Hemoperitoneum caused by the rupture of a granulosa cell tumor in a Holstein heifer

Abstract

A case of a hemoperitoneum caused by the rupture of a granulosa cell tumor in a 9-month-old Holstein heifer is reported. Management of hemorrhagic shock in cattle is discussed.

A 9-month-old Holstein heifer (290 kg) was referred (day 1) to the Centre Hospitalier Universitaire Vétérinaire (CHUV) at the Université de Montréal with clinical signs of sudden weakness, cold extremities, and tachycardia, identified by the referring veterinarian 3 h before presentation. The heifer was able to stand but preferred to remain recumbent. No treatment was instituted at the farm and the animal was referred immediately.

Physical examination revealed the following problems: weakness, pale mucous membranes, tachycardia (180 beats/ min), dehydration (estimated to be 8%), increased capillary refill time (>4 s), normal respiratory rate (36 breaths/min) but deep breathing, cold extremities, and abdominal pain. The rectal temperature was 39.3°C. On transrectal palpation, the uterine horns appeared enlarged (2.5 to 3 cm) and flaccid for an animal of this age. A 5- to 7-cm diameter mass was present on the right ovary. The dimensions of the left ovary were considered to be normal; the ovary was without functional structure

The results of ancillary tests performed upon arrival at the CHUV included measurement of packed cell volume (PCV: 0.21 L/L, reference range: 0.24 to 0.46 L/L) and total protein concentration (TP: 70 g/L, reference range 60 to 80 g/L); an arterial blood gas analysis that was compatible with respiratory alkalosis (pH: 7.46, reference range: 7.35 to 7.45; PaCO₂: 34.2 mmHg, reference range: 35 to 53 mmHg; HCO₃⁻: 24.5 mmol/L, reference range: 20 to 28 mmol/L); hypokalemia (3.5 mmol/L, reference range 3.83 to 4.45 mmol/L); hypochloremia (91 mmol/L, reference range: 99.3 to 113.7 mmol/L); and hypocalcemia (serum ionized calcium: 0.24 mmol/L, reference range: 0.54 to 0.99 mmol/L).

Before performing further diagnostic procedures, the animal was stabilized by administering, IV, 250 mL of hypertonic saline (5% NaCl) followed by 10 L of sterile saline (0.9% NaCl) supplemented with calcium (500 mL of 23% calcium borogluconate; Vétoquinol, Lavaltrie, Québec). At this time, the differential diagnoses were hypovolemic shock caused by the rupture of an ovarian cyst or an ovarian tumor; laceration of the spleen or liver; or a mesenteric aneurysm or hematoma. Ultrasonography of the abdomen was performed. Peritoneal fluid was abundant, and abdominocentesis revealed a large quantity of blood. A tentative diagnosis of hemoperitoneum was made.

Initially, medical treatment was attempted. After the administration of fluids, the PCV and TP concentration had decreased to 0.15 L/L and 36 g/L, respectively. A whole blood transfusion (6 L) was administered (3.3 mL/kg body weight [BW]/h), IV. Oxytetracycline (Oxytetracycline hydrochloride, Oxymycine LP; Ayerst, Guelph, Ontario), 10 mg/kg BW, IV, q12h, and ketoprofen (Anafen; Merial, Baie D’Urfé, Québec) 900 mg, IV, were also given. The animal was then left to be quiet and observed regularly (q30min) for the rest of the night.

Six hours later, the heifer was brighter and her appetite had improved. Pack cell volume and serum TP concentration had increased to 0.17 L/L and 47 g/L, respectively. Venous blood gas analysis results were within normal limits. The heart rate (120 beats/min) had drastically decreased, although it was still elevated, while the rectal temperature (39.0°C) and the respiratory rate (28 breaths/ min) were considered normal. During the day, the heart rate was monitored every hour and remained stable (120 beats/min). The PCV and TP concentration were evaluated every 6 h. By the end of the day, the PCV and TP had increased to reach a value of 0.20 L/L and 56 g/L, respectively.

By day 2, the heifer’s general status had deteriorated. She was severely depressed and could rise only with assistance. She appeared uncomfortable while in sternal recumbency, continuously shifting from side to side. The heart rate was elevated (160 beats/min) and the extremities were cold. Rectal temperature had decreased from 39.4°C to 38.3°C between 08:00 and 10:00. Pack cell volume and TP concentration had decreased to 0.17 L/L and 40 g/L, respectively. A whole blood transfusion (6 L) from a different donor was initiated (20 mL/kg BW/h), IV. Despite the blood transfusion, the heifer’s status continued to deteriorate rapidly. The clinical signs and ancillary test results suggested that the abdominal bleeding was still present. At this time, the heifer was prepared for an emergency right flank laparotomy in an attempt to control the abdominal bleeding. The surgery was performed with the animal in left lateral recumbency. Local anesthesia was used (Lidocaine 2%, Lurocaïne; Vétoquinol). A 3rd whole blood transfusion (6 L) was prepared from another donor and administered in combination with 20 L of lactated Ringer’s solution at the beginning of the surgery. During abdominal exploration, the liver, abomasum, spleen, and kidneys were palpated and considered normal. A 6- × 6-cm mass was identified and visualized on the right ovary. When exteriorized, a continuous faint oozing of blood was evident from the mass. Three transfixed ligatures were placed on the ovarian pedicle and an ovariectomy was performed using a chain écraseur (Jorvet; Jorgensen Laboratories, Loveland, Colorado, USA). The abdominal cavity was lavaged rapidly with 10 L of sterile saline (0.9% NaCl) solution before closure. Flunixin meglumine (Influx-50; P.V.U., Calgary, Alberta), 1 mg/kg BW, and oxytetracycline hydrochoride (Oxymycine LP; Ayerst), 10 mg/kg BW, were administered, IV, after surgery.

The animal’s general status improved rapidly after the surgery. The heifer was discharged from the hospital on day 5. The heart rate was normal (76 beats/min) and the PCV and TP concentration were 0.45 L/L and 82 g/L, respectively. Administration of procaine penicillin G (Depocillin; Intervet, Whitby, Ontario), 22 000 IU/kg BW, IM, q24h, was prescribed for 7 d.

The resected ovary was multicystic with 2 predominant cysts. One cyst had a thin friable wall and contained watery red brown fluid and clots of blood. The other cyst contained similar fluid, but its wall was covered by fibrinous yellow brown material resembling luteal tissue. Portions of both cysts were fixed in 10% formalin and stained with hematoxylin-eosin-saffron. On microscopic examination (40 to 400X), the sample from the 1st cyst contained a dense cellular mass adjacent to a loose and well vascularized fibrovascular tissue that was multifocally infiltrated by neoplastic cells. The mass was composed of lobules or papillary structures of fibrovascular tissue. The lobules were supported by a thin fibrovascular stroma. In some lobules, the peripheral layer of neoplastic cells was palisading. The neoplastic cells were round and of medium size with scant amphophilic cytoplasm. The nuclei were large, round to oval with clumped chromatin and 1 medium-sized basophilic nucleolus. Anisocytosis and anisocaryosis were mild. There were 1 to 3 mitoses per 400X field. In the sample from the 2nd cyst, there were structures resembling ovarian follicles lined by a population of neoplastic cells that were similar to those in the 1st cyst. These structures were dispersed in an abundant and well vascularized fibrous tissue. On the basis of histologic appearance, the diagnosis was granulosa cell tumor.

Hemoperitoneum caused by the rupture of a granulosa cell tumor is an uncommon condition observed in heifers (1). It has been reported in a 12-hour-old filly (2), in a 9-year-old mare (3), and in women (4). The clinical manifestations were similar to those observed in this animal, including anemia, abdominal pain and distension, and signs of hypovolemic shock. Ultrasonography of the ovary per rectum was not performed, in this case, to avoid disruption of an immature blood clot.

Granulosa cell tumors are the most common ovarian tumor in cattle (5). They occur in all age groups (6–7) and, in some cases, malignant tumors have been reported (5,6). Clinical manifestations of the disease include nymphomanic behavior (7), and udder development and lactation in heifers (5). The underlying cause of these changes was attributed to the secretion of progesterone and estrogen. These signs usually disappeared after removal of the tumor (7). In the present report, the heifer did not present any of these changes, but palpation per rectum revealed a spherical, multilobulated, and enlarged ovary associated with a flaccid uterus (7).

The severity of the anemia was probably underestimated upon arrival, since a redistribution of the extravascular and extracellular fluid is necessary to reduce the PCV (approximately 12 to 24 h) (8). For the same reason, the TP concentration was probably over estimated. A more important indicator of the development of hypovolemic shock may have been the magnitude of the tachycardia (160 beats/min), associated with weakness, increased capillary refill time, and pale mucous , membranes. While preparing the whole blood transfusion, administration of hypertonic saline at a rate of 3 to 5 mL/kg BW will allow reduction of the heart rate and peripheral vascular resistance, as well as an increase in arterial pressure, cardiac output, stroke volume, and mesenteric blood flow (9). The use of hypertonic saline is controversial when hemorrhage is not controlled, since an increase in blood loss and mortality have been reported in association with its administration (10). The beneficial effects of the hypertonic saline prevailed in this case in our opinion.

Blood donor cows should be healthy and tested free of important infectious diseases. Since bovine blood isoantibodies are often absent or present in low quantities and compatibility tests are not easily performed, unmatched blood transfusions can be administered without major concern (8). Anaphylactic reactions can occur during the administration of whole blood transfusions. These are more likely to occur if the transfusions are separated by at least a week and especially if the same donor is used. In our case, the risk of an anaphylactic reaction was reduced, since the interval between transfusions was short and multiple donors were used.

Ovariectomy has been reported previously in cows as a treatment for granulosa cell tumors (7). Depending on the position of the affected ovary and the age of the animal, different approaches can be selected. Success by using a ventral midline approach in the area just cranial to the udder when the left ovary was affected has been reported (7). We selected a right flank approach, since we wanted to perform a complete laparotomy and to avoid possible compression of the vena cava in a hypovolemic animal in dorsal recumbency.

Calving after the removal of a granulosa cell tumor in a heifer has been reported (7), and in the case being reported here, 14 mo after surgery, the heifer was doing well and was 4 mo pregnant.