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Hydatidiform mole metastasizing to the lung.

Pulmonary lesions developed in three patients with an invasive hydatidiform mole. At open thoracotomy the modules were found to contain molar tissue. Therapy with twice-weekly methotrexate induced complete clinical and biologic remission of the disease in all three patients.

Adolescent

Selective expression of paternal human major histocompatibility antigens on the surface of hydatidiform mole cells.

The typing of human major histocompatibility antigens (HLA) of two cases of invasive hydatidiform mole showed that the fibroblast-like cells as well as trophoblasts from the mole selectively expressed paternal HLA haplotype specificity but not maternal HLA on the surface. This result was completely in agreement with the notion of androgenetic origin of hydatidiform mole from the aspects of HLA specificity. Immunological implication of this finding and development of chorionic tumor were discussed in the light of fetomaternal relationship and host immune surveillance against the tumor.

Epitopes

Detection of pregnancy specific beta1-glycoprotein in formalin-fixed tissues.

Using an enzyme-bridge immunoperoxidase method, pregnancy specific beta1-glycoprotein (PSbetaG) has been demonstrated in the cytoplasm of the trophoblast in several formalin-fixed tissues, namely, implantation sites of ovum, normal placentae, hydatidiform moles, invasive moles, and choriocarcinomata of uterus and testis. It is suggested that this technique may prove helpful in the detection of choriocarcinomatous elements in malignant tumours.

Choriocarcinoma

Gestational trophoblastic neoplasms: morphologic considerations.

Abnormal trophoblastic proliferation is the hallmark of a spectrum of lesions constituting the gestational trophoblastic neoplasms. Rapid proliferation, infiltration, vascular invasion, hematogenous dissemination, and spontaneous regression are features of both normal and neoplastic trophoblast. Trophoblastic hyperplasia without hydrops, hydatidiform mole, invasive mole, and gestational choriocarcinoma are related lesions, characterized by increasingly aberrant trophoblastic growth and worsening prognosis, if untreated. Difficulties in diagnosis may arise with respect to the normal early implantation site, the hydropic abortus, and postgestational, involuting, residual trophoblast. Histologic grading or hydatidiform moles is relevant to their prognosis and biologic behavior. Trophoblastic neoplasia may begin at any stage of pregnancy or puerperally with immediate or late and local or distant manifestations in the mother or the child. Cognizance of the capricius potential behavior of trophoblast permits successful management of its proliferative lesions, monitored by serial measurement of gonadotropin secretion.

Choriocarcinoma

Worldwide controversies in gestational trophoblastic neoplasms.

This article reviews worldwide controversies concerning gestational trophoblastic neoplasms (hydatidiform mole, invasive mole, and choriocarcinoma). The epidemiology, endocrinology, histopathologic grading, classification, diagnosis, treatment, management and follow-up (including chemotherapy, irradiation, and immunotherapy) of gestational trophoblastic neoplasms - particularly molar pregnancies - are discussed; and ways to help create a standardized classification system and provide optimal treatment for each type of patient are suggested.

Chorionic Gonadotropin

Serum-SP1-pregnancy-specific-beta-glycoprotein in choriocarcinoma and other neoplastic disease.

A radioimmunoassay for a plancental glycoprotein, beta1SP1, capable of detecting 2 microgram/l of the glycoprotein in serum was used to measure concentrations of beta1,SP1 in patients with choriocarcinoma, teratoma, colonic cancer, breast cancer, and ovarian cancer. 12 out of 94 (13%) healthy men and health non-pregnant women had detectable serum-beta1SP1 concentrations. Concentrations up to 50 000 microgram/l were found in the sera of patients with hydatidiform mole, invasive mole, choriocarcinoma, and malignant teratoma. beta1-glycoprotein concentrations were generally much lower than corresponding concentrations of chorionic gonadotrophin which is the most reliable marker for trophoblastic tumours. In a few cases, however, beta1-glycoprotein measurements may be useful in the detection of minimal residual tumour. The slightly raised values found in some patients with carcinoma of the colon, breast, or ovary seem unlikely to be useful for diagnostic purposes of for monitoring the course of these cancers.

Beta-Globulins

[Gestational trophoblastic tumors].

The term gestational trophoblastic tumours covers hydatidiform moles, invasive moles and choriocarcinomas. These are rare diseases remarkable for their high chemosensitivity. The current objective is to cure all patients while preserving their potential for child bearing. Several studies have elicited prognostic factors, so that treatment can be adjusted to each individual patient. Advances in immunochemistry have led to the discovery of a highly reliable marker (HCG and beta-HCG) which has proved valuable to confirm the diagnosis and to follow the patients during and after treatment.

Choriocarcinoma

[The excretion of chorionic gonadetropin in 55 cases of hydatidiform mole (author's transl)].

In 55 cases of hydatidiform mole, 323 quantitative assays of chorionic gonadotropin were evaluated. In cases of molar degeneration the mean HCG excretion was 20% below normal. In cases of hydatidiform mole and invasive mole the mean HCG excretion was significantly above normal. Many cases of hydatidiform mole and all cases of invasive mole showed a repeat rise of the HCG titres after curettage. The pattern of HCG excretion in hydatidiform mole is shown in diagrams.

Chorionic Gonadotropin

[Invasive mole with uterine rupture].

A case of chorioadenoma destruens with uterine rupture is reported. The patient was admitted because a persistent uterine bleeding after abortion about two months before. The titulation of gonadotrophic hormone resulted in 25,000 unities. After curettage she was complicated with hemoperitoneum and went to surgery. During hysterectomy were identified trophoblastic tissue in the broad ligament and partial blocking of the right ureter. After repeated chemotherapy she presented severe immuno depression and sepsis complicated with hemopericardium and died five months after the first admission. The pathology study demonstrated a perforation because a trophoblastic invasion in the right side of the cervix and in the autopsy was demonstrated right ureteral obstruction due to a fibro necrotic an inactive trophoblastic tissue determining significant right hydro-uretero nephrosis.

Adult

Treatment of malignant trophoblastic tumors. An analysis of 209 cases.

From 1948 to 1985, a total of 630 cases of choriocarcinoma and invasive mole were treated in our hospital. The methods of treatment varied in different periods of time. In the third period (1972-1985), 5 Fu and/or KSM were the main therapeutic agents used in the treatment of 110 cases of choriocarcinoma and 99 cases of invasive mole. Metastases were observed in more than 90% of cases of choriocarcinoma and nearly 1/4 belonged to stage IV. The mortality of choriocarcinoma decreased from 84.3% to 32.7% after treatment and that of invasive mole from 32.4% to 8.1%. 43 of 80 patients treated with chemotherapy alone conceived after recovery, resulting in a total of 50 pregnancies including 31 term deliveries by 28 women. All the children are normal and healthy, the eldest being 11 years old now.

Adult

Study and treatment of gestational trophoblastic diseases at the John I. Brewer Trophoblastic Disease Center, 1962-1990.

From 1962 through 1989, 5063 patients were referred to the John I. Brewer Trophoblastic Disease Center of the Northwestern University Medical School. Among these were 564 patients treated with chemotherapy for gestational trophoblastic tumors (choriocarcinoma and invasive mole). The overall cure rate was 94%, 100% for 323 patients without evidence of metastases and 85% for 241 patients with metastatic disease. Four factors were determined to significantly influence treatment response: (1) clinicopathologic diagnosis of choriocarcinoma, (2) metastases to sites other than the lung or vagina, (3) number of metastases, and (4) previous failed chemotherapy.

Antineoplastic Combined Chemotherapy Protocols

Spontaneous regression in choriocarcinoma and related gestational trophobalstic neoplasms.

Gestational trophoblastic neoplasia represents a biologic spectrum of tumors progressing from the hydatid mole, to invasive mole, and to choriocarcinoma. This progression is reflected in increasing degrees of aneuploidy in the respective lesions. Just as there is a natural tendency for the rejection of the trophoblast of a normal pregnancy culminating either in parturition or in spontaneous abortion, rejection of tumors of trophoblast occurs at any point in the progression of the disease spectrum. The unusual effectiveness of chemotherapy in trophoblastic disease may be related to this natural tendency to rejection. This tendency, in turn, is thought to derive from the genetic disparity between the maternal host and the tumor tissue of fetal origin, since the fetus possesses both maternal and fetal antigens.

Aneuploidy

[Chemotherapy in placental tumors].

Chemotherapy is a useful element, but not the only element, for controlling placental tumours. In cases of simple mole routine chemotherapy does not seem to be justified and usually, in 9 cases out of 10, it is useless. It is certainly not always effective and sometimes it may even be dangerous because of the development of chemoresistance. Invasive mole and tumours where a histological diagnosis has not been made and where there is no particularly unfavourable prognosis, usually heal with twice weekly methotrexate carried on for two months after cure has been confirmed clinically, radiologically and biologically. Choriocarcinomata and cases where histology has not been carried out but which have poor prognosis (extra-pulmonary metastases, numerous or large pulmonary metastases, long delay in treatment and the excretion of high levels of HCG) justify chemotherapy in which vincristine is followed by methotrexate or vincristine is followed by actinomycine D. For cure in these bad cases secondary surgery to remove residual lesions, either in the uterus or the lungs, may be necessary.

Brain Neoplasms

Elevated sera levels of SP-1 induced by chemotherapy in patients with metastatic gestational trophoblastic diseases.

6 patients with invasive mole and 5 patients with choriocarcinoma were treated from 1983 till 1986. Serum samples were analyzed by simultaneous determining of pregnancy-specific beta-1-glycoprotein (SP-1) using enzyme-linked immunosorbent assay (ELISA) and beta subunit of human chorionic gonadotropin (beta-hCG) using Serono radioimmunoassay kit. In 2 patients with metastatic gestational trophoblastic disease (MGTD) SP-1 peaks were found during chemotherapy. In patients with MGTD with normalized beta-hCG levels a repeated, temporary elevation of isolated SP-1 levels was observed within some months following chemotherapy. After the last isolated peak of SP-1 the pulmonary metastases disappeared. This phenomenon was interpreted as a consequence of the oncolytic process in the affected tissue. In 1 patient with nonmetastatic choriocarcinoma SP-1 ELISA pseudoreaction was found. To recognize these pseudoreactions, a control plate with nonimmunized rabbit IgG was used, simultaneously with SP-1 determinations.

Adolescent

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.

ABO Blood-Group System

Hydatidiform mole in southern Iran: a statistical survey of 113 cases.

A statistical review of 113 cases of hydatidiform mole (HM) seen at Pahlavi University Hospital from January 1970 to December 1975 is presented. The incidence of the disease was found to be 1:314 pregnancies. In this study, 73.5% of the patients presumably had acceptable socioeconomic circumstances. The highest incidence of the disease was found in patients 15-25 years old, and it increased with parity. All patients presented with a period of amenorrhea and vaginal spotting. More than 50% of the patients sought treatment after 1-2 weeks of uterine bleeding. Signs and symptoms of the disease are discussed. The management of patients with HM and coexisting difficulties are presented.

Adolescent