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Background: Histiocytic tumors in felines are nodules that commonly develop on limbs and head extremities. They can be divided into many subtypes including cutaneous histiocytoma, histiocytic sarcoma, reactive fibrohistiocytic nodule, Langerhans cell histiocytosis, and progressive feline dendritic cell. Despite the same origin, they have behaviors that differ from each other, thus it is important to confirm diagnosis with histopathological and immunohistochemical tests, because early identification can facilitate prognosis and treatment. In this study, we describe the pathological and immunohistochemical characteristics, enabling differentiation feline neoplasms derived from histiocytes. Case: A 5-year-old, crossbreed, male, feline presented with a nodulation at the base of the left ear. The mass was slow growing, partially alopecic, with no other changes associated with tumor development. The nodule was round and circumscribed, movable, with an elevated surface. He was referred for surgery and an elliptical sample around the tumor was carefully dissected. Routine histopathological evaluation was performed with hematoxylin and eosin (HE), as well as immunohistochemistry. Histopathology showed circumscribed proliferation of histiocytic cells, with abundant and eosinophilic cytoplasm. The proliferative cells were large and rounded, extending from the superficial dermis and basement membrane to the deep dermis. At the extremities, some cells had visible vacuoles. Mitotic activity ranged from 3 to 4 mitoses per field in 40x magnification. Immunohistochemistry showed positive staining for histocompatibility complex MCII and lysozyme antibodies, marking histiocytic cells. Labeling was positive for CD20 in cells of lymphoid lineage B and negative for E-cadherin. Histiocytic cells did not invade the epidermis; hence, proliferation was classified as nonepitheliotropic. These methods contribute to the literature regarding the diagnosis of this rare tumor. Therefore, histological as well as immunohistochemical evaluation are important bfor confirming clinical diagnosis of histiocytic proliferation non-epitheliotropic. Discussion: Progressive histiocytosis of feline dendritic cells, in both epitheliotropic and non-epitheliotropic forms, is considered a clinically progressive and rare disorder. There are reports which include cytological, clinical, histological and immunohistochemical examinations, but the diagnostic characteristics regarding the non-epitheliotropic classification have not yet been properly identified. Nodulations are predominantly observed in head and limb regions, usually non-ulcerated, which can both increase and decrease in size, and are typically painless. The tumor in the present case was restricted to the base of the ear and no evidence of infiltration or metastasis was found. Progressive histiocytosis may spread and reach the lymphatic system through the lymph nodes, subsequently becoming systemic. The non-aggressive behavior observed in this case is possibly related to the non-epitheliotropic pattern. In the present case, MHC II histocompatibility complex markers, a phenotype compatible with dendritic cells, were used. Lysozyme antibodies marked histiocytic cells and the reactive lymphoid infiltrate was composed of CD20-positive B lymphoid lineage cells. Staining for E-cadherin was negative, negative results in labeling experiments is common, it is dependent upon the cellular origin of the leukocytes present in the sample. Staining for these molecules is recommended for differentiating feline progressive histiocytosis from Langerhans cells. Langerhans cells can be characterized by E-cadherin expression in about 10% of cases and marked T lymphocyte and neutrophil expression in the affected tissue. In this case, the histopathological exam along with immunohistochemistry was essential for differentiating them.

Progressive Histiocytosis of Non-Epitheliotropic Dendritic Cells in a Feline