Spontaneous mural gallbladder hematoma in a dog

Abstract

A 12-year-old spayed female Maltese dog was evaluated because of a 12-hour history of vomiting, mucoid diarrhea, and anorexia. There was no history of trauma or injury. Abdominal ultrasound revealed a well-defined mass associated with the gallbladder. Abdominal computed tomography (CT) confirmed a non-contrast enhancing mass emanating from the gallbladder wall causing separation of the serosal and mucosal margins. Exploratory celiotomy followed by cholecystectomy was performed. Histology of the gallbladder mass was consistent with a mural hematoma and there were no signs of significant inflammation or neoplasia present. The patient remained clinically normal in the 3 months after surgery and is reported to be alive and well 4 years after the procedure.

Key clinical message:

To the author’s knowledge, this is the first reported case of a spontaneous mural hematoma of the gallbladder in the veterinary literature.

Case description

A 12-year-old spayed female Maltese dog was referred to the University of Florida Small Animal Emergency and Critical Care service because of a 12-hour history of vomiting, mucoid diarrhea, and anorexia. The owners reported no history of trauma, injury, or drug/toxin exposure. Abnormalities observed on complete blood (cell) count (CBC) and serum chemistry tests performed at the referring veterinarian’s clinic included: a platelet concentration of 654 × 10³/μL [reference range (RR): 147 to 423 × 10³/μL], serum potassium of 3.4 mmol/L (RR: 3.8 to 5.3 mmol/L), serum chloride of 94 mmol/L (RR: 102 to 120 mmol/L), alanine aminotransferase (ALT) > 1000 U/L (RR: 21 to 97 U/L), alkaline phosphatase (ALP) 531 U/L (RR: 15 to 164 U/L), and gamma-glutamyl transferase (GGT) 48 U/L (0 to 5 U/L). Treatment at the referring veterinarian comprised buprenorphine (Buprenex; Reckitt Benckiser, Slough, UK) 0.02 mg/kg body weight (BW), IM and acepromazine (PromAce; Boehringer Ingelheim Vetmedica, St. Joseph, Missouri, USA), 0.03 mg/kg BW, IM, maropitant (Cerenia; Zoetis, Parsippany, New Jersey, USA), 1.2 mg/kg BW, SC, and famotidine (Pepcid; Merck & Co., Kenilworth, New Jersey, USA), 1.2 mg/kg BW, SC, vitamin B12 (Cyanocobalamin; Rochem International, Hauppauge, New York, USA), 0.08 mg/kg BW, IM, and Lactated Ringers Solution (Medline, Tolleson, Arizona, USA), 30 mL/kg BW, SC, before referral.

On presentation at the University of Florida, the dog was bright, alert, and responsive. On physical examination, rectal temperature was 38°C, heart rate was 140 beats/min, and respiratory rate was 40 breaths/min. Mucous membranes were pink and capillary refill time was < 2 s. The patient had a body condition score of 8/9. Additional findings were: sinus arrhythmia, soft abdomen on palpation, and mild conscious proprioceptive placing deficits in the right hind limb. These proprioceptive deficits were presumed secondary to a C4–C5 ventral slot procedure, which was performed 3 mo before presentation.

On abdominal ultrasound, a well-defined, round, heterogenous mass within the right division of the liver, which measured 1.7 cm in diameter, appeared to be causing compression of the gallbladder. The mass did not appear to be vascularized on color Doppler flow. Hepatocellular carcinoma and biliary carcinoma were considered most likely, with hepatoma, extramedullary hematopoiesis, and hematoma, gallbladder carcinoids, and gallbladder mural mass being less likely (Figure 1). Additionally, there were multiple well-defined, round, hypoechoic nodules throughout the liver, measuring up to 6 mm in diameter. Within the splenic parenchyma, along the visceral margin, a well-defined, oval, hyperechoic nodule was present, measuring 2.4 mm in length. Fine-needle aspirates were obtained of the liver mass and nodules, with no evidence of complications. The gastric and pyloroduodenal lymph nodes were mildly rounded, heterogenous, and enlarged, measuring up to 5 mm in height. The cranial aspect of the right lobe of the pancreas was mildly hyperechoic, with normal margins, shape, and peripancreatic mesentery.

Figure 1.

Abdominal ultrasound showing a well-defined, round, heterogenous mass within the right division of the liver, which measured 1.7 cm in diameter and was causing compression of the gallbladder.

The dog was discharged awaiting fine-needle aspirate results and was prescribed 27 mg/kg BW S-adenosylmethionine with 2.7 mg/kg BW Silybin (Denamarin; Nutramax, Lancaster, South Carolina, USA) and maropitant (Cerenia; Zoetis), 2.4 mg/kg BW, PO, q24h. The diagnosis at the time of discharge was primary neoplasia of hepatic or biliary origin, although the possibility of a gallbladder mural mass could not be excluded based on the ultrasound alone.

The dog was taken to the Emergency and Critical Care service the next day because of continued anorexia and a new onset of mucoid diarrhea. At this time, the dog was admitted for extended care.

Pertinent abnormalities comprised an ALP of 650 U/L (RR: 8 to 114 U/L), an ALT of 1845 U/L (RR: 18 to 64 U/L), and an AST of 63 U/L (RR: 15 to 52 U/L). All other chemistry values were within the normal reference ranges. On blood gas analysis, pH was 7.476 and pCO₂ was 26.2 mmHg.

Treatment at this stage comprised maropitant (Cerenia; Zoetis), 1 mg/kg BW, IV, q24h and Plasmalyte 148 with 20 mEq KCl/L (Medline), 60 mL/kg BW, IV/day. Metronidazole (Flagyl; Pfizer, New York, New York, USA) was also given at 10 mg/kg BW, IV, q12h to treat empirically for clinical signs consistent with large bowel diarrhea. N-Acetylcysteine (Acetodote; Cumberland Pharmaceuticals, Nashville, Tennessee, USA) was given at 70 mg/kg BW, IV, q6h to treat for possible acetaminophen toxicity, although there was a very low likelihood of such exposure. The dog was kept on this protocol, with the addition of acepromazine (PromAce; Boehringer Ingelheim), 0.02 mg/kg BW, IV, as needed for anxiety, throughout the weekend and was transferred to the oncology department at the beginning of the week for further evaluation of suspected neoplasia of hepatic or biliary origin.

An abdominal CT scan was performed 72 h after initial presentation. In the gallbladder, there was an approximately 19 mm × 24 mm × 16 mm soft tissue attenuating, non-contrast enhancing mass that emanated from the gallbladder wall causing separation of the serosal and mucosal margins. The result was the impression of an eccentric, non-circumferential, well-defined mass within the wall of the gallbladder (Figure 2). The regional lymph nodes were within normal limits.

Figure 2.

An abdominal CT scan showing a 19 mm × 24 mm × 16 mm soft tissue attenuating, non-contrast enhancing mass that emanated from the gallbladder wall.

Based on the findings, a gallbladder wall mass originating from the muscularis was suspected as the most likely diagnosis; however, benign etiologies such as hematoma could not be ruled out. Surgical cholecystectomy was recommended. A CBC and serum biochemistry were repeated 72 h after the initial blood analysis and revealed a packed cell volume of 39% (RR: 41% to 60%), total protein of 68 g/L (RR: 57 to 79 g/L), and a platelet concentration of 610 × 10³/μL (RR: 147 to 423 × 10³/μL). Serum chemistry abnormalities included an ALP of 367 U/L (RR: 15 to 164 U/L), ALT of 590 U/L (RR: 21 to 97 U/L), and blood urea nitrogen 0.7 mmol/L (RR: 2.9 to 8.9 mmol/L), glucose 7.4 mmol/L (RR: 4.4 to 6.7 mmol/L). Since the liver enzyme values had improved and clinical signs had resolved, the owners were given the option of continuing medical therapy and monitoring the patient for improvement. The owners elected to proceed with surgery and the patient was scheduled for cholecystectomy and liver biopsies.

The gallbladder was removed via blunt dissection and cautery and two 5-mm punch biopsies were taken of the nodules on the right medial liver lobe (Figures 3, 4).

Figure 3.

Intra-operative photograph showing the gallbladder hematoma and right medial liver lobe nodules.

Figure 4.

Post-operative photograph showing the gallbladder hematoma.

Histopathological evaluation of the liver nodules identified nodular hyperplasia. The gallbladder lumen contained a dark red to black gelatinous material approximately 19 mm × 24 mm × 16 mm in size. Segmentally, separating the serosa and smooth muscle layers of the wall was a focal large lake of hemorrhage that subtly blended into a small amount of granulation tissue and the lamina propria. Small numbers of lymphocytes, plasma cells, and macrophages infiltrated the lamina propria. The gallbladder mass was diagnosed as a mural hematoma.

Recovery was uneventful and the patient was discharged the following day. Post-operative medications included amoxicillin and clavulanic acid (Clavamox; Zoetis), 19.5 mg/kg BW, PO, q12h for 7 d and tramadol (Ultram; Johnson & Johnson, New Brunswick, New Jersey, USA), 3.8 mg/kg BW, PO, q6 to 8h as needed for pain. The patient remained clinically normal in the 3 mo after surgery and is reported to be alive and well 4 y after the procedure.

Discussion

Based on presenting complaints, initial serum chemistry values combined with ultrasound and CT imaging, and the lack of trauma, this patient was believed to have a gall bladder tumor. Adenomas are the most common benign tumors associated with the gallbladder (1) and gallbladder carcinomas are the most common malignant tumors (2). Hemobilia and hemoholecyst secondary to gallbladder carcinoids have been reported in only 2 cases in dogs (3); these patients exhibited upper gastrointestinal bleeding, abdominal pain, and extrahepatic biliary duct obstruction resulting in jaundice. Diagnosis in both of these patients was made on histopathology of the gallbladder. Bile duct carcinoma of the gallbladder is rare and associated with high rates of systemic metastasis: in 1 study, almost 90% of cases presented with systemic metastasis with lymph nodes, lungs, and peritoneum representing the most common sites (4). Surgical excision is the treatment of choice for bile duct tumors (5,6) {Morrell, 2002, A carcinoid tumor in the gallbladder of a dog}, although local recurrence or distant metastasis is expected within 6 mo after therapy (4).

Anaphylaxis may also be a consideration given the imaging findings. Although gallbladder hematoma has not been reported in canine anaphylaxis, it may be possible following the massive release of histamine and resulting hepatic venous congestion that occurs when dogs experience anaphylaxis (7). This is an unlikely cause in this case due to the dog’s bright clinical presentation with no signs of shock, as well as no gallbladder wall edema found on histopathology.

In the case reported here, the improving liver enzyme activities over 72 h were surprising considering the suspected diagnosis. A conservative approach was offered to the owner, which included continuing medical management and repeat abdominal ultrasound. Despite this, the owners elected to proceed with the exploratory celiotomy and cholecystectomy.

Mural gallbladder hematomas are rare in humans (8,9) and, to the authors’ knowledge, have not been reported previously in the veterinary literature. In humans, gallbladder hematomas are often associated with blunt force or iatrogenic trauma (10–12). In this patient, there were no skin abrasions, areas of swelling, or bruising to suggest a blunt trauma event. No pain could be elicited at any point during the physical examination. The owners also stated that the patient was never outside unattended and had not become loose prior to the onset of symptoms. She also had not undergone a recent surgical abdominal procedure. Due to these reasons, trauma was ruled out as a cause of the hematoma. Medical causes of gallbladder hematoma include cholecystitis, cholelithiasis, hepatic or biliary tumors, vascular abnormalities, or coagulopathy (13,14). In this case, the reduction in liver enzyme activities with metronidazole treatment may support the possibility of cholecystitis; however, this is considered doubtful in the absence of neutrophilic inflammation within the gall bladder. In humans, rupture of an aneurysm of the hepatic or cystic artery has been a rare yet reported cause of hemocholecyst (15,16).

Since spontaneous hematoma was not a top differential prior to surgery, no coagulation testing was done on this patient. Clinically significant coagulopathy as the main cause of the gallbladder hematoma was less likely considering the unremarkable physical examination, the stable blood parameters, the lack of unexpected hemorrhage during and following surgery, and the excellent recovery of this patient. There was no evidence of trauma or tissue damage that could explain this patient’s thrombocytosis; therefore, a physiologic response due to inflammatory conditions was the most likely explanation for the thrombocytosis in this case.

In humans, intramural hematomas have been reported to resolve within 3 to 6 mo (17). Because the liver enzyme values had improved, and the clinical signs resolved, it is possible that the dog herein would have had a successful outcome without cholecystectomy. However, intramural gallbladder hematomas can mimic any of the diseases previously discussed that result in the appearance of echogenic masses within the lumen of the gallbladder (8,9,18). Therefore, a definitive diagnosis of gallbladder hematoma cannot reliably be made from imaging alone.

For a patient with signs highly suspicious for a mural gallbladder hematoma that is otherwise stable, medical management may be acceptable. With this case report, a benign differential can be added to the list when discussing disease potential with pet owners. However, in this patient’s case, neoplasia was suspected and could not be ruled out, even though liver enzyme values were improving. In such cases, exploratory laparotomy and potential cholecystectomy is recommended (6). CVJ