CD8‐positive mycosis fungoides and primary cutaneous aggressive epidermotropic CD8‐positive cytotoxic T‐cell lymphoma

Most cutaneous T-cell lymphomas (CTCLs) have the phenotype of T-helper lymphocytes (CD3, CD45RO and CD4 positive). CD8-positive T-cell lymphomas involving the skin are relatively rare and have been of significant interest in the recent literature. Some cases have the clinical presentation of mycosis fungoides (MF) or pagetoid reticulosis, while other have an aggressive clinical course with frequent extracutaneous dissemination. In this review, we chart some of the earlier observations, together with current insights into this disease entity. In the process, we will see how our understanding of this entity has evolved over the years. In 1999, Berti et al. studied 17 cases of CTCL that were positive for CD8. They were interested in determining whether this phenotype represented a subset of CTCL. Of the cases studied, slightly more than half behaved like other entities such as typical MF, pagetoid reticulosis and lymphomatoid papulosis. However, 8 of the 17 cases behaved in a different fashion. Clinically, they presented a spectrum ranging from patches to tumors. They generally behaved aggressively, withmetastases to viscera and the central nervous system rather than lymph nodes, with a median survival of only 32 months. Histologically, these lesions showed epidermotropism of atypical Tcells within an acanthotic or hyperplastic epidermis. Varying degrees of spongiosis and even keratinocytic necrosis were frequently detected, unlike the usual scenario in MF. Immunohistochemical studies showed these cells to be CD3 and CD8 positive, often with loss of CD2 and CD5 (CD7 was usually retained). bF1 and TIA-1 were also expressed. Berti et al. concluded from this study that a CD8-positive MF is an aggressive variant or subset of MF, with the CD8-positive cells likely derived from cytotoxic Tcells (given the positivity for TIA and CD45RA). None of the lesions studied by them were g/d-positive. Thirteen of their 17 cases showed rearrangement of the T-cell receptor (TCR) g-chain. Consistently, primary cutaneous epidermotropic CD8 CTCL was not associated with Epstein-Barr Virus, unlike the aggressive Natural Killer/T-cell lymphomas, nasal type. The findings of Berti et al. echo an even earlier report by Agnarsson et al., who in 1990 reported two subsets of CD8-positive MF: those with a chronic course and those that behaved more aggressively. Histologic findings were similar in both types (epidermotropism). Interestingly, two of the five cases that behaved aggressively lost CD2 expression and were CD7 positive, similar to the CD2 loss and CD7 positivity described in the cases by Berti et al. (in all Agnarsson et al. evaluated nine cases, of which five were aggressive). The observation that there was an aggressive CD8positive CTCLwas cemented by other reports as well. For example, Quarterman et al. reported an aggressive CD8-positive CTCL that involved the tongue. Urrutia et al. also documented a case that was resistant to therapy. Fujiwara et al. described a case of a 68-year-old woman who progressed in a short time from scaly macules to plaques to ulcerated lesions, leading to infiltrates in the lung and death. This case had a feature that is different from other reported cases, namely angioinvasion, and so it is possible that it is a different entity from the others being described in this review. In contrast to these, Dummer et al. reported a study of three patients in the Archives of Dermatology in February 2002, where the patients fared much better. The lesions in all three patients were hyperpigmented, and the diagnosis was missed for several years. Two of the three patients had a long course of 9 and 10 years, and therewas no tendency to