Bulgarian Journal of Veterinary Medicine, 2017, 20, No 4, 400–407 ISSN 1311-1477; DOI: 10.15547/bjvm.994

Case report

HISTOPATHOLOGIC FINDINGS IN MULTICENTRIC PLACENTAL CHORANGIOMA WITH TROPHOBLASTIC PROLIFERATION IN A SHEEP

S. AZIZI1, R. KHEIRANDISH1, M. M. OLOUMI2 & N. NADIMI3

1Department of Pathobiology, Faculty of Veterinary Medicine, Shahid Baho- nar University of Kerman, Kerman, Iran; 2Department of Veterinary Surgery, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran; 3Graduated of Veterinary Medicine Faculty, Shahid Bahonar University of Kerman, Kerman, Iran

Summary Azizi, S., R. Kheirandish, M. M. Oloumi & N. Nadimi, 2017. Histopathologic findings in multicentric placental chorangioma with trophoblastic proliferation in a sheep. Bulg. J. Vet. Med., 20, No 4, 400–407.

The present study described chorangioma in a sheep with clinical signs of dystocia. During surgery, foetus was not found and both of the uterine horns were distended with a lot of liquid. Multiple well- demarcated nodules of firm consistency, yellow-tan colour and 2.5–4 cm diameter were projected from the cotyledons into the lumens. Histopathologically, the nodules showed expanded chorionic villi composed of proliferated blood vessels in a variable amount of loose perivascular stroma. Syncytial trophoblast cells with hyperchromatic nucleus were dispersed in the tumour’s parenchyma. Based on pathologic characteristics and according to the abundant vascular proliferation and nodular form, a neoplastic lesion named chorangioma was diagnosed. To the author’s knowledge, it is the first report of chorangioma in sheep. Key words: chorangioma, histopathology, sheep

Chorangioma, also referred to the placen- Maternal age increases the occurrence of tal haemangioma, is a benign tumour that this tumour. Chorangiomas are reported originates from the primitive angioblastic often in women more than 30 years old tissue of the (Lifschitz-Mercer et with primipara and twin pregnancies al., 1989). It is characterised with abun- (Guschmann et al., 2003). Some compli- dant vascular proliferation supported by cations in foetus or pregnant patients may villous stroma. In humans, the prevalence be associated with this tumour. Polyhy- rate of chorangioma is estimated about dramnia, preterm delivery and increased 1% of (Benirschke et al., 2006). toxaemia may occur in pregnant patients S. Azizi, R. Kheirandish, M. M. Oloumi & N. Nadimi

(Bashiri et al., 1998; Taori et al., 2008). obstetric examination, the cervix was The foetus could be affected by nonim- found closed. The vital parameters were in mune hydrops, cardiomegaly, congestive the normal range. A survey laparotomy cardiac failure, circulatory disturbances was designed from the left paralumbar (anaemia, thrombocytopenia, consumptive fossa. coagulopathy) and growth defects (prema- The animal was positioned in the right turity, growth retardation) (Demiriz et al., lateral recumbency and left low flank pre- 1997; Sepulveda et al., 2000; Batukan et pared for surgery. Inverted L local block al., 2001). was performed for analgesia with 1% li- In humans, placental tumours occur docaine (1 mL/cm2). Following approach frequently but in animals, few reports of to the uterus, foetus was not observed. placental tumours are available (Karlson & Both of the uterine horns were distended Kelly, 1941; Corcoran & Murphy, 1965; by a large volume of liquid. Multiple Kirkbride et al., 1973). The present study translucent cysts of different sizes were describes a rare case of chorangioma with notable on the endometrial surface of ute- trophoblastic proliferation in a sheep. To rine horns (Fig. 1). Under every cyst, a the author’s knowledge, it is the first re- well-demarcated nodule, 2.5–4 cm in dia- port in veterinary medicine. meter, was present. These nodules had A 3.5-year-old sheep, with distended firm consistency and yellow-tan colour. abdomen and severe straining, was re- On their cut surface, red-brown foci were ferred to the Veterinary Teaching Hospi- visible (Fig. 2). The sheep survived after tal, Shahid Bahonar University of Ker- the surgery. man. The animal was submitted to the De- Some tissue samples (1 cm3 thickness) partment of Surgery with the impression were taken from the nodules, fixed in 10% of pregnancy term, according to the date neutral-buffered formalin and then, pro- of mating as declared by the owner. In the cessed according to the standard procedure.

Fig. 1. Multiple translucent cysts in different sizes are visible on the endometrial surface of uterine horn.

BJVM, 20, No 4 401 Histopathologic findings in multicentric placental chorangioma with trophoblastic proliferation ...

Fig. 2. Gross appearance of chorangioma as a well-demarcated nodule of firm consistency and yellow-tan colour. *

Fig. 3. Cystic uterine glands (arrow) and placental chorangioma mass as a haemangiomatous lesion (asterisk) (HE, Bar=1 mm). Sections (5 µm thickness) were stai- containing proliferated blood vessels that ned with haematoxylin-eosin (HE) and were surrounded by a loose stroma. The studied by light microscopy. blood vessels had different calibers from The histopathologic study identified capillaries to arterioles that some of them two portions including haemangiomatous anastomosed together (Fig. 4). Amyloid- and cystic parts were visible for each nod- like materials (or hyalinisation) were de- ule (Fig. 3). The haemangiomatous lesion posited intervillously. Abundant syncytial was composed of expanded chorionic villi trophoblast cells with hyperchromatic

402 BJVM, 20, No 4 S. Azizi, R. Kheirandish, M. M. Oloumi & N. Nadimi nuclei were dispersed in the tumoural pa- neoplastic lesion named chorangioma was renchyma (Fig. 5). Microcalcified foci and diagnosed. necrotic changes were present in the Foetus was not found in the uterine stroma. Cellular atypia and polymorphism horns. It is supposed that it was absorbed were not observed. The remaining glands or aborted before. Since removal of all the of uterine tubes were dilated and cystic. masses was not possible, some samples According to the abundant vascular pro- were taken and the uterine incision and liferation and the nodular appearance, a the abdominal wall were closed routinely.

Fig. 4. Histopathologic features of placental chorangioma consisting of proliferated blood vessels surrounded by a loose stromal connective tissue (HE, Bar=100 μm).

*

Fig. 5. Chorangioma with hyperchromatic syncytial trophoblastic cells (arrows) and amyloid-like materials in the stroma (asterisk) (HE, Bar=10 μm).

BJVM, 20, No 4 403 Histopathologic findings in multicentric placental chorangioma with trophoblastic proliferation ...

The animal was slaughtered by the owner humans and animals (Kirkbride et al., the day after. 1973; Batukan et al., 2001; Kurman, 2002; The placenta is responsible for trans- Fox, 2003). We reported chorangioma ferring the immunity, and exchanging nu- associated with trophoblastic proliferation trients and waste products between mother in a sheep. In this form, proliferation of and foetus. The placental structure is com- placental villous vessels and trophoblastic posed of the chorionic villus (villi and cells are present that in the precious re- chorion). Vascular projections of foetal ports are used from term of chorangiocar- tissue (villi) are surrounded by the cho- cinoma by Jauniaux et al. (1988) and rion. The chorion is made of two cellular Trask et al. (1994). Khong (2000) stated layers including the outer syncytiotro- that “chorangioma with trophoblastic pro- phoblast (in direct contact with maternal liferation” is more applicable to choran- blood) and inner cytotrophoblast (Power giocarcinoma. Chorangiomas occur usu- & Kam, 2011). Placentitis is common but ally in the foetal side of placenta or in the other placental disorders such as tumours umbilical cord as single to multiple nodu- are almost unique to the human and ex- les. Taori et al. (2008) described three tremely rare in the animal species. Proli- types of chorangioma in humans including ferative lesions of the placenta are classi- angiomatous, cellular, and degenerative fied into trophoblastic and nontrophoblas- with the predominance of the angiomatous tic tumours. Nontrophoblastic tumours chorangioma type. Lez et al. (2010) stated comprise chorangiomas, , hae- that chorangioma forms could be classi- mangiomas, and haematomas that origi- fied as haemangioma endotheliomatous, nate from the blood vessels of the foetus capillarious, cavernous and fibromatous but some researchers categorise it as a form and that the most common is the containing primitive chorionic capillarious one. mesenchyme (Benirschke et al., 2006; Lez Zabka et al. (2006) reported a placen- et al., 2010). tal tumour in an East African bongo foe- In animals, placental tumours are ex- tus. They presumed a placental stem cell tremely rare. The present study described tumor on the basis of histomorphology, pathologic characteristics of multiple pla- histochemical and immunophenotypic cental chorangioma with trophoblastic results and comparing with 21 human cells in a sheep. In this case, only placenta cases of chorangioma. Kirkbride et al. was present and a foetus was not found. In (1973) described placental chorangioma gross inspection, multiple nodules with associated with in the skin firm texture and yellow-tan colour were and tongue of a bovine fetus. Placental observed in the uterine horns. Histopa- mass was 13×10×8 cm and placed be- thologically, the nodules were composed tween the chorionic and allantoic epithe- of proliferated vascular channels placed in lial layers of the placenta. Its cut surface a loose perivascular stroma. Hyperchro- had yellow color and were contained some matic trophoblastic cells were distributed dark red areas and necrotic centers. Mi- in throughout the tumour, and sometimes croscopically, proliferated capillaries with formed syncytial knots. Hyalinisation, large numbers of erythrocytes were pre- necrotic and calcified foci were the other sent in a loose fibrous stroma and these findings. In the current case, our findings findings were similar to the microscopic were consistent with previous studies in results of the present report. Other reports

404 BJVM, 20, No 4 S. Azizi, R. Kheirandish, M. M. Oloumi & N. Nadimi of placental tumours are (Leaux, ledge, it is the first report of chorangioma 1846) and myxoma (Morot, 1893) both of in veterinary medicine. them cited by Drieux & Thiéry (1948). Also, Karlson & Kelly (1941) stated a REFERENCES choriohaemangioma in the placenta of a 2- year-old Holstein cow with healthy partu- Akbulut, M., H. C. Sorkun, F. Bir, A. Eralp & rition of a male calf. E. Duzcan, 2009. Chorangiosis: the poten- Chorangioma may be misdiagnosed tial role of smoking and air pollution. Pa- with infarction or intervillous thrombi. thology Research and Practice, 205, 75– Small size chorangiomas are incidental 81. findings and not clinically significant or Al-Riyami, N., R. Al-Hadabi, T. Al-Dughaishi detectable during gross inspection (Asa- & M. Al-Riyami, 2013. Placental tumor: dourian & Taylor, 1968; Leonidas et al., what could it be? Sultan Qaboos Univer- 1975; Fox, 2003). Multicentric masses or sity Medical Journal, 13, E459–E462. those larger than 5 cm are usually associ- Asadourian, L.A. & H. B. Taylor, 1968. Clini- ated with different complications in the cal significance of placental . mother or foetus (Asadourian & Taylor, Obstetrics and Gynecology, 31, 551–555. 1968; Leonidas et al., 1975). Chorangio- Bashiri, A., E. Maymon, A. Wiznitzer, E. Ma- ma can be identified by sonography as or & M. Mazor, 1998. Chorangioma of the hypoechoic protuberant mass on the foetal placenta in association with early severe polyhydramnios and elevated maternal se- surface of the placenta. In addition, calci- rum HCG: A case report. European Jour- fication and necrosis are occasionally nal of Obstetrics and Gynecology and Re- visible (Eldar-Geva et al., 1988; Zalel et productive Biology, 79, 103–105. al., 2002). Bacon, B. J., R. D. Gilbert, P. Kaufmann, A. Pathogenesis of chorangiomas is not D. Smith, F. T. Trevino, L. D. Longo, entirely understood. It seems that hypoxic 1984. Placental anatomy and diffusing ca- conditions induce vascular growth factors pacity in guinea pigs following long-term (Kirkpatrick et al., 2007). Schwartz (2001) maternal hypoxia, Placenta, 5, 475–487. described chorangioma as a compensatory Batukan, C., W. Holzgreve, E. Danzer, E. response to improve foetal hypoxia. In an Bruder, I. Hosli, S. Tercanli, 2001. Large experimental study, proliferation of endo- placental chorangioma as a cause of sud- thelial cell had occurred in the guinea pigs den intrauterine fetal death. A case report. placentas following chronic hypoxia (Ba- Fetal Diagnosis and Therapy, 16, 394–397. con et al., 1984). Rare recurrency of cho- Benirschke, K. 1999. Recent trends in choran- rangioma suggests that some genetic or giomas, especially those of multiple and environmental risk factors such as smok- recurrent chorangiomas. Pediatric and De- ing and air pollution contribute to forma- velopmental Pathology, 2, 264–269. tion of this proliferative lesion (Akbulut et Benirschke, K., P. Kaufmann & R. N. Baer- al., 2009; Imdad et al., 2009). Dominant gen, 2006. Benign tumors and choran- opinions believe that the chorangioma is a giosis. In: Pathology of Human Placenta, 9th edn, eds K. Benirschke & P. Kauf- hamartomatous lesion rather than a true mann, Springer, New York, pp. 863–876. (Al-Riyami et al., 2013). Corcoran, C. J. & E. C. Murphy, 1965. Rare It is probable that the incidence of pla- bovine placental tumor – a case report. The cental tumours in animal species is higher Veterinary Record, 77, 1234–1235. than considered. To the author’s know-

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Ultrasound in Medicine, 21, 909–913. Dr. Shahrzad Azizi Department of Pathobiology, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Paper received 12.01.2016; accepted for Kerman, Iran publication 26.02.2016 e-mail: [email protected]

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