Feline histiocytic skin diseases have not been widely documented. Feline progressive histiocytosis has been increasingly reported since 1995. The disease appears to be most closely related to multiple persistent histiocytomas or Langerhans' cell histiocytosis in dogs. Affected cats usually have multiple nodules which are firm, non-pruritic and non-painful. Lesions are distributed on the head, lower extremities or trunk. Middle aged to older cats are most commonly affected and a sex or breed predisposition has not been seen. Whilst the lesions may wax and wane in severity, spontaneous remission has not been seen. Ultimately, internal lesions usually develop and to date no treatment has been successful.
Localised histiocytic sarcoma has also been documented in cats. Tumours have been poorly defined and located in the subdermis of the ventral abdomen or extremities. The spleen has also been the site of the primary lesion. Cytology of feline histiocytic sarcoma is similar to the canine disease, with mononuclear and multinucleated round cells and discrete to aggregated spindle cells. Immunohistochemistry is required to distinguish between histiocytic sarcomas and vaccine induced or anaplastic sarcomas with giant cells (misnamed as a malignant fibrous histiocytoma).
The morphologic term histiocyte includes monocytes, macrophages and dendritic antigen presenting cells (DAPC). They are considered closely related cells and arise from a common precursor in the bone marrow. As differentiated cells in the periphery, macrophages and DAPC are characterized by morphologic, phenotypic and functional differences and are therefore considered to represent different cell lineages. Although their primary functions differ, macrophages and DAPC are closely related and have a lot of functions in common.
As professional antigen presenting cells, dendritic antigen presenting cells (DAPC) are primarily involved in processing and presenting antigens. The result is an activation of the adaptive immune system. DAPC express MHC I, MHC II and CD1, which allows them to efficiently present processed proteins and glycolipids to T lymphocytes. Moreover, professional DAPC express accessory molecules (B-7 family, CD40) that play a crucial role in the induction of the primary immune response. The DAPC system itself consists of phenotypically and functionally diverse cells, located in distinct parts of the body. Langerhans cells (LC) reside in epidermis. They have Birbeck's granules (except in dogs) and they co-express E-cadherin. Interstitial (dermal) dendritic cells lack Birbeck's granules and reside mainly in the perivascular area of tissues. They lack expression of E-cadherin, but they co-express CD90 and as activated cells CD4. As DAPC process the antigen, they migrate to the lymph node, where they present the peptides in context with their MHC molecules to T cells.
Macrophages perform several key functions of the innate immune system. With various receptors they interact with extracellular proteins and polysaccharides of pathogens and internalize them by phagocytosis and endocytosis. The contents of phagosomes are subsequently subjected to digestion within the phagolysosomes. During this process the macrophages secrete proteases, complement factors, cytokines (TNF-α·, IL-1, IL-6), chemokines (MIP1,2,3; IL-8), toxic oxygen metabolites (O2-, OH-), nitrogen metabolites (NO2-), and arachidonate derivatives, which all have an important role in the development of inflammation.
1) Feline progressive dendritic cell histiocytosis
Cats may initially present with a solitary skin nodule. Usually multiple non-painful intradermal nodules develop. Predilection sites are head, neck, or lower extremities, but lesions may occur at any location. Occasionally, the lesions are limited to one extremity. The nodules may measure up to 1.5 cm in diameter. Lesions have an intact skin surface or may be ulcerated. The nodules may wax and wane in size, but complete spontaneous regression has not been seen. Some nodules progress in size over time, and may coalesce to large plaques. Sex or breed predilection has not been observed. Cats affected are usually between 2 to 13 years of age. Lymph node involvement is common and at a terminal stage, internal organs (lungs, liver, kidney, heart) may be affected. Clinical signs vary depending on the organ systems involved.
Histology and immunophenotyping
Feline progressive dendritic cell histiocytosis may be non-epitheliotrophic or epitheliotrophic. Early lesions may appear as multinodular histiocytic infiltrates that gradually coalesce. The nodules are composed of a dense proliferation of large round and polygonal cells with discrete cell borders and a moderate to abundant amount of lightly eosinophilic, occasionally vacuolated cytoplasm and centrally located, large, vesicular, oval or reniform and indented nuclei; the chromatin is marginated or finely clumped. The tumour cells are CD1+, CD11b+ and MHC II+ histiocytes of most likely DAPC lineage. With epitheliotrophic lesions, single cells and aggregates of cells can be observed in the epidermis. Multinucleated tumour cells may be present. Mitotic activity varies. Intralymphatic tumour cell aggregates are occasionally seen and the surface may be intact, eroded or ulcerated. Reactive inflammatory response varies.
Treatment with corticosteroids may help intermittently, but does not stop the progressive process. Interferon, nitrogen mustard (CCNU) and Cyclosporin A have been tried in very few cases with little success. If there are only few nodules surgical removal is advised. However, it does not prevent development of additional lesions in other locations.
A guarded prognosis must be given as lesions are progressive.
2) Feline histiocytic sarcoma
Histiocytic sarcomas do occur in cats, but less frequently than in dogs. Some of the progressive dendritic cell histiocytosis eventually become very anaplastic and have features of histiocytic sarcoma. Alternatively, histiocytic sarcomas develop as solitary sarcomas.
Histology and immunophenotyping
The lesions resemble histiocytic sarcomas in dogs, either individualized round cells or spindle cells can be seen. The pleomorphic tumor cells are CD1+, CD11b+, MHC II+ dendritic antigen presenting cells.
Surgery is advised if solitary lesions are present.
Histiocytic sarcomas are locally invasive and can metastasize to draining lymph nodes.
1. Brain, PH (2006) Canine and feline histiocytic diseases. The Veterinarian March edn.
2. Affolter, VK, WSAVA http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2004&PID=8600&O=Generic