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A 2-year-old, neutered, male golden retriever was referred to the Ontario Veterinary College, with a 6-week history of hind limb weakness and back pain. Magnetic resonance imaging of the lumbar vertebral column, and histopathology and immunohistochemistry following euthanasia identified an uncommon solitary T-cell lymphoma in the paralumbar area.
Paralysie des pattes postérieures chez un chien atteint de lymphome solitaire paralombaire à lymphocytes T. Un golden retriever mâle stérilisé âgé de 2 ans a été dirigé à l’Ontario Veterinary College avec des antécédents de faiblesse des pattes postérieures et de douleur dorsale depuis 6 semaines. L’imagerie par résonance magnétique de la colonne vertébrale lombaire et l’histopathologie et l’immunohistochimie après l’euthanasie ont identifié un rare lymphome solitaire à lymphocytes T dans la région paralombaire.
(Traduit par Isabelle Vallières)
Lymphoid tumors are one of the most common groups of neoplasias in domestic animals (1, 2). Canine lymphomas are classified according to the cytological characteristics of the neoplastic cells, the cell pattern, the immunophenotype, and the anatomical distribution of the tumor (2). Immunophenotype classification is based on the fundamental distinction between B-cell and T-cell lymphomas, and is a powerful prognostic indicator when treatment options need to be considered (3, 4). In dogs, epidemiological studies have demonstrated a higher prevalence of lymphomas of B-cell origin (4), but Fournel-Fleury et al (1) reported a notable increase in the number of T-cell lymphomas in a more recent study.
According to the anatomical classification, multicentric lymphoma is the most common form of canine lymphoma and represents about 80% of all cases reported in dogs (3). In contrast, the isolated organ form, known as solitary lymphoma, is uncommon in dogs and has been reported only occasionally (3, 5–7). Involvement of the central nervous system (CNS) in extranodal canine lymphomas occurs more commonly as part of a multicentric process (2, 8). Nevertheless, lymphoid neoplasia in the CNS may be solitary or multifocal, primary or secondary, and may present with a variety of neurological signs that vary depending on the location of the lesion (3, 6). In the present case report, the clinical and pathologic findings of a dog with an uncommon solitary T-cell lymphoma in the paralumbar area are described.
A 2-year-old, neutered, male golden retriever was referred to the Neurology Service of The Ontario Veterinary College, Veterinary Teaching Hospital (OVC-VTH) with a 6-week history of hind limb weakness and back pain. According to the owners, the dog fell from a deck at the owner’s home 6 wk prior to presentation. At that time, the dog did not yelp or experience any adverse symptoms. The following day the dog was in pain and the owners brought him to the referring veterinarian. The referring veterinarian took hip radiographs showing hip dysplasia, and meloxicam (2 mg/kg, q24h) oral suspension was prescribed for daily use. The dog initially improved with the non-steroidal anti-inflammatory drug (NSAID), but 1 wk prior to the referral to the OVC-VTH, the dog was in more acute pain and codeine (1 mg/kg, PO, q24h) was prescribed, as necessary, given in conjunction with the meloxicam oral suspension.
Initial examination at the OVC-VTH determined that the physical parameters were within normal limits. Neurological examination revealed appropriate mental status and cranial nerve examination showed results that were within normal limits. On gait and posture examination, hind limb paresis was observed with the presence of proprioceptive ataxia and occasional bunny-hopping gait. On postural reactions, proprioception was absent for both hind limbs, worse on the right, along with reduced ability to hop bilaterally. Patellar reflexes were absent and withdrawal reflexes were markedly reduced for both hind limbs. The results of examination of the front limbs were unremarkable. Decreased muscle tone was noted in the hind limbs, perineal reflex was weak, and anal tone was decreased. The owner reported urinary and fecal incontinence for 1 wk before presentation to the OVC-VTH. Back pain was elicited in the lumbar region (from L2 downwards). Based on history and neurological examination, the lesion was localized to the lumbar enlargement (L4-S3 spinal cord segments), and was worse on the right side. Differential diagnoses included degenerative disease (intervertebral disc disease), trauma (hematoma, vertebral fissure, fracture), tumor (spinal cord neoplasia, vertebral body tumor), inflammatory infectious conditions (discospondylitis, meningomyelitis, myelitis). Results of a complete blood (cell) count (CBC) and biochemical profile were within normal values.
Magnetic resonance imaging (MRI) of the lumbar vertebral column was performed with a 1.5 Tesla MRI unit. Images were acquired on sagittal, transverse, and dorsal planes. Fast spin echo pulse (FSE) sequences included T2 (TR = 4000 ms, TE = 88 ms), T1 precontrast (TR = 566 ms, TE = 9 ms), T1 post contrast with fat saturation (TR = 750 ms, TE = 12 ms) and single shot FSE (TR = 3000 ms, TE = 1100 ms). Transverse plain gradient echo (TR = 500 ms, TE = 15 ms, Flip Angle = 30°) pulse sequence images were also obtained. The MRI showed a large mass that extended ventral to the vertebral body of L5 and to the cranial aspect of the vertebral body of L6. The mass was approximately 5.5 cm long, 3.1 cm high, and 5.0 cm wide. The mass had heterogeneous signal intensity on the T1 and T2 weighted images (WI), showing patchy hyperintense and hypointense areas on T2. On T1WI the mass was isointense to the spinal cord and adjacent epaxial muscles with some hypointense zones. The mass showed a heterogeneous pattern of strong contrast enhancement on T1 post contrast WI. The mass extended dorsally and to the right into the epaxial muscles and through the intervertebral foramen at L4–L5 and L5–L6, resulting in severe compression of the spinal cord and displacement of the spinal cord to the left (Figure 1). Due to the extension of the mass through the spinal cord canal it was difficult to classify it as extradural or intradural-extramedulary based on the MRI imagines. The intra-abdominal portion of the mass was in intimate contact with the abdominal aorta and caudal vena cava, producing displacement and severe compression of the latter. On T2WI a very hyperintense elongated tubular structure was identified dorsal to the aorta. This structure was thought to be the distended cisterna chyli and the sublumbar portion of the thoracic duct (Figure 2). There was no apparent osteolysis or osseous involvement. The hyperintense signal noted within the epaxial muscles and especially on the right was considered as infiltration of the mass.
Based on the MRI findings and invasiveness of the mass, the most probable differential diagnoses were neoplasia including primary soft-tissue tumors, sarcomas of muscle and connective tissue, lymphoma and metastatic neoplasia for extradural lesion and nephroblastoma and nerve sheath tumor for intradural-extremedullary lesion.
Due to the size and localization of the mass, surgery was not considered curative. The possibility of performing a fine-needle aspiration or biopsy to achieve a definitive diagnosis and start treatment (radiation therapy, chemotherapy) was discussed with the owners. Because of the rapid deterioration of the dog and the difficulty in providing an encouraging prognosis, the owners elected humane euthanasia and the dog was submitted for pathologic examination.
Necropsy confirmed the presence of a round, firm, infiltrative mass of approximately 6 cm in diameter located near to the vertebral column, adjacent to L4–L6. The mass was firmly attached to the vertebral bodies and infiltrated the spinal canal through the vertebral foramen, expanding to the dorsal aspect of the spinal cord, slightly displacing it to the left and causing mild compression of the cord. The dorsal nerve root at the level of L5–L6 was completely surrounded by the mass, but no nerve infiltration was observed. On the cut surface, the mass was firm and had white and red to dark-red colored areas. As the mass infiltrated the spinal canal it became softer and less well-demarcated.
No peripheral lymph node enlargement was evident, and no other gross abnormalities were observed in the rest of the systems examined. An impression smear of the sublumbar mass was air-dried, fixed and stained by the modified Wright-Giemsa stain. The smear revealed a heterogeneous, neoplastic round cell population. The cells were variable in shape and size, had round to ovoid nuclei, fine dusty chromatin and distinctly visible, single or multiple nucleoli. The cytoplasm was scant and moderately basophilic (Figure 3).
Tissue specimens (tumor mass, spinal cord, nerve root, liver, spleen, kidney, lung, gastrointestinal tract, pancreas, and all lymph nodes) were fixed in neutral-buffered 10% formalin. Histologic sections of all tissues were stained with hematoxylin and eosin (H&E).
Histopathological examination of the mass revealed a poorly demarcated, infiltrative and unencapsulated, heterogeneous population of closely packed neoplastic round cells surrounded by fibrous stroma. The cells varied in size, had distinct cell borders and irregularly distributed pale basophilic cytoplasm. The nuclei were large, round, central to paracentral with heterogeneous chromatin distribution and staining, and contained single to multiple amphophilic nucleoli. Anisocytosis, anisokaryosis, and karyomegaly were prominent with 3–5 mitoses per high power field (HPF). Several areas of neovascularization, necrosis, hemorrhage and infiltration of peripheral fat were observed (Figure 4).
The spinal cord and the nerve root showed swollen axons and occasional digestion chambers consistent with Wallerian degeneration of the ascending and descending tracts (Figure 5). No neoplastic cells were observed in the rest of the tissues examined.
Paraffin embedded sections were used for immunohistochemical staining against B-cell antigen (CD79a) and T-cell antigen (CD3). Immunohistochemical examination revealed strong immunolabeling of numerous neoplastic cells by the anti-CD3 antibody (Figure 6) and occasional staining of cells by the anti-CD79a antibody. Based on the morphological features and the immunophenotype of the cells, the tumor was diagnosed as a diffuse solitary T-cell lymphoma.
The case reported here is an unusual presentation of one of the most prevalent tumors in dogs. Based on morphological features and immunophenotype of the cells, the present case was diagnosed as a diffuse solitary T-cell lymphoma. According to Fournel-Fleury et al (1) no study has established the epidemiology and clinical behavior of T-cell lymphomas in dogs. Since extranodal, atypical T-cell lymphomas may not be easily recognized, cases may not be referred to diagnostic centers and the prevalence of these tumors may be underestimated (1).
Lymphadenopathy is a common finding in most cases of canine T-cell lymphoma reported (1). This observation contrasts with this particular case and with reports in human and canine cases of solitary lymphomas, in which systemic involvement was not a landmark of the disease.
The MRI features found in this case are correlated with the MRI characteristics of primary and metastatic extradural tumors described in humans. The most consistent finding is a hypointense signal on T1-weighted images and isointense or hyperintense on T2-weighted images (9). On the other hand, the signal characteristics described by Kippenes et al (9) for extradural lymphosarcoma are hyperintense on T1 and isointense in T2 with moderate homogenous contrast enhancement. The appearance of lymphoma can vary and be mistaken for other soft tissue tumors. Although MRI should be considered as a complementary diagnosis test, biopsy sampling remains the gold standard for diagnosis.
Long et al (6) reported a primary T-cell lymphoma of the CNS in a 5-year-old female Labrador retriever that was referred with clinical signs related primarily to cranial nerve dysfunction. In this case, the tumor involved the leptomeninges and the cranial and cervical nerve roots, but no neoplastic cells were observed in nonneural tissues. Kaldrymidou et al (10) reported a T-cell lymphoma confined to the nasal cavity and paranasal sinuses of a 2-year-old male crossbred German shepherd, with no other organ involvement. Ponce et al (11) relate this difference in clinical presentation to a later diagnosis of the disease in dogs and consequent disease dissemination. The anatomical site in the case presented here prompted a rapid diagnosis as neurological signs were evident without overt systemic disease. Solitary lymphomas may arise in various anatomical sites and the clinical signs manifested in patients may be related to the extent to which the tumor may be interfering with normal physiological functions. In this case, the mass affected a spinal nerve root and compressed the spinal cord causing neurological signs. Thus, solitary lymphomas should be included in the differential diagnosis for dogs with spinal masses with or without manifest systemic disease.
Detection of canine lymphocytic malignancies relies on the cytologic assessment of circulating lymphocytes or lymphoid tissue or on the histological examination of lymphoid tissue (1, 2, 12). Determination of B-cell or T-cell lineage offers valuable prognostic information when treatment options need to be considered (1). Additional methods of detecting malignant lymphocytes are currently being developed and can be used as an adjunct to morphology and phenotyping for the diagnosis and classification of canine lymphoma (1, 11, 12). In this case, immunohistochemical examination revealed immunolabeling of numerous neoplastic cells by the anti-CD3 antibody and occasional staining of cells by the antiCD79a. This may be explained by the presence of residual normal lymphoid tissue or by the fact that maturing lymphoid cells may undergo rearrangements of genes encoding the immunoglobulin and the T-cell receptor that direct sequential expression of the receptors of both B- and T-lineage (2, 13).
The development of new more specific techniques will enable proper recognition and classification of lymphoid tumors and may improve the adequacy of treatment and thus better prognosis in canine lymphoma cases.
We thank Drs. Dorothee Bienzle and Tony Hayes for supervision of the histopathologic and immunohistochemical examination of the tissues and Drs. Roberto Poma and Robert Cruz for their help with the clinical description of the case. CVJ
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