Hiroaki Soma

Characteristics of histopathological and ultrastructural features of placental villi in pregnant Nepalese women.

The placenta is an important functional unit for gas transfer between mother and fetus. The placental membrane, consisting of trophoblast layer interposed between maternal and fetal blood, plays an active role for intensity of respiration, but no morphological evidence has been documented. Until now, it has been reported that fetal growth retardation and increased fetal mortality rate usually could be seen at high altitude. In an attempt to find the cause of high perinatal mortality rate in Nepal, this study was undertaken to examine pathologically about 1000 Himalayan placentas obtained in Nepal and Tibet since 1977, and the results were compared with those of 5500 Japanese placentas at Saitama Medical School since 1990. In this study, characteristics of ultrastructural features of the Nepalese placental villi investigated in recent years are reported. (1) The gross characteristics of placental pathology in the Himalayan group were represented by marked subchorionic fibrin deposits and increased chorionic cysts in contrast to low incidence of intervillous thrombosis compared with those of the Japanese group. (2) As characteristics of histological findings of the placental villi between Himalayan and Japanese groups, the incidence of chorangiosis and chorangioma in the Himalayan group was significantly higher than that in the Japanese group. (3) Accompanying an increase of vasculosyncytial membrane (VSM) in the villi, thickness and separation of basement membrane of the syncytium in addition to increased apoptosis of syncytial cell nuclei were recognized. (4) As characteristic ultrastructural features of chorionic villi of Nepalese placentas, an increase of mitochondria and cystic formation of rough endoplasmic reticulum (rER), in addition to appearance of lamellar bodies similar to alveolar epithelial type II cell in organellae of the syncytium, were observed. These ultrastructural changes of the placental villous capillaries may be ascribed to hypevascularization caused by the chronic hypoxic state. It is, therefore, presumed that trophoblast cells may play an important role for gas transfer mecha-nism under such a hypoxic state at high altitude.

Epithelioid trophoblastic tumor of the lung

Epithelioid trophoblastic tumor (ETT) is a rare type of gestational trophoblastic disease and only 25 cases have been reported so far. It was first proposed by Mazur and Kurman in 1994 as an unusual type of trophoblastic tumor that is distinct from placental site trophoblastic tumor and choriocarcinoma and has features resembling carcinoma. A case of ETT of the lung in a 38‐year‐old Japanese woman is reported. The patient had suffered from a hydatidiform mole at the age of 27 years, and had four normal deliveries at the ages of 24, 31, 35 and 37 years. Because no tumor lesions were detected in the uterus, the patient was suspected of having metastatic choriocarcinoma with multiple lesions in the lung accompanied by an elevated level of human chorionic gonadotropin (hCG). In order to make an exact diagnosis, a partial resection of metastatic foci in the lung was performed. Microscopically, the tumor showed hemorrhagic necrotic foci and was composed of mainly mononuclear tumor cells and some giant tumor cells resembling trophoblastic cells. Immunohistochemical examination showed that a few large cells were stained positively for hCG, and that other cells were positive for human placental lactogen, pregnancy‐specific β1‐glycoprotein, cytokeratin 7 and inhibin‐α. In the ultrastructure, the tumor cells contained large nuclei and rich organella with desmosomes and well‐formed filaments. The diagnosis of ETT was confirmed from the findings as described above.

P57kip2 immunohistochemical expression and ultrastructural findings of gestational trophoblastic disease and related disorders

Gestational trophoblastic disease (GTD) is a unique spectrum of diseases ranging from complete hydatidiform mole (CHM), partial hydatidiform mole (PHM), and invasive mole (IM) to choriocarcinoma (CC). Placental site trophoblastic tumor (PSTT) and epithelioid trophoblastic tumor (ETT) have been classified as related disorders. Mesenchymal dysplasia (MD) may be misdiagnosed as PHM; however, it is said to have a quite different histogenesis from PHM. P57kip2 is the protein product of a paternally imprinted or maternal gene that inhibits cyclin-dependent kinases (CDK), thus serving to inhibit cell proliferation and to suppress tumor growth. Its lack of expression in trophoblastic disease plays a role in its abnormal proliferation and differentiation. In this study, P57kip2 immunostaining was absent in the trophoblastic layers of CHM and was positive in the trophoblast layer of nonmolar villi and MD. Ultrastructure of complete molar cystic villi showed tree-like branching of microvillous processes and intracytoplasmic lacunae without capillaries in the stroma, whereas MD contained many newly formed blood vessels and collagen. Also, large lacunae with microvilli and polymorphic nuclei of syncytiotrophoblast cells with well-developed organelles were observed in IM. Lung ETT following CHM and normal deliveries showed two types of large mononuclear cells and binuclear cells with abundant organelles and bundles of intermediate-type filaments in the stroma.

Placental site trophoblastic tumor of the uterine cervix occurring from undetermined antecedent pregnancy

A cervical polyp complicated by severe hemorrhage was removed from a 43‐year‐old Japanese woman (gravida 0), who had undergone tubectomy on the right side 10 years previously. The polyp was diagnosed by immunohistochemical studies as placental site trophoblastic tumor of the cervix, but no metastatic foci were found in any other uterine site. The tumor was further demonstrated by PCR polymorphisms to possess two genomic DNA of the patient and her husband. Serum β‐hCG and urinary hCG titers were both low, which rapidly fell to 0.8 mIU/mL after a total hysterectomy and remained 0.2mIU/mL after dismission.

IFPA Meeting 2011 workshop report III: Placental immunology; epigenetic and microRNA-dependent gene regulation; comparative placentation; trophoblast differentiation; stem cells

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialised topics. At IFPA meeting 2011 there were twelve themed workshops, five of which are summarized in this report. These workshops related to various aspects of placental biology: 1) immunology; 2) epigenetics; 3) comparative placentation; 4) trophoblast differentiation; 5) stem cells.

Notes on the morphology of the chimpanzee and orang-utan placenta.

The placentae of 11 chimpanzees and five orang-utans were collected from Japanese zoos immediately after delivery and were examined according to the methods routinely used for the human placenta. Placenta extrachorialis (circumvallate and circummarginate placenta) occurred in 80 per cent of the specimens collected from each species. In both groups, the placental vessels were distributed predominantly in the magistral pattern, and the umbilical cord was eccentrically inserted. Subchorionic fibrin, sometimes marked, was seen in all 16 placentae, and there was a high incidence of small intervillous thrombi and deposits of intervillous fibrin. These observations, together with the histological and ultrastructural findings, confirm the previously reported similarity between the placentae of the great apes and the human placentae.

Review: Exploration of placentation from human beings to ocean-living species

This review covers four topics. 1) Placental pathology in Himalayan mountain people. To determine morphological changes of the placenta at high altitude, pathological examination was made of 1000 Himalayan placentas obtained in Nepal and Tibet and the results compared with Japanese placentas delivered at sea level. Characteristic findings in the placental villi of the Himalayan group included high incidences of villous chorangiosis and chorangioma. These processes were clarified by ultrastructural observation. 2) Placentation in Sirenians. The giant Takikawa sea cow, which lived 5 million years ago, was discovered on Hokkaido, Japan. It was an ancestor of the dugong as well as the manatees. Sirenia, the sea cow group, shares a common ancestor with Proboscidea, the elephants, even though they now inhabit quite different environments. A comparison was made of their zonary endothelial type of placentation. 3) Placentation in sharks and rays. The remarkable placentation of hammerhead sharks and manta rays is described. 4) Placentation in the Antarctic minke whale. Placental tissue samples of this whale were obtained from the Japan Institute of Cetacean Research. In an ultrastructural study of the utero-placental junction, microfilamental processes of the allantochorionic zone and crypt formation were visualized.

Hemangioma of the Umbilical Cord with Pseudocyst

A case of umbilical cord hemangioma with a large cystic mass, diagnosed by ultrasound at 18 weeks of gestation, is reported. A normal female infant was born at 39 weeks of gestation. The umbilical cord was 32 cm long with a cystic mass (10 × 10 × 8 cm). Histopathologic examination of the umbilical cord revealed a hemangioma with myxomatous degeneration, presenting as a large cyst with thinning of the umbilical venous wall. A total of 33 umbilical cord hemangioma cases have been reported in detail, and only seven cases had a pseudocystic degeneration. The associated pathologic findings of umbilical cord hemangioma are reviewed.

IFPA Meeting 2012 Workshop Report I: Comparative placentation and animal models, advanced techniques in placental histopathology, human pluripotent stem cells as a model for trophoblast differentiation

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2012 there were twelve themed workshops, three of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of models and technical issues involved in placenta research: 1) comparative placentation and animal models; 2) advanced techniques in placental histopathology; 3) human pluripotent stem cells as a model for trophoblast differentiation.

Nitric oxide synthase from human placenta

Summary Nitric Oxide Synthase (NOS) from both soluble and insoluble fractions of human placenta was purified completely to a single protein band having molecular weight of 135 kDa by using calmodulin affinity chromatography after 2′,5′-ADP agarose affinity chromatography. The Western Blot analyses using the three types of antibodies against NOSs clearly demonstrated that NOSs from human placenta were endothelial type of NOS, and not brain or macrophage type. Using immunohistochemistry at the light and electron microscopy level, NOS was localized in syncytiotrophoblast of human chorionic villi in both early and third trimester of pregnancy. NOS was localized in microvilli of syncytiotrophoblast. In placenta from third trimester of pregnancy, the localization of NOS was at the microvilli of syncytiotrophoblast from the maternal side and the cytoplasm of endothelial cell from the fetal side. These results demonstrated that NO is produced during pregnancy mainly by endothelial type of NOS in human placenta and may play an important role in maintaining pregnancy.