1Department of Nephrology 2INSERM U 574 and Department of Pathology Pitié-Salpétrière Hospital Paris France Email: hassan.izzedine{at}psl.ap-hop-paris.fr
Case
A 79-year-old Vietnamese woman was hospitalized with a 2-month history of progressive fatigue and dyspnoea. Her past history included hypertension, hypercholesterolemia and cholecystectomy. Her physical examination revealed dyspnoea at rest, bilateral crepitus, ascites, peripheral leg oedema, hypertension (150/100 mmHg), ecchymosis, left subconjunctival haemorrhage jugulo-carotidian and axillary lymphadenopathies and barely palpable liver and spleen.
Laboratory data are presented in Table 1; among them were serum creatinine of 85 mmol/l, blood urea nitrogen 9.4 mmol/l, proteinuria (2.56 g/l) and microscopic haematuria. A renal ultrasound was normal, and bone marrow biopsy demonstrated megakaryocytic hyperplasia and distinct interstitial plasmocytosis with polytypical expression of light chain immunoglobulins. No signs of malignancy were observed. Multiple axillary and infra- and supra-mesenteric nodes, bilateral pleural effusions, effusion in the Douglas sack and cardiomegaly with associated pericarditis were seen on computed tomography. Biopsies were done of periclavicular lymph nodes, the bone marrow, and a kidney (Figures 1 and 2).
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What is your diagnosis?
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Pathological diagnosis: renal thrombotic microangiopathy associated with the mixed type of multicentric Castelman's disease
Castelman's disease (CD) (also called giant lymph node hyperplasia or angiofollicular lymph node hyperplasia) is a clinicopathological entity of unknown etiology characterized by non-malignant hyperplasia of lymph nodes. Three histological patterns of CD have been described: the plasma cell type (10% of cases); the hyaline-vascular type (90%) and the mixed type [1,2]. Lymph node hyperplasia may occur at different sites, among them mediastinal (60%), superficial (25%) and intra-abdominal nodes (15%).
CD includes lymphadenopathy and systemic manifestations such as thrombocytopaenia, anaemia, fever, weight loss, hepatosplenomegaly, arthralgias, skin rashes, pleural effusion, circulating autoantibodies, and neurological and renal abnormalities [3]. The clinical and systemic manifestations in our patient included acute illness, haemolytic anemia, thrombocytopaenia, hypergammaglobulinaemia, a monoclonal immunoglobulin G peak on serum immunoelectrophoresis, pleural and pericardial effusions, ascites and autoimmune manifestations (positive Coomb's test, positive ANA, anticardiolipin antibodies, prolongation of activated partial thromboplastin time). These symptoms and haematologic manifestations associated with lymphadenopathy in our patient mimicked malignant lymphoma, lupus-like syndrome, or infection. The diagnosis of CD was made only after the histological examination of a lymph node.
In addition to hypertension, the renal manifestations of CD include proteinuria, nephrotic syndrome [4,5], haematuria, rapidly progressive renal failure [6], renal colic [7], and acute [8] or chronic renal insufficiency [9]. The histology of renal involvement is varied: glomerular [1012], interstitial [6,13], vascular [8,14] and amyloidosis [45,9]. In our patient, urinary abnormalities consisted of proteinuria and haematuria. Renal biopsy revealed thrombotic microangiopathy. Only three cases of CD-associated thrombotic microangiopathy have been reported in the literature [8,14]. Acute renal failure was present in each case, and was associated with proteinuria in two of them; antinuclear antibodies were present in two patients and antiphospholipid antibodies in one. Their clinical courses were variable. Of the two patients with the multicentric form of CD, one achieved complete clinical recovery after high-dose corticosteroid therapy, whereas the other suffered chronic renal insufficiency despite treatment with prednisone and azathioprine. In the third patient, who had a unicentric form of CD, resection of the lymph node led to complete remission.
For solitary CD, the treatment of choice is the surgical removal of the tumour, which results in improvement of the clinical manifestations of CD, the laboratory abnormalities, and the nephrotic syndrome attributable to renal amyloidosis [4,5]. Renal function usually recovers [8]. When the lymphadenopathy is generalized, resection is difficult or even impossible. In the multicentric form of CD, corticosteroids offer an effective alternative treatment, resulting in improved renal function [6,11]. Our patient was treated with i.v. prednisolone 1 g/day for 3 days followed by oral corticotherapy, 1 mg/kg/day. After 1 month, her anaemia, proteinuria and haematuria resolved. Danazol was then introduced to treat her persistent thrombopaenia.
Our case draws nephrologists attention to a rare instance of renal injury in the setting of CD. Diagnosing CD is not easy, given the non-specificity of its systemic manifestations, lack of knowledge on its etiology, and the necessity of a histopathological examination to confirm the diagnosis.
Conflict of interest statement. None declared.
References