Polyostotic Lymphoma With Vertebral Involvement and Spinal Extradural Compression in a Dog
A 10-year-old, male, mixed-breed dog that developed cervical pain and neurological deficits was diagnosed with primary lymphoma of the second cervical vertebra. The cervical lesion was not surgically resectable. A dorsal cervical hemilaminectomy was performed to provide temporary decompression. The dog had complete pain relief after surgery but was euthanized 6 weeks later with recurrent clinical signs and evidence of lymphoma in the right femur.
Introduction
Spinal tumors in dogs predominantly affect the extradural space rather than the intradural-extramedullary space.1 Most extradural neoplasms in dogs are primary malignant lesions of bone, such as osteosarcoma, chondrosarcoma, fibrosarcoma, hemangioendothelioma, myeloma, and plasmocytoma.2–6 Lymphoma in dogs rarely results in primary proliferative and osteolytic osseous lesions of the appendicular skeleton, and vertebral involvement by lymphoma has rarely been described.7–10 Malignant lymphoma in dogs usually occurs as a multicentric form, with involvement of multiple lymph nodes, liver, spleen, and bone marrow.11
About 70% of all canine vertebral tumors are associated with clinical signs of pain.12 Unilateral or bilateral neurological abnormalities may also develop from spinal cord compression or nerve root involvement.13 In addition, muscular tremors, muscle atrophy, difficulty rising from a recumbent position, fecal and urinary incontinence, anorexia, and lethargy may occur.12 Because of the limited number of reported cases, little is known about the clinical, epidemiological, diagnostic, and therapeutic data of dogs affected by polyostotic lymphoma with vertebral and appendicular skeleton involvement. The purpose of this report is to describe the clinical, diagnostic, and therapeutic findings of a case of polyostotic lymphoma with vertebral involvement and spinal extradural compression in a dog.
Case Report
Clinical Data
A 10-year-old, 15-kg, intact male, mixed-breed dog was referred to the Naples University Veterinary Teaching Hospital because of acute cervical pain, slowly developing ataxia, anorexia, and lethargy. The duration of clinical signs was 3 weeks. The dog had been treated by the referring veterinarian with prednisolone. The signs of pain had decreased slightly, but cervical pain worsened during the week prior to referral.
On physical examination at the time of presentation, pain was elicited with manipulation of the neck, and proprioceptive deficits were present in the pelvic limbs. The dog was unable to extend his neck. No other abnormalities were found.
Hematological data obtained by the referring veterinarian before glucocorticoid administration showed a mild, normocytic, normochromic anemia (hematocrit 25%, reference range 37% to 55%; red blood cell [RBC] count 3.97 × 103/μL, reference range 5.5 to 8.5 × 103/μL; hemoglobin 9.6 g/dL, reference range 12 to 18 g/dL) and a very mild thrombocytopenia (147 × 103/μL, reference range 200 to 500 × 103/μL). No variations in total leukocyte counts were found (white blood cell [WBC] count 10.7 × 103/μL, reference range 6.0 to 17.0 × 103/μL; lymphocytes 3.0 × 103/μL, reference range 1.5 to 5.0 × 103/μL). Serum alkaline phosphatase activity was normal (60 U/L, upper reference value 67 U/L). Total serum calcium concentration was also normal (9.5 mg/dL, upper reference value 12 mg/dL). Results of serum protein electrophoresis showed an increase in α2 (13.9 g/L, reference range 3 to 11 g/L), β2 (17.2 g/L, reference range 6 to 14 g/L), and γ globulins (32.7 g/L, reference range 8 to 18 g/L).
With the dog under general anesthesia, survey radiography, myelography, and ultrasonographic examination were performed. The lateral radiographic view of the cervical spine revealed a rounded area of radiolucency with loss of bone in the lamina of the second cervical vertebra. The margins of the lesion were well defined [Figure 1A]. The ventrodorsal radiographic view revealed lytic bony changes of the lamina and right pedicle of the second cervical vertebra, with morphology alteration of the homolateral vascular canal. The margins of the lesion in this radiographic view were poorly defined [Figure 1B].
Myelography revealed thinning of the dorsal dye column near the rounded area of radiolucency on the lateral view [Figure 2A]. The ventrodorsal view showed extradural thinning and obliteration of the right dye column lateral to the osteolytic lesion [Figure 2B]. Survey radiography of the appendicular skeleton, thorax, and abdomen revealed no other lesions. Ultrasonography of the abdomen was normal.
Treatment
On the basis of the above radiographic findings, neoplasia of the second cervical vertebra was considered a likely diagnosis. Because of the cervical pain and neurological deficits, surgery was performed in order to achieve local spinal decompression and allow histological examination of surgical biopsy specimens. Decompressive right hemilaminectomy via a dorsolateral approach was performed [Figure 3]. Tissue that appeared neoplastic was identified within bone in the lamina of the vertebra and in the vertebral body, forming an actual mass. Neoplastic tissue was resected along the vertebral lamina. The vascular canal edges and large part of the vertebral body were involved; therefore, complete resection of the tissue could not be achieved for fear of destabilizing the cervical vertebral column.
Histological Examination
Samples of the abnormal tissue were fixed in 10% neutral-buffered formalin, decalcified in 5% trichloroacetic acid for 48 hours, embedded in paraffin wax, and stained with hematoxylin and eosin and periodic acid-Schiff (PAS) to differentiate myelogenous cells from lymphoid cells. Paraffin sections (after dewaxing) were labeled immunohistochemically using a streptavidinbiotin peroxidase method for the detection of monoclonal antibodies against myeloid/histiocyte antigen (clone MAC 387), cluster differentiation (CD) 79 – B cell (clone HM 57), CD3 – T cell, lysozyme (muramidase), α1–antitrypsin, and antivimentin (clone V9).a
Histological examination of surgical biopsy specimens revealed a diffuse, dense population of neoplastic lymphoblasts [Figure 4]. The neoplastic cells had large, irregularly shaped or indented nuclei, with a coarse chromatin pattern and at least one nucleolus. The cytoplasm was lightly basophilic. A high number of mitotic figures (3 to 4 per field at 40× magnification) was observed. The neoplastic cells packed the marrow cavity, intertrabecular spaces, and haversian canals of the vertebra and often obliterated fat and hematopoietic tissues.14 In some areas, lymphoblasts extended throughout cortical bone and invaded the periosteum. The neoplastic cells were negative on PAS staining. Immunohistochemically, most tumor cells showed moderate positivity for CD3 antibody [Figure 5]. Based on these findings, the tumor was classified as a T cell type of malignant, lymphoblastic lymphoma.
Postoperative Clinical Outcome
Twelve hours after surgery, the dog was ambulatory. Within 48 hours, signs of pain were considerably reduced, and the dog was able to extend his neck. Improvement was also observed in conscious proprioception. Systemic chemotherapeutic protocols were considered for the dog but were declined by the owners. It was not possible to perform radiation therapy. Six weeks later, the dog was presented with recurrence of cervical pain, ataxia, and proprioceptive deficits in the pelvic limbs. Lameness in the right pelvic limb was also present. Palpation of the proximal portion of the right femur was painful to the dog. No swelling of the femur was detected, and the regional lymph nodes were normal. Cervical myelography confirmed a local relapse of the tumor. An osteolytic lesion was also detected radiographically in the right proximal femur. Affected bone had an irregularly shaped area of radiolucency, creating a moth-eaten appearance. Periosteal proliferation and considerable lysis of cortical bone were also present [Figure 6]. The dog was euthanized, and a necropsy was performed.
Postmortem Examination
At necropsy, extensive neoplastic involvement of the second cervical vertebra and right femur was evident. The lymphomatous lesions appeared as soft, gray-white, confluent masses with necrotic, hemorrhagic areas. The neoplastic cells replaced cortical and trabecular bone and created several foci of osteolysis of the cortices of the vertebra and femur. Pathological fractures in the femur were detected. No other significant lesions were observed in lymph nodes, spleen, liver, gastrointestinal tract, kidneys, or lungs. The histological findings in the femur and vertebra were similar to those previously described.
Discussion
Lymphoma primarily affecting bone is an uncommon diagnosis in dogs, and only nine cases have been described in the literature.8–10,15–21 Of these cases, only two may be classified as primary lymphoma of bone.9,19 One was monostotic, and one was polyostotic with vertebral involvement.9,19 In the other cases, although the lymphoma affected primarily bone, other organs were also involved.8,10,15–18,20,21 In prior reports of mature dogs with lymphoma affecting bone, most lesions affected the long bones.17,20 In only one dog, multiple ribs and thoracolumbar vertebrae were involved.9 Involvement of lumbar vertebrae has also been described in a young dog.10 In cats, lymphoma with vertebral involvement has been associated with radiographically apparent spinal lytic lesions; but recently, bony destruction has only been rarely recognized radiographically in cats with spinal lymphoma.22,23
Because of the limited number of reported cases, little is known about the clinical signs, epidemiology, diagnosis, treatment, and clinical course of primitive osseous lymphoma with vertebral involvement in dogs. The dog of this report was admitted for acute cervical pain and slowly developing ataxia. On the basis of examination findings at presentation, the lesion was localized to the cervical spine. Six weeks after surgery, involvement of the right femur was also detected, indicating rapid progression of the disease.
In the present case, several abnormalities were detected in the complete blood count—namely, mild normocytic, normochromic anemia and very mild thrombocytopenia. Neither abnormality was typical of bone marrow involvement, which is usually manifested as a more severe pancytopenia.24 Unfortunately, a bone marrow biopsy was not performed in the dog, so involvement of marrow was not completely ruled out. These laboratory abnormalities could be secondary to chronic inflammation associated with the disease, decreased RBC survival time, platelet sequestration, or immunomediated destruction. Anemia and thrombocytopenia, however, mildly worsened after surgical debulking. Absence of variations in total leukocyte count could support the absence of bone marrow infiltration. Although neoplastic osteolysis and lymphosarcoma are recognized as causes of hypercalcemia in dogs, hypercalcemia was not observed in this dog.25
Different serum protein changes have been described on electrophoresis evaluation in dogs with neoplastic diseases 26 Increases in α2 and β2 globulins have been reported in dogs with lymphosarcomas and osteosarcomas.26 Dogs with osteosarcomas have also had significantly increased γ globulins.26 In the dog reported here, elevations in α2, β2, and γ globulins were detected. Abnormalities in serum protein electrophoresis from dogs with lymphoma primarily affecting bone have not been previously reported. In two prior cases, results of serum protein electrophoresis were normal.9,19
Histologically, primary bone lymphomas in people are characterized by several patterns of proliferation and different cell phenotypes. In animals, Raskin and Krehbiel have identified and distinguished four histological growth patterns for lymphoproliferative disorders affecting bone marrow (i.e., focal, mixed, interstitial, packed), based on the distribution and location of neoplastic cells.14 In the present case, neoplastic cells totally replaced fat and hemopoietic tissue within the bone marrow of the affected vertebra, so the morphological pattern was defined as packed. In humans, this type of proliferation may be indicative of T cell phenotype, as B cell lymphomas are frequently focal and paratrabecular.14 In the dog reported here, immunohistochemical stains indicated that the neoplastic lymphoid cells were positive for CD3, a marker of T cells. Phenotyping of lymphoma cells in prior cases of lymphoma affecting bone has not been reported previously in dogs. In humans, the different bone marrow histological patterns and phenotypes may have prognostic importance in terms of survival times, but this has not been confirmed in dogs.14
Unfortunately, in the case reported here, the owners refused systemic chemotherapy for the dog, and complete excision of the tumor was not possible. Surgical debulking of the tumor and decompression of the spine provided only short-term pain relief.
Conclusion
A 10-year-old, mixed-breed dog was diagnosed with lymphoma involving the second cervical vertebra. Decompressive hemilaminectomy alleviated the dog’s clinical signs for only a few weeks. Necropsy examination of the dog revealed lymphoma confined to the second cervical vertebra and the right femur. Although lymphoma rarely involves vertebrae in dogs, it should be considered as a differential diagnosis in dogs with pain, neurological deficits, and vertebral osteolysis.
Provided by DakoCytomation, Dako A/S Produktionsuej 42 DK-2600, Glostrup, Denmark
Citation: Journal of the American Animal Hospital Association 42, 1; 10.5326/0420071
Citation: Journal of the American Animal Hospital Association 42, 1; 10.5326/0420071
Citation: Journal of the American Animal Hospital Association 42, 1; 10.5326/0420071
Citation: Journal of the American Animal Hospital Association 42, 1; 10.5326/0420071
Citation: Journal of the American Animal Hospital Association 42, 1; 10.5326/0420071
Citation: Journal of the American Animal Hospital Association 42, 1; 10.5326/0420071
Lateral (A) and ventrodorsal (B) radiographic view of the cervical spine of a 10-year-old, mixed-breed dog with cervical pain. In the lateral view, a round area of radiolucency (arrows) is evident in the lamina of the second cervical vertebra. In the ventrodorsal view, lytic bony changes are present in the vertebral lamina and right pedicle (arrows), with alteration of the vascular canal (arrowhead).
Intraoperative image of the neoplasm after right hemilaminectomy. The spinal process of the second cervical vertebra (arrowhead) is evident. Vertebral body involvement by neoplastic tissue can be seen (arrow).
Moderate intracytoplasmic positivity (brown granular staining) for CD3 is evident in many of the neoplastic cells (Streptavidin-biotin peroxidase method, bar=20 μm).
Ventrodorsal radiographic view of the right femur 6 weeks after surgical debulking of the lymphoma of the cervical vertebra. An extensive lesion is evident in the proximal femur, causing considerable cortical bone lysis and periosteal proliferation.
