Saudi Journal of Kidney Diseases and Transplantation

: 2011  |  Volume : 22  |  Issue : 1  |  Page : 116--119

A rare association of Castleman's disease and nephrotic syndrome

I Tazi, M Rachid, A Quessar, S Benchekroun 
 Hematology and Pediatric Oncology Department, Hospital 20 Aout 1953, Casablanca, Morocco

Correspondence Address:
I Tazi
Hematology and Pediatric Oncology Department, Hospital 20 Aout 1953, Rue Lahcen Laarjoune, Casablanca


Castleman«SQ»s Disease (CD) is an uncommon and poorly understood disorder of lymph node hyperplasia of unknown etiology. This entity belongs to the atypical lymphoproliferative disorders, a heterogeneous group of diseases characterized by a hyperplastic reactive process involving the immune system. The association of the nephrotic syndrome and CD is extremely rare and their interrelation remains enigmatic. We report a case of CD of the hyaline-vascular type with unicentric localization complicated by nephrotic syndrome.

How to cite this article:
Tazi I, Rachid M, Quessar A, Benchekroun S. A rare association of Castleman's disease and nephrotic syndrome.Saudi J Kidney Dis Transpl 2011;22:116-119

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Tazi I, Rachid M, Quessar A, Benchekroun S. A rare association of Castleman's disease and nephrotic syndrome. Saudi J Kidney Dis Transpl [serial online] 2011 [cited 2020 Oct 25 ];22:116-119
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Castleman's Disease (CD) is an uncommon and poorly understood disorder of lymph node hyperplasia with unknown etiology that was described first in 1956. [1] This entity belongs to the atypical lymphoproliferative disorders, a heterogeneous group of diseases characterized by a hyperplastic reactive process involving the immune system. [2],[3] CD is classified into two clinical subtypes: a localized (or unicentric) subtype and a multicentric subtype. Localized disease manifests as a solitary mass, which may be well circumscribed or infiltrative. It is associated with lymphadenopathy confined to one lymph node or nodal area, [4] and usually follows a benign course. Multicentric disease carries a worse prognosis, and subsequent infection or malignancy may lead to death. [4] CD can also be classified into two major histolo­gical subtypes: a hyaline-vascular subtype and a plasma cell subtype. The hyaline-vascular subtype is more common and contains nume­rous regressively transformed follicles and associated vascular proliferation. The plasma cell type contains hyperplastic follicles and marked plasma cell proliferation in the inter­follicular region. A mixed form, also called the hyaline-vascular-plasma cell subtype, is unco­mmon. [5] CD may occur anywhere along the lymphatic chain, although the mediastinum is the most common location (70%). Extratho­racic sites have been reported in the neck, axilla, pelvis and retroperitoneum. [5]

We report here an unusual case of CD of the hyaline-vascular type with unicentric localiza­tion complicated by nephrotic syndrome.

 Case Report

A 45-year-old Moroccan man was admitted to our institution, with a 2-year history of cervical lymphadenopathy, progressive fatigue, poor appetite and loss of body weight of 6 kg without fever. His past medical history was significant for insulin-dependent type-2 diabe­tes mellitus. He was afebrile and had pulse of 96 per minute, the blood pressure was 120/80 mmHg, and respiration was 22 per minute. No jaundice, skin rashes, or petechiae were pre­sent. The cervical lymph nodes were enlarged, 1-3 cm in diameter, firm, mobile, and not ten­der. Rest of the physical examination was un­remarkable.

Laboratory investigations showed hemoglo­bin of 13 g/dL, mean cell volume (MCV) of 83 fL, white cell count of 4700/L and platelet of 164,000/L. The bleeding time and coagula­tion time were normal. Erythrocyte sedimen­tation rate was 40 mm/1 h and C-reactive pro­tein was 12 mg/L. Renal investigation and liver tests were normal. Hepatitis B and C serology and HIV serology were negative. Chest X-ray was normal. Ultrasound examination of the abdomen showed normal kidneys, liver, spleen and pancreas. Computed tomography (CT) scan of the abdomen and the chest was normal. Histopathological examination of the surgical sample revealed hyaline-vascular CD (giant lymph node hyperplasia). Bone marrow biopsy was negative for malignancy. Activity of lac­tate dehydrogenase was normal.

The patient received steroids orally at a dose of 15 mg of prednisone per day. He developed impaired glucose tolerance which was con­trolled with insulin. One year after the start of steroid therapy, the patient was admitted to our hospital with complaints of vomiting and pro­found peripheral edema of several days dura­tion. Peripheral edema was present. The lung fields were clear. Abdominal examination re­vealed ascites, without splenomegaly.

Checkups for possible propagation of CD, including the activity of lactate dehydrogenase, chest X-ray and abdominal ultrasonography, were normal.

The 24-hour urinary protein was 7.2 g and the serum cholesterol and albumin levels were 9.1 mmol/L and 19 g/L, respectively. Serum creatinine and serum urea were normal. Urine analysis did not show hematuria or leukocy­turia. Cryoglobulins were also absent. Diabetic retinopathy was absent on ophthalmoscopic examination. A renal biopsy was performed. The findings were consistent with membra­nous glomerulonephritis.

Intravenous methylprednisolone, 1 g/day for 3 days, was administered, followed by oral prednisone, 50 mg/day for 2 months. The neph­rotic syndrome disappeared after 3 months of treatment. Corticosteroids were slowly tapered down and stopped 12 months after their initia­tion. Since that remission, at 2 years of follow­up, still the nephrotic syndrome is in remission, nor has the CD relapsed.


CD is known as a giant lymph node hyper­plasia which was first described in 1956 by Castleman. CD is a rare clinicopathologic entity classified among atypical lymphoproliferative disorders. [1] Since its initial description, CD has been redefined from a localized tumor-like mass of lymphoid tissue, considered to be ha­martomatous, to a systemic disease with gene­ral manifestations and multiple organ involve­ment. Our patient had a classical picture of the unicentric CD. He had a cervical localization of the plasma cell type which remained loca­lized for one year. He had a long history of illness and the nephrotic syndrome developed two years after the discovery of the cervical lesion. The extremely rare association between CD and nephrotic syndrome prompted us to report this case.

Humpherys et al described the first patient, an 18-year-old girl whose nephrotic syndrome remitted promptly after the removal of a me­senteric mass which showed angiofollicular lymph node hyperplasia of the plasma cell type. [9] The renal biopsy showed minimal change nephropathy. Weisenburger [10] described a 51­year-old man who had a membranous nephro­pathy associated with multicentric angiofolli­cular lymph node hyperplasia, also of the plas­ma cell type. The nephrotic syndrome in that patient apparently developed one year after the onset of the lymph node enlargements similar to our case.

Although the pathogenesis of CD is entirely unknown, several investigators consider the localized plasma cell form to be an inflam­matory response to an unknown antigenic stimulus. The plasma cells in the lymph node would represent an exuberant B-cell response that results in the local production of high levels of antibodies. [11]

Nephrotic syndrome is a very rare compli­cation of CD. Only a few cases have been described. [12],[13],[14] Other reported forms of renal involvement in CD are rare and heterogeneous and include minimal-change disease, membra­nous GN, membranoproliferative GN, mesan­gial proliferative GN and interstitial nephritis. [15],[16]

As currently understood, CD is considered to be a heterogeneous entity related to conditions of immune deregulation. In this respect, it is interesting that various disorders of the im­mune system may be characterized by Castle­man-like histological changes, such as infec­tions (HIV) and primary auto-immune diseases (systemic lupus erythematosus, POEMS syn­drome, etc.). [17] Moreover, nephrotic syndrome appeared after the CD was diagnosed and subsequent to lymph node regression. Sugges­ting the triggering of the inflammatory res­ponse with consequent autoimmune organ ma­nifestations.

There are some unusual features about the patient, which make one hesitate to attribute the nephrotic syndrome to diabetic nephro­pathy. His diabetes developed two years be­fore renal biopsy. The nephrotic syndrome in diabetic patients with such a short history of disease is unusual. The absence of retinopathy and a significant degree of hyaline arterioscle­rosis from diabetic patients with overt neph­rotic syndrome is again exceptional.

There is a strong possibility that his renal lesions had some more direct relation with his underlying long history of angiofollicular hy­perplasia and immunological disturbance.

Lui et al have demonstrated an association of CD with excess production of the cytokine interleukin-6 (IL-6). [15] IL-6 is a pleiotrophic cytokine produced by several cell types, inclu­ding activated monocytes, B cells, endothelial cells, fibroblasts and mesangial cells. It has a panoply of biological effects, including a ma­jor regulatory effect on acute-phase response in humans. Large amounts of IL-6 were shown to be produced at the germinal centers of hyper­plastic lymph nodes from patients with CD and clinical improvement was observed along with decreases in IL-6 levels after the removal of the involved lymph nodes [15] or treatment with anti-IL-6 antibodies. [18] Corticosteroid therapy has also been shown to reduce IL-6 levels.

The treatment of CD and the possible re­versal of both amyloidosis and the nephrotic syndrome are controversial issues, based es­sentially on case reports, since controlled cli­nical studies are lacking because of the rarity of the disease. In some reports on monocentric forms, it was shown that the surgical removal of the lymph node mass was curative [11],[19] and led to the regression of the nephrotic syndrome and of amyloidosis, as detected by abdominal fat aspiration biopsy. [11]

However, Keven et al, although confirming the regression of the nephritic syndrome after excision of an abdominal lymph node, docu­mented no regression of renal amyloid depo­sits, one year after surgery. [12] Some reports do­cumented no regression of the nephritic syndrome after lymph-node excision, [20],[21] whereas some showed regression with colchicine the­rapy. [21] Current approaches include high-dose corticosteroids and in some cases the addition of antineoplastic agents, with poor clinical benefits. [4]


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