Alimentary lymphosarcoma in a 4-year-old Labrador retriever

Abstract

Lymphosarcoma, a common canine hematopoietic neoplasm, occurs in multicentric, alimentary, mediastinal, and extranodal forms. Alimentary lymphoma accounts for approximately 5% of cases and is less easily diagnosed than the more common multicentric form. Chemotherapy is often effective, but recent therapeutic advances hold great promise for success in treating canine lymphoma. A 4-year-old, black Labrador retriever was presented (day 1) with a 2-day history of vomiting, polyuria/polydipsia, lethargy, and anorexia. The heart and respiratory rates were within normal limits, and the rectal temperature was 38.9°C. Abdominal splinting was noted on palpation, which elicited urination. No obvious additional abnormalities were detected.

A 4-year-old, black Labrador retriever was presented (day 1) with a 2-day history of vomiting, polyuria/ polydipsia, lethargy, and anorexia. The heart and respiratory rates were within normal limits, and the rectal temperature was 38.9°C. Abdominal splinting was noted on palpation, which elicited urination. No obvious additional abnormalities were detected.

An in-clinic fecal flotation and a complete blood (cell) count (CBC), serum biochemical profile, and urinalysis were performed. The fecal flotation was negative for parasitic ova or cysts, and no abnormalities were noted on the CBC. The urine was hyposthenuric, with a specific gravity of 1.004, but other urinalysis results were unremarkable. The urea and creatinine levels were within normal limits. Serum biochemical abnormalities included hypoalbuminemia (21 g/L; reference range, 25 to 36 g/L), low total protein (54 g/L; reference range, 55 to 76 g/L), hypocalcemia (2.09 mmol/L; reference range, 2.12 to 2.54 mmol/L), and high alkaline phosphatase (154 IU/L; reference range, 11 to 140 IU/L). The differential diagnoses included transient gastrointestinal insult, such as dietary indiscretion, and protein-losing enteropathy. The animal was prescribed a bland diet and released, with instructions to owner to return if no improvement was noted. On day 4, the owners reported improvement, so plans were made to continue the bland diet while gradually reinstating the regular food. The owners were advised of the need to reassess the total serum protein and albumin levels at a later date.

On day 10, the animal was presented to the clinic with diarrhea and tenesmus of 1 day’s duration. The dog had lost 1.8 kg of bodyweight (BW), and appeared lethargic and bloated. The abdomen was very distended, with no obvious palpable masses. Ascites was suspected. The respiratory rate was within normal limits; however, the heart rate was elevated at 132 bpm and rectal temperature was 40.0°C. A CBC and biochemical analysis revealed mild leukocytosis (21.9 × 10⁹ cells/L; reference range, 6.0 to 17.0 × 10⁹ cells/L) with mature neutrophilia (18.4 × 10⁹ cells/L; reference range, 2.9 to 10.6 × 10⁹ cells/L) and lymphopenia (0.2 × 10⁹ cells/L; reference range, 0.8 to 5.1 × 10⁹ cells/L), consistent with stress or an acute inflammatory process. The hypoalbuminemia persisted (21 g/L); however, total serum protein had increased slightly to 55 g/L. Alkaline phosphatase had returned to normal limits, alanine amino-transferase was slightly decreased (14 IU/L; reference range, 16 to 90 IU/L), and serum phosphorus was elevated (1.81 mmol/L; reference range, 0.55 to 1.45 mmol/L).

Protein-losing enteropathy was still suspected, so lateral and ventrodorsal abdominal radiographs were taken to assess the liver, verify the source of the abdominal distension, and screen for foreign bodies. Radiographs revealed large amounts of gas in the bowel and an incomplete loss of detail, attributed to fluid in the abdomen. It was also noted that the bowel appeared bunched upon itself. In order to better assess these findings, abdominal ultrasonography was performed. This verified the presence of free fluid in the abdomen; it was also detected in the caudal part of the abdomen, a mass approximately 3.6 cm × 3.6 cm, filled with fluid and gas, which resembled extremely thickened bowel.

Abdominocentesis was performed by using the four-quadrant approach to evaluate the source of the abdominal fluid, and approximately 3 mL of serosanguineous fluid was recovered. Cytological analysis of the fluid revealed predominantly toxic neutrophils, a few macrophages, and rod-shaped bacteria, both free and engulfed within phagocytic cells. Accordingly, on the suspicion of a ruptured bowel, the animal was treated with amoxicillin (Amoxi-Inject [Dogs and Cats]; Pfizer Animal Health, Exton, Pennsylvania, USA), 22 mg/kg BW, SC, and enrofloxacin (Baytril 2.27%; Bayer, West Haven, Connecticut, USA), 4.95 mg/kg BW, IM. The dog was immediately prepared for exploratory laporotomy.

At surgery, the omentum and the serosal surface of the jejunum appeared extremely hyperemic. A solid, white, round mass, 12 cm in diameter, was observed surrounding the distal jejunum, with adhesions extending to adjacent bowel and omentum. The destruction caused by the mass was suspected to be the cause of bowel rupture; the affected jejunum and approximately 10 cm of necrotic bowel on either side of the mass were resected. The remaining jejunum and ileum were anastomosed by using 3-0 polydioxanone (PDS Elhicon, Somerville, New Jersey, USA) in a simple interrupted pattern. Biopsies of the mass were placed in 10% buffered formalin and submitted for histopathological analysis. The abdominal cavity was lavaged with 1.0 L of sterile normal saline 3 times before closing.

From day 10 to day 12, the dog was maintained on lactated Ringer’s solution, 3 mL/kg BW/h, IV; amoxicillin, 22 mg/kg BW, SC, q12h; and enrofloxacin, 5 mg/kg BW, IM, q12h. By day 12, the dog appeared to have recovered: the rectal temperature was 39.1°C and the appetite had returned. Medication was changed to amoxicillin (Amoxil; SmithKline Beecham Pharmaceuticals, Philadelphia, Pennsylvania, USA), 27.5 mg/kg BW, PO, q12h, and enrofloxacin, 3.8 mg/kg BW, q24h for 10 d. Sucralfate (Watson Laboratories, Corona, California, USA), 27.5 mg/kg BW, PO, q8h, and cimetidine (Tagamet; SmithKline Beecham Pharmaceuticals), 8.3 mg/kg BW, PO, q8h for 7 d, were prescribed for gastro-protection, and carprofen (Rimadyl; Pfizer), 2.1 mg/kg BW, PO, q12h for 3 d, was prescribed for analgesia. The dog was discharged from the hospital on day 12, with instructions to the owner to return in 7 d for reevaluation and suture removal.

The results of the biopsy indicated high grade alimentary lymphoma (lymphosarcoma, malignant lymphoma) with a poor long-term prognosis. On day 15, the dog was returned to the clinic and was euthanized because of lethargy, bloody diarrhea, and vomiting. On postmortem examination, numerous multifocal, solid, white nodular masses were observed in the kidneys, liver, spleen, heart, diaphragm, and stomach, as well as throughout the small intestine. Mesenteric and mediastinal lymph nodes were not evaluated. Impression smears from the cut surfaces of several lesions revealed lymphoid cells with large hyperchromatic nuclei, prominent nucleoli, and frequent mitotic figures. These findings were consistent with a diagnosis of widely metastasized lymphoma.

The prevalence of lymphoma in canines is approximately 13 to 30 cases per 100 000 dogs (1,2), which accounts for approximately 8.5% to 9% of all canine tumors (3). Four anatomical variations of canine lymphoma have been described: multicentric, alimentary, mediastinal, and extranodal (2). The multicentric form is most common, accounting for 84% of all cases (2). Affected dogs most often present with a generalized, nonpainful peripheral lymphomegaly, which is attributed to large numbers of malignant lymphocytes (2). Depending on the stage of disease when the animal is assessed, these lymphocytes may have infiltrated other organs, causing dysfunction. The alimentary form of canine lymphoma is much less common and accounts for approximately 5% of all cases (2,4). As in this case, vomiting, diarrhea, anorexia, and hypoalbuminemia are commonly associated with the alimentary form of lymphoma, in which malignant lymphocytes proliferate segmentally or diffusely within the submucosa and lamina propria of the small intestine (4). Metastases are frequent, often involving the liver, spleen, and kidneys (2). Intestinal lymphoma may therefore occur either as a primary phenomenon, as was likely in this case, or as an extension of other forms of lymphoma.

Multicentric lymphoma may be easily diagnosed clinically on the basis of generalized lymphomegaly. Fine needle aspirates of enlarged lymph nodes contain monomorphic populations of malignant lymphocytes. A CBC and serum biochemical analysis, as well as abdominal and thoracic imagining, should be performed to screen for metastasis (5,6). In contrast, alimentary lymphoma is much harder to diagnose. The lack of peripheral lymph node involvement (4) and nonspecific clinical signs suggest a wide range of more common differential diagnoses. Results of CBC and serum biochemical results are largely nonspecific (8) and, with the exception of hypercalcemia, tend to reveal evidence of secondary organ damage. Lymphoma is the most common cause of hypercalcemia of malignancy, which occurs in approximately 20% of affected dogs (7). Observation of hypercalcemia and clinical signs consistent with intestinal malignancy should raise the index of suspicion for alimentary lymphoma. Endoscopy may reveal mucosal erosions and ulcerations or an abnormally thickened or bumpy mucosa (4). As in this case, a definitive diagnosis may be made by biopsy of affected intestine, which reveals a monomorphic population of large lymphoblastic cells.

Histologically, lymphoma may be graded as low, intermediate, or high. A high grade lymphoma generally responds best to chemotherapy, yet patients with high grade lymphoma experience shorter survival times than those with low grade lymphoma (2). Additional indicators of a poor prognosis include the presence of systemic illness (World Health Organization clinical substage B), tumors of T lymphocytes, and dogs with diffuse alimentary, central nervous system, cutaneous, or intrathoracic disease (2).

Lymphoma is usually quite responsive to chemotherapy, the most widely used therapeutic option. No standard protocol has been settled on for the treatment of lymphoma; however, multiple-agent therapies appear to generate the most favorable results, with response rates of 88% to 96% and median survival times of 350 to 356 d (6). Three types of protocols are of importance in treating lymphoma: the induction protocol, the maintenance protocol, and the rescue protocol (used when the patient comes out of remission). The combination of L-asparginase, vincristine, cyclophosphamide, and doxyrubicin is a commonly used, highly successful induction protocol. The addition of doxyrubicin to a regime appears to significantly increase survival times (9). Despite the relative success of chemotherapy in this disease, lymphoma is almost invariably fatal, and new treatment strategies are constantly being developed to improve survival time and quality of life. Recombinant immunotoxins, such as the diphtheria toxin targeted towards receptors expressed on malignant lymphocytes, are already in use in humans for treatment of cutaneous T-cell lymphoma and hold promise for future treatment of canine lymphoma (2). Monoclonal antibodies targeted towards cell surface markers on malignant lymphocytes represent another promising future treatment (2). The perfection of these technologies may hold the key to extending the quality and length of life of patients affected with lymphoma; however, for the time being, the mainstay of most treatment protocols still relies upon the use of chemotherapeutic agents. CVJ