Histiocytic Diseases.

Canine cutaneous histiocytomas originate from Langerhans cells. Multiple histiocytomas are referred to as cutaneous Langerhans cell histiocytosis. Feline pulmonary Langerhans cell histiocytosis causes respiratory failure owing to extensive lung infiltration. Localized and disseminated histiocytic sarcomas usually arise from interstitial dendritic cells. Primary sites include spleen, lung, skin, brain (meninges), lymph node, bone marrow, and synovial tissues of limbs. An initially indolent form of localized histiocytic sarcomas, progressive histiocytosis, originates in the skin of cats. Hemophagocytic histiocytic sarcomas originates in splenic red pulp macrophages. Canine reactive histiocytoses (systemic histiocytosis and cutaneous histiocytosis) are complex inflammatory diseases with underlying immune dysregulation.

Immunophenotyping of Nonneoplastic and Neoplastic Histiocytes in Cats and Characterization of a Novel Cell Line Derived From Feline Progressive Histiocytosis.

Histiocytic proliferative diseases are rare in cats, and their pathogenesis is poorly understood. In the present study, 25 cases of histiocytic sarcoma (HS) and 6 of feline progressive histiocytosis (FPH) were examined, and survival times were recorded in 19 cases. The immunophenotypes of tumor cells in these cases as well as of nonneoplastic feline histiocytes were characterized using formalin-fixed, paraffin-embedded tissues. An FPH cell line (AS-FPH01) and xenotransplant mouse model of FPH were also established. The median survival time of HS (150 days) was significantly shorter than that of FPH (470 days). Immunohistochemically, nonneoplastic histiocytes were immunopositive for various combinations of Iba-1, HLA-DR, E-cadherin, CD204, CD163, CD208, and MAC387. By immunohistochemistry, dermal interstitial dendritic cells (iDCs) and macrophages were CD204+/E-cadherin-, while epidermal Langerhans cells (LCs) were CD204-/E-cadherin+. Neoplastic cells of 4 FPH and 18 HS were CD204+/E-cadherin- (iDC/macrophage immunophenotype), while 2 FPH and 2 HS were CD204-/E-cadherin+ (LC immunophenotype), and 5 HS were CD204+/E-cadherin+ (LC-like cell immunophenotype). Furthermore, immunohistochemical and western blot analyses of AS-FPH01 cells derived from E-cadherin-negative FPH revealed that cultured cells were immunopositive for both CD204 and E-cadherin in vitro and in vivo. These results indicate that the neoplastic cells of feline HS and FPH were variably positive for iDC/macrophage and LC markers, and their immunophenotype changed in different microenvironments. The novel cell line established in the present study may serve as an experimental model of FPH that will enable further molecular and therapeutic studies on this disease.

Feline progressive histiocytosis: a retrospective investigation of 26 cases and preliminary study of Ki67 as a prognostic marker.

Feline progressive histiocytosis (FPH) is an uncommon and infrequently reported cutaneous histiocytic proliferative disorder, whose clinical presentation is solitary or multiple cutaneous nodules and papules, with late-course internal metastasis. We describe herein the clinical, epidemiologic, histologic, and immunohistochemical features of this entity, and document the outcome of FPH based on a retrospective study of 26 cases. Female and male cats were affected equally. Lesions were evident either as solitary (16 of 26 cases) or multiple (10 of 26 cases) nonpruritic and alopecic nodules or plaques, preferentially located on the legs and extremities (73%). Follow-up was complete for 19 cats, and ranged from 41 to 1,449 d. Nine died of FPH with a median overall survival of 96 d (range: 41-238 d). The disease recurred in 14 cats after surgical excision of the nodules, and the median disease-free survival was 175 d (range: 21-1,449 d). Five of the 26 cats were alive at the end of the study, and 4 had no progression of the disease. Histologically, lesions were characterized by poorly circumscribed, unencapsulated histiocytic infiltration of dermis and subcutis. Epitheliotropism was observed in 11 (42%) cats. Atypical histiocytes diffusely and consistently expressed MHC II, CD18, and Iba1. Statistically significant higher E-cadherin expression was observed in epitheliotropic cases compared to non-epitheliotropic cases. A negative correlation between overall survival and proliferation index was evident, thus suggesting Ki67 as a promising prognostic marker.