Dr Shasta Lynch
BVSc(hons) MANZCVS(SAM) DipECVIM-CA(Oncology) MRCVS
RCVS, Australian and European Veterinary Specialist in Oncology
Ella, an 8 year old, female neutered, Lakeland Terrier presents to you with a 4 week history of polyuria, polydipsia and reduced appetite.
On examination, Ella was quiet but responsive. Body condition score was 3/9. Oral mucous membranes were pink but tacky with a capillary refill time of <2 seconds. The right and left mandibular, prescapular and popliteal lymph nodes were moderately enlarged. Heart rate was 100 beats/minute with synchronous femoral pulses. Respiratory rate was 26 breaths/minute with normal effort. No adventitious cardiac or respiratory sounds were auscultated. Abdominal palpation was unremarkable. Rectal examination was unremarkable. Remaining clinical examination did not reveal any abnormalities. Rectal temperature was 38.3C.
What is the problem list?
The problems are peripheral lymphadenopathy, polyuria/polydipsia and reduced appetite.
Possible causes of painless peripheral lymphadenomegaly/lymphadenopathy include:
- Neoplasia (primary haemolymphatic, metastatic) – this seemed most likely based on the presentation.
- Infectious (bacterial, viral, parasitic, rickettsial, fungal) disease
- Immune mediated disease
- Reactive hyperplasia
Polyuria/polydipsia may be related to peripheral lymphadenopathy if due to hypercalcemia of malignancy. Hypercalcemia of other causes can also cause polyuria/polydipsia as can renal disease, endocrine/metabolic disease (including diabetes mellitus, hyperadrenocorticism, hypoadrenocorticism, diabetes insipidus), liver disease, psychogenic and iatrogenic causes.
Reduced appetite is non-specific and may be due to systemic disease, dietary or environmental changes, difficulty eating or loss of smell.
What investigations would you perform?
We performed the following investigations:
- Haematology
- Serum biochemistry
- Ionised calcium
- Urinalysis
- Urine culture
- Fine needle aspirate of the enlarged peripheral lymph nodes
The results were as follows:
Haematology
| Parameter | Day 1 | Day 3 | Reference Interval |
| Total WBC (x109/l) | 9.79 | 9.13 | 6-17.1 |
| Segmented neutrophils (x109/l) | 6.853 | 6.391 | 3-11.5 |
| Lymphocytes (x109/l) | 2.35 | 1.826 | 1-4.8 |
| Monocytes (x109/l) | 0.294 | 0.73 | 0.15-1.5 |
| Eosinophils (x109/l) | 0.294 | 0.183 | 0-1.3 |
| Basophils (x109/l) | 0 | 0 | 0-0 |
| RBC (x109/l) | 7.28 | 6.18 | 5.5-8.5 |
| Hgb (g/dl) | 16.7 | 14.4 | 12-18 |
| Hct (%) | 50.5 | 42.6 | 37-55 |
| MCV (fL) | 69.4 | 69 | 60-77 |
| MCHC (g/dL) | 33.1 | 33.7 | 31-37 |
| PLT (x109/l) | 171 | 160 | 150-900 |
Clinical Biochemistry
| Parameter | Day 1 | Day 3 | Reference Interval |
| Total protein (g/l) | 68.6 | 59 | 49-71 |
| Albumin (g/l) | 31.4 | 28.1 | 28-39 |
| Globulin (g/l) | 37.4 | 30.9 | 21-41 |
| Sodium (mmol/l) | 151 | 148 | 146-155 |
| Potassium (mmol/l) | 4.9 | 4.3 | 4.1-5.3 |
| Chloride (mmol/l) | 110 | 111 | 107-115 |
| Calcium (mmol/l) | 4.39* | 2.14 | 2.13-2.7 |
| Inorganic phosphorus (mmol/l) | 1.5 | 1.08 | 0.8-2 |
| Urea (mmol/l) | 21.7* | 13.5* | 3-9.1 |
| Creatinine (µmol/l) | 205* | 166* | 59-138 |
| Cholesterol (mmol/l) | 5.8 | 4.8 | 3.3-8.9 |
| Total Bilirubin (µmol/l) | 1.6 | 1.8 | 0-2.4 |
| Amylase | 952 | 952 | 176-1245 |
| Lipase | 184 | 200 | 72-1115 |
| ALT (U/l) | 31 | 30 | 13-88 |
| CK | 334 | 151 | 61-394 |
| ALP (U/l) | 143 | 139 | 19-285 |
| Glucose (mmol/l) | 4.2 | 4.7 | 3-6 |
| iCa (mmol/l) | 1.71 | 1.13 | 1.13-1.33 |
Urine analysis
| Parameter | Day 1 |
| Source | Cystocentesis |
| Colour | Pale straw and clear |
| Specific Gravity | USG 1.011 |
| pH | 5.5 |
| Protein | Negative |
| Glucose | Negative |
| Ketones | Negative |
| Bilirubin | Negative |
| Blood | Negative |
| Urobilinogen | Negative |
| Casts | Negative |
| Leukocytes/HPF | 0-1 per HPF (x400) |
| Epithelial cells/HPF | None |
| Erythrocytes/HPF | 0-10 per HPF (x400) |
| Crystals | Negative |
| Bacteria | Negative |
Cytology of right and left popliteal, mandibular and prescapular lymph nodes:
The cell population is predominantly a mixed lymphocyte population.
A 100 cell differential of the right prescapular lymph node gives 63% small lymphocytes, 25% medium lymphocytes and 12% large lymphocytes.
A 100 cell differential of the right popliteal (image above) gives 67% small lymphocytes, 19% medium lymphocytes and 14% large lymphocytes.
Focally on all slides there are small areas where the large lymphocytes appear increased (30-40% of cells present).
Occasional plasma cells are noted.
Mitotic figures are noted regularly over the smear.
Occasional pyknotic cells are noted.
Low to moderate numbers of metarubricytes and polychromatophilic rubricytes are noted.
Rare mast cells are noted.
Occasional eosinophil is noted with oval nucleus, (possible eosinophilic myelocyte).
Occasional neutrophil, including band neutrophils are noted. Rare macrophage is noted with haem pigment in the cytoplasm.
Background contains moderate to high numbers of lymphoglandular bodies and moderate amount of debris.
How would you interpret these results?
Haematology results were within normal limits.
Biochemistry showed azotaemia (urea 21.7mmol/l; reference range 3-9.1mmol/l, creatinine 205µmol/l; reference range 59-138 µmol/l).
Ionised calcium was increased (1.71mmol/l; reference range 1.13-1.33mmol/l).
Urine analysis showed USG 1.011. Remaining results were unremarkable.
Urine culture was negative.
Lymph node cytology was most consistent with reactive hyperplasia – all nodes. Possible extramedullary haematopoiesis.
What is your updated problem list and the most likely causes of these abnormalities?
Problem list:
- Peripheral lymphadenopathy
- Azotaemia
- Ionised hypercalcemia
Azotaemia is most likely related to renal causes in this patient. This may be due to ionised hypercalcemia and/or underlying renal disease.
The ionised hypercalcemia together with the peripheral lymphadenopathy, certainly make lymphoma a strong differential.
However, the cytology of the peripheral lymph nodes was not consistent with lymphoma and was instead suggestive of reactive hyperplasia and extra-medullary hematopoiesis.