Signalment:  

Adult female B6 mouse, Mus musculusThe mouse was mated and suspected to be pregnant. About 14 days later the keepers suggested that the animal was not pregnant, but an abdominal swelling was reported. The animal showed a good general constitution, and food and water intake were unremarkable. The abdominal swelling was indolent. The animal was euthanized and a necropsy was performed. Formalin-fixed samples of the abdominal wall, ovaries, liver, colon and spleen were submitted for microscopic investigation.

Gross Description:  

The spleen was moderately enlarged and multiple, whitish nodules measuring up to 2 mm in diameter were observed. The liver showed a light brown coloration and was extensively and firmly attached to the small and large intestines as well as to abdominal fatty tissue. The ovaries and abdominal wall could not be identified grossly with certainty. 

Histopathologic Description:

The slide shows a section of an abdominal mass of approximately 0.75 cm in diameter with adjacent skeletal muscle of the abdominal wall and abdominal fatty tissue. The mass is surrounded by a thick capsule consisting of fibroblasts and large amounts of collagenous fibers. In the center large areas of amorphous acellular eosinophilic material is present (necrosis). Additionally, there are segments of necrotic skin with keratin lamellae and necrotic hair follicles characterized by round to oval circles with central accumulation of dark brown coarse granular pigment. Furthermore, necrotic skeletal muscles are identifiable as eosinophilic straps with cross-striations. Islands of large pale basophilic cells arranged in a honey-comb-like pattern measuring up to 40 μm in diameter with pale eosinophilic predominantly centrally located shadows of nuclei (necrotic cartilage) are present. Adjacent to the necrotic cartilage, there are partly mineralized areas of necrotic bone tissue consisting of thin cortical structures and trabeculae without identifiable cellular elements. At the periphery of the mass, there is a marked accumulation of cellular debris mostly consisting of degenerate neutrophils with numerous viable neutrophils and as well as foamy macrophages. Within and around the fibrous capsule, a mild to moderate infiltration of plasma cells and lymphocytes is found. The serosa, abdominal striated muscle, and fatty tissue show a multifocal to coalescing moderate infiltration of lymphocytes and plasma cells. Adjacent to the mass parts of the exocrine pancreas are present (not in all sections), which is similarly infiltrated as described above. 

Morphologic Diagnosis:  

Abdominal cavity, Serositis, severe, pyogranulomatous, chronic with necrotic skin, musculature, cartilage and bone; findings consistent with abdominal pregnancy.

Myositis, pancreatitis, steatitis, multifocal to coalescing, moderate, lymphoplasmacytic, chronic.

Condition:  

Ectopic pregnancy

Contributor Comment:  

Abdominal pregnancy is a form of ectopic or extrauterine pregnancy that is characterized by an abdominal location of the embryo or fetus.(1,2,5) Especially in early stages of gestation, the zygote has the ability to adhere to several maternal tissues and to connect to maternal blood vessels. Due to limitations of space and nutritional resources, embryonic or fetal death occurs in some cases concurrent with the observation of clinical signs of the mother.(2)

A distinction is made between primary and secondary ectopic pregnancy. In cases of primary ectopic pregnancy the zygote directly adheres to maternal tissue other than the uterus. Primary ectopic pregnancies in humans can be categorized into three subgroups.(1)

Ovarian pregnancy (graviditas avarice): In these cases, the embryo develops in direct contact with the ovary. Only human cases have been reported so far. 

Tube pregnancy (graviditas tub aria): It is the most frequently occurring primary ectopic pregnancy in humans that is often associated with severe intraabdominal hemorrhages. No cases have been reported in animals other than non-human primates.

Abdominal pregnancy (graviditas abdominal is): A true primary abdominal pregnancy has not been described in animals. One reason might be the fact that due to gastrointestinal movements in animals, the implantation of the zygote is inhibited. In contrast, due to the upright body position in humans, the zygote has a better chance to connect with extra-uterine maternal tissue caused by the relatively small pelvic cavity and the lesser influence of gastrointestinal movements in this area. 

In secondary abdominal pregnancy the embryo or fetus starts to develop within the uterus. Subsequently, it is dislocated to the abdominal cavity and attached to extra-uterine maternal tissue with connection to maternal blood vessels. Secondary abdominal pregnancies are reported in all domestic animals with a declining frequency: cattle, rabbit, sheep, dog, pig, cat, goat and horse.(1,2,5) In mice, abdominal pregnancy has also been induced experimentally with living fetuses placed into the abdominal cavity.(4)

Secondary abdominal pregnancy is often caused by trauma or spontaneous uterine rupture. This process is called internal birth (parts interns). In most cases, when the abdominal pregnancy is recognized the cause of the uterine rupture cannot be identified anymore. Spontaneous uterine ruptures are often a consequence of uterine torsions or other pathological uterine conditions. Directly after dislocation of the embryo or fetus into the abdominal cavity the uterus contracts and uterine contractions stop immediately. The fate of the abdominal embryo or fetus depends on the ability to connect to maternal tissue and to ensure the connection to maternal blood vessels to guarantee nutritional supply. In cases with intact amniotic membranes the probability for an embryonic or fetal survival increases.(1,2,5)

In the maternal abdominal cavity, the embryo or fetus is initially recognized as a foreign body and within hours a circumscribed, serofibrinous inflammation starts which develops to an adhesive peritoneal reaction without involvement of infectious agents. Often a capsule is formed. In cases with neoplacentation, the placental fragments lose their species-specific properties and transform into irregularly formed islets of diffuse placental connections. Neoplacentations can occur in various abdominal organs. Neoplacentations within the mesentery or the great omentum normally do not cause clinical signs of the mother. Neoplacentations in other organs may be associated with severe clinical signs of the mother due to disturbances of normal organ function. 

During the whole duration of abdominal pregnancy the embryo or fetus can die due to nutritional failure. If this happens the embryo or fetus will undergo mummification or maceration and may induce a reactive inflammatory reaction. This may lead to abscess formation and fistulation through the abdominal wall or inflammatory involvement of several abdominal organs.(2)

JPC Diagnosis:  

Uterus, abdominal cavity: Metritis and peritonitis, pyogranulomatous, focal, encapsulated, with myositis and a macerated fetus. 

Conference Comment:  

This is an interesting and descriptively challenging case during which many participants debated whether the fetus was within the uterus or free in the abdominal cavity. Some sections contained a small piece of epithelium that to most looked like gestational uterine epithelial cells. Immunohistochemical staining of the section for smooth muscle actin demonstrated that smooth muscle was present surrounding much of the lesion. The combined findings left many to conclude the pregnancy began in the uterus that subsequently ruptured and adhered to the peritoneal wall. The contributor provides an excellent overview of ectopic pregnancies, of which only secondary abdominal pregnancy has been reported in animals, which supports the opinion of most participants. 

Another important question pertaining to this case is regarding the age of the fetus. Many deliberated as to its gestational age, and subsequently, how long prior to necropsy it had died. Ectopic pregnancies occur most commonly in the fallopian tube in people, and fetal development occurs as usual until, in some instances, its size outgrows the tissues ability to expand. This may cause a rupture 6-8 weeks into gestation of a fallopian tube pregnancy.(3) With an average gestation of just 20 days in mice, the history of mating 14 days prior to necropsy indicates this fetus may have been close to term. Whether the majority of this development occurred within the uterus prior to a rupture or largely took place while attached to the abdominal wall as observed in these slides remains a point of speculation. 

References:

1. Corpa JM. Ectopic pregnancy in animals and humans. Reproduction. 2006;131:631-640. 

2. De Kruif. Von den Fr+�-+chten ausgehende St+�-�rungen der Gravidit+�-�t. In: Richter J, G+�-�tze R eds. Tiergeburtshilfe. 4th ed. Berlin, Germany: Parey; 1993:146-147.

3. Ellenson LH, Pirog EC. The female genital tract. In: Kumar V, Abbas AK, Aster JC, eds. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Philadelphia, PA: Elsevier Saunders; 2015:1036.

4. Hreshchyshyn MM, Hreshchyshyn RO. Experimentally induced abdominal pregnancy in mice. Am J Obstet Gynecol. 1964;89:829-832.

5. Weisbroth SH, Scher S. Spontaneous multiple abdominal pregnancies in a multiparous NCS mouse. Lab Anim Care. 1969;19:528-530.

Click the slide to view.

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2-1. Ectopic pregnancy

2-2. Ectopic pregnancy

2-3. Ectopic pregnancy

2-4. Ectopic pregnancy

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