QJM Advance Access originally published online on April 21, 2007
QJM 2007 100(5):311-312; doi:10.1093/qjmed/hcm026
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Cold agglutinin disease revealing mediastinal seminoma
Sir,Cold agglutinin disease (CAD) is an autoimmune haemolytic anaemia in which cold-reactive auto-antibodies bind to erythrocyte carbohydrate antigens, causing hemagglutination and complement-mediated haemolysis.1–4 It is associated with various conditions, including infections (Mycoplasma pneumoniae, hepatitis C), autoimmune diseases (especially systemic lupus erythematosus) and lymphoproliferative disorders (mainly lymphoma.1–8 However, it has rarely been described in patients with malignant solid tumours. We report a case of interest, where a patient developed CAD-associated haemolytic anaemia related to mediastinal seminoma, with a favourable outcome after chemotherapy.
A 61-year-old man presented in December 2001 with a 1-month history of asthenia. On admission, he was pale, but general physical examination was otherwise normal, and in particular hepatosplenomegaly and lymphadenopathy were absent. Laboratory studies showed: haemoglobin 6.4 g/dl, mean corpuscular volume 104 fl with reticulocytes 298 000/mm3, leukocytes 5.6 x 109/l, platelets 404 x 109/l; other routine biochemical assessments, including renal tests and erythrocyte sedimentation rate, were normal. Blood electrophoresis (IgG 10.1 g/l, IgM 1.37 g/l, IgA 2.17 g/l) as well as both blood and urinary immunoelectrophoresis, were also within normal limits. Serum lactate dehydrogenase was 640 IU/l, total bilirubin 29 µmol/l, and haptoglobin <0.1 g/l. A direct Coombs’ test was positive (4+), showing anti-C3d with anti-I specificity; the anti-I titre was 1:4096. Blood cultures, both viral (hepatitis B and C, cytomegalovirus, Epstein-Barr virus, parvovirus B19, human immunodeficiency virus) and bacterial (Mycoplasma pneumoniae) serologies were all negative. Autoantibody screening tests, particularly for rheumatoid factors, anti-nuclear antibodies, anti-phospholipid and anti-cardiolipin antibodies, anti-neutrophil cytoplasmic antibodies and cryoglobulin, were all negative.
Abdominal and thoracic computed tomography showed a mass involving the anterior mediastinum (Figure 1). Both sternal bone marrow aspirate and bone marrow biopsy specimens of the right posterior iliac crest proved normal, with no abnormal cells or dysplastic changes in erythroid, myeloid or megakaryocyte lineage, and no clonal lymphocyte infiltration (particularly CD20). Because we suspected mediastinal malignancy, surgery was done; histological examination of biopsy specimens demonstrated damage consistent with seminoma. A diagnosis of CAD related to mediastinal seminoma was made. Combined therapy of bleomycin, etoposide and cisplatin was initiated monthly for 4 months, resulting in complete resolution of the tumoural mass. In May 2002, the patient did not exhibit evidence of anaemia (haemoglobin 14.8 g/dl). A direct Coombs’ test was slightly positive (1+), but lactate dehydrogenase level and haptoglobin were within normal limits. At 3 years follow-up, the patient remained asymptomatic.
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CAD has been described in association with various conditions, including mainly lymphoproliferative disorders (78% of cases).1–8 In a review of the Medline database (1966–2006), we found 22 observations of patients with CAD who developed malignancies (breast, ovary, kidney, colon, thyroid, prostate, skin, tongue, urinary bladder or carcinoid tumor). We did not find another report of mediastinal seminoma-associated CAD. At seminoma diagnosis, the patient did not exhibit clonal population in his bone marrow. Other authors have previously reported autoimmune haemolytic anaemia in five patients with seminoma, although none of these five exhibited cold agglutinin disease.9 In our patient, the diagnosis of paraneoplastic CAD seems reasonable, as other causes were excluded, particularly haematologic malignancies, and after initiation of chemotherapy, the anaemia disappeared, Coombs’ test being slightly positive.
When unexplained CAD is observed in patients, check for an underlying solid tumour. CAD should be included within the spectrum of paraneoplastic manifestations of seminoma.
Department of Internal Medicine
Rouen University Hospital
Rouen
France
email: isabelle.marie{at}chu-rouen.fr
Acknowledgement
The authors thank Richard Medeiros for his advice in editing the manuscript.
References
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