In April 2022, an 11.5-year-old intact female Border Collie was presented after experiencing a single generalized seizure. In May 2022, the dog experienced a second seizure episode during which the owner measured the dog's glucose which was 1.5 mmol/l. Apart from these episodes, the dog was considered healthy and had not shown any signs of illness in the past year. In addition, the dog was also known to have biceps tendinopathy.
During the first presentation, the dog weighed 17.4 kg (BCS 5) and appeared clinically unremarkable, except for a slight bradycardia (heart rate: 54/BPM) and a 2/6 left-sided systolic heart murmur. Multiple fractured teeth were also observed.
Blood work revealed a moderate increase in liver enzymes (GPT 734 U/L, reference range: 17-78; ALP 157 U/L, reference range: 13-83) and mild thrombocytopenia (PLT 101 E3mul, reference range: 148-484) but was otherwise normal. Blood glucose at presentation was 4.2 mmol/L (reference range: 4.2-7.1). An abdominal ultrasound revealed a mildly enlarged and rounded liver with multiple small nodular areas with mixed echogenicity, sludge accumulation within the gallbladder, a small (19 mm diameter) heterogeneous cavitary lesion at the tail of the spleen, and a 9-mm sharply circumscribed, highly vascularized nodular structure in the left pancreatic branch. A single enlarged (7 mm) mesenteric lymph node with a heterogeneous echotexture in the cranial abdomen was also identified, along with multiple small mural cystic lesions and minimal intraluminal fluid in the uterus. Figure 1 shows the ultrasonographic findings of the pancreas and the enlarged lymph node. The ventrodorsal and right lateral thoracic radiographs were unremarkable.
The dog was then presented for work up at the Clinic for Small Animal Surgery, Vetsuisse Faculty, Zurich University. Helical CT scans were performed using a Philips Brilliance16 scanner (Philips AG, Zurich, Switzerland) for the thorax and abdomen, which were reconstructed using a soft tissue, bone, and lung algorithm for the thorax and a soft tissue and bone algorithm for the abdomen. A triple-phase CT scan of the abdomen was timed with bolus tracking in the descending aorta and reconstructed using a soft tissue algorithm, with 2 ml/kg Accupaque 350 (GE Healthcare, Glattbrugg, Switzerland) administered through a power injector (Accutron CT-D Medtron Injector, SMD Medical Trade GmbH, Salenstein, Switzerland). The images were reviewed on a workstation (IntelliSpace PACS 4.4 Radiology, Philips AG, Zurich, Switzerland), revealing a well-defined focal, round, soft tissue-attenuated nodule (1 cm in diameter) located in the caudal third of the left pancreatic branch. The nodule exhibited marked contrast enhancement during the arterial phase, with attenuation differing from normal pancreatic tissue, which equalized in the venous phase (early wash in late wash out). A lymph node (considered hepatic) was found to be mildly enlarged but showed normal contrast uptake. An intraparenchymal nodule measuring 2 cm with rim enhancement was detected in the body of the spleen. The liver presented with multiple ill-defined, hypoattenuating areas in all stages of contrast distribution. A small amount of mineral attenuating material occurred in the gallbladder. The uterus contained a single oval-shaped lesion in the left horn and minimal fluid.
Based on the imaging results, the suspected diagnoses were malignant insulinoma (with potential differential diagnoses of carcinoma) with concurrent lymphadenopathy (although a metastatic lesion was considered less likely), nodular hepatopathy (unspecific), a splenic lesion (hematoma, hyperplasia, or neoplasia), and an endometrial cyst.
Repeat blood glucose testing revealed a glucose level of 5.6 mmol/L. Despite a high suspicion of insulinoma, no additional insulin analysis was performed since the dog had euglycemia at presentation, and insulin concentration is only reliable during hypoglycemia (< 3.3 mmol/L). Surgery was recommended and scheduled for 10 days after the workup. Initial therapy involved administering 2 mg/kg of oral prednisone one time daily until surgery.
Anesthesia was induced using fentanyl (3 mug/kg IV) and alfaxalone (1 mg/kg IV Alfaxalon Multidose, Dr. Graeub AG, Bern) and maintained after endotracheal intubation using sevoflurane (Sevorane , AbbVie AG, Cham) delivered in oxygen. During surgery, analgesia was maintained by administering fentanyl (10 mug/kg/h, Fentanyl Sintetica, Sintetica, Mendrisio, CRI). In addition, the dog received lidocaine (30 mug/kg/h, Lidocaine HCL Bichsel, Bichsel AG, Interlaken, CRI) and dobutamine (2.5 mug/kg/min, Dobutrex , Teva AG, Rapperswil). At induction, the blood glucose level was 3.7 mmol/L.
After performing a standard coeliotomy, the mass in the pancreas was visualized, and a complete inspection of the abdomen was conducted. Apart from the jejunal (1.5 x 1.5 x 0.5 cm) and right colic lymph nodes (1.5 x 1 x 0.5 cm), one additional node was identified between the pancreas and the stomach (the duodenal lymph node, 1.4 x 0.8 x 0.3 cm). Subsequently, 0.2 ml of ICG (2.5 mg/kg, Verdye, Diagnostic Green GmbH, Kirchheim) was injected into the tumor. Lymphatics became visible within seconds (Supplementary Video 1, Visionsense, VS3 Iridium, Medtronic, Switzerland), resulting in the identification of a total of six draining nodes, including the three nodes previously identified prior to injection, as well as the right (0.6 x 0.4 x 0.4 cm) and left hepatic nodes (0.2 x 0.2 x 0.2 cm) and a splenic node (0.5 x 0.5 x 0.5 cm) (please refer to Figure 2).
All nodes were removed using a ligature (LigaSureTM Small Jaw Instrument, Medtronic, Switzerland). The ligature also removed the pancreatic mass through an en-bloc resection of the left branch of the pancreas. After completion of the lymphadenectomies, blood glucose was measured at 4.1 mmol/L. Blood glucose levels were recorded again after partial pancreatectomy and were found to be 5.9 mmol/L and 6 mmol/L at the end of surgery. Liver biopsies were taken from the left and central lobes of the liver, where nodular areas were visible. Finally, a splenectomy and an ovariohysterectomy were performed. The total surgical time was 68 m (the total anesthesia time was 145 m).
Before wound closure, 2 mg/kg ropivacaine (total volume 4.3 ml; Ropivacaine Sintetica, Sintetica, Mendrisio) was administered into the abdomen. Postoperative analgesia was maintained using methadone 0.1 mg/kg IV (Methadon Streuli, Streuli Pharma AG, Uznach) q4 h for 24 h and metamizole (Minalgin, Streuli Pharma AG, Uznach) 25 mg/kg IV q8 h for 24 h, followed by oral administration for 7 days. Prednisone was gradually tapered by administering 0-5 mg/kg every other day for two additional doses. The dog remained hypoglycemic after surgery and was stable enough to be discharged the following day.
Histopathologic examination confirmed the presence of a well-demarcated and densely cellular neoplasm with a diameter of 15 mm, surrounded by a fibrous capsule invaded by neoplastic cells. The mitotic rate was low (1 in 10 HPF), and immunohistochemistry was negative for CAM-5.2 and strongly positive for anti-insulin, leading to a final diagnosis of malignant insulinoma. No signs of lymph node metastasis were detected (Stage I). The splenic lesion was diagnosed as nodular hyperplasia and the liver lesions as vacuolar hepatopathy.
The dog's recovery was unremarkable, and up until the time of drafting the manuscript, no further seizures or hypoglycemic episodes were detected. A timeline with progression of the case is depicted in Figure 3.