Correlation between mycosis fungoides and pregnancy

Results

We identified 6 MF patients who had been pregnant during the course of their disease. Four patients were on their first gestation and 2 patients had 2 pregnancies during the course of their disease; therefore, a total of 8 pregnancy cases, were reviewed. The median age of patients at the time of diagnosis 26.7 (range 21-30 years) and pregnancy 29.4 (range 27-31 years). The patient characteristics are summarized in Table 1. Immunohistochemistry was possible in all cases. Five cases showed predominant CD4-positive epidermotropic infiltrates (Figure 1) and in one case the lymphocytic infiltration was CD4- and CD8-negative. Four of the patients had monoclonal TCR gene rearrangement. Most patients were staged as Ia or Ib and only one case was stage IIIa. All patients were in complete remission before pregnancy, except for one case, which had been newly diagnosed (patient 3). In all cases, the erythematous scaly patch/plaque areas were histologically confirmed as present during the course of pregnancy and at postpartum (Figure 2). One case was afflicted by erythrodermic and tumoral lesions. Except for one case that had anaplastic large cell transformation, none of the other patients experienced progression to advanced stages (Table 2). Most relapse cases occurred in the first 2 months after childbirth; however, 2 cases showed progression (patient 3) and relapse (patient 6) of disease during pregnancy. The patient who was diagnosed as stage IIIa before pregnancy refused the recommended treatment during pregnancy, but underwent combination chemotherapy during the puerperium period. Other patients who had flares shortly after delivery were treated with narrow-band ultraviolet B phototherapy. All patients had normal pregnancy and normal delivery, except for one ectopic pregnancy (patient 2). No complications were observed during the gestational period. The outcomes of the 7 pregnancies were normal and healthy neonates were delivered (Table 2).

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Figure 1

Histopathological feature of the patch stage of mycosis fungoides. Sections from the patch show epidermotropism of atypical lymphocytes, mostly in basal layer and dermis, mild interstitial infiltrate of small lymphocytes are seen (Hematoxylin and eosin ×100) (arrow).

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Figure 2

Mycosis fungoides, an erythematous scaly patch in the upper part of left tight in a 31 years-old female during pregnancy.

Discussion. The results of the present study showed that all patients experienced disease relapse, or aggravation during the course of pregnancy, or shortly after delivery. Nevertheless, MF did not adversely affect pregnancy outcomes, as suggested in previous reports. Immunophenotyping studies11 have revealed that MF is one of many cutaneous T-cell lymphomas, typically of the CD4 helper T-cell phenotype. Recent studies,12,13 suggest that CD8-positive cytotoxic T-cells play a crucial role in the antitumor response in MF; a correlation between high percentages of CD8-positive cytotoxic T-cells in the dermal infiltrates and better survival has been described. The CD8-positive T-cells exert their antitumor effect through a direct cytotoxic effect as well as by the production of cytokines, particularly interferon. Further more, they can mediate tumor cell lysis by exocytosis of cytotoxic granules containing perforin, granzymes, and T-cell intracellular antigen, and by expression of the Fas ligand, which interacts with Fas on the neoplastic T-cells.12,13 Both pathways ultimately lead to the activation of caspase 3 and tumor cell death.14 Decline in the number of peripheral blood CD8-positive T-cells, natural killer cell, and increasing circulating malignant T-cell totally associated with progression of MF.15 A gradual shift from a predominantly type I cytokine profile in MF plaques to a predominantly type 2 cytokine profile in MF tumors has been suggested.16 Also, a similar shift toward T-helper type 2 immunity has been suggested during the pregnancy.17 Therefore, the lack of strong maternal cellular immune response, and a more dominant humeral immune response toward the fetus have been thought to promote maternal acceptance of the fetal allograft.18 Thus, the decreased immune response accounts for the findings of the present study regarding flares and the occasional progression of MF during pregnancy and postpartum. Nevertheless, very little is known regarding the exact relationship between MF and pregnancy, and there is no clear consensus concerning the effect of pregnancy on MF flares and the effect of MF on pregnancy outcomes. Castelo-Branco et al,19 reported of a pregnant woman with advanced-stage MF around the conception time that managed with photon radiotherapy during the pregnancy, the outcome of her pregnancy was good and a healthy neonate was delivered. In another case report in 2001, Echols et al,20 described 3 cases of pregnancy with MF, but only one case of a 26-year-old black woman diagnosed to be suffering from MF showed an increase in skin lesions. At the commencement of her third trimester, she presented with an acute exacerbation of MF, and complete remission with trial treatment with alpha-interferon was achieved. In a series of 9 pregnant women with MF,21 there was no evidence confirming the change of course of MF during pregnancy. They reported that pregnancy appeared to have had no impact on the course of early-stage of MF.21 In 2012, Ozturk et al,22 described a 30-year-old pregnant woman with MF in its early stages. They concluded that there were no changes in the severity and frequency of the lesions both during pregnancy and in the postpartum period. Our findings regarding the exacerbation or even the progression of MF, correlate well with some of the previously mentioned reports. The limitations of this study were the short mean duration of follow-up, and the small sample size of subjects. Nevertheless, larger, long-term studies must be performed in order to firmly establish the exact relationship between MF and pregnancy.

In conclusion, on the basis of cases presented and the observed immunosuppression that occurs during pregnancy, in particular, the relative bias toward T-helper type 2 immunity, it follows that pregnancy may cause exacerbation or even progression of MF. However, on the contrary, MF does not have an adverse impact on pregnancy.