Pf. Moore et al., CANINE CUTANEOUS HISTIOCYTOMA IS AN EPIDERMOTROPIC LANGERHANS CELL HISTIOCYTOSIS THAT EXPRESSES CD1 AND SPECIFIC BETA(2)-INTEGRIN MOLECULES, The American journal of pathology, 148(5), 1996, pp. 1699-1708
Canine cutaneous histiocytoma (CCH) is a common, benign neoplasm of th
e clog, Histiocytomas most commonly occur as solitary lesions that und
ergo spontaneous regression. The age-specific incidence rate for histi
ocytomas drops precipitously after 3 years, although histiocytomas occ
ur in dogs of all ages. Langerhans cells (LCs) in humans and dogs expr
ess abundant major histocompatibility complex class II molecules and a
variety of leukocyte antigens characteristic of dendritic cell differ
entiation including CD1a, CD1b, CD1c, and CD11c, The immunophenotype o
f CCH resembled that of cutaneous LCs by virtue of the expression of c
ol molecules (CD1a, -b, and -c), CD11c, and major histocompatibility c
omplex class II. Furthermore, histiocytoma cells had a tropism for epi
dermis, which was also consistent with an epidermal LC lineage. The ex
pression of adhesion molecules such as CD11b (variable), CD44, CD54 (I
CAM-1), and CD49d (VLA-4) ill ccn indicated that the infiltrating cell
s had some of the characteristics of activated LCs, as these molecules
are not expressed by normal, resting canine epidermal LCs, CCH did no
t express Thy-1 or CD4. Thy-1 expression is a characteristic of human
and canine dermal dendrocytes, which are perivascular dendritic antige
n-presenting cells closely related to epidermal LCs, CD4 expression is
prevalent in human LC histiocytosis, and in this respect CCH differed
front human LC histiocytosis. Here we demonstrate that CCH is a local
ized form of self-limiting LC histiocytosis, which predominately expre
sses an epidermal LC phenotype. CCH occurs as solitary or, less common
ly, as multiple cutaneous nodules or plaques, which rarely may extend
beyond the skin to local lymph nodes. Regression of CCH occurs spontan
eously in the vast majority of cases in primary, and secondary sites,
and is mediated by CD8(+) alpha beta T cells. The high frequency, of c
cn within the general canine population offers the potential that the
dog may provide an interesting model system to further the understandi
ng of LC proliferative disorders, particularly the self-limiting, cuta
neous form of human LC histiocytosis.