Decreased CD117 expression in hypopigmented mycosis fungoides correlates with hypomelanosis: lessons learned from vitiligo

Abstract

Hypopigmented mycosis fungoides is an uncommon clinical variant of cutaneous T-cell lymphoma. We hypothesized that hypomelanosis in hypopigmented mycosis fungoides may have a similar mechanism as in vitiligo, a condition in which it is believed that alterations in expression of CD117 (stem cell factor receptor/KIT protein) on epidermal melanocytes and abnormal interactions between melanocytes and surrounding keratinocytes may play a pathogenic role. To test the hypothesis that similar mechanisms might also explain hypopigmentation in hypopigmented mycosis fungoides, skin specimens from five cases each of hypopigmented mycosis fungoides and vitiligo were studied immunohistochemically for immunophenotype of the infiltrating cells, CD117 (expressed by epidermal melanocytes), and pan melanoma cocktail of antigens (gp100, tyrosinase, and MART-1) expression; cases of conventional mycosis fungoides and normal skin were studied in parallel as controls. Our findings confirm a predominance of CD8 þ neoplastic T cells in hypopigmented mycosis fungoides. Similarly, the epidermal lymphocytic infiltrate in vitiligo was also composed of CD8 þ cytotoxic T cells, in contrast to an epidermal infiltrate composed of CD4 þ T cells in conventional mycosis fungoides. The average number of epidermal CD117 expressing cells followed the same pattern of decreased expression in hypopigmented mycosis fungoides as in vitiligo, whereas the levels in conventional mycosis fungoides were higher, and similar to that observed in normal skin. Furthermore, a decreased number of melanocytes per high-power field of the length of the biopsy was present in hypopigmented mycosis fungoides and vitiligo, as compared with either conventional mycosis fungoides or normal skin, suggesting a correlation between decreased expression of CD117 and decreased number of melanocytes. We propose that decreased expression of CD117 and its downstream events in melanocytes may be initiated by cytotoxic effects of melanosomal-antigen-specific CD8 þ neoplastic T lymphocytes, resulting in destabilization of CD117 and leading to dysfunction and/or loss of melanocytes in the epidermis of hypopigmented mycosis fungoides.

Hypopigmented Mycosis Fungoides versus Mycosis Fungoides with Concomitant Hypopigmented Lesions: Same Disease or Different Variants of Mycosis Fungoides?

“…Unlike conventional MF, a disease typical of the fifth to sixth decades of life, HMF affects a younger population, even children [2,4,7,8,9,10]. Our data confirm the relatively young age at onset.…”

“…In HMF, however, several studies have shown a predominant CD8+ cell epidermotropism [4,5,9,11]. On the other hand, some papers have confirmed a predominance of CD4+ T cells [8].…”

Juvenile-Onset Hypopigmented Mycosis Fungoides Mimicking Vitiligo

“…Histologic studies have observed a decrease or absence of melanocytes within the lesions of vitiligo, 3,9 a finding that has also been seen, to a lesser extent, in hypopigmented MF. 6,10 Aside from this finding, vitiligo usually shows unremarkable changes with routine histologic staining.…”

“…This uncommon hypopigmented variant of MF has been more often observed in dark-complexioned individuals and predominantly in children, 1,2 comprising 17% of juvenile-onset cases. 3 The diagnosis of hypopigmented MF in children can be a challenging one to make. It initially may not be clinically suspected and therefore may be underdiagnosed or misdiagnosed as a more common condition, such as atopic dermatitis, postinflammatory hypopigmentation, or vitiligo.…”

Immunohistochemical Expression of c-kit Receptor (CD117) in Two Pigmentary Disorders

“…within the epidermis [17]. So, the aim of this study was to assess the immunohistochemical expression of CD117 in some pigmentary disorders such as melasma and vitiligo.…”