History and Clinical Findings
An 8-year-old 43.7-kg (96.1-lb) castrated male Labrador Retriever was referred for evaluation of progressive left thoracic limb lameness of 4 weeks’ duration. The lameness started suddenly following play with another dog, and the referring veterinarian localized pain to the lateral aspect of the left elbow joint upon palpation. Empirical treatment was not effective.
The referral physical examination revealed a grade 4/5 left thoracic limb lameness with offloading of the left paw when at rest. The dog's prostate was not palpable on rectal examination. Palpation of the left elbow region and flexion and extension of the left elbow joint elicited signs of pain; there was moderate thickening of the joint capsule and marked joint effusion.
Arthrocentesis of the left elbow joint was performed, and the synovial fluid obtained was submitted for cytologic analysis and aerobic bacterial culture. A fine-needle aspirate biopsy specimen of the thickened tissue that diffusely surrounded the left elbow was also obtained.
Cytologic Findings
The fine-needle aspirate biopsy preparations from the thickened tissue surrounding the left elbow joint were nondiagnostic owing to poor cellularity. The synovial fluid obtained from the left elbow joint was blood tinged (likely procedure related) and cloudy with high total protein concentration (5.7 g/dL; reference interval, < 3 g/dL). The total nucleated cell count was 880 nucleated cells/μL (reference interval, < 3,000 nucleated cells/μL). Direct synovial fluid smears were poorly cellular, but a 100-cell differential count revealed a predominance of large mononuclear cells (94%), consistent with macrophages and synoviocytes, and fewer neutrophils (3%), lymphocytes (2%), and eosinophils (1%). The smear background was composed of a small amount of blood (RBC count, 50 RBCs/μL) and stippled pink material consistent with hyaluronic acid. In addition, a small but distinct population of atypical cells with variable nuclear-to-cytoplasmic ratio, round to oval nuclei, finely stippled chromatin, and 1 to 5 prominent nucleoli that varied in shape and size was present (Figure 1). Anisocytosis and anisokaryosis were marked. The cytoplasm was moderately to deeply basophilic and sometimes contained granular eosinophilic material (possible mucoprotein or mucopolysaccharide). Rare macrocytic or karyomegalic cells, atypical mitotic figures, and bi- and trinucleate cells with nuclear molding were visible. One multinucleated cell compatible with an osteoclast or chondroclast was seen.
Photomicrographs of a synovial fluid preparation from the left elbow joint of a dog with progressive left thoracic limb lameness. A—Atypical cells with variable nuclear-to-cytoplasmic ratios and marked anisocytosis and anisokaryosis are arranged individually or in small, cohesive clusters. Macrocytic, karyomegalic, and trinucleate cells with nuclear molding are seen. Granular eosinophilic material is seen within the cytoplasm. Wright-Giemsa stain; bar = 20 μm. B—A multinucleated cell is visible. Notice the erythrocytes in the background for size comparison. Wright-Giemsa stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 253, 10; 10.2460/javma.253.10.1277
Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page→
Additional Findings
Moderate diffuse disuse muscle atrophy of the dog's left thoracic limb was evident. On neurologic examination, there was absent paw replacement and reduced withdrawal reflex of the left thoracic limb, with no other notable abnormalities.
Ultrasonography of the left elbow joint confirmed the presence of joint effusion and revealed irregular new bone formation along the medial and lateral margins of the humeral condyle, most consistent with degenerative changes. There was accumulation of hyperechoic irregular tissue on the capsular joint margins, which was interpreted as synovial proliferation. Results of a CBC and serum biochemical profile were unremarkable.
The cytologic findings were suggestive of metastatic carcinoma in the subchondral bone with erosion into the left elbow joint. On the basis of the cytomorphologic features and imaging localization, peri-articular and primary bone tumors (synovial cell sarcoma and osteosarcoma) were considered less likely.
Because of the cytopathologic appearance of the cells, screening for a primary carcinoma—particularly a neoplasm of the urogenital tract given the propensity of such neoplasms to metastasize to bone—was recommended. Aerobic bacterial culture of the synovial fluid sample yielded no growth after 6 days.
On repeated rectal examination, the prostate was symmetric but prominent to mildly enlarged for a castrated dog. Computed tomography of the thorax, abdomen, and left thoracic limb was performed for further evaluation of a primary tumor. Computed tomography revealed an ovoid (2.2 × 2.7 × 2.0-cm) region of ill-defined, irregular osteolysis of the distal humeral metaphysis and epiphysis, with a soft tissue–attenuating, mildly contrast-enhancing mass in the same region. The mass extended into the adjacent lateral soft tissue structures. Spiculated osseous proliferation was evident on the medial and lateral aspects of the humeral condyle. Two additional aggressive bone lesions involving the right iliac body and the T13 vertebral body were detected. The mildly symmetrically enlarged (2.2 × 2.8 × 2.6-cm) prostate had heterogeneous contrast enhancement and 2 focal cystic inclusions. Despite the lack of evidence of peripheral lymphadenopathy on physical examination, multiple lymph nodes including the medial iliac, internal iliac, sternal, axillary, and cranial mediastinal lymph nodes appeared mildly to moderately enlarged. The CT findings were interpreted as prostatic neoplasia with multifocal polyostotic aggressive bone lesions and multicentric lymphadenopathy, most consistent with metastatic neoplasia. Thoracic radiography and CT revealed no evidence of pulmonary metastasis.
Ultrasound-guided, fine-needle aspirate biopsy specimens of the prostate, left medial iliac lymph node, and the lytic portion of the left humeral condyle were obtained. Cytologically, the prostatic specimens were mildly cellular and had small numbers of pleomorphic epithelial cells arranged individually or in small sheets. The cells were similar to the neoplastic cell population detected in the synovial fluid, but these cells had mild to moderate anisocytosis and anisokaryosis and lacked granular eosinophilic material within the cytoplasm (Figure 2). In addition, necrotic cellular material was present in the background of the aspirate specimens. Aspirate specimens of the lateral condyle of the left humerus and the left medial iliac lymph node were highly cellular with epithelial cells similar to those in the synovial fluid and in the prostate samples. The cells from the lateral condyle of the left humerus and the left medial iliac lymph node often contained small to large amounts of bright pink granular material or a single colorless vacuole (not shown) within the cytoplasm. Mitotic figures, bi- and multinucleated cells, macrocytes, and karyomegalic cells were visible. Small numbers of osteoblasts and osteoclasts and a small amount of bright pink extracellular matrix were present in the specimen from the humerus. Necrotic cells and small numbers of small lymphocytes were seen in the lymph node specimen. Characterization of cell origin (ie, glandular or urothelial) by immunocytochemical staining with cytokeratin and uroplakin III was not performed because of limited tissue sample availability.
Photomicrographs of cytologic specimens from the prostate (A,B), left humerus (C), and left medial iliac lymph node (D) of the dog in Figure 1. Neoplastic cells have moderate to marked anisocytosis and anisokaryosis. A—Occasional binucleated cells with nuclear molding (bottom left) are present. Wright-Giemsa stain; bar = 20 μm. B—Viable cells (center) are surrounded by necrotic cellular debris (upper) and erythrocytes. Wright-Giemsa stain; bar = 20 μm. C—Occasional neoplastic cells containing bright pink granular material within the cytoplasm are seen (upper center). Wright-Giemsa stain; bar = 20 μm. D—Small lymphocytes and necrotic cells are present in addition to occasional neoplastic cells containing bright pink granular material within the cytoplasm (upper left). Wright-Giemsa stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 253, 10; 10.2460/javma.253.10.1277
Owing to its poor prognosis, the dog was euthanized by IV infusion of pentobarbital solution at the referring veterinarian's clinic 11 days after diagnosis. Necropsy and histologic assessment of affected tissues were declined by the owners.
Cytologic Interpretation and Case Summary
Cytologic interpretation: prostatic carcinoma with widespread lymphatic and bony metastasis, including the distal portion of the left humerus, and suspected involvement of subchondral bone and cartilage erosion with exfoliation of neoplastic cells into the synovial fluid.
Case summary: metastatic prostatic carcinoma of either prostatic glandular or urothelial cell origin in a dog.
Comments
The common clinical signs in dogs with prostatic cancer are reflective of local disease as well as metastatic disease.1–4 Clinical signs of prostatic tumors related to the local mass effect include dysuria, hematuria, stranguria, tenesmus, and change in stool shape (flattened or ribbon-like).1,2 The dog of the present report had no abnormal urogenital signs, which was consistent with the mild enlargement of the prostate on physical examination and imaging. Instead, the dog had an unusual initial manifestation of thoracic limb lameness. Signs of skeletal disease as the initial clinical manifestation in dogs with metastatic prostatic carcinoma are uncommon and reportedly affected 0 of 312 and 9 of 761 dogs in 2 studies.
Canine prostatic tumors are highly metastatic and most commonly spread to the pulmonary parenchyma, iliac lymph nodes, and bone.1 Approximately 15% to 42% of dogs with prostatic carcinoma develop skeletal metastasis, often to the lumbar vertebrae and pelvis1,3,5; however, metastasis to skeletal sites distant to the prostate, such as long bones, ribs, and bones of the skull, has been reported.2,3 Multiple sites of metastases are common.1 In 1 report,1 most dogs with skeletal metastases (82%) also had extraskeletal metastases. To the authors’ knowledge, there is only a single published case report6 of a dog with prostatic transitional cell carcinoma with bone metastases in which neoplastic cells were found in synovial fluid samples from both stifle joints.
Overall, metastasis of carcinoma to subchondral bone with invasion of the synovial space by neoplastic cells has rarely been reported in veterinary medicine, including a case of 1 dog with pulmonary adenocarcinoma7 and 1 dog with carcinosarcoma of the mammary gland.8 Synovial fluid assessment in those cases was an important tool for diagnosis of metastatic disease. For the dog in the present report, assessment of synovial fluid was also important for directing a search for the primary neoplasm. Cytologic analysis of synovial fluid samples from dogs with lameness is an important diagnostic tool; in some cases, results of such analysis can indicate metastatic disease before dogs develop signs more commonly associated with the primary tumor.6,7
References
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2. Bell FW, Klausner J, Hayden DW, et al. Clinical and pathologic features of prostatic adenocarcinoma in sexually intact and castrated dogs: 31 cases (1970–1987). J Am Vet Med Assoc 1991;199:1623–1630.
3. Durham SK, Dietze AE. Prostatic adenocarcinoma with and without metastasis to bone in dogs. J Am Vet Med Assoc 1986;188:1432–1436.
4. Lawrence JA, Saba CF. Tumors of the male reproductive system. In: Withrow SJ, Vail DM, Page RL, eds. Withrow & MacEwen's small animal clinical oncology. 5th ed. St Louis: Elsevier Inc, 2013;557–571.
5. Cooley DM, Waters DJ. Skeletal metastasis as the initial clinical manifestation of metastatic carcinoma in 19 dogs. J Vet Intern Med 1998;12:288–293.
6. Colledge SL, Raskin RE, Messick JB, et al. Multiple joint metastasis of a transitional cell carcinoma in a dog. Vet Clin Pathol 2013;42:216–220.
7. Meinkoth JH, Rochat MC, Cowell RL. Metastatic carcinoma presenting as hind-limb lameness: diagnosis by synovial fluid cytology. J Am Anim Hosp Assoc 1997;33:325–328.
8. Lowseth LA, Herbert RA, Muggenburg BA, et al. What is your diagnosis? Vet Clin Pathol 1989;18:88–89.
