Q & A: Unexplained Hypercalcemia in a Middle-Aged Boxer Dog

My patient is an 8-year-old F/S Boxer, F/S, 8.5 years, 58.2 lb. The owners main presenting complaint was excessive thirst and urination, poor appetite, and occasional urinary accidents.

My physical examination was noncontributory. Results of a complete blood count and serum chemistry panel were normal except for hypercalcemia (14.6 mg/dl) with a high-normal phosphorus (4.9 mg/dl). The urine specific gravity was 1.008. Results of a urine culture was negative.

An abdominal ultrasound revealed an irregularly shaped left kidney with 2-3 mm calculi in renal pelvis. No other abnormalities in abdomen noted.

I repeated the serum total and ionized calcium which confirmed hypercalcemia. The total calcium was 14.9 mg/dl with a high ionized calicum of 3.72 mmol/L (normal, 2.2-3 mmmol/L). A serum PTH concentration was low at 0.4 pmol/L (reference range, 0.5-5.8 pmol/L).

Based on the high calcium with low serum PTH values, I'm worried about hypercalcemia of malignancy. I'm not sure where the cancer could be hiding, but the only place that I haven't looked is in the chest. Your thoughts?

My Response:
The thorax would certainly be a good place to look for un underlying malignancy. Did the peripheral lymph nodes all palpate normally? Did you check the anal glands for tumors?

You might also want to run a serum parathyroid hormone-related protein (PTHrp) level to help diagnose or exclude hypercalcemia of malignancy (1). If the PTHrP is positive, it's strongly suggestive for malignancy but it cannot tell you what the cancer is located.

If the dog does not have any lymphadenopathy or anal gland tumors, then you might want to do the following to help rule out lymphosarcoma:

• take chest radiographs, looking for a mediastinal mass
• aspirate multiple peripheral lymph nodes, even if not enlarged
• aspirate liver and spleen while doing an ultrasound exam, even if they're not grossly abnormal
• do a bone marrow aspirate

Follow-up and Diagnosis:
I repeated the physical examine and found that the dog had lost 2 more pounds. The dog's lymph nodes all palpated normally and no anal gland tumors were found. The chest films were normal, with no masses found.

I referred the dog to an oncologist who did fine needle aspirate and PCR testing on an slightly enlarged prescapular lymph nodes. This was diagnostic for lymphoma and PCR indicated primarily B cell lymphoma (with a T cell component).

The dog was also started on prednisone, which normalized the serum calcium concentration within 2 days. We also started on a 20-week course of a COAP chemotherapy protocol (2) with includes the following agents: cyclophosphamide (Cytoxan), vincristine (Oncovin), cytosine arabinoside (Cytosar-U), and prednisone.

Outcome:
This dog had the 20 weeks of chemotherapy and the lymphoma remained in remission. The serum total and ionized calcium concentrations continue to be normal when rechecked at the 20-week recheck.

References:

1. Kubota A, Kano R, Mizuno T, et al. Parathyroid hormone-related protein (PTHrP) produced by dog lymphoma cells. Journal of Veterinary Medical Science 2002: 64:835-837.
2. Rebhun RB, Kent MS, Borrofka SA, et al. CHOP chemotherapy for the treatment of canine multicentric T-cell lymphoma. Veterinary Comparative Oncology 2011: 9: 38-44.