Cystic endometrial hyperplasia and uterine adenocarcinoma in two miniature pigs.

One week after the ovariohysterectomy of the related partner-pig, the second 13-year-old female minipig started to show purulent vaginal discharge. The owner was advised to take the animal to the University Clinic for Swine at the University of Veterinary Medicine in Vienna for examination. The clinical examination revealed physiological findings; however, the vaginal discharge was purulent as proven by the cytological examination, indicating secondary bacterial infection. During the sonographical examination, enlarged uterine horns with a variable diameter up to 10 cm and large fluid filled cysts inside the endometrium were seen. On the ovaries, round anechogenic and hypoechogenic structures up to 0.5 cm in diameter were visible. The preliminary diagnosis was CEH/pyometra and the minipig was prepared for ovariohysterectomy. The abdominal wall was opened as described above. A 5 × 7 cm mass was localized in the corpus uteri and in the middle of the right uterine horn. The consistency was hard, the uterine wall thin and the serosa showed a dark reddish color with fibrinous coatings. Both horns were fluid filled with a diameter of 2–10 cm and some areas showed hard consistency as well. Both ovaries had corpora lutea and cysts with a diameter of 0.5 cm. The ovariohysterectomy and wound closure were performed as described above. A formalin-fixed sample of the uterine tissue was submitted to the pathohistological examination. Another sample was examined bacteriologically. The pathohistological examination revealed a well-differentiated adenocarcinoma of the endometrium with a papillary pattern and pleomorphism of the tumor cells. The irregularly arranged epithelial cell nests were accompanied by purulent inflammatory reaction and necrosis. In several locations the tumor extended into the myometrium, forming a dense and fibrous connective tissue stroma ( Fig. 7 ). Additionally, in the immediate vicinity of the adenocarcinoma, strongly dilated endometrial cysts containing small amounts of secretion in the lumen as well as a flattened epithelium could be seen, which are characteristic for cystic hyperplasia of the endometrium ( Fig. 6 ). The bacteriological finding was high grade Streptococcus equi subsp. zooepidemicus. Adenocarcinoma of the endometrium (H & E staining, bar = 80 μm). Source: R. Brunthaler. Abb. 7 Adenokarzinom des Endometriums (H & E-Färbung, Balken = 80 μm). In both cases the animals received antibiotic treatment (Amoxicillin 7 mg/kg and clavulanic acid 1,75 mg/kg) during the surgery. Post-surgery, the animals were clinically examined, and the surgical wounds were assessed daily. The animals received antibiotic treatment and pain medication (Meloxicam 0,4 mg/kg) for a period of three days after surgery. In both cases, the surgical wound healed properly, no more vaginal discharge occurred, and the animals recovered well. Five days after the respective surgery, the animals could be discharged from the clinic.

In general, the term “miniature” in miniature pigs is interpreted differently. Minipigs often grow significantly larger than their owners expect and have a life expectancy of 15–20 years, which exceeds the age expected by the owners 1 . Therefore, owners and veterinarians of minipigs have to deal with diseases, which are typical for older age, such as for example neoplasia 5 . As in our case, symptoms of uterine pathologies are often very unspecific 9 . This complicates the diagnosis and leads to the fact that the frequency of genital/uterine tumors in female pigs is often underestimated. It should be kept in mind that neoplasms of the genital tract in female minipigs, especially in older animals, can be considered as a differential diagnosis for infectious diseases and that they have to be excluded by further diagnostic measures, such as ultrasound examination. In many cases, the diagnosis can also be complicated by the lack of experience of minipig owners in handling and keeping the animals. Many owners are not properly informed before purchasing a minipig and are therefore unaware that minipigs also need routine veterinary care. These circumstances often result in not seeking help from a veterinarian until serious medical problems occur 14 . Furthermore, in many areas, there are hardly any veterinarians specialized in minipigs. In case of a young minipig, oophorectomy, ovariohysterectomy or immunocastration shortly after puberty should be considered a routine procedure, since the risk of anesthesia increases with the age of the animal and the surgery itself can be much more complicated in case of pathological uterine changes compared to a physiological uterus. The operation is easily done with a sealing device like LigaSure™; this requires significantly less time and causes significantly less bleeding than the ovariohysterectomy of a miniature pig with CEH, especially when the latter is complicated by bacterial infections and ovarian cysts. The here described operation method is highly effective in the prevention of bleeding; however, the thickness of the tissue (mesovary, mesometrium) and the tissue edema sometimes caused by ovarian cysts, require utmost care and thorough sealing or suturing. When the thickness of the tissue exceeds 8 mm, an additional suture is recommended. In young healthy animals, these problems will barely occur and the use of LigaSure™ for ovarectomy is highly recommendable. As an alternative option to surgical castration of minipigs, immunocastration should be kept in mind. For male pigs, there is a commercial vaccine against gonadotropin releasing hormone (GnRH) available (Improvac®, Zoetis, Belgium). It is used in male pigs as an alternative to surgical castration in order to reduce the boar odor, which occurs in uncastrated boars after sexual maturity, and the typical boar behavior. In males, immunized against GnRH, the production of LH and FSH is reduced, which results in reduction of the production of sexual hormones by the testes 15 . It is assumed that the immunization against GnRH in female pigs also reduces LH and FSH production, thus having similar effects on the female gonads and suppressing the estrus 16 . In Austria, Improvac® has not been licensed for the use in female pigs until now, but in a few other countries, such as Spain, Canada and several Central and South American countries it has been licensed for female pigs as well 17 . However, it should be kept in mind that for immunocastration the application of the vaccine has to be repeated regularly. Conventionally raised, food-producing male pigs, which are fattened in about 6 months, are usually injected subcutaneously with 2 doses at least 4 weeks apart, the 2. dose is administered between 3 and 10 weeks before slaughter 17 . In case of the Iberian pigs, which are slaughtered for ham production with an age of about 14–15 months, 3 injections are usually sufficient 16 . It still has to be figured out, how often an application of a gonadotropin-releasing-factor-analogue should be performed in pigs, which reach a relatively high age as pets. In addition, it has to be considered that for repeated injections in certain intervals the compliance between pet-owners and veterinarians must be assured. Since more and more cases of female pigs with pathological uteri were presented to our clinic in recent years and some similar case reports have already been described in the literature, it seems important to draw attention to this clinical picture and its consequences. For the 2 pigs in this case report, the ovariohysterectomy was performed in time, in other cases and as described in other reports, the pigs were often presented too late 5 , 9 , 11 , 12 ; therefore, sepsis and/or metastases are frequent consequences. In conclusion, CEH, pyometra and uterine tumors often occur in minipigs that are not used for breeding. The incidence increases with increasing age. Regular prophylactic examinations including abdominal sonography are recommendable, as in other pets. Ovariectomy or immunocastration of healthy female minipigs at the age of 6 months would be desirable to effectively prevent uterine neoplasia and cystic endometrial hyperplasia. The use of a vaccine for long-term immunocastration of young female minipigs is currently under investigation. Regular prophylactic examinations including abdominal sonography in minipigs kept as pets are recommendable, because CEH, pyometra and uterine tumors often occur in pigs that are not used for breeding. To effectively prevent uterine neoplasia and especially cystic endometrial hyperplasia, ovariectomy or immunocastration of healthy female minipigs may be considered. So far, no negative late effects of castration of female minipigs are known.

Miniature pigs, also called minipigs, are varieties of the domesticated pig, Sus scrofa domestica , and are considered as highly interesting laboratory animals for human research, because of their similarity in anatomy and physiology 1 , 2 . However, over the years they became popular pets as well 3 . In the Austrian animal husbandry regulation, pigs are classified as minipigs, if, due to their breed, they do not exceed a body weight of 120 kg as adult animals 4 . The owners are often not aware that adult animals can achieve a rather high body weight, which can result in a challenge to keep and handle these animals. However, it is important to know, that the same legal requirements regarding animal transportation, identification, and medication as to food-producing animals apply to minipigs, which are kept as companion animals. Unlike in horses, there is no possibility to change this status. In contrast to pigs kept as farm animals, minipigs often reach a relatively high age of 15 to 20 years as pets, which can be accompanied by diseases that are typical of older age, such as neoplasia 1 , 5 . Like in many other neoplasias, the incidence of uterine tumors increases significantly with the age of the animals. This could be the reason why tumors are rarely diagnosed in farm animals, which are slaughtered at a relatively young age 6 , 7 . It has been described that in 32 female, ovariohysterectomized minipigs, uterine lesions, such as cystic endometrial hyperplasia, leiomyoma, leiomyosarcoma, adenocarcinoma, adenoma and adenomyosis were more often found in older animals 8 . There are already several case reports describing uterine leiomyoma, uterine adenocarcinoma, and cystic endometrial hyperplasia of the endometrium (CEH) in minipigs aged between 8 and 16 years. In these cases, the symptoms usually started unspecific and ranged from reduced general behavior, anorexia, and weight loss to lameness, abdominal distension, and vaginal discharge 5 , 8 , 9 , 10 , 11 , 12 , 13 . Due to the non-specific symptoms, genital tumors are often diagnosed very late. In some of the case reports, the neoplasms where even diagnosed too late and euthanasia was indicated 5 , 9 , 11 , 12 . The following case report describes in detail the diagnostic procedure and the ovariohysterectomies in 2 13-year-old female minipigs, which were siblings and kept by the same owner. In both cases, successful ovariohysterectomy was performed after the tentative diagnosis of a uterine pathology; the clinical symptoms were variable and unspecific, and sonography was essential for decision-making. Finally, a uterine adenocarcinoma and a uterine carcinoma, in both cases combined with cystic hyperplasia of the endometrium, were diagnosed. This case report shall help practitioners to be able to diagnose and treat these animals correctly, and to advice owners concerning the prophylaxis.