a 12 year old (terrier cross) having seasons bleeding

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The etiology of persistent estrus depends on the source of persistent circulating estradiol (exogenous or endogenous). The most common etiology is estrogen-secreting follicular cysts or granulosa cell tumors. Follicular cysts have been reported to occur in up to 62% of dogs with ovarian cystic disorders. The initial database should consist of a CBC (anemia, thrombocytopenia?), a serum biochemistry profile, and urinalysis. Exfoliative vaginal cytologic examination should be indicative of estrus: >90% cornification of epithelial cells. Abdominal ultrasonography is necessary to look for endogenous sources of estradiol such as a follicular cyst or granulosa cell tumor.

Medical therapy for follicular cysts in dogs consists of treatment with gonadotropin-releasing hormone (GnRH, 25mcg IM; use 2.2 mcg/kg if Lucy is >11kg); or human chorionic gonadotropin (hCG,(NNN) NNN-NNNNIU IM) which results in luteinization of the follicles. If acute medical treatment isn't effective, only surgical removal of the ovaries will be effective. Signs of estrus should subside within 5-7 days following successful medical therapy,

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Biochemistry could suggest metastasis of tumor to major organs or concomitant disorders. The CBC is useful for cystic endometrial hyperplasia/pyometra complex, and bone marrow suppression. Granulosa cell tumors will cause an imbalance of either estrogen or progesterone. Here's a case study: Granulosa cell tumor in a bitch -Case report
Koivisto, MB
1
, Carvalho, IR
1
, Carreira, JT
1
,Trevizan, JT
1
, Machado, GF
1
, Sueiro, FAR
2
,Ciarlini, LDRP
1
, Gomes, PBCG
1
1
Department of Clinics, Surgery and Animal Reproduction, Univ Estadual Paulista, Araçatuba, Brazil, Postal Code 16050-680 and
2
Veterinay Pathology and Molecular Biology, Campinas - São Paulo, Brazil, PostalCode 13073022
[email protected]
OBJECTIVES AND METHODS: Granulosa cell tumor (GCT) originates from ovarian sex cords and may be unilateral, measuring 4 to 16 cm diameter. Females with GCT generally have hormonal unbalance such as excessive estrogen and/or progesterone production, triggering prolonged estrus, dermatological changes, and cystic endometrial hyperplasia with serosanguineous, mucupurulent or purulent (pyometra) discharge. GCT incidence increases with age, and approximately 20% cases show metastasis. Diagnosis is generally based on abdominal palpation, abdominalradiography,exploratory laparotomy and histopathology. The initial treatment is ovariohysterectomy (OHE) and in cases of metastasis, chemotherapy (1).
The objective of this study was to report a case of a young bitch with granulosa cell tumor and absence of clinical signs. The 4-year-old bitch, attended at Araçatuba Veterinary Hospital, was nulliparous, had history of contraceptive use of
unknown date, and scheduled to undergo elective OHE. During clinical examination,however, an increased volume in the ventral abdominal epigastric region of firm consistency was identified, while no change was noted in the specific physical
examination. Complementary tests such as hemogram and abdominal radiography were performed. There were no changes in the hemogram and the radiograph showed presence of a mass, but the exact location of the latter could not be concluded.
The animal underwent exploratory laparotomy which evidenced a mass occupying the whole right ovarian region with partial adherence of the kidneys and pancreas. Nephrectomy and OHE were carried out. Surgical specimens were sent to
the Pathology Sector.
RESULTS: Following surgery, biochemical assays (ALT, creatinine and urea) were carried out, indicating an increase in the enzyme creatinine (149.17µmol/L). Results of the histopathological test revealed no significant uterine changes, whereas neoplasm showed infiltration by continuity of the renal capsule and kidney compression due to its expansive growth. The neoplasm was constituted of cells arranged in distinct areas,some showing tubular arrangement and morphologically similar to follicular granulosa cells, some with areas of luteinization and others with papillary growth
areas suggestive of ovarian carcinoma. The result of immunohistochemistry favored the diagnosis of granulosa cell tumor, since cells stained positive for vimentin,
cytokeratinAE1/AE2 and inhibin, and the latter is considered the most sensitive and specific marker for granulosa cell tumors (2,3). Histological sections were subjected to an immunohistochemistry panel, leading to the following results: CKAE1/AE3
(pan-cytokeratin): positive with focal distribution (++), Vimentin: positive (+++), Inhibin;positive (+), alpha-fetoprotein: negative, CA125 (cancer associated antigen 125): negative, CK7 (cytokeratin 7): negative, CK20: negative, EMA (epithelial membrane antigen): negative.
CONCLUSION: The immunohistochemical and histopathological results characterized the neoplasm as granulosa cell tumor (GCT). Apart from the morphological variety of the cell population, there was no clinical manifestation, characterizing a probable nonfunctional tumor, which is a rare manifestation for this type of neoplasm.
(1) Morrow DA. (1986): Canine In: Current Therapy in Theriogenology 2. USA: Saunders Company 1986: 524 -525.
(2) Pelkey TJ, Frierson HF Jr, Mills SE, Stoler MH. The diagnostic utility of inhibin staining in ovarian neoplasms. Int J,
Gynecol Pathol 1998; 17 (2): 97-105.
(3) Riccardi E, Greco V, Verganti S, Finazi M. Immunohistochemical diagnosis of canine ovarian epithelial and granulosa cell tumors. J Vet Invest 2007; 19: 431-435.
Reprinted in IVIS with the permission of the Organizers

Yes, I would expect an ultrasound to be informative. Barring exploratory, it's the only practical imaging. No, 25mcg IM of GnRH is appropriate or 500IU IM of hCG. If estrus persisted in spite of treatment, there should be an increased suspicion of neoplasia. Not necessarily. We don't know if follicular cysts will reform. I don't know of any studies in that regard because dogs who fail medical treatment are invariably spayed in order to avoid chronic estrogen exposure.

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