CD30 expression and proliferative fraction in nontransformed mycosis fungoides

Abstract

The major differential diagnosis for a primary cutaneous T-cell lymphoproliferative disorder with CD30 (Ki-1) positivity includes primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, pagetoid reticulosis and transformed mycosis fungoides (MF). Little is known, however, about CD30 expression in nontransformed MF, whether it simply reflects the proliferative fraction and if either CD30 staining or the proliferative fraction are of prognostic significance. Therefore, 47 nontransformed MF biopsies were stained for CD30 and Ki-67. The proportions of positive cells were determined and correlated with each other as well as with age, stage at diagnosis, maximum stage and survival. All cases had at least rare dermal CD30-positive cells. Higher percentages of dermal CD30 and Ki-67-positive cells were associated with a higher stage at diagnosis, and together with epidermal CD30, associated with a higher maximum stage. The proportion of CD30 and Ki-67-positive cells did not correlate with each other. Survivals were shorter if the dermal CD30 or epidermal or dermal Ki-67% were greater than the median (4.7%, 14%, 13%) and in patients of greater than or equal to 60 years of age or with a high stage. Dermal Ki-67 as a continuous variable was an independent prognostic indicator (P<0.001), as were dermal Ki-67 (P=0.004) and dermal CD30 (P=0.027) when analyzed as dichotomous variables but not stage. Therefore, CD30 expression is not restricted to transformed MF but higher levels of dermal CD30 expression and, even more so, dermal Ki-67 levels are independent adverse prognostic indicators.

Figure 1

Proportion of Ki-67+ and CD30+ cells in the epidermis and dermis.

Figure 2

CD30 and Ki-67 staining. A. CD30 epidermis low: Numerous intraepidermal lymphocytes are negative with only occasional positive cells. B. CD30 epidermis high: Numerous intraepithelial lymphocytes are positive. C. CD30 dermis low: Only scattered positive lymphocytes are present in the dermis. D. CD30 dermis high: The dermis demonstrates numerous positive lymphocytes. As seen best in the inset, while the size of the positive cells is variable, many positive cells are not very large. E. Ki-67 epidermis low: While numerous positive keratinocytes are seen, the intraepithelial lymphocytes (circle) are negative. F. Ki-67 epidermis high: Numerous positive intraepithelial lymphocytes are admixed with positive keratinocytes. G. Ki-67 dermis low: Only scattered positive lymphocytes are present. H. Ki-67 dermis high: A much higher proportion of positive lymphocytes are present in this dermal infiltrate. (Immunohistochemical stains with hematoxylin counterstain)

Figure 3

A. The case with >25% CD30 positive cells in the dermis illustrated in figure 2D demonstrates prominent epidermal involvement as well as a dense dermal infiltrate. B. The dermal infiltrate includes occasional large cells, but most are small with some showing irregular nuclear contours. (hematoxylin and eosin stain)

Figure 4

Overall survival from time of biopsy based on age. The median survival for those <60 years was 109 months with a 5-year survival of 89% compared to a median survival of 77.5 months with a 5-year survival of 77% for those ≥60 years (p = 0.001).

Figure 5

Overall survival from time of biopsy based on stage at diagnosis. The median survival for those with a low stage was 103 months with a 5-year survival of 96% compared to a median survival 60.5 months with a 5-year survival of 61% for those with a high stage (p = 0.023).

Figure 6

Overall survival from time of biopsy based on dichotomized immunohistochemical findings: A. Epidermal Ki-67 positivity (< vs. >14%), B. Dermal Ki-67 positivity (< vs. >13%), C. Epidermal CD 30 positivity (< vs. >14%), D. Dermal CD 30 positivity (< vs. >4.7%).