenström macroglobulinemia is a critical point in the setting of a new immunoglobulin M monoclonal gammopathy onset. These patients should undergo a complete diagnostic workup with pathological, radiological, and serological examinations to establish the diagnosis and plan the most appropriate treatment in order to improve the prognosis.

Non-occlusive Mesenteric Ischaemia and Acute Kidney Injury: A Case Report of Severe Idiopathic Systemic Capillary Leak Syndrome.

Systemic capillary leak syndrome is a rare, underdiagnosed and life-threatening disease characterized by periodic episodes of hypovolaemic shock due to leakage of plasma from the intravascular to the extravascular space. It is associated with haemoconcentration, hypoalbuminaemia and generalized oedema. We report the case of a patient with a history of emergent extensive small and large bowel resection and several episodes of hypovolaemic shock with acute renal injury, who presented with abdominal pain, headache and generalized oedema. Severe systemic capillary leak syndrome was diagnosed after a complex diagnostic approach. This case report describes the acute and prophylactic treatment administered to the patient and the 4-year follow-up. We highlight the importance of timely recognition and prompt treatment, as well as the need for new investigations to prevent the serious and unusual complications seen in this case. LEARNING POINTS: Idiopathic systemic capillary leak syndrome (ISCLS) should be suspected in the presence of the triad of hypotension, haemoconcentration and hypoalbuminaemia; the diagnostic work-up is challenging and requires exclusion of several causes of hypotension and shock of uncertain aetiology.Acute mesenteric ischaemia leading to extensive and emergent bowel resection is an irreversible but atypical complication of ISCLS; other complications include myocardial oedema and deep vein thrombosis.ISCLS is characterized by three phases; supportive as well as prophylactic treatment adapted to each phase is crucial for prognosis and to avoid end-organ damage.

A case report of paraproteinemia-associated pauci-immune glomerulonephritis - a new form of monoclonal gammopathy of renal significance?

BACKGROUND: Renal disease associated with paraproteinemias is classically predicated upon pathologic paraprotein deposition in the kidney. However, growing evidence suggests that paraproteins may be able to systemically activate complement or neutrophils to drive renal damage. This may provide an alternative pathologic mechanism for renal injury in rare cases. CASE REPORT: We report a case of a patient with crescentic pauci-immune glomerulonephritis presenting with rapidly progressive renal failure, polyarthropathy, and a purpuric rash in association with a monoclonal immunoglobulin G κ-light-chain producing multiple myeloma. Serum anti-neutrophil cytoplasmic antibodies were not detected. Kidney biopsy, including with Pronase digestion, did not reveal pathologic paraprotein deposition. Two previously published similar case reports are also discussed. CONCLUSION: We propose a novel pathologic mechanism involving monoclonal proteins as a trigger for pauci-immune glomerulonephritis, potentially via complement dysregulation and/or neutrophil activation. This requires further epidemiologic and mechanistic study.

A Case of Diffuse Plane Xanthoma Associated with Diffuse Large B Cell Lymphoma / 대한피부과학회지

Diffuse plane xanthoma is a group of plane xanthomas that present in yellow to yellowish-brown flat patches on the periorbital area, neck, upper trunk and flexural folds. It is rare and often associated with reticulo-endothelial malignancies such as multiple myeloma, monoclonal gammopathy of unknown significance and other lympho-proliferative disorders. We report a case of diffuse plane xanthoma associated with monoclonal gammopathy of unknown significance and diffuse large B cell lymphoma in a 75 year-old woman.

A Case of Diffuse Plane Xanthoma Associated with Monoclonal Gammopathy of Unknown Significance and Normolipoproteinemia / 대한피부과학회지

Diffuse plane xanthoma is a group of plane xanthomas that appear as yellow-brown flat patches or slightly elevated plaques with a wide-spread distribution. Cutaneous xanthomas may occur either hyperlipoproteinemic or normolipoproteinemic states. Diffuse plane xanthoma with normolipoproteinemia is often associated with multiple myeloma, other reticulo-endothelial malignancies and monoclonal gammopathy of unknown significance(MGUS). We report a case of diffuse plane xanthoma associated with monoclonal gammopathy of unknown significance(MGUS) and normolipoproteinemia.