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Granulosa Cell Tumors in two cycling mares
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g
J:
Reviewed
GRANULOSACELLTUMORSIN TWOCYCUNGMARES P. M. McCue, DVM1; M. M. LeBIanc,DVM 4; G. Y. Akita,DVM 2; J. R. Pascoe, DVM, Phil; D. M. Witherspoon, DVMS; G. H. Stabenfeldt, DVM. PhD 1
The granulosa-theca cell tumor (GTCT) is the most common ovarian tumor of the horse.4,7 Mares with a GTCT may exhibit continuous or intermittent estrus, stallion-like behavior or may remain anestrus. 4 The hormone secretory profile of the tumor dictates the behavior expressed, with mares having elevated plasma testosterone concentrations (>100 pg/ml) exhibiting stallion-like behavior] The ultrasonic appearance of the affected ovary ranges from a homogenous echogenic mass to a multicystic or 'honeycomb' pattern. 1The contralateral ovary is usually small and inactive,4,7 although one mare with a functional contralateral ovary was recently described.2 Mares with an inactive contralateral ovary resume normal cyclic ovarian activity 2-16 months after removal of the affected ovary? Clinical diagnosis of a GTCT is based on history, behavior, presence of a unilaterally enlarged ovary with an inactive contralateral ovary, and in some cases, elevated plasma testosterone concentrations. This report documents the presence of a granulosa cell tumor in two mares which exhibited normal follicular development, ovulation and luteal function in the contralateral ovary.
Case One A 13 year old Quarter Horse mare was referred to the Veterinary Medical Teaching Hospital, University of CaliforAuthors addresses: 1Departmentsof Reproduction,2pathology,3Surgery School of Veterinary Medicine, University of California, Davis, California 95616. '%arge Animal Clinic, College of Veterinary Medicine, University of Florida, Gainesville,FL 32610.5Bridlewood Farm, 8318 NW 90th Terrace, Ocala, FL 32675.
Volume 11, Number 5, 1991
Figure 1. Corpus luteum adjacent to the multicystic GTCT (Case No. 1). nia, Davis, in April 1990 for evaluation of the left ovary which had been enlarged for at least three months. The mare did not exhibit any estrous behavior during the previous three month period. Palpation and ultrasonography of the ovaries per rectum revealed a left ovary that was 10 cm in diameter and multicystic in appearance. The right ovary had a 40 mm follicle and edema was present in the uterus. The plasma testosterone concentration was 26.9 pg/ml. The follicle on the right ovary ovulated three days after presentation. Progesterone concentrations in plasma collected daily confirmed the presence of active luteal tissue. The differential diagnosis for an enlarged ovary in a cycling mare included ovarian hematoma, or a tumor such as a teratoma or cystadenoma. Due to the persistence of the mass over three months, the ultrasonic appearance of the mass and the ability
281
Figure 2. Histologic appearance of the multicystic ovarian mass consistent with a granulosa-theca cell tumor (100x). (Case No. 1)
of the mare to have normal follicle development which culminated in ovulation and corpus luteum formation, a cystadenoma was suspected. At the request of the owner, the enlarged ovary was removed by ventral midline laparotomy with the mare under general anesthesia. Anesthesia consisted of guaifenesin and ketamine induction with maintenance on halothane. The ovary was 9.5 cm in diameter and weighed 380 gins. A 2 cm diameter focus of firm, yellow-brown tissue, presumed to be a corpus luteum, was noted adjacent to the multicystic mass (Fig. 1). Histopathologic evaluation of this tissue confirmed the presence of luteal cells within a fibrovascular stmma. The remainder of the ovary was composed of multiple cysts lined by single to multiple layers of granulosa cells and surrounded by a variable population of thecal cells (Fig. 2), consistent with the appearance of granulosa-theca cell tumor.3 The mare was examined two weeks after surgery and the remaining ovary had 2-3 follicles 10 mm in diameter. Subsequent examinations over the next 2 months indicated that the right ovary had become inactive.
Case Two A 13 year old Thoroughbred mare was noted to have an enlarged ovary in April 1990 during a routine reproductive examination performed 30 days after foaling. The left ovary exhibited normal follicular development and the mare was bred during two estrous cycles and was confn'med to be pregnant on ultrasound examination at days 16 and 37 postovulation in June 1990. However, examination of the mare in November indicated ~at she was no longer pregnant. Reproductive evaluation in February 1991 revealed that the right ovary had enlarged markedly, whereas the left ovary was of normal size and had numerous follicles present. The mare was referred to the veterinary Medical Teaching Hospital, University of Florida, for further evaluation. Palpation of the reproductive tract per rectum disclosed a relaxed cervix, edematous uterus and a soft 45 mm follicle on the left ovary. The right ovary was large (>30 cm) with numerous fluid filled cystic structures visible on ultrasound. When presented to a stallion the mare exhibited normal estrous behavior. Differential diagnoses for the enlarged ovary included hematoma, 282
cystadenoma and granulosa cell tumor. The enlarged right ovary was removed via a ventral midline laparotomy. To facilitate removal of the ovary, 2.5 liters of yellow transudate was suctioned off a large cyst on the ovary. Surgery was completed without complications. Antibiotic administration (gentamicin and potassium penicillin) was initiated prior to surgery and flunixin meglumine (125 mg, 4 times daily) was added to the treatment regimen after surgery. Treatment was continued for seven days post surgery because the mare experienced moderate swelling at the suture line. Histopathologic evaluation indicated that the mass was a granulosa cell tumor. Transrectal ultrasound examination of the left ovary 48 hours after surgery revealed the presence of a corpus hemorrhagicum in the location oftheprevious 45 mm follicle. Serum progesterone concentrations rose from 0.64 ng/ml the day after surgery to 2.88 ng/ml five days later, confirming the present of active luteal tissue. The mare returned to estrus 16 days after the corpus hemorrhagicum was detected and ovulated 3 days later. The mare continued to develop follicles regularly on the left ovary and became pregnant on the third cycle following surgery. Granulosa cell tumors have been reported in two pregnant mares4 and in one cycling mares,2 but a majority of reports indicate that the ovary contralateral to the GTCT is inactive. 4-8The decrease in follicular activity in the contralateral ovary has been suggested to be a result of suppression of gonadotropin secretion from the pituitary secondary to ovarian steriod and inhibin production, s.7 The tumor in the first mare may have been established recently and the negative feedback effects not fully realized until the time of surgical removal. The tumor in the second mare was known to have been present for greater than one year and yet the contralateral ovary was still active. It is possible that hormone secretion by the tumor was not sufficient to suppress gonadotmpin secretion to the point where follicular development was affected.
REFERENCES 1. Hinrichs K, Hunt P R: Ultrasound as an aid to diagnosis of granulosa cell tumour in the mare. Equine VetJ 22:99-103,1990. 2. Hinrichs, K et al: Granulosa cell tumor in a mare with a functional contralateral ovary. J Amer Vet Med Assoc 1297:1037o 1038, 1990. 3. Jubb KVF, Kennedy PC, Palmer N: Pathology of domestic animals, Vol. III, 3rd ed, Academic Press, Inc., NY, 527pp, 1985. 4. Meagher DM et al.: Granulosa cell tumors in mares: a review of 78 cases. Proceedngs Amer Assoc Equine Pract, 133-143,1978. 5. Perino LJ, Didier PJ: Equine granulosa cell tumors. Equine Pract 7:14-17,1985. 6. P.iquette,GN et al: Equine granulosa-theca cell tumors express inhlbin c¢-and 8 A- subunit messenger ribonucleic acids and proteins. Biol Reprod 43:1050-1057, 1990. 7. Stabenfeldt GH et al.: Clinical findings, pathological changes and endocrinological secretory patterns in mares with ovarian tumours. J Reprod Fert Suppl. 27:277-285,1979. 8. Stickle RL et al.: Equine granulosa cell tumors. J Amer Vet Med Assoc 167:148-151,1975.
EQUIN E VETERINARY SCI ENCE
g
J:
Reviewed
GRANULOSACELLTUMORSIN TWOCYCUNGMARES P. M. McCue, DVM1; M. M. LeBIanc,DVM 4; G. Y. Akita,DVM 2; J. R. Pascoe, DVM, Phil; D. M. Witherspoon, DVMS; G. H. Stabenfeldt, DVM. PhD 1
The granulosa-theca cell tumor (GTCT) is the most common ovarian tumor of the horse.4,7 Mares with a GTCT may exhibit continuous or intermittent estrus, stallion-like behavior or may remain anestrus. 4 The hormone secretory profile of the tumor dictates the behavior expressed, with mares having elevated plasma testosterone concentrations (>100 pg/ml) exhibiting stallion-like behavior] The ultrasonic appearance of the affected ovary ranges from a homogenous echogenic mass to a multicystic or 'honeycomb' pattern. 1The contralateral ovary is usually small and inactive,4,7 although one mare with a functional contralateral ovary was recently described.2 Mares with an inactive contralateral ovary resume normal cyclic ovarian activity 2-16 months after removal of the affected ovary? Clinical diagnosis of a GTCT is based on history, behavior, presence of a unilaterally enlarged ovary with an inactive contralateral ovary, and in some cases, elevated plasma testosterone concentrations. This report documents the presence of a granulosa cell tumor in two mares which exhibited normal follicular development, ovulation and luteal function in the contralateral ovary.
Case One A 13 year old Quarter Horse mare was referred to the Veterinary Medical Teaching Hospital, University of CaliforAuthors addresses: 1Departmentsof Reproduction,2pathology,3Surgery School of Veterinary Medicine, University of California, Davis, California 95616. '%arge Animal Clinic, College of Veterinary Medicine, University of Florida, Gainesville,FL 32610.5Bridlewood Farm, 8318 NW 90th Terrace, Ocala, FL 32675.
Volume 11, Number 5, 1991
Figure 1. Corpus luteum adjacent to the multicystic GTCT (Case No. 1). nia, Davis, in April 1990 for evaluation of the left ovary which had been enlarged for at least three months. The mare did not exhibit any estrous behavior during the previous three month period. Palpation and ultrasonography of the ovaries per rectum revealed a left ovary that was 10 cm in diameter and multicystic in appearance. The right ovary had a 40 mm follicle and edema was present in the uterus. The plasma testosterone concentration was 26.9 pg/ml. The follicle on the right ovary ovulated three days after presentation. Progesterone concentrations in plasma collected daily confirmed the presence of active luteal tissue. The differential diagnosis for an enlarged ovary in a cycling mare included ovarian hematoma, or a tumor such as a teratoma or cystadenoma. Due to the persistence of the mass over three months, the ultrasonic appearance of the mass and the ability
281
Figure 2. Histologic appearance of the multicystic ovarian mass consistent with a granulosa-theca cell tumor (100x). (Case No. 1)
of the mare to have normal follicle development which culminated in ovulation and corpus luteum formation, a cystadenoma was suspected. At the request of the owner, the enlarged ovary was removed by ventral midline laparotomy with the mare under general anesthesia. Anesthesia consisted of guaifenesin and ketamine induction with maintenance on halothane. The ovary was 9.5 cm in diameter and weighed 380 gins. A 2 cm diameter focus of firm, yellow-brown tissue, presumed to be a corpus luteum, was noted adjacent to the multicystic mass (Fig. 1). Histopathologic evaluation of this tissue confirmed the presence of luteal cells within a fibrovascular stmma. The remainder of the ovary was composed of multiple cysts lined by single to multiple layers of granulosa cells and surrounded by a variable population of thecal cells (Fig. 2), consistent with the appearance of granulosa-theca cell tumor.3 The mare was examined two weeks after surgery and the remaining ovary had 2-3 follicles 10 mm in diameter. Subsequent examinations over the next 2 months indicated that the right ovary had become inactive.
Case Two A 13 year old Thoroughbred mare was noted to have an enlarged ovary in April 1990 during a routine reproductive examination performed 30 days after foaling. The left ovary exhibited normal follicular development and the mare was bred during two estrous cycles and was confn'med to be pregnant on ultrasound examination at days 16 and 37 postovulation in June 1990. However, examination of the mare in November indicated ~at she was no longer pregnant. Reproductive evaluation in February 1991 revealed that the right ovary had enlarged markedly, whereas the left ovary was of normal size and had numerous follicles present. The mare was referred to the veterinary Medical Teaching Hospital, University of Florida, for further evaluation. Palpation of the reproductive tract per rectum disclosed a relaxed cervix, edematous uterus and a soft 45 mm follicle on the left ovary. The right ovary was large (>30 cm) with numerous fluid filled cystic structures visible on ultrasound. When presented to a stallion the mare exhibited normal estrous behavior. Differential diagnoses for the enlarged ovary included hematoma, 282
cystadenoma and granulosa cell tumor. The enlarged right ovary was removed via a ventral midline laparotomy. To facilitate removal of the ovary, 2.5 liters of yellow transudate was suctioned off a large cyst on the ovary. Surgery was completed without complications. Antibiotic administration (gentamicin and potassium penicillin) was initiated prior to surgery and flunixin meglumine (125 mg, 4 times daily) was added to the treatment regimen after surgery. Treatment was continued for seven days post surgery because the mare experienced moderate swelling at the suture line. Histopathologic evaluation indicated that the mass was a granulosa cell tumor. Transrectal ultrasound examination of the left ovary 48 hours after surgery revealed the presence of a corpus hemorrhagicum in the location oftheprevious 45 mm follicle. Serum progesterone concentrations rose from 0.64 ng/ml the day after surgery to 2.88 ng/ml five days later, confirming the present of active luteal tissue. The mare returned to estrus 16 days after the corpus hemorrhagicum was detected and ovulated 3 days later. The mare continued to develop follicles regularly on the left ovary and became pregnant on the third cycle following surgery. Granulosa cell tumors have been reported in two pregnant mares4 and in one cycling mares,2 but a majority of reports indicate that the ovary contralateral to the GTCT is inactive. 4-8The decrease in follicular activity in the contralateral ovary has been suggested to be a result of suppression of gonadotropin secretion from the pituitary secondary to ovarian steriod and inhibin production, s.7 The tumor in the first mare may have been established recently and the negative feedback effects not fully realized until the time of surgical removal. The tumor in the second mare was known to have been present for greater than one year and yet the contralateral ovary was still active. It is possible that hormone secretion by the tumor was not sufficient to suppress gonadotmpin secretion to the point where follicular development was affected.
REFERENCES 1. Hinrichs K, Hunt P R: Ultrasound as an aid to diagnosis of granulosa cell tumour in the mare. Equine VetJ 22:99-103,1990. 2. Hinrichs, K et al: Granulosa cell tumor in a mare with a functional contralateral ovary. J Amer Vet Med Assoc 1297:1037o 1038, 1990. 3. Jubb KVF, Kennedy PC, Palmer N: Pathology of domestic animals, Vol. III, 3rd ed, Academic Press, Inc., NY, 527pp, 1985. 4. Meagher DM et al.: Granulosa cell tumors in mares: a review of 78 cases. Proceedngs Amer Assoc Equine Pract, 133-143,1978. 5. Perino LJ, Didier PJ: Equine granulosa cell tumors. Equine Pract 7:14-17,1985. 6. P.iquette,GN et al: Equine granulosa-theca cell tumors express inhlbin c¢-and 8 A- subunit messenger ribonucleic acids and proteins. Biol Reprod 43:1050-1057, 1990. 7. Stabenfeldt GH et al.: Clinical findings, pathological changes and endocrinological secretory patterns in mares with ovarian tumours. J Reprod Fert Suppl. 27:277-285,1979. 8. Stickle RL et al.: Equine granulosa cell tumors. J Amer Vet Med Assoc 167:148-151,1975.
EQUIN E VETERINARY SCI ENCE