Immunophenotypic and Ultrastructural Evidence of the Langerhans Cell Origin of the Canine Cutaneous Histiocytoma

Abstract

Canine cutaneous histiocytoma (CCH), a histiocytic benign, dermal, self-healing tumor in the young dog, and epidermal Langerhans cells (LC) are thought to be related. In this study, we used immunohistochemical staining and transmission electron microscopy for 5 fresh CCH and 17 fixed tumors, to examine if, on the basis of their immunophenotype and their ultrastructural morphology, these tumor cells originate as LCs. The immunophenotype of CCH: canine CD 11a, lie, 18, 45, MHC II positive and ACM1, human CD 14 negative, was different from canine macrophage immunophenotype but very similar to the canine LC phenotype. Furthermore, we have described ultrastructural markers in CCH cells for the first time: these consist of coated vesicles, regularly laminated bodies, pleiomorphic inclusions, paracrystalline structures, and deep invaginations of the plasma membrane, usually observed in congenital self-healing histiocytosis, a human LC tumor, or occasionally observed in human LC. The occurrence of such immunophenotype and ultrastructural markers confirmed the common lineage of LCs and CCH cells.

A Review of Histiocytic Diseases of Dogs and Cats

“…8,27,33,40,41,54,62 As discussed previously, BGs have not been conclusively illustrated in normal canine LCs or in cutaneous histiocytoma. 27,33,[40][41][42]52 Histiocytomas do exhibit ultrastructural features characteristic of DCs, and they also express CD1a and E-cadherin, which are important functional markers expressed by LCs. 8,40,41,54,62 Histiocytomas arise in the dermis and may invade the epidermis in a subset of lesions.…”

Canine Hemophagocytic Histiocytic Sarcoma: A Proliferative Disorder of CD11d+ Macrophages

“…1,2,28,[33][34][35] A common element to these diseases is proliferation of dendritic cells (DC) of either Langerhans cell (epithelial DC) or interstitial DC lineage. 1,2,27,35 Canine cutaneous histiocytoma is a common localized tumor of epidermal Langerhans cells. 27,35 Disseminated histiocytomas and Langerhans cell histiocytosis occur uncommonly in dogs; these diseases closely resemble some forms of human Langerhans cell histiocytosis.…”

“…1,2,27,35 Canine cutaneous histiocytoma is a common localized tumor of epidermal Langerhans cells. 27,35 Disseminated histiocytomas and Langerhans cell histiocytosis occur uncommonly in dogs; these diseases closely resemble some forms of human Langerhans cell histiocytosis. 35,37 Reactive histiocytoses are complex disorders likely arising in the context of disordered immune regulation and manifest with infiltration or proliferation of lymphocytes and perivascular interstitial DC of the dermis and subcutis.…”

Multiple Atypical Mucosal Xanthomas in a Dog Similar to Human Verruciform Xanthoma

“…It is similar to CD68 reactivity and identifies cells of histiocytic lineage. 13,14 Lysozyme is associated with lysosomes of granulocytes and monocytes/macrophages. 16 The reactivity appears as small brown precipitates in the cytoplasm at the sites of antibody binding.…”

“…20 In the present canine case, the xanthoma cells stained positively for lysozyme and ACM1, confirming their macrophage origin. 13,14 The lipid overload in the cytoplasm of the foamy cells might explain the lack of staining for MAC387, which is considered a marker of activated macrophages. 18 Despite numerous features common to human verruciform xanthoma, the present canine case showed distinct differences.…”