Lung-Digit syndrome associated with idiopathic pulmonary fibrosis: clinical, pathological and immunohistochemical findings in three cats

Abstract

Feline lung-digit syndrome (FLDS) and idiopathic pulmonary fibrosis (IPF) are rare diseases, recently diagnosed in feline patients. FLDS is a particular condition recognised, so far, only in cats and not in other species. IPF was also described in humans and, as in cats, it was associated with pulmonary cancer. Primary pulmonary cancer in cats is rarely encountered, representing about 0.69-0.75%. Most of the digital tumors diagnosed in feline patients represent metastasis of the pulmonary tumors (87.5%). The aim of this study is to describe clinical, pathological and immunohistochemical aspects in three cases of lung-digit syndrome associated with IPF. Two cats with chronic respiratory distress were submitted to the Department of Pathology, Faculty of Veterinary Medicine (Cluj-Napoca) for pathological examination. The third cat was clinically diagnosed with lung-digit syndrome and only the affected digit was submitted for histopathological diagnosis. The complete history, physical and radiological exams were available in two of the cases. The samples collected during necropsy were evaluated by cytological (Dia Quick Panoptic stain) and histopathological (H&E and TM stains) exams. The previous exams were followed by immunohistochemistry, using antibodies against multi-cytokeratin (MCK) and vimentin (VIM). Additionally, K-RAS and P-53 immunoexpression was evaluated in all samples. The thoracic radiographs showed a diffuse mixt pattern (bronchial and alveolar) with evidence of a pulmonary mass; the affected digit presented severe osteolysis of the third and second phalanx. Histologically, 2 cases of adenosquamous carcinoma and one case of adenocarcinoma (tubulo-papillary type) were diagnosed. Lung- digit syndrome was confirmed in all cases. The histopathological diagnosis was supported in all cases by IHC results, including positive reaction of the neoplastic epithelial cells for MCK and negative for Vimentin. Moreover, the neoplastic epithelial cells showed an intense positive reaction for KRAS and negative reaction for P53. FLDS and IPF are rarely encountered in cats. An association between these two syndromes was identified in 2 out of the three cases. KRAS mutation may represent an important predisposing factor in development of pulmonary adenocarcinoma in cats. Further and more complex studies using a larger number of cases are required in order to establish the role of KRAS pathway in feline pulmonary cancer). Other studies are also required in order to establish the responsible trigger mechanism for lung-digit syndrome and if there is a correlation with the idiopathic pulmonary fibrosis.