A 9-year-old female spayed indoor-only American Domestic Shorthair cat (3.72 kg, 8.20 lb) was presented for progressive ill-defined pain, malaise, in appetence, and reluctance to jump. Fourteen days prior, the primary veterinarian had evaluated the cat. At that time, physical and neurologic examinations were unremarkable. Diagnostics performed included a complete blood count (Protocyte Dx, Idexx Laboratories, Westbrook, ME, USA), serum chemistry panel (Catalyst Dx, Idexx Laboratories, Westbrook, ME, USA), and thyroid level (SNAPshot Dx, Idexx Laboratories, Westbrook, ME, USA. Abnormalities identified on the CBC included leukopenia (2.83 K/muL, reference interval 2.87-17.02 K/mul), eosinopenia (0.09 K/mul, reference interval 0.17-1.57 K/mul), and thrombocytopenia (120 K/mul, reference interval 151-600 K/mul). The serum panel was suggestive of an inflammatory process with hyperproteinemia (9.2 g/dl, reference interval 5.7-8.9 g/dl) characterized by hyperglobulinemia (6.0 g/dl, reference interval 2.8-5.1 g/dl). The total thyroxine level was within the normal range. The patient was prescribed buprenorphine (0.04 mg/kg PO q 8-12 h) for pain with recommendations for activity restriction and monitoring at home. Clinical signs did not resolve, and cervical, thoracic, and abdominal radiographs were performed which were within normal limits. A presumptive diagnosis of soft tissue injury was made and recommendations given for continued activity restriction and pain management with buprenorphine. Due to refractory pain, the patient was presented to the emergency service at our institution 11 days later.
On presentation, abnormalities noted on physical examination included pain on palpation of the caudal aspect of the humeri. Abnormal neurologic findings were anisocoria, left pupil miosis, bilaterally decreased flexor withdrawal reflex of thoracic limbs and pain upon palpation of the tricep muscles bilaterally. These findings were consistent with a neuroanatomic localization of C6-T2 spinal cord segments, left lateralized. Differential diagnoses were neoplasia and meningomyelitis. Four days later the patient presented for further work-up including repeat blood work, MR imaging and cerebrospinal fluid (CSF) analysis.
Complete blood count abnormalities were leukopenia (3.8 K/mul, reference range: 6.0-18.0 K/mul), characterized by neutropenia (2.6 K/mul, reference range: 3.0-12.0 K/mul) and lymphopenia (0.9 K/mul, reference range: 1.5-7.0 K/mul), and thrombocytopenia (191 K/mul, reference range: 3.0-12.0 K/mul). Serum panel abnormalities included hyperproteinemia (9.7 g/dl reference range: 5.5-7.1 g/dl) characterized by hyperglobulinemia (6.1 g/dl, reference range: 2.3-3.8 g/dl) and bilirubinemia (0.6 mg/dl reference range: 0.0-0.4 mg/dl). Serological immunoassays for feline leukemia virus (FeLv) antigen and feline immunodeficiency virus (FIV) antibody test (SNAP* Combo, Idexx Laboratories, Toronto, ON, Canada) were both negative. Urinalysis obtained via cystocentesis indicated normal renal concentrating ability (urine specific gravity, 1.053) and 1+ protein with negative blood contamination.
Cervicothoracic spine MRI with a 1.5-Telsa unit (GE Signa LXi, Waukesha, WI) revealed a diffuse homogeneous reduction of T1-weighted and T2-weighted signal intensity of the second thoracic vertebral body (T2) in comparison to normal bone (Figures 1A,B). There was no abnormal hyperintense signal observed within the vertebral body on short tau inversion recovery (STIR) (Figure 1C). The caudal aspect of the T2 vertebra was T1-hyperintense post gadopentetate administration. At the level of mid-body of the T2 vertebra, there was a symmetric, extradural lesion causing ventral spinal cord compression. The lesion was isointense relative to spinal cord parenchyma on T2-weighted and hyperintense on T1-weighted non-contrast images and T1-weighted contrast and fat saturation images (Figures 1D-F). Lumbar cerebrospinal fluid had an elevated protein concentration (73.4 mg/dl, reference interval <45 mg/dl) and total nucleated cell count (8 TNCC/mul, reference interval <5 TNCC/mul). Cytologic evaluation revealed no evidence of neoplasia or infectious agents. The considerably increased protein was suggestive of an inflammatory process within the central nervous system or compromise of the blood brain barrier. Considering the persistent hyperglobulinemia in conjunction with the presence of a solitary, contrast-enhancing vertebral body lesion on MRI, a round cell neoplasia or infectious granuloma became the most likely etiological differentials. Submission of infectious disease titers (Toxoplasma gondii, Cryptococcus spp.), protein electrophoresis, abdominal ultrasound, bone marrow aspirate and core biopsy were recommended to the owner. Sampling from the T2 vertebral body was not performed because of its challenging location to access without surgical intervention.
Abdominal ultrasound revealed small, poorly defined hypoechoic and hyperechoic nodules within the spleen. The remainder of the abdominal ultrasound was normal. Ultrasound-guided fine needle aspirates of the liver and spleen were performed; cytologic evaluation of the liver was unremarkable and extramedullary hematopoiesis was reported from the splenic nodules. Bone marrow (right humerus) aspirate revealed myeloid, erythroid, and megakaryocytic hypoplasia. Plasma cells along with small lymphocytes and activated macrophages were noted but comprised <1% of the total nucleated cell population. All nucleated cells had unremarkable morphology. There was no evidence of infectious agents, inflammation, or neoplastic cells. Following decalcification, the biopsy core sample contained only normal cortical bone:the sample was devoid of marrow. To further assess the persistent hyperglobulinemia, serum samples were submitted (Idexx Laboratories) for the purpose of protein electrophoresis, Cryptococcus antigen and Toxoplasma antibody titers. A distinct peak in the gamma range (Gamma 1, 3.31 g/dl, reference range: 0.3-2.5 g/dl) was identified with no increase in any other proteins, confirming monoclonal gammopathy. Urine was negative for Bence-Jones proteins (Idexx Laboratories). Cryptococcus antigen titer was negative. Toxoplasma IgG indirect immunofluorescence assay (IFA) titer was positive (1:1,600), IgM was negative, suggestive of exposure rather than active infection. Recommendations were made to repeat convalescent Toxoplasma titers in 2-3 weeks. Given all the diagnostic results, a presumptive diagnosis of solitary plasma cell tumor of the T2 vertebral body with secondary spinal cord compression was made. The patient was discharged on buprenorphine (0.04 mg/kg PO q 8-12 h) and gabapentin (6.7 mg/kg PO q 8 h) for pain control and referred to oncology for consultation.
One month later, the patient was presented to the oncology service for consultation and repeat diagnostics to obtain a more definitive diagnose. Neurologic consultation revealed progressive clinical signs of ambulatory tetraparesis with mild proprioceptive ataxia. The patient now exhibited a "two-engine" gait and proprioceptive placing deficits in both pelvic limbs with the left worse than right. Previously noted anisocoria and bilaterally decreased flexor withdrawal reflex of thoracic limbs were static. Repeat CBC and chemistry panel, abdominal ultrasound with FNA of the liver and spleen, and submission of convalescent Toxoplasma titers was performed. Repeat bone marrow core biopsy was declined due to concerns of morbidity. Complete blood count abnormalities were persistent leukopenia (4.2 K/mul, reference range: 6.0-18.0 K/mul) and thrombocytopenia (218 K/mul, reference range: 3.0-12.0 K/mul). Serum panel abnormalities included persistent hyperglobulinemia (5.5 g/dl, reference range: 2.3-3.8 g/dl). Repeat ultrasound revealed no significant findings. Fine needle aspirates of the liver and spleen were repeated and revealed minimal vacuolar hepatopathy with mild plasma cell infiltration and minimal lymphoid reactivity, respectively. While convalescent toxoplasmosis titers were pending, the patient was discharged with empirical prednisolone (1.5 mg/kg PO q 24 h) and clindamycin (13 mg/kg PO q 12 h) therapy for the presumptive treatment of plasma cell tumor and toxoplasmosis. Over the following 3 days, neurologic status improved. Clients were offered but declined radiation therapy for the treatment of the T2 vertebral lesion. The convalescent Toxoplasma titer was unchanged, confirming exposure rather than active infection. Clindamycin therapy was discontinued, prednisolone was tapered (1 mg/kg PO q 24 h) and empirical therapy with melphalan (0.1 mg/kg PO q 24 h) was initiated. The patient did well, eventually being tapered to a lower dose of melphalan (0.1 mg/kg PO q 72 h) and prednisolone (0.5 mg/kg PO q 24 h) at which she was maintained.
Two years following initial presentation, the patient was re-presented to the neurology service for follow-up examination. Neurologic status at this time was normal, however owners noted a circular cutaneous mass located at the tail base. Current medications were prednisolone (0.8 mg/kg PO q 24 h) and melphalan (0.1 mg/kg PO q 72 h). Diagnostics performed included CBC and chemistry panel, follow-up cervicothoracic MRI, FNA of tail base mass, protein electrophoresis, and Bence-Jones protein test. Complete blood count abnormalities were persistent leukopenia (3.0 K/mul, reference range: 6.0-18.0 K/mul) and thrombocytopenia (134 K/mul, reference range: 3.0-12.0 K/mul). Serum panel abnormalities included persistent hyperglobulinemia (5.0 g/dl, reference range: 2.3-3.8 g/dl). Magnetic resonance imaging of the cervicothoracic spine revealed resolution of previous abnormalities (Figure 2). Fine needle aspiration of the tail base mass was consistent with plasma cell tumor (Figure 3). Protein electrophoresis revealed a narrow peak in the gamma range (Gamma 1, 1.81 g/dl, reference range: 0.3-2.5 g/dl). Although within the reference range, the shape and overall protein profile was strongly suggestive of monoclonal gammopathy. Bence Jones proteins were negative. Given the definitive diagnosis of cutaneous plasma cell tumor, the patient was again referred to our oncology service to address disease progression. Melphalan was temporarily discontinued due to moderate leukopenia. At consultation with the oncology service 2 weeks later, repeat CBC revealed resolving leukopenia. Cyclophosphamide in lieu of melphalan was offered but declined. The owners elected to reinitiate melphalan due to known benefits indicated by a normal neurologic exam and resolution of the T2 vertebral lesion. Over the following 8 months, the tail base mass enlarged, and additional cutaneous masses developed, one of which was confirmed via histopathologic evaluation as plasma cell tumor. Repeat staging was offered but declined by the owner. Several chemotherapies: cyclophosphamide, chlorambucil, and lomustine were trialed but unsuccessful at halting disease progression. Three years following initial diagnosis, the patient remained neurologically normal, but owners requested elective euthanasia due to progression of cutaneous masses.