A 1.5-year-old spayed female domestic shorthair cat was admitted to the primary veterinarian for evaluation of progressive hind limb locomotor difficulties and signs of pain along the lumbar portion of the vertebral column of 2 months duration. Serologic tests for FeLV and FIV infection performed at that time were negative. Meloxicam (4 drops [0.05 mg/drop], PO, q 24 h for 5 days) was prescribed, but the owner reported no perceived benefit, and 1 month later, the cat was admitted with signs of pain along the lumbar portion of the vertebral column. A CBC revealed a neutropenia of 1.7 × 109 neutrophils/L (reference range, 2.5 to 12.5 × 109 neutrophils/L). Survey radiographs of the vertebral column were available for review, and these revealed a subtle osteolytic lesion of the body of L5 and irregular end plate margins at the L4-L5 disk space. Survey radiography was repeated 6 days later and revealed progression of an expansile lytic lesion within the cranial aspect of the vertebral body of L5 as well as the appearance of punched-out areas of osteolytic lesions in the distal portion of both femurs.
Approximately 8 weeks after admission to the primary veterinarian, the cat was referred to the Ontario Veterinary College. The cat was paraparetic, and a pain response was consistently elicited on palpation of the lumbar area of the vertebral column. The cat required support to stand. A moderate reduction in voluntary motor function in the right hind limb and minimal voluntary motor function in the left hind limb were observed. Tail tone and function and anal tone were within reference limits. Moderate muscle atrophy was appreciated in both hind limbs. Patellar reflexes were normal. The cat had a decreased right hind limb withdrawal reflex and an absent withdrawal reflex in the left hind limb. Perianal reflex was normal. The cat was able to use its forelimbs to pull itself into the litter box and then urinate and defecate normally. The cutaneous trunci reflex was normal. Forelimbs were neurologically normal in terms of musculature and voluntary motor and withdrawal reflexes. The cat had normal mentation (alert, responsive, and aggressive) and ocular movements. The remainder of the neurologic examination to assess cranial nerves was not performed because of the disposition of the cat. The neuroanatomic localization was consistent with a spinal cord lesion at the level of L6-S2 and worse on the left, corresponding approximately to L4-L6 vertebral bodies.
Hematologic abnormalities included neutropenia (1.7 × 109 neutrophils/L; reference range, 2.1 to 8.3 × 109 neutrophils/L) and mild lymphocytosis (9.2 × 109 lymphocytes/L; reference range, 1.1 to 8.1 × 109 lymphocytes/L). Lymphocytes were morphologically unremarkable. Red blood cells had moderate poikilocytosis comprised predominantly of ovalocytes (elliptocytes). Results of serum biochemical analysis, including total globulin concentration (35 g/L; reference range, 27 to 48 g/L), were unremarkable. Findings on 3 radiographic views of the thorax were unremarkable.
Fluoroscopic-guided aspirate of the vertebral lesion at the level of L4-L5 was performed; cytopathologic assessment only identified blood. Magnetic resonance imaging of the thoracic and lumbar portions of the vertebral column was performed.a Pre- and postcontrastb T1weighted, STIR, T2* gradient echo, and T2-weighted fat sequences in sagittal, transverse, and dorsal planes were obtained. Sagittal T2 fat saturation MR images of the proximal portion of both hind limbs were also obtained and evaluated. On the T2- and STIR-weighted sequences, there was a poorly margined lesion in the epaxial muscles from L4 to L6 that was characterized by a high T2 signal intensity, intermediate T1 signal intensity (isointense to muscle), and moderate contrast enhancement. The cranial aspect of the vertebral body of L5 had decreased signal intensity on T2- and T1-weighted sequences and increased signal intensity on the STIR-weighted sequences. New bone formation was appreciated on the ventral aspect of L4-L5 vertebral bodies. Decreased signal intensity was observed in the L4-L5 intervertebral disk on T2-weighted sequences.
Nerve roots of L4 and L5 and the left nerve root of L3 were abnormally large, isointense to the spinal cord on T1-weighted sequences, hyperintense to the spinal cord on the T2- and STIR-weighted sequences, and mildly contrast enhanced. The intervertebral foramen at these sites was wide. A lesion with the same signal characteristics as the nerve roots, which was surrounding the spinal cord from the cranial aspect of L4 to the midbody of L6, obliterating the subarachnoid space and causing mild circumferential compression of the spinal cord, was observed. On the T2-weighted sequences, there were patchy areas of high signal intensity within the spinal cord. Within the medullary cavity of the distal portion of the right femur there was a focal lesion that had a high T2 signal intensity (Figures 1–3).
Dorsal T2-weighted MR image of the caudal lumbar region in a cat examined because of hind limb locomotor difficulties. The L5 spinal nerves are enlarged and have a high signal intensity (arrow = left L5 spinal nerve). In the muscles lateral to L4 and L5 there is a high T2 signal intensity.
Citation: Journal of the American Veterinary Medical Association 233, 5; 10.2460/javma.233.5.743
Dorsal T2-weighted MR image of the caudal lumbar region in a cat examined because of hind limb locomotor difficulties. The L5 spinal nerves are enlarged and have a high signal intensity (arrow = left L5 spinal nerve). In the muscles lateral to L4 and L5 there is a high T2 signal intensity.
Citation: Journal of the American Veterinary Medical Association 233, 5; 10.2460/javma.233.5.743
Dorsal T2-weighted MR image of the caudal lumbar region in a cat examined because of hind limb locomotor difficulties. The L5 spinal nerves are enlarged and have a high signal intensity (arrow = left L5 spinal nerve). In the muscles lateral to L4 and L5 there is a high T2 signal intensity.
Citation: Journal of the American Veterinary Medical Association 233, 5; 10.2460/javma.233.5.743
Transverse T1-weighted postcontrast MR image of the cat in Figure 1 obtained at the level of the L5-6 intervertebral foramen. Notice the enlarged L5 spinal nerves that are contrast enhanced (A = left L5 spinal nerve).
Citation: Journal of the American Veterinary Medical Association 233, 5; 10.2460/javma.233.5.743
Transverse T1-weighted postcontrast MR image of the cat in Figure 1 obtained at the level of the L5-6 intervertebral foramen. Notice the enlarged L5 spinal nerves that are contrast enhanced (A = left L5 spinal nerve).
Citation: Journal of the American Veterinary Medical Association 233, 5; 10.2460/javma.233.5.743
Transverse T1-weighted postcontrast MR image of the cat in Figure 1 obtained at the level of the L5-6 intervertebral foramen. Notice the enlarged L5 spinal nerves that are contrast enhanced (A = left L5 spinal nerve).
Citation: Journal of the American Veterinary Medical Association 233, 5; 10.2460/javma.233.5.743
Transverse T1-weighted postcontrast MR image of the cat in Figure 1 obtained at the level of the midbody of L5. Notice the contrast enhancement of the epaxial muscles (A) and a circumferential contrast-enhancing lesion around the spinal cord (B).
Citation: Journal of the American Veterinary Medical Association 233, 5; 10.2460/javma.233.5.743
Transverse T1-weighted postcontrast MR image of the cat in Figure 1 obtained at the level of the midbody of L5. Notice the contrast enhancement of the epaxial muscles (A) and a circumferential contrast-enhancing lesion around the spinal cord (B).
Citation: Journal of the American Veterinary Medical Association 233, 5; 10.2460/javma.233.5.743
Transverse T1-weighted postcontrast MR image of the cat in Figure 1 obtained at the level of the midbody of L5. Notice the contrast enhancement of the epaxial muscles (A) and a circumferential contrast-enhancing lesion around the spinal cord (B).
Citation: Journal of the American Veterinary Medical Association 233, 5; 10.2460/javma.233.5.743
Magnetic resonance imaging revealed an intramedullary spinal cord lesion from L4 to L6 and abnormalities affecting multiple tissues in the L4-L5 region and involving the meninges and nerve roots. Surrounding lumbar epaxial muscles were abnormal, and the cat had intervertebral disk degeneration at L4-L5. Enhancing tissue around the spinal cord was interpreted to represent meningeal tumor infiltrates rather than fat tissue. Lastly, a focal bone marrow lesion was appreciated in the distal portion of the right femur and the vertebral body of L5. Although it appeared likely that the tumor originated in bone, the precise site of origin could not be identified. Soft tissue lesions were centered in the epidural space and epaxial muscles, and in comparison, the boney involvement was less extensive but could represent edema or inflammation. Magnetic resonance imaging revealed changes to soft tissue structures, such as the changes within the spinal cord, nerve roots, and meninges not otherwise appreciated by use of survey radiography of the vertebral column, and provided greater detail on the bony changes. It did not identify any lesions in the femurs that were not appreciable on survey radiography.
Analysis of CSF samples collected from the cerebellomedullary cistern disclosed a markedly increased protein concentration (2.9 g/L; reference range, 0.1 to 0.3 g/L) and an increased total nucleated cell count (0.008 × 109 cells/L; reference range, < 0.003 × 109 cells/L). Cytologic evaluation revealed 89% mononuclear cells and 11% neutrophils. More than 80% of the mononuclear cells were large and had eccentric round to oval nuclei with clumped chromatin; blue cytoplasm; and prominent, variably sized, bluish cytoplasmic aggregates (Figure 4). Several mitotic figures were observed among the latter cells, which were interpreted to be abnormal plasma cells with cytoplasmic immunoglobulin aggregates. Cytopathologic interpretation of the CSF was malignant plasma cell pleocytosis.
Photomicrograph of CSF cells from a cat with myeloma comprised of abnormal plasma cells with cytoplasmic aggregates. Wright stain; bar = 10 μm.
Citation: Journal of the American Veterinary Medical Association 233, 5; 10.2460/javma.233.5.743
Photomicrograph of CSF cells from a cat with myeloma comprised of abnormal plasma cells with cytoplasmic aggregates. Wright stain; bar = 10 μm.
Citation: Journal of the American Veterinary Medical Association 233, 5; 10.2460/javma.233.5.743
Photomicrograph of CSF cells from a cat with myeloma comprised of abnormal plasma cells with cytoplasmic aggregates. Wright stain; bar = 10 μm.
Citation: Journal of the American Veterinary Medical Association 233, 5; 10.2460/javma.233.5.743
A bone marrow aspirate was obtained from the right trochanteric fossa (an area with no evidence of lytic lesions on radiographic views or MR images). Bone marrow smears were cellular, and all hematopoietic cell lines were present. A 500-cell differential count indicated a myeloid-to-erythroid ratio of 6:1 with synchronous maturation in both cell lines. Megakaryocytes were adequate; iron stores were not evident. Throughout the smears, there were scattered plasma cells that comprised approximately 7% of all cells. Mitotic figures, biand trinucleation, and cytomegaly were prominent among the plasma cells. In addition, most plasma cells had intracytoplasmic inclusions similar to those seen in the CSF. A bone marrow core biopsy specimen was obtained from the right humeral head (an area with no evidence of lytic lesions on radiographic views or MR images). Histologic analysis did not result in identification of abnormalities.
Serum protein electrophoresis did not reveal an abnormal globulin pattern, although there was a mild broad-based increase in the α2-globulin fraction. Immunofixation did not reveal any M-protein. Urine protein electrophoresis disclosed a sharp γ-globulin peak consistent with a monoclonal band (globulin light chains) of Bence-Jones proteins. The cat was diagnosed with a myeloma-related disorder on the basis of a light chain proteinuria, multiple osteolytic lesions (including classic punctate osteolytic lesions), myeloma cell infiltration on a bone marrow aspirate, and a suspected (epidural) lesion identified on MRI that infiltrated the L4-L6 vertebral body region.
The cat commenced a chemotherapeutic induction protocol of melphalan (0.4 mg, PO, q 24 h for 14 days) and prednisolone (2 mg, PO, q 24 h for 14 days).1–3 Radiation therapy was discussed with the owners and declined. The cat initially responded well to the treatment, and the owners reported that within 3 weeks, the cat was able to ambulate and appeared to be pain free in the lumbar region of the vertebral column. Within 2 weeks of treatment, a repeat CBC was obtained that revealed a mild to moderate persistent neutropenia. Approximately 6 weeks after its initial admission and after tapering the melphalan to every other day, the owners and the referring veterinarian reported that the cat had lost weight and developed left hind limb lameness, a right head tilt, and anisocoria with the left pupil smaller than the right. Deficits resolved within a week when the owner resumed once-daily administration of melphalan and recurred when the owner again tried to taper to every-other-day administration. Continuing daily melphalan was recommended. A CBC at the referring veterinarian approximately 1 week later revealed neutropenia (0.9 × 109 neutrophils/L; reference range, 2.5 to 12.5 × 109 neutrophils/L). We recommended temporarily discontinuing the melphalan treatment until recovery of the neutrophil count to > 1.5 × 109 neutrophils/L and increasing the prednisolone dose from 0.5 mg/kg/d (0.23 mg/lb/d) to 2 mg/kg/d (0.91 mg/lb/d) for 3 days, then decreasing and maintaining the prednisolone at 1 mg/kg/d (0.45 mg/lb/d). Reintroduction of the melphalan every other day and regular monitoring of the CBC were recommended once the neutrophil count improved.
The cat was not reevaluated at the Ontario Veterinary College until 5 months after diagnosis. At that time, the owners reported normal eating, drinking, grooming, urination, and defecation. Neurologic examination indicated generalized weakness without a pain reaction elicited with palpation of the vertebral column. The cat was non–weight bearing on the left forelimb and had a plantigrade stance in both hind limbs. Muscle atrophy was present in both forelimbs. The patellar reflex was absent in the left hind limb and decreased on the right. Withdrawal reflex was present in both hind limbs, absent on the left forelimb, and diminished on the right forelimb. The cutaneous trunci reflex was adequate. The cat had a right head tilt with suspected vestibular ataxia, a tendency to lean to the right, and anisocoria with a left miotic pupil. The lesion was considered multifocal, involving the right vestibular system and mainly left cervical and lumbar enlargements. Lesions in the spinal cord were considered to be mainly in the gray matter (lower motor neuron). Horner's syndrome was observed, likely related to a left-sided lesion at the level of T1-T2.
Four months later, the owners reported that the cat was losing hind limb function and that it appeared to be in pain. The owners increased prednisolone administration to twice daily and melphalan administration to once daily. The owners subsequently increased the melphalan to twice-daily administration and, in accordance with prior possible therapeutic protocols discussed with the owners, switched from prednisolone to dexamethasone at a dose of 2 mg, PO, once daily. The cat apparently did not respond well to the dexamethasone, which the owners discontinued before resuming twice-daily prednisolone. The owners reported mild improvement in the hind limbs but not the forelimbs. Eight months after diagnosis, the cat had substantial weight loss and was nonambulatory with dysfunction in all 4 limbs. The cat was euthanatized 9 months after initial diagnosis.
Discussion
Multiple myeloma is rarely diagnosed in cats, representing < 1% of all malignant neoplasms, and clinical signs at admission of this cat were unique in several respects.1,4,5 Multiple myeloma typically affects older cats with a mean age of approximately 10 to 12 years.2,4,5 To our knowledge, although a myeloma-related disorder has been described for a 19-month-old cat,3 multiple myeloma has not previously been reported for a cat this young. Clinical signs at admission are often vague and nonspecific, including lethargy, anorexia, vomiting, and diarrhea.1,2,4–7 Although there have been reports4,5,8,9 of cats admitted for hind limb paresis, ataxia, or lameness, as in the cat of this report, such clinical signs at admission are uncommonly attributed to multiple myeloma or a myeloma-related disorder. Bone lesions were historically reported less commonly in cats than dogs, although more recent reports indicate a more comparable percentage of bony lesions in cats and dogs.4 Involvement of CSF in this cat was highly unusual1,2,6 and has not previously been described, although 1 cat with an intracerebral plasmacytoma had neoplastic, possibly lymphoid, cells in the CSF.10
Traditional diagnostic criteria for multiple myeloma in cats as adapted from human medicine require 2 of the following: paraproteinemia or monoclonal gammopathy, radiographic evidence of osteolytic bone lesions, Bence-Jones proteinuria, and > 5% neoplastic cells or > 10% to 20% plasma cells in the bone marrow.1,2,4–6 The cat of our report met 3 of the 4 criteria, having osteolytic bone lesions, Bence-Jones proteinuria, and bone marrow infiltrates.
The applicability of the mentioned human-derived criteria to cats has recently been questioned, and in 1 retrospective study4 of 16 cats, only 50% fulfilled 2 of the 4 stated criteria for antemortem diagnosis, whereas 6 cats met 3 of the criteria, and 1 cat met all 4 criteria. Although results in that study revealed that affected cats most commonly had paraproteinemia and bone marrow plasmacytosis, the authors suggested that bone marrow aspirates and serum protein concentrations should be sufficient for diagnosing multiple myeloma and that diagnostic criteria should also include visceral organ infiltration and atypical plasma cell morphology. Noncutaneous extramedullary plasmacytoma and intramedullary myeloma have similar features, including clinical signs of systemic disease, paraproteinemia, paraproteinuria, and nonbenign behavior in the clinical evolution of the disease.5 Bone marrow involvement is used to distinguish between the 2 neoplasms.1,2,6 Neither appear to be related to FeLV, FIV, or feline infectious peritonitis virus infection.1,2,5 A diagnosis of multiple myeloma in cats includes both intramedullary myeloma and combined intra- and extramedullary myeloma.3,4,6,7
The cat of our report met the historical criteria for a diagnosis of multiple myeloma as extrapolated from humans. This cat lacked a serum gammopathy. Extramedullary neoplasia was not definitively excluded as abdominal ultrasonography, or other advanced abdominal imaging was not performed. Evaluation of the bone marrow aspirate and CSF revealed a substantial plasma cell infiltrate with morphologically abnormal cells, and the MR image revealed a lesion predominantly in the epidural and surrounding muscular tissues; however, the lesion did have bony involvement. Given the bone marrow involvement, the cat had both intra- and extramedullary involvement and was diagnosed with multiple myeloma.
Most (87.7% to 100%) cats with a diagnosis of multiple myeloma have paraproteinemia.1,4,5 In the cat of this report, paraproteinemia was not evident by serum protein electrophoresis. However, urine protein electrophoresis revealed a monoclonal light chain proteinuria. To our knowledge, this is the first report documenting this phenomenon in a cat with myeloma. In humans, 11% of affected patients have been reported to have normal serum electrophoresis results, and 1% have been reported to have an increase in the α2 protein region.11 Of the patients with normal serum electrophoresis results, 94% had an abnormality in the urinary protein electrophoretic pattern.11 Separation of serum proteins by acetate electrophoresis has relatively poor sensitivity for detection of monoclonal immunoglobulins, compared with immunofixation and 2-dimensional separation of proteins; however, absence of a paraprotein in our cat was further supported by normal immunofixation results, which in humans is a more sensitive technique.11
The most commonly recommended treatment for multiple myeloma is a combination of prednisolone (0.5 mg/kg [0.23 mg/lb], PO, q 24 h) and melphalan (0.1 mg/ kg [0.05 mg/lb], PO, q 24 h for 14 days, then every other day until clinical improvement or leukopenia, then maintenance at 0.1 mg/kg, PO, q 7 days), although combination chemotherapy with cyclophosphamide, vincristine, prednisolone, chlorambucil, and melphalan has been used in a limited number of cats.1,5 Of 7 cats treated with melphalan and prednisolone, 5 survived 4 to 8 weeks, 1 survived 4 months, and 1 survived 6 months.4 All were ultimately euthanatized. In 1 study1 of 9 cats with multiple myeloma, it was found that hypocalcemia, pathologic fractures, anemia, Bence-Jones proteinuria, azotemia, persistent elevations in serum protein concentration at 8 weeks after treatment, and little or no clinical improvement were poor prognostic indicators and reflected a more aggressive form of the disease. Survival time for such cats did not exceed 14 days, with a median of 5 days. In contrast, normocalcemia, lack of azotemia, absence of pathologic fractures, no anemia, absence of Bence-Jones proteinuria, and a normal serum protein 8 weeks after commencement of treatment reflected a less aggressive form with a median survival of 387 days (range, 120 to 720 days).1 The cat of this report adds to the known features of multiple myeloma in cats because of the young age of the patient, the presence of light chain proteinuria in the absence of an electrophoretically detectable paraproteinemia, the CSF infiltration, and the first reported MRI description of the bone and soft tissue lesions associated with multiple myeloma in the CNS of a cat. Expected response to treatment was largely unknown, but the few weeks to months of improvement followed by a prolonged deterioration suggests limited chemotherapy sensitivity.
ABBREVIATIONS
| MR | Magnetic resonance |
| MRI | Magnetic resonance imaging |
| STIR | Short tau inversion recovery |
GE Signa MRI system with 1.5 Tesla magnet field strength and phased array surface spine coil, GE Healthcare, Piscataway, NJ.
Omniscan (Gadodiamide), GE Healthcare, Piscataway, NJ.
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