Pathological features of fetal anasarca in Pekingese puppies

Fotal anasarka, vucutta asiri sivi birikimi ve subkutan odem ile tanimlanan konjenital bir bozukluktur. Dokuz aylik bir Pekinez disi kopek Ankara Universitesi, Veteriner Fakultesi, Dogum ve Jinekoloji Anabilim Dali’na, guc dogum sikâyeti ile getirildi. Sezaryen operasyonuyla uc adet olu dogmus yavru cikarildi ve Ankara Universitesi Veteriner Fakultesi Patoloji Anabilim Dali’na nekropsi amaciyla gonderildi. Makroskobik olarak iki yavru normalden daha buyuktu. Bu yavrularda visseral efuzyon ve subkutan odeme rastlandigi icin fotal anasarka tanisi konuldu. Ucuncu yavruda ise pulmoner hiperplazi ile karsilasildi. Tum yavrularda ayrica, palatosizis, kus dili ve lissensefali anomalilerine rastlandi. Histopatolojik yonden incelenmesi icin organlardan ornekler alinarak rutin doku takibine koyuldu. Anasarka’li fotuslarin deri, karaciger, kalp ve bobreklerinde siddetli odem ve dejeneratif degisikliklere rastlandi. Tum fotuslarin karaciger ve dalaklarinda farkli derecelerde ekstrameduller hematopoez gozlendi. Bu calisma Turkiye’de histopatolojik olarak kopeklerde tanimlanan ilk fotal anasarka olgusunu olusturmustur. Ayrica, brakisefallik kopeklerin resesif kalitsal bir bozuklugu olan fotal anasarkaya yatkinlik gosterdikleri vurgulamistir.


Introduction
"Fetal anasarca" also known as "hydrops fetalis", "congenital edema" and "walrus syndrome" is a condition characterized by massive generalized subcutaneous edema with or without fluid accumulation in body cavities. Affected puppies are typically bigger in size which causes dystocia and neonatal mortality is very high (5,6). Multiple puppies within the litter or even the whole litter may be affected. Fetal anasarca has been commonly described in bovine and ovine species with less reports in small animals (4,5,6,7).
This report provides a pathomorphological description of canine fetal anasarca associated with various congenital abnormalities that appeared within the same litter of a Pekingese dog. To the authors knowledge this is the first histopathologically described case of canine fetal anasarca in Turkey.

Case Story
A 9-month-old Pekingese bitch was presented to the Obstetrics and Gynecology Department of Ankara University, Faculty of Veterinary Medicine with a 2-day history of dystocia. After clinical evaluation, the patient was submitted to caesarian section and three stillborn puppies were removed from the uterus. The three stillborn puppies showed different congenital abnormalities and were sent to the Pathology Department of Ankara University, Faculty of Veterinary Medicine for necropsy.
On gross examination, two out of three puppies showed generalized soft tissue edema and filling of abdominal and thoracic cavities with serous fluid and were diagnosed as fetal anasarca (Figure 1).  On skin examination, the subcutaneous tissue appeared diffusely thickened with a wet and shiny cut section ( Figure 2). One puppy had no signs of anasarca but showed a significant reduced lung weight in comparison with the other two puppies and was diagnosed as pulmonary hypoplasia. Examination of the oral cavities of all puppies revealed a deep cleft dividing the hard palate and a narrow tongue with folded margins (Figure 1). The previous malformations were respectively defined as palatoschisis or cleft palate and bird tongue. Besides, loss of cerebral gyri was noted in the brain of all fetuses and it was described as lissencephaly or agyria ( Figure 2). Samples from all organs were collected, fixed in 10% buffered formalin solution, processed routinely, embedded in paraffin, sectioned at 4μm thickness and stained with hematoxylin-eosin (HE) for histopathological examination. Histologically, the liver, kidneys, heart and skin of the anasarcous fetuses showed severe edema. Fluid accumulation in the parenchymal organs was shown as severe reticular degeneration in the liver, interfascicular edema in the heart and loose connective tissue cells separated by wide gaps in the skin and kidneys (Figure 3). Extramedullary hematopoiesis was observed to different degrees in the livers and the spleens of all fetuses. While neutrophil leucocytes surrounded the central veins (extramedullary myelopoiesis); nuclear erythrocytes and megakaryocytes were scattered between the hepatocytes and in the portal tracts (extramedullary erythropoiesis) (Figure 3).

Discussion and Conclusion
Fetal anasarca is a congenital abnormality resulting from factors that lead to failure in the homeostasis of fetal fluid. The factors or causative diseases that result in fetal anasarca are different among species and no precise etiology has so far been described in dogs. In human medicine, many factors like alpha-1 thalassemia, primary and secondary cardiac failure, renal vein thrombosis etc. were reported (2,5,6). Many literatures referred to fetal anasarca as a heritable anomaly in animals, determined by recessive genes (1,4,10). In puppies, cardiac malformations were considered as the most common reason leading to hydrops fetalis but similarly to the present case, no evidence of cardiac abnormality has been determined in many published cases of canine fetal anasarca (1,4,10).
On the other hand, genetic predisposition plays a major role in the prevalence of canine hydrops fetalis. Anasarca puppies were specially reported in brachycephalic breeds like Bulldogs, English Bulldogs, French Bulldogs, Boston Terriers, Pugs and Pekingese (2, 10, 11). The former breed was the one reported in the present case.
Additionally, the Pekingese bitch has a family history of dystocia, which may confirm the possibility of familial inheritance of fetal anasarca in dogs.
Brachycephalic breeds are also at high risk of developing other birth defects like cleft palate and are more susceptible to dystocia (9). In our case, along with anasarca, other congenital abnormalities such as cleft palate, bird tongue, lissencephaly and pulmonary hypoplasia were reported. Histologically, extramedullary hematopoiesis was also revealed in the liver and spleen of the fetuses. This latter finding was associated with the majority of previously reported cases of hydrops fetalis in different animals (4,6). Moreover, extramedullary hematopoiesis is considered a normal condition in new-born puppies (8).
This case describing a case of fetal anasarca in a Pekingese breed dog enlighten the importance of genetic factors in the development of certain congenital abnormalities such as hydrops fetalis. Inbreeding within closed familial lines may have major disadvantages such as the inheritance of undesirable disease-causing genes. These diseases can be developed when two versions of recessive genes are inherited (3). Proper breeding strategies and inbreeding avoidance play a major role in preventing some genetic diseases. This study serves also to promote further investigations of pathological findings of anasarca, wish may also help to clarify more its etiology.