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Oviductal Adenoma in a Mare
REFEREED
CASE STUDY Oviductal Adenoma in a Mare Dickie J. Vest, DVM, Dipl. ACT INTRODUCTION A 10-year-old Rocky Mountain Saddle Horse mare presented with a 2-year history of irregular estrous cycles and failure to maintain pregnancy. The referring veterinarian’s examination revealed an enlarged right ovary with one large follicle (70 mm diameter). Attempts to induce ovulation were unsuccessful. The mare was referred for evaluation and treatment of the enlarged ovary. An enlarged ovary in the mare can result from neoplasia, infection, trauma (eg, ovulation), and abnormal functional processes (eg, anovulatory follicles, hemorrhagic follicles). Ovarian enlargement is generally divided into neoplastic and nonneoplastic causes. Neoplastic differentials include granulosa cell tumor, teratoma, dysgerminoma, and serous cystadenoma. Nonneoplastic conditions that can result in an enlarged ovary include abscess, hematoma, ovarian cyst, hemorrhagic anovulatory follicle, and normal enlargement caused by the development of multiple secondary follicles. Hemorrhagic follicles, hemorrhagic anovulatory follicles, and persistent anovulatory follicles are all similar in their descriptions in the literature.1 Hemorrhagic anovulatory follicle will be used in this case report. Hemorrhagic anovulatory follicles have been classified as hematoma formation in the follicular antrum in lieu of ovulation.1 An ovarian hematoma is the result of excessive hemorrhage into the antrum after ovulation. Corpora hemmorhagica differ from both hemorrhagic anovulatory follicles and hematomas in that they are the normal result of ovulation and formation of the corpus luteum. Maximum diameter of the blood clot tends to be greater in hemorrhagic anovulatory follicles than in corpora hemorrhagica.1 Ovarian neoplasms are rare in horses. The most common tumor of the equine ovary is the granulosa cell tumor followed by the teratoma.2,3 In addition to categorizing conditions producing an abnormally sized ovary into neoplastic and nonneoplastic causes, neoplastic conditions can be divided into those tumor types that are typically functional and those that are not. A functional ovarian tumor is typified by the granulosa cell tumor that overproduces steroid hormones, primarily testosterone. Additionally, granulosa cell tumors can produce high levels of the From Equine Reproductive Medicine, Magnolia, TX. Reprint requests: Dickie J. Vest, DVM, Dipl. ACT, Equine Reproductive Medicine, 23910 Decker Prairie Rosehill, Magnolia, TX 77355. 0737-0806/$ - see front matter Ó 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.jevs.2007.11.004
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hormone inhibin, causing atrophy of the contralateral ovary and anestrus by suppression of follicle-stimulating hormone produced in the anterior pituitary. The contralateral ovary in mares with a granulosa cell tumor may continue to ovulate normally, with the mare having normal estrous cycles.4,5 Based on histologic characteristics, tumors of the ovary can be divided into three broad categories: surface epithelial tumors (eg, papillary adenoma, papillary adenocarcinoma, cystadenoma, and cystadenocarcinoma), sex cordgonadostromal tumors (eg, granulosa cell tumor, thecoma, and luteoma), and finally germ cell tumors (eg, dysgerminoma).6 Oviductal abnormalities resulting in infertility are rarely reported in the mare.7 Additionally, tumors of the oviduct are extremely rare in domestic animals; however, they have been reported in the bitch and the mare.6 Tumors of the oviduct include adenoma, adenocarcinoma, and lipoma.6
CLINICAL REPORT A 10-year-old Rocky Mountain Saddle Horse mare was presented for evaluation of an enlarged ovary, irregular cycles, and failure to conceive over a 2-year period. The mare was maintained with other horses at the owner’s home, and vaccinations for rabies, equine influenza, equine rhinopneumonitis, Streptococcus equi, tetanus, and West Nile virus were current. The mare was negative for equine infectious anemia antibodies, and no other problems were noted by the owners at the time of presentation. The mare was purchased 2 years before presentation as a maiden mare. The mare was bred through artificial insemination with fresh-extended semen during the natural breeding season to a proven sire with known fertility. Verification of a preovulatory follicle was performed using ultrasonography before insemination. Subsequent examination indicated that the mare failed to ovulate and a uterine culture sample was obtained at that time. Uterine culture results indicated that the mare had a bacterial infection and uterine treatment was instituted. Later in the same breeding season, follow-up uterine sampling failed to yield any bacterial growth and the mare was inseminated during the following estrous cycle. The mare returned to estrus later the same month. The mare was inseminated once again and found to be barren 45 days later by palpation per rectum; however, ultrasonographic examination 1 month later revealed a viable fetus with visible heartbeat at approximately 80 days’ gestation. Examination near term showed the mare had lost the pregnancy at an
Journal of Equine Veterinary Science Vol 28, No 1 (2008)
DJ Vest Vol 28, No 1 (2008)
unknown time. The mare had not shown any signs of estrus or illness during the previous 10 months. The mare had vague signs of estrus in the spring of the following year, with behavioral signs becoming more evident as the natural breeding season progressed. Ultrasonic examination during the breeding season revealed a recent ovulation, and the mare was bred on the following estrous cycle. The mare did not show behavioral signs of estrus for the following 3 months; however, examination revealed that the mare was not pregnant. Uterine swabs were submitted for bacteriology and were found to be negative for any pathogens. Approximately 1 month before presentation, ultrasonic examination by the referring veterinarian revealed an enlarged right ovary with one large (60-mm diameter) follicle. Additionally, a corpus luteum was noted during examination of the left ovary. The veterinarian attempted to induce luteolysis and return to estrus with 250 mg cloprostenol (Estrumate, Schering-Plough Animal Health Corp., Summit, NJ) administered intramuscularly. Additionally, 1.5 mg deslorelin (BioRelease Deslorelin Injection, BET PHARM, LLC, Lexington, KY) was administered intramuscularly simultaneously in an attempt to induce ovulation of the anovulatory follicle. On presentation, the mare was in good body condition and appeared to be in good health. Physical examination findings were unremarkable. Examination by palpation and ultrasonography per rectum was performed. Ultrasonography was performed using an Aloka SSD-500V (Aloka Co., Ltd., Wallingford, CT) ultrasound, using a 5.0-mHz linear rectal probe. Examination of the left ovary (4.0-cm diameter) showed multiple small (1520 mm diameter) follicles, one corpus luteum, and normal stromal architecture. The ovulation fossa was readily palpable. Examination of the right ovary (12.0 cm diameter) showed one large (6.47 cm 6.30 cm) well-defined follicle containing echogenic particles (Fig. 1). The ovulation fossa was difficult to identify clearly. Additionally, the right ovary was immobile and the uterus was difficult to manipulate. Very mild edema was present throughout the uterus and the cervix was soft on palpation. The presence of a corpus luteum with mild edema indicated that the mare was cycling and nearing estrus. Hemorrhagic anovulatory follicle, granulosa cell tumor, and ovarian hematoma were discussed with the owner. Other tumor types were discussed, particularly nonfunctional types, but they were considered unlikely. The decision was made to pursue induction of ovulation once more, before hormone testing. The mare was administered 1.5 mg deslorelin (BioRelease Deslorelin Injection, BET PHARM, LLC, Lexington, KY) intramuscularly. The mare was rechecked ultrasonographically over the following 2-week period. No change in ovarian size was noted during the subsequent examinations.
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Figure 1. Ultrasound image of right ovary with anovulatory follicle.
At the 2-week examination, serum was harvested for determination of inhibin, testosterone, and progesterone levels (Table 1). These values would support or contradict a diagnosis of granulosa cell tumor. The mare was returned home awaiting laboratory results. Laboratory results were within normal limits for a cycling nonpregnant mare. Although granulosa cell tumor could not be ruled out completely, that tumor type was less likely with the normal laboratory results. Because of the chronic nature of the condition and apparent infertility as a result, exploratory laparotomy was discussed and scheduled for the following week. On return, preoperative blood samples were collected for complete blood count (Table 2) and serum biochemistry analysis (Table 3). The complete blood count showed a mild lymphopenia and neutrophilia based on percent distribution. The absolute white blood cell counts were within normal limits. The white blood cell percentage changes were very slight and were attributed to a stress response to the long trailer ride from the owner’s farm. Mild anemia was also detected on the complete blood count. The absolute count was low; however, the hematocrit was within normal limits. Potential causes for the decreased red blood cell count included blood loss, increased erythrocyte destruction, and decreased erythrocyte production.8 EPG testing yielded normal results; thus, the anemia was attributed to chronic inflammation or neoplasia. The serum biochemistry was normal except for slightly increased aspartate aminotransferase (AST), glucose, and creatine kinase (CK) values. The increased glucose level was attributed to stress and that the blood sample was postprandial. The increased AST and CK levels were not considered pathologic, with less than 50% and 250% increase in AST and CK respectively, regardless of fitness.9
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Table 1. Serum inhibin, testosterone and progesterone analysis
Table 3. Serum biochemistry results Test
Value
Reference Range
Hormone
Result
Reference Range
Inhibin Testosterone Progesterone
0.23 ng/ml 35.0 pg/ml 5.9 ng/ml
0.10.7 ng/ml 2045 pg/ml 1.015þ ng/ml
Albumin AST TBIL GGT TP GLOB BUN CREA GLU CK
2.7 g/dl 373** 1.3 mg/dl 23 U/l 6.1 g/dl 3.4 g/dl 12 mg/dl 1.6 mg/dl 146 mg/dl** 1,128 U/l**
2.23.7 g/dl 175340 U/l 0.52.3 mg/dl 524 U/l 5.78.0 g/dl 2.75.0 g/dl 725 mg/dl 0.62.2 mg/dl 65110 mg/dl 120470 U/l
Table 2. Complete blood count results Test
Value
Reference Range
WBC
8.69 1000/ml
LYMPH MONO GRAN LYMPH MONO GRAN RBC
19.5%** 2.7% 77.8%** 1,690/ml 230/ml 6,770/ml 6.50 3 100,000/ml** 52.8 fl 34.3% 18.6 pg 35.2 g/dl 12.1 g/dl 399,000/ml
5.012.0 1,000/ml 20.040.0% 2.08.0% 50.070.0% 1,0004,800/ml 100900/ml 2,5008,400/ml 7.013.0 100,000/ml 35.060.0 fl 32.053.0% 13.020.0 pg 30.042.0 g/dl 11.017.0 g/dl 100,000400,000/ml
MCV HCT MCH MCHC Hb PLT
The mare was fasted overnight in preparation for standing flank laparotomy the following morning. Flunixin meglumine (500 mg) and gentamicin (3 g) were administered intravenously 30 minutes before surgery. Additionally, tetanus toxoid and procaine penicillin G (9.0 106 units) were given intramuscularly. An intravenous catheter was placed in the left jugular vein for administration of sedation and analgesics. Sedation and analgesia were provided by intravenous infusion of butorphanol (10 mg) and detomidine (10 mg; Dormosedan, Pfizer Animal Health, Exton, PA) diluted in 1 liter lactated Ringer’s solution administered to effect throughout surgery. The entire surgery was performed with the mare standing in stocks with side bars modified for surgical procedures. Additional doses of butorphanol (10 mg) were given intravenously at two instances during surgery to increase analgesia during painful manipulation of the reproductive tract. The right paralumbar fossa was clipped and scrubbed for aseptic surgery. Local anesthesia was achieved by infusion of mepivacaine (Carbocaine-V, Pfizer Animal Health, Exton, PA) subcutaneously dorsally and proximal to the surgical site; additional local anesthetic was infused directly at the surgery site. A 35-cm, full-thickness incision was made midway between the tuber coxae and last rib. The ovary was easily
identified; however, the ovary could not be adequately exteriorized for removal. Further exploration revealed a large pedunculated mass that was attached to either the ovary or the distal tip of the right uterine horn. The mass extended far down into the ventral abdomen, preventing exteriorization of the ovary. Although the borders of the mass were difficult to palpate, no other abdominal attachments other than the stalk could be identified. The stalk was ligated with 2 PDS (polydioxanone, Ethicon, Somerville, NJ) and severed using Reimer emasculators to allow for exteriorization of the ovary. Mobility of the ovary was increased and allowed for ligation and removal also using Reimer emasculators. Next, the tumor was exteriorized slowly while searching for additional attachments or adhesions. The incision had to be extended to accommodate tumor removal. No attachments were found and the tumor was removed in its entirety (Fig. 2). Fortunately, the tumor was loosely organized; otherwise, the sheer size of the tumor would have prevented its removal through a flank incision. Incision closure was performed with two layers of muscle closure in an interrupted cruciate pattern with 2 PDS, one skin layer in an interrupted horizontal mattress pattern with 0 PDS and skin staples for wound apposition. A sterile stent was placed over the wound and held in place with umbilical tape and simple interrupted sutures. The mare was allowed to recover from sedation while standing in the stock. Tissue samples were collected from the ovary and the mass to be submitted to Texas Veterinary Medical Diagnostic Laboratory for histopathology. The histopathologic diagnosis was adenoma of the oviduct. The sections of periovarian mass consisted of a vascular collagenous stroma with extensively papillated surfaces lined by columnar cells. The columnar cells were crowded into a pseudostratified appearance with basal orientation of nuclei and luminal cilia, consistent with oviductal tissue. The ovarian tissue samples displayed normal stroma, corpus luteum, and tertiary follicle. The mare was administered enrofloxacin (3 g Baytril, Bayer HealthCare, LLC, Shawnee Mission, KS) intravenously every 24 hours and 500 mg flunixin meglumine intravenously
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Figure 3. Ultrasound image of left ovary with normal follicle.
Figure 2. Oviductal adenoma with ipsilateral ovary. every 12 hours for the following 4 days, followed by 500 mg flunixin meglumine intravenously every 24 hours for 2 additional days. The mare recovered well except for sporadic elevations in heart rate with corresponding decreases in gastrointestinal borborygmi. The mare was administered 3 liters mineral oil via nasogastric intubation 2 days after surgery and was only hand grazed on green grass during her recovery. Subsequently, the mare’s heart rate and gastrointestinal motility improved and the mare was discharged 8 days after surgery with instructions to return for staple removal in 1 week. The mare returned 15 days after surgery for staple removal and evaluation of the reproductive tract. The surgical site had healed well and the owners reported the mare was eating well and showed no signs of discomfort after discharge. Rectal palpation and ultrasonography revealed a uterus that was easily palpable with no apparent adhesion formation and a left ovary with one 20-mm follicle and one corpus luteum. The mare was administered cloprostenol (250 mg; Estrumate, Schering-Plough Animal Health Corp., Summit, NJ) intramuscularly and discharged with instructions to return in 7 days for evaluation. On return, rectal examination revealed two 20-mm follicles and an absence of luteal tissue. Additionally, slight uterine edema was developing throughout the uterus.
The mare was discharged with instructions to return in 2 weeks to verify whether ovulation occurred. The mare returned 17 days later with a normal-appearing corpus luteum, small follicles (approximately 20 mm diameter), no uterine edema, and a closed cervix. The mare was administered cloprostenol (250 mg; Estrumate, Schering-Plough Animal Health Corp., Summit, NJ) intramuscularly and discharged with instructions to return in 6 days for evaluation. On return, rectal examination revealed one large (34 mm 40 mm) follicle (Fig. 3), moderate uterine edema, and a relaxed cervix. The mare was administered deslorelin (1.5 mg; BioRelease Deslorelin Injection, BET PHARM, LLC, Lexington, KY) intramuscularly and discharged with instructions to inseminate the mare that evening and return in 2 days to confirm ovulation. The mare was examined 2 days later and was found to have ovulated, as evidenced by a normal-appearing corpus luteum (Fig. 4). The corpus luteum appeared to be approximately 12 to 24 hours old, evidenced by organization of luteal tissue. The mare was sent home with instructions to return in 2 weeks for pregnancy examination. The mare returned 16 days later (approximately 17 days post-ovulation). On examination, the corpus luteum was still present and a 26-mm vesicle was present at the base of the left uterine horn. The mare was diagnosed pregnant and the owners were asked to return the mare in 10 days to confirm pregnancy. Examination confirmed presence of an embryo with a heartbeat 20 days later (Fig. 5). The mare was confirmed pregnant on three additional examinations through the embryonic and fetal periods. The mare subsequently delivered a healthy foal the following year and is currently in foal with her second pregnancy. The mare conceived the second pregnancy without complication.
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Figure 4. Ultrasound image of left ovary with corpus luteum.
DISCUSSION This case of a 10-year-old mare ultimately diagnosed with adenoma of the oviduct was unusual in that the primary clinical finding was an enlarged ovary. The pedunculated tumor was inaccessible by rectal palpation and therefore evaded detection. The immobility of the ovary and difficulty in manipulating the uterus was, in retrospect, due to the large tumor attached to the ovary. The clinical findings in this case could easily support a tentative diagnosis of ovarian neoplasia; however, confounding factors included a cyclic contralateral ovary and hormone analysis that was within normal parameters. Although granulosa cell tumor was a likely differential diagnosis, the mare did not have all the typical findings to strongly support the diagnosis. Hormone testing, in this case, was an important component in the decision to proceed to exploratory laparotomy for a definitive diagnosis. Whether the tumor, its location, or another factor played a role in producing the enlarged ovary is not known. The attachment site of the stalk may have obliterated the ovulation fossa, yielding it nonfunctional and thus preventing ovulation. Because of the chronic nature of the condition and apparent infertility as a result, the ovary was appropriately considered abnormal and removed. The clinical hypothesis hoped for a normal functioning remaining ovary after surgical removal of the abnormal ovary. The clinical decision to proceed to surgical removal of the ovary was supported by the owner’s desire to breed the mare and the fact that medical attempts at treatment had failed. In this case, laparoscopy may have proved superior to laparotomy for diagnosis of the oviductal tumor. Visualization, manipulation, and removal of this tumor through
Figure 5. Ultrasound image of embryo.
a flank laparotomy was very difficult. Had the tumor been visualized via laparoscopy, general anesthesia and an alternative surgical approach may have been selected.
SUMMARY A 10-year-old Rocky Mountain Saddle Horse mare was initially presented for erratic estrous cycles, infertility, and an enlarged ovary. The initial differential diagnosis list comprised neoplastic and nonneoplastic ovarian conditions. The primary differential diagnosis of granulosa cell tumor was deemed less likely because of clinical findings and laboratory results. Because of the chronic nature and apparent infertility resulting from the abnormal ovary, surgery was elected to remove the affected ovary. Exploratory laparotomy confirmed the presence of the enlarged ovary; however, a larger oviductal tumor was discovered. Both the ovary and tumor were removed and the mare recovered uneventfully. The mare cycled normally, conceived, delivered a healthy foal, and is currently in late gestation with her second pregnancy. REFERENCES 1. Ginther OJ, Gastal EL, Gastal MO, Beg M. Incidence, endocrinology, vascularity, and morphology of hemorrhagic anovulatory follicles in mares. J Equine Vet Sci 2007;27:130–139. 2. McEntee K. Reproductive pathology of domestic mammals. San Diego: Academic Press Inc.; 1990:52–93. 3. Clark TL. Clinical management of equine ovarian neoplasms. J Reprod Fertil 1975;23(suppl.):331–334. 4. Nie GJ, Momont H. Ovarian mass in three mares with regular estrous cycles. J Am Vet Med Assoc 1992;201:1043–1044.
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5. Hinrichs K, Watson ED, Kenney RM. Granulosa cell tumor in a mare with a functional contralateral ovary. J Am Vet Med Assoc 1990; 197:1037–1038. 6. Nielsen SW, Kennedy PC. Tumors of the genital systems. In: Moulton JE, ed. Tumors in domestic animals, 3rd ed. Berkeley: University of California Press; 1990:479–517. 7. Blanchard TL. Breeding soundness examination of the mare. In: Blanchard TL, Varner DD, Love CC, Brinsko SP, Rigby SL,
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Schumacher J, eds. Manual of equine reproduction. 2nd ed. St. Louis: Mosby; 2003:35. 8. Morris DD. Diseases of the hemolymphatic system. In: Reed SM, Bayly WM, eds. Equine internal medicine. Philadelphia: WB Saunders Co.; 1998:560–572. 9. Harris PA, Mayhew IG. Musculoskeletal disease. In: Reed SM, Bayly WM, eds. Equine internal medicine. Philadelphia: WB Saunders Co.; 1998:380–381.
CASE STUDY Oviductal Adenoma in a Mare Dickie J. Vest, DVM, Dipl. ACT INTRODUCTION A 10-year-old Rocky Mountain Saddle Horse mare presented with a 2-year history of irregular estrous cycles and failure to maintain pregnancy. The referring veterinarian’s examination revealed an enlarged right ovary with one large follicle (70 mm diameter). Attempts to induce ovulation were unsuccessful. The mare was referred for evaluation and treatment of the enlarged ovary. An enlarged ovary in the mare can result from neoplasia, infection, trauma (eg, ovulation), and abnormal functional processes (eg, anovulatory follicles, hemorrhagic follicles). Ovarian enlargement is generally divided into neoplastic and nonneoplastic causes. Neoplastic differentials include granulosa cell tumor, teratoma, dysgerminoma, and serous cystadenoma. Nonneoplastic conditions that can result in an enlarged ovary include abscess, hematoma, ovarian cyst, hemorrhagic anovulatory follicle, and normal enlargement caused by the development of multiple secondary follicles. Hemorrhagic follicles, hemorrhagic anovulatory follicles, and persistent anovulatory follicles are all similar in their descriptions in the literature.1 Hemorrhagic anovulatory follicle will be used in this case report. Hemorrhagic anovulatory follicles have been classified as hematoma formation in the follicular antrum in lieu of ovulation.1 An ovarian hematoma is the result of excessive hemorrhage into the antrum after ovulation. Corpora hemmorhagica differ from both hemorrhagic anovulatory follicles and hematomas in that they are the normal result of ovulation and formation of the corpus luteum. Maximum diameter of the blood clot tends to be greater in hemorrhagic anovulatory follicles than in corpora hemorrhagica.1 Ovarian neoplasms are rare in horses. The most common tumor of the equine ovary is the granulosa cell tumor followed by the teratoma.2,3 In addition to categorizing conditions producing an abnormally sized ovary into neoplastic and nonneoplastic causes, neoplastic conditions can be divided into those tumor types that are typically functional and those that are not. A functional ovarian tumor is typified by the granulosa cell tumor that overproduces steroid hormones, primarily testosterone. Additionally, granulosa cell tumors can produce high levels of the From Equine Reproductive Medicine, Magnolia, TX. Reprint requests: Dickie J. Vest, DVM, Dipl. ACT, Equine Reproductive Medicine, 23910 Decker Prairie Rosehill, Magnolia, TX 77355. 0737-0806/$ - see front matter Ó 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.jevs.2007.11.004
40
hormone inhibin, causing atrophy of the contralateral ovary and anestrus by suppression of follicle-stimulating hormone produced in the anterior pituitary. The contralateral ovary in mares with a granulosa cell tumor may continue to ovulate normally, with the mare having normal estrous cycles.4,5 Based on histologic characteristics, tumors of the ovary can be divided into three broad categories: surface epithelial tumors (eg, papillary adenoma, papillary adenocarcinoma, cystadenoma, and cystadenocarcinoma), sex cordgonadostromal tumors (eg, granulosa cell tumor, thecoma, and luteoma), and finally germ cell tumors (eg, dysgerminoma).6 Oviductal abnormalities resulting in infertility are rarely reported in the mare.7 Additionally, tumors of the oviduct are extremely rare in domestic animals; however, they have been reported in the bitch and the mare.6 Tumors of the oviduct include adenoma, adenocarcinoma, and lipoma.6
CLINICAL REPORT A 10-year-old Rocky Mountain Saddle Horse mare was presented for evaluation of an enlarged ovary, irregular cycles, and failure to conceive over a 2-year period. The mare was maintained with other horses at the owner’s home, and vaccinations for rabies, equine influenza, equine rhinopneumonitis, Streptococcus equi, tetanus, and West Nile virus were current. The mare was negative for equine infectious anemia antibodies, and no other problems were noted by the owners at the time of presentation. The mare was purchased 2 years before presentation as a maiden mare. The mare was bred through artificial insemination with fresh-extended semen during the natural breeding season to a proven sire with known fertility. Verification of a preovulatory follicle was performed using ultrasonography before insemination. Subsequent examination indicated that the mare failed to ovulate and a uterine culture sample was obtained at that time. Uterine culture results indicated that the mare had a bacterial infection and uterine treatment was instituted. Later in the same breeding season, follow-up uterine sampling failed to yield any bacterial growth and the mare was inseminated during the following estrous cycle. The mare returned to estrus later the same month. The mare was inseminated once again and found to be barren 45 days later by palpation per rectum; however, ultrasonographic examination 1 month later revealed a viable fetus with visible heartbeat at approximately 80 days’ gestation. Examination near term showed the mare had lost the pregnancy at an
Journal of Equine Veterinary Science Vol 28, No 1 (2008)
DJ Vest Vol 28, No 1 (2008)
unknown time. The mare had not shown any signs of estrus or illness during the previous 10 months. The mare had vague signs of estrus in the spring of the following year, with behavioral signs becoming more evident as the natural breeding season progressed. Ultrasonic examination during the breeding season revealed a recent ovulation, and the mare was bred on the following estrous cycle. The mare did not show behavioral signs of estrus for the following 3 months; however, examination revealed that the mare was not pregnant. Uterine swabs were submitted for bacteriology and were found to be negative for any pathogens. Approximately 1 month before presentation, ultrasonic examination by the referring veterinarian revealed an enlarged right ovary with one large (60-mm diameter) follicle. Additionally, a corpus luteum was noted during examination of the left ovary. The veterinarian attempted to induce luteolysis and return to estrus with 250 mg cloprostenol (Estrumate, Schering-Plough Animal Health Corp., Summit, NJ) administered intramuscularly. Additionally, 1.5 mg deslorelin (BioRelease Deslorelin Injection, BET PHARM, LLC, Lexington, KY) was administered intramuscularly simultaneously in an attempt to induce ovulation of the anovulatory follicle. On presentation, the mare was in good body condition and appeared to be in good health. Physical examination findings were unremarkable. Examination by palpation and ultrasonography per rectum was performed. Ultrasonography was performed using an Aloka SSD-500V (Aloka Co., Ltd., Wallingford, CT) ultrasound, using a 5.0-mHz linear rectal probe. Examination of the left ovary (4.0-cm diameter) showed multiple small (1520 mm diameter) follicles, one corpus luteum, and normal stromal architecture. The ovulation fossa was readily palpable. Examination of the right ovary (12.0 cm diameter) showed one large (6.47 cm 6.30 cm) well-defined follicle containing echogenic particles (Fig. 1). The ovulation fossa was difficult to identify clearly. Additionally, the right ovary was immobile and the uterus was difficult to manipulate. Very mild edema was present throughout the uterus and the cervix was soft on palpation. The presence of a corpus luteum with mild edema indicated that the mare was cycling and nearing estrus. Hemorrhagic anovulatory follicle, granulosa cell tumor, and ovarian hematoma were discussed with the owner. Other tumor types were discussed, particularly nonfunctional types, but they were considered unlikely. The decision was made to pursue induction of ovulation once more, before hormone testing. The mare was administered 1.5 mg deslorelin (BioRelease Deslorelin Injection, BET PHARM, LLC, Lexington, KY) intramuscularly. The mare was rechecked ultrasonographically over the following 2-week period. No change in ovarian size was noted during the subsequent examinations.
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Figure 1. Ultrasound image of right ovary with anovulatory follicle.
At the 2-week examination, serum was harvested for determination of inhibin, testosterone, and progesterone levels (Table 1). These values would support or contradict a diagnosis of granulosa cell tumor. The mare was returned home awaiting laboratory results. Laboratory results were within normal limits for a cycling nonpregnant mare. Although granulosa cell tumor could not be ruled out completely, that tumor type was less likely with the normal laboratory results. Because of the chronic nature of the condition and apparent infertility as a result, exploratory laparotomy was discussed and scheduled for the following week. On return, preoperative blood samples were collected for complete blood count (Table 2) and serum biochemistry analysis (Table 3). The complete blood count showed a mild lymphopenia and neutrophilia based on percent distribution. The absolute white blood cell counts were within normal limits. The white blood cell percentage changes were very slight and were attributed to a stress response to the long trailer ride from the owner’s farm. Mild anemia was also detected on the complete blood count. The absolute count was low; however, the hematocrit was within normal limits. Potential causes for the decreased red blood cell count included blood loss, increased erythrocyte destruction, and decreased erythrocyte production.8 EPG testing yielded normal results; thus, the anemia was attributed to chronic inflammation or neoplasia. The serum biochemistry was normal except for slightly increased aspartate aminotransferase (AST), glucose, and creatine kinase (CK) values. The increased glucose level was attributed to stress and that the blood sample was postprandial. The increased AST and CK levels were not considered pathologic, with less than 50% and 250% increase in AST and CK respectively, regardless of fitness.9
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Table 1. Serum inhibin, testosterone and progesterone analysis
Table 3. Serum biochemistry results Test
Value
Reference Range
Hormone
Result
Reference Range
Inhibin Testosterone Progesterone
0.23 ng/ml 35.0 pg/ml 5.9 ng/ml
0.10.7 ng/ml 2045 pg/ml 1.015þ ng/ml
Albumin AST TBIL GGT TP GLOB BUN CREA GLU CK
2.7 g/dl 373** 1.3 mg/dl 23 U/l 6.1 g/dl 3.4 g/dl 12 mg/dl 1.6 mg/dl 146 mg/dl** 1,128 U/l**
2.23.7 g/dl 175340 U/l 0.52.3 mg/dl 524 U/l 5.78.0 g/dl 2.75.0 g/dl 725 mg/dl 0.62.2 mg/dl 65110 mg/dl 120470 U/l
Table 2. Complete blood count results Test
Value
Reference Range
WBC
8.69 1000/ml
LYMPH MONO GRAN LYMPH MONO GRAN RBC
19.5%** 2.7% 77.8%** 1,690/ml 230/ml 6,770/ml 6.50 3 100,000/ml** 52.8 fl 34.3% 18.6 pg 35.2 g/dl 12.1 g/dl 399,000/ml
5.012.0 1,000/ml 20.040.0% 2.08.0% 50.070.0% 1,0004,800/ml 100900/ml 2,5008,400/ml 7.013.0 100,000/ml 35.060.0 fl 32.053.0% 13.020.0 pg 30.042.0 g/dl 11.017.0 g/dl 100,000400,000/ml
MCV HCT MCH MCHC Hb PLT
The mare was fasted overnight in preparation for standing flank laparotomy the following morning. Flunixin meglumine (500 mg) and gentamicin (3 g) were administered intravenously 30 minutes before surgery. Additionally, tetanus toxoid and procaine penicillin G (9.0 106 units) were given intramuscularly. An intravenous catheter was placed in the left jugular vein for administration of sedation and analgesics. Sedation and analgesia were provided by intravenous infusion of butorphanol (10 mg) and detomidine (10 mg; Dormosedan, Pfizer Animal Health, Exton, PA) diluted in 1 liter lactated Ringer’s solution administered to effect throughout surgery. The entire surgery was performed with the mare standing in stocks with side bars modified for surgical procedures. Additional doses of butorphanol (10 mg) were given intravenously at two instances during surgery to increase analgesia during painful manipulation of the reproductive tract. The right paralumbar fossa was clipped and scrubbed for aseptic surgery. Local anesthesia was achieved by infusion of mepivacaine (Carbocaine-V, Pfizer Animal Health, Exton, PA) subcutaneously dorsally and proximal to the surgical site; additional local anesthetic was infused directly at the surgery site. A 35-cm, full-thickness incision was made midway between the tuber coxae and last rib. The ovary was easily
identified; however, the ovary could not be adequately exteriorized for removal. Further exploration revealed a large pedunculated mass that was attached to either the ovary or the distal tip of the right uterine horn. The mass extended far down into the ventral abdomen, preventing exteriorization of the ovary. Although the borders of the mass were difficult to palpate, no other abdominal attachments other than the stalk could be identified. The stalk was ligated with 2 PDS (polydioxanone, Ethicon, Somerville, NJ) and severed using Reimer emasculators to allow for exteriorization of the ovary. Mobility of the ovary was increased and allowed for ligation and removal also using Reimer emasculators. Next, the tumor was exteriorized slowly while searching for additional attachments or adhesions. The incision had to be extended to accommodate tumor removal. No attachments were found and the tumor was removed in its entirety (Fig. 2). Fortunately, the tumor was loosely organized; otherwise, the sheer size of the tumor would have prevented its removal through a flank incision. Incision closure was performed with two layers of muscle closure in an interrupted cruciate pattern with 2 PDS, one skin layer in an interrupted horizontal mattress pattern with 0 PDS and skin staples for wound apposition. A sterile stent was placed over the wound and held in place with umbilical tape and simple interrupted sutures. The mare was allowed to recover from sedation while standing in the stock. Tissue samples were collected from the ovary and the mass to be submitted to Texas Veterinary Medical Diagnostic Laboratory for histopathology. The histopathologic diagnosis was adenoma of the oviduct. The sections of periovarian mass consisted of a vascular collagenous stroma with extensively papillated surfaces lined by columnar cells. The columnar cells were crowded into a pseudostratified appearance with basal orientation of nuclei and luminal cilia, consistent with oviductal tissue. The ovarian tissue samples displayed normal stroma, corpus luteum, and tertiary follicle. The mare was administered enrofloxacin (3 g Baytril, Bayer HealthCare, LLC, Shawnee Mission, KS) intravenously every 24 hours and 500 mg flunixin meglumine intravenously
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Figure 3. Ultrasound image of left ovary with normal follicle.
Figure 2. Oviductal adenoma with ipsilateral ovary. every 12 hours for the following 4 days, followed by 500 mg flunixin meglumine intravenously every 24 hours for 2 additional days. The mare recovered well except for sporadic elevations in heart rate with corresponding decreases in gastrointestinal borborygmi. The mare was administered 3 liters mineral oil via nasogastric intubation 2 days after surgery and was only hand grazed on green grass during her recovery. Subsequently, the mare’s heart rate and gastrointestinal motility improved and the mare was discharged 8 days after surgery with instructions to return for staple removal in 1 week. The mare returned 15 days after surgery for staple removal and evaluation of the reproductive tract. The surgical site had healed well and the owners reported the mare was eating well and showed no signs of discomfort after discharge. Rectal palpation and ultrasonography revealed a uterus that was easily palpable with no apparent adhesion formation and a left ovary with one 20-mm follicle and one corpus luteum. The mare was administered cloprostenol (250 mg; Estrumate, Schering-Plough Animal Health Corp., Summit, NJ) intramuscularly and discharged with instructions to return in 7 days for evaluation. On return, rectal examination revealed two 20-mm follicles and an absence of luteal tissue. Additionally, slight uterine edema was developing throughout the uterus.
The mare was discharged with instructions to return in 2 weeks to verify whether ovulation occurred. The mare returned 17 days later with a normal-appearing corpus luteum, small follicles (approximately 20 mm diameter), no uterine edema, and a closed cervix. The mare was administered cloprostenol (250 mg; Estrumate, Schering-Plough Animal Health Corp., Summit, NJ) intramuscularly and discharged with instructions to return in 6 days for evaluation. On return, rectal examination revealed one large (34 mm 40 mm) follicle (Fig. 3), moderate uterine edema, and a relaxed cervix. The mare was administered deslorelin (1.5 mg; BioRelease Deslorelin Injection, BET PHARM, LLC, Lexington, KY) intramuscularly and discharged with instructions to inseminate the mare that evening and return in 2 days to confirm ovulation. The mare was examined 2 days later and was found to have ovulated, as evidenced by a normal-appearing corpus luteum (Fig. 4). The corpus luteum appeared to be approximately 12 to 24 hours old, evidenced by organization of luteal tissue. The mare was sent home with instructions to return in 2 weeks for pregnancy examination. The mare returned 16 days later (approximately 17 days post-ovulation). On examination, the corpus luteum was still present and a 26-mm vesicle was present at the base of the left uterine horn. The mare was diagnosed pregnant and the owners were asked to return the mare in 10 days to confirm pregnancy. Examination confirmed presence of an embryo with a heartbeat 20 days later (Fig. 5). The mare was confirmed pregnant on three additional examinations through the embryonic and fetal periods. The mare subsequently delivered a healthy foal the following year and is currently in foal with her second pregnancy. The mare conceived the second pregnancy without complication.
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Figure 4. Ultrasound image of left ovary with corpus luteum.
DISCUSSION This case of a 10-year-old mare ultimately diagnosed with adenoma of the oviduct was unusual in that the primary clinical finding was an enlarged ovary. The pedunculated tumor was inaccessible by rectal palpation and therefore evaded detection. The immobility of the ovary and difficulty in manipulating the uterus was, in retrospect, due to the large tumor attached to the ovary. The clinical findings in this case could easily support a tentative diagnosis of ovarian neoplasia; however, confounding factors included a cyclic contralateral ovary and hormone analysis that was within normal parameters. Although granulosa cell tumor was a likely differential diagnosis, the mare did not have all the typical findings to strongly support the diagnosis. Hormone testing, in this case, was an important component in the decision to proceed to exploratory laparotomy for a definitive diagnosis. Whether the tumor, its location, or another factor played a role in producing the enlarged ovary is not known. The attachment site of the stalk may have obliterated the ovulation fossa, yielding it nonfunctional and thus preventing ovulation. Because of the chronic nature of the condition and apparent infertility as a result, the ovary was appropriately considered abnormal and removed. The clinical hypothesis hoped for a normal functioning remaining ovary after surgical removal of the abnormal ovary. The clinical decision to proceed to surgical removal of the ovary was supported by the owner’s desire to breed the mare and the fact that medical attempts at treatment had failed. In this case, laparoscopy may have proved superior to laparotomy for diagnosis of the oviductal tumor. Visualization, manipulation, and removal of this tumor through
Figure 5. Ultrasound image of embryo.
a flank laparotomy was very difficult. Had the tumor been visualized via laparoscopy, general anesthesia and an alternative surgical approach may have been selected.
SUMMARY A 10-year-old Rocky Mountain Saddle Horse mare was initially presented for erratic estrous cycles, infertility, and an enlarged ovary. The initial differential diagnosis list comprised neoplastic and nonneoplastic ovarian conditions. The primary differential diagnosis of granulosa cell tumor was deemed less likely because of clinical findings and laboratory results. Because of the chronic nature and apparent infertility resulting from the abnormal ovary, surgery was elected to remove the affected ovary. Exploratory laparotomy confirmed the presence of the enlarged ovary; however, a larger oviductal tumor was discovered. Both the ovary and tumor were removed and the mare recovered uneventfully. The mare cycled normally, conceived, delivered a healthy foal, and is currently in late gestation with her second pregnancy. REFERENCES 1. Ginther OJ, Gastal EL, Gastal MO, Beg M. Incidence, endocrinology, vascularity, and morphology of hemorrhagic anovulatory follicles in mares. J Equine Vet Sci 2007;27:130–139. 2. McEntee K. Reproductive pathology of domestic mammals. San Diego: Academic Press Inc.; 1990:52–93. 3. Clark TL. Clinical management of equine ovarian neoplasms. J Reprod Fertil 1975;23(suppl.):331–334. 4. Nie GJ, Momont H. Ovarian mass in three mares with regular estrous cycles. J Am Vet Med Assoc 1992;201:1043–1044.
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5. Hinrichs K, Watson ED, Kenney RM. Granulosa cell tumor in a mare with a functional contralateral ovary. J Am Vet Med Assoc 1990; 197:1037–1038. 6. Nielsen SW, Kennedy PC. Tumors of the genital systems. In: Moulton JE, ed. Tumors in domestic animals, 3rd ed. Berkeley: University of California Press; 1990:479–517. 7. Blanchard TL. Breeding soundness examination of the mare. In: Blanchard TL, Varner DD, Love CC, Brinsko SP, Rigby SL,
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Schumacher J, eds. Manual of equine reproduction. 2nd ed. St. Louis: Mosby; 2003:35. 8. Morris DD. Diseases of the hemolymphatic system. In: Reed SM, Bayly WM, eds. Equine internal medicine. Philadelphia: WB Saunders Co.; 1998:560–572. 9. Harris PA, Mayhew IG. Musculoskeletal disease. In: Reed SM, Bayly WM, eds. Equine internal medicine. Philadelphia: WB Saunders Co.; 1998:380–381.