Regional Nodal Metastasis of Humeral Chondrosarcoma in a Dog

Introduction

The purpose of this article is to report a rare case of chondrosarcoma with locoregional lymph node metastasis in a dog. Like most sarcomas, chondrosarcoma generally metastasizes by hematogenous spread, although lymphatic spread can occur with any sarcoma.¹ The most common site for metastasis of chondrosarcoma is the thoracic cavity.^2–7. Documented cases of lymphatic spread of chondrosarcoma are very rare with only one reported case in which the dog was found to have disseminated disease.⁵ The dog described in the current case had metastasis to the locoregional lymph nodes despite no palpable peripheral lymphadenopathy and no evidence of metastasis to other tissues. This signifies the importance of locoregional lymph node evaluation in cases of chondrosarcoma and warrants further study to determine prognostic implications and the best treatment options for dogs with lymph node metastasis.

Case Report

A 6 yr old castrated male English springer spaniel was presented to the Veterinary Health Center at Kansas State University with a 1 mo history of progressive, intermittent, right forelimb lameness. A soft-tissue swelling around the elbow joint had also developed. Restricted activity and carprofen prescribed by the primary care veterinarian were unsuccessful at resolving the lameness.

At the time of referral, the dog had a body condition score of 4 out of 5, a moderate amount of dental tartar and gingivitis, a grade 2/6 left holosystolic heart murmur, and grade 3/4 lameness on the right forelimb. He was intermittently nonweight bearing with activity on physical exam. Pain was not elicited on palpation of the affected limb, but the dog was reluctant to extend the elbow. Muscle atrophy was noted in the region of the right shoulder, and mild soft-tissue swelling was noted at the level of the right elbow. The results of a complete blood cell count and serum biochemical analysis were unremarkable with the exception of a mild increase in alkaline phosphatase (ALP; 368 U/L; reference range, 128–328 U/L). Radiographs of the right elbow were taken and revealed a mixed lytic and proliferative osseous lesion involving the humeral trochlea and medial humeral epicondyle with extensive amorphous periosteal reaction along the border of the medial epicondyle and permeative lysis of the distomedial humerus (Figure 1). Periarticular/periosteal bone was present at the cranial radial head and soft-tissue swelling was observed centered at the distal humerus. Radiographic interpretation was most consistent with either neoplasia or infection. Thoracic radiographs were unremarkable, and an echocardiogram revealed normal parameters with no evidence of valvular or myocardial disease. A fine-needle aspirate of the bone lesion was performed (Figure 2). The cytological preparations had high nucleated cellularity, erythrocytes, and an abundant amount of a deeply eosinophilic matrix throughout the backgrounds. Nucleated cells were pale staining and consisted of individualized cells with round nuclei containing finely granular chromatin patterns and indistinct nucleoli. The cells had a moderate amount of lightly basophilic cytoplasm that occasionally contained small, discrete vacuoles. Anisocytosis and anisokaryosis were moderate. An ALP stain was applied to an unstained preparation, and the cells were negative for ALP activity. The cytological findings were suggestive of a malignant mesenchymal neoplasm. In the absence of ALP positivity and presence of a strong eosinophilic matrix background, a tentative diagnosis of chondrosarcoma was made.

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The dog was anesthetized and a right forelimb amputation was performed. Although not noticeably enlarged, three axillary lymph nodes were collected at the time of surgery. On histopathological examination of the elbow region of the right forelimb, an irregular mass that formed lobule-like patterns that were separated by bands of fibrous connective tissue was observed in the distal humerus (Figure 3). The mass was composed of disorderly arranged plump spindle cells with minimal eosinophilic cytoplasm. The cells were separated by abundant poorly staining chondroid substance. Occasional mitotic figures were identified within the neoplastic population. Occasional fragments of woven bone were present. Multiple clusters of the neoplastic cells producing similar chondroid substance were present in the axillary lymph nodes. Grade 3 chondrosarcoma with metastasis to the locoregional lymph nodes was diagnosed based on these findings.

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The patient was treated with doxorubicin^a q 3 wk for a total of five treatments. At the time this manuscript was prepared, the dog was doing well with no further evidence of metastasis 8 mo following amputation.

Discussion

Chondrosarcoma is a malignant tumor characterized by the production of chondroid matrix by neoplastic chondrocytes.^2–5,8 It is the second most common bone tumor in dogs and humans, behind only osteosarcoma (OSA), and accounts for 5–10% of bone tumors in dogs.^2–6,9 It is the third most common bone tumor in cats, behind OSA and fibrosarcoma.⁴ Commonly reported tumor locations include the bones of the extremities, ribs, nasal cavity, and pelvis.^2–6,10 Extraskeletal chondrosarcoma has been reported in several tissues, primarily visceral organs, but is rare.⁸ Middle-aged, medium- to large-breed dogs appear to be more at risk for chondrosarcoma. In one study, boxers and German Shepherd dogs were overrepresented, while other studies found Labrador retrievers, golden retrievers, Doberman pinschers, and mixed-breeds to be overrepresented.^2,3,5 No sex predilection has been found.^2,9

Chondrosarcoma is often clinically indistinguishable from OSA. Clinical signs vary depending on the location of the lesion.^2,8 Common presenting complaints include epistaxis and sneezing (nasal cavity), lameness (appendicular skeleton and pelvis), firm mass near costochondral junction (rib), and swelling (facial, appendicular skeleton, nasal cavity, etc.).²

Initial diagnostics generally consist of radiographs that often reveal a lytic and/or proliferative lesion that may extend across the joint.^2–4 Radiographs of nasal cavity tumors may have evidence of increased soft-tissue opacity and extraskeletal tumors may reveal ossification and mineralization of the neoplasm.^3,8 On cytological examination chondrosarcoma may appear similar to other sarcomas. Neoplastic cells typically have eccentrically placed nuclei and there are variable amounts of a pink extracellular matrix.¹¹ To help differentiate from OSA using cytological examination, an ALP stain can be applied to either a stained or unstained preparation.^11,12 Although ALP is present in many tissues, bone is the only connective tissue shown to produce ALP in dogs. Therefore, a negative result makes OSA a less likely diagnosis but will not differentiate between chondrosarcoma and other sarcomas, including synovial cell sarcoma, fibrosarcoma, amelanotic melanoma, and other soft-tissue sarcomas.^11,12 Although a positive ALP test typically indicates bone origin (the specificity is 89%), it does not differentiate between neoplastic and reactive osteoblasts.¹¹ Grossly, chondrosarcoma is similar in appearance to OSA. Both neoplasms are generally gray to white in color, lobular, and may contain ossified regions and/or cyst-like structures.^3,8 Histological examination generally reveals a lobulated neoplasm composed of pleomorphic cartilaginous cells producing chondroid tissue. Mitosis is usually rare.⁸ It is not unusual for calcification and ossification of the neoplastic cartilage to occur. Alcian blue stain may be helpful in differentiating chondrosarcoma with ossification from OSA of the chondroblastic type. In chondrosarcomas, Alcian blue will stain the cartilaginous or mucoid material that surrounds the osteoid deep blue.³ A grading scale of low (grade 1), intermediate (grade 2), or high (grade 3) grade using histological criteria of cellularity, pleomorphism, mitotic index, amount of matrix present, differentiation, and invasiveness can be used to further classify the tumor.^4–7

Metastasis generally occurs by hematogenous spread in which the blood-borne cells follow the flow of blood away from the site of the tumor and come to rest in the first capillary bed they encounter, often in the liver or lungs. While tumors do not contain lymphatics, neoplastic cells at the tumor margins can enter the lymphatics, but that is more common with carcinomas than sarcomas.¹ Metastasis and local recurrence of chondrosarcoma occur at a relatively slow rate and later in the course of disease compared with OSA.^3,4,7 In one study, 4 out of 22 dogs with chondrosarcoma that underwent postmortem examination had metastasis to the lungs, parietal pleural, and kidney.³ Another study found 7 out of 25 dogs with appendicular chondrosarcoma had radiographic evidence of pulmonary metastasis.⁶ Out of 12 dogs with chest wall chondrosarcoma, 2 had local recurrence and 2 had evidence of lung metastasis after surgical excision.⁷ A study involving nonnasal chondrosarcomas found 23% of the dogs had evidence of metastasis during the course of disease.⁵ Metastasis occurs most commonly to the lungs and pleura with other reported sites including kidney, liver, adrenal gland, and (rarely) lymph nodes.^2–5,10 The dog in the current case had no radiographic evidence of metastasis to the thoracic cavity; however, locoregional lymph node metastasis was identified by histopathological examination despite no palpable evidence of lymphadenopathy on physical exam. This demonstrates the importance of histological evaluation of locoregional lymph nodes for metastasis.

Surgical resection or limb amputation, with or without chemotherapy or radiation, is the treatment of choice for chondrosarcoma depending on tumor location. Chemotherapy and radiation used as sole modalities have not been shown to affect progression of metastasis of chondrosarcoma in either humans or dogs.^4–7 However, metastasis has been shown to occur in dogs treated with amputation alone, indicating amputation alone may not be curative.^2,5,6

Both doxorubicin and carboplatin have been used in conjunction with surgical resection or amputation with varying results. For example, a vertebral chondrosarcoma in a dog treated with surgical excision and doxorubicin continued to grow despite the chemotherapy.⁴ Another dog with mandibular chondrosarcoma treated with incomplete surgical excision and given six doses carboplatin was euthanized after 17 mo due to local tumor recurrence and presumed metastasis.⁵ Conversely, a dog with humeral chondrosarcoma was treated surgically and with alternating doses of doxorubicin and carboplatin. This dog had no evidence of metastasis after 16.5 mo and was still alive 27 mo after surgery.⁵ In the current case, chemotherapy was chosen because of the atypical, aggressive behavior with the presence of lymph node metastasis, the lack of information in the literature as what to expect with this disease, and the concern for further progression. Although doxorubicin has not been thoroughly evaluated for chondrosarcoma, it is often chosen for other sarcomas, such as OSA and hemangiosarcoma.^13,14 Data are lacking to show that multiagent chemotherapy is more efficacious than single-agent doxorubicin in the treatment of these other sarcomas.¹³

Interestingly, for dogs with digital chondrosarcoma, digit amputation appears to have a better long-term prognosis than amputation of the tumor when it occurs at other anatomic locations. There was neither local recurrence nor evidence of metastasis at the time of follow up in one study involving four dogs with digital chondrosarcomas.² In that study, the mean follow-up time was 370 days. Additional and long-term follow up of dogs is required to confirm that hypothesis.

Tumor location rather than histologic grade appears to be a better prognostic indicator according to one study.⁴ In a more recent study, location of the tumor did not affect metastatic rate and histologic grade was prognostic for survival in the treated group.⁵ Histological grade was not prognostic for dogs with rib chondrosarcoma.⁷ Given the conflicting findings, more studies are required to evaluate prognostic indicators, including locoregional lymph node metastasis.

To the authors' knowledge there is only one other published report of locoregional lymph node metastasis with chondrosarcoma in a dog. In that study, the dog was part of the treated group in which curative intent surgery was performed. Unfortunately, neither the primary tumor location nor the time from initial diagnosis or surgery to time of death was reported. However, at necropsy, the dog had evidence of disseminated disease with metastasis to lung, liver, kidney, adrenal gland, and lymph node.⁵

Conclusion

The dog in the current case had no radiographic evidence of pulmonary metastasis at the time of diagnosis. Further, despite no palpable lymphadenopathy, the axillary lymph node was the only detectable site of metastasis. Sampling of the regional lymph nodes with accompanying histopathology may help to understand whether chondrosarcoma is truly rarely metastatic to the lymph nodes as currently believed, or if lymph nodes have not been closely evaluated histopathologically on a routine basis. Therefore, for all cases of chondrosarcoma, the authors' recommend staging to involve routine evaluation of locoregional lymph nodes for evidence of metastasis. This information will allow for further studies to determine effective treatment options and the prognostic implications associated with lymph node metastasis.