A Fibromyxoid Stromal Response is Associated with Muscle Invasion in Canine Urothelial Carcinoma

Abstract

Canine urothelial carcinoma (UC) is the most common type of cancer of the lower urinary tract and tends to affect elderly neutered female dogs, with a high predisposition for Scottish terriers. Tumour stroma, inflammation and necrosis are poorly characterized in canine UC and their role as prognostic factors is unknown. The aims of this study were to (1) assess histologically 381 canine UCs, with emphasis on myxoid tumour stroma, inflammation and necrosis, and (2) assess possible associations between these features and the available epidemiological data as well as bladder wall muscle invasion. In 103 of 381 (27%) of cases, the stroma was mixed collagenous and myxoid (fibromyxoid), which was strongly associated with invasive growth of muscle (P <0.0001). Peritumoral and intratumoural inflammation was present in 308 of 345 (89%) and 287 of 381 (75%) of cases, respectively, and was mostly mild and lymphoplasmacytic. One hundred and fifteen of the 381 (30%) cases showed a variable eosinophilic inflammation, and 58 of 381 (15%) presented with formations of one or several lymphoid follicles. Twenty-four percent (91 of 381) of cases had tumour necrosis, which was typically mild. In 83 of 91 (91%) of cases, the necrosis was comedo-like.Moderate to severe tumour necrosis was associated with the presence of moderate to predominant fibromyxoid tumour stroma (P <0.02). The results of this study indicate that fibromyxoid stroma is common in canine UC and is a strong indicator for invasive growth of muscle, which is consistent with a poor prognosis. Based on histomorphology, tumour necrosis in canine UC is best described as comedonecrosis.

Urothelial cell carcinoma with widespread local and distant metastasis and associated osseous metaplasia in a dog

“…The presence of collagenous or fibromyxoid stroma accompanying muscular invasion of canine urothelial cell carcinoma has previously been described 1 . However, in the veterinary literature, reported cases describing osseous metaplasia secondary to metastatic neoplasia are rare.…”

“…18 The presence of collagenous or fibromyxoid stroma accompanying muscular invasion of canine urothelial cell carcinoma has previously been described. 1 However, in the veterinary literature, reported cases describing osseous metaplasia secondary to metastatic neoplasia are rare. On post-mortem examination, an adult female neutered cat presenting with hindlimb stiffness was found to have metastatic adenocarcinoma infiltrating the musculature of both pelvic limbs and accompanied by marked fibrosis, mineralisation and osseous metaplasia.…”

“…The vulval mass was composed of similar neoplastic cells that were arranged in large clusters supported by fibrous stroma. Central foci of necrosis were frequently noted within neoplastic aggregates (comedone pattern of necrosis 1 ) (Figure 5). Neoplastic cells multifocally exhibited a single clear vacuole that exceeded nuclear diameter (signet ring cells) with rare homogenous eosinophilic material present within the vacuole (Melamed‐Wolinska bodies).…”

Effective detection of BRAFV595E mutation in canine urothelial and prostate carcinomas using immunohistochemistry

“…1,2 There is a significant predisposition for Scottish Terriers, West Highland White Terriers, Shelties and others breeds for tumour development, and other risk factors include female sex and being spayed or neutered. [3][4][5][6] The high breed predisposition indicates an underlying genetic basis for the disease. 3,[6][7][8][9] In multiple studies, the activating BRAF V595E mutation, the canine homologue of human BRAF V600E , was identified as somatic driver mutation to be frequently present in 65%-87% of UC of dogs.…”

“…15,16 Interestingly, canine UC and human muscle-invasive bladder cancer share many similarities at the cellular and molecular level, with similar propensity and site of metastases, as well as response to therapy. 1,3,4,17,18 The dog is therefore considered a highly relevant animal model for studies of human UC. 3,11 However, in contrast to dogs, BRAF mutations are only sporadically described in human muscleinvasive UC.…”