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Case Report:Central Nervous System Lymphoma in a Springer Spaniel

A four year old, female, entire Springer Spaniel was presented with a history of progressive neurological signs. A week prior to presentation she had developed lethargy. Signs had then progressed to reduced mentation with ataxia and cranial nerve deficits. She had been in the owner’s possession since a puppy and had no known previous medical problems. She was up to date with her routine vaccinations, worming and prophylactic flea treatment and was receiving no other medications. She was fed a proprietary diet, had never been abroad and there was no known exposure to toxins.

On presentation, the dog was subdued and markedly ataxic but in good body condition (bodyweight 14kg). Vital signs were otherwise unremarkable (mucous membranes pink, capillary refill time less than two seconds, a heart rate of 100bpm, respiratory rate of 24bpm, peripheral lymph nodes not enlarged, chest auscultation and abdominal palpation unremarkable, rectal temperature 38.2oC). Neurological examination revealed postural deficits in all four limbs. Corneal sensation and vision were absent in the right eye and hearing was impaired.  These findings were consistent with a multi-focal brain lesion.

fig. 1 — dorsal FLAIR slice of brain showing patchy increased signal intensity and mass-effect within the left parietal/ temporal lobe and similar, less marked changes to the right side of the forebrain.

Routine haematology, serum biochemistry and electrolytes were unremarkable as were serum thyroxine levels and coagulation times. Toxoplasma and Neospora spp. antibody titres were not supportive of active infection. Urinalysis was unremarkable and faecal parasitology was negative for Angiostrongylus vasorum. Survey radiography of the chest and abdomen was unremarkable as was abdominal ultrasonography. Magnetic resonance imaging of the brain revealed extensive multi-focal pathology. Poorly defined, multi-focal hyper-intensities were present throughout the cerebral hemispheres on T2W and FLAIR sequences (fig. 1).  Similar lesions were noted within the cerebellum and brain stem and there was coning of the cerebellum indicative of raised intracranial pressure.  Gadolinium contrast enhancement was evident in small focal areas within the left cerebral hemisphere (see fig. 2).

fig. 2 — dorsal T1W slice (post gadolinium administration) showing a small area of enhancement within the left parietal/temporal lobe.

Since there was an increased risk of damaging the herniated portion of the cerebellum, a lumbar (rather than cisternal) cerebrospinal fluid tap was taken. This revealed elevated microprotein levels and pleocytosis with a predominance of lymphocytes. Although classic features of malignancy were not identified on cytology (see for comparison, example from a similar case – fig. 3) , the MRI findings in combination with a marked lymphocytic pleocytosis was very suggestive for CNS lymphoma.

Immunophenotyping (B– or T-cell) with comprehensive staging (fine needle aspiration of lymph nodes, liver, spleen and kidneys +/- bone marrow biopsy) would ideally be performed so as to refine the prognosis prior to starting treatment.  However, costs were a significant concern and this information was unlikely to alter the initial treatment plan. A standard COP protocol was used with the addition of cytosine arabinoside for improved CNS penetration (table 1). Symptomatic therapy for suspected meningitis (table 2) had already been started whilst awaiting the remaining results and this was continued until seven-day treatment courses had been completed.

fig. 3 - cerebrospinal fluid cytology from a similar case, showing pleocytosis with a predominance of lymphocytes. The cells display classic characteristics of malignancy including a granular and vacuolar cytoplasmic appearance, predominant and multiple nucleoli and frequent mitotic figures.

There was a good clinical response with significant improvement in demeanour and neurological deficits seen within a few days.  A week following the start of chemotherapy marked neutropaenia was noted, necessitating a treatment break and prophylactic antibiotics. Moderate neutropaenia was also noted following the second vincristine dose necessitating a second short treatment break. However, after a small dose reduction (from 0.5mg/m2 to 0.4mg/m2), weekly dosing was well-tolerated. Four weeks following the introduction of treatment the dog remains mildly ataxic but is very bright and happy.

Summary

Although the long-term prognosis is guarded, many lymphoma patients do achieve a good quality of life for many months and, if the chemotherapy and associated monitoring are well tolerated, the outcome, as in this case, can be very rewarding.

Table 1—Induction chemotherapy protocol (first 8 weeks)

vincristine 0.5mg/m2 once weekly by intravenous injection
cyclophosphamide 50mg/m2 every other day per os
cytarabine arabinoside 50mg/m2 twice daily by subcutaneous injection for two days
prednisolone 40mg/m2 once daily for seven days then 20mg/m2 every other day

Table 2—Empirical therapy for suspect meningitis

prednisolone 1mg/kg twice daily
sucralfate 0.5g three times daily
clindamycin 12.5mg/kg twice daily
trimethoprim-sulphur 4mg/kg (trimethoprim dose) twice daily
fenbendazole 50mg/kg once daily