Carcinoma of Unknown Primary Origin Presenting as Rapidly Progressive Multifocal Skeletal Lesions and Fatal Systemic Thrombosis in a Dog: A Case Report.

Carcinoma of unknown primary origin (CUP) involving the skeletal system is rare in dogs and may closely mimic primary bone neoplasia or multicentric lymphoma, creating substantial diagnostic challenges. A 15-year-old spayed female Jindo-mix dog was referred for rapidly progressive tetralimb lameness and inability to stand following a 2-week history of worsening forelimb lameness. Computed tomography revealed aggressive multifocal osteolytic and osteoproliferative lesions involving the pelvis, distal femur, and lumbar vertebra, accompanied by generalized lymphadenopathy, raising differential diagnoses including osteosarcoma, lymphoma, and metastatic neoplasia. Serial CT examinations demonstrated rapid progression of the dominant left ischial lesion, which was considered most consistent with a primary bone neoplasm and was surgically excised for definitive diagnosis. MRI failed to identify clinically significant neurologic disease. Histopathologic examination of a surgically excised ischial lesion favored poorly differentiated epithelial malignancy, although lymphoma could not initially be excluded. During hospitalization, serial thromboelastography (TEG) and coagulation testing demonstrated a predominantly hypercoagulable profile despite antithrombotic therapy. Following acute clinical deterioration, contrast-enhanced CT identified thrombosis involving the splenic vein and caudal vena cava, pulmonary thromboembolism (PTE), and concurrent multi-organ infarction. Cytology of an enlarged peripheral lymph node suggested metastatic carcinoma, and postmortem immunohistochemistry supported epithelial differentiation, and in the absence of an identifiable primary tumor despite comprehensive diagnostic evaluation, the case was clinically classified as carcinoma of unknown primary origin. This case highlights an unusual diagnostic presentation of skeletal CUP mimicking osteosarcoma or lymphoma and complicated by fatal cancer-associated thrombosis. Rapidly progressive multifocal bone lesions accompanied by hypercoagulability should prompt consideration of metastatic carcinoma, including carcinoma of unknown origin, even in the absence of an identifiable primary tumor.