A Rare Case of Combined Choriocarcinoma and Placental Site Trophoblastic Tumor Presenting as Skin Lesion: A Case Report.

BACKGROUND Despite the tendency to metastasize widely, Gestational Trophoblastic Neoplasia (GTN) is one of the most curable solid tumors with chemotherapy. CASE REPORT A 41-year-old female, G4P2A2, presented with a slowly growing lump on the left side of the scalp associated with a headache. The patient had intermittent, sharp left eye pain which radiated to the side of her face, photophobia, early morning blurring of vision, and nausea. Palpation over scalp lesion produced deep retro-orbital pain and pain was exacerbated with bending over. An ophthalmological evaluation was unremarkable. Ultrasonography (USG) of the left scalp showed an intramuscular mass superficial to the left frontal bone. During excision biopsy, the mass was found to be invading the frontal bone. Histopathology showed a metastatic trophoblastic tumor with mixed features of choriocarcinoma and placental site trophoblastic tumor. A pregnancy test was positive, the beta HCG level was elevated but USG did not show intrauterine pregnancy. CT head demonstrated an intracranial, dural-based mass that extended against the brain but did not breach the pial membrane. CT chest, abdomen, pelvis, and PET scan showed no evidence of metastatic disease. She was successfully treated with resection of the transcranial lesion followed by aggressive chemotherapy - Etoposide, Methotrexate, Actinomycin-D, Vincristine, and Cyclophosphamide. CONCLUSIONS This was an unusual case of GTN due to its primary presentation as skin metastasis, without any lung metastasis and no identifiable primary lesion. It is also very unusual to see a combination of choriocarcinoma and placental site trophoblastic tumor cells in the same tumor mass.

Term Pregnancy After Complete Response of Placental Site Trophoblastic Tumor to Immunotherapy.

BACKGROUND: Standard treatment for placental site trophoblastic tumor is hysterectomy. This may be unacceptable to women desiring fertility. Cells aberrant in placental site trophoblastic tumor display an ability to invade normal tissue while evading the immune system. CASE: We present a case of a 23-year-old woman with stage I placental site trophoblastic tumor who declined hysterectomy. Tumor assay for program cell death-ligand 1 staining was performed and suggestive of an immune-responsive tumor. The patient initiated intravenous pembrolizumab 200 mg every 2 weeks, and by cycle 3 her ß-hCG level fell to undetectable. She subsequently conceived and went on to have an uncomplicated term vaginal birth after cesarean. At 6 weeks postpartum, she remained without evidence of disease. CONCLUSION: Immunotherapy can eliminate early program cell death-ligand 1-positive placental site trophoblastic tumor with subsequent normal pregnancy.

Treatment of gestational trophoblastic disease in the 2020s.

PURPOSE OF REVIEW: This review demonstrates the evidence for new systemic anticancer treatments and how they integrate within conventional management for gestational trophoblastic neoplasia (GTN). We present the evidence on atypical placental site nodules, and how they incorporate within the GTN spectrum, as well as updates regarding GTN staging and follow-up. RECENT FINDINGS: First-line treatment for GTN still lies in conventional chemotherapy, although the introduction of anti-PD1/PD-L1 immune checkpoint inhibitors has shown significant promise in management of relapsed disease, with responses reported in multiple relapsed choriocarcinomas as well as epithelioid trophoblastic tumours and placental site trophoblastic tumours (ETT/PSTT). Following completion of treatment, ETT/PSTT still require life-long surveillance but for other GTN, no recurrences have been detected after 7 years. SUMMARY: Checkpoint inhibitors are likely to play an increasing role in the future management of GTN management. Further refinement of prognostic factors to identify those most at risk of GTN recurrence is warranted so that surveillance can be focussed on those most at risk, whilst minimizing unnecessary intervention for those at lower risk.

Postoperative chemotherapy on placental site trophoblastic tumor in early stage: analysis of 60 cases.

PURPOSE OF INVESTIGATION: To review the literature of placental site trophoblastic tumor (PSTT) and explore the effect of postoperative chemotherapy in patients with Stage I. MATERIALS AND METHODS: The authors searched literature on Medline, Excerpta Medica Database (EMBASE), and other resources using the keywords "placental site trophoblastic tumor" and "PSTT" from 1981 ito 2014. RESULTS: A total number of 60 patients with Stage I disease were identified, and the presentation, treatment, tumor response, disease status, and follow-up were retrieved and reviewed. According to the authors' knowledge, 725 cases associated with PSTT have been reported in 29 nations/areas since 1981. In this series, the probability of overall survival at ten years in the group of surgery alone and postoperative chemotherapy were 96.7% and 79.1% (p = 0.199), and recurrence-free survival rates were 91.8% and 63.3%, respectively. CONCLUSION: The benefit from postoperative chemotherapy is still equivocal. There is a need for scrupulousness before adding postoperative chemotherapy.

Extrauterine Placental Site Trophoblastic Tumor Involving the Vagina.

Very few cases of placental site trophoblastic tumor (PSTT) primarily involving extrauterine sites have been reported to date. We report a case of a 29-year-old female who presented with a vaginal nodule 9 months after delivery at an outside hospital which was initially diagnosed as a poorly differentiated squamous cell carcinoma. Subsequently she was referred to our institute, and on the basis of histology, mildly elevated serum ß-HCG level, and immunohistochemistry, PSTT was diagnosed. After the completion of chemotherapy, the vaginal nodule completely regressed and serum ß-hCG returned to baseline. Her follow-up has been unremarkable. This case highlights the importance of the fact that PSTT can be easily misdiagnosed at extrauterine sites in the absence of proper clinical, histologic, and immunohistochemical correlation.

Nonchoriocarcinomatous Trophoblastic Tumors of the Testis: The Widening Spectrum of Trophoblastic Neoplasia.

Tumors of trophoblastic derivation other than choriocarcinoma are very rare in the testis but have been reported on occasion in association with other germ cell tumors. Their morphologic spectrum is analogous to the trophoblastic tumors of the female genital tract including epithelioid trophoblastic tumor (ETT) and placental site trophoblastic tumor (PSTT). Herein we report our experience with 8 cases of trophoblastic tumors of testicular origin that lacked the features of choriocarcinoma; these included 4 ETTs, 1 PSTT, 1 unclassified trophoblastic tumor (UTT), 1 partially regressed choriocarcinoma with a monophasic morphology, and 1 hybrid tumor showing a mixture of adenocarcinoma and a UTT. All tumors occurred in young men 19 to 43 years old. Five arose de novo within the testis (2 ETTs, 1 UTT, 1 regressing choriocarcinoma, and the hybrid tumor) as a component of mixed germ cell tumors, and 3 (2 ETTs and 1 PSTT) were found in metastatic sites after chemotherapy. The trophoblastic component was minor (5% to 10%) in 6 tumors but was 95% of 1 metastatic tumor (ETT) and 50% of the hybrid tumor. Other germ cell tumor elements were identified in all cases, most commonly teratoma. The ETTs consisted of nodules and nests of squamoid trophoblast cells showing abundant eosinophilic cytoplasm, frequent apoptotic cells, extracellular fibrinoid material, and positivity for p63 and negativity for human placental lactogen (HPL). The PSTT showed sheets of discohesive, pleomorphic, mononucleated trophoblast cells that invaded blood vessels with fibrinoid change and were p63 negative and HPL positive. The UTT showed a spectrum of small and large trophoblast cells, some multinucleated but lacking distinct syncytiotrophoblasts, and was patchily positive for both p63 and HPL. The hybrid tumor had ETT-like and adenocarcinomatous areas that coexpressed inhibin and GATA3 but were negative for p63 and HPL, leading to classification of the trophoblastic component as UTT. Seven of the patients were alive and well on follow-up (8 to 96 mo; median, 39 mo), whereas the patient with the hybrid tumor died of liver metastases at 2 years. Our study verifies that trophoblastic neoplasms often having the features of nonchoriocarcinomatous gestational trophoblastic tumors may arise from the testis, occur either in the untreated primary tumor or in metastases after chemotherapy, and should be distinguished from choriocarcinoma given what appears to be a less aggressive clinical course.

[Placental-site trophoblastic tumour]. / Placental-site trophoblastic tumour.

Placental-site trophoblastic tumour (PSTT) is the rarest type of gestational trophoblastic tumours. It typically occurs in the reproductive age arising weeks to years after any kind of pregnancy. Although the pathohistology is benign, it may resemble a malignant tumour with metastases, relapse or even fatal outcome. Unlike other types of gestational tumours PSTT is relatively unresponsive to chemotherapy. Hysterectomy is the best treatment.

Attempted conservative management of a placental site trophoblastic tumor: a case report.

BACKGROUND: Placental site trophoblastic tumors (PSTTs) are rare malignant forms of gestational trophoblastic neoplasia (GTN). Controversy exists regarding the most important pathologic or radiologic predictors of extent of disease. Consequently, there is limited information as to the best candidates for conservative surgery. CASE: A 28-year-old female presented 18 months after a term delivery with a biopsy confirmed PSTT. She declined hysterectomy. Imaging revealed a locally limited lesion without myometrial invasion, and no evidence of metastatic disease. She was given two cycles of neoadjuvant etoposide, methrotrexate, actinomycin D, cyclophosphamide, and vincristine (EMA/CO) chemotherapy followed by an attempt at laparoscopically guided hysteroscopic resection. Pathology showed extensive myometrial invasion with positive surgical margin, and our recommendation for hysterectomy with pelvic lymph node dissection was accepted. Postoperatively, she was given two cycles ofpaclitaxel, cisplatin alternating with paclitaxel, etoposide (TP/TE) chemotherapy. CONCLUSION: Fertility sparing options are desirable and should be considered. However, as our case and much of the literature demonstrates, hysterectomy remains the most successful treatment.

Extragestational ßHCG secretion due to an isolated lung epithelioid trophoblastic tumor: microsatellite genotyping of tumoral cells confirmed their placental origin and oriented specific chemotherapy.

CONTEXT: Persistent secretion of ß-human chorionic gonadotropin (ßHCG) in the absence of an ongoing or recent pregnancy and without persistent uterine gestational disease is a rare but challenging situation that requires locating the extrauterine secreting tumor and distinguishing between extragestational choriocarcinoma and gestational trophoblastic neoplasms. CASE PRESENTATION: An unexplained, persistent extragestational ßHCG secretion occurring in a 29-year-old, nonsmoking woman with abnormal uterine bleeding 4 years after a normal pregnancy and without persistent gestational disease led to the discovery by whole-body computed tomography/positron emission tomography of an isolated pulmonary tumor. OBJECTIVE: Characterization of paternal alleles in tumoral cells in order to establish their fetal origin, which may be helpful for the diagnosis and treatment of such tumors. METHODS AND RESULTS: After the surgical procedure, clinical, histological, and immunocytochemical analysis ruled out primary or metastatic bronchopulmonary carcinoma or choriocarcinoma and supported the diagnosis of an isolated, primary, epithelioid trophoblastic tumor. Microsatellite genotyping of tumoral cells identifying paternal alleles confirmed their placental origin and their migration to the lungs, with likely secondary malignant transformation, and guided the choice of postsurgical chemotherapy needed to completely eradicate ßHCG secretion. CONCLUSION: Persistent extragestational secretion of ßHCG in a young nonsmoking woman with a precedent pregnancy and an isolated lung tumor suggests the diagnosis of epithelioid trophoblastic tumor, a very rare malignant tumor for which placental origin needs to be confirmed, especially when occurring several years after the patient's last pregnancy. Simple microsatellite genotyping of tumoral cells will allow this confirmation of diagnosis and help in personalizing chemotherapy.

[Reservation of fertility for seventeen patients with placental site trophoblastic tumor].

OBJECTIVE: To approach the efficiency and feasibility of preserving the fertility for patients with placental site trophoblastic tumor (PSTT). METHODS: Totally 2 086 cases of gestational trophoblastic neoplasm (GTN) patients registered in Peking Union Medical College Hospital between 1998 and 2013. Fifty-seven of them were PSTT patients, 40 cases of which suffered hysterectomy, the rest 17 PSTT patients who preserved their fertility were analyzed retrospectively. The computerized database of clinical and pathological reports was reviewed in this cohort. RESULTS: The clinical manifestation of PSTT was not specific compared to other types of GTN. The average age of the 17 patients was 29.5 years old (range 22-39 years). The most common antecedent pregnancy was term birth (8 cases), the others were spontaneous abortion in 4 case, artificial abortion in 3 cases and molar pregnancy in 2 cases. The baseline serum ß-hCG was slightly elevated and 12 patients (12/15) were less than 1 000 U/L. In this cohort, nine of the patients were in stage I, while the other eight cases were in stage III . The patients suffered conservative surgery, including dilation and curettage of uterus in 7 cases, open abdomen uterine lesion excision in 4 cases, laparoscopic uterine lesion excision in 3 cases, hysteroscopic uterine lesion excision in 1 case, and pulmonary lobectomy in 2 cases. Two of the patients didn't received chemotherapy, while the other 15 cases suffered combination chemotherapy. Compared with 40 patients who suffered hysterectomy during the same interval, fertility preservation group did not result in poor outcomes or high risk of relapse rate. Six subsequent pregnancies happened after the therapy, two of them were during their second-trimester, while four patients had healthy babies by vaginal delivery in two and cesarean section in two. The scar of the uterus was fairly well during the cesarean sections. CONCLUSIONS: Reservation of fertility therapy could be considered in highly-selected patients for young women who strongly desired to preserve their fertility and with localized lesion. Exactitude follow-up after therapy should be recommended. Contraception should also be recommended for at least one year after the chemotherapy. Vaginal delivery could be an option for the future pregnancies.

Combination chemotherapy for primary treatment of high-risk gestational trophoblastic tumour.

BACKGROUND: This is an update of the original review that was published in The Cochrane Database of Systematic Reviews, 2009, Issue 2. Gestational trophoblastic neoplasia (GTN) are malignant disorders of the placenta that include invasive hydatidiform mole, choriocarcinoma, placental-site trophoblastic tumour (PSTT) and epithelioid trophoblastic tumour (ETT). Choriocarcinoma and invasive hydatidiform mole respond well to chemotherapy: low-risk tumours are treated with single-agent chemotherapy (e.g. methotrexate or actinomycin D), whereas high-risk tumours are treated with combination chemotherapy (e.g. EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine)). Various drug combinations may be used for high-risk tumours; however, the comparative efficacy and safety of these regimens is not clear. OBJECTIVES: To determine the efficacy and safety of combination chemotherapy in treating high-risk GTN. SEARCH METHODS: For the original review, we searched the Cochrane Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL; Issue 2, 2008), MEDLINE, EMBASE and CBM in May 2008. For the updated review, we searched Cochrane Group Specialised Register, CENTRAL, MEDLINE and EMBASE to September 2012. In addition, we searched online clinical trial registries for ongoing trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing first-line combination chemotherapy interventions in women with high-risk GTN. DATA COLLECTION AND ANALYSIS: Two review authors independently collected data using a data extraction form. Meta-analysis could not be performed as we included only one study. MAIN RESULTS: We included one RCT of 42 women with high-risk GTN who were randomised to MAC (methotrexate, actinomycin D and chlorambucil) or the modified CHAMOCA regimen (cyclophosphamide, hydroxyurea, actinomycin D, methotrexate, doxorubicin, melphalan and vincristine). There were no statistically significant differences in efficacy of the two regimens; however women in the MAC group experienced statistically significantly less toxicity overall and less haematological toxicity than women in the CHAMOCA group. During the study period, six women in the CHAMOCA group died compared with one in the MAC group. This study was stopped early due to unacceptable levels of toxicity in the CHAMOCA group. We identified no RCTs comparing EMA/CO with MAC or other chemotherapy regimens. AUTHORS' CONCLUSIONS: CHAMOCA is not recommended for GTN treatment as it is more toxic and not more effective than MAC. EMA/CO is currently the most widely used first-line combination chemotherapy for high-risk GTN, although this regimen has not been rigorously compared to other combinations such as MAC or FAV in RCTs. Other regimens may be associated with less acute toxicity than EMA/CO; however, proper evaluation of these combinations in high-quality RCTs that include long-term surveillance for secondary cancers is required. We acknowledge that, given the low incidence of GTN, RCTs in this field are difficult to conduct, hence multicentre collaboration is necessary.

Healthy women with persistently elevated hCG levels: a case series of fourteen women.

OBJECTIVE: To review our own data and that in the literature in order to assess likely morbidity and mortality risks and enhance the information that we can provide to patients suffering with this condition. STUDY DESIGN: This was a retrospective case series using data from the Sheffield Trophoblastic Disease Centre Database combined with data from prior publications. RESULTS: A diagnosis of elevated human chorionic gonadotropin (hCG) in an otherwise healthy woman carries an 11-19% risk of malignancy and 1-3% risk of mortality. Irrespective of persistently elevated hCG, however, pregnancy appears to be a viable and safe prospect. CONCLUSION: Persistently elevated hCG in healthy, nonpregnant women is a rare clinical scenario. Due to the rarity of this condition and potential future malignancy risk, we believe that reporting of future cases is crucial, as is a liaison between national and international trophoblastic disease centers, if we are to gain a more thorough understanding of this possibly premalignant condition.

Placental site trophoblastic tumor (PSTT) with multiple metastases and extremely poor prognosis.

Placental site trophoblastic tumor (PSTT) is a rare type of gestational trophoblastic disease. There is a wide clinical spectrum of presentation and behavior ranging from a benign condition to an aggressive disease with a fatal outcome. PSTT limited to the uterus is in a good prognosis group, but PSTT with metastasis is a lethal disease. We document a case of PSTT with multiple metastases and extremely poor prognosis. A 36-year-old woman had abnormal irregular vaginal bleeding 14 months after her third pregnancy and delivery. The mitotic count of the tumor cells was quite high (23/10 high-power fields). It would have been difficult to remove the tumor by surgery because of the tumor size and its invasion, so we suggested chemotherapy. We treated her with EMA/CO (etoposide, methotrexate, actinomycin-D, cyclophosphamide, vincristine) as a first-line regimen. During the sixth cycle of EMA/CO, the disease became drug-resistant and she died 8 months after the first symptom. This was a rare case among documented patients with PSTT with metastasis, with the patient having short-term survival (<1 year). We conclude that a high mitotic count and atypical undifferentiated pathological features are significant poor prognostic factors for survival in PSTT.

Combination chemotherapy for high-risk gestational trophoblastic tumour.

BACKGROUND: Gestational trophoblastic disease (GTD) includes gestational trophoblastic tumour and hydatidiform mole. Many women of reproductive age are affected by this disease although its incidence differs by geographical location. A number of chemotherapy regimens are used for treating the disease, such as methotrexate, actinomycin D and cyclophosphamide (MAC), methotrexate, actinomycin D, cyclophosphamide, doxorubicin, melphalan, hydroxyurea and vincristine (CHAMOC), etoposide, methotrexate and actinomycin (EMA) plus cyclophosphamide and vincristine (CO) (EMA-CO), etoposide, methotrexate and actinomycin (EMA) plus etoposide and cisplatin(EP) (EMA-EP). The efficacy of these drugs has not been systematically reviewed. OBJECTIVES: To determine the efficacy and safety of combination chemotherapy in treating high-risk GTT. SEARCH STRATEGY: Electronic searches of Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2008), MEDLINE, EMB and CBM, May 2008. Four journals were handsearched and other searching methods were used for identifying more studies. SELECTION CRITERIA: The review included randomised controlled trials (RCTs) or quasi-RCTs of combination chemotherapy for treating high-risk GTT. Patients with placental-site trophoblastic tumour (PSTT), who had received chemotherapy in the previous two weeks, or patients with chemotherapy intolerance were excluded. DATA COLLECTION AND ANALYSIS: Two investigators independently collected data using a data extraction form. Meta-analysis was not performed and the review was conducted as a narrative review. MAIN RESULTS: One study with 42 participants was included in this review. It indicated that a MAC regimen was better than a CHAMOCA regimen for high-risk GTT because of lower toxicity. The quality of the study was unclear. AUTHORS' CONCLUSIONS: The methodological limitations of the included study prevent any firm conclusions about the best combination chemotherapy regimen for high-risk GTT. High quality studies are required.

Management of gestational trophoblastic neoplasia with 5-fluorouracil and actinomycin D in northern China.

OBJECTIVE: To study risk factors associated with the number of chemotherapy courses required to obtain normal beta-human chorionic gonadotropin (beta-hCG) levels and evaluate the effectiveness of combination chemotherapy using 5-fluorouracil (5-FU) and actinomycin D (Act D) (FA) for gestational trophoblastic neoplasia (GTN). STUDY DESIGN: A retrospective study of GTN cases from January 1995 to July 2007 at the Beijing Obstetrics and Gynecology Hospital was performed. RESULTS: During the study period, 240 cases of GTN were diagnosed and managed at our institution. A stepwise regression analysis revealed that the interval between evacuation and chemotherapy, parity, age and beta-hCG level were associated with number of chemotherapy courses required to obtain normal beta-hCG levels. In addition to 4 patients with placental site trophoblastic tumor, FA was used in 218 patients (136 low risk and 82 high risk). CONCLUSION: Early detection of GTN and timely administration of chemotherapy decreases the number of chemotherapy courses required. The combination chemotherapy of 5-FU and Act D is effective in low- and high-risk patients with GTN, but not in patients with placental site trophoblastic tumor; it can be used as primary chemotherapy regimen in high-risk patients with GTN, except those with extensive metastases.