Revealing the Unanticipated: An Uncommon Case of Colorectal Adenocarcinoma Transitioning to Choriocarcinoma - A Case Report and Literature Review.

Choriocarcinomas are uncommon tumors, with non-gestational types occurring in both males and females. Primary choriocarcinoma of the colon is extremely rare. It presents significant diagnostic and therapeutic challenges due to its aggressive nature and poor prognosis, with no cure available, and a mean survival of 8 months. This case report describes a 48-year-old woman who presented with abdominal pain and an ovarian mass, initially suspected to be ovarian cancer. Further workup showed a primary tumor in the colon, with extension to the ovary and liver metastasis. The pathology findings confirmed the presence of colorectal adenocarcinoma with choriocarcinomatous differentiation, as indicated by immunohistochemistry. The patient initially responded to the cisplatin/etoposide regimen; however, she relapsed shortly after. The patient received additional treatments with pembrolizumab, paclitaxel, and olaparib, which resulted in partial remission. Despite challenges during treatment, such as suspected uveitis related to immune-checkpoint inhibitors and potential interference of antibodies with beta-human chorionic gonadotropin (ß-hCG) testing, the patient maintained a good performance status for over 1.5 years after being diagnosed. The case emphasizes the difficulties in treating choriocarcinomas, primarily because of their aggressiveness and the absence of standardized therapy. Our goal with this case is to draw multidisciplinary attention to this rare condition. Further studies are necessary to comprehend its clinical characteristics, prognosis factors, molecular markers, and treatment approaches. Such studies may be crucial in establishing targeted and personalized therapy. LEARNING POINTS: Primary choriocarcinoma of the colon is rare and often misdiagnosed due to its atypical presentation, complicating timely and accurate diagnosis.The aggressive nature of this tumor and lack of standardized therapy necessitates a multidisciplinary approach and personalized treatment plans, especially following relapse.Molecular profiling guided the use of immunotherapy, which showed potential but also presented challenges, highlighting the need for further research in treating this rare malignancy.

Trophoblastic disease and choriocarcinoma.

Gestational trophoblastic disease (GTD) is a group of diseases associated with pregnancies that demonstrate abnormal development of trophoblastic cells. GTD includes hydatidiform moles (HM) that may continue to further develop into gestational trophoblastic neoplasms (GTN), such as choriocarcinoma (CC). Gestational CC is a malignant mass development that may arise from HM, from other (normal) pregnancies or from other gestational events (such as ectopic pregnancies). The aim of this review is to outline current understating of the genetics and epigenetics of GTD and gestational CC and the link between the two diseases.

Gestational choriocarcinoma presenting with hemorrhagic venous infarct and multiple lung metastases: A case report.

Choriocarcinoma is a rare and aggressive form of gestational trophoblastic disease with a high potential for metastasis. We report the case of a 31-year-old female who presented with severe headaches, left-sided weakness, and speech difficulties. Her past medical history included a molar pregnancy, and she had elevated ß-hCG levels of 200,000 mIU/mL. Imaging revealed a right frontoparietal hemorrhagic venous infarct and multiple lung metastases. Based on these findings and the patient's clinical history, a diagnosis of gestational choriocarcinoma with multiple metastases was confirmed. This case highlights the importance of considering choriocarcinoma in the differential diagnosis of young women presenting with neurological symptoms and a history of gestational trophoblastic disease. Early recognition and prompt treatment are crucial to improving outcomes in such cases.

Primary mediastinal choriocarcinoma in a woman treated with VIP therapy instead of BEP therapy for the prevention of postoperative acute respiratory distress syndrome.

Primary mediastinal germ cell tumor (PMGCT) is an extragonadal germ cell tumor (GCT) that is classified as a poor-prognosis subtype among GCTs. Among them, choriocarcinoma accounts for 2% and its prognosis is considered to be notably poor. The standard treatment for advanced germ cell tumors is BEP therapy (bleomycin, etoposide, cisplatin), followed by surgical resection. However, treatments containing bleomycin are associated with postoperative acute respiratory distress syndrome (ARDS). We report a 38-year-old woman with locally advanced primary mediastinal choriocarcinoma. A computed tomography (CT) of the chest showed a 6.5 cm solid mass in the anterior mediastinum that had invaded the superior vena cava. Laboratory data revealed a serum total human chorionic gonadotropin (hCG) value of 298,220 mIU/mL. After one course of BEP therapy, her total hCG level decreased markedly, and the patient was switched to VIP therapy (etoposide, ifosfamide, cisplatin), a bleomycin-free regimen, to reduce the risk of ARDS. Three courses of VIP therapy and one course of salvage therapy enabled a complete surgical resection without any complications including ARDS. The patient has been disease-free for 16 months since the resection. Supplementary Information: The online version contains supplementary material available at 10.1007/s13691-024-00708-z.

Ultra High-risk Gestational Trophoblastic Neoplasia.

Ultra high-risk gestational trophoblastic neoplasia (GTN) refers to patients with World Health Organization prognostic risk scores of at least 13. The mortality risk for these patients averages 30%. Ultra high-risk GTN more frequently presents with higher tumor volume, liver and/or brain metastases, and very high human chorionic gonadotropin levels. The diagnostic evaluation must include a thorough evaluation for central nervous system disease. Prompt initiation of cisplatin - etoposide induction chemotherapy reduces the risks of early death. Collaborative services such as neurosurgery, radiation oncology, and interventional radiology may be required to manage hemorrhagic lesions.

Tislelizumab for treatment of a pediatric patient with primary mediastinal choriocarcinoma: a case report.

Background: Primary mediastinal choriocarcinoma (PCC) is a rare, highly vascular invasive, and prognostically unfavorable malignant tumor. When occurring outside the gonads, primary choriocarcinoma is commonly found in midline locations such as the mediastinum or retroperitoneum. Currently, there is no standardized treatment strategy for PCC. In the case reported herein, we employed tislelizumab and chemotherapy in the treatment of a patient with PCC, and as in March 2024, the patient remained survive. Case Description: A 15-year-old boy who presented with symptoms of fever and cough for a year. Chest computed tomography (CT) scan showed a relatively large soft tissue shadow in the right upper anterior mediastinum, measuring approximately 5.4 cm × 3.8 cm. The patient's soft tissue exhibited unclear demarcation from surrounding mediastinal structures and was accompanied by lung metastasis. The patient underwent a fine needle aspiration biopsy for a mediastinal mass, and the pathology results indicated a germ cell tumor with solid malignant components in the mediastinum, along with pulmonary metastasis of the solid malignancy. The patient's serum levels of beta-human chorionic gonadotropin (ß-HCG) were elevated at 125,554 mIU/mL (normal range: <5 mIU/mL), and alpha-fetoprotein (AFP) was 75.8 ng/mL (normal range, 0.605-7 ng/mL). The patient's cranial magnetic resonance imaging (MRI) plain scan indicated multiple scattered abnormal signals in both cerebral hemispheres. Subsequently, the patient was transferred to Children's Hospital of Nanjing Medical University for his further treatment. During the treatment period, we employed various therapeutic approaches, including chemotherapy, radiotherapy and tislelizumab therapy. After five cycles of tislelizumab treatment, the patient's symptoms of cerebral edema significantly improved, ß-HCG levels decreased. Brain MRI of the patient revealed multiple abnormal signals within the skull, with some lesions showing reduction in size and significant improvement in the surrounding edema zones. The clinical symptoms of the patient improved and he achieved partial remission (PR). At the moment, the patient is living with the disease. Conclusions: The effectiveness of chemotherapy for PCC is limited. Tislelizumab may potentially serve as salvage treatment options for PCC.

Epidemiology of Gestational Trophoblastic Disease.

Worldwide incidence rates of gestational trophoblastic disease (GTD) are difficult to estimate and compare due to large methodological differences within and between countries. Asia has generally reported higher incidence rates than Europe and North America, but modern reports have demonstrated a temporal decrease of GTD incidence rates in Asia and an increase in some European countries and North America. The main risk factors for hydatidiform mole are maternal age and previous molar events. Future studies on the epidemiology of GTD should include gestational trophoblastic neoplasia and international collaborative studies on this rare disease should be encouraged.

Surgical Management of Gestational Trophoblastic Neoplasia.

Gestational trophoblastic neoplasia (GTN) is primarily treated with chemotherapy, but surgery plays a key role at different steps in disease management, including initial diagnosis, primary therapy, and salvage options. Initial diagnosis is usually made by electric or manual vacuum aspiration for molar pregancy or uterine curettage for other forms of GTN. Excisional procedures of localized disease, whether second curettage or hysterectomy, can obviate chemotherapy, but patients still require monitoring for relapse. Resection remains a useful adjunct for either the management of isolated foci of chemoresistant disease or the management of bleeding complications.

A Case of Metastatic Vulvar Choriocarcinoma Misdiagnosed as Vulvar Abscess: A Case Report.

Background: Metastatic vulvar choriocarcinoma, a rare ectopic gestational trophoblastic neoplasia (GTN), often presents a diagnostic challenge due to its mimicry of other conditions, particularly in resource-limited settings. Its primary symptom is abnormal vaginal bleeding without a clear cause. Consequently, diagnosing and managing it poses difficulties for many low-resource health facilities, as evidenced by the current case. Case Presentation: We present the case of a 25-year-old, P2+2+2L2, who had a large painless, bleeding vulva mass for nearly 5 months. This followed a spontaneous abortion the month prior. The mass gradually increased in size and was accompanied by fever, pus discharge, and weight loss. Despite being treated at multiple health facilities for a vulvar abscess, there was no improvement. A diagnosis was finally made at a tertiary facility where elevated quantitative serum beta-human chorionic gonadotropin (hCG) (ß-hCG) was noted. Due to uncontrollable vulva bleeding, she was referred to another tertiary facility for emergency radiotherapy. Following stabilization, chemotherapy was administered using the EMA-CO protocol. Conclusion: The report highlights the difficulty in diagnosing vulvar choriocarcinoma, underscoring the importance of a high index of suspicion. Clinical tests such as serum (ß-hCG) and imaging studies are crucial for diagnosis. In resource-limited settings, a simple strip-based urine pregnancy test with serial dilutions can be sufficient for diagnosing and managing vulvar choriocarcinoma.

Equol exerts anti-tumor effects on choriocarcinoma cells by promoting TRIM21-mediated ubiquitination of ANXA2.

Choriocarcinoma is a malignant cancer that belongs to gestational trophoblastic neoplasia (GTN). Herein, serum metabolomic analysis was performed on 29 GTN patients and 30 healthy individuals to characterize the metabolic variations during GTN progression. Ultimately 24 differential metabolites (DMs) were identified, of which, Equol was down-regulated in GTN patients, whose VIP score is the 3rd highest among the 24 DMs. As an intestinal metabolite of daidzein, the anticancer potential of Equol has been demonstrated in multiple cancers, but not choriocarcinoma. Hence, human choriocarcinoma cell lines JEG-3 and Bewo were used and JEG-3-derived subcutaneous xenograft models were developed to assess the effect of Equol on choriocarcinoma. The results suggested that Equol treatment effectively suppressed choriocarcinoma cell proliferation, induced cell apoptosis, and reduced tumorigenesis. Label-free quantitative proteomics showed that 136 proteins were significantly affected by Equol and 20 proteins were enriched in Gene Ontology terms linked to protein degradation. Tripartite motif containing 21 (TRIM21), a E3 ubiquitin ligase, was up-regulated by Equol. Equol-induced effects on choriocarcinoma cells could be reversed by TRIM21 inhibition. Annexin A2 (ANXA2) interacted with TRIM21 and its ubiquitination was modulated by TRIM21. We found that TRIM21 was responsible for proteasome-mediated degradation of ANXA2 induced by Equol, and the inhibitory effects of Equol on the malignant behaviors of choriocarcinoma cells were realized by TRIM21-mediated down-regulation of ANXA2. Moreover, ß-catenin activation was inhibited by Equol, which also depended on TRIM21-mediated down-regulation of ANXA2. Taken together, Equol may be a novel candidate for the treatment for choriocarcinoma.

Gestational Trophoblastic Neoplasia Rate and Its Related Factors in Women With a Partial Hydatidiform Mole at Tudu Hospital, Vietnam.

Background Minimal studies have been carried out on a partial hydatidiform mole (PHM) in Vietnam, so the treatment outcomes for patients with PHM are unknown. This study aimed to determine the occurrence rate of gestational trophoblastic neoplasia (GTN) and its related factors in women with PHM at Tu Du Hospital, Vietnam. Materials and methods This retrospective cohort study included 370 women with PHM diagnosed through a histopathological assessment following termination of pregnancy at Tu Du Hospital from January 2020 to December 2021. Survival analysis was used for GTN cumulative rate estimation and the Cox regression model for determining GTN-related factors. Results After a 1-year follow-up, 21 patients were found to have GTN, exhibiting a rate of 5.7% (95% confidence interval (CI): 3.5 - 8.4). GTN occurred 4.67±2.23 weeks following curettage with peaks at weeks 3-6. No cases of GTN were recorded eight weeks following termination by curettage. After multivariate analysis, the GTN rate was higher in patients with a history of miscarriage/termination (hazard ratio (HR)=2.84; 95% CI: 1.05-7.69). Conclusion The rate of GTN in PHM patients was 5.7%. Patients who had a history of miscarriage or termination were 2.84 times more likely to develop GTN than patients who did not.

Metastatic choriocarcinoma presenting as upper gastrointestinal bleeding: A case report.

Choriocarcinoma is a type of gestational trophoblastic disease that occurs as a complication of pregnancy-related events. The gestational trophoblastic disease includes both benign and malignant conditions including complete and partial mole, invasive mole, choriocarcinoma, and placental site trophoblastic disease. Choriocarcinoma generally presents with pervaginal bleeding, symptoms of anemia, and symptoms of its metastatic lesion. The common sites of metastasis are the lung, vagina, brain, and liver. The gastrointestinal (GI) tract is an uncommon site of metastasis occurring in <5% of patients. Upper GI bleeding as presenting complaints without pervaginal bleeding is also very rare with only a few reported cases. Here we present a case of 29 years young female who presented in our emergency department with complaints of hematemesis and altered sensorium where clinical suspicion was peptic ulcer disease but imaging modality with computed tomography showed hypervascular lesions in the brain with suspicion of choriocarcinoma. With further imaging and laboratory tests, confirmatory diagnosis of choriocarcinoma was made. This case highlights the importance of imaging in the diagnosis of choriocarcinoma where the history of the patient is misleading.

Pathology of Gestational Trophoblastic Disease (GTD).

Gestational trophoblastic disease (GTD), comprising hydatidiform moles (HM) and gestational trophoblastic tumors (GTT), is extremely rare. HM originate from villous trophoblast and are considered preneoplastic. GTT originate from the intermediate, largely extravillous trophoblast and includes choriocarcinoma, placental site trophoblastic tumor, epitheloid trophoblastic tumor, and mixed trophoblastic tumor. The abnormal (non-molar) villous lesions, non-malignant tumour-like conditions, and non-gestational tumors add to the diagnostic dilemma. The correct diagnosis and classification of these rare conditions are important. This review intends to provide an update on changes in the World Health Organization classification and focusses on the morphologic aspects in diagnosis of GTD.

Treatment of High-Risk Gestational Trophoblastic Neoplasia.

High-risk gestational trophoblastic neoplasia encompasses patients with high volumes of disease or diffuse metastatic involvement who are unlikely to achieve remission with single-agent chemotherapy. Etoposide-based multi-drug regimens form the core of high-risk therapy. Second-line therapy includes platinum-based regimens. Increasingly, third-line therapy uses immunotherapy. Surgical intervention may be required to resect foci of resistant disease or manage complications. Treatment should continue until the hCG is less that the reference range for normal, followed by at least 3 cycles of consolidation therapy. At least 2 years of hCG surveillance are advisable for most patients requiring multiagent therapy to encompass 95% of relapses.

Non-gestational Choriocarcinoma of the Ovary: A Report of a Rare Case From Saudi Arabia.

Non-gestational choriocarcinoma of the ovary is extremely rare and presents diagnostic and therapeutic challenges. Early recognition, appropriate surgical intervention, and adjuvant chemotherapy are essential for successful management. This case underscores the importance of considering choriocarcinoma in the differential diagnosis of ovarian tumors, especially in perimenopausal women with vascular mass. We present the case of a 47-year-old sexually active woman with a history of pelvic pain, diagnosed with non-gestational choriocarcinoma of the ovary. The patient underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy with successful management using the bleomycin, etoposide, and platinum (BEP) regimen. This case highlights the importance of early detection and appropriate management of this rare entity.

Heterotopic Tubal Choriocarcinoma Coexistent with a Viable Intrauterine Pregnancy: A Case Report.

Background and Objectives: Choriocarcinoma is an aggressive oncological disease that manifests as trophoblast tissue proliferation. The vast majority of primary lesions affect the uterus, with primarily extrauterine lesions being a rarity. Choriocarcinoma with an ongoing pregnancy is extremely rare because fetuses usually do not survive the third trimester. Case Report: We present a case of heterotopic tubal choriocarcinoma coexisting with a viable intrauterine pregnancy. A 30-year-old, 39-week pregnant woman (gravida 2, para 2) came to our hospital complaining of acute upper abdominal pain. During routine prenatal screening in the first trimester, no pathological ultrasound findings were detected. Similar abdominal pain episodes had been recorded at 18, 27, and 32 weeks of gestation, when patient was hospitalized for examination and observation, but the cause of symptoms at that time of gestation remained unclear. The patient underwent an emergency caesarean section due to severe abdominal pain and fetal compromise. She delivered a live male infant. During the surgery, around 1000 mL of blood clots were evacuated, and the excision of the right fallopian tube and masses, as well as the control of significant blood loss was performed. Postoperative serum beta-hCG was elevated to 139 482 IU/L, while imaging studies showed no metastasis. The histological examination of the excised tissue samples confirmed a diagnosis of tubal choriocarcinoma. With a FIGO score of 8, the patient received three courses of the EP/EMA regimen. After more than a year, the patient showed no radiographic signs of distant metastasis and is now in complete remission. Conclusions: This case highlights the diagnostic complexity of such extremely rare scenarios. Even though such cases are rare, it demonstrates the necessity for improved diagnostic measures to enhance patient outcomes in similar clinical situations.

Hypermethylated RASAL1's promotive role in chemoresistance and tumorigenesis of choriocarcinoma was regulated by TET2 but not DNMTs.

BACKGROUND: Patients with choriocarcinoma (CC) accompanying chemoresistance conventionally present a poor prognosis. Whether ras protein activator like-1 (RASAL1) functions as a tumor promoter or suppressor depends on tumor types. However, the role of RASAL1 in process of chemoresistance of CC and underlying molecular mechanism remain elusive. METHODS: The expression pattern of RASAL1 in CC cells and tissues was measured using Western blotting, immunohistochemistry and qRT-PCR. Cell viability and proliferative ability were assessed by MTT assay, Tunnel assay and flow cytometric analysis. Additionally, the stemness was evaluated by the colony formation and tumor sphere formation. Methotrexate (MTX) was applied to exam the chemosensitivity of CC cells. RESULTS: The expression of RASAL1 was reduced both at the protein and mRNA levels in CC tissues and cells compared to hydatidiform mole (HM) and invasive mole (IM). Loss of RASAL1 was attributed to its promoter hypermethylation and could be restored by 5-Aza. Knock-down of RASAL1 promoted the viability, proliferative potential, stemness and EMT phenotype of JEG-3 cells. However, induced overexpression of RASAL1 by 5-Aza significantly prohibited cell proliferation and stemness potential of the JAR cell. Additionally, the xenograft model indicated that knockdown of RASAL1 led to a remarkable increase of tumor volume and weight in comparison with its counterpart. Moreover, the stimulatory activity brought by decrease of RASAL1 could be deprived by ß-catenin inhibitor XAV 939, yet the suppressive activity resulted from its promoter demethylation could be rescued by ß-catenin activator BML-284, indicating that function of RASAL1 depends on ß-catenin. Besides, the co-immunoprecipitation assay confirmed the physical binding between RASAL1 and ß-catenin. Further investigations showed hypermethylated RASAL1 was regulated by TET2 but not DNMTs. CONCLUSION: Taken together, the present data elucidated that reduced RASAL1 through its promoter hypermethylation regulated by TET2 promoted the tumorigenicity and chemoresistance of CC via modulating ß-catenin both in vitro and in vivo.

Molecular Basis of Hydatidiform Moles-A Systematic Review.

Gestational trophoblastic diseases (GTDs) encompass a spectrum of conditions characterized by abnormal trophoblastic cell growth, ranging from benign molar pregnancies to malignant trophoblastic neoplasms. This systematic review explores the molecular underpinnings of GTDs, focusing on genetic and epigenetic factors that influence disease progression and clinical outcomes. Based on 71 studies identified through systematic search and selection criteria, key findings include dysregulations in tumor suppressor genes such as p53, aberrant apoptotic pathways involving BCL-2 (B-cell lymphoma), and altered expression of growth factor receptors and microRNAs (micro-ribose nucleic acid). These molecular alterations not only differentiate molar pregnancies from normal placental development but also contribute to their clinical behavior, from benign moles to potentially malignant forms. The review synthesizes insights from immunohistochemical studies and molecular analyses to provide a comprehensive understanding of GTD pathogenesis and implications for personalized care strategies.

Endometrial Clear Cell Carcinoma with Non-Gestational Uterine Choriocarcinoma Differentiation.

Choriocarcinoma is a rare and highly malignant tumor that primarily occurs in women of reproductive age. Choriocarcinoma can be classified as gestational or nongestational, based on its pathogenetic origin. Although primary nongestational choriocarcinoma has been described in the ovaries, it is very rare in the uterus, especially in postmenopausal women. It is crucial to differentiate between gestational and non-gestational choriocarcinoma, as it affects the choice of treatment and prognosis. Endometrial clear cell carcinoma is an aggressive subtype of endometrial cancer, accounting for less than 10% of all uterine carcinomas. Trophoblastic differentiation in uterine cancer is unusual and very rare, with only three examples of the subtype of clear cell endometrial cancer with gestational choriocarcinoma reported in the literature, including only one with nongestational choriocarcinoma. Here, we present an example of clear cell carcinoma with nongestational uterine choriocarcinoma differentiation in a postmenopausal woman.

Case report: A case with atypical presentation oftesticular choriocarcinoma.

Testicular choriocarcinoma is a relatively rare malignancy with a highly aggressive nature. Timely diagnosis and treatment can help prolong the survival of patients and even cure them. This case reports a 29-year-old male who presented to the clinic for a month with epigastric pain. On examination, a massive mass of approximately 9*10 cm could be palpated in the upper abdomen. When asked about his previous history, the patient only described a history of a right inguinal hernia that had been repaired 12 years earlier. The admission diagnosis was considered the retroperitoneal tumor, which was found to have metastasized to the liver and lungs after the completion of relevant tests. We then performed a CT-guided lune puncture biopsy on day 8 of admission. The biopsy pathology suggested metastatic cancer was considered. As the symptoms of tumor compression gradually worsened, we performed surgical treatment (retroperitoneal tumor resection + partial duodenal resection + enteroanastomosis) on day 13 of admission. The postoperative pathology was choriocarcinoma. We subsequently conducted a detailed inquiry with the patient's family about his medical history and found a history of inguinal testicle. Through testicular ultrasound examination, it was preliminarily determined to be testicular choriocarcinoma (not yet pathologically confirmed). We wanted to start salvage chemotherapy as soon as possible after surgery. However, the patient's postoperative condition was poor, with rapid progression of hepatopulmonary metastases and gradually increased thyrotoxicosis, and we started salvage chemotherapy (EP regimen: etoposide and cisplatin) on postoperative day 12. However, the patient was forced to stop due to a severe chemotherapy reaction and died of respiratory and cardiac arrest in the hospital. For male patients with retroperitoneal mass, the possibility of germ-cell neoplasm should first be excluded. By inquiring in detail about a history of cryptorchidism and in the initial days of hospitalization, testicular exploration, ultrasounds, and serum tumor markers (AFP, ß-HCG) tests can be conducted to rule out the possibility of germ-cell neoplasm, thereby preventing misdiagnosis and treatment delays. If the clinical diagnosis is metastatic germ-cell tumor with severe symptoms of metastatic disease, surgery should never be used as the initial treatment.