Malignant histiocytosis was diagnosed in 4 cows. In all cases the tumor tis
sues were composed of cytologically atypical histiocytes with evidence of e
rythrophagocytosis. The tumor in case 1 appeared highly anaplastic with mar
ked nuclear pleomorphism, and had areas of spindle cell differentiation, bu
t had no relation to malignant fibrous histiocytoma. The neoplastic tissue
in case 2, characterized by cohesive growth of tumor cells, was distinguish
able from anaplastic carcinoma cells by cytokeratin immunostaining. There w
ere many hemosiderin-laden neoplastic cells suggestive of high phagocytic a
ctivity in a lymph node of case 3. The neoplastic cells in case 4, frequent
ly multinucleated, were less atypical than in the other cases. All cases ex
pressed histiocyte-associated markers (lysozyme and HAM56), and were negati
ve for cytokeratin, S100, and T- and B-cell lineage-specific markers (CD3 a
nd CD79a). The most frequent HAM56 immunoreactivity was detected in case 4,
and the giant, multinucleated forms, reminiscent of epithelioid cell diffe
rentiation, seemed not to indicate cytological pleomorphism as a result of
neoplastic transformation.