Concomitant Essential Thrombocythemia and Mature B -Lymphoproliferative Disorder in a Patient

A-64-year old male presented with cough, weight loss, and maculopapular rash for 15-20 days. On examination, he was found to have cervical lymphadenopathy and splenomegaly. His leukocyte count was 62.1x109/L, platelets were 1169x109/L and LDH was 816 IU/L. Peripheral blood film showed a leukoerythroblastic picture with thrombocytosis. He was started on hydroxyurea and allopurinol. Subsequently, bone marrow evaluation was done which depicted increased lymphoid cells with an M:E ratio of 4:1. Cellular areas exhibited an increase in myeloid precursors along with prominent lymphoid cells and abundant megakaryocytes. Immunohistochemistry showed an increase in B-lymphocytes. Grade MF-2 reticulin fibrosis was noted. Overall findings suggested essential thrombocythemia (ET). On flow cytometry, CD45-positive lymphoid cells population was 31% and showed reactivity to Pan-B-markers with lambda light chain restriction. Janus Kinase 2 (JAK 2) mutation was detected while BCR-ABL1 translocation was negative. A diagnosis of ET progressing to myelofibrosis and mature B-lymphoproliferative disorder was made. Hydroxyurea and allopurinol were stopped while ruxolitinib was introduced and 2.5 years later he remains stable on this treatment.

Can Antinuclear Antibodies (ANA) be Monoclonal?

Background. Nuclear staining by immunofluorescence in a kidney biopsy is often seen in patients with positive antinuclear antibodies (ANA) in the serum. These ANA are usually polyclonal, but herein we report 9 cases with an unusual finding of monoclonal nuclear staining by immunofluorescence on kidney biopsy. Case Presentation. Nine cases with predominant stain for kappa or lambda light chain were identified by searching the renal pathology laboratory database for the past 10 years. All cases had positive stain for only kappa (six cases) or lambda (three cases) light chain in the nuclei. Eight out of nine cases had positive nuclear IgG stain, and one case had positive nuclear IgA stain. Among cases with positive nuclear IgG staining, six cases were positive for IgG1 subclass, one case was positive for IgG2 subclass, and one case was positive for IgG3 subclass. All patients with positive IgG nuclear stain, who had testing for ANA, had positive ANA. Patients with positive IgG1 subclass did not have monoclonal protein in the serum or urine, but the patient with positive IgG2 subclass and lambda light chain stain in the nuclei had IgG lambda monoclonal gammopathy. Conclusions. We identified a new unique pattern of nuclear stain by immunofluorescence in kidney biopsies that suggests the presence of monoclonal ANA. Workup for underlying monoclonal gammopathy is warranted in such patients.

Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis with Kidney Involvement in a Patient with AL Amyloidosis

Antineutrophil cytoplasmic autoantibody (ANCA) vasculitis has occasionally been associated with other systemic glomerulonephritis, such as anti-glomerular basement membrane disease. Here, we report the first clinical case of ANCA-associated crescentic glomerulonephritis with AL amyloidosis. An 81-years-old gentleman presented to the hospital with acute kidney injury (serum creatinine 4.7 mg/dL) on a background of chronic kidney disease and volume overload. Autoimmune serology was remarkable for p-ANCA and myeloperoxidase positivity. A renal biopsy confirmed pauci-immune glomerulonephritis and lambda light-chain amyloid deposition (confirmed on liquid chromatography and tandem mass spectrometry). The patient was initially managed with rituximab and subsequently transitioned to bortezomib-based chemotherapy but died due to decompensated heart failure. This case report promotes greater awareness of the unusual presentation of amyloidosis and guides future research and treatment.

A Rare Case of Immunotactoid Glomerulopathy Associated with Hodgkin Lymphoma

Immunotactoid glomerulopathy (ITG) is characterized by Congo red-negative microtubular deposits, and it has been reported as a rare paraneoplastic syndrome due to hematologic malignancies, viral infections, or autoimmune diseases. In hematologic malignancies, multiple myeloma and other mature B-cell malignancies are the most common hematologic malignancies, and Hodgkin lymphoma (HL) is extremely rare. A 59-year-old woman was admitted to our hospital because of a pulmonary mass and proteinuria. Computed tomography-guided lung biopsy confirmed the presence of HL stage IIA. Immunofixation of peripheral blood was positive for immunoglobulin G (IgG) kappa. Renal biopsy showed mesangial proliferation with deposits in the subendothelial lesion and no invasion of the HL. These deposits were positive for IgG3, C3, and kappa light chain but negative for C1q and lambda light chain. Electron microscopy showed randomly aligned tubular structures with a diameter of approximately 50 nm. We diagnosed the patient with immunotactoid nephropathy and HL. After systemic chemotherapy, the patient achieved a complete response and loss of proteinuria. On the contrary, her serum monoclonal gammopathy was observed after chemotherapy. The existence of a monoclonal antibody itself might not be a sufficient factor for ITG in some cases, and an additive trigger is necessary for development.

Comparison of lambda and kappa light-chain cardiac amyloidosis in Polish patients diagnosed in cardiology department

Background Lambda (λ) and kappa (κ) types of light-chain amyloidosis (AL amyloidosis) are believed to have a similar prognosis. Data on the comparison of these two types of cardiac amyloidosis is scanty. Objectives The aim of the study was to investigate wether lambda light-chain cardiac amyloidosis indicates worse prognosis than the kappa variety. Methods The initial analysis covered all consecutive pts with cardiac AL amyloidosis diagnosed in the cardiology department from August 2011 to August 2019. Diagnosis was confirmed by increased serum free light-chains and positive tissue biopsy. Amyloid type was identified using immunohistochemical reactions. Blood pressure and heart rate (HR) were measured on admission. The difference between involved and uninvolved serum free light chains (dFLC), NT-proBNP, high-sensitivity troponin T (hs-TnT), creatinine, potassium, albumin and total protein were measured. During echocardiography, tissue Doppler imaging was used to assess early lateral (e' lat) and septal mitral annulus velocities and longitudinal myocardial velocities of ventricles. Standard parameters were measured. The presence of pleural effusion was assessed in chest X-ray. Results Sixty-four pts were diagnosed with AL amyloidosis. Four pts were excluded from the final analysis due to ambiguous amyloid typing. Median (interquartile range, IQR) age was 61 (52–67) yrs. Median (IQR) dFLC was 19.9 (5.5–50.6) mg/dL. Median NT-proBNP and hs-TnT concentrations were 4948 (2251–10206) pg/ml and 77 (39–139) ng/l, respectively. Forty-four pts had a λ type AL amyloidosis (73.3%). There were significant differences (p<0.05) between the λ and the κ groups in regard to: HR (80 vs. 73.5 BPM), systolic blood pressure (102 vs. 117 mmHg), serum creatinine (88 vs. 116 umol/L) and potassium (4.4 vs. 4.9 mmol/L), e' lat (5 vs. 7.5 cm/sec), left ventricular end-diastolic diameter (LVEDD, 42 vs. 46 mm), right ventricular end-diastolic diameter (RVEDD, 35 vs. 40 mm) and right ventricular wall thickness (8 vs. 6 mm). Pleural and pericardial effusions were more frequent in the λ group (59% vs. 19% and 80% vs. 44%, respectively) according to Fisher's exact test (p<0.05). Median (IQR) survivals for the λ and the κ groups were 3 (2–9) and 16 (5.5–22) months, respectively (p=0.03). The Kaplan-Meier curves analysis showed a trend towards worse survival of the λ group (Log rank test, p=0.08). Conclusions Cardiologists should be aware that lambda light-chain cardiac amyloidosis may indicate shorter survival than the kappa variety, although kappa AL amyloidosis may be associated with worse kidney function. Further research would be worth considering. Kaplan-Meier curves, Time (months) Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Institute of Cardiology

P0140RENAL PATHOLOGICAL CHANGES AFTER SUCCESSFUL TREATMENT OF LCDD USING CYCLOPHOSPHAMIDE, THALIDOMIDE AND DEXAMETHASONE: A CASE REPORT

Background and Aims The combined of cyclophosphamide, thalidomide and dexamethasone (CTD) haven’t reported in treatment of LCDD, and how the renal pathologic injury changes after treatment is still unknown. Method Here we descript a LCDD patients who undergone repeated renal biopsy after treatment. Results We report a 56-year-old woman presented with nephrotic syndrome, impaired renal function, and serum M-protein of IgG lambda. First renal biopsy showed severe nodular glomerulosclerosis with single lambda light chain linear deposit along GBM. The patient treated with 14 cycles CTD regimen, and reached the complete hematologic response and renal response. At the 29 months of follow up, the repeated biopsy showed the glomerular nodular sclerosis attenuated significantly, only trace granular electron-dense deposits along inner side of GBM.(Details in figure 1: The pathological findings of the first (A-D) and second (E-H) renal biopsy.) Conclusion This case highlights the hematologic response not only can improve the renal function, but also alleviate the renal nodular sclerosis. And the low-cost regimen, CTD, maybe a good choice.

Lambda light chain crystalline proximal tubulopathy with probable light chain cast nephropathy and clonal plasma cell infiltrate – uncommon manifestations of a rare form of multiple myeloma

Light chain proximal tubulopathy (LCPT) is an uncommon renal disease characterized by the accumulation of monoclonal light chains within proximal tubular epithelial cells, with or without crystal formation. We report a rare case of lambda LCPT with crystals. Renal biopsy showed substantial acute tubular injury with unusual cytoplasmic changes affecting proximal tubules. In addition, abnormal tubular casts suggested concomitant light chain cast nephropathy. A clonal plasma cell infiltrate was present in the tubulointerstitial compartment. Immunofluorescence demonstrated strong staining for lambda light chain in tubular epithelial cells. Despite the absence of discernible crystals on light microscopy (LM), they were readily identified when ultrastructural evaluation was undertaken. Crystalline inclusions demonstrated positive immunogold labelling for lambda.