alexa
Reach Us +44-1477412632
Clinical Presentation and Pathology Spectrum of Kidney Damage in Nonhodgkin Lymphoma/Leukemia and Lymphoplasmacytic Lymphomas | OMICS International
ISSN: 2329-6917
Journal of Leukemia
Make the best use of Scientific Research and information from our 700+ peer reviewed, Open Access Journals that operates with the help of 50,000+ Editorial Board Members and esteemed reviewers and 1000+ Scientific associations in Medical, Clinical, Pharmaceutical, Engineering, Technology and Management Fields.
Meet Inspiring Speakers and Experts at our 3000+ Global Conferenceseries Events with over 600+ Conferences, 1200+ Symposiums and 1200+ Workshops on Medical, Pharma, Engineering, Science, Technology and Business

Clinical Presentation and Pathology Spectrum of Kidney Damage in Nonhodgkin Lymphoma/Leukemia and Lymphoplasmacytic Lymphomas

Zakharova EV1* and Stolyarevich ES2

1Nephrology Unit, City Clinical Hospital, Moscow, Russian Federation

2Pathology, City Nephrology Centre, Moscow, Russian Federation

*Corresponding Author:
Zakharova EV
Nephrology Unit, City Clinical Hospital
Moscow, Russian Federation
Tel: +7967-134-6936
E-mail: [email protected]

Received date: December 16, 2015 Accepted date: December 28, 2015 Published date: December 30, 2015

Citation: Zakharova EV, Stolyarevich ES (2015) Clinical Presentation and Pathology Spectrum of Kidney Damage in Non-hodgkin Lymphoma/Leukemia and Lymphoplasmacytic Lymphomas. J Leuk 3:201. doi:10.4172/2329-6917.1000201

Copyright: © 2015 Zakharova EV, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Visit for more related articles at Journal of Leukemia

Abstract

Kidney damage in non-Hodgkin lymphoma/leukemia (NHL/CLL) and lymphoplasmacytic lymphomas (LPCL) are caused by several mechanisms: tumor mass localization; clonal cell expansion; hormones, cytokines and growth factors secretion; metabolic, electrolyte and coagulation disturbances; deposition of paraproteins and treatment complications. Symptoms of kidney damage may dominate and even preclude overt NHL/CLL or LPCL, and only renal pathology findings give the clue to the diagnosis. We aimed to evaluate clinical presentation and pathology of kidney damage in patients with NHL/CLL or LPCL. Using electronic database and purposely designed chart, we searched data for 158 patients with lymphoproliferative disorders (LPD) and pathology proven kidney lesions. Patients with multiple myeloma, Hodgkin’s lymphoma, Castleman disease, “primary” AL amyloidosis and “primary” light chain deposition disease were excluded from further analysis. Study group consisted of 24 patients, 14 (58.3%) male and 10 (41.7%) female, median age 67 (17;76) years. 16 patients (66.6%) were diagnosed with NHL/CLL, 7 patients (29.1%) with Waldenström’s Macroglobulinemia (WM) and 1 (4.1%) with Franklin’s disease (FD). 10 (41.7%) of patients presented with nephrotic syndrome (NS), 17 (70.8%)–with impaired kidney function, and 6 (25.2%) with both NS and renal dysfunction. By pathology glomerulonephritis (GN) was found in 11 (45.8%) of patients, in 4 cases GN pattern was associated with monoclonal paraproteins, and in 7 cases GN was considered to be paraneoplastic. Interstitial nephritis was seen in 10 (41.6%) patients, in 8 of them due to specific lymphoid infiltration; and amyloidosis complicated only 3 (12.5%) cases. Patients with NHL/CLL or LPCL, presenting with renal abnormalities, show variety of pathology patterns hardly predictable on clinical basis. Most often in our patient series was specific lymphoid interstitial infiltration and paraneoplastic glomerulonephritis with MN and MPGN patterns. In many cases of NS and/or acute kidney injury (AKI) renal biopsy was crucial for the diagnosis of NHL/CLL and LPCL.

Abstract

Kidney damage in non-Hodgkin lymphoma/leukemia (NHL/CLL) and lymphoplasmacytic lymphomas (LPCL) are caused by several mechanisms: tumor mass localization; clonal cell expansion; hormones, cytokines and growth factors secretion; metabolic, electrolyte and coagulation disturbances; deposition of paraproteins and treatment complications. Symptoms of kidney damage may dominate and even preclude overt NHL/CLL or LPCL, and only renal pathology findings give the clue to the diagnosis. We aimed to evaluate clinical presentation and pathology of kidney damage in patients with NHL/CLL or LPCL. Using electronic database and purposely designed chart, we searched data for 158 patients with lymphoproliferative disorders (LPD) and pathology proven kidney lesions. Patients with multiple myeloma, Hodgkin’s lymphoma, Castleman disease, “primary” AL amyloidosis and “primary” light chain deposition disease were excluded from further analysis. Study group consisted of 24 patients, 14 (58.3%) male and 10 (41.7%) female, median age 67 (17;76) years. 16 patients (66.6%) were diagnosed with NHL/CLL, 7 patients (29.1%) with Waldenström’s Macroglobulinemia (WM) and 1 (4.1%) with Franklin’s disease (FD). 10 (41.7%) of patients presented with nephrotic syndrome (NS), 17 (70.8%)–with impaired kidney function, and 6 (25.2%) with both NS and renal dysfunction. By pathology glomerulonephritis (GN) was found in 11 (45.8%) of patients, in 4 cases GN pattern was associated with monoclonal paraproteins, and in 7 cases GN was considered to be paraneoplastic. Interstitial nephritis was seen in 10 (41.6%) patients, in 8 of them due to specific lymphoid infiltration; and amyloidosis complicated only 3 (12.5%) cases. Patients with NHL/CLL or LPCL, presenting with renal abnormalities, show variety of pathology patterns hardly predictable on clinical basis. Most often in our patient series was specific lymphoid interstitial infiltration and paraneoplastic glomerulonephritis with MN and MPGN patterns. In many cases of NS and/or acute kidney injury (AKI) renal biopsy was crucial for the diagnosis of NHL/CLL and LPCL.

Keywords

Kidney biopsy; Lymphoma; Nephropathy

Introduction

Kidneys are affected in patients with NHL/CLL and LPCL not that often as in multiple myeloma, however, kidney damage is represented with a broad spectrum of clinical and pathology variants. Renal involvement is defined by several mechanisms (Table 1) tumor mass localization; clonal cell expansion; hormones, cytokines and growth factors secretion; metabolic, electrolyte and coagulation disturbances; infectious, drug-induced and radiation complications etc., affecting urinary tract, renal arteries and veins and all parenchymal compartments-intra-renal vasculature, glomeruli, tubules and interstitial space, sometimes simultaneously. Rarely kidney damage may be caused by deposition of secreted paraproteins, including organized (fibrils, microtubules), and non-organized deposits of monoclonal immunoglobulin’s or fragments thereof [1-6].

Pre-renal acute kidney injury
Hyperviscosity syndrome
Specific infiltration Interstitial infiltration
Intraglomerular lymphoma
Paraneoplastic glomerulonephritis Membranous nephropathy
Membranoproliferative glomerulonephritis
Minimal change disease/Focal segmental glomerulosclerosis
Metabolic nephropathies Tumor-lysis syndrome (uric acid/phosphate nephropathy)
Thrombotic damages Renal vein thrombosis
Thrombotic microangiopathy
Urinary tract obstruction Compression with lymph nodes
Retroperitoneal fibrosis
Infectious complications Sepsis
Urinary tract infection
AA amyloidosis caused by chronic infections and inflammation
Radiation-induced nephritis
Drug-induced nephritis Minimal change disease
Membranous nephropathy
Interstitial nephritis
Paraprotein deposition Organized paraprotein deposits Cryoglobulinemic glomerulonephritis
  Glomerulonephritis with organized microtubular monoclonal deposits (Immunotactoid Glomerulonephritis)
Al and AH amyloidosis
Non-organized paraprotein deposition Glomerulonephritis with monoclonal intracapillaryIgM deposits
Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (Nasr disease)
Monoclonal immunoglobulin deposition disease

Table 1: Mechanisms and patterns of kidney damage in non-Hodgkin lymphoma/leukemia and lymphoplasmacytic lymphomas.

Clinical presentation of renal involvement in patients with NHL/CLL and LPCL include AKI, NS, proteinuria and/or hematuria, arterial hypertension or chronic kidney disease (CKD). Differential diagnostics is the major challenge, often, but not obligatory demanding pathology evaluation. Pre-renal AKI, tumor-lysis syndrome, or urinary tract obstruction by lymph nodes can be diagnosed on clinical basis, but many conditions cannot be differentiated in solely clinical setting. Importantly, symptoms of kidney damage may dominate and even preclude overt NHL/CLL or LPCL, and only pathology findings give the clue to the diagnosis.

Pathology patterns (Table 1) include interstitial or glomerular specific infiltration; cryoglobulinemic GN (CryoGN); proliferative (PGNMID) and non-proliferative GN with monoclonal immunoglobulin deposits; immunotactoid (GOMMID) and fibrillary GN; paraneoplastic GN-mostly membranous nephropathy (MN) and membranoproliferative GN (MPGN); AL/AH amyloidosis, and even AA amyloidosis [4-13]. In turn, MN and MPGN are known to be often secondary to lymphomas, and immunotactoid and fibrillary GN, defined by electron microscopy (EM), may present like MN and MPGN by light microscopy (LM) evaluation [14-16].

Given the serious prognosis for NHL/CLL and LPCL as such, and for kidney damage in this setting in particular, and also the fact that overall and kidney survival depend to the considerable extent on early diagnostics, we aimed to evaluate the clinical presentation and the pathology patterns in patients, admitted to nephrology unit and diagnosed with NHL/CLL and LPCL.

Materials and Methods

Patient’s population

In this retrospective study from a single center, using electronic database with 10277 records for primary admissions over last 21 years (1994-2015), and purposely designed chart, we searched and analyzed data for 315 patients (3.0%) with LPD and plasma cell dyscrasias. We found 158 cases (50.1%) with pathology proven diagnosis. Patients with multiple myeloma, Hodgkin’s lymphoma, Castleman disease, “primary” AL amyloidosis and “primary” light chain deposition disease were excluded from further analysis. 24 patients with NHL/CLL and LPCL and biopsy proven kidney lesions were carefully evaluated (Figure 1).

leukemia-pathology-proven-LPD

Figure 1: Proportion of study group versus total patient’s population, all patients with lymphoproliferative disorders and patients with pathology-proven LPD.

Main diagnosis

Diagnosis of NHL/CLL and LPCL was determined in collaboration with hematologist according to WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues [17].

Work-up

Work-up, beyond routine, included serum and urine immunoelectrophoresis; peripheral blood immunophenotyping; abdomen, kidneys and peripheral lymph nodes ultrasound; skeletal X-ray; chest and abdomen CT; bone marrow aspiration and/or biopsy; and/or lymph node biopsy with light microscopy and immunohistochemistry; and kidney biopsy.

Kidney biopsy

Indications for kidney biopsy included NS, proteinuria (>0.3 g/24 h) and/or hematuria and/or decreased kidney function (in cases with ruled out intra- and extra-renal tumor masses, urinary tract obstruction, coagulation, electrolyte and metabolic disturbances and sepsis). Kidney core biopsy was taken with BARD-Magnum biopsy guidance facility and evaluated by one pathologist. In selected cases second opinion and/or re-processing and re-evaluation was requested from external pathologists. Obtained specimens were divided into two or three parts and processed for LM, immunofluorescence (IF) or immunhistochemistry, and, in selected cases, EM. Formalin fixed/paraffin embedded sections for LM were stained with hematoxylin and eosin, Masson’s trichrome, periodic acid-Shiff and Congo red. Unfixed cryo-sections for IF were routinely stained for IgA, IgG, IgM, C3, C1q, kappa and lamda light chains and fibrinogen. In selected cases immunofluorescence on formalin fixed/paraffin embedded sections with FITC-conjugated anti IgA, IgG, IgM, C1q, C3, fibrinogen, λ and κ light chains antibodies, and immunoperoxidase staining for amyloid A-protein was performed. Also in 5 (20.8%) cases Toluidune blue stained semi-thick sections were examined and 1 glomerulus was identified for EM study (by external pathologist).

Results and Discussion

Study group comprised 15.1% of all cases of LPD with pathology proven kidney damage, and included 24 patients, 14 (58.3%) male and 10 (41.7%) female, median age 67 (17;76) years.

Clinical diagnosis and presentation

16 patients (66.6%) were diagnosed with NHL/CLL, 7 patients (29.1%) with Waldenström’s Macroglobulinemia (WM) and 1 (4.1%) with Franklin’s disease (FD). In 11 cases diagnosis of NHL/CLL or LPCL was primarily established in the nephrology unite.

10 (41.7%) patients presented with NS; 17 (70.8%) had impaired kidney function at the time of biopsy; and 6 (25.2%) presented with both NS and renal dysfunction. 12 (50%) patients were diagnosed with CKD stage 3-5, and 5 (20.8%) patients had AKI, totally 4 (16.6%) of them required urgent dialysis at presentation (Figure 2).

leukemia-Clinical-presentation-LPD

Figure 2: Clinical presentation in the study group.

Pathology findings

Pathology data (Table 2) showed that kidney damage in patients with NHL/CLL and LPCL presented with 11 different patterns described in the literature [4-13]. Glomerulonephritis comprised almost half of cases and was found in 11 (45.8%) of patients, in 4 cases GN was associated with monoclonal paraproteins, and in 7 cases was considered to be paraneoplastic. Interstitial nephritis was found in 10 (41.6%) patients, with 8 of them due to specific lymphoid infiltration, and amyloidosis complicated only 3 (12.5%) cases.

Pathology pattern N
Glomerulonephritis 11
Associated with monoclonal immunoglobulin’s  4
Cryoglobulinemic glomerulonephritis 1
Glomerulonephritis with monoclonal IgM deposits 3
Paraneoplastic 7
Membranoproliferative glomerulonephritis 2
Membranous nephropathy 3
Focal segmental glomerulosclerosis 1
Diffuse glomerulosclerosis 1
Amyloidosis 3
Immunoglobulin related 2
AL amyloidosis 1
AH amyloidosis 1
Non-immunoglobulin related 1
AA amyloidosis 1
Interstitial nephritis 10
Specific interstitial infiltration 8
Drug-induced interstitial nephritis 2

Table 2: Kidney pathology data in the study group.

Clinical and pathology correlations

As it is shown in the Table 3, some pathology patterns were strictly associated with the particular diagnosis, but on the other hand same pathology findings could be seen in different clinical setting and vice versa.

Pathology/Main diagnosis Non-Hodgkin lymphoma/leukemia Waldenströ m’s macroglobulinemia Franklin disease
Cryoglobulinemic glomerulonephritis   1  
Glomerulonephritis with monoclonal IgM deposits   3  
Membranoproliferative glomerulonephritis 2    
Membranous nephropathy 2 1  
Focal segmental glomerulosclerosis   1  
Diffuse glomerulosclerosis 1    
AL amyloidosis   1  
AH amyloidosis     1
AA amyloidosis 1    
Specific interstitial infiltration 8    
Drug-induced interstitial nephritis 2    

Table 3: Diagnosis and pathology correlations.

Monoclonal immunoglobulin–associated glomerulonephritis

A case of cryoglobulinemic glomerulonephritis, as well as 3 cases of glomerulonephritis with monoclonal IgM deposits were not surprisingly found in patients with WM (Figures 3 and 4), In all four cases patients were referred to our unit with NS and only kidney biopsy findings lead to further specifically directed work-up and to the final diagnosis.

leukemia-Cryoglobulinemc-GN

Figure 3: Cryoglobulinemc GN, PAS x 250.

leukemia-IgM-deposits-Masson

Figure 4: GN with IgM deposits, Masson x 400.

Paraneoplastic glomerulonephritis

Membranoproliferative glomerulonephritis was found in 2 patients with MALT lymphoma, membranous nephropathy was revealed in 2 patients with MALT lymphoma (Figures 5 and 6) and in 1 patient with WM. The single case of focal segmental glomerulosclerosis was also seen in WM. As both MPGN and MN are known to be “secondary” to NHL and these LM and IF patterns may represent fibrillary GN, we can speculate, that our 4 patients with MALT lymphoma had in fact fibrillary GN. Unfortunately, we were not able to prove this by EM in that particular cases. Again, in one of these patients only kidney biopsy, performed because of NS, lead to diagnostic search for the possible cause of “secondary” MN and allowed to diagnose gastric MALT lymphoma.

leukemia-Membranous-nephropathy

Figure 5: Membranous nephropathy, IF IgGx400.

leukemia-MPGN-PASx250

Figure 6: MPGN, PASx250.

Amyloidosis

AL amyloidosis was in one cases of WM, AH amyloidosis was seen in a patient with FD, and AA amyloidosis was the complication of Burkitt lymphoma with spinal chord damage and bed sores. All these variants are rare, interestingly that diagnosis of FD was again established on the basis of kidney pathology-renal AH amyloidosis in a patient with moderate proteinuria gave a clue to the diagnosis, which was confirmed by bone marrow biopsy and immunelectrophoresis of serum and urine proteins (Figures 7 and 8).

leukemia-Congo-red-x250

Figure 7: AH amyloidosis, Congo red x250.

leukemia-IF-IgGx250

Figure 8: AH amyloidosis, IF IgGx250.

Interstitial lymphoid infiltration

Specific lymphoid infiltration was found in 8 cases, all in patients with NHL/CLL-mostly follicular lymphoma and small lymphocyticl lymphoma, and only one patient with acute lymphoblastic T-cell leukemia (Figures 9 and 10).

leukemia-Lymphoid-infiltration

Figure 9: Lymphoid infiltration, PAS x 100.

leukemia-infiltration-PAS-x-400

Figure 10: Lymphoid infiltration, PAS x 400.

Conclusion

Our retrospective single-center study of 24 patients with pathology-proven kidney damage showed, that patients with non-Hodgkin lymphomas and lymphoplasmacytic lymphomas, presenting with renal abnormalities, show variety of pathology patterns, hardly predictable on clinical basis. Most often in our patient series turned to be specific lymphoid interstitial infiltration and paraneoplastic glomerulonephritis with MN and MPGN patterns. In many cases of nephrotic syndrome and/or acute kidney injury, renal biopsy, precluded or followed by scrutinous hematological work-up is crucial for the diagnosis of NHL/CLL and LPCL.

Conflict of Interest

Nothing to declare

Acknowledgments

Maria Ratner, Alexander Lokshin, Alexander Vorobjev, Alexey Sukhanov, Mikhail Brodsky, Elena Ipatjeva, Arthur Cohen, Olga Vorobjeva, Natalia Tomilina, Aida Melikyan, Elena Tareeva, Olga Vinogradova, Anastasia Tareeva, Tatiana Makarova, Alina Anilina, Elena Zvonova, Vladimir Lunin, Nuriette Khuajeva, Alexander Kostin, Anna Shubina, Alla Kovrigina, Irina Kaplanskaya, Sergey Loginov.

References


Select your language of interest to view the total content in your interested language
Post your comment

Share This Article

Relevant Topics

Article Usage

  • Total views: 9461
  • [From(publication date):
    December-2015 - Mar 27, 2019]
  • Breakdown by view type
  • HTML page views : 9303
  • PDF downloads : 158
Top