Sustained response of primary cutaneous CD30 positive anaplastic large cell lymphoma to bexarotene and photopheresis

Primary cutaneous CD30 positive anaplastic large cell lymphoma accounts for around 8% of T cell skin lymphomas [1]. Lesions are usually localized, only 20% of cases have multicentric cutaneous disease at diagnosis [2]. Prognosis is usually very good, with spontaneous remission of lesions occurring fairly frequently (42% reported by Dutch Cutaneous Lymphoma Group, [2]). Five year survival for the condition has been reported at 77% by Stanford University [3] and 95% by the Dutch Cutaneous Lymphoma Group [2]. Neither of these groups was able to establish histological or clinical features which predicted poor survival. In the Stanford study [3], patients with multifocal skin involvement were more likely to develop extracutaneous disease and to die from lymphoma, although these differences were not statistically significant, which was likely to be a reflection of the small numbers involved. A 40-year-old female presented to us with a fungating lesion of her left cheek [Figure 1(A)]. Biopsy of this was consistent with CD30 positive anaplastic large cell lymphoma [Figures 1(B) and 1(C)], clonal T cell receptor gene rearrangement was confirmed in the sample by polymerase chain reaction [Figure 1(D)]. Similar lesions were present on her abdominal wall and left thigh. Staging CT and bone marrow revealed these to be primary cutaneous lesions. She was treated with six courses of CHOP chemotherapy in light of the multifocal skin involvement, with excellent resolution of the lesions, confirmed by biopsy. Unfortunately, she relapsed 6 weeks after the end of treatment, with lesions on her face, neck and left breast, again this was confirmed by biopsy. The outlook was felt likely to be poor as she had multifocal skin involvement which relapsed rapidly, again in multiple sites, after systemic therapy. A range of salvage therapies were discussed. A combination of 525 mg bexarotene per day plus fortnightly photopheresis was initiated, along with a statin and omega 3 oils to control lipids, and the lesions responded well. She did, however, require local radiotherapy to two larger lesions which were causing cosmetic concerns. Although a number of new lesions have appeared in the interim, these have regressed on continuing therapy and she remains in clinical remission 4 years after commencing the bexarotene and extracorporeal phototherapy combination, phototherapy consisting of two procedures on consecutive days, currently every 8 weeks. The dose of bexarotene remains 525 mg daily. Lipids and thyroid function are within normal ranges. Bexarotene is a synthetic retinoid which selectively binds to the retinoid X receptor (RXR) family of nuclear receptors, causing their activation. These activated receptors act as transcription factors, aiding cellular differentiation, proliferation and apoptosis. Bexarotene has been shown to induce apoptosis of cell lines, including cutaneous T cell lymphoma (CTCL) lines, in vitro [4]. Extra corporeal photopheresis is well established as an effective therapy for CTCL [5]. Mononuclear cells are separated by leukophoresis, psoralen is