Primary Osseous Melanoma in the Tibia of a Dog
An 18-month-old, female Cane Corso dog was presented with a suspected primary tumor of the tibia. Plain radiographs and computed tomography (CT) of the tibia were highly suggestive of a primary bone neoplasm. A diagnosis of malignant melanoma was made by cytology. Total body survey radiographs, CT scan of the thorax, and abdominal ultrasound excluded the presence of neoplastic lesions other than in the tibia. Limb amputation was performed. Histology and immunohistochemical analysis of the tibial neoplasm confirmed the diagnosis of a melanoma with secondary metastasis to the popliteal lymph node. The dog was alive and in good physical condition 43 months after surgery.
Introduction
Osteosarcoma is the most common appendicular skeletal neoplasm in dogs, accounting for approximately 80% of canine primary bone tumors.1 Chondrosarcoma, fibrosarcoma, and hemangiosarcoma are reported to be the most prevalent nonosteogenic primary tumors of the canine appendicular skeleton.1 Other reported primary tumors of bone are less common and include liposarcoma, lymphoma, myeloma, giant cell tumor of bone, and malignant fibrous histiocytoma.1,2 Primary appendicular skeletal neoplasms are more common in large breeds.1 Older dogs are generally affected, although a biphasic peak (2 and 9 years) has been reported for osteosarcoma.1
Canine melanoma most frequently affects the oral cavity, mucocutaneous junctions, nail bed, skin, and eye.3–7 A poor prognosis is associated with the first three anatomical locations, due to local infiltration and development of distant metastases.3,4,8 Typically, primary cutaneous and ocular melanomas have a better prognosis than those in the oral cavity.4,6,7 In dogs, the development of distant metastases has been described for most internal organs, but metastases are more common in regional lymph nodes and lungs.9 In veterinary medicine, reports of bone metastasis from distant primary sites is limited, but prostate, mammary gland, and urinary bladder tumors are most often the sources of bone metastasis.10 Occasionally, metastases of melanomas to bone have been reported, but the authors are unaware of previous cases of primary osseous melanoma in dogs.
This report describes the clinical, radiological, and pathological findings in a dog with primary osseous melanoma.
Case Report
An intact female Cane Corso dog was evaluated at 11 months of age by a private practitioner for a moderate lameness of the right hind limb. Radiographs of the coxofemoral and stifle joints under general anesthesia were made and interpreted as normal. The dog was discharged with carprofen (2 mg/kg per os [PO] q 12 hours for 10 days). The lameness progressively worsened, and 6 months after initial presentation, the dog underwent reevaluation by the same practitioner. A painful 2 cm by 2 cm swelling of the proximal tibia was noted. Nail beds and digits were clinically normal. No bone lysis of the phalanxes was observed on radiographs made at that time. Based on radiographic findings, a primary osteosarcoma or an osteomyelitis was suspected. The dog was discharged with no therapy.
At 18 months of age, 30 days after the second evaluation, the dog was referred for a second opinion. On physical examination, the dog was severely lame, and a painful softtissue swelling (10 cm by 5 cm) of the right proximal tibia was found. Radiographic examination revealed an extensively lytic lesion associated with a pathological fracture of the tibial diaphysis, with disorganized periosteal proliferation. Transitional areas were enlarged and poorly defined [Figure 1].
A free-hand fine-needle aspiration biopsy from the lesion was performed with a 21-gauge needle. Clear fluid (2 mL) was collected and submitted for cytology. Cytological specimens were highly cellular and characterized by a population of pleomorphic cells. Cells were round to polygonal to spindle-shaped, and they were occasionally organized in highly cohesive groups. Cells had distinct borders and light-blue cytoplasm. Variable amounts of finely granular, black pigment (i.e., melanin) were present in cytoplasm. Nuclei were round with finely dispersed chromatin and one to two nucleoli. Rare atypical mitotic figures were present. Occasionally, atypical multinucleated giant cells (two to six nuclei) were detected. Foamy, reactive macrophages often containing coarsely clumped melanin (i.e., melanomacrophages) were also observed [Figure 2]. Based on cytology, a melanoma was diagnosed. To better evaluate the extent of the tumor, computed tomography (CT) was performed with a fourth-generation scanner.a Transverse, 5-mm, contiguous slices of the right tibia were obtained. Pre- and postcontrast examinations, using a bolus intravenous (IV) injection of 600 mg/kg body weight of nonionic iodine contrast medium, were performed. Reformatted dorsal and sagittal planes were also obtained.
Regions of interest were drawn in the medullary cavity (i.e., center of the lesion), in the abnormal perilesional soft tissues, and in the muscle tissue not invaded by the neoplasm. Density attenuation data were measured before and after contrast medium administration. The CT study showed a space-occupying mass characterized by a precontrast mean attenuation value of 62.7 Hounsfield unit (HU). The mass was located mainly in the medullary cavity and invaded the surrounding tissues that were characterized by hypoattenuated areas [Figure 3A]. The mass showed a strong contrast enhancement with a peak attenuation value of 161.5 HU. The contrast medium examination better demonstrated the heterogeneous soft-tissue swelling secondary to multifocal necrosis [Figure 3B].
A complete clinical examination was performed to exclude metastatic disease from a primary melanoma. The dog underwent ophthalmological, dermatological (including mucocutaneous junctions and nail beds), and oral cavity examinations. Clinical staging of the neoplasm included total body survey radiographs, CT scan of the thorax, and abdominal ultrasound. No paronychia, nail deformity, or nail loss were observed. No lesions other than in the tibia were detected. Amputation of the right hind limb at the coxofemoral joint was performed.
The entire leg, including the popliteal lymph node, was submitted for histopathological examination. No gross lesions were found in the skin, nails, or nail beds. Histology revealed severe and diffuse bone lysis with substitution and effacement of the compact bone and the medullary cavity by a densely cellular population of neoplastic cells. Cells were organized in nests and cords embedded in abundant fibrovascular stroma.Anisocytosis was prominent, and cells were round to spindle-shaped with distinct cell borders and variably abundant, lightly eosinophilic cytoplasm. Variable numbers of cytoplasmic, black, fine granules were present in approximately 30% of the cells. Nuclei were round with finely dispersed chromatin and one to two magenta, round to triangular nucleoli. Mitotic figures ranged from zero to two per 400-magnification field. Multifocal necrosis and accumulation of melanomacrophages were evident [Figure 4]. A diagnosis of lightly pigmented, epithelioid-type melanoma was made. The popliteal lymph node was characterized by expansion of corticomedullary sinuses. One portion of the cortex was completely substituted by cohesive cells with similar morphology as the bone tumor. Immunohistochemical analysis was performed on the bone lesion and on the popliteal lymph node. Atypical cells stained positive for vimentin, neuron-specific enolase, S 100 protein, and Melan A protein [Figure 5]. Cells stained negative for cytokeratin, factor VIII, actin, and glial fibrillary acidic protein. These immunohistochemical findings were consistent with melanoma.
A final diagnosis of primary osseous melanoma with metastasis to the popliteal lymph node was made based on clinicopathological, ultrasonographic, and radiotomographic findings.
The dog rapidly improved after surgery and was discharged with a guarded prognosis. The owner refused adjuvant chemotherapy for the dog. Regular follow-ups (every 4 months) included routine clinical examinations and chest and abdominal radiographs. The patient was alive and in good physical condition 43 months after surgery.
Discussion
This case seems to be the first report of primary bone melanoma in a dog.1 The dog of this report survived for an extended period (at least 43 months). This is in contrast to the poor prognosis associated with malignant melanoma in the oral cavity or nail bed.3,5,12,13
Distant metastases of malignant melanoma are most frequently to regional lymph nodes and lungs.9 Secondary involvement of vertebrae, ribs, and radius has occasionally been documented in association with melanomas of the lips, eyes, and digits.3,9–12,14 In this dog, the main challenge was to define with certainty the primary intraosseous origin of the tumor. The main differential diagnosis was a primary nail bed melanoma.
Nail bed melanomas are generally diagnosed in dogs with a mean age of 9.3 years (range 5 to 13 years). The dog in this case was younger (1.5 years).15 The clinical findings considered typical of nail bed melanoma (such as paronychia, nail deformity, and nail loss9) were not present in this case. Additionally, neither phalanx lysis nor digital masses were found. The long disease-free interval without adjuvant therapy documented in this case is unusual and is markedly different from what would be expected from other types of primary skeletal neoplasia. A long disease-free interval could have resulted from the so-called “tumor dormancy” that is well documented in humans and is described in a case of canine uveal melanoma.14,16–18
Hart hypothesized that malignant cells shed from the primary mass could remain dormant but viable, and that they could subsequently express their tumorigenic potential as a consequence of shifts in the balance between the host immune system and the tumor.17–19 However, the dog in the authors’ study had a disease-free interval of almost 3.5 years, while the reported case of uveal melanoma metastasized after 1.5 years.14
Primary osseous melanoma reported in humans may have a good prognosis.20–26 In the dog of this study, the tumor could have been derived from melanocytes of the endosteum. However, this hypothesis cannot be substantiated, since melanocytes have not been described in canine bone (although they have been identified in the endosteum of reptiles and birds).27,28 Another hypothesis for this unusual primary location could be the derivation from pluripotent bone marrow stem cells that are able to differentiate into melanocytic, adipocytic, osteocytic, and chondrocytic lineages.29,30 Moreover, cancer stem cells from human melanomas (called melanoma cells) have been demonstrated to differentiate into osteocytes, chondrocytes, or adipocytes. This further substantiates the hypothesis that stem cells and phenotypically distinct cancer cells may be related in some circumstances.29–31 Another possible hypothesis in this case is that the lesion could have resulted from an inborn error of migration of melanocytes from the neural crest into the bone, with subsequent neoplastic transformation.
Conclusion
A primary tibial melanoma was diagnosed in a juvenile dog based on history and clinical and pathological examinations. Despite popliteal lymph node invasion, no other distant metastases developed 43 months after diagnosis. This case resembles primary osseous melanoma in humans.
PQ2000S Philips MS; Philips Medical System S.p.A., Monza, Italy 20052
Citation: Journal of the American Animal Hospital Association 44, 3; 10.5326/0440139
Citation: Journal of the American Animal Hospital Association 44, 3; 10.5326/0440139
Citation: Journal of the American Animal Hospital Association 44, 3; 10.5326/0440139
Citation: Journal of the American Animal Hospital Association 44, 3; 10.5326/0440139
Citation: Journal of the American Animal Hospital Association 44, 3; 10.5326/0440139
Medial-lateral radiograph of the right tibia in an 18-month-old, female Cane Corso dog demonstrating an osteolytic lesion with extensive destruction of the cortex and soft-tissue swelling (arrow). Note the very large transitional area (arrowhead).
Photomicrograph of a fine-needle aspirate of the right tibial lesion. The biopsy sample is highly cellular, characterized by round to spindle-shaped cells. Cytoplasmic, granular black pigment (melanin) is evident in some neoplastic cells (arrows). An osteoclast is also present (arrowhead). (Giemsa d stain, 1000×; bar=30 μm)
Computed tomographic images of the proximal aspects of the right tibia. (A) Precontrast image, showing severe absence of the cortex and a moderate periosteal response in the lateral aspect of the tibia (arrow). Rounded, slightly hyperattenuated area (67 HU) is present in the medullary cavity (arrowhead). (B) Postcontrast image, showing the high enhancement (200 HU) in the medullary cavity and replacement by the tumorous tissue following intravenous contrast medium (arrowhead)
Photomicrograph of the osseous melanoma, showing densely packed sheets of spindle (small, white arrows) to polygonal cells (small, black arrow) surrounded by fibrovascular stroma (large, black arrows). Cells are characterized by variable amounts of cytoplasmic, granular to clumped black pigment (arrowheads). (Hematoxylin stain, 200×; bar=200 μm)
Photomicrograph of the osseous melanoma, showing intense cytoplasmic, Melan A positive staining of neoplastic cells (arrowheads), identified as red chromogen/ aminoethylcarbazole. (Hematoxylin counterstain, 100×; bar=100 μm)
