Ovarian tumours are not very common in the bitch, occurring with a frequency of about 6%, which is equivalent to 0.5-1.2% of all canine tumours, and accounting for 3.7% of tumours of female reproductive organs and 20% of ovarian pathologies. The frequency of primary ovarian tumours in the queen is even lower, ranging between 0.7 and 3.6%. In both species the real incidence is unknown because of frequent spaying of subjects at a young age as a fertility control measure. The pathogenesis is unknown, although the action of oestrogens and environmental factors are considered as possible elements which may contribute to tumour development.
SIGNALMENT AND HISTORY
Among bitches the mean age for the development of epithelial ovarian tumours is around 8 to 10 years old (range, 3.5-15 years), while that for granulosa cell tumours is around 7 years old (range 14 months-16 years), for dysgerminomas 9.5 years old (range, 7-13 years) and for teratomas 6.5 years old (range, 20 months-13 years). Epithelial tumours have been reported with a higher frequency in Pointer bitches, while granulosa and theca cell tumours occur at a higher frequency in the English Bulldog and in nulliparous bitches. In the cat ovarian tumours have been reported in queens aged between 2 months and 20 years old, occurring at a mean age of 6.7 years old. Granulosa cell tumours affect subjects between 3 and 16 years old, dysgerminomas affect subjects over 6 years old (range, 1-18 years) while teratomas usually develop in subjects between 2 and 6 years old.
BIOLOGICAL BEHAVIOUR
The three main types of primary ovarian cancers in the bitch are epithelial tumours, sex cord-stromal tumours and germinal cell tumours; about 80-90% of cases are epithelial and sex cord-stromal tumours. Tumours that metastasise to the ovary are lymphosarcomas and intestinal, pancreatic and mammary carcinomas.
Ovarian tumours are often unilateral (>80%), with the left ovary more commonly affected, although epithelial neoplasms may affect both ovaries. The rate of metastasis of ovarian tumours is variable, with the peritoneum being the main site for metastatic spread.
Epithelial ovarian tumoursaccount for 20-64% (mean, 40-50%) of ovarian tumours, around 60% of which are malignant, and include adenocarcinoma, serous and papillary cystoadenocarcinomas, pseudomucous cystoadenoma, fibroma and undifferentiated carcinoma. The size and morphology of epithelial ovarian tumours are variable: the formations can grow to a considerable size (>10 cm in diameter), be smooth or cauliflower-shaped and be cystic or not. Cystic formations are more frequent in serous cystoadenomas (which probably originate from the rete ovarii) and in cystoadenocarcinomas, in which the variably sized cysts have a watery content, while the multilobulated pseudomucous cystadenomas contain a mucous, viscid fluid. Both adenomas and adenocarcinomas are often bilateral.
Stromal tumoursor sex cord-stromal tumours account for about 30-50% of ovarian tumours, and include granulosa cell tumours (around 50%) and, in lower numbers, thecomas and luteomas. Granulosa cell tumours are frequently unilateral, extremely variable in size (from <1 to >10 cm), with a texture that varies with the size, being typically hard when small and cystic and friable when larger, and all are potentially hormone-secreting, even if hormone secretion is actually observed in around 50% of cases.
The anomalous growth of embryonic cells leads to the development of two types of tumours, dysgerminomas and solid tumours, derived from the undifferentiated ovarian epithelium. The former are histologically similar to seminomas in males. Teratomas (Figs. 1 and 2) and teratocarcinomas are particular types of solid tumours containing two or three cell lines; the tissues of these tumours, of ectodermal, mesodermal and/or endodermal derivation, may contain hair, sebaceous or sudoriparous glands and nerve tissue (ectodermal derivation), cartilage, bone, teeth and smooth or striated muscle tissue (mesodermal derivation) and intestinal or respiratory epithelium (endodermal derivation). In teratomas these tissues are well differentiated, while in teratocarcinomas mature and undifferentiated tissues coexist. In the dog, teratomas/teratocarcinomas have a metastatic rate of 32%, with the involvement of multiple abdominal sites, the lungs, anterior mediastinum and bones. Dermoid cysts are teratomas that contain cysts covered by epidermis.
Germinal cell tumours (often unilateral) account for around 6-20% of ovarian tumours, with dysgerminomas and teratomas being among the more frequent. Dysgerminomas are usually of considerable size, even reaching a diameter of 30 cm, smooth, hard and multilobulated, with haemorrhagic and necrotic areas, but without cysts; they metastasise in about 10-30% of cases. Abdominal lymph nodes are the most frequent site of metastasis, however the liver, kidneys, omentum, pancreas and adrenal glands can also be involved. Teratomas, which are smaller (1-12 cm), are irregular, hard and non-cystic and contain hair, bones, teeth and other differentiated tissues. Epithelial and germinal cell tumours have an elevated metastasising potential (around 50%), while the metastatic potential of granulosa cell tumours is lower, at about 20%; these latter tumours metastasise to sub-lumbar lymph nodes, the liver, pancreas, peritoneum and lungs. Thecomas and luteomas are benign tumours.
In the queen, although adenomas, cystoadenomas and adenocarcinomas have sporadically been reported, the most frequent ovarian tumours are granulosa cell tumours, followed by dysgerminomas (20% of ovarian tumours in the queen) and teratomas. Sporadic cases of interstitial cell tumours, androblastoma and sertolinoma have also been reported. Granulosa cell tumours are frequently unilateral, can also reach a considerable size, are usually oestrogen- and progesterone-secreting, are responsible for paraneoplastic syndromes and have a relatively high potential to metastasise (reported in 6/8 cases) to regional lymph nodes, the omentum, liver, kidneys and/or lungs. Dysgerminomas are malignant tumours, usually unilateral, which are slow growing and vary in size between 2 and 30 cm. They have necrotic and haemorrhagic areas which can be seen on a sectioned surface of the tumour. These tumours can metastasise to the omentum, thoracic and abdominal lymph nodes, lungs, liver, kidneys and adrenal glands. Teratomas are benign tumours, in some cases associated with dysgerminomas, which are extremely variable in size and are characterized by the presence of ectodermal, mesodermal and endodermal derived tissues, as described in the dog.
SIGNS AND DIAGNOSIS
The more frequently encountered clinical signs of epithelial ovarian tumours are abdominal distension and a malignant effusion, caused by intratumoural oedema with fluid loss through the tumour capsule, exfoliation of tumour cells with the formation of transcoelomic metastases and a consequent possible obstruction of peritoneal or diaphragmatic lymphatic vessels, and secretion by the peritoneal metastatic foci; in some cases a pleural effusion is also found. Some bitches are asymptomatic and the tumour is found incidentally, while in other cases palpation of the cranial part of the abdomen enables the ovarian mass to be detected.
Small tumours can be detected in proximity to the caudal pole of the kidney, while large masses may deform the abdominal wall profile or, if pedunculated, may be found in the central part of the abdomen. Although radiographic examinations can be useful in the diagnosis of ovarian tumours, as they may show a mass caudal to the kidney, with ventral displacement of the caudal pole of the same kidney or medial shifting of the colon, the presence of an effusion can prevent the visualisation of abdominal organs. In such cases ultrasonography is indicated, as epithelial ovarian tumours appear as large anechoic formations, with irregular margins, located caudally to the kidney. Pyelography may be helpful in distinguishing between kidney or ovarian involvement. Cytology of any abdominal or pleural fluids may be suggestive of a malignant effusion.
Transabdominal needle biopsies for cytology should not be performed because of the high probability of disseminating neoplastic cells within the peritoneum should a malignant epithelial tumour be present. In the presence of a granulosa cell tumour the main signs are abdominal distension and ascites, caused by the obstruction of the peritoneal lymphatic vessels or by fluids deriving from the ovarian capsule.
Granulosa cell tumours, which are often hormone-secreting (oestrogens and progesterone), may cause alterations in the oestrous cycle, such as persistent or erratic cycles, vulvar oedema, with or without serous, bloody or purulent vaginal discharges and, sometimes, polydipsia/polyuria or other signs typical of cystic endometrial hyperplasia-pyometra, [7] which is observed in over 90% of bitches with granulosa cell tumours, especially when the tumours secrete progesterone. High concentrations of oestrogen in the blood may cause haematological alterations such as non-regenerative anaemia and thrombocytopenia, bilateral symmetrical alopecia of the trunk with possible lichenification and hyperkeratosis. Anorexia, loss of weight, vomiting and diarrhoea are other signs which may be present in the case of metastases.
The presumptive diagnosis is based on the identification of an abdominal mass and on the results of colpocytology and hormonal assays, taking the necessary caution in interpreting the hormone concentrations depending on the different phases of the oestrous cycle. The predominant clinical sign in both dysgerminomas and teratomas is abdominal distension, with no peritoneal effusion; there may be no other signs at all, with the exception of cases with metastases, nor any alterations in ovarian function. Large masses may be detected by transabdominal palpation and seen on X-rays as soft tissue masses; in cases of teratoma, mineralisation of bone elements may be seen. Around 50% of epithelial ovarian tumours metastasise, with the spread of 1-2 mm nodules to the peritoneum and to the serosal surface of various abdominal organs; these small nodules are often not identifiable by either radiography or ultrasonography. Granulosa cell tumours are usually well capsulated and do not present signs of local or metastatic invasiveness; metastases are present in about 10-20% of cases, infiltrating the omentum, mesentery, diaphragm, liver, kidneys, urinary bladder and intra-abdominal lymph nodes. Metastases occur in about 10-20% of dysgerminomas and preferentially infiltrate the intra-abdominal lymph nodes, liver and kidneys, while in teratomas the rate of metastasis is 33-50% with infiltration of the skeleton, intra-abdominal and peripheral lymph nodes, lungs and omentum. The definitive diagnosis is always based on histological findings.
In the queen ovarian tumours may be identified by transabdominal palpation of the central or cranial part of the abdomen, with the detection of variable sized masses, accompanied by different signs, depending on whether there are metastases and their site (ascites, vomiting, etc.) and on the presence of paraneoplastic syndromes related to the production of hormones. In this latter case signs may include prolonged oestrous cycles, vulvar oedema, occasional bloody vaginal discharge, cystic endometrial hyperplasia-pyometra complex, alopecia, oestrogen-induced aplastic pancytopenia, a special attraction for males and virilisation. The diagnosis is based on a complete clinical examination with the help of abdominal and chest X-rays and abdominal ultrasonography in order to confirm the presence, site and characteristics of the tumour and to ascertain the presence of any metastases. Colpocytology and hormone assays may be helpful, while a complete blood count is indicated to demonstrate the possible presence of oestrogen-induced pancytopenia. Just as for the bitch, the final diagnosis is based on histology.
For both dogs and cats, the Tumour, Node, Metastasis (TNM) staging system requires the collection of clinical and post-operative information on the primary tumour, on lumbar regional lymph nodes and on any remote metastases, together with evaluation of imaging studies (chest radiography, nuclear magnetic resonance imaging, computed tomography).
TREATMENT
The management of epithelial ovarian tumours, in both the bitch and the queen, is based on surgical excision, together with total ovariohysterectomy to avoid metastases or the effects of the tumour on the uterus. Chemotherapy is necessary when there are metastases. In a dog with a granulosa cell tumour, surgical excision combined with total ovariohysterectomy is indicated, also in view of the possible infiltration of the uterus by a malignant neoplasm. However, in subjects used for breeding, excision of only the ovary may be considered, if it has first been ascertained that the uterus is normal (absence of cystic endometrial hyperplasia-pyometra or of other contraindications). It should be noted that in one third of cases, unilateral granulosa cell tumours are associated with inactivity of the contralateral ovary. For ovaries affected by germinal cell tumours surgical excision is the management of choice and total ovariohysterectomy is suggested to contain the risk of metastases. Tumours must be handled with great care during ovariohysterectomy in order to avoid cell dissemination, which is typical of some malignant tumours. The abdominal organs and the serosae must also be inspected carefully in order to verify the absence of macroscopically evident metastatic lesions and, in the case of suspicious lesions, to excise or take targeted biopsies of the affected organs. Radiotherapy is not indicated, while chemotherapy (with different protocols) has given positive results as palliative therapy.
PROGNOSIS
Information on the life expectancy of bitches affected by ovarian tumours is scarce. There are reports of survival of up to 4 years following surgical excision of dysgerminomas and of up to 6 years after removal of teratomas. The prognosis seems to be independent of the type of ovarian tumour. The prognosis is good for single and totally excised tumours, while it is guarded or poor in the presence of metastases. Chemotherapy has proven useful in prolonging survival. Information from queens is even scarcer, and only one case of feline teratoma has been reported in which the patient had no signs of disease 1 year after surgical excision, and one case of granulosa cell tumour in which the queen was euthanized 5 months after the surgical excision for reasons related to the tumour. In general terms, it can be stated that the general principles outlined for the bitch may be considered valid also for the queen.
Suggested readings
- Argyle DJ, Brearley MJ, Turek MM (2008) Tumors of the female genital tract. In: Decision making in small animal oncology, Blackwell, Ames: 315-318.
- Klein MK (2007) Tumors of the female reproductive system. In: Withrow SJ, Vail D. Withrow and MacEwen’s small animal clinical oncology. Saunders, S.Louis: 610-618.
- McEntee MC (2002) Reproductive oncology. Clin Tech Small Anim Pract,17: 133-149.
- JohnstonSD, Root Kustritz MV, Olson PNS (2001) Disorders of the feline ovaries. In:Canine and Feline Theriogenology. Saunders 3rd ed Philadelphia: 453-462.
- JohnstonSD, Root Kustritz MV, Olson PNS (2001) Disorders of the canine ovary. In:Canine and Feline Theriogenology. Saunders 3rd ed Philadelphia: 193-205.
- Morris J, Dobson JM (2001) Genital tract. In: Small animal oncology, Blackwell, Oxford: 166-174.