| Abstract|| |
We report the case of a 70-year-old man with no relevant past medical history who presented with acute kidney injury. Kidney biopsy showed diffuse interstitial infiltration with typical chronic lymphocytic leukemia (CLL) phenotype B-cells. Subsequent studies revealed a normal lymphocyte count in the peripheral blood, and there was no evidence of lymphadenopathy or hepatosplenomegaly. Blood flow cytometry demonstrated a clonal B-cell population with a CLL phenotype. Without renal involvement, this case should be classified as monoclonal B-cell lymphocytosis. Renal function improved with steroid therapy. However, the patient developed CLL with significant lymphocytosis approximately two years later.
|How to cite this article:|
Wen YK. Monoclonal B-cell lymphocytosis with renal involvement. Saudi J Kidney Dis Transpl 2018;29:1502-5
| Introduction|| |
Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. It is defined as white blood cell count >5000/mm3 of circulating monoclonal B-lymphocytes expressing a typical cell surface marker signature. If lymphadenopathy or hepatosplenomegaly is present with <5000/mm3 circulating monoclonal B-lymphocytes, a diagnosis of small lymphocytic lymphoma (SLL) is made. The concept of monoclonal B-cell lymphocytosis (MBL) is relatively new. The increasing identification of low levels of circulating monoclonal B-cell lymphocytes with CLL phenotype in apparently healthy individuals, due to more sensitive immune-phenotyping methods, led to the definition of MBL in the 2005 International Familial CLL Consortium as the presence of a monoclonal B-cell population in the peripheral blood of <5000/mm3 with a CLL phenotype without other features of CLL/ SLL. The newly published 2016 revision of the World Health Organization classification of lymphoid neoplasms has officially accepted MBL as an independent disease entity. Recent studies suggested that CLL is almost always preceded by a period of MBL. It has been estimated that the rate of progression of MBL to CLL is 1%–2% per year. MBL with tissue involvement has been rarely described and its significance is still uncertain. We report an unusual case of MBL with an initial presentation of renal involvement that progressed to obvious CLL approximately two years later.
| Case Report|| |
Informed consent was obtained from the patient’s relatives before reporting the case. A 70-year-old man was referred to our hos-pital due to acute kidney injury (AKI). The patient had no significant past medical history. On admission, his blood pressure was 160/95 mm Hg. Physical examination of the chest, heart, and abdomen was unremarkable. Neither significant lymphadenopathy nor hepatosplenomegaly was present. Laboratory data included the following values: white blood cell count 7100/mm3 (lymphocyte 17%), hemoglobin 8.8 g/dL, platelet count 125,000/mm3, blood urea nitrogen 44 mg/dL, creatinine 5.2 mg/dL, potassium 4.8 mmol/L, calcium 7.6 mg/dL, phosphorus 6.5 mg/dL, uric acid 8.9 mg/dL, total protein 5.0 g/dL, and albumin 2.4 g/dL. Urinalysis showed protein 100 mg/dL, red blood cells >100/high-power field, and white blood cells 4.9/high-power field. Urine protein-to-creatinine ratio was 1002 mg/g. Abdominal ultrasonography revealed unremarkable findings. A kidney biopsy was performed and the specimen showed normal glomeruli. However, there was marked diffuse interstitial infiltration with small monotonous lymphoid cells [Figure 1]. Immuno-histochemical studies showed that the interstitial lymphoid cells consisted of CD-20-positive B-cells with aberrant co-expression of CD-5. Blood flow cytometry demonstrated a clonal B-cell population with a CLL phenotype (CD-20+, CD-5+, CD-19+, and CD-23+). The patient was treated with oral prednisone (1.0 mg/kg/day). Kidney function began to improve, but he refused additional workup or treatment. During the next several months, kidney function stabilized at a crea-tinine level of 1.2 mg/dL. Approximately two years after the kidney biopsy, the patient had a relapse of AKI with a creatinine value of 8.72 mg/dL. At this time, a white blood cell count of 69,000/mm3 (lymphocyte 3%, variant lymphocyte 73%) was noted. Repeated blood flow cytometry still showed a CLL phenotype. The patient was initially treated with oral steroids and hydroxyurea. Because of uremic syndrome, hemodialysis was commenced. Unfortunately, approximately two weeks after admission, he developed pneumonia and died of complications from this event.
|Figure 1: Kidney biopsy showing diffuse interstitial infiltration with small monotonous lymphoid cells (H and E, ×400).|
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| Discussion|| |
We present a case of AKI due to kidney infiltration by CLL phenotype B-cells in a patient with normal peripheral blood lymphocyte count that otherwise would be classified as MBL. Despite relatively low B-cell count, MBL is not always a benign disorder. It is now known that MBL is a precursor of CLL. Furthermore, MBL with tissue involvement has been increasingly recognized. Clonal CLL-like cells can be detected in up to 0.4% of prostatic tissues at the time of prostatectomy and in 1.9% of liver biopsy specimens in the absence of meeting any other diagnostic criteria for CLL/SLL., MBL with skin involvement also has been reported anecdo-tally. Furthermore, it is not uncommon to find bone marrow infiltration of CLL phenotype B-cells in patients staged for other hematologic malignancies. Of interest, most individuals with MBL who have a bone marrow biopsy at the time of diagnosis have a concomitant bone marrow infiltration.
MBL with renal involvement has been rarely reported. We found only three cases reported in the literature. Henriksen et al reported a case of pauci-immune crescentic glomerulo-nephritis, in which kidney infiltration by CLL phenotype B-cells was incidentally found on kidney biopsy. Poitou-Verkinder et al reported a case of MBL with initial presentation of membranoproliferative glomerulonephritis and progression to obvious CLL two years later without treatment. Soldarini et al reported a case of membranoproliferative glomerulo-nephritis in a patient with MBL with bone marrow involvement, in which nephrotic syndrome went into remission after treatment for CLL.
MBL with renal involvement could be under reported since immune-phenotype analysis is not routinely performed on kidney biopsy. Interstitial infiltration by CLL cells can be confused with acute interstitial nephritis, a much more common lesion in the kidney. Therefore, it is important to carefully assess the interstitial inflammatory cell infiltration in every kidney biopsy. In routine histology, a mixed population of inflammatory cells points to an inflammatory response rather than a neoplastic process. However, the presence of lymphoid aggregates of monotonous lymphocytes without associated tubulitis favors CLL infiltration. In these cases, immune-phenotype analysis is helpful to confirm or exclude CLL infiltration.
The treatment of MBL with renal involvement is a challenge. Given the rarity of this condition, there is no standard of care on how these patients’ treatment should be approached. Rituximab-based regimens have been proposed in the past as therapy for these patients with concomitant renal complications, given their limited toxicity, but with unsatisfactory results.
| Conclusion|| |
Our case suggests that MBL with renal involvement could lead to severe renal damage. We are surprised at the dramatic response to oral steroid therapy alone. Furthermore, MBL is now considered a premalignant condition. Patients with MBL should be monitored longitudinally.
Conflict of interest: None declared.
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Dr. Yao-Ko Wen
Department of Internal Medicine, Division of Nephrology, Changhua Christian Hospital, Changhua, 500