Invasive Mole Research Articles

Use of diagnostic ultrasound in trophoblastic neoplasms and ovarian tumors.

Analyses of the data on the ultrasonic diagnostic accuracies are presented for the cases of hydatidiform mole and ovarian tumors. These data are derived from two sources: the State University of New York Downstate Medical Center (SUNY-DMC) and the Chiba University School of Medicine (Chiba U.), Japan. Diagnosis of hydatidiform mole was correct in 47 (92.2%) of 51 (SUNY-DMC) and 66 (91.6%) of 72 cases (Chiba U.). The incidences of lutein cysts were 29.4% (SUNY-DMC) and 18.1%. (Chiba U.). Ultrasound plays an important role in the postmolar follow-up: increased intrauterine echoes in the subinvoluted uterus may signal a developing invasive mole or choriocarcinoma. Ultrasonic diagnoses of 223 (SUNY-DMC) and 183 (Chiba U.) ovarian tumors have been analyzed and the rates of diagnostic errors for the individual tumors are presented. Solid ovarian tumors appear to be more difficult to diagnose than cystic ovarian tumors.

Angiographische Diagnose der Trophoblasttumoren

Pelvic angiograms were performed on ten patients with trophoblastic tumours. Together with a history and HCG determinations the diagnosis can be made with certainty. It is not possible to differentiate between invasive moles and chorion carcinomas. The results of chemotherapy can be clearly evaluated. A normal pelvic angiogram does not exclude a trophoblastic tumour with complete certainty, since this can be localised to other organs. It has the advantage over curettage of being able to show very small tumours, as well as tumours not situated in the uterine cavity.

Pituitary-Thyroid Function in Trophoblastic Disease

Pituitary-thyroid function was assessed in 12 patients with trophoblastic disease (4 hydatidiform mole, 3 invasive mole, and 5 choriocarcinoma). Thyroid-stimulating activity was detectable, by means of the McKenzie bioassay, in 6 patients (Group 1) but not in the other 6 patients (Group 2). In Group 1 serum thyrotropin (TSH) determined by radioimmunoassay was mostly undetectable and did not respond to the administration of thyrotropin-releasing hormone (TRH) determined by radioimmunoassay was mostly undetectable and did not respond to the administration of thyrotropin-releasing hormone (TRH), while in Group 2 basal TSH was detectable in half of the patients and responded to TRH in all cases. Serum concentrations of total thyroxine (T4) (18.7 +/- 2.0 mug/100 ml, mean +/- SE), free T4 (4.9 +/- 0.04 ng/100 ml), total triiodothyronine (T3) (352 +/- 72 ng/100 ml), and free T3 (0.57 +/- 0.11 ng/100 ml) in Group 1 were statistically greater than those in Group 2 (total T4, 9.2 +/- 1.0 mug/100 ml, free T4, 2.0 +/- 0.2 ng/100 ml; total T3 156 +/- 20 ng/100 ml, and free T3 0.23 +/- 0.03 ng/100 ml). Free T4 and T3 fractions were within normal limits in both groups. After treatment of 5 patients in Group 1, the thyroid stimulating activity determined by bioassay dropped to undetectable levels, the serum concentrations of thyroid hormones decreased to normal limits, and TSH response to TRH became positive. These findings indicate that an abnormal thyroid stimulator, derived from the trophoblastic tissue, stimulated the thyroid hormone secretion from the thyroid gland and in turn suppressed TSH response to TRH in some patients with trophoblastic disease.

The HL‐A and ABO Antigens in Trophoblastic Disease

No statistically significant deviations in phenotype frequencies of the 25 HL-A antigens or the ABO antigens were seen when 111 Caucasian patients with trophoblastic disease were compared with 1,259 healthy Caucasian controls. However, an increasein the incidence of HL-A11 was found in 39 patients who currently had the disease, but not in 72 who had recovered from the disease. Further, an increase in the frequency of W18 was observed among 18 patients who currently had 'invasive' disease (choriocarcinoma or invasive mole), but not in 44 who had recovered from such disease. If valid for larger patient population, these increases may suggest association of HL-A11 and W18 with the 'morbidity' of the trophoblastic disease. No increase in histocompatibility was seen in 45 patient-couples over 67 control-couples in terms of decrease in the number of male spouse's HL-A incompatibilities, and no significant difference was seen in the distribution of pregnancies in the two groups. No significant difference was observed in the incidence of different male-female combinations of ABO blood groups between 95 patient-couples and an equal number of control-couples. Lymphocytotoxic antibodies were found in 64 patients (158 sera) or 36% of the 178 patients (413 sera) examined. HL-A specific antibodies were found in 30 or 17% patients (39 sera). Of these 30, 24 patients had molar pregnancies and six had choriocarcinoma. Whether these antibodies have a role in the destruction of neoplastic tissue remains to be determined.

Immunohistochemical Demonstration of Chorionic Gonadotrophin in Trophoblastic Tumors

Chorionic gonadotrophin has immunohistochemically been localized to trophoblastic tissue. In normal placenta immunoreactivity was found in syncytiotrophoblastic cells. However, in trophoblastic neoplasms, chorioadenoma destruens and choriocarcinoma, the hormone was also found in cytotrophoblastic cells. The tumor cells showing immunoreactivity appeared to have distinct light microscopic features.

GESTATIONAL TROPHOBLASTIC NEOPLASIA

This review covers the development of chemotherapeutic treatment during the past 25 years for gestational trophoblastic neoplasia; there is now a cure rate of 80% of the cases of hydatiform mole invasive mole and choriocarcinoma. The clinician pathologist investigator will have the prime role in future breakthroughs as he has had in the preceeding developments. A review of the investigation of the pathogenesis and classification of these diseases is given. The etiology of hydatiform mole and choricarcinoma is still unknown; the incidence varies from 18 per 1000000 live births in Asia to 2 per 100000 live births in Connecticut. Dietary habits among the different ethnic groups studied were not significantly different and there has been no dietary factor associated with hydatiform mole. Malignancy rates were 36.6% in women 40 years and older and 14.3% in women with 3 or more children (versus 3.8% for women with 2 or less children). Mothers of twins has a significantly higher incidence of molar pregnancies than mothers of singleton babies. Cellular characteristics and chromosomal patterns are discussed as are hormonal tests and chemotherapy. A general management plan is outlined.

Cellular reaction in trophoblastic tumours.

The presence of a mononuclear cell reaction to 41 gestational choriocarcinomata, 10 invasive moles and 13 malignant trophoblastic teratomata has been investigated. The intensity of the reaction was graded; there was a significantly better response to therapy and survival rate in those with a "severe" cellular reaction than in those with a "mild" reaction to gestational choriocarcinoma. The pathological and clinical features of invasive moles showed no relationship with the cellular reaction to the tumour. The cellular reaction to trophoblastic teratomata was generally poor but there was a marked cellular reaction to the tumour of one patient who has enjoyed a sustained remission.The relationship of cellular reaction and response to treatment with other histological and clinical features was examined. With the exception of a positive correlation between the degree of vascular invasion and response to treatment, none was found.It is suggested that an infiltrate of mononuclear cells in gestational choriocarcinoma is probably a response to the presence of tumour antigens. The infiltrate favourably affects the response to chemotherapeutic agents, suggesting that it contributes to tumour cell death and it may be interpreted as an immunological response directed at tumour rejection.

Cellular reaction to gestational choriocarcinoma and invasive mole.

Cellular reaction to primary and metastatic gestational choriocarcinoma (CHC) was observed in histological sections from all but one of the 23 patients included in this series. The reaction was slight in 8, moderate in 5, and marked in 9. The infiltrates consisted of lymphocytes and plasma cells. A statistically significant correlation (p < 0.05) was demonstrated between the intensity of the reaction and the recovery of the patients. In 8 cases of primary invasive mole (IM), a similar reaction was observed. All these patients recovered. None of the 31 patients had had any treatment before the removal of the histological specimens examined in this study.

Invasive mole and gestational choriocarcinoma in Denmark, 1940-1969. Biological and clinical aspects.

Abstract. A survey has been made of all invasive moles and gestational choriocarcinomata registered during a 30‐year period in Denmark, a nation with a population of about 5 million (1971). All the diagnoses have been verified histologically by reappraisal. Based on clinical data the 2 groups of patients are described with reference to the following criteria: incidence and age; gravidity, parity, and latency; dissemination and course of disease; and treatment. Some case histories are reported which contrast with the view generally prevailing before the era of chemotherapy, viz. that choriocarcinoma was a highly malignant and rapidly progressive disease. All the 19 patients who had an invasive mole, including 5 with metastases, became free from symptoms, and transition from this lesion to choriocarcinoma did not occur in any of these cases. Among the 50 choriocarcinoma patients the over‐all mortality was 64%; 18 patients (36%) —10 of them with metastases—recovered. A decreasing mortality was observed during the period under investigation, but much additional work has to be done before the prognosis of the disease approaches that of invasive mole. In conclusion, the results of this study illustrate the many difficulties encountered in the diagnosis, treatment and follow‐up of these rare trophoblastic tumours. The need for collaboration in prospective cases and for centralized treatment is strongly indicated from scientific as well as therapeutic points of view.

Recent Observations Related To The Chemotherapy And Immunology Of Gestational Choriocarcinoma

Publisher Summary The tumors of human trophoblast form a spectrum of increasing malignancy ranging from benign hydatidifonn mole (through invasive mole) to choriocarcinoma. They are unique tumors in three respects: (1) they are natural allografts because the trophoblast is a fetal tissue and the tumors generally occur only in the maternal host, (2) trophoblastic tumors are endocrinologically active and the synthesis of human chorionic gonadotropin (HCG) provides an indicator of tumor activity and the effect of exogenous agents upon them, (3) many widely disseminated choriocarcinomas are curable by chemotherapy; however, they are not at all curable by present methods as some show drug resistance initially and others become resistant during therapy. Defining the basis of curability and noncurability of choriocarcinoma could have implications for a much wider range of tumors. To provide perspective for the studies of specific topics related to choriocarcinoma, some general aspects of these tumors are summarized in the chapter. It covers topics such as the general aspects of trophoblastic tumors, human chorionic gonadotropin as a “tumor index substance,” and the immunological aspects related to choriocarcinoma.

The concept of benign metastasizing hydatidiform moles.

Two patients having hydatidiform moles (chorioadenoma destruens), with histologically proven “metastases” to the lungs, survived without definitive therapy. The difficulties encountered in distinguishing this “deportation” of villi in molar pregnancies from the metastases of choriocarcinoma are presented from a clinical and pathologic viewpoint with their implications regarding therapy. The question is raised whether many so-called spontaneously “cured” cases of metastatic choriocarcinoma are the result of regression of transported molar villi and resolution of the associated pulmonary reaction, rather than regression of choriocarcinoma. The term “metastases” may have to be redefined when used in regard to trophoblastic diseases.

A review of 31 cases of malignant trophoblastic tumours.

Summary: In a series of 31 consecutive patients with malignant trophoblastic disease there were 28 patients with choriocarcinomas and 3 with invasive moles. More than three‐quarters of the patients were less than 30 years of age. Of the patients with choriocarcinoma, 13 died in hospital, 6 died at home within 3 months, 1 survived, and 8 were lost to follow‐up.

Gestational choriocarcinoma in Denmark 1940-1969. A reappraisal based on modern histologic criteria.

In Denmark, 94 cases of trophoblastic disease were classified as choriocarcinoma (CHC) or “probably CHC” during the period 1940–1969. All these cases were subjected to a reappraisal in the study presented here. Based on the criteria laid down by the Armed Forces Institute of Pathology, 50 of the cases were classified as CHC, 18 as invasive moles (IM), and 26 as other trophoblastic proliferations (OTP).Among the CHC patients, 30 died of generalized disease and one from postoperative complications. Eighteen patients (36%)—10 of them with metastases—recovered. Four of these patients have been observed for 2–5 years and 14 for more than 5 years. Finally, one patient has still active disease.Forty‐four patients suffering from IM (18) or OTP (26) were cured of their disease, including 5 with metastases. Determination of chorionic gonadotrophs was performed in 88 of the 94 patients at the time of the original diagnosis. Based on the findings at the re‐evaluation, the frequencies of IM and CHC were one case per 126 000 and 49 000 births, respectively. The ratio of IM to CHC was 1 to 2.6. As compared with Norway and Sweden, Denmark seems to have the lowest incidence of these diseases. During the years 1943–1963, CHC accounted for approx. 0.03% of all malignant neoplasms in Danish females.The study reported here forms the basis of subsequent immunologic investigations into the transplantation aspects of CHC and IM.

Malignant trophoblastic disorders: Epidemiologic aspects and relationship to hydatidiform mole

Records of all women with newly diagnosed choriocarcinoma and chorioadenoma destruens in Israel between 1950 and 1965 were reviewed. The mean annual incidence of all malignant trophoblastic disorders was 1:15,000 live births in Jewish women. Incidence was highest beyond the age of 40. There was no difference among ethnic groups in the incidence per live births except for a higher incidence among European-born women above the age of 45; birth rank had no effect. There was a secular decrease in incidence of choriocarcinoma from 1:11,700 in 1950 to 1954 to 1:40,000 in 1960 to 1965. Similarly, the risk to develop malignant trophoblastic disorders in women who previously had a hydatidiform mole declined with chronologic time period. The maximal estimate of the risk was 21.8 per cent for 1950 to 1954 and 4.4 per cent for the period from 1960 to 1965. This decline most probably reflects earlier and better recognition and therapy of hydatidiform mole.

Angiography of trophoblastic tumors. A correlation of pelvic angiography with direct four-fold magnification angiography of uterine specimens.

ANGIOGRAPHY OF TROPHOBLASTIC TUMORS A CORRELATION OF PELVIC ANGIOGRAPHY WITH DIRECT FOUR-FOLD MAGNIFICATION ANGIOGRAPHY OF UTERINE SPECIMENSMUTSUMASA TAKAHASHI, M.D. and YUKIHIRO NAGATA, M.D.Audio Available | Share

Metastatic choriocarcinoma of the tonsil following hysterectomy for an invasive mole and a period of “inactivity” of trophoblastic tissue: Report of a case

In view of the rarity of reports of metastatic choriocarcinoma of the tonsil, the occurrence of such a tumor 4 years following a hysterectomy for correction of persistent vaginal bleeding is considered worthy of recording. The period of “inactivity” of trophoblastic tissue in the mother was characterized by the absence of a metastatic deposit at the usual site and the absence of chorionic gonadotrophins in the urine.

Gestational trophoblastic disease: A comparative study of the results of therapy in patients with invasive mole and with choriocarcinoma

A study was made to compare the results of chemotherapy in patients with invasive mole and with choriocarcinoma as obtained in a Center for Trophoblastic Diseases with those obtained in 82 individual hospitals. In the Center 179 patients were treated. In the 82 hospitals 93 patients were treated, in most instances there being only one patient treated in an individual hospital. The data indicate that successful treatment is statistically better in the Center. In only one category of disease—choriocarcinoma, nonmetastatic—is the success of therapy equal in the Center and in the individual hospitals. In the 28 patients transferred to the Center, after failure of therapy in the 82 hospitals, treatment was successful in 17 (60.8 per cent). Possible reasons for the better results obtained in the Center are mentioned.

A cytophotometric study of nuclear DNA content of cyto-and syncytiotrophoblast in trophoblastic disease.

Microspectrophotometric measurements of Feulgen-stained syncytiotrophoblastic and cytotrophoblastic nuclei were carried out in 3 cases of hydatidiform mole, 1 case of chorioadenoma destruens, and 2 cases of choriocarcinoma. In all but the earliest mole studied, nuclear DNA values of the cytotrophoblast were widely dispersed in the tetraploid to hyperoctaploid range. The nuclear DNA values of syncytiotrophoblastic nuclei were restricted to a diploid to tetraploid distribution except in the 2 cases of choriocarcinoma in which the wide dispersion of values in both syncytiotrophoblast and cytotrophoblast rendered the two cell types indistinguishable.

Hydatidiform mole, invasive mole and choriocarcinoma in Sweden 1958-1965.

Abstract. All cases of hydatidiform mole, invasive mole and choriocarcinoma reported to the Swedish Cancer Registry as first diagnosed during the years 1958 through 1965 have been analyzed. The series comprises 631 cases of hydatidiform mole not followed by malignancy, 13 cases of invasive mole, 10 of choriocarcinoma developing after hydatidiform mole and 14 of choriocarcinoma without proven preceding mole. The frequency calculated on the number of medically registered pregnancies (births and abortions) was 1: 1 560 for hydatidiform mole, 1: 77 000 for invasive mole and 1: 41 000 for choriocarcinoma (Table III). The age specific rates per pregnancy rise significantly after the age of 40 both for benign mole and the malignant conditions (Table IV). The 37 cases of invasive mole and choriocarcinoma have been analyzed as to parity, clinical course, metastasis, and survival time (Tables V–IX). It is of considerable prognostic value to separate invasive mole and choriocarcinoma (following the definitions of Hertig and Novak). In this series (histologically revised by the author) all 13 patients with invasive mole (all of them treated with hysterectomy) were living and free from symptoms 2–9 years after the mole delivery. In the group, choriocarcinoma after mole 5 patients are living symptom‐free more than 9 years after the mole delivery, but 5 died from the tumour within 5 years. The group, choriocarcinoma without preceding mole proved most malignant; only 2 out of 14 survived 6–7 years. Of the 9 patients in this group with choriocarcinoma after term or near term pregnancy 8 died within 18 months. The evaluation of chorioepithelial atypia in mole curettages (3 step grading of Hertig) was not shown to be of prognostic value in this study. Regressing lung metastases were shown in 3 out of 13 patients with invasive mole. Five patients dead by metastases of choriocarcinoma were shown to have a normal uterus at autopsy.

Choriocarcinoma after hydatidiform mole. Studies related to effectiveness of follow-up practice after hydatidiform mole.

Chemotherapy, in conjunction with other methods of treatment, was used in 100 patients with invasive hydatidiform mole or choriocarcinoma following mole. When treatment was instituted within two to six months of the antecedent mole serious drug resistance was not encountered, drug toxicity was slight, the duration of treatment was comparatively short, and sustained remissions were obtained in 57 out of 60 patients. When the start of chemotherapy was delayed beyond six months drug resistance occurred in many instances, toxicity was often severe, the duration of treatment was much longer, and sustained remissions were obtained in 22 out of 40 patients.The practice of giving prophylactic chemotherapy to all patients with mole is not established as effective or safe. Differences in the social background to hydatidiform mole in different geographical areas may be such that conclusions based on evidence from one area are not necessarily applicable to another.Careful follow-up after mole remains essential, though present methods often fail to ensure recognition of choriocarcinoma while it is still curable. Standard qualitative and quantitative methods for detecting the continued excretion of chorionic gonadotrophin, though useful, are sometimes too insensitive. It is suggested that to supplement local arrangements some form of centralized or regionalized follow-up service based on notification of patients with hydatidiform mole, and making use of radioimmunoassays for chorionic gonadotrophin, could reduce deaths attributable to late diagnosis.