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[Malignant trophoblastic tumors (MTT) treated in the years 1955-2004 in trophoblastic disease center in the Czech Republic (TDC-CZ): clinical-pathological features, curability, typing, pathogenesis].

OBJECTIVE: Clinical- pathological features, typing, curability and pathogenesis of malignant tumors of trophoblast (MTT). DESIGN: A retrospective analysis. SETTING: Trophoblastic Disease Center in the Czech Republic (TDC-CZ), Mother and Child Care Institute, 3rd Medical Faculty, Charles University, Prague. METHODS: Revision of 379 MITT cases treated at TDC-CZ and comparison of their histological picture with developmental stages of orthologic trophoblast from the standpoint of MTT typing and pathogenesis. The determination of curability of different histological types and risk stages (RS) used in TDC-CZ and a comparison with RS axccording to FIGO, WHO and NIH. Differentiation of undifferentiated choriocarcinoma (CH-Und) alias Epitheloid Trophoblastic Tumor (ETT) from the given cohort of MIT and establishment of its clinical and biological properties, curability and formal pathogenesis. RESULTS: Three hundred and seventy nine MTT cases were classified into 5 histological types onthe basis of analogy with developmental stages of 7 to 14 days old trophoblast. 1: typical "classical" choriocarcinoma - No Special Type (CH-NST), which forms more than 80% of MTT. Moreover, the degree of differentiation of tumorous trophoblast and its prevailing (cytological) type made it possible to define other 4 types, i.e.: 2: CH-syncytio-trophoblastic (CH-Syn), representing 3.8%; 3: CH-cytotrophoblastic CH-Cyt with 3.3%; 4: CH-dissociated (CH-Dis), representing 6%; 5: CH-undifferentiated (CH-Und) with 6.8%. Mortality due to MIT of all mentioned types reached 94% until 1963, decreased to 43% until 1980 and has been 5.8% in the period of 1981-2004. In the latter period of time (1981-2004), mortality due to CH-Cyt proved to be 40%, that due to CH-Dis being 11%, and CH-Und 18%, though. Mortality of s.c. Placental Site Trophoblastic Tumor, which includes our CH-Cyt and CH-Dis therefore forms 21.4%. We have been using four RS in TDC-CZ. The following outline includes only the main features: 1st RT includes CH-NST < 30mm limited to uterus in connection with mole. 2nd RS includes CH-NST > 30mm after birth. 3rd RS includes CH-NST with multiple metastases outside GIT and CNS and MTT with the CH-Cyt, Dis, Und component < 75%. 4th RS includes CH-NST with metastases in CNS or GIT. MTT with CH-Cyt Dis, Ned component < 75% with metasteses and MTT with the same components > 75% In the last 23 years 1st RS and 2nd RS includes 85 % of all MTT in the TDC-CZ and curability is 100%. In the 3rd RS curability decreases to 64.3% and decreases to 55.6% in the 4th RS. According to FIGO classification the 1st RS forms 48%, 2nd RT represents 17% and 100% curability applies for both of them. 3rd a RS includes 20% of 100% curability, 3rd bc RS forms 10% with 67% curability and 4th abc RS includes 5 % with 50% curability. In using the WHO classification with four RS, their percentage representation is similar to our classification with similar curability; nevertheless the 1st RS and 2nd RS did not detect almost 8% of MTT, which ended with exitus. 3rd RS according to FIGO is overestimated in view of 100% curability and the abc degree in 1st and 2nd RS are only of theoretical significance and irrelevant for the choice of treatment. The closest results comparable with our classification were those of NIH. A very careful clinical-pathological analysis of 25 CH-Und-ETT, detected among 379 MTT revealed that CH-Und-ETT is anaggressive malignant form of CH, which is best derived from undifferentiated 7-8 days old trophoblast. It is insidious for its seemingly primary extragenital symptomatology in seven out of 25 cases, low hCG values and poor sensitivity to chemotherapy. CONCLUSION: 1) The comparison of histological pictures of 379 MTT with developmental stages of orthologic trophoblast of 7-14 days old embryo was the basis for classification of 5 types of choriocarcinoma (CH): 1. Differentiated CH "No Special Type" (CH-NST), 2. Syncytiotrophoblastic CH (CH-Syn), 3. Cytotrophoblastic CH (CH-Cyt), 4. Dissociated CH (CH-Dis), and 5. Non-differentiated CH (CH-Und); 2) We have determined their percentual (and absolute) occurrence in the group of 379 MTT treated in CTN in the years 1955-2004. 3) We have described biological properties of individual types of CH and established the way they influence curability. 4) Four degrees of risk (RS) were specified in relation to 7 types of risk factors observed (1. size of tumor, 2. type of preceding pregnancy, 3. interval from pregnancy to the diagnosis, 4. histological type of CH, 5. number of metastases, 6. localization of metastases, 7. values of hCG). It has become obvious how RS influenced curability of CH (1st and 2nd RS forms 85% of all CH's and their curability is 100% (!), 3rd and 4th RS are represented in 15% and their curability is 64% in the 3rd RS and 55% in the 4th RS. 6) The curability reached in CTN was compared with that determined according to FIGO, WHO and NIH, respectively. The results proved to be similar, but in case of FIGO the 3rd degree was overestimated and the degrees abc in the 1st and 2nd RS were of theoretical importance only, therefore being of no values for the choice of treatment. Low and medium score according to WHO did not detect 8% of women who had died. The CH curability according to RS, having been recommended by NIH and used in the American Centers was virtually the same as our results. 7) It has been proved that the histological type of CH significantly influenced the determination of RS in the given patient. 8) CH-Und-ETT represents the least differentiated form of MTT, in other words choriocarcinoma. This is associated with a low production of HCG, mostly between 10(1) and 10(3) mIU/ml. 9) Pathogenesis of CH-Und ETT-ETT we derive from the earliest, undifferentiated stage of orthological trophoblast. The origin from the differentiated intermediate trophoblast chorion leeve we considerei improbable. 10) There are continuous transitions from CH-Und-ETT and PSTT to CH-NST, representing an analogy to grading in other malignant epithelial tumors.

Choriocarcinoma↗

Clinical characteristics of placental site trophoblastic tumor (PSTT).

Placental site trophoblastic tumor (PSTT) has been demonstrated to be a rare variant of gestational trophoblastic disease, with only 43 cases of this disorder having been reported in the English language literature since 1976. It is associated with a 20% mortality rate, occurs in young women, is very resistant to standard trophoblastic disease chemotherapy, and is generally treated by hysterectomy. This report describes an additional 5 cases of PSTT, two of whom died of their disease. It aims to clarify the varied clinical characteristics of the condition through a comparative analysis of these patients with those previously reported. Specific factors in the analysis include age, mitotic count, presence of marker hormones, preceding gestational situation, cause of death, survival time from diagnosis, tumor karyotype, and treatment. The study suggests that a preceding term pregnancy, a high mitotic ratio, and an older age group may be associated with a higher mortality rate. It also supports the premise that some patients, with a low mitotic ratio and other favorable histologic features, may be treated conservatively with curettage and very careful follow-up monitoring if they wish to preserve reproductive potential.

Adult↗

Cyclin E and p16 immunoreactivity in epithelioid trophoblastic tumor--an aid in differential diagnosis.

Epithelioid trophoblastic tumor (ETT) is a relatively uncommon trophoblastic tumor that can be confused with several trophoblastic and nontrophoblastic lesions, notably the placental site nodule and invasive squamous carcinoma of the cervix. In this report, we analyzed the immunoreactivity of two cell cycle-regulated proteins, cyclin E and p16, in ETTs, placental site nodules and cervical squamous carcinomas to determine whether they are useful in their differential diagnosis. Other trophoblastic lesions were also evaluated. Using an H-score based on both percentage of positively stained cells and immunointensity, we found that ETTs demonstrated a much higher cyclin E staining score than placental site nodules (P<0.0001) permitting distinction of ETTs and placental site nodules with a sensitivity of 94.7% at a specificity of 91.7% using a cutoff H-score value of >40. Only two placental site nodules had scores above the cutoff and both showed morphologic features that placed them in an intermediate position between a typical placental site nodule and an ETT, so-called "atypical PSN." p16 immunoreactivity, was not detected in any of the ETTs and placental site nodules, whereas it was strongly and diffusely positive in the vast majority of cervical squamous carcinomas examined (83/87 cases) (P<0.001). Therefore, cyclin E expression is useful in distinguishing an ETT from a placental site nodule and p16 expression is useful in distinguishing an ETT from a cervical squamous carcinoma. The majority of other types of trophoblastic lesions showed diffuse and intense nuclear immunoreactivity for cyclin E whereas none were positive for p16.

Carcinoma, Squamous Cell↗

Treatment of placental site trophoblastic tumor with hysterotomy and uterine reconstruction.

BACKGROUND: Placental site trophoblastic tumor is an unusual variant of gestational trophoblastic neoplasia that is usually confined to the uterus, although 10% of patients have metastases. Because this tumor occurs in women of reproductive age, preservation of fertility may be relevant. Therefore, local excision of placental site trophoblastic tumor by hysterotomy may have a place in management. CASE: A 25-year-old woman, gravida 1, para 1, presented with irregular bleeding. Uterine curettage revealed intermediate trophoblasts that on immunostaining were positive for hCG and human placental lactogen, consistent with placental site trophoblastic tumor. Endovaginal ultrasonography and magnetic resonance imaging demonstrated tumor localized to the anterior fundal myometrium. The patient underwent local excision of the tumor by hysterotomy followed by uterine reconstruction. Pathologic examination confirmed that the surgical margins were free of tumor. The patient has had no recurrence. Two subsequent pregnancies resulted in two spontaneous abortions. A third pregnancy was carried to term. The patient was delivered by cesarean because of the hysterotomy. The hysterotomy scar was intact at cesarean. CONCLUSION: Hysterectomy has been recommended by most authors for treatment for placental site trophoblastic tumor. In some patients with localized placental site trophoblastic tumor who desire preservation of fertility, more conservative surgical therapy may be considered.

Adult↗

[Placental site trophoblastic tumor. Morphology, differential diagnosis and prognosis].

A placental-site trophoblastic tumor is a rare neoplasia that is derived from the cells of the intermediate trophoblast. Morphological, biochemical, and Doppler ultrasound findings are presented regarding differential diagnosis using material from three recent cases. Essentially, placental-site trophoblastic tumors can be diagnosed if infiltration of the myometrium is seen by a monomorphic trophoblastic proliferation that is not interrupted by decidual cells. Necrosis and hemorrhages are not features of placental-site trophoblastic tumors. However, there is a peculiar behavior towards the uterine vasculature as spiral arteries are dilated and transformed the same way as occurs at the site of physiological implantation of pregnancy. It appears that as a result of this phenomenon there is a characteristic finding in ultrasound. Examination of this type of tumor demonstrates cystic spaces that can be defined as blood vessels by their Doppler signal. In two of the three cases a hysterectomy was performed, and criteria for the assumption of malignant placental-site tumors are therefore presented. However, only the mitosis rate seems to possess some predictive value.

Adult↗

The role of contraception in the development of postmolar gestational trophoblastic tumor.

From January 1974 to June 1988, 299 evaluable patients were referred to the John I. Brewer Trophoblastic Disease Center of Northwestern University Cancer Center for treatment and/or follow-up of a hydatidiform mole (N = 162) or postmolar gestational trophoblastic tumor (N = 137). The type of contraception and other prognostic factors before and after evacuation were correlated with the development of gestational trophoblastic tumor using both univariate and multivariate analysis. There was no relationship between pre-hydatidiform mole contraception and the development of gestational trophoblastic tumor. Oral contraceptives (OCs) were used by 139 patients (46%), barrier methods by 141 patients (47%), intrauterine devices (IUDs) by two patients (1%), and no contraception by 17 patients (6%). The risk of developing gestational trophoblastic tumor was compared between patients using versus not using: OCs--33 versus 57% (P less than .001), barrier methods--53 versus 40% (P = .30), IUD--100 versus 46% (P = .21), and any contraceptive method--43 versus 88% (P less than .001). The dose of estrogens could be determined in 75 patients taking OCs; 14 of 49 (29%) of the patients taking less than 50 micrograms versus nine of 26 (35%) taking 50 micrograms or more developed gestational trophoblastic tumor (P = .78). Stepwise logistic regression analysis demonstrated that the type of contraceptive used was the most important prognostic factor in gestational trophoblastic tumor development (P less than .0001), followed by the occurrence of theca-lutein cysts (P less than .0001), Asian maternal race (P = .02), lesser time from the last menstrual period (P = .005), and greater maternal age (P = .04).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Placental site trophoblastic tumor: a 17-year experience at the New England Trophoblastic Disease Center.

OBJECTIVE: We reviewed cases of placental site trophoblastic tumors from the New England Trophoblastic Disease Center (NETDC) database from 1982-1999 in an effort to identify prognostic factors for recurrent disease. METHODS: A chart review was performed utilizing patients identified from the NETDC database. Data obtained included patient age at diagnosis, antecedent pregnancy, duration and extent of disease, presenting symptoms, pre- and posttreatment hCG levels, diagnostic and therapeutic procedures, treatment and outcome of patients. Statistical analysis was performed using Student's t test and chi(2) test when appropriate. RESULTS: Thirteen patients were identified. All ultimately underwent hysterectomy although initial treatment of 1 patient was uterine resection. There were 5 recurrences (43%)--3 among the 9 patients who had no metastases on presentation (33%) and 2 of 3 patients who presented with metastases (66%). The 5 patients who recurred were among 8 who had received peri- or postoperative chemotherapy (62.5%). Treatment of recurrences included continued or alternate chemotherapy, radiotherapy, and/or excision of locally recurrent disease. Follow up time averaged 56.2 months (range 12-182 months). One of the 4 patients receiving chemotherapy < or =1 week after hysterectomy recurred, whereas all 4 patients who received chemotherapy 3 weeks or more after hysterectomy recurred. Uterine tumor volume was significantly greater, 154.1 cm(3), in patients with initial metastases versus 42.3 cm(3) in patients without initial metastases (P = 0.04). Mitotic index (P = 0.04) was significantly increased in patients who developed recurrent disease. CONCLUSION: High mitotic index appears to be an adverse prognostic indicator for recurrence. Hysterectomy remains the mainstay of treatment. Chemotherapy is indicated for patients with metastases and may be indicated when the mitotic index is >5 mitoses/10 HPF. Radiation treatment may play a role in recurrent disease but must be evaluated on a case-by-case basis.

Adult↗

Metastatic placental site trophoblastic tumor.

Since our publication, which first defined the malignant potential of placental site trophoblastic tumor (PSTT), we have had a keen interest in this rare, unique entity. This histologic entity is noted by its monomorphic population of trophoblast-like cells which are classified as originating in the intermediate trophoblast. These cells contain hymman placental lactogen (HPL). This is in contrast to cytotrophoblastic and syncytiotrophblastic tissues as the histologic, cytologic and immunohistochemical stain characteristics are disparate. Its rarity and the wide spectrum of clinical behavior combined with the lack of sensitivity of serum levels of beta hCG in predicting disease recurrence and spread have lead to anecdotal reports outlining clinical management. Most discerning to the clinician is the high mortality of metastatic placental site trophoblastic tumor. At our institution, we have treated two patients with a metastatic disease with a successful conclusion. The durability of responses is 3 and 8 years. This report will present these patients in detail and define the important characteristics of successful treatment. The use of dose-intensive, multi-agent chemotherapy, early intervention when metastatic disease is discovered, imaging techniques to define disease spread, surgery for localized disease and the use of growth factors, most notably granulocyte colony-stimulating factor (G-CSF), are the fundamentals of clinical care of placental site trophoblastic tumor in patients with metastatic placental site trophoblastic tumor.

Antineoplastic Combined Chemotherapy Protocols↗

Ki-67 labeling index in the differential diagnosis of exaggerated placental site, placental site trophoblastic tumor, and choriocarcinoma: a double immunohistochemical staining technique using Ki-67 and Mel-CAM antibodies.

The diagnosis of placental site trophoblastic lesions, particularly the distinction of a placental site trophoblastic tumor from an exaggerated placental site, can be difficult. Mel-CAM (also known as CD146 and MUC18) is a recently recognized cell adhesion molecule belonging to the immunoglobin gene superfamily that specifically identifies intermediate trophoblast (IT). In this study, we evaluated immunohistochemical staining of Ki-67 (using Mib-1 antibody) in Mel-CAM defined IT as an aid in the differential diagnosis of these lesions. Formalin-fixed tissue samples from 24 normal implantation sites, 19 exaggerated placental sites, five molar implantation sites, 16 placental site trophoblastic tumors, and 12 choriocarcinomas were stained with a Mel-CAM-specific polyclonal antibody and a Ki-67 antibody using streptavidin-biotin immunoperoxidase with two different chromagens. No Ki-67 nuclear labeling was seen in IT of normal implantation sites. The Ki-67 index (mean +/- standard deviation) in IT of exaggerated placental site was near zero, but in the molar implantation sites the Ki-67 index was 5.2% +/- 4.0%. In contrast, the Ki-67 index in IT of placental site trophoblastic tumor was 14% +/- 6.9% and in choriocarcinoma was 69% +/- 20%. The differences in the Ki-67 labeling index were statistically significant (P < .001) between exaggerated placental site, placental site trophoblastic tumor, and choriocarcinoma. In conclusion, a double-staining technique using MIB-1 antibody to determine the Ki-67 proliferative index in Mel-CAM defined IT is a useful technique in the differential diagnosis of exaggerated placental site versus placental site trophoblastic tumor and placental site trophoblastic tumor versus choriocarcinoma.

Antigens, CD↗

[Effects of ACM sequential chemotherapy on ovarian function in trophoblastic tumors].

OBJECTIVE: To study the changes of ovarian function during and after ACM sequential chemotherapy on trophoblastic tumors. METHODS: 17 patients with trophoblastic tumors, received totally 48 cycles of ACM chemotherapy. Of these, 7 underwent hysterotomy and focal ectomy and ovarian biopsy. Changes of menstruation and BBT were observed. beta-hCG, E2, FSH and LH were assayed and histological and immunohistochemical studies in ovaries biopsied were made. RESULTS: Amenorrhea and anovulatory BBT were predominant at the onset of chemotherapy and high level of beta-hCG. Following chemotherapy and decrease of beta-hCG, menstruation recovered with less amount and BBT transformed into ovulatory types with shorter luteal phase. The E2 level appeared to be lower and the FSH and LH level higher. The different kinds of follicles were decreased, but estrogen receptors unchanged. Follow-up showed that ovarian function of 12 of the 17 patients returned to normal in one year. CONCLUSION: ACM chemotherapy suppresses ovarian function mildly and temporarily. Trophoblastic tumor also affects ovarian function. ACM chemotherapy seems to be suitable for young patients with trophoblastic tumors who desire child-bearing.

Adult↗

Placental site trophoblastic tumor presenting with a pneumothorax during pregnancy.

BACKGROUND: Placental site trophoblastic tumor is a rare form of gestational trophoblastic disease that commonly presents with vaginal bleeding and amenorrhea after pregnancy. CASE: A women with a normal gestation at 37 weeks presented with a pneumothorax. The patient underwent placement of a chest tube and a subsequent thoracoscopic pulmonary bullous resection for persistence of the pneumothorax. Histological examination of the specimen revealed a metastatic placental site trophoblastic tumor. CONCLUSION: Gestational trophoblastic disease must be considered in the differential diagnosis of pneumothorax during pregnancy.

Adult↗

[Immuno-capacity in the patients with trophoblastic tumors].

In patients with trophoblastic tumors, changes in immuno-capacity through their clinical courses were examined, by 1) 3H-thymidine uptake by PHA-stimulated peripheral lymphocytes using whole blood microculture assay (common cellular immunity), and 2) the effects of patients' sera to 3H-thymidine uptake by PHA-stimulated peripheral blood lymphocytes (humoral factor). Hydatidiform mole: After molar delivery, cellular immunity accelerated, and humoral suppressive factor significantly increased. Invasive mole: No significant change was observed in the cellular immunity, but humoral suppressive factors increased gradually as the therapies proceeded. And the suppressive apex came at about the 60th day of admission, but these factors decreased afterwards. Choriocarcinoma: At initial time, cellular immunity accelerated significantly, and from the 60th day to the 90th day of admission, this cellular immunity declined significantly compared with that in the pretreated state. But cellular immunity was not entirely eliminated by the courses of treatment. The humoral suppressive apex came at about the 120th day of admission. Nevertheless, where death unfortunately occurred, humoral suppressive factors were not so numerous. As a whole, from the viewpoint of immunotherapy in patients with choriocarcinoma, common immunity which was observed in this study did not decline, so that specific immunotherapy must be regarded as likely kept in mind.

Female↗

Placental site trophoblastic tumor: imaging findings.

Placental site trophoblastic tumor (PSTT) is the least common form of gestational trophoblastic disease, with only about 100 cases having been reported. Although the imaging findings of PSTT have seldom been reported, previous findings of the tumor indicate that it can be divided into two types, a hypervascular type and a relatively hypovascular type. We reported the imaging findings of these two representative types of PSTT. In the hypervascular type, massive bleeding following dilatation and curettage have been reported. When prominent vascularity of the tumor is indicated by imaging findings, dilatation and curettage should be avoided. On the other hand, uterine conservative surgery may be possible in patients with the localized hypovascular type. The main role of imaging diagnosis of PSTT is to clarify the vascularity of the tumor.

Adult↗

Human chorionic gonadotropin (hCG) beta-core fragment is produced by degradation of hCG or free hCG beta in gestational trophoblastic tumors: a possible marker for early detection of persistent postmolar gestational trophoblastic disease.

The present study was undertaken to investigate whether human chorionic gonadotropin (hCG) beta-core fragment (hCG beta cf) was directly produced by gestational trophoblastic tumors. Immunoreactivity of hCG beta cf was demonstrated in the extracts as well as in the culture media of hydatidiform mole tissues. It was also present in the extracts of choriocarcinoma tissues, and its molar concentration exceeded that of intact hCG. The presence of hCG beta cf was then confirmed by gel chromatography and Western blot analysis. Immunohistochemistry showed localization of hCG beta cf immunoreactivity to the syncytiotrophoblasts and scattered cells in the stroma of mole tissue, and to syncytiotrophoblastic cells in choriocarcinoma. Immunoreactivity of hCG beta cf was also detected in the sera of the patients with gestational trophoblastic disease, although the hCG beta cf/hCG ratio was less than one hundredth of that in the tissue extracts. Serial measurement of serum hCG beta cf levels after mole evacuation showed that they declined much more rapidly than those of hCG and became undetectable in the patients with subsequent spontaneous resolution, while hCG beta cf remained or became detectable before the rise of hCG was observed in the patients with subsequent persistent trophoblastic disease. Taken together, these results suggest that hCG beta cf is directly produced by gestational trophoblastic tumors, and monitoring of hCG beta cf in the serum after mole evacuation may be useful for early prediction of subsequent development of postmolar persistent trophoblastic disease.

Animals↗

Adrenal metastatic placental site trophoblastic tumor. Case report.

Placental site trophoblastic tumor is a rare disease. Since its first description in the literature only about 100 cases have been reported. Initially considered a benign pathology, its malignant potential with metastases was later recognized. About 30% of the cases described metastatised, thereby aggravating the prognosis. The therapy is surgical and in cases of metastatised disease has to be supplemented by chemotherapy. A case of placental site trophoblastic tumour with a single metastasis to the left adrenal gland treated with adrenalectomy and chemotherapy is reported.

Adrenal Gland Neoplasms↗

A study of early pregnancy factor activity in the sera of women with trophoblastic tumor.

PROBLEM: To detect whether or not the early pregnancy factor (EPF)-like activity, or chaperonin 10, could be in the sera of patients with trophoblastic tumor in order to find another more efficient means to diagnose this kind of tumor. METHOD OF STUDY: The rosette inhibition assay was used to detect EPF-like activity in 216 sera, collected from patients with gestational trophoblastic tumor, including 47 sera of patients with choriocarcinoma, 68 sera of patients bearing invasive mole, and 101 sera of patients with vesicular mole. RESULTS: The accuracy of diagnosing malignant trophoblastic tumor by detecting EPF-like activity is 91.3% (105/115), with a false positive rate of 14.58% and a false negative rate of 4.8% by this method. Furthermore, the rosette inhibition titer (RIT) values have significant difference (P < 0.001) between the sera in patients with malignant trophoblastic tumor before treatment and those after treatment. CONCLUSIONS: This study demonstrated that diagnosis of malignant trophoblastic tumor could be made with an accuracy of 91.3% by detecting EPF-like activity and that EPF-like activity could be used as an indicator to distinguish benign from malignant trophoblastic tumor.

Adult↗

Diagnostic and prognostic significance of circulating tumor suppressor gene p53 autoantibodies in patients with gestational trophoblastic tumors.

Seventy-two patients with gestational trophoblastic tumors (GTTs) and 20 first-trimester healthy pregnant women (controls) participated in this study. According to the WHO scoring system, GTTs were subgrouped into 24 hydatiform mole spontaneous regression (HMSR), 18 postmolar high-risk (PMHR) and 16 low- and 14 high-risk cases of choriocarcinoma. Patients with choriocarcinoma were treated with hysterectomy and methotrexate chemotherapy, whereas molar pregnancy was managed by either oxytocin infusion followed by suction evacuation or by hysterectomy. Serum p53 autoantibodies were determined by enzyme-linked immunosorbant assay and serum hCGbeta was determined by radioimmunoassay before and throughout the 12 months after treatment. p53 autoantibodies were not detected in normal pregnancy and cases of HMSR but were detected in all cases of PMHR and choriocarcinoma. Concentrations of p53 autoantibodies were higher in choriocarcinoma than in PMHR cases. Serial measurements of p53 autoantibodies dropped to an undetectable level within 1 and 6 months after treatment in cases of PMHR and low-risk choriocarcinoma, respectively. Decreasing values of p53 autoantibodies in high-risk choriocarcinoma remained higher than the cut-off level of controls. There was a significant positive correlation between p53 autoantibodies and serum hCGbeta concentration in GTTs. In conclusion, detection of p53 autoantibodies has a high potential for the differential diagnosis of GTTs and their serial measurements are clinically useful to monitor disease progression and to assess response to therapy in GTTs.

Adolescent↗

Epithelioid trophoblastic tumor of the uterus in a postmenopausal woman: a case report and review of the literature.

We report an epithelioid trophoblastic tumor (ETT), a recently delineated type of gestational trophoblastic tumor (GTT), discovered in the uterus of a 66-year-old woman. She had been treated for a hydatidiform mole 17 years previously without chemotherapy. The resected uterus contained a solid/cystic tumor located entirely within the myometrium. Microscopically, there was an epithelial-like growth pattern. The tumor was circumscribed, with a pushing border, and the tumor cells grew in cords, nests, and sheets within which were aggregates of hyaline material and necrotic debris. Most tumor cells were mononuclear and had an epithelioid appearance with distinct cell borders, eosinophilic cytoplasm, and nuclei with occasional indistinct nucleoli. Scattered multinucleated cells consistent with syncytiotrophoblastic cells were also present. Immunohistochemical staining revealed strong diffuse reactivity for cytokeratins (CK7, AE1/AE3, CAM 5.2, CK18) and epidermal growth factor receptor, and focal reactivity, mainly in syncytiotrophoblastic cells, for beta-human chorionic gonadotropin, human placental lactogen, and inhibin-alpha. The histologic and immunohistochemical features were characteristic of ETT, and helped to distinguish the tumor from other trophoblastic tumors and squamous cell carcinoma. An unusual observation was a high mitotic count, reflected in a Ki-67 proliferative index of 68.6%. Our findings indicate that ETT, like other types of GTT, can occur in postmenopausal women, even years after a gestational event.

Aged↗