Case Reports

Indian Pediatrics 2002; 39:677-680

Renal Amyloidosis in A Child with Hodgkin Disease

From the Pediatric Oncology Division, Department of Pediatrics and *Department of Pathology, All India Institute of Medical Sciences, New Delhi 110 029, India.

Correspondence to: Dr Vasantha Thavaraj, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi 110 029, India.

Manuscript received: September 21, 2001;

Initial review completed: November 21, 2001;

Revision accepted: December 28, 2001.

Nephrotic syndrome in Hodgkin’s disease may occur as a result of glomerular injury due to local alteration of fixed glomerular antigens or localization of tumor antigens deposited in the glomeruli leading to the formation of local immune complexes(1), due to renal vein thrombosis and due to renal amyloidosis(2). Since 1930-1986, 40 cases of Hodgkin’s disease with amyloidosis have been reported(3). Amyloidosis which used to be the commonest lesion prior to 1962 has nearly disappeared due to improved modalities of treatment. In a large series reported by Dabb’s et al., renal amyloidosis in association with Hodgkin’s disease was seen only in 0.1% of cases(3).

In a series of immunofluorescence studies of 57 patients in childhood biopsy proven renal amyloidosis, all the cases had underlying familial mediterranean fever(4). Since association of renal amyloidosis in a case of Hodgkin’s disease presenting as nephrotic syndrome is very rare, we report one such child.

An eight year old boy complained of multiple swellings on both sides of the neck which were progressively increasing in size for the last two and half years. He was treated for tuberculosis by a private practioner. Lymph node biopsy was done in private hospital and the child was diagnosed as a case of lymphoma and one cycle of COPP (Cyclophosphamide, Vincristine, Prednisolone and Procarbazine) was given. The lymph node biopsy was reviewed in a medical college hospital which was reported as reactive lymphadenitis. The anticancer therapy was stopped. The swelling in the neck recurred and progressively increased in size for the last 3 months. There was also associated fever with an evening rise. There was a hacking cough for the same duration. He also developed respiratory distress for the last one month. His maternal grand mother had suffered from carcinoma of the tongue. On physical examination his body weight was 30 kg and the body surface area was 0.8m2. He had pallor and puffy face. There was no jaundice or cyanosis. There was pedal edema. The cervical lymph nodes were massively enlarged on both sides, 5-8 in number, on the right side of the neck the lymph nodes were 2 cm × 4 cm in size mobile, discrete, rubbery and 10-15 lymph nodes on the left side 1 cm × 5 cm, rubbery, mobile. There were no other lymph nodes. On abdominal examination there was a vaugue mass in the left para umbilical region, firm in consistency, borders not well defined, suggestive of retroperitoneal lymphadenopathy. Liver was palpable 2 cm below costal margin. Spleen and kidneys were not palpable.

The laboratory investigations included complete blood count. The initial hemoglobin was 7.2 g/dl. The total leukocyte count was 8.7 × 106/L. The erythrocyte sedimentation rate by Westergreen method was 60 mm in the first hour. The blood chemistry including blood sugar and serum electrolytes and renal function tests including blood urea nitrogen and serum creatinine were normal. The liver enzymes, serum protiens, albumin, globulins were also normal. The chest rotengenogram showed a mediastinal widening. Contrast enhanced computerized tomography of chest, abdomen and pelvis showed large mediastinal, retroperitoneal and pelvic lymphadenopathy with hepatosplenomegaly. Lymph node biopsy showed features of Hodgkin’s disease, mixed cellularity type. The bone marrow biopsy and touch smears did not show infiltrations by Hodgkin’s lymphoma.

He was treated with 4 alternating cycles of COPP (Cyclophosphamide, Vincristine, Prednisolone and Procarbazine) and ABVD (Adriamycin, Bleomycin, Vinblastin and Dacarbazin). Involved field radiotherapy was advised but the patient did not agree. At the completion of therapy clinically he was in complete remission. The CECT of chest, abdomen and pelvis suggested a significant regression of lymphnodes in the mediastinum and retro peritoneal and pelvic regions. There was no mediastinal widening in the chest x-ray.

The patient was followed up for 15 months. During this time he remained in remission and gained weight and was doing well. At the end of 15 months he came with generalized body swelling and puffiness of face for a duration of one week. Oliguria was present for the same period. There was generalized anasarca including huge scrotal swelling which was preceded by an episode of diarrhea. There was no fever, cough, jaundice, burning micturition or hematuria. On examination there was edema of abdominal wall, scrotal edema, sacral edema and puffy face. Blood pressure was normal. There were no lymph nodes and no organomegaly. The laboratory investigation revealed anemia with a hemoglobin of 7.4 g/dl, WBC count 9.8 x 106/L with a normal differential count, with increased platelet count of 8.54 × 106/L. Blood urea nitrogen was 17 mg/dl, serum creatinine was 0.4 mg/dl, total serum protein was 4.1 g/dl, serum albumin was 1.3g/dl, and serum cholesterol was 279 mg/dl. The peritoneal aspiration was a transudate. The urine examination showed a protein of 3+. The 24 hour urinary creatinine was 0.38 g, albumin was 1.6 g. The 24 hour albuminuria was in the nephrotic range according to body surface area. Mantoux test with 1TU was negative. Ultrasound screening of abdomen suggested bilaterally enlarged kidneys. Kidney biopsy was done, which showed 14 glomeruli. Ten glomeruli showed deposition of eosinophilic material in the mesangium with nodular expansion without any increase in measangial cellularity. Such material was also seen in the wall of afferent arteriole of some glomeruli. The basophilic material was positive for stains for amyloidosis. The tubules, endothelium and blood vessles were unremarkable. Immunofluorescence was negative for IgA, IgG and C3. He was put on a salt restricted diet and diuretics. Initially there was a symptomatic improvement but again he developed anasarca and was lost to follow up.

This case report is the second case developing renal amyloidosis in Hodgkin’s disease in children in Indian literature. The other case report is from Bombay group(5).

The commonest cause of nephrotic syndrome in Hodgkin’s disease is minimal change glomerulonephritis(6). Renal amyloidosis is a very rare complication of Hodgkin’s disease. Falkson and Falkson expressed that incidence of renal amyloidosis is less than 1%(7). Champion et al. described 4 cases of renal amyloidosis associated with Hodgkins disease and suggested an incidence of less than 1%(8). Amyloidosis is a chronic disease usually progressive and is a terminal event. Our patient also did not improve and nephrotic syndrome recurred. The patient had completed chemotherapy and for fifteen months he was asymptomatic and in remission. During these 15 months he had 3 visits to the Pediatrics Oncology Clinic.

The development of renal amyloidosis in this case was 15 months after completion of chemotherapy. In the earlier reported case, renal amyloidosis occured in one case when he was undergoing chemotherapy and he improved with continuation of chemotherapy and remained well for 2 years post treatment(5). The duration of Hodgkin’s disease needed to produce amyloidosis is reported to be 3 years(9) and 7 years(5). In our case the development of amyloidosis was 15 months after the treatment for Hodgkin’s disease was completed.

The administration of nitrogen mustard has been shown apparently to precipitate amyloidosis in Hodgkin’s disease in man(10). Renal amyloidosis may develop in individuals with Hodgkins disease who had received no chemotherapy but were treated with only radiotherapy(11). When proteinuria occurs in a patient with Hodgkins disease, we should investigate for nephrotic syndrome.

Amyloid AA is the type of amyloid deposit seen in secondary systemic amyloidosis as in Hodgkin’s disease(12). Amyloid AA is still frequent in carcinoma and is seen in as much as 3% of renal adenocarcinomas(13). We had not analyzed the type of amyloid in this case.

Mixed cellularity is the type of histology of Hodgkin’s disease developing renal amyloidosis as described in the literature(5). In the present case also, the histology was mixed cellularity. Immunofluorescence studies were negative for the immunoglobulin complexes, thereby excluding the possibilities of membranous glomerulopathies in this case. Renal amyloidosis as a cause of secondary amyloidosis due to underlying familial mediterranean fever in children has been reported(4).

Nephrotic syndrome due to renal secondary amyloidosis can go into remission following removal of the primary cause. But in our case it was resistant to symptomatic treatment and there was no evidence that he had relapse of Hodgkin’s disease for us to restart chemotherapy. As there is no treatment for secondary amyloidosis we discharged the patient with advise to follow up.

Contributors: VT and LSA treated the case and drafted the manuscript. RD did the histopathological diagnosis. VT will act as the guarantor for the paper.

Funding: None.

Competing interests: None stated.

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