A case of hypereosinophilic syndrome developing Hodgkin's disease after 4 years.

Abstract

The key findings of idiopathic hypereosinophilic syndrome include leucocytosis with striking eosinophilia. Exaggerated eosinophilia has been reported in association with a variety of lymphoid (Chang et al, 1999) and solid tumours (Stefanini et al, 1991). The clonal nature of eosinophils has been confirmed in some cases, suggesting that in these patients this syndrome is a neoplastic disorder (Chang et al, 1999). Other cases may be a reflection of polyclonal or monoclonal expansion of T-lymphocytes (Roufosse et al, 1999) in which the eosinophilia is thought to be the result of eosinophilopoietic cytokines, including interleukin-5 and other cytokines or chemokines elaborated by tumour cells (Owen et al, 1989). The expression of tumour necrosis factor-alpha family receptors by eosinophils suggests that these cytokines could regulate tumour growth. The eosinophilia may precede the clinical diagnosis of tumour and it may require longer period of observation. We report a patient who presented with a high eosinophil count and was monitored for 4 years. The patient ultimately developed Hodgkin's disease. A 55-year-old male presented in November 1999 with a history of itching all over the body. A general physical examination revealed no lymph node enlargement, and the liver and spleen were not palpable. Examination of cardiovascular respiratory and other systems revealed no abnormality. Complete blood counts (CBC) showed white blood cells (WBC) 245·6 × 109/l, platelets 225 × 109/l and Hb 9·8 g/dl. The differential leucocyte count showed 95% eosinophils (Fig 1A). Peripheral blood eosinophils did not show any degranulation that was suggestive of a malignant eosinophilic disorder. Bone marrow and trephine biopsy examination revealed hypercellular marrow, with diffuse infiltration with mature eosinophils. There was no increase in blast cells and also there was no evidence of lymphoma or metastatic tumour. The patient was investigated to eliminate any underlying cause of the eosinophilia, most importantly lymphoproliferative disorders including Hodgkin's disease and non-Hodgkin's lymphoma. Radiological examination including a chest X-ray, echocardiogram, computed tomography scan of the chest and abdomen revealed no abnormality. Consecutive stool examinations were negative for parasitic ova/cysts. Cytogenetic studies did not detect the Philadelphia chromosome. (A) Bone marrow aspirate showing increased eosinophils. (B) Lymph node showing pleomorphic population of lymphoid cells and prominent eosinophils. A Reed-Sternberg cell is also seen. Original magnification ×400. Immunophenotyping of the peripheral blood using a lymphocyte gate showed CD3+ 63%, CD7+ 33%, CD4+ 45%, CD8+ 37%, CD4+ CD8+ 3%, CD19+ 9%, CD20+ 8%, CD22+ 12%, CD20+CD5+ 1%, CD10+ 0%, CD13+ 4%, CD33+ 3%, CD16+ CD56+ 11%, γ/δ T-cell receptor (TCR) 2%, α/β TCR 64% and HLA-DR+ 29%. These immunophenotyping results did not suggest a monoclonal proliferation. Based on the clinical examination and laboratory investigations, a diagnosis of idiopathic hypereosinophilic syndrome was made, which was confirmed upon review of the peripheral blood and bone marrow slides at the Department of Haematology, St Mary's Hospital, London. The patient was started on hydroxyurea 1 g/d, zyloric 300 mg/d and deltacortil 45 mg/d. He showed remarkable clinical improvement and a CBC carried out after 4 weeks of treatment showed WBC 10.5 × 109/l, and Hb 11.2 g/dl. The differential leucocyte count showed 60% neutrophils, 25% lymphocytes, 5% monocytes and only 10% eosinophils. He was monitored in the Haematology outpatient clinic with serial blood counts. He reported in March 2003 with history of anorexia, generalized weakness and lymph node enlargement in the inguinal region. There was no history of fever, night sweats and weight loss. The enlarged lymph node was biopsied. Microscopic examination showed effaced architecture, pleomorphic population of lymphoid cells, prominent eosinophils and a few Reed-Sternberg cells were also seen (Fig 1B). Lymph node findings were consistent with a diagnosis of Hodgkin's disease (mixed cellularity type). Eosinophilia with Hodgkin's disease is well known and a direct correlation of eotaxin expression and tissue eosinophilia in Hodgkin's disease is well established (Pinto et al, 1997; Teruya-Feldstein et al, 1999). However, the development of Hodgkin's lymphoma preceded by hypereosinophilia is rare, particularly after the long period seen in our patient.