Specific Cancers And

4.1. Hematologic Malignancies

While the overall frequency of cancers may not increase in patients with SLE, cohorts from various centers have shown that patients with SLE have an increased risk of lymphoproliferative and hematopoietic malignancies. A 4.1 - to 44-fold increased risk for these cancers was observed [12, 13, 15, 16], However, from this group of cancers, only NHL was significantly associated with an increased risk of cancer. The SIR of NHL in SLE was 5.38 in Toronto [12], 9.3 in Pittsburgh [15] and 44 in Finland [13]. In a recent study of 1585 patients with SLE from the nationwide Danish Hospital Discharge Register [16], there was a significant excess of NHL among the SLE patients with RR = 5.2.

A literature review has revealed numerous case reports of patients with SLE who developed NHL, Burkitt's lymphoma and Hodgkin's disease [3, 4, 17-19].

The development of neoplasia in patients with SLE was not related to specific clinical features or a certain subtype of SLE. Lymphoproliferative tumors were identified in patients with mild and severe forms of SLE, in patients with discoid lupus and in patients with subacute cutaneous lupus (SCLE) [12, 13, 15, 16, 20].

Twenty cases (3 males, 17 females) of NHL were included in four cohorts of SLE patients [12, 13, 15, 16]. In all cases, NHL occurred after the diagnosis of SLE. The mean age at the diagnosis of SLE was 41 years (range 12-83 years), and the mean interval between the diagnosis of SLE and NHL was 12 years (range 1-30 years). However, in a few case reports [21, 22], SLE developed after the diagnosis of lymphoma. In one case, a 62-year-old woman developed SLE 6 years following chemotherapy for malignant lymphoma [21], and in an another case, SLE developed in a patient with small cleaved cells lymphoma 3 years after treatment with total body irradiation [22],

In the majority of cases of the four SLE cohorts [12, 13, 15, 16], the lymphomas were localized to lymph nodes, however, cases of extra-nodal disease were also noted. Extra-nodal locations included the breast (one case), vertebra (one case) and central nervous system (CNS) in another case. Similarly, in a review of the reported cases of SLE patients who developed lymphoma [23-26], the malignant cells were identified in the spleen [23], liver [24], bones [25] and CNS [26],

Peripheral lymphadenopathy is a very common feature of SLE and lymphoma. However, in patients with SLE the lymph nodes may regress following treatment, while in lymphoma the lymph nodes are large, persistent and progressive. Furthermore, the presence of eosinophilia and pruritis may also suggest lymphoma.

One of the 2 SLE patients from Pittsburgh who developed NHL [15] also had Sjogren's syndrome, suggesting that this syndrome may trigger the development of NHL in patients with SLE. However, the association between SLE, NHL and Sjogren's syndrome has not been addressed in the other cohorts of SLE patients who developed malignancies. [12, 13, 16],

Table 1. The risk estimates for cancer in 4 SLE cohorts compared with the general population

Cancer risk RR, CI

Petterson et al. [12]

Abu-Shakra et al. [13]

Sweeney et al. [15]

Mellemkjaer et al. [16]

All cancers

2.5 (1.3-4.3)

1.08(0.7-1.62)

1.36 (0.6-3.03)

1.3(1.06-1.58)

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