Clinicopathological and Genomic Characterization of a Simmental Calf with Generalized Bovine Juvenile Angiomatosis

Abstract

Bovine juvenile angiomatosis (BJA) comprises a group of single or multiple proliferative vascular anomalies in the skin and viscera of affected calves. The purpose of this study was to characterize the clinicopathological phenotype of a 1.5-month-old Simmental calf with multiple cutaneous, subcutaneous, and visceral vascular hamartomas, which were compatible with a generalized form of BJA, and to identify genetic cause for this phenotype by whole-genome sequencing (WGS). The calf was referred to the clinics as a result of its failure to thrive and the presence of multiple cutaneous and subcutaneous nodules, some of which bled abundantly following spontaneous rupture. Gross pathology revealed similar lesions at the inner thoracic wall, diaphragm, mediastinum, pericardium, inner abdominal wall, and mesentery. Histologically, variably sized cavities lined by a single layer of plump cells and supported by a loose stroma with occasional acute hemorrhage were observed. Determined by immunochemistry, the plump cells lining the cavities displayed a strong cytoplasmic signal for PECAM-1, von Willebrand factor, and vimentin. WGS revealed six private protein-changing variants affecting different genes present in the calf and absent in more than 4500 control genomes. Assuming a spontaneous de novo mutation event, one of the identified variants found in the PREX1, UBE3B, PCDHGA2, and ZSWIM6 genes may represent a possible candidate pathogenic variant for this rare form of vascular malformation.

Clinico-pathological and immunohistochemical findings in a case of bovine cutaneous angiomatosis in a Holstein heifer

“…Skin vascular proliferations and tumors may have distinct and complex morphological features, and their classification is challenging in humans and animals. Cutaneous angiomatosis in cattle displays at least two distinct forms: juvenile bovine angiomatosis affecting calves under one year old; and BCA, mainly reported in adult cattle but can also be observed in young animals (WATSON & THOMPSON, 1990;RUETTEN et al, 2014;HENDRICK, 2017;JACINTO et al, 2021). For the first time in Brazil, this report showed a case of BCA affecting an eight-month-old Holstein heifer.…”

“…Brazil has one of the most important commercial cattle herds worldwide, significantly contributing to the country's economy and international trade. Considering bovine cutaneous vasoproliferative conditions have never been reported in Brazil, the first identification of an unprecedented disease in Brazilian cattle herds may be of great relevance for the knowledge of cattle diseases, and considering its pathogenesis is likely related to abnormal chromosomal changes (JACINTO et al, 2021). Therefore, this report characterized the clinical and pathological aspects of BCA in a Holstein heifer.…”

“…Ciência Rural, v.53, n.10, 2023. Cerqueira et al form likely affecting cattle under one year old (WATSON & THOMPSON, 1990;JACINTO et al, 2021). The etiology of cutaneous angiomatosis is not entirely determined in veterinary medicine, but chromosomal mutations (HENDRICK, 2017;JACINTO et al, 2021), infections, and inflammation have been related in the pathogenesis (YAGER et al, 2010).…”

“…Cerqueira et al form likely affecting cattle under one year old (WATSON & THOMPSON, 1990;JACINTO et al, 2021). The etiology of cutaneous angiomatosis is not entirely determined in veterinary medicine, but chromosomal mutations (HENDRICK, 2017;JACINTO et al, 2021), infections, and inflammation have been related in the pathogenesis (YAGER et al, 2010). These vascular malformations may occur as a result of failure in angiogenesis during early embryonic development (BORST et al, 2020) or in the repair of traumatic injuries in the integumentary blood vessels (WATSON & THOMPSON, 1990).…”

“…Angiomatosis is a complex of proliferative vascular lesions with several clinical and pathological manifestations, presenting with single or multifocal distribution and affecting the skin and other various organ systems (RICHARD et al, 1995;DIAZ-DELGADO et al, 2012;LUDWIG et al, 2015;HENDRICK, 2017;BARON et al, 2020;JACINTO et al, 2021). Although rare, cutaneous angiomatosis has already been reported in humans, domestic and wild animals (LUPPI et al, 2010;DIAZ-DELGADO et al, 2012;LUDWIG et al, 2015;HENDRICK, 2017;BARON, et al, 2020;JACINTO et al, 2021). Among these vascular lesions in domestic animals, bovine cutaneous angiomatosis (BCA), progressive angiomatosis in dogs and cats, and scrotal vascular hamartoma in dogs have been mainly reported (HENDRICK, 2017).…”