1. Introduction

Autoimmune manifestations are common in splenic marginal zone lymphoma (SMZL) and are sometimes the presenting feature of the disease ^[1]. Autoimmune cytopenia (anemia, thrombocytopenia) are the most frequently reported autoimmune conditions. However, other immunological manifestations may be associated with SMZL. We report hereby the case of a 72-year-old woman presenting with a systemic lupus erythematosus (SLE) revealing a SMZL.

2. Case Report

A 72-year-old female patient without medical history presented with prolonged fever and pallor. The patient’s symptoms had begun 6 months before and worsened progressively. She complained of fever (>39°C) spiking once a day, usually in the evening, with undefined abdominal pain; she also reported recent palpitations, dyspnea and vertigo. Physical examination showed, besides fever (>39°C), blood pressure of 110/70 mmHg, heart rate of 120 beat per minute, mucocutaneous pallor, malar rash, proteinuria on urine dipstick, bilateral axillary, and cervical lymph node enlargement. Pulmonary examination revealed dullness on the right basis and abdominal palpation concluded to a liver and spleen enlargement. Cell blood count revealed bicytopenia with normochromic normocytic anemia of 6 g/dl, low platelet count of 77000 elements/mm³, and lymphopenia of 600 elements/mm³. Liver tests revealed anicteric cholestasis and transaminases elevated twice the normal range. Creatinine rate was 6 mg/l and 24-hour proteinuria was 0.7 g. Serum protein electrophoresis showed monoclonal type hypergammaglobulinemia of 27 g/l, and serum immune-electrophoresis confirmed Ig M kappa type. Direct Coombs’s test was positive IgG type. Immunological investigation revealed positive antinuclear antibodies with a level of 1/1280, anti-DNA and antiphospholipid antibodies were negative. Infectious investigations including repeated bacteriological and fungal blood cultures, Mycobacterium tuberculosis throat examination, and viral serological investigations (Hepatitis C virus, Hepatitis B virus, Epstein-Barr virus, and Cytomegalovirus) were negative. Chest X-ray revealed right pleural effusion. Echocardiography was normal. Thoracic and abdominal computed tomography scan revealed diffuse lymph node enlargement on cervical, mediastinal and hepato-splenic hilar adenopathy associated to right mild pleural effusion. Bone marrow and liver biopsies concluded to lymphoid infiltrate, and immunohistochemical study showed that tumor cells stained positive with CD20⁺, CD3⁺, CD5⁺ phenotype thus, concluding to a splenic marginal zone lymphoma (SMZL). The diagnosis of SLE revealing stage 4 SMZL was retained. The treatment was as follows: 1 mg/kg/day of prednisone with progressive tapering associated to 375 mg/m² of body surface of rituximab once weekly during 4 weeks. The patient’s outcome was favorable and the decline was 12 months.

3. Discussion

Splenic marginal zone lymphoma (SMZL) was reported for the first time in 1992 ^[2] and is considered to be a non-Hodgkin-B-lymphoma (NHBL) with a primitive splenic localization ^[3]. Its prevalence varies between 1 and 2 % of NHBL ^[3] and is often associated to hepatitis C virus infection ^[4]. Its clinical presentation is often limited to a spleen enlargement associated to hilar spleen adenomegaly and liver enlargement and multiple lymph node enlargement are reported in only 15 % of cases ^{[5, 6]}. Autoimmune disorders associated to SMZL are reported in 20% of cases, which is often limited to biological abnormalities such as positive rheumatoid factor, auto immune cytopenia, positive antinuclear antibodies and antiphospholipid antibodies ^{[1, 5, 7]}. To our knowledge, there are only 3 case reports of SLE associated to SMZL ^{[1, 8, 9]} and SLE was inaugural in only one case ^[1] (Table 1). In fact, in a national Swedish systemic lupus erythematosus cohort including 6438 patients, 16 patients developed NHBL and only 2 patients developed SMZL ^[10]. In the previous reports, SMZL occurred 3 and 7 years after lupus diagnosis ^{[8, 9]}. These patients had not previously received immunosuppressive agents ^{[8, 9]}. Our patient had some unusual features such as her advanced age at onset, the tumor syndrome and the monoclonal gammapathy. These abnormalities have made us look for a possible association with a lymphoma. In our case, the SMZL diagnosis was based on liver and bone marrow histological findings; in fact, marrow biopsy was contributive because of a medullar invasion reported in 95% of cases ^[5]. Furthermore, in our case, HCV serology was negative as in the case reported by Voinchet et al ^[1]. In the other cases, HCV serology was not mentioned ^{[8, 9]}. Splenectomy, chemotherapy, and anti viral agents (for HCV related SMZL) are the alternatives used to treat SMZL. In our case, a combined treatment of rituximab-prednisone was successful, with a favorable outcome concerning the two conditions. In previous data, the treatment was reported in only one case and consisted of a splenectomy with a chemotherapy associating cyclophosphamide, adriamycine, vincristine, and prednisone, with a favorable outcome ^[8]. Further studies with larger effectives are needed to conclude about the appropriate treatment. SMZL associated to SLE is extremely rare.

Table 1. Clinical, immunological features, and outcome in patients with SLE and SMZL

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4. Conclusion

SMLZ can be associated to auto-immune abnormalities and more rarely to auto-immune diseases such as SLE which may be inaugural at clinical presentation. SMLZ associated to SLE is a rare condition.

References

[1]	H. Voinchet, G. Etienne, C.B. Ghiringelli, et al. Splenic marginal zone lymphoma and autoimmunity: Report of six cases. Rev Med Interne 2010; 31: 4-11.
	In article		CrossRef PubMed
[2]	Schmid C, Kirkham N, Diss T, et al. Splenic marginal zone cell lymphoma. Am J Surgical Pathology 1992; 16: 455-66.
	In article		CrossRef
[3]	Thieblemont C, Felman P, Berger F, et al. Treatment of splenic marginal zone B-cell lymphoma: an analysis of 81 patients. Clin Lymph 2002; 3: 41-7.
	In article		CrossRef
[4]	Arcaini L, Paulli M, Boveri E, et al. Splenic and nodal marginal zone lymphomas are indolent disorders at high hepatitis C virus seroprevalence with distinct presenting features but similar morphologic and phenotypic profiles. Cancer 2004; 100: 107-15.
	In article		CrossRef PubMed
[5]	Thieblemont C, Felman P, Callet-Bauchu E, et al. Splenic marginal-zone lymphoma: a distinct clinical and pathological entity. Lancet Oncol 2003; 4: 95-103.
	In article		CrossRef
[6]	Oscier D, Owen R, Johnson S. Splenic marginal zone lymphoma. Blood Rev 2005; 19:39-51.
	In article		CrossRef PubMed
[7]	Manner H, Jung B, Tonassi L, et al. Successful treatment of catastrophic antiphospholipid antibody syndrome (CAPS) associated with splenic marginal-zone lymphoma with low-molecular-weight heparin, rituximab and bendamustine. Am J Med Sci 2008; 335: 394-7.
	In article		CrossRef PubMed
[8]	Hayem G, Perdu J, Belmatoug N, et al. Syndrome lupique révélant un lymphome B lymphoplasmocytique splénique de la zone marginale. Rev Med Interne 1999; 20: 182-4.
	In article		CrossRef
[9]	Buskila D, Gladman DD, Hannah W, et al. Primary malignant lymphoma of the spleen in systemic lupus erythematosus. J Rheumatol 1989; 16: 993-6.
	In article
[10]	Löfström B, Backlin C, Sundström C, et al. A closer look at non-Hodgkin’s lymphoma cases in a national Swedish systemic lupus erythematosus cohort: a nested case-control study. Ann Rheum Dis 2007; 66: 1627-32.
	In article		CrossRef PubMed