P.D. Ziakas et al.
`
`Lymphoma development in a patient receiving anti-
`TNF therapy
`
`Haematologica 2007; 88:(8)e108-e109
`
`The development of a lymphoma after antibody ther-
`apy with anti-tumor necrosis factor (TNF) is described. A
`70 year-old-male was admitted in February 2003, com-
`plaining of a painless growth on his upper right arm. The
`patient had been suffering from rheumatoid arthritis
`(RA) for the past 15 years and had been treated with
`low-dose corticosteroids and methotrexate for the previ-
`ous 5 years. One year ago he was started on concurrent
`courses of therapy with the humanized monoclonal anti-
`TNF antibody, adalimumab.1 On examination the
`growth had two areas of palpable masses. The patient's
`face was edematous and the upper anterior chest wall
`showed distended collateral superficial veins. His neck
`veins were also dilated. The soft palate, Waldeyer's ring
`and the rhinopharynx were edematous. The parotid
`glands were enlarged and the presence of a submaxillary
`lymph node of 3 cm was evident. The remainder of the
`physical examination proved negative. His white blood
`cell count was 12,300/L with 66% neutrophils, 31%
`lymphocytes and 3% monocytes. A few atypical lym-
`phocytes with scanty cytoplasm and irregular nuclear
`contours and inconspicuous nuclei were present. A bed-
`side diagnosis of superior vena cava syndrome (SVCS)
`was made. The diagnosis was confirmed by a computed
`chest tomography (CT), which further revealed mild
`mediastinal lymphadenopathy (Figure 1, right hand
`side). Magnetic resonance imaging (MRI) of the right arm
`revealed two soft-tissue masses, the larger having a
`diameter of 16cm, being discretely separated from the
`underlying biceps brachii muscle (Figure 1, left hand
`side). Gastroscopy, colonoscopy and abdominal CT scan
`were negative. Bone marrow biopsy revealed 20% infil-
`tration of monoclonal CD5+, CD23-, CD19+, CD20+,
`cyclin D1+ B-lymphocytes, consistent with a mantle cell
`lymphoma (MCL) phenotype. The histologic examina-
`tion of soft-tissue and node biopsies also revealed MCL,
`an aggressive lymphoproliferative disorder with distinc-
`tive clinicopathologic features, accompanied by the char-
`acteristic cytogenetic abnormality, t(11;14)(q13;q32). A
`minor salivary gland biopsy did not reveal lymphocytic
`infiltration compatible with Sjogren's syndrome or non-
`Hodgkin's lymphoma (NHL). The patient received com-
`bination therapy with rituximab (anti-CD20 monoclonal
`antibody), mitoxantrone and fludarabine with improve-
`ment of all signs and symptoms. This is the first report
`in the literature of adalimumab-associated NHL. The fac-
`tors predisposing to lymphoma development and the
`atypical presentation of MCL are the main points of this
`case. Although chronic antigenic stimulation contributes
`to an increased risk of lymphoma development, the
`prevalence of NHL in RA in the absence of immunosup-
`pressive treatment is low.2 Furthermore, RA patients
`treated with methotrexate may develop lymphoprolifer-
`
`| 108 | haematologica/the hematology journal | 2003; 88(online)
`
`Figure 1, Left: MRI of the right arm showing two soft tissue mass-
`es (arrows).
`Figure 1, Right: CT of the chest showing dilated collateral veins
`(arrows).
`
`ative disorders that share similar characteristics with
`those NHLs described in immunosuppressed patients.3
`Despite the controversy about the occurrence of NHL
`induced by low-dose MTX therapy in RA patients, the
`characteristics of these lymphomas and the possibility of
`a complete remission after MTX withdrawal militate
`against a chance association.4 Recently 21 cases of NHLs
`were reported in patients with RA or Crohn's disease fol-
`lowing treatment with infliximab and etanercept, agents
`which inhibit TNF alpha activity.5 The known immuno-
`suppressive effect of the anti-TNF drugs and the well
`established predisposition to lymphoma development in
`immunosuppressed transplant recipients could explain
`the potential risk of an anti-TNF induced lymphomato-
`genesis. MCL commonly presents as an extranodal dis-
`ease involving multiple sites such as bone marrow the
`gastrointestinal tract, central nervous system and sali-
`vary glands. However, extranodal soft-tissue involve-
`ment, mimicking sarcomas as well as SVCS are extreme-
`ly rare manifestations.6 In conclusion, patients with RA
`receiving immunosuppressive and biological therapies
`such as anti-TNF reagents should be monitored closely
`for lymphoma development, taking into consideration
`that the clinical picture may be characterized by atypical,
`extranodal manifestations.
`
`P.D. Ziakas, S. Giannouli, A.G. Tzioufas, M. Voulgarelis
`Correspondence: Dr M.Voulgarelis,
`Department of Pathophysiology, Medical School, National
`University of Athens, M. Asias 75, Goudi, 11527 Athens, Hellas.
`Tel : 32-10-7462512-14, Fax: 32-10-7462664
`Acknowledgment: Our thanks to Prof. H.M. Moutsopoulos for his
`guidance, recommendations and continuous support
`
`References
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`haematologica online 2003
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