D. NAK, A. ALASONYALILAR DEMİRER, B. TUNA, Y. NAK, M. Ö. ÖZYİĞİT
T urk. J. Vet. Anim. Sci.
2012; 36(1): 61-66 
Case Report © TÜBİTAKdoi:10.3906/vet-1012-7
Vaginal prolapse related to ovarian granulosa cell tumor in an 
Anatolian Shepherd.
Deniz NAK1,*, Aylin ALASONYALILAR DEMİRER1, Bilginer TUNA1, Yavuz NAK1, M. Özgür ÖZYİĞİT2
1Department of Obstetrics and Gynecology; Faculty of Veterinary Medicine, University of Uludağ,
16059 Bursa - TURKEY 
2Department of Pathology, Faculty of Veterinary Medicine, University of Uludağ, 16059, Bursa - TURKEY 
Received: 03.12.2010
Abstract: A 4-year old, primiparous, female Anatolian Shepherd dog was presented for evaluation of type II 
vaginal prolapse with alopecia of the left  perineal skin. Hematological analyses demonstrated leukocytosis and 
thrombocytopenia. Estradiol (E2) and progesterone (P4) levels were 156 pg/mL and 2.3 ng/mL, respectively. Th e 
vaginal smear was predominantly (at least 80%) made up of anuclear superfi cial cells. An abdominal ultrasonography 
revealed a heterogeneous multicystic mass with anechoic areas adjacent to the caudal pole of the left  kidney. An 
ovariohysterectomy was performed. Ten days aft er the surgery, the prolapsed vagina was completely regressed. A 
histopathological examination of the ovarian mass demonstrated that it was a granulosa cell tumor.
Key words: Dog, ovarian tumor, vaginal prolapsed
Kangal ırkı bir köpekte ovaryumdaki granulosa  hücre tümörü ile ilişkili prolapsus 
vajina olgusu
Özet: Kangal ırkı 4 yaşlı, daha önce bir doğum yapmış dişi bir köpek sol perineal bölgede alopesi ile birlikte prolapsus 
vajina tip II şikayetleri ile Doğum kliniğine getirildi. Kan muayenesinde lökositosis ve trombositopeni tespit edildi. 
Östradiol (E2) ve progesteron (P4) seviyeleri sırasıyla 156 pg/mL ve 2.3 ng/mL idi. Vajinal smearda anükleer süperfi siyel 
hücreler (en az % 80) baskın hücre topluluğunu oluşturduğu dikkati, çekti. Ultrasonografi de sol böbreğin kaudaline 
yakın anekoik alanlar içeren heterojen multikistik bir kitle gözlendi. Overiohisterektomi sonrası operasyondan 10 gün 
sonra prolapsus vajinanın tamamen gerilediği görüldü. Ovaryumun histopatolojik muayenesinde granulosa hücre 
tümörü teşhis edildi.
Anahtar sözcükler: Köpek, ovaryum tümörü, prolapsus vajina
* E-mail: deniznak@gmail.com
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Vaginal prolapse related to ovarian granulosa cell tumor in an Anatolian Shepherd.
Introduction
Th e most common causes of vaginal/vestibular 
masses in the bitch are vaginal prolapse, vaginal 
neoplasia, and urethral neoplasia protruding into the 
vaginal vault (1). Vaginal prolapse is the protrusion 
of edematous vaginal tissue into and through the 
opening of the vulva, occurring during the pro-estrus 
and estrus stage of the sexual cycle (1,2). It does not 
occur during anestrus (2). Although it occurs almost 
always in intact female bitches (2), it has also been 
reported in an ovariohysterectomised bitch (3). True 
vaginal prolapse may occur near parturition, as the 
serum concentrations of progesterone decline and 
oestrogen increase (2,4). It occurs less commonly in 
diestrus and normal pregnancy (2,5). Th e disease can 
be caused by vaginal tumors (6) or trauma (7), but 
this is fairly rare.
Ovarian tumors are relatively uncommon in the 
bitch. Th e majority of ovarian tumors are epithelial 
tumors, sex cord stromal tumors, and germ cell 
tumors. Sex cord stromal tumors include granulosa Figure 1. Alopecia and type II vaginal prolapse in an Anatolian 
cell tumors (GCTs), theca cell tumors or thecomas, Shepherd bitch.
and luteomas (2). Granulosa cell tumors may have 
the ability to produce estrogen and progesterone, 
resulting in clinical signs related to the reproductive Results and discussion
tract. However, to the best of our knowledge, there 
are no published data available about vaginal prolapse During a physical examination, the animal 
related to ovarian granulosa cell tumors. Th e present appeared healthy with no abnormalities other than 
report describes a clinical case of a vaginal prolapse, a protruding tissue of vulva, lichenifi cation, and 
type II, which developed due to an ovarian granulosa hyperpigmentation, with alopecia on the left  perineal 
cell tumor in a 4-year-old Anatolian Shepherd bitch. skin. Rectal temperature, heart rate, respiratory rate, 
mucous membrane color, and capillary refi ll time 
were all within normal ranges. A hematological 
Case history examination (Abbott Cell-Dyn 3500 hematological 
A 4-year-old, primiparous Anatolian Shepherd bitch, analyzer, Gml Inc, Ramsey, Minnesota, USA) revealed 
weighing 34 kg, was presented to the University of an increased total white blood cell count (WBC) 
Uludağ, Department of Obstetrics and Gynecology (17.3 × 109/L; normal range 5.4-15.3 × 109/L) and a 
clinic with a 7-day history of type II vaginal decreased platelet count (118 × 109/L; normal range 
prolapsed (Figure 1). Th e bitch had been in estrus, 4 160-525 × 109/L). Th e diff erential cell count indicated 
weeks before this presentation, and the estrus cycle an increased neutrophil count (89.9%; normal range 
was regular. Th e bitch was treated with aglepristone 51%-84%). Th e remaining hematological fi ndings 
(Alizine, Virbac) in a dose of 10 mg/kg of body were within normal ranges (8). Neutrophilic 
weight subcutaneously, once daily, on 2 consecutive leukocytosis and thrombocytopenia were determined 
days, for the prevention of pregnancy aft er 2 weeks in the bitch. Estradiol (E2) and progesterone (P4) 
of unwanted mating. No vaginal prolapse had been concentrations were assayed by the Immulite System 
observed during any previous pro-estrus or estrus (Immulite 1000, Siemens/DPC, New Jersey, USA) 
periods. Th e bitch was fed a home-prepared diet and using Immulite estradiol and progesterone test kits 
housed as a bandog. (Diagnostic Products Corporation, California, USA). 
62
D. NAK, A. ALASONYALILAR DEMİRER, B. TUNA, Y. NAK, M. Ö. ÖZYİĞİT
Concentrations of estradiol (E2) and progesterone was recommended for treatment of the ovarian mass 
(P4) were 156 pg/mL and 2.3 ng/mL, respectively. and vaginal prolapse. Th e dog was premedicated 
Vaginal cytology revealed more than 80% anuclear with 2 mg/kg intramuscular xylazine HCl (Alfazyne 
superfi cial vaginal epithelial cells, which was 2%, Alfasan) and anesthesia was induced with 4 mg/
compatible with a smear from late pro-estrus or early kg intravenous propofol (Propofol 1%, Fresenius 
estrus. An ultrasound examination (Terason Portable Kabi AB). General anesthesia was maintained with 
Ultrasonography System, Teratech Corporation, isofl urane (Forane Likid, Abbott) in oxygen. For 
Burlington, USA) of the abdomen identifi ed a large, prophylaxis, at induction, 8.75 mg/kg intramuscular 
12-cm, roundish, heterogeneous ovarian mass in the Amoxicillin/clavulanic acid (Synulox, Pfi zer) was 
left  mid-abdomen, just caudal to the left  kidney. Th e administered and then the standard protocol was 
mass was composed of large, multiple, ill-defi ned, continued. Th e dog was closely monitored during the 
hypoechoic structures and multiple echogenic surgery with pulse oximetry and electrocardiography. 
septa were visible internally (Figure 2). Scanty fl uid Th e ovariohysterectomy was performed through 
was seen in the uterine lumen and the uterus was a midline incision. Th e bitch had an uneventful 
mildly increased in size. Other abdominal organs recovery. Th e protruding vagina was completely 
were considered within normal limits and no other regressed 10 days aft er the ovariohysterectomy.
pathological structures were revealed. Radiographic Grossly, the left  ovarian tumor (12 × 12 cm) had 
examination of the thorax and abdomen revealed no irregular, protruding nodules, red to brownish in 
specifi c pathological fi ndings related with metastasis. color. Its cut surface displayed solid and multicystic 
Th e ovarian mass was not well viewed. A presumptive components. Th e cysts (2-4 cm in diameter) 
diagnosis was made as type II vaginal prolapse contained serous reddish fl uid. Th e right ovary (1.5 
related to an ovarian mass. An ovariohysterectomy × 2.0 cm) was normal in size (Figure 3). Th e uterine 
horns were mildly enlarged (up to 2 cm in diameter) 
and showed slightly annular constrictions (Figure 
3). A mild amount of red-brown serous exudate was 
seen in the uterine lumen. Th e endometrial surface 
was covered in a disseminate manner by a dark red-
brownish exudate. Th e endometrium was slightly 
thickened, hemorrhagic, and edematous. Ovarian 
and uterine samples were fi xed in 10% neutral 
formalin and embedded in paraffi  n. Th e sections 
(5 μm) were stained with hematoxylin and eosin 
Figure 2. Sagittal ultrasonographic image of the left  ovary 
including the ovarian granulosa cell tumor in the 
dorsal recumbency. A mass was heterogeneous with 
multicystic anechoic fl uid-fi lled areas (right arrow) Figure 3. Reproductive tract of the bitch, showing mild 
separated by echoic septa (left  arrow). enlargement of uterine horns and a left  ovarian tumor.
63
Vaginal prolapse related to ovarian granulosa cell tumor in an Anatolian Shepherd.
(HE). A histological examination revealed that the and estrus stage of the sexual cycle and the fi rst 3 
ovarian neoplasm consisted of a central population estrous cycles in younger bitches (<2 to 3 years). No 
of proliferating granulosa cells, with interposed breed predisposition has been described, although it 
irregular fi brovascular septa. An outer capsule of appears that the incidence of the condition is higher 
fi brous tissue surrounded the neoplastic tissue. Th e in large breed bitches (2). In accordance with this 
neoplastic cells were mostly cuboidal and occasionally literature, the bitch was a large breed bitch, but was 5 
slim columnar cells with central nuclei and a years old and in diestrus. 
moderate amount of pale staining foamy cytoplasm. Th e mean age at diagnosis of GCT is 7.7 years, 
Th ere were extensive areas of hemorrhage within the with a reported range of 14 months to 15 years (2,9). 
center of the tumor. A “Call-Exner” body formation Most of the bitches with GCT were nulliparous. GCTs 
was detected in the neoplastic areas, whereas mitoses are usually unilateral, although bilateral masses have 
were not observed (Figure 4). A left  ovarian GCT was been reported. GCTs vary between 0.4 cm to greater 
diagnosed, while the contralateral ovary presented a than 10 cm in diameter. Smaller tumors are usually 
corpus luteum formation. In the uterus, moderate solid, and larger tumors oft en are friable and cystic 
cystic glandular hyperplasia of the endometrium was (2,9-11). Th e present case was in agreement with 
observed. A moderate lymphoplasmacytic infi ltrate the above reports, except for being primiparous. 
with neutrophils and mononuclear phagocytes and Th e tumor was unilateral and there were corpora 
diff use hemorrhage with edema were also observed lutea on the other ovarium. Clinical signs referable 
within the endometrial connective tissue. A moderate to increased serum estrogen concentrations include 
hypertropia has been observed in the myometrium. persistent or erratic estrus, vulvar swelling and 
Compared to other vaginal disorders, vaginal serosanguineous vulvar discharge, purulent vulvar 
prolapse is an uncommon condition in the bitch (4). discharge, polyuria/polydipsia, and other signs 
Vaginal prolapse is usually seen during the pro-estrus of concurrent cystic endometrial hyperplasia-
A B
C D
Figure 4. A: Granulosa cell tumor (GCT), composed of clusters of neoplastic cells 
(NC) surrounded by fi brovascular tissue (Fvt), HE. Bar 200 μm. B: Cystic 
pattern in the tumor disrupted by a hemorrhage (H) HE. Bar, 100 μm C: GCT 
demonstrating “Call-Exner” body formation (arrow). HE. Bar, 100 μm D: 
GCT, demonstrating “Call-Exner” body formation (arrow). HE. Bar, 50 μm.
64
D. NAK, A. ALASONYALILAR DEMİRER, B. TUNA, Y. NAK, M. Ö. ÖZYİĞİT
pyometra complex, non-regenerative anemia with tumors can be recognized ultrasonographically as a 
agranulocytosis and thrombocytopenia resulting mass lesion in one or both ovaries. Tumors may be 
from estrogen-induced bone marrow toxicity, and predominantly solid, solid with a cystic component, 
skin changes characteristic of hyperestrogenism, or primarily cystic and complex (2,12,13). In 
including bilateral symmetrical alopecia of the the present case, an ovarian mass was imaged 
trunk, lichenifi cation, and hyperkeratosis (2,9- ultrasonographically as a cystic component, caudal to 
11). In our case, there was type II vaginal prolapse the left  kidney. Most likely, the tumor could not be well 
and changes in the skin on the left  perineal area. shown radiographically because it had a multicystic 
Neutrophilic leukocytosis and thrombocytopenia structure. Ultrasonography was considered 
were detected in the hematological examination. diagnostic because it revealed information on organ 
GCTs are oft en functional, elevations in serum architecture and relationships of radiographically, 
estrogen concentration alone, or together with silhouetting soft  tissue structures. Surgical removal 
serum progesterone elevation may occur. Reported of the ovary with the tumor is the recommended 
serum estrogen concentrations in a functional treatment, with complete ovariohysterectomy most 
GCT range from 55 to 166 pg/mL. Reported serum oft en indicated. Ovariohysterectomy may hasten 
progesterone concentrations range from 0.64 to 11.0 the resolution of vaginal prolapse by removing the 
ng/mL, with values greater than 2 ng/mL indicative primary endocrine stimulus, the estrogen-secreting 
of active progesterone secretion by the tumor (2). ovary. Th e regression of prolapsed vaginal tissue 
In our case, estradiol (E2) and progesterone (P4) is reported to occur aft er 4 to 8 days or within 21 
levels were 156 pg/mL and 2.3 ng/mL, respectively. days of the ovariohysterectomy (2). In our case, the 
GCTs are usually well encapsulated, with no local prolapsed vagina was completely regressed 10 days 
invasion. Metastasis is reported to occur in 10%- aft er the ovariohysterectomy. 
20% of cases. Reported sites of metastasis include Initially, in this case, only a type II vaginal prolapse 
the omentum, mesentery, peritoneum, diaphragm, was diagnosed during the clinical examination, 
liver, kidneys, urinary bladder, and intra-abdominal but aft er the detailed clinical and histopathological 
lymph nodes (2,10,11) In this case, no evidence of examinations, an ovarian granulosa cell tumor was 
metastatic disease was observed. Th e tumor may diagnosed as the cause of the vaginal prolapse. An 
be visualized by radiography as a soft  tissue density exact diagnosis led us to a suitable treatment choice. 
mass or by ultrasonography as a mass, with complex Both the ovarian tumor and prolapsed vagina 
echogenicity caudal to the kidney. Ultrasonography were completely treated by ovariohysterectomy. 
is helpful for diagnosing the origin of ovarian masses Furthermore, a cause was demonstrated for the 
and for checking for abdominal metastasis. Ovarian uncommon prolapsed vagina in the bitch. 
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