Metastatic Mixed Germ Cell Tumour with Embryonal Carcinoma and Choriocarcinoma in a Female Eurasian Harvest Mouse (Micromys minutus).

Mixed germ cell tumours occur rarely in veterinary species. This report describes a case of metastatic mixed germ cell tumour in a female Eurasian harvest mouse (Micromys minutus). The tumour was extensive in one ovary and the uterus, and was characterized by two distinct tumour cell populations with features typical of embryonal carcinoma (EC) and choriocarcinoma (CC). Metastases of CC to the lungs and liver were observed. The exact origin of the CC was unclear, but the possibility of a non-gestational CC is favoured, given the context of a mixed germ cell tumour and lack of p53 expression. EC diagnosis was confirmed by immunohistochemical labelling of CD30 and lack of immunoreactivity for c-Kit. In addition, membranous ß-catenin expression was present in the EC component, indicating an inactive Wnt/ß-catenin pathway, which is required for the maintenance of pluripotency.

Endometrial adenocarcinoma with choriocarcinomatous differentiation in the uterus of a goat.

An 11-year-old female goat had invasive and metastatic endometrial adenocarcinoma in the uterus. There was a notable proliferation of endometrial epithelial cells in a tubular growth pattern, with a desmoplastic response. The endometrial epithelial tumor cells metastasized to the kidney, liver and lung. In contrast to the primary and metastatic tumor cells, pleomorphic tumor cells with a choriocarcinoma-like growth pattern infiltrated the mesometrium. Cell proliferation activity was high in both types of tumor cells. Both types of tumor cells expressed cytokeratins AE1/AE3, 7 and CAM5.2; choriocarcinomatous cells also had positive immunoreactions to human chorionic gonadotropin, human placental alkaline phosphatase and α-inhibin. The present case was diagnosed as endometrial adenocarcinoma with choriocarcinomatous differentiation.

Ectopic pregnancy with associated gestational choriocarcinoma in a California sea lion (Zalophus californianus).

A wild-born, captive-reared, 14 yr old, primiparous female California sea lion Zalophus californianus presented for anorexia of 14 d duration and abdominal distention. Routine complete blood cell count revealed leukocytosis with a neutrophilia, and serum chemistry revealed hypoalbumenemia and hyponatremia. Treatment with broad spectrum antibiotics and non-steroidal anti-inflammatories were started, but the animal continued to decline. Abdominal radiographs revealed a mature mineralized fetal skull and spine in the caudal abdomen and abdominal ultrasound revealed ascites but could not confirm the fetus. The patient was taken to surgery where a full term fetus was found outside of the uterus but within the fetal membranes, representing a secondary ectopic pregnancy. The patient passed away during surgery and was taken to necropsy. Gross necropsy revealed a diffuse peritonitis with yellow deposits over the serosal surfaces of the abdominal organs. The uterus appeared intact grossly and the ovaries appeared abnormal. The mesenteric, renal, and sub-lumbar nodes were enlarged and edematous. Histopathology revealed choriocarcinoma in the right uterine horn with evidence of chronic uterine rupture and protrusion of the placental tissue into the abdomen. The choriocarcinoma had metastasized locally as well as to the liver, spleen and lung. Choriocarcinoma is a highly malignant trophoblastic neoplasm that is rare in domestic animals. This case represents, to the authors' knowledge, the first report of gestational choriocarcinoma causing secondary ectopic pregnancy in a California sea lion and presents questions regarding pregnancy monitoring and management in a population of captive, minimally trained California sea lions.

Immunohistological Description of Nongestational Ovarian Choriocarcinoma in Two Female Mice With Conditional Loss of Trp53 Driven by the Tie2 Promoter.

Nongestational ovarian choriocarcinoma (NGCO) is a tumor of germ cell origin seldom described in nonhuman species. Few spontaneous cases are reported in macaques and mice, with the B6C3F1 strain overrepresented. This report describes 2 cases of ovarian choriocarcinoma in nulliparous female mice with conditional loss of Trp53 under the Tie2 promoter. The mouse line was maintained on a mixed genetic background including Crl: CD1(ICR) and 129X1/SvJ strains. In both cases, affected ovary was partially replaced by blood-filled lacunae lined by neoplastic trophoblast-like giant cells. Immunohistochemically, neoplastic cells expressed folate-binding protein and prolactin and were invariably negative for p53. To the authors' knowledge, this is the first report characterizing this entity in a genetically engineered mouse (GEM) line. Considering that germ cells (the cell population from which NGCO originates) constitutively express Tie2 receptor, it can be speculated that Tie2-driven deletion of Trp53 may have played a role in the development of these tumors.

Choriocarcinoma-like tumor in a potbellied pig (Sus scrofa).

A uterine tumor, with histological and immunohistochemical features consistent with those of human choriocarcinoma, was identified in a 10-year-old unmated female pot-bellied pig (Sus scrofa). The tumor showed biphasic proliferation of cytotrophoblast-like cells and syncytiotrophoblast-like cells. Immunohistochemically, the syncytiotrophoblast-like cells were positive for human chorionic gonadotropin, and both types of cells were positive for cytokeratin and negative for vimentin, octamer-binding transcription factor 4, and α-fetoprotein. Because syncytiotrophoblasts are absent in the normal porcine placenta, the tumor was diagnosed as a choriocarcinoma-like tumor.

Intrauterine fetal death with subsequent quill exfoliation and dissemination in a North American porcupine (Erethizon dorsatum).

An adult female, wild North American porcupine (Erethizon dorsatum) presented with bilateral cataracts and naso-ocular discharge. A pregnancy was identified by radiography with a near-full-term fetus, which was delivered stillborn 4 wk later with hard, developed quills. At that time, a repeated examination and further imaging, including computed tomography, demonstrated a uterine mass that was identified as a choriocarcinoma following ovariohysterectomy. Additionally, numerous exfoliated quills were discovered throughout the abdomen, most of which were removed during the surgical procedure. Ultimately, development of peritonitis despite medical care led to the porcupine's death. Necropsy confirmed a wide migration of the quills with extensive serosal adhesions and granulomas affecting liver, lungs, urinary bladder, kidneys, and gastrointestinal tract.

Primary gastric choriocarcinoma in a dog.

Primary gastric choriocarcinoma (PGC) is a rare neoplasm to date only reported in humans. This report describes a canine gastric tumour with microscopical, histochemical and immunohistochemical features of PGC. The tumour diffusely infiltrated the submucosa and muscularis propria of the pylorus and anterior duodenum, and metastasized to the gastric lymph node. Immunohistochemically, the neoplastic cells displayed aberrant expression of beta-catenin and E-cadherin, but normal expression of the adenomatous polyposis coli (APC) protein. Expression of the oncogenes c-myc and Ras was also increased. These observations suggest that this canine PGC had synchronous activation of both the Wnt/beta-catenin and Ras signalling pathways of carcinogenesis.

Non-gestational malignant placental site trophoblastic tumor of the ovary in a 4-year-old rhesus monkey.

We report a case of ovarian malignant intermediate-type trophoblastic tumor in a clinically normal, nonpregnant 4-year-old rhesus monkey (Macaca mulatta). A large solid lobulated mass replaced the right ovary and filled the pelvis. Multiple metastases were observed within the lungs and the liver. The tumor was histologically identified as predominantly composed of intermediate trophoblastic cells, without prominent hemorrhages and the classic bilaminar pattern of cyto- and syncytiotrophoblastic cells characteristic of choriocarcinoma. Immunohistochemical analysis showed the presence of placental lactogen hormone in many tumor cells and chorionic gonadotropin in a few multinucleated cells consistent with syncytiotrophoblastic differentiation. No other germ cell differentiation was identified in the pelvis mass nor in the metastases. In the absence of previous and present pregnancy, this neoplasm has to be considered as a nongestational malignant placental site trophoblastic tumor of the ovary.

Choriocarcinoma with metastasis in a rabbit (Oryctolagus cuniculi).

A 3-year-old female rabbit (Oryctolagus cuniculi) presented with apathy and indisposition for 2-3 days. Palpation revealed a mass in the caudal abdomen, namely, in the wall of the uterus. Ovariohysterectomy was performed, and the tissues were submitted for histopathologic examination. The mass consisted of 3 different (trophoblastic, syncytiotrophoblastic, and cytotrophoblastic) neoplastic cell types originating from the uterus. Immunohistochemistry was positive for cytokeratin in all 3 neoplastic cell types, and the syncytiotrophoblasts were positive also for human chorionic gonadotropin. Together these features allow the diagnosis choriocarcinoma. This report documents the first case of a spontaneous choriocarcinoma in a rabbit.

Ovarian choriocarcinoma in a rhesus monkey associated with elevated serum chorionic gonadotropin levels.

A clinically normal, 3-year-old female rhesus monkey (Macaca mulatta), which was part of a routine toxicology study, had a mass in the right ovary with metastases to the adjacent mesentery and lungs. The histologic features and immunohistochemistry results were consistent with the diagnosis of choriocarcinoma. Neoplastic cell types included cytotrophoblast (positive for cytokeratin), syncytiotrophoblast (positive for human chorionic gonadotropin), and extravillous trophoblast (positive for human placental lactogen). Because the neoplasm was present in the ovary, the uterus was normal, and the animal was not currently pregnant, this was considered a primary ovarian neoplasm of germ cell origin. The monkey had elevated serum levels of chorionic gonadotropin at the beginning of the study, indicating that, as in women, choriocarcinomas in monkeys can be associated with increased gonadotropin levels and that the tumor was preexisting at the start of the toxicology study.

Choriocarcinoma and teratoma in the ovary of a cynomolgus monkey.

An ovarian choriocarcinoma was found in a 13-year-old cynomolgus monkey (Macaca fascicularis). The tumor was accompanied by a mature teratoma in the contralateral ovary. Histologically, the choriocarcinoma was characterized by nests of cells where cytotrophoblasts occupied the periphery with syncytiotrophoblasts at the center. Immunohistochemical staining for anti-human chorionic gonadotropin was positive in the syncytiotrophoblasts. The teratoma consisted of well-differentiated epidermal cells, sebaceous glands, hair follicles, cartilage, bone, and teeth. Choriocarcinoma metastases were in multiple organs. The concomitant development of choriocarcinoma and teratoma in the ovary is a consistent finding with the human counterparts of these lesions.

Ovarian choriocarcinoma in the mouse.

Choriocarcinoma is one of the rarest ovarian tumors in any animal species. This paper describes the gross and microscopic appearance of seven such neoplasms in B6C3F1 mice. Mean age at death was 47 weeks. Tumors were described at necropsy as dark or hemorrhagic cystic lesions. On microscopic examination tumors were composed of hematocysts, intercellular hemorrhage, and cytotrophoblasts, syncytiotrophoblasts, and/or trophoblastic giant cells. Cytotrophoblasts, syncytiotrophoblasts, and occasional giant cells were present in three cases while the other four tumors contained only trophoblastic giant cells.