Page 133 - Haematologica3

T-cell non-Hodgkin lymphoma arising in patients with immunodeficiencies
Figure 2 . The hematoxylin and eosin stain shows large atypical cells in a background of small monomorphic lymphocytes. (A) The large atypical cells are positive for CD3 (B) and show loss of expression of CD5. (C) The small lymphocytes in the background are B-cells (CD20) with co-expression of CD5 (D), consistent with resid- ual B-CLL in the background of this T-cell lymphoma.
201139 out of a population of 16,574,98938 leads to an expected number of 1.46 compared to an actual number of 3 patients. The numbers of expected cases for IBD and RA are probably overestimated, since the prevalence of IBD and RA in the general population that we used for these calculations also included all non-treated patients, who were excluded in our case series. Regarding RA, it is known that only about 10% of the patients with this dis- ease who are registered are treated by a rheumatologist or other medical specialist, which generally corresponds with the use of immunosuppressive drugs.39 Using this information, when we recalculated the expected number of patients with RA in our cohort, we found a number of only 0.146 compared to the actual number of three. The probability of observing a certain number of cases, given an expected number of cases, can be calculated via the Poisson distribution. By using this method, we found a probability of 4.34E-05 that at least seven cases of IBD would occur given an expected number of 0.90. The prob- ability of at least four cases of B-CLL compared to an expected number of 0.063 is 6.24E-07. For RA the proba- bility of three cases occurring is 0.00047 when the expect- ed number is 0.146. These calculations, even when bear- ing in mind the referral bias of our center, suggest that for B-CLL patients and those on immunosuppressive drugs for the treatment of IBD and RA, the risk of developing a T-NHL is higher than in the general population.
Taking into account the additional 596 cases we found in the literature of T-NHL in patients with impaired immunity due to HIV, hematologic malignancies and immunosuppressive drugs, this observation might be extrapolated to all patients with secondary immunodefi- ciencies. Whether patients with primary immunodefi- ciencies are also at risk for developing T-NHL is less clear, since we found only nine such cases in the literature. In this particular group of patients polyclonal T-cell prolifer- ations are seen more often than overt T-cell lymphomas.8
The pathogenesis of T-NHL in immunodeficient patients is unclear. In our series the majority of lym- phomas were EBV-negative, suggesting that, in contrast to B-cell lymphoproliferative disorders in immunocompro- mised patients, EBV does not play a role in this setting. Infection by other viruses, such as human T-lymphotropic virus type 1 (HTLV1) and human herpes virus (HHV)-6, possibly plays a role in development, as is suggested for T- cell PTLD.40-42 Another possible mechanism is that immune dysfunction contributes to lymphomagenesis by dimin- ished immunosurveillance when malignant mutations arise in lymphoid cells due to other causes, for instance chronic antigenic stimulation or environmental factors, including mutagenic effects of chemotherapeutic or immunosuppressive drugs.42,43 Furthermore, a common biological basis of the first and second malignancy in hematologic malignancies has been suggested, ie., due to
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