Morphologic anomalies in triploid liveborn fetuses.

Analysis of the morphologic features of 43 complete and 11 mosaic triploid infants delivered at or after 22 weeks of gestation revealed, in addition to well-delineated gross features, a number of new or previously little emphasized histopathologic features. These included testicular Leydig cell hyperplasia, increased levels of hematopoiesis, and ovarian, adrenal, and pulmonary hypoplasia. Some of these findings appeared to be linked to partial hydatidiform mole replacing the normal placenta, which was present in about 70 per cent of the triploid cases. It is important to recognize the breadth of the triploidy spectrum, which ranges from near normalcy to multisystem involvement, and to pay special attention to the placenta. The importance of correct morphologic diagnosis of triploidy is stressed in view of the fact that its occurrence apparently does not prejudice the future reproductive performance of the parents.

Human triploidy: association with partial hydatidiform moles and nonmolar conceptuses.

A retrospective pathologic review of nearly 100 spontaneous abortions of cytogenetically verified triploid constitution revealed a majority (86 per cent) falling within the category of partial hydatidiform mole, the chief criteria being focal syncytiotrophoblastic hyperplasia, focal villous edema leading to cistern formation, scalloped outline of villi, and frequent "trophoblastic inclusion" formation. The minority (14 per cent) of the conceptuses were nonmolar with a normal or hypoplastic trophoblast. The triploid fetuses in both groups tended to die at about eight weeks' menstrual age. Intrauterine retention was generally prolonged in the partial moles, whereas nonmolar conceptuses tended to abort within the first trimester, often with live or recently dead fetuses. The problem of two distinct morphologic entities within triploidy remains to be further investigated, especially with respect to the etiologic factors responsible for the division.

The clinicopathologic profile of the partial hydatidiform mole.

Having delineated the complete and the partial hydatidiform moles as 2 separate entities on the basis or morphology and cytogenetics, the authors studied 201 molar pregnancies at the Magee-Womens Hospital in an attempt to characterize the clinicopathologic profile of the partial mole syndrome. This was done mainly by comparison and contrast with the established and more familiar syndrome of the classic complete mole. The partial mole syndrome displays most of the pathologic and clinical features of the classic mole and seems to represent a milder, dilute version of the latter. This applies to placental morphology, to the fate of the embryo/fetus, and to human chorionic gonadotropin (hCG) levels as well as to the incidence and severity of clinically persistent trophoblastic disease. Preeclampsia can be equally severe in both syndromes, but tends to occur later in patients with partial mole. No metastatic disease was encountered in association with partial moles and no case of overt choriocarcinoma has yet been described. The occurrence of trophoblastic disease (as determined by postoperative hCG titers) following partial moles requires further inquiry, including study of the pathology of the underlying lesion(s), which remain virtually unexplored.

Residual trophoblastic disease in association with partial hydatidiform mole.

A 10-year retrospective study was carried out of cases diagnosed as hydatidiform mole at the University of Hong Kong. Strict morphologic criteria established in a previous report were used to study the association of the partial mole syndrome with residual trophoblastic disease. Of the total of 138 cases available, 13 were found to be partial moles, 1 of which was followed by trophoblastic disease that required chemotherapy. This subsequently proved to be an invasive (partial) mole, the first example of its kind to be verified by pathology. The extent of the association between partial mole and subsequent trophoblastic disease and the spectrum of the pathologic lesions actually underlying the latter remain to be determined by further retrospective and prospective studies.

Examination of the early conceptus.

The pathologist encounters the early, first-trimester conceptus as a product of spontaneous or surgical abortion or as a specimen from ectopic, usually tubal, gestation. In the vast majority of cases of spontaneous abortion, the embryo/fetus has been dead for 1 week to several weeks and is most often lost in the process of uterine emptying; the placenta, accordingly, stands as the main "witness" of the abortive process. The fact of embryonic/fetal death is established and dated through an interpretation of gross and microscopic changes in the villous stroma, including its vessels and the embryonic erythrocytes therein. Elective abortions performed for social reasons occasionally yield abnormal findings that suggest gestations otherwise destined to eventual spontaneous abortion. Other therapeutic abortions are indicated by abnormal sonographic or cytogenetic findings that may be correlated with the morphologic features of the evacuated conceptus. Cytogenetic abnormalities correlate to a high degree with embryonic growth disorganization and with early death, usually before the fetal stage (30 mm) is reached. Adequate sampling of the placenta, its membranes, and of the embryo/fetus is recommended. For cytogenetic studies, clean, viable specimens must be obtained; these are most often required in cases of habitual abortion.

Trophoblastic disease: clinical pathology of hydatidiform moles.

Hydatidiform moles are divided into two syndromes: those of complete and partial moles. Both forms are genetically, morphologically, and clinically distinct. Choriocarcinoma can be associated with the complete mole that has not been described for the partial syndrome. Residual trophoblastic disease, on the contrary, can be found with either syndrome, the substrate being locally invasive (nonembolic) behaviour.

Clinicopathologic features of partial hydatidiform mole.

Partial hydatidiform mole (PHM) is a distinct entity, a triploid, diandric conceptus the placenta of which shows focal trophoblastic hyperplasia (a sine qua non of diagnosis) and focal hydatidiform change; the fetus usually survives until eight to nine weeks' menstrual age. The clinical presentation is varied and preevacuation diagnosis often difficult. No choriocarcinoma has been documented in association with PHM, but residual, nonmetastatic disease can occur. The diagnosis rests ultimately with the pathologist, who has to distinguish PHM from a common abortus with villous edema and from twins in which the partners are a complete mole and a normal conceptus.

Syndromes of hydatidiform moles. Partial vs. complete.

Comparative cytogenetic studies of hydatidiform moles delineated two separate syndromes, the classic complete mole with a diploid karyotype and the partial mole with 69 chromosomes. The two syndromes are pathologically distinct, and although they have morphologic resemblances, they differ in their biology, and no transition between them is possible. In contrast to the complete mole, no choriocarcinoma has been found in association with the partial mole.

The syndromes of hydatidiform mole. II. Morphologic evolution of the complete and partial mole.

Hydatidiform moles studied with respect to cytogenetics and morphologic constitution were divisible into two syndromes: (1) complete, classical mole giving a 46 XX karyotype and (2) partial mole with an ascertainable embryo/fetus, dead or alive, giving a triploid karyotype. The complete moles undergo early and total hydatidiform change from edema to central cistern formation, the embryos proper having perished before the establishment of a functioning circulation. Trophoblastic hyperplasia is conspicuous and the connection of this group to chorioncarcinoma is well established. In the partial moles there is a slow hydatidiform change that affects only some of the villi, but which seems to follow along the same lines as in complete moles. There is focal moderate trophoblastic hyperplasia, villous "trophoblastic inclusions" (that appear in triploids only), and maze-like central cisterns in the later cases. The partial mole, 46 XX, partakes of morphologic characteristics of both main syndromes and may represent an unusual syndrome of its own. The two main syndromes can now be distinguished morphologically and the question of the association of the partial mole with chorioncarcinoma has now to be further studied.

The syndromes of hydatidiform mole. I. Cytogenetic and morphologic correlations.

Cytogenetic and morphologic analysis of 23 hydatidiform moles allowed the division into at least two syndromes: (1) the syndrome of complete (classical) mole is without an ascertainable embryo/fetus, gives a diploid karyotype, and manifests a progressive fluid engorgement of the villi as well as a gross, haphazardly distributed trophoblastic hyperplasia; (2) the syndrome of partial (incomplete) mole has an ascertainable fetus (alive or dead), gives a triploid karyotype, and exhibits a slowly progressing hydatidiform swelling in the presence of functioning villous capillaries that spares many villi; trophoblastic immaturity is constant and focal hyperplasia is inconspicuous but present. A single case of diploid mole with unusual morphologic features, complete with a fetus, may herald yet another syndrome. Human chorionic gonadotropin levels were initially high in practically all cases. There was no malignant trophoblastic disease in this small series, but a plea is made that partial moles be followed carefully in order to establish their relation to choriocarcinoma.

The effect of immune lymphocytes on reaggregation of fetal mouse tissues.

Mouse fetal metanephric tissue was disaggregated and allowed to reaggregate in hanging drop culture in the presence of syngeneic or allogeneic immune lymphocytes. Reaggregation was not obviously impaired.

Choriocarcinoma in a term placenta with maternal metastases.

Choriocarcinoma of the nonmolar placenta is presumptively a rare entity and is usually associated with widespread maternal metastases at the time of diagnosis. Nonmetastatic disease goes unrecognized and undiagnosed because placental carcinoma can be limited to a few villi, and grossly evident disease is often misinterpreted as a placental infarct. The optimal treatment for patients with choriocarcinoma of the placenta is not known but aggressive combination chemotherapy is suggested for patients with metastatic disease. Historically, the prognosis for both mother and infant has been poor.

Dispermic origin and clinical outcome of three complete hydatidiform moles with 46,XY karyotype.

Three new cases of complete, classic hydatidiform mole with a 46,XY karyotype are described. They originated by dispermy as demonstrated by chromosome and enzyme analyses. Levels of human chorionic gonadotropin decreased to normal spontaneously within a short time, indicating a benign course in these three cases. Of a total of 18 cases reported to data, postoperative clinical information was available for 10 patients. Two of these 10 patients had a malignant course with lung metastases. It is of theoretical and clinical importance to establish the magnitude of the risk of malignancy for hydatidiform mole with a 46,XY karyotype.

The pattern of hydatidiform moles in Singapore.

Hydatidiform mole is common in Singapore, and the the incidence of malignant trophoblastic neoplastic neoplasia is significantly higher than in Western countries. Within a 10-year period (1968-1977), 538 cases of hydatidiform mole were diagnosed. On retrospective study, 498 (92.6%) were considered to be complete and 40 (7.4%) partial. The ratios of complete to partial moles were similar for the major population groups. In the present study, only complete moles were found to give rise to persistent trophoblastic disease. The lack of such association in partial hydatidiform moles is in keeping with their known low malignant potential. Occasional abnormal post-evacuation hCG curves, however, are being described from other centres, and while the underlying pathology remains largely undocumented, partial moles have to be dealt with on an empirical basis in the light of the hCG follow-up levels.

Effect of hydatidiform molar vesicular fluid on blood coagulation.

The effect of fluids from both complete and partial hydatidiform moles on blood coagulation was determined. Coagulation was evaluated with use of the one-stage prothrombin time and the activated partial thromboplastin time. These studies demonstrated that the fluids shortened the activated partial thromboplastin time but not the prothrombin time. The use of plasmas deficient in factors V, VIII, IX, and X as substrate showed that the fluids shortened the activated partial thromboplastin time in the presence of plasmas deficient in factors VIII and IX but had no effect on the activated partial thromboplastin time in the presence of plasmas deficient in factors V and X. These data suggest that hydatidiform mole fluids possess procoagulant activity and that the activation of blood coagulation takes place at the level of factor X. These findings may have relevance to the placental and decidual focal necrosis seen in molar pregnancies, especially those of the complete variety.