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Cutaneous expression of Thy-1 in mycosis fungoides
D P Fivenson1, M C Douglass, B J Nickoloff
1Department of Dermatology, Henry Ford Hospital, Detroit, MI 48202.
Insights
Mycosis fungoides (MF) involves an increased number of Thy-1 positive dermal dendritic cells in the papillary dermis. These cells, resembling factor XIIIa positive dermal dendrocytes, suggest a key role in MF pathogenesis.
Area of Science:
- Dermatology
- Immunohistochemistry
- Cell Biology
Background:
- Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma.
- The role of dermal dendritic cells in MF pathogenesis is not fully understood.
Purpose of the Study:
- To characterize dermal dendritic cells in mycosis fungoides using immunohistochemistry.
- To investigate the expression of Thy-1 and other markers on dermal dendritic cells in normal skin, pre-MF, and MF.
Main Methods:
- Immunohistochemical analysis of skin biopsies from normal individuals, pre-MF, and MF patients.
- Utilized antibodies against Thy-1, factor XIIIa, CD34, ICAM-1, VCAM-1, and other markers.
- Quantified Thy-1 positive dendritic cells in the dermal interstitium.
Main Results:
- An extensive network of Thy-1 positive dendritic cells was observed in the papillary dermis of MF cases, significantly increased compared to normal skin.
- These Thy-1 positive cells shared immunophenotypic characteristics with factor XIIIa positive dermal dendrocytes.
- A distinct population of CD34 positive, Thy-1 negative dendritic cells was found in the reticular dermis.
Conclusions:
- MF is characterized by an increased and distinct population of Thy-1 positive dermal dendritic cells in the papillary dermis.
- These cells, potentially dermal dendrocytes, may play a significant role in the pathophysiology of mycosis fungoides.
- Differential expression of Thy-1, factor XIIIa, and CD34 highlights compartmentalization of dendritic cells in the skin.
Abstract:
Dermal dendritic cells from eleven cases of mycosis fungoides (MF) (six patch and five plaque stage), two cases of pre-MF, and five specimens of normal human skin, were characterized immunohistochemically using a panel of antibodies including anti-human Thy-1, intercellular adhesion molecule-1 (ICAM-1; CD54), endothelial leukocyte adhesion molecule-1 (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1), CD1a, CD2, CD14, CD18, CD34, MAC387, KP-1, EBM-11, factor XIIIa, factor XIIIs, and S100. Thy-1 expression in normal skin was limited to the microvascular endothelium and perivascular dendritic cells. An extensive interstitial network of Thy-1+ dendritic cells was seen in the papillary dermis of all cases of MF, whereas no epidermal cells were Thy-1+. The mean +/- standard deviation of interstitial Thy-1+ cells per high power field in the dermis was: normal skin, 2.86 +/- 0.34; pre-MF, 15; patch stage MF, 13.4 +/- 7.08; plaque stage MF, 49.96 +/- 21.29. Thy-1+ dendritic cells morphologically resembled the factor XIIIa+ "dermal dendrocyte" (DD) and shared their VCAM-1+, ICAM-1+, CD1a, CD2-, CD14+, CD18+, EMB11+, factor XIIIa+, factor XI-IIs-, S100-, MAC387- and KP-1-immunophenotype in MF. Double labeling studies revealed up to 50% of Thy-1+DD were also factor XIIIa+ in MF. Immediately beneath these cells was a similar network of CD34+, Thy-1-, factor XIIIa- dendritic cells limited to the reticular dermis. Strong microvascular endothelial cell expression of Thy-1 and VCAM-1, and focal vascular ELAM-1 expression were also seen in MF. Distinct cellular compartmentalization (papillary dermis versus reticular dermis versus epidermis) of dendritic cells is demonstrated by the differential expression of Thy-1, factor XIIIa, and CD34 antigens. The extensive number and prominent dermal dendritic network in the papillary dermis juxtaposed between epidermal keratinocytes (KC) and dermal/epidermal T cells, suggests an important pathophysiologic role for this newly recognized and immunophenotypically distinctive cell population in MF.