On opening the doe carcass, about 100 -150 ml of transparent fluid was noticed in the abdominal cavity. Grossly, a yellowish pink and soft growth measuring 5.45 cm in diameter with the weight of 140 g in the right ovary was observed. Cut section revealed oozing of blood. The body of the uterus showed 8.5 × 6.5 × 4.9 cm size, multi nodular yellowish grey, soft growth weighing 250 g approximately. The cut surface of the growth revealed oozing of transparent watery fluid. The mammary glands were mildly hardened with mucus secretion. The inguinal and mesenteric lymph nodes, lungs and liver showed enlargement, mild congestion and multifocal yellowish white foci.

Cytological studies of ovarian growth showed cell with cytoplasmic vacuolation and centrally located round to oval nuclei arranged individually or in loose clusters surrounded by pink, fibrillar matrix material. The uterine smear revealed epithelial cells with pinkish cytoplasm and centrally located nucleus, suggestive of a neoplasm of epithelial cell origin. Cytological examination of uterine growth revealed epithelial cells with pinkish cytoplasm and centrally located nucleus.

Microscopically, the ovary was completely obliterated with neoplastic tissue, and there was little evidence of normal structural components, ovarian follicles, or stromal tissue. The ovarian tumour consisted of dense multiple nodules or bundles of neoplastic cells. Each bundle of neoplastic lobes was surrounded with fine fibrovascular stroma with spindle or oval hyperchromatic nuclei which were infiltrating into the neoplastic lobules and compressing the ovarian follicles. (Fig. 1). The neoplastic cells in the bundles revealed dense sheets and nests of pleomorphic round to polyhedral irregularly shaped cells with abundant finely vesiculated/vacuolated cytoplasm. The nuclei were hyperchromatic and or vesicular, centrally located, uniformly small and of round to oval shape. A few mitotic figures (1–2/hpf) were seen (Fig.2). Among the neoplastic cells, the anisocytosis and anisokaryosis were observed. However, the cells with hyperchromatic nuclei had eosinophilic cytoplasm with distinct cell border. Based on location, cytopathology and histopathology the neoplasm was diagnosed as luteoma.

Histopathologically, the myometrium showed hypertrophy of smooth muscular bundles with severe dilatation and engorgement of blood capillaries. The blood vessel walls were lined by hypertrophic endothelial cells that bulged into the vascular lumina. The endothelial cells had single or multiple hyperchromatic or euchromatic nuclei with indistinct cell margins. The uterine growth revealed well differentiated papillary type of endometrial adenocarcinoma (Fig. 3). The lining cells of the numerous papillomatous projections were supported by a thin, highly vascularized, fibrous stroma and the neoplastic cells were lined by one or two layers of highly pleomorphic columnar to cuboidal, often ciliated, epithelial cells similar to the neoplastic cells infiltrating the uterine wall (Fig. 4). The nuclei were pleomorphic (round to oval or rectangular in shape) located at the base or centrally and had multiple (4–5) nucleoli. Cytoplasm was of eosinophilic and or vacuolated type. The cell margins were distinct. A few mitotic figures were seen. Based on the location, cytopathology and histopathology the neoplasm was diagnosed as well differentiated papillary adenocarcinoma.

The other vital organs also revealed significant histopathological changes with the secondary effects of neoplastic conditions. The fallopian tube showed hyperactivity of lining epithelial cells with multifocal hyperplasia. Similarly, the mammary gland revealed severe dysplasia and hyperplasia. Fatty changes in hepatocytes in liver and proximal and distal convoluted tubules of kidneys and severe meningeal congestion/haemorrhages, multifocal gliosis, mild ependymal cell hyperplasia in brain were recorded histopathologically.

As rabbits are induced ovulators and are in estrus much of the times. The resulting persistent estrogenic stimulus may be the underlying cause. Ovarian sex cord- gonadostromal tumours are granulosa cell tumour, thecoma and luteoma. These tumours are derived from the sex cords and gonadal stroma and are differentiated from other ovarian neoplasms such as surface epithelial tumours, teratomas and dysgerminomas by their capacity to form hormonally active steroids¹¹. The cytological, gross and histopathological studies of the present case was similar to the lesion of cats reported by earlier worker¹². Nagarajan et al.¹³, recorded granulosa cell tumour accompanied with luteoma in bonnet monkey. Similarly Yamini et al.¹⁴, reported luteoma associated with hyperadrenocorticism. Histologically, they consisted of irregular glandular elements in loose vascular/myxoid stroma, and they were estrogen and progesterone receptor positive.

Severe anorexia associated with prolonged estrus caused secondary hepatic lipidosis and hepatocytic vacuolar degeneration¹². In human beings, luteomas are caused by hormone dependent proliferation of luteinized ovarian stromal cells³. Luteomas are thought to arise due to the excessive response of stromal cells to pregnancy hormones, especially hCG⁴. Continuous estrus in laboratory animals and the subsequent persistent high estrogen/progesterone ratio are thought to induce the development of endometrial carcinoma in animals¹⁵,¹⁶.

Endometrial adenocarcinomas arise in the uterine body and the adenocarcinomas develop from the glandular epithelium and usually are initially situated in the mucosal folds adjacent to the mesometrial insertion. It has been suggested that there is a progression of lesions from cystic hyperplasia to dysplasia to carcinoma-zn-sztM to carcinoma¹⁷. The hyperplastic and pre-neoplastic conditions recorded in fallopian tube and mammary glands could possibly be due to secondary effects of hormonal changes that occurred due to luteoma. Excessive estrogen production by luteomas is related to vulvar enlargement, sanguineous vulvar discharge, persistent estrus, alopecia, and aplastic pancytopenia; excessive progesterone production may cause cystic endometrial hyperplasia/pyometra complex¹².

In the present investigation, debilitation with fatty changes in liver and kidneys, severe meningeal congestion/haemorrhages, multifocal gliosis mild ependymal cell hyperplasia in brain were recorded.

Similarly, severe anorexia associated with prolonged estrus caused secondary hepatic lipidosis and hepatocytic vacuolar degeneration in cat¹². The results suggested that the ovarian luteoma could have induced an abnormally high concentration of estrogen at an initial level, later on progesterone, which might have been responsible for the present uterine endometrial adenocarcinoma. In the present investigation, rare case of the complex neoplasia of luteoma and uterine endometrial adenocarcinoma in rabbit is recorded.

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