Unexpected diagnosis of canine lymphoma when performing an ultrasound-guided cystocentesis on a 3-year-old Rottweiler dog

Abstract

A 3-year-old spayed female Rottweiler dog was brought to a veterinary clinic because of weakness, lethargy, and hair coat changes. Hematology and clinical chemistry assessments revealed anemia, hypoalbuminemia, hyperglobulinemia, and hypothyroid. After persistent pyuria, an ultrasound-guided cystocentesis was completed, which revealed a large abdominal mass. A presumptive diagnosis of canine lymphoma with renal spread was made. Due to a poor prognosis, the dog was euthanized.

Case description

A 3-year-old spayed female Rottweiler dog was brought to a veterinary clinic with the primary complaints of hair loss and weakness of several weeks’ duration. Prior to the most recent episode, the dog was largely healthy; the only recurring issue was inconsistent mucoid discharge bilaterally from the eyes, which was presumed due to a slight bilateral entropion.

On initial examination, it was noted that the dog was thin [body condition score (BCS) 2/5] and had muscle wasting over the pelvis and through the quadriceps muscles. The dog had hair loss in tufts, scaly skin, and dandruff across her body, and was tense on abdominal palpation. There was also a hygroma evident on the right elbow. Hematologic and clinical chemistry assessments showed anemia [0.26 L/L; reference interval (RI): 0.37 to 0.61 L/L], hypoalbuminemia, hyperglobulinemia, and low total T4. A SNAP 4Dx Test (IDEXX) was negative for Dirofilaria immitis, Borellia burgdoferi, Ehrlichia canis, E. ewingii, and E. chaffeensis, as well as for Anaplasma phagocytophilum and A. platys. There were also target cells on a blood smear. The urinalysis showed specific gravity > 1.050, 4 to 5 WBC/high-power field (HPF), 4 to 5 RBC/HPF, and 4+ cocci (free-catch sample). At this point, differential diagnoses for the protein loss were lymphoma (intestinal versus renal) or renal protein loss (primary or secondary to a urinary tract infection). Differential diagnoses for hair loss were hypothyroid, allergy, or other. Further tests were recommended, including a free-T4 immunoassay to rule out euthyroid sick syndrome, and abdominal ultrasound to assess the structure of kidneys and intestines. These were declined due to financial constraints. The dog was started on a therapeutic treatment of L-thyroxine (Thyro-Tab 0.4 mg; Lloyd, Toronto, Ontario), 0.01 mg/kg BW, PO, q12h, for possible hypothyroidism; and a course of amoxicillin-clavulanic acid (Clavaseptin; Vetoquinol, Lavaltrie, Quebec), 18 mg/kg BW, PO, q12h for 7 d, for the urinary tract infection.

On follow-up examination 1 mo later, the dog had additional wasting of the temporalis muscles, the skin condition was largely unchanged from the previous visit, and the dog continued to be tense on abdominal palpation. Enlarged popliteal lymph nodes were also noted at this time. In addition, the dog had moderate bilateral conjunctivitis and a 3- to 4-millimeter corneal ulcer on the lateral aspect of the left eye. As well, mild entropion of the left eye was noted to be worse than the historic findings.

At the time of the recheck, a free-catch urine sample still showed pyuria on urinalysis, so a urine culture and sensitivity test was recommended and informed consent for ultrasound-guided cystocentesis was obtained. However, while locating the bladder in the caudal abdomen/groin region with the ultrasound probe, a large mass was identified. Based on the images, the mass appeared to be sitting adjacent to the aorta on the right side of the caudal abdomen. The dog’s kidney on that side was also very deformed in appearance (i.e., cystic-like; medullary cortex was not well-defined). The differential diagnoses for this mass included a lymph node, a renal lymphoma, or a mass of other abdominal origin (such as spleen). A tentative diagnosis of lymphoma with renal spread was made based on the clinical picture and in conjunction with the animal’s signalment, as Rottweilers are predisposed to developing lymphoma (1). The prognosis for renal lymphoma was poor to grave. Without immunohistochemical assessment to determine the type of lymphoma present, it was impossible to give a more accurate prognosis, but the median survival times (MST) for different types of lymphomas range from 5 mo to > 1 y depending on treatment, time of diagnosis, and lymphoma subtype (2).

Treatment options and prognosis were discussed with the client. However, due to a variety of factors, including financial constraints and quality of life, the client elected euthanasia as a humane alternative to treatment.

Discussion

Canine lymphoma (cL) is the most common malignant neoplasia in domestic dogs and one of the most commonly diagnosed diseases in small animal practice (3). Despite often being described as a single disease, cL is actually a large group of similar neoplasms that develop from lymphoid cells (3). Although any dog could potentially develop lymphoma, some breeds are predisposed; and beyond that, certain breeds may be more prone to developing a certain immunophenotype of lymphoma (1,3–5.) Due to the large body of information available in the literature concerning cL, it was possible for the clinicians in this case to provide sufficient information to the client concerning diagnosis, treatment options, and prognosis to achieve an acceptable standard of care.

Renal lymphoma can occasionally develop as a primary neoplasia, but < 20 such cases have been reported since 1954. Thus, without evidence to the contrary, it is reasonable to assume that this case of renal lymphoma occurred secondary to a multicentric lymphoma (5). Multicentric lymphomas typically affect middle-aged dogs and present with nonspecific clinical signs including lethargy, vomiting, weakness, polydipsia, and non-painful lymphadenopathy (3). Diagnosis is generally made with biopsies or fine-needle aspirates of affected lymph nodes submitted for cytological and/or immunohistochemical analysis (6). However, in some cases, due to financial or other constraints, a working diagnosis must be made using signalment, clinical presentation, and diagnostic imaging. Determining the immunophenotype of lymphoma is important for selecting the appropriate therapy and prognosis. This can be accomplished by flow cytometry to immunophenotype cells; however, since this is unavailable in many general practices, simple “in-house” cytology often remains the preferred diagnostic technique, despite its inferiority for subclassifying cL (7). Due to this, statistics are frequently used to determine the most likely immunophenotype of cL present in each case, and thus inform the choice of treatment. For this reason, it is vital to continue updating and refining the literature regarding cL subtypes so that clinicians can effectively treat animals despite financial, physical, or other constraints.

Treatment for cL is largely aimed at extending life rather than curing the disease. Therapies for lymphoma include chemotherapy, prednisone alone, or no treatment (2). Since Rottweilers are prone to developing B-cell-type lymphomas (3), a chemotherapy protocol for a multicentric B-cell lymphoma will be discussed. The current standard of care is a multi-agent protocol including hydroxydaunorubicin (doxorubicin) (4). This consists of weekly drug administrations that alternate between vincristine (0.7 mg/m² BW, IV), cyclosphamide [250 mg/m² body surface area (BSA), IV or PO], and doxorubicin (30 mg/m² BSA, IV), accompanied by prednisone starting at 2 mg/m² BSA, PO, q24h and tapering to none in 0.5 mg/m² BSA increments over the first 5 wk of treatment (8). There are several potential adverse effects of this therapy, including gastrointestinal signs (vomiting, diarrhea, hyporexia) as the most common, followed by neutropenia (8). Alternatively, prednisone (generally given at 2 mg/kg BW, PO, q24h) can be used alone as a palliative treatment option due to its effect of inducing apoptosis in lymphocytes (9).

In cases where chemotherapy is not pursued, palliative therapy consisting of daily oral prednisone is associated with a far shorter MST than any of the many chemotherapy protocols available (2,3,6). For a high-grade lymphoma, the MST with chemotherapy is 160 d, whereas the MST with prednisone alone is 60 to 90 d (2,3). Unfortunately, depending on progression of clinical signs, quality of life, financial considerations, and other factors, humane euthanasia is a very common outcome from a diagnosis of cL. Quality-of-life assessments should be made regularly, and end-of-life care should be appropriately planned for and provided.

Lymphoma is similarly a common disease in humans. Because of this, therapy protocols for cL are largely adopted from human medicine (10). The multi-agent chemotherapy protocol discussed above (CHOP protocol) is adapted from human lymphoma treatments, understanding the different pharmacokinetics and potential adverse effects in dogs. It has become the standard of care in the treatment of cL (3,8,10). However, treatment in humans will usually involve immunotherapy in addition to chemotherapy (10). Unfortunately, this is not currently a feasible approach in veterinary medicine. To make this possible moving forward, further genetic mapping and screening to identify high-risk groups in the canine population will need to become the norm (10). As immunotherapy is not commonly available for dogs, treatment is potentially less effective than might otherwise be possible.

This case consisted of a disparate and nonspecific collection of clinical signs that needed to be prioritized and investigated in such a manner as to maximize yield with the minimum cost. A reasonable order of tests was completed, but the tentative diagnosis was made coincidentally while carrying out an ultrasound-guided cystocentesis. Further conclusions and discussions with the client were based on the body of knowledge available in the literature. This case stands out as a prominent example of stepwise diagnostics and spectrum of care in general practice. In veterinary medicine, diagnostic and therapeutic plans must be individually tailored to the animal, the client, and the circumstances surrounding them. In cases where further diagnostic procedures or advanced treatments are not feasible, veterinarians must work with clients to discuss the probabilities and come to an evidence-based decision on how to proceed. This case demonstrates the importance of a widely accessible, current, and relevant body of literature. Without these resources, the standard of care would become difficult to uphold for all animals, as not every situation will allow for full diagnostic workups for every animal. In this case, the diagnosis of cL was made based on the statistical likelihood of the disease considering the signalment, presentation, and results of the limited diagnostic testing available.