Challenges in the diagnosis and treatment of pure non-gestational uterine choriocarcinoma in a child: a case report.

BACKGROUND: Diagnosing non-gestational uterine choriocarcinoma in children is challenging because of its rarity and nonspecific imaging findings. Herein, we report a case of non-gestational uterine choriocarcinoma in a child, which was unexpectedly found during exploratory laparotomy and confirmed by histopathological findings. However, the tumor did not respond to chemotherapy. CASE PRESENTATION: A 4-year-old Indonesian female patient was brought into the emergency unit with chief complaint of vaginal bleeding. She had suffered from vaginal spotting 4 months before being admitted to the hospital. Physical examination revealed a distended abdomen in the left lumbar region and a palpable fixed mass with a smooth surface. Abdominal computed tomography scans revealed a large mass (10 × 6 × 12 cm) with fluid density and calcification. Thus, we suspected left ovarian teratoma. The patient's luteinizing hormone, follicle-stimulating hormone, and lactate dehydrogenase levels were 25.2 mIU/ml, 0.1 mIU/ml, and 406 U/l, respectively. According to the clinical and radiological findings, we decided to perform an exploratory laparotomy and found a tumor originating from the uterus, not the ovarium. We did not observe liver nodules and any enlargement of abdominal lymph nodes. Subsequently, we performed hysterectomy. The histopathological findings supported the diagnosis of choriocarcinoma. The patient was discharged uneventfully on postoperative day 5. Thereafter, the patient underwent nine cycles of chemotherapy, including carboplatin (600 mg/m2 IV), etoposide (120 mg/m2 IV), and bleomycin (15 mg/m2 IV). However, on the basis of the clinical findings of a palpable mass and partial intestinal obstruction, the tumor relapsed soon after the ninth cycle of chemotherapy. Currently, the patient is undergoing chemotherapy again. CONCLUSIONS: Although pure non-gestational uterine choriocarcinoma is rare, it should be considered as one of the differential diagnoses for intraabdominal tumors in a child, so as to better guide and counsel families regarding the surgical plan and prognosis, respectively. In the present case, the patient's response to chemotherapy was poor, implying that the treatment of non-gestational choriocarcinoma is still challenging, particularly in the pediatric population.

Nongestational ovarian choriocarcinoma with bilateral teratoma: A rare case report and literature review.

INTRODUCTION: Trophoblastic neoplasms are often associated with pregnancy, and nongestational trophoblastic neoplasms are extremely rare. Nongestational ovarian choriocarcinoma (NGCO) is a highly aggressive germ cell-derived tumor frequently presenting with early hematogenous metastasis. PATIENT CONCERNS: Herein, we report a case of a 28-year-old unmarried woman with regular menstruation who experienced vaginal bleeding 1 week after her last menstrual cycle. Doppler ultrasound revealed bilateral adnexal masses and elevated serum human chorionic gonadotropin (hCG) levels. The patient was initially misdiagnosed as presenting an ectopic pregnancy. DIAGNOSIS: The final pathology confirmed an International Federation of Gynecology and Obstetrics stage IA NGCO with bilateral mature teratoma of the ovary. This is an extraordinary instance of ovarian choriocarcinoma which emerged without any prior gestation, and the patient's lack of a history of pregnancy made the diagnosis ignored. INTERVENTIONS: After initial surgery and 1 cycle of bleomycin, etoposide, and cisplatin (BEP) chemotherapy, a laparoscopic fertility-preserving comprehensive staging surgery was performed. Two cycles of chemotherapy with BEP were administered as supplemental therapy postsurgery, and leuprorelin was administered to protect ovarian function. OUTCOMES: Menstruation resumed 4 months after chemotherapy completion, and tumor indicators were within the normal range. No signs of recurrence were observed at the 36-month follow-up. CONCLUSION: NGCO should be considered if a female patient exhibits irregular vaginal bleeding and masses in the adnexal area. The present case and our literature review also highlighted that fertility-sparing surgery and multidrug chemotherapy are effective methods for treating NGCO.

Non-gestational choriocarcinoma: unraveling the similarities and distinctions from its gestational counterpart.

Choriocarcinoma is a highly vascular and invasive tumor of anaplastic trophoblast, predominantly made up of cytotrophoblasts and syncytiotrophoblasts without villi. Based on its origin, choriocarcinoma can be either gestational or non-gestational. Non-gestational choriocarcinoma can be of germ cell origin, or can be seen in association with a somatic high-grade malignancy. It is difficult to differentiate gestational from non-gestational choriocarcinoma, especially in the reproductive age group. It is important to distinguish between the two, for accurate staging and prognostication, deciding the primary treatment modality, (ie, surgery or chemotherapy), and tailoring follow-up timeframes after diagnosis. An extensive literature search was performed regarding all cases of non-gestational choriocarcinoma, published before March 2023. A note was made of whether the origin of choriocarcinoma was ascertained and how gestational choriocarcinoma was differentiated from non-gestational choriocarcinoma. The keywords used for literature search were "non-gestational choriocarcinoma", "primary choriocarcinoma", "ovarian choriocarcinoma", "ovarian germ cell tumors", or "choriocarcinomatous differentiation". This review aims to summarize the similarities and differences in the epidemiology, pathogenesis, clinical presentation, and management guidelines between gestational and non-gestational choriocarcinoma, which can form an important educational resource for clinicians and laboratory physicians dealing with such cases.

A rare case of gestational ovarian choriocarcinoma coexistent with intrauterine pregnancy.

OBJECTIVE: To report the rare case of gestational primary ovarian choriocarcinoma coexistent with intrauterine pregnancy, successfully treated with surgery and systemic chemotherapy. We also describe the utility of short tandem repeat (STR) genotyping in the diagnosis of choriocarcinoma. CASE REPORT: A 38-year-old woman at 17 gestational weeks presented with an ovarian tumor rupture in the left ovary. Left salpingo-oophorectomy was performed and the patient was diagnosed with gestational ovarian choriocarcinoma via histopathology and STR genotyping. After artificial abortion, the patient underwent 8 cycles of chemotherapy. Abdominal hysterectomy was performed because of the presence of low levels of human chorionic gonadotropin and the tumor that developed behind the uterus. However, no viable choriocarcinoma cells were found in the residual tumor, suggesting that the patient achieved full remission. CONCLUSIONS: Early detection is crucial in treating choriocarcinomas; thus, clinicians should consider the possibility of choriocarcinoma at the presence of an ovarian tumor during pregnancy. Gestational and non-gestational choriocarcinomas differ in prognosis and sensitivity to chemotherapy due to their different etiologies. Therefore, STR genotyping may be beneficial in predicting the patient's prognosis or selecting the appropriate regimen.

Clinical Experience of Male Primary Choriocarcinoma at the Samsung Medical Center.

PURPOSE: The objective of this study was to describe and analyze the clinicopathological features of primary choriocarcinoma (PCC) observed in male patients treated at the Samsung Medical Center between 1996 and 2020. MATERIALS AND METHODS: We reviewed the clinical records of 14 male patients with PCC retrospectively to assess their demographic, histological, and clinical characteristics at the time of diagnosis as well as identify the treatment outcomes. RESULTS: The median age of the patients was 33 years. The primary tumor site was the testicles in seven cases (50%), the mediastinum in six cases (43%), and the brain in one case (7%). The most common metastatic site was the lungs (79%), followed by the brain (43%). All patients with PCC received cytotoxic chemotherapy. Twelve patients had records of their response to cytotoxic chemotherapy; of these 12 patients, eight (8/12, 67%) achieved an objective response, and four (4/12, 33%) achieved stable disease response as the best response during chemotherapy. CONCLUSION: It is known that most male PCC patients eventually develop resistance to cytotoxic chemotherapy and die. Factors such as poor response to chemotherapy, high disease burden, brain metastasis, and hemoptysis at the time of diagnosis are associated with shorter survival time in male PCC patients. Programmed death-1/programmed death-ligand 1 blockade therapy can be a salvage treatment for chemotherapy-resistant male PCC patients.

[Endometrioid adenocarcinoma with a co-existing non-gestational choriocarcinoma in uterus].

This is a case report of a 56-year-old woman with a history of postmenopausal bleeding, who presented with an endometrioid adenocarcinoma and a co-existing non-gestational choriocarcinoma. We performed robotic assisted hysterectomy, bilateral oophorectomy and pelvic lymphadectomy, and histopathologic examination revealed a malignant tumour showing an endometrioid adenocarcinoma grade 2 with a minor component of choriocarcinoma incorporated into the adenocarcinoma. We compared data from exome sequencing of DNA from tumour and blood to show, that the choriocarcinoma component was most likely non-gestational.

Using short tandem repeat analysis for choriocarcinoma diagnosis: a case series.

BACKGROUND: Choriocarcinoma is a highly aggressive, malignant trophoblastic neoplasm that can be gestational or non-gestational in origin. Accurate discrimination between these two subtypes, the causative pregnancy type, and the pregnancy-to-treatment interval for gestational choriocarcinoma are vital for clinical management. METHODS: Fifteen choriocarcinomas were genotyped using multiplex fluorescent polymerase chain reaction amplification of 15 short tandem repeat (STR) loci and the amelogenin locus (XY determination). Genotype patterns at each locus from tumoral and maternal tissues were compared, and any prior or concurrent mole/placenta was also compared when available. According to STR results showing the presence or absence of the paternal chromosomal complement, the gestational or non-gestational origin of the tumor and the nature of the causative pregnancy was identified. RESULTS: Fourteen tumors were gestational. Of these, seven were androgenetic/homozygous XX, and two were androgenetic/heterozygous XX, indicating that the causative pregnancies were molar pregnancies. Among the nine molar pregnancies, five were of the occult type. A menopausal patient developed a tumor from a mole that occurred seven years ago, identified by the genetically identical allele from the tumor and prior mole. One tumor originating from a previous mole was interrupted by term delivery. Two tumors found eight weeks postpartum were identified as originating from a prior occult mole. A pelvic choriocarcinoma was separated from a genetically distinct third trimester intrauterine placenta. Five gestational tumors were biparental: 2 XX, 3 XY. Of three ovarian tumors, two were confirmed gestational (1 androgenetic/homozygous XX; 1 biparental XY), and one was an ovarian tumor (XX) with a complete match of the genotype for all 15 loci, therefore ascertaining its non-gestational origin. CONCLUSION: Gestational choriocarcinoma can originate in an androgenetic or biparental manner. The majority are androgenetic/homozygous XX, while a large number of them might be occult molar pregnancies. The origin of ectopic androgenetic choriocarcinoma with concurrent intrauterine placenta might be from either dispermic twin gestation (mole and coexistent nonmolar fetus) or an antecedent molar pregnancy. Choriocarcinoma shortly postpartum might not be associated with the last placenta. STR analysis can be useful in distinguishing gestational choriocarcinoma from non-gestational, as well as the causative pregnancy, and serve as a helpful examination tool for guiding clinical management.

Pure nongestational uterine choriocarcinoma in postmenopausal women: a case report with literature review.

Nongestational choriocarcinoma is rare, especially in postmenopausal women. It may be derived from the transformation of germ cells or dedifferentiation of other tumor tissue cells. It is usually found in the ovaries but rarely in the uterus. Pure nongestational uterine choriocarcinoma in postmenopausal women is exceptional. Thirty-four cases of choriocarcinoma have been found during the past 25 y at the Tianjin Medical University General Hospital. We retrospectively reviewed the medical records of these 34 cases and found only two cases of nongestational uterine choriocarcinoma, both of which were postmenopausal women. We also reviewed 19 other cases previously reported during the past 50 y (from 1970 to 2018) that were identified as uterine choriocarcinoma in postmenopausal women. Analysis of these combined data indicates that nongestational choriocarcinoma is a rare neoplasm in postmenopausal patients. It genetically originates entirely in the patient, and short tandem repeat (STR) analyses are usually required to differentiate gestational and nongestational choriocarcinoma. Although nongestational choriocarcinoma shows some response to chemotherapy, sensitivity is much poorer than that in gestational choriocarcinoma. The prognosis for nongestational choriocarcinoma is poor and the long-term survival rate is low.

Primary non-gestational uterine choriocarcinoma mimicking leiomyoma.

Uterine choriocarcinoma is a trophoblastic neoplasm that is most commonly gestational but can also be non-gestational in origin. However, primary non-gestational uterine choriocarcinoma is very rare, with only few cases having been reported. We report a case of a premenopausal woman who had initially been diagnosed with myoma delivery but who was discovered to have primary non-gestational uterine choriocarcinoma. This 46-year-old woman had no history of pregnancy. She was referred to our hospital for treatment of the myoma delivery. After tumor removal, histological examination led to the diagnosis of choriocarcinoma. The serum human chorionic gonadotropin level (207,300 mIU/mL) prior to surgery was abnormally high, and because the computed tomography scans additionally revealed lung metastasis, the patient was diagnosed with FIGO stage III choriocarcinoma. Due to the lack of pregnancy history and abstinence from sexual intercourse for >1 year, we performed short tandem repeat analysis, and diagnosed the patient with non-gestational choriocarcinoma. Despite treatments using multiple anticancer agents after the surgery, the patient died 1 year after starting the treatments. On this occasion, we report a very rare case of a premenopausal woman who was diagnosed with primary non-gestational uterine choriocarcinoma mimicking leiomayoma.

Spontaneous renal hemorrhage secondary to choriocarcinoma in a man with congenital hypospadias and cryptorchidism: a case report and literature review.

BACKGROUND: Choriocarcinoma is a rare malignant germ-cell tumour, most commonly found in adult women. It infrequently presents as spontaneous renal haemorrhage (SRH). Genital malformation and SRH secondary to choriocarcinoma has previously been only reported in females. We present what we believe to be the first case of a male patient with genital malformation (hypospadias and cryptorchidism) and SRH at presentation of choriocarcinoma. CASE PRESENTATION: A 25-year-old man presented to the department with intense pain in the right flank region and lower back. Initial investigations showed spontaneous renal haemorrhage, for which an emergency partial nephrectomy was performed. Clinical, radiological, and pathological investigations suggested a diagnosis of testicular choriocarcinoma with metastases to the right kidney, both lungs, and brain. Initial treatment was with a chemotherapy regimen of cisplatin, etoposide and bleomycin and whole brain radiotherapy; however, 6 months after diagnosis the patient developed liver metastasis, after which time the BEP protocol was switched to ITP with oral apatinib. Despite best efforts, the liver and lung metastasis continued to grow and a decision was made to discontinue active treatment and provide only palliative care until the patient passed away. CONCLUSION: Choriocarcinoma is a difficult cancer to diagnose pre-operatively. In male patients with early metastasis, prognosis may be much poorer than in the commoner gestational choriocarcinoma. A multidisciplinary with comprehensive post-surgical intervention is of great importance in the treatment of these patients.

Primary Gastric Choriocarcinoma Presenting as a Pregnancy of Unknown Location.

BACKGROUND: Pregnancy of unknown location presents a diagnostic challenge, in rare occasions leading to the diagnosis of malignancy. We describe a case of ß-hCG-secreting nongestational primary gastric choriocarcinoma presenting as a pregnancy of unknown location. CASE: A 37-year-old woman, gravida 4 para 3013, presented with several days of vaginal bleeding and rising ß-hCG level without ultrasound localization of pregnancy. The diagnosis of pregnancy of unknown location was made and methotrexate administered at a ß-hCG level of 7,779 milli-international units/mL. A 40% decrease in ß-hCG level was noted between days 4 and 7. One week later, an inappropriate ß-hCG level rise to 10,937 milli-international units/mL was noted, prompting a second dose of methotrexate and computed tomography imaging, leading to the discovery of gastric and liver lesions. Pathology from gastric biopsies revealed nongestational choriocarcinoma. The patient was treated with chemotherapy, with death from cardiac arrest 7 months after diagnosis. CONCLUSION: Malignancies that can secrete ß-hCG include gestational trophoblastic disease, gonadal and extragonadal germ cell tumors, and malignancies with choriocarcinoma differentiation. Although ectopic pregnancy compromises approximately 2% of first-trimester pregnancy, gestational trophoblastic neoplasia and gestational choriocarcinoma can be seen in 1 of 1,500 and 1 of 20,000 pregnancies, respectively. When ß-hCG levels do not fall appropriately in women undergoing medical management for pregnancy of unknown location, ectopic ß-hCG secretion by a malignancy must be considered.

Primary Choriocarcinoma of the Bladder: A Case Report and Review of Literature.

Primary choriocarcinoma of the urinary bladder is a rare entity, and should be distinguished from urothelial carcinoma with trophoblastic differentiation. The leading treatment modalities include surgical extirpation, chemotherapy, and radiation; however, survival remains poor. Herein we describe a rare case of choriocarcinoma of the bladder in a man who presented for evaluation with hematuria and subsequently underwent radical cystectomy with urinary diversion. Diagnosis of extragonadal germ cell tumor was confirmed using fluorescence in situ hybridization identification of isochromosome 12p.

Primary mediastinal choriocarcinoma with brain metastasis in a female patient.

Nongestational choriocarcinoma is very rare and carries a poor prognosis in female patients. In this report, the authors present a case of nongestational choriocarcinoma with brain metastasis in a female. A 58-year-old female with intermittent back pain was referred to a private hospital. On examination, a mediastinal tumor and a pancreatic tumor were detected. Endoscopic ultrasound-guided fine needle aspiration biopsy of the tumor was performed for histological evaluation. Pathological diagnosis was difficult because only a small amount of tissue was collected. Head MRI showed multiple metastatic tumors in the brain. The patient was diagnosed with primary mediastinal choriocarcinoma with brain metastasis. She was treated with one course of an etoposide, methotrexate, dactinomycin, cyclophosphamide, and vincristine regimen, but her general condition gradually deteriorated, and she died on day 41. Nongestational choriocarcinoma is drug resistant, whereas gestational choriocarcinoma has better chemotherapeutic sensitivity.

Pure non-gestational choriocarcinoma arising in the ovary.

Non-gestational choriocarcinoma (NGCO) is a rare primary ovarian cancer with poor prognosis. It is important to distinguish it from gestational ovarian choriocarcinoma (GCO), because there are different treatment options. However, it is difficult to distinguish the two types by routine histologic, ultrastructural, or immunohistochemical examination. The authors present NGCO in a 41-year-old woman, which was confirmed by DNA polymorphism analysis. All tested microsatellite markers had identical DNA profiles with the same allelic sizes between tumor and normal myometrium of the patient, indicating that both tissues originated from the same person. The results confirmed that the tumor was non-gestational in origin. Although the tumor was large, the authors performed hand- assisted laparoscopic surgical (HALS) staging. After three cycles of combination chemotherapy and surgery, the patient has not had any evidence of disease 48 months after treatment. This case demonstrates the usefulness of HALS staging and DNA polymorphism analysis in NGCO.

A pipeline to quantify serum and cerebrospinal fluid microRNAs for diagnosis and detection of relapse in paediatric malignant germ-cell tumours.

BACKGROUND: The current biomarkers alpha-fetoprotein and human chorionic gonadotropin have limited sensitivity and specificity for diagnosing malignant germ-cell tumours (GCTs). MicroRNAs (miRNAs) from the miR-371-373 and miR-302/367 clusters are overexpressed in all malignant GCTs, and some of these miRNAs show elevated serum levels at diagnosis. Here, we developed a robust technical pipeline to quantify these miRNAs in the serum and cerebrospinal fluid (CSF). The pipeline was used in samples from a cohort of exclusively paediatric patients with gonadal and extragonadal malignant GCTs, compared with appropriate tumour and non-tumour control groups. METHODS: We developed a method for miRNA quantification that enabled sample adequacy assessment and reliable data normalisation. We performed qRT-PCR profiling for miR-371-373 and miR-302/367 cluster miRNAs in a total of 45 serum and CSF samples, obtained from 25 paediatric patients. RESULTS: The exogenous non-human spike-in cel-miR-39-3p and the endogenous housekeeper miR-30b-5p were optimal for obtaining robust serum and CSF qRT-PCR quantification. A four-serum miRNA panel (miR-371a-3p, miR-372-3p, miR-373-3p and miR-367-3p): (i) showed high sensitivity/specificity for diagnosing paediatric extracranial malignant GCT; (ii) allowed early detection of relapse of a testicular mixed malignant GCT; and (iii) distinguished intracranial malignant GCT from intracranial non-GCT tumours at diagnosis, using CSF and serum samples. CONCLUSIONS: The pipeline we have developed is robust, scalable and transferable. It potentially promises to improve clinical management of paediatric (and adult) malignant GCTs.

Laparoscopic Fertility-preserving Treatment of a Pure Nongestational Choriocarcinoma of the Ovary: Case Report and Review of Current Literature.

This case report demonstrates the feasibility of laparoscopic and fertility-preserving approach in nongestational choriocarcinoma of the ovary (NGCO). Pure NGCO is a rare malignant condition. In the last decade, only 14 cases have been reported in the literature. The use of laparoscopy and fertility-preserving procedures in nonepithelial ovarian malignancies is extremely controversial. A 23-year-old woman underwent emergency laparoscopy due to acute abdominal pain associated with an 8-cm large adnexal mass. The initial procedure consisted only of a left oophoroplasty, and histology revealed a tumor of high malignant potential compatible with a primary NGCO. Approximately 3 weeks after initial surgery, she was submitted to a laparoscopic staging surgery, including left adnexectomy, omentectomy, peritoneal biopsies, and retroperitoneal lymphadenectomy. Final pathology confirmed an International Federation of Gynecology and Obstetrics stage IIB NGCO. Before initiation of adjuvant chemotherapy based on 3 courses of bleomycin, etoposide, and cisplatin, the patient received goserelin for ovarian suppression. Nine months after therapy, the patient presented no signs of recurrence and reassumed normal menstruation cycles with normal levels of gonadotropins and tumor markers. The current report brings new insights into the possibility of using use minimally invasive surgery and a combination of fertility-preserving methods for the treatment of NGCO.

Primary pulmonary choriocarcinoma: a diagnostic dilemma.

We present a case of a 25-year-old Hispanic woman who presented to emergency department with chief complaint of left lower quadrant abdominal pain. Initial workup revealed positive pregnancy test. Serum human chorionic gonadotropin was 36,478 (normal range, 0 to 8.0) IU/mL. She underwent diagnostic laparoscopy with dilatation and curettage, which did not reveal any evidence of intrauterine or extrauterine pregnancy. Chest and abdomen radiographic findings were significant for a heterogenously enhancing 2.2×1.7×1.6 cm nodule in superior segment of the right lower lobe of the lung and a large perinephric hematoma. We performed radial endobronchial ultrasound-guided transbronchial biopsies of the right lower lobe lesion. Pathologic specimen revealed choriocarcinoma.

Pure nongestational uterine choriocarcinoma in a postmenopausal Chinese woman confirmed with short tandem repeat analysis.

Nongestational choriocarcinomas have been observed in the ovaries but rarely the uterus in postmenopausal women. Choriocarcinomas of gestational and nongestational origin have distinct prognoses but cannot be distinguished with routine histologic examination. We report a case of nongestational uterine choriocarcinoma in a 62-year-old Chinese woman that was confirmed with short tandem repeat analysis.