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PubMed2003

[Undifferentiated choriocarcinoma--epithelioid trophoblastic tumors treated at the Center for Trophoblastic Diseases in the Czech Republic 1955-2003].

OBJECTIVE: The clinical-pathological picture, pathogenesis, biological behavior and therapy of epithelioid trophoblastic tumor (ETT) alias undifferentiated choriocarcinoma (CH-Ned). DESIGN: A retrospective analysis. SETTING: Trophoblastic Disease Center in the Czech Republic (TDC-CZ), Department of Gynecology and Obstetrics, 3rd Medical Faculty, Charles University, Institute for the Care of Mother and Child, Prague. METHODS: The identification of all tumors complying with histopathological criteria of ETT-CHNed among 372 malignant tumors of trophoblast (MTT), treated at TDC-CZ in the years 1955-2003. Their morphological analysis was done from the standpoint of formal pathogenesis, correlation with clinical picture, laboratory and therapeutic results. RESULTS: Among 372 malignant tumors of trophoblast (MTT) we detected 25 ETT-CHNed. The size of the tumor was in the range of 15 to 45 mm except two cases. One tumor diffusely infiltrated thyroid gland and clinically imitated struma. In the other case a massive dissemination of ETT-CHNed in the lungs was supposed to be tuberculosis. The tumor in the uterus and metastases was predominantly of solid character, not infrequently with necroses and haemorrhages. The microscopic analysis revealed larger irregular cells with frequent mitoses, resembling eight-day orthologic trophoblast. There were also infrequent elements of cyto-intermediate and syncytium-trophoblastic character. The mitotic index (3-7), proliferation markers (20%), inhibitin alpha, hCG and PLAP with histological picture suggest a specific form of MTT or choriocarcinoma. The age of the female patients was in the range of 22 to 43 years. In 18 cases (72%) the tumor displayed gynecological symptomatology, in 7 cases (28%) a non-gynecological one (pulmonary 3 times, thyroid once, CNS once, GIT once, mamma once). In the case history there was delivery in 10 cases, abortion in eight, mola hydatiosa completa twice, anamnesis was uncertain once and extra-uterine pregnancy was suspected also once. The interval between pregnancy and established diagnosis was in the range of one to 64 months. The ETT-CHNed diagnosis was established 18 times from curettage of endometrium, six times from biopsies of organs considered as primary localization of the tumor and once during post mortem examination. The hCG values upon admission were in the range of 10(1) to 10(3) mIU/ml in connection with a small number of differentiated syncitium-trophoblastic cells. In the first period (1955-1963) before introduction of chemotherapy all five patients died (100%) in the range of 4 months to 3 years. In the second period (1964-1980), hysterectomy with subsequent monochemotherapy resulted in permanent remission (20 years) in four women out of nine (44%). In the third period (1981-2003), hysterectomy with subsequent polychemotherapy resulted in complete remission from two to 18 years in 9 out of 11 women (82%), while in two cases with absent ETT-CHNed in uterus the intervention was limited to tumor extirpation in the lung or mamma with subsequent treatment with chemotherapy. CONCLUSION: The revision of 372 MTT treated in TDC-CZ (1955-2003) uncovered 25 ETT-CHNed. Their clinical-pathological analysis revealed that ETT-CHNed is a malignant tumor, which is not less aggressive than choriocarcinoma (CH-NST). It becomes manifest by frequent metastases, often with absent demonstrable tumor in the uterus. It represents a less differentiated form of MTT, becoming manifest in a low production of hCG. It can be derived by formal pathogenetics from non-differentiated earliest orthologic trophoblast. There are differentiated transitions between ETT-CHNed and CH-NST, which are analogous to grading of other malignant epithelial tumors. Hysterectomy with subsequent intensive chemotherapy decreased the original 100% mortality in the years 1955-1963 to 18.1% in the years 1980-2003.

Adult↗

PubMed2001

The pathology of intermediate trophoblastic tumors and tumor-like lesions.

An intermediate trophoblast is a distinctive trophoblastic cell population from which four trophoblastic lesions are thought to arise: exaggerated placental site (EPS), placental site nodule (PSN), placental site trophoblastic tumor (PSTT), and epithelioid trophoblastic tumor (ETT). EPSs and PSTTs are related to the differentiation of the intermediate trophoblast in the implantation site (implantation site intermediate trophoblast), whereas PSNs and ETTs are related to the intermediate trophoblast of the chorion laeve (chorionic-type intermediate trophoblast). EPSs and PSNs are nonneoplastic lesions, whereas PSTTs and ETTs are neoplasms with a potential for local invasion and metastasis. Microscopically, intermediate trophoblastic lesions can be confused with a variety of trophoblastic and nontrophoblastic tumors, but an appreciation of the morphologic features and immunophenotype allows their diagnosis to be relatively straightforward in most instances. Correct diagnosis is important because each of these lesions may require different therapeutic approaches.

Diagnosis, Differential↗

PubMed1992

Resolution of pulmonary metastases with chemotherapy in a patient with placental site trophoblastic tumor.

Placental site trophoblastic tumor (PSTT), a rare variant of gestational trophoblastic disease, was first described in 1976. PSTT is usually seen in young women, generally treated by hysterectomy, and is associated with a 20% fatality rate. The development of metastases secondary to PSTT is associated with an extremely poor prognosis. Metastatic PSTT has generally been resistant to chemotherapy although one complete and some partial responses have been noted previously. We report a case of a complete chemotherapeutic response in a patient with pulmonary metastases.

Journal Article↗

PubMed2003

Placental site trophoblastic tumor.

Placental site trophoblastic tumor (PSTT) is an uncommon form of gestational trophoblastic disease (GTD) with variable spectrum of clinical behavior. PSTT can occur after a normal pregnancy, spontaneous abortion, termination of pregnancy, ectopic pregnancy or molar pregnancy. Surgery is the primary treatment. Chemotherapy has an established role in loco-regionally advanced and metastatic disease. Many studies indicate that mitotic index is an important prognostic indicator. This article reviews the literature on this rare disease.

Adult↗

PubMed1992

Flow cytometric DNA analysis of placental-site trophoblastic tumors.

The placental-site trophoblastic tumor is a rare form of gestational trophoblastic neoplasia. Although originally considered benign, it is now apparent that this lesion can be associated with aggressive clinical behavior. Our study examined the DNA ploidy status and clinicopathologic features of four new cases of placental-site trophoblastic tumor. Three cases demonstrated diploid DNA stemlines with S-phase fractions ranging from 6% to 16%. These patients were alive and well at follow-up and had low-serum human chorionic gonadotrophin (hCG) levels. A fourth patient, who had a large tumor, demonstrated a tetraploid DNA peak with a prominent S-phase fraction. This patient exhibited an elevated serum hCG at limited follow-up. Flow cytometric DNA analysis may be a useful adjunct for the identification of placental-site trophoblastic tumors with malignant potential.

Adult↗

PubMedDate not supplied

Epithelioid trophoblastic tumor: a case report.

Epithelioid trophoblastic tumor is a rare and distinctive pathologic entity within the complex family of gestational trophoblastic disease. We describe a case of epithelioid trophoblastic tumor occurring in a 34-year-old woman, who presented with a large uterine tumor 3 years following an uncomplicated pregnancy. The clinicopathologic findings in this case are typical of this unusual entity and consistent with current literature, with the exception of negative beta-human chorionic gonadotrophin levels. The distinguishing features from other intermediate trophoblastic tumors and tumor-like lesions are discussed.

Adult↗

PubMed1978

[Angiographic features of trophoblastic tumors (author's transl)].

Trophoblastic tumors are characterized by typical angiographic features with marked pathological vascularization, arteriovenous shunts and early filling of veines. If the HCG-titer increases after removing of a hydatidiform mole pelvic angiography is indicated in cases of negative histological finding also. In 3 cases the typical angiographic feature was found. Two times remaining changes of gravidity are histologicaly found on an abrasio. In 1 case with increased HCG-titer and negative histological finding a trophoblastic tumor was ascertained angiographicaly. Diagnostic value of pelvic angiography is demonstrated by above mentioned cases.

Abortion, Therapeutic↗

PubMed1992

[Flow cytometric analysis of trophoblastic tumors].

19 cases of malignant trophoblastic tumors were studied by flow cytometry in comparison with 9 cases of benign hydatidiform mole that had been followed up for 1.5 years with no history of malignancy. The results showed that there were significant differences in DNA index (DI), S phase of cells and the pattern of ploidies between the malignant trophoblastic tumor and benign hydatidiform mole. It is considered that flow cytometry is a useful parameter in reference to the diagnosis, chemotherapy and assessing prognosis of malignant trophoblastic tumor.

Aneuploidy↗

PubMed1989

Differences between white and Chinese populations in human leukocyte antigen sharing and gestational trophoblastic tumors.

The prevalence of gestational trophoblastic tumors varies widely among different populations: it is lowest in whites (3 to 6/100,000) and highest in Chinese (68 to 202/100,000). This observation suggests that the origin of the disease is different in the two populations. To test this hypothesis, we examined couples in whom the woman developed a gestational trophoblastic tumor in a white population (Pittsburgh) and a Chinese population (Taiwan) for sharing of human leukocyte A, B, DR, and DQ antigens, which we consider markers for sharing of major histocompatibility complex-linked recessive genes affecting both embryogenesis and carcinogenesis. No human leukocyte antigen sharing occurred between partners in Pittsburgh, but there was significant human leukocyte antigen sharing in Taiwan. The latter couples shared human leukocyte antigen B (p less than 0.04) and human leukocyte antigen DQ (p less than 0.007) and shared three or more human leukocyte A, B, DR, and DQ antigens (p less than 0.02) significantly more frequently than did normal couples. However, there was no increased sharing of any specific human leukocyte antigen allele. These findings support the hypothesis that gestational trophoblastic tumors occur on a sporadic basis in whites and on a genetic basis in Chinese.

Asian People↗

PubMed1995

Current views on the management of trophoblastic tumors.

Gestational trophoblastic disease has been recognized as a form of abnormal pregnancy as early as 1600 AD, and choriocarcinoma was the first cancer to be cured with chemotherapy even in the presence of distant and widespread metastases. Important advances in the past include the standardization of terminology, the concept of assignment of risk and the use of staging systems, the centralization of care and the establishment of regional registries, and of course the development of the radioimmunoassay for the beta subunit of human chorionic gonadotropin. The current views on the management of this disease recognizes the need for a multidisciplinary approach, with chemotherapy remaining at the forefront but also utilizing newer diagnostic techniques when necessary, and keeping in mind the crucial role that surgery can play especially in resistant cases. At the same time, the importance of basics such as careful follow up after evacuation of a hydatidiform mole cannot be overemphasized. There will be a continual refinement of the chemotherapy regimes used, and the aim is to achieve a similar level of response with decreased toxicity to the patient.

Female↗

PubMed1983

[Genetic factors in gestational trophoblastic tumors].

Gestational trophoblastic tumours group together the complete hydatidiform mole (classical) and partial mole (with fetus), invasive mole and choriocarcinoma. Genetically, trophoblastic tumours can arise in different ways: they can derive from normal zygotes with the maternal and paternal haplotype (normal pregnancy), or from a triploid zygote (partial mole) or from an XX zygote possessing only a duplicated male haplotype and no maternal contribution (complete mole). The low malignancy rate in partial mole (2.4%) compared to the complete mole (10 to 20%) remains unknown. Further analysis of the genetics of these tumours may well contribute to the understanding of the process of carcinogenesis.

Choriocarcinoma↗

PubMed2004

Placental site trophoblastic tumor in a late recurrence of a nonseminomatous germ cell tumor of the testis.

Placental site trophoblastic tumor (PSTT) is a well-defined entity in the female genital tract. In the male genital tract, a single case of PSTT in the testis of a young boy has been reported. Despite its very rare occurrence, PSTT of the testis has been incorporated in the latest WHO classification of tumors of the male genital tract. In this article, a case of a PSTT in a late retroperitoneal recurrence of a testicular nonseminomatous germ cell tumor in an adult male patient is presented. The tumor was discovered due to an elevated serum level of beta-human chorionic gonadotropin 4 years after chemotherapy. Upon review of the primary testicular tumor, small foci of intermediate trophoblastic tumor cells were discerned. This case illustrates that tumor cells resembling intermediate trophoblastic cells may metastasize to regional retroperitoneal lymph nodes. Because of their resistance to chemotherapy, these cells may invade surrounding tissue in due time, acquiring the typical morphology of PSTT.

Adult↗

PubMed2003

Coexisting epithelioid trophoblastic tumor and choriocarcinoma of the uterus following a chemoresistant hydatidiform mole.

The epithelioid trophoblastic tumor is an unusual type of trophoblastic tumor. Herein, we describe a patient with coexisting epithelioid trophoblastic tumor and choriocarcinoma in the uterus. The patient had a history of hydatidiform mole with recurrent elevation of human chorionic gonadotrophin level that is resistant to chemotherapy. Histopathologic and immunohistochemical examination showed distinctive differences between the 2 trophoblastic tumors. The development of epithelioid trophoblastic tumor may be related to the persistence of locally invasive disease, which was unresponsive to chemotherapy. The patient responded well to surgery. The presence of an epithelioid trophoblastic tumor should be considered in chemoresistant gestational trophoblast tumor.

Choriocarcinoma↗

PubMed1994

Correlation of uterine hemodynamics with chemotherapy response in gestational trophoblastic tumors.

OBJECTIVE: To assess the uterine hemodynamics in gestational trophoblastic tumors and to correlate them with response to chemotherapy. METHODS: Using transvaginal color Doppler ultrasound, we measured the peak systolic velocity and the resistance index (RI) of the uterine arteries in 23 women with gestational trophoblastic tumors before each course of chemotherapy. Fifty-five nonpregnant women and another 15 women who had uneventful molar evacuation were enrolled as controls. Two-tailed Student t test was used for statistical analysis. RESULTS: A hyperdynamic uterine circulation was noticed at diagnosis in all gestational trophoblastic tumors, manifested as higher peak systolic velocity (mean +/- standard deviation 57.5 +/- 20.4 cm/second) of the uterine arteries compared to nonpregnant (28.3 +/- 3.41 cm/second; P < .0001) and uneventful post-mole uteri (26.8 +/- 3.08 cm/second; P < .0001). The RI values of the uterine arteries in gestational trophoblastic tumors at diagnosis ranged from 0.21-0.80. However, the mean value (0.56 +/- 0.19) was lower than those of nonpregnant (0.80 +/- 0.05; P < .0001) and post-mole uteri (0.75 +/- 0.06; P < .0001). A higher pre-treatment uterine artery RI (mean 0.71 +/- 0.09) was noted in ten patients with gestational trophoblastic tumors requiring fewer than five courses of chemotherapy, compared with the mean in 13 patients requiring longer courses of treatment (0.47 +/- 0.14; P < .0001). There was a marked decrease of peak systolic velocity during the first three courses of treatment in the former group (54.2 to 23.6 cm/second; P < .001), in contrast to no change in the latter group (60.1 to 60.5 cm/second). CONCLUSION: Uterine hemodynamic characteristics assessed by color Doppler ultrasound might predict and monitor the response to chemotherapy in gestational trophoblastic tumors.

Adult↗

PubMed1992

Erythrocytosis associated with a placental-site trophoblastic tumor.

We present a case of placental-site trophoblastic tumor associated with erythrocytosis. This 42-year-old woman had persistent amenorrhea and low elevations of her hCG titer after term delivery of a healthy female infant. The woman was noted to have polycythemia of uncertain etiology and was treated with serial phlebotomy. Placental-site trophoblastic tumor was diagnosed and hysterectomy was performed, with subsequent resolution of the polycythemia. Although erythrocytosis has been reported with other gynecologic tumors, this is the first reported association with a placental-site trophoblastic tumor. A role has been suggested for placental lactogen in erythropoiesis during pregnancy based on previous animal studies. Diffuse positive staining for hPL is characteristic of placental-site trophoblastic tumors. We postulate that hPL may have played an ancillary role to erythropoietin in the erythrocytosis demonstrated in this case. Spider angiomata and splenomegaly are interesting clinical features previously described in association with placental-site trophoblastic tumors, and were demonstrated in this patient.

Adult↗

PubMed2006

Gestational trophoblastic diseases: 3. Human chorionic gonadotropin-free beta-subunit, a reliable marker of placental site trophoblastic tumors.

OBJECTIVES: Placental site trophoblastic tumor (PSTT) commonly presents with low and variable concentration of hCG immunoreactivity in serum which can be difficult to differentiate from early stage choriocarcinoma/gestational trophoblastic neoplasm (GTN) or quiescent gestational trophoblastic disease (quiescent GTD). Nontrophoblastic malignancies such as germ cell tumors or other tumors secreting low hCG must also be considered in the differential diagnosis. Because treatments for these conditions are different, a means of differentiating PSTT from other diagnoses is important. We investigate the usefulness of hCG-free beta-subunit to make this discrimination. METHODS: Data collected on cases referred to the USA hCG Reference Service for consultation served as a basis for this retrospective analysis. There were 13 cases with histology proven PSTT and 12 with nontrophoblastic malignancy. hCG-free beta-subunit was measured by immunoassay and reported as a proportion of total hCG (hCG-free beta-subunit(%)). hCG-free beta-subunit(%) results were determined for all histologically proven cases of PSTT and for the nontrophoblastic malignancies. Comparisons of hCG-free beta-subunit(%) were made and compared with those of the 82 choriocarcinoma/GTN cases and 69 quiescent GTD cases. The accuracy of hCG-free beta-subunit(%) to discriminate these malignancies was analyzed by investigating the areas under receiver-operating characteristics curve +/- standard error. RESULTS: hCG-free beta-subunit(%) was the predominant hCG form in cases of PSTT (mean +/- standard deviation, 60 +/- 19%) and nontrophoblastic malignancies (91 +/- 11%), thus discriminating these diagnoses from choriocarcinoma/GTN (9.3 +/- 9.2%) and from quiescent GTD (5.4 +/- 7.8%). The cutoff of >35% free beta-subunit is proposed. At this cutoff, 100% detection at 0% false-positive is achieved. The accuracy of hCG-free beta-subunit(%) for this discrimination is 100 +/- 0%. At a proposed cutoff of >80%, the free beta-subunit test will also distinguish PSTT from nontrophoblastic malignancy, with 77% detection at 23% false-positive or an accuracy of 92 +/- 3.2%. CONCLUSION: Measurement of the proportion hCG-free beta-subunit(%) was found to be useful in the diagnosis of PSTT using proposed cutoff values of >35% and >80%. While this finding needs to be confirmed by larger studies, it would be reasonable to measure hCG-free beta-subunit(%) whenever the diagnosis of PSTT is considered.

Choriocarcinoma↗

PubMed1991

Placental site trophoblastic tumor in a postmenopausal woman.

Placental site trophoblastic tumor is a rare neoplasm that arises in the trophoblastic tissue of the placental bed. This case report is unusual because of the patient's advanced age at the time of diagnosis and the favorable response of the disease to chemotherapy. Although the clinical course is benign for most patients with placental site trophoblastic tumor, the malignant variant of the disease is characterized by recurrence, relative insensitivity to radiation and chemotherapy, and death. To the authors' knowledge, the 53-year-old woman reported is the oldest patient with histologically confirmed placental site trophoblastic tumor. Initially, surgery, radiation, and multiagent chemotherapy failed to control vaginal and pulmonary metastatic disease. After administration of four treatment cycles of a "second-line" chemotherapeutic regimen consisting of cyclophosphamide and cisplatin, complete clinical and radiologic remission was achieved. The patient's serum level of human chorionic gonadotropin has remained undetectable, and she has been without measurable evidence of disease for 16 months.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

Ovarian epithelioid trophoblastic tumor in a cynomolgus monkey.

Epithelioid trophoblastic tumor (ETT) is an unusual type of trophoblastic tumor, with features resembling carcinoma. In this study, we describe a 4-year-old cynomolgus monkey (Macaca fascicularis) showing, at necropsy, a lobulated mass replacing the left ovary and several nodular lesions within the lungs. Histologically, the mass in the ovary and lung metastases were characterized by nests of epithelioid cells, with intermingled, occasional, multinucleate tumor cells consistent with syncytiotrophoblasts and moderate amount of eosinophilic, hyaline-like material. Immunohistochemically, the tumor cells were diffusely positive for cytokeratins (AE1/AE3) and inhibin-alpha, but only focal immunoreactivity was observed for human chorionic gonadotropin, whereas placental alkaline phosphatase was always negative. On the basis of morphology and immunohistochemical reactivity, tumor cells were identified as intermediate trophoblast.

Animals↗