Diagnosis and Multimodal Treatment of Metastatic Maxillofacial Juvenile Embryonal Rhabdomyosarcoma in a Young Golden Retriever.

A 2 yr old male castrated golden retriever was evaluated for a rapidly progressing maxillofacial spindle cell tumor. On examination, an ill-defined left maxillary mass, a 2 cm swelling under the left eye, and an enlarged left mandibular lymph node were noted. The dog was bright and alert but appeared painful upon jaw extension. Cytology from the lymph node revealed metastatic disease. Thoracic radiographs and computed tomography scan revealed pulmonary nodules. Computed tomography of the head and neck revealed a 6.7 × 4.1 × 6.5 cm mass at the rostral aspect of the left zygomatic arch invading the orbit. A second opinion of the biopsy specimen in conjunction with positive immunohistochemical staining for desmin led to a revised diagnosis of rhabdomyosarcoma. Treatment consisted of three doses of palliative radiation therapy, in 8 Gy fractions, and chemotherapy with vincristine, cyclophosphamide, and doxorubicin. A rapid clinical response was noted shortly after treatment initiation; however, the response was temporary, and the dog was euthanized due to widespread metastatic disease and associated clinical signs 74 days after initial therapy. This is one of the first reports describing positive results from multimodal treatment with chemotherapy and radiation therapy of a maxillofacial juvenile rhabdomyosarcoma in the veterinary literature.

Identification of prognostic collagen signatures and potential therapeutic stromal targets in canine mammary gland carcinoma.

Increasing evidence indicates that the tumor microenvironment plays a critical role in regulating the biologic behavior of breast cancer. In veterinary oncology, there is a need for improved prognostic markers to accurately identify dogs at risk for local and distant (metastatic) recurrence of mammary gland carcinoma and therefore would benefit from adjuvant therapy. Collagen density and fiber organization have been shown to regulate tumor progression in both mouse and human mammary tumors, with certain collagen signatures predicting poor outcomes in women with breast cancer. We hypothesized that collagen signatures in canine mammary tumor biopsies can serve as prognostic biomarkers and potential targets for treatment. We used second harmonic generation imaging to evaluate fibrillar collagen density, the presence of a tumor-stromal boundary, tumor associated collagen signatures (TACS) and individual collagen fiber characteristics (width, length and straightness) in grade I/II and grade III canine mammary tumors. Collagen density, as well as fiber width, length and straightness, were inversely correlated with patient overall survival time. Notably, grade III cases were less likely to have a tumor-stromal boundary and the lack of a boundary predicted poor outcome. Importantly, a lack of a defined tumor-stromal boundary and an increased collagen fiber width were associated with decreased survival even when tumor grade, patient stage, ovariohysterectomy status at the time of mammary tumor excision, and histologic evidence of lymphovascular invasion were considered in a multivariable model, indicating that these parameters could augment current methods to identify patients at high risk for local or metastatic progression/recurrence. Furthermore, these data, which identify for the first time, prognostic collagen biomarkers in naturally occurring mammary gland neoplasia in the dog, support the use of the dog as a translational model for tumor-stromal interactions in breast cancer.