1Department of Internal Medicine, Nephrology Division and 2Department of Oncology, Transplants and New Technologies in Medicine, Hematology Division, University of Pisa, 3Histology Division and 4Urology Division, Azienda Ospedaliera Pisana, Pisa, Italy
Correspondence and offprint requests to: Dott. Adamasco Cupisti, Dipartimento di Medicina Interna, Università di Pisa, Via Roma 67, 56126 Pisa, Italy. Email: acupisti{at}med.unipi.it
Keywords: chemotherapy; chronic renal failure; hypercalcaemia; nephrectomy; primary renal lymphoma
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Introduction |
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The median age at PRL diagnosis is 64 years, and the disease is more frequent in males than in females. Acute renal failure, flank pain and detection of a renal mass are the most frequent manifestations [3]. Renal failure may result from a large variety of causes, such as lymphomatous infiltration of renal tissue or hypercalcaemia [4]. Histological examination is mandatory, as clinical and radiological findings often evoke renal carcinoma [5].
The prognosis is poor, but long-term survivors have been reported occasionally after surgical resection and combination chemotherapy, in unilateral renal lymphoma [2]. Bilateral renal involvement has a prevalence of 43% [6]: in this case, the prognosis is very severe and chemotherapy is the usual proposed treatment because surgery has never been described (Table 1).
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Case |
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Values found to be in the normal range were those for serum uric acid, phosphorus, sodium, potassium, glucose, cholesterol, triglycerides, bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, serum and urine protein electophoresis, hepatitis C virus and hepatitis B virus.
The patient's chest X-rays were normal. Abdominal sonography showed an enlarged right kidney diameter with irregular borders, mesorenal scarring and hypertrophic areas; the left kidney measured 9 cm in diameter with irregular borders. No signs of stones or urinary tract obstruction were detected. No enlarged lymph node was detected by sonography of the neck, inguinal and axillary regions.
Hypercalcaemia was treated by saline and furosemide, leading to normalization of serum calcium to 2.52.7 mmol/l and progressive reduction of serum creatinine to 309 µmol/l.
Abdominal magnetic resonance confirmed a right kidney of increased size, with multiple nodules and complete subverting of the normal structure. The larger nodule measuring 8 cm diameter was located in the upper posterior region of the right kidney; a nodule involving the upper pole of the left kidney was also detected, whereas the remaining kidney tissue appeared preserved (Figure 1). No abnormalities were described as far as lymph nodes, liver or spleen were concerned.
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Suspicion of a cancer or of a lymphoproliferative disease with bilateral renal involvement arose. Therefore, the patient underwent xipho-pubical laparotomy. The right kidney appeared completely subverted by proliferative tissue, while exploration of the left kidney confirmed a proliferative lesion apparently limited to its upper region.
Consequently, right radical nephrectomy and upper pole resection of the left kidney were performed, preserving approximately half of the left kidney. Seven inter-aortic lymph nodes were sampled. The abdominal exploration was unremarkable. The right kidney measured 15 x 8 x 8 cm and the removed portion of the left kidney measured 6 x 3 x 3 cm.
Histological examination showed a diffuse, large B-cell lymphoma (REAL classification), centroblastic variant, which diffusely infiltrated interstitium and glomeruli. This variant was composed of medium to large sized lymphoid cells with oval to round, vesicular nuclei with fine chromatin and 23 membrane-bound nucleoli. This case was characterized by many multilobated cells. The immuno-phenotype was CD20+, CD79a+ and Bcl-2/+. These findings were observed both in the right and in the left kidney tissue. However, adrenal glands, peri-renal fat or inter-aortic lymph nodes were not involved.
During the days following nephrectomy, serum creatinine improved to 247 µmol/l together with reduction of serum calcium (2.3 mmol/l) and calcitriol (6.0 pg/ml) serum levels.
Additional post-operative staging, including whole body CT and bone marrow biopsy, did not show any abnormality or lymphomatous localization.
Six months after surgery, re-staging of the disease was carried out, leading to detection of a bone marrow infiltration. Translocation of the Bcl2 gene was detected using polymerase chain reaction (PCR) for clonal immunoglobulin heavy chain (IgH) gene rearrangement [7]. Thus the patient underwent chemotherapy according to the Pro-MECE-CytaBOM schedule and, after four cycles, residual infiltration of the bone marrow was detected by PCR analysis for IgH rearrangement. Therefore, a second line chemotherapy was performed according to the Flu-Ctx-Idec protocol (four cycles) [8]. Successive examination did not show any relapse and renal function remained stable with time; serum creatinine ranged between 186 and 210 µmol/l. Follow-up consisted of regular physical examination and biochemistry. Bone marrow biopsy, chest X-ray and sonography were performed every 6 months for 3 years, and then once a year. Abdomen CT scans were performed every year for the first 3 years and then every 2 years. At this time, 67 months after surgery and 36 months after the end of the chemotherapy, no sign of disease relapse has been detected. Serum creatinine remains stable at 186 µmol/l (Figure 2).
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Discussion |
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Historically, the patient has been diagnosed with a chronic pyelonephritis and a pseudo-inflammatory tumour in the right kidney. It is known that this lesion can precede the onset of a lymphoproliferative disease. Moreover, as far as the involvement of other extra-nodal organs is concerned, the lymphoid tissue formed by chronic inflammatory disease is regarded as the source for the development of malignant lymphoma [9].
The rapid deterioration of the residual renal function was likely to have been related to parenchyma infiltration and to the hypercalcaemia, probably induced by vitamin D overproduction from the lymphoid cell mass. Accordingly, after restoration of normal calcium levels and subtotal ablation of the renal mass, renal function did ameliorate and returned to the patient's basal values (Figure 2).
Because of the low incidence of this disease, randomized studies aiming to compare different therapy approaches have not been reported. Systemic chemotherapy, with or without radiotherapy, is a widely used treatment for PRL [10], as well as the option of surgery in the case of PRL affecting one kidney.
The limited available literature reports that the prognosis of patients affected by PRL is poor, despite no disseminated disease. Chemotherapy usually improves or normalizes the renal function, but the few cases reported showed a high prevalence of deaths because of rapid relapse or infections incurred in the course of neutropenia. Long-term survivors occasionally have been reported after combined surgerychemotherapy treatment where one kidney is involved [1]. The patients whose lymphomatous masses were removed completely by surgical resection, and who were treated by combination chemotherapy, had longer disease-free and overall survival: this usually occurs in monolateral cases. Patients with bilateral involvement or with residual lymphoma mass after surgical resection show a very bad prognosis. Our patient showed bilateral renal involvement with no signs of other nodal or extra-nodal localization. Bone marrow involvement was found only several months following the surgical resection, and nodal involvement was never detected. This phenomenon is difficult to interpret, but certainly this is not in keeping with a lymphomatous infiltration of the kidney in disseminated lymphoma.
Bilateral renal lymphomas are usually treated by aggressive chemotherapy as front line therapy [1,5]: this approach could preserve the organ function, but generally the prognosis is poor. Alternatively, bilateral nephrectomy invariably leads to the need for dialysis treatment.
In our patient, the resection of the apparent tumour mass preserved approximately one-quarter residual renal mass which successfully allowed the patient to avoid dialysis. The choice of initial surgery depended on the need for a definite diagnosis, on the presence of an underlying chronic renal failure and on the importance of the tumour mass.
The present case report suggests that surgery can be beneficial in the treatment of renal lymphoma with bilateral involvement. This kind of treatment was possible because the left kidney had macroscopic involvement limited to the upper pole. Although microscopic involvement could also be present in the remaining renal tissue, a conservative surgical resection was possible in the left kidney, allowing for a residual renal function sufficient to make the patient free from the need for dialysis. The tumour mass was dramatically reduced, thus increasing the likelihood of success of the ensuing chemotherapy treatment. A 67 month period of survival in bilateral renal lymphoma has been never described in the literature: we believe that, as is typical with other types of cancers, reduction of tumour cell mass is a crucial point for successful treatment and response to chemotherapy.
Table 1 lists the cases of PRL with involvement of both kidneys which exist in the literature. The overall poor prognosis is evident, as only 11 cases of remission at 136 months are reported. Various combined chemotherapy regimens were the main therapeutic strategy adopted, but surgery was never described. Actually, the urological intervention represents the most original aspect of the present case and it is likely that this could have contributed to the favourable outcome of the disease by means of a critical reduction of neoplastic cell mass giving more chance of a better response to chemotherapy. The surgical approach we used is the same as is usually performed in bilateral renal cancer, i.e. the removal of as much tumour mass as possible, provided there is preservation of enough (macroscopically) tumour-free kidney tissue.
In conclusion, this case report shows a case of bilateral PRL successfully treated by extensive surgical resection and combination chemotherapy. It is difficult to discuss the relative role of surgery and chemotherapy in the favourable outcome of this patient. Nevertheless, the unusual long-term remission, together with preservation of a residual renal function, shows that surgery, in association with a combined chemotherapy protocol, may be an option in selected cases of bilateral PRL.
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Acknowledgments |
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Conflict of interest statement. None declared.
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References |
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