Syncytiotrophoblastic Giant Cells Research Articles

Dysgerminoma with Syncytiotrophoblastic Giant Cells Associated with a Concurrent Ectopic Pregnancy

Dysgerminoma with Syncytiotrophoblastic Giant Cells Associated with a Concurrent Ectopic Pregnancy

Factors Influencing Craniospinal Relapse of Intracranial Germinoma After Complete Remission

To evaluate the pathomechanism of the recurrence of intracranial germinoma after complete response and to confirm the associationof the initial magnetic resonance imaging and therapeutic factors with recurrence. This study included patients who were followed up for ≥5years and who were treated in our hospital from 1980 to 2021. Those with germinoma and germinoma with syncytiotrophoblastic giant cells were diagnosed pathologically. Data were categorizedbased on "gender," "single region," "intraventricular dissemination at the initial diagnosis," "hydrocephalus," "types of radiation therapy (RT)," and "chemotherapy." Fisher's exact probability test was used to assess differences between the no recurrence and recurrence groups. Among 43 patients, 34 had no recurrence, 5 had delayed recurrence (≥60months), and 4 had early recurrence (<60months). Follow-up periods were 143.5 (60-380), 198 (88-222), and 132.5 (75-291) months for the no recurrence, delayed recurrence, and early recurrence groups, respectively. Five patients with delayed recurrence showed 3 intracranial lesions and 2 spinal lesions. Four patients with early recurrence showed 3 intracranial lesions and 1 spinal lesion. Differences in delayed recurrences (focal RT vs. RT including whole-ventricle system; P=0.0491) were significant in Fisher's exact test. RT including the whole-ventricle system reduces delayed craniospinal relapses including dissemination, local, and distant recurrences even ≥5years after complete response in patients with primary central nervous system germinoma.

So-called bifocal tumors with diabetes insipidus and negative tumor markers: are they all germinoma?

The Delphi consensus statements on the management of germ cell tumors (GCTs) failed to reach agreements on the statement that the cases with (i) pineal and neurohypophyseal bifocal lesion, (ii) with diabetes insipidus, and (iii) with negative tumor markers can be diagnosed as germinoma without histological verification. To answer this, multicenter retrospective analysis was performed. A questionnaire on clinical findings, histological diagnosis, and details of surgical procedures was sent to 86 neurosurgical and 35 pediatrics departments in Japan. Fifty-one institutes reported 132 cases that fulfilled the 3 criteria. Tissue sampling was performed in 91 cases from pineal (n = 44), neurohypophyseal (n = 32), both (n = 6), and distant (n = 9) lesions. Histological diagnosis was established in 89 cases: pure germinoma or germinoma with syncytiotrophoblastic giant cells in 82 (92.1%) cases, germinoma and mature teratoma in 2 cases, and granulomatous inflammation in 2 cases. Histological diagnosis was not established in 2 cases. Although no tumors other than GCTs were identified, 3 (3.4%) patients had non-germinomatous GCTs (NGGCTs). None of the patients developed permanent complications after endoscopic or stereotactic biopsy. Thirty-nine patients underwent simultaneous procedure for acute hydrocephalus without permanent complications, and hydrocephalus was controlled in 94.9% of them. All patients who fulfilled the 3 criteria had GCTs or granulomatous inflammation, but not other types of tumors. However, no fewer than 3.4% of the patients had NGGCTs. Considering the safety and the effects of simultaneous procedures for acute hydrocephalus, biopsy was recommended in such patients.

Metastases of Urothelial Carcinoma with Trophoblastic Differentiation that Responded to Combination Chemotherapy with Gemcitabine and Oxaliplatin : A Case Report

A 70-year-old man was admitted with complaint of gross hematuria. Cystoscopy and computed tomography (CT) revealed a 2.5 cm nodular tumor in the urinary bladder. Pathological diagnosis after the transurethral resection of bladder tumor (TURBT) was invasive urothelial cancer with trophoblastic differentiation of pT1. The tumor was positively stained with human chorionic gonadotropin (HCG). The serum HCG level was 12.8 IU/l in the fourth week after TURBT, and it increased to 35.7 IU/l in the 20th week after TURBT. However, radiological examination at this point did not reveal tumor recurrence or metastases. Three months later, the patient coughed up bloody sputum. Lung metastases (up to 2.4 cm) were identified, and they were surgically removed. The pathological specimen consisted of syncytiotrophoblastic giant cells with hemorrhage and necrosis, but no urothelial cancer element. Because the lung and lymph node metastases developed soon after surgery, chemotherapy was planned. Because the patient had impaired renal function with a creatinine clearance of 33.7 ml/min, we selected combination chemotherapy with gemcitabine and oxaliplatin (GEMOX) rather than cisplatin -based chemotherapy. CT after two courses of GEMOX showed stable disease, but HCG levels markedly decreased from 1,240 IU/l to 7.9 IU/l. This marker of response continued through six courses of GEMOX. Then, the chemotherapy was discontinued due to grade 2 neuropathy. He died of cancer 12 months after development of metastases. Autopsy revealed only tumor cells with trophoblastic differentiation, but no urothelial carcinoma in multiple metastatic sites.

Results of Biopsy-Proven Sellar Germ Cell Tumors: Nine Years' Experience in a Single Center.

The biopsy is recognized as the most accurate method to determine the histologic characterization of sellar germ cell tumors. It is difficult to evaluate the prognosis before histologic confirmation. This study aimed to evaluate the independent prognostic risk factors of patients with sellar germ cell tumors (GCTs). From January 2008 to December 2015, 61 patients who were histologically diagnosed as having sellar GCTs were followed up and were included in this retrospective study. Of 61 patients in this study, 40 (65.6%), 10 (16.4%), and 11 (18.0%) were diagnosed as having pure germinomas, germinomas with syncytiotrophoblastic giant cells and non-germinomatous GCTs (NGGCTs), respectively. The patients with pure germinomas had a significantly better overall survival time than did those with NGGCT (56.47 ± 3.01 months vs. 43.09 ± 10.58 months; P= 0.01). Multivariate analysis showed that the independent poor prognostic risk factors of patients with sellar GCTs were diameters >15 mm (odds ratio [OR], 7.40; 95% confidence interval [CI], 2.01-27.19), octamer-binding transcription positivity (OR, 5.97; 95% CI, 1.40-25.48), and NGGCT (OR, 11.88; 95% CI, 2.37-59.50), whereas the combination of chemotherapy and radiotherapy was associated with a better prognosis (OR, 0.15; 95% CI, 0.04-0.55). Diameter >15 mm, octamer-binding transcription positivity, or NGGCT was associated with a poorer prognosis for patients with sellar GCTs, whereas the combination of chemotherapy and radiotherapy was associated with a better prognosis.

Human chorionic gonadotropin is expressed virtually in all intracranial germ cell tumors

Human chorionic gonadotropin (hCG) production has been utilized as a diagnostic marker for germinoma with syncytiotrophoblastic giant cells (STGC) and choriocarcinoma. Elevated hCG in germinoma is considered to predict less favorable prognosis, and an intensive treatment strategy may accordingly be applied. However, there is some evidence that any germinoma may produce hCG to varying extent. We investigated mRNA expression of the hCG β subunit (hCGβ) using real time quantitative polymerase chain reaction in 94 germ cell tumors (GCTs). Most (93.3%) GCTs showed higher expression levels compared with that of normal brain tissue (1.09×10(0)-1.40×10(5) fold). The expression was the highest in GCTs which harbor choriocarcinoma or STGC components. The expression level of hCGβ in germinoma was highly variable (1.09×10(0)-5.88×10(4) fold) in linear but not bimodal distribution. hCG concentrations in serum and CSF correlated with gene expression, especially when GCTs with single histological component were analyzed separately. The expression was not significantly associated with recurrence in pure germinoma. These results suggest that the serum/CSF hCG levels may need to be interpreted with caution as most GCTs appear to have the capacity of producing hCG irrespective of their histology. The clinical significance of ubiquitous hCG expression in GCTs needs further investigation.

Primary Spinal Germ Cell Tumors: A Case Analysis and Review of Treatment Paradigms

Objective. Primary intramedullary spinal germ cell tumors are exceedingly rare. As such, there are no established treatment paradigms. We describe our management for spinal germ cell tumors and a review of the literature. Clinical Presentation. We describe the case of a 45-year-old man with progressive lower extremity weakness and sensory deficits. He was found to have enhancing intramedullary mass lesions in the thoracic spinal cord, and pathology was consistent with an intramedullary germ cell tumor. A video presentation of the case and surgical approach is provided. Conclusion. As spinal cord germinomas are highly sensitive to radiation and chemotherapy, a patient can be spared radical surgery. Diverse treatment approaches exist across institutions. We advocate biopsy followed by local radiation, with or without adjuvant chemotherapy, as the optimal treatment for these tumors. Histological findings have prognostic value if syncytiotrophoblastic giant cells (STGCs) are found, which are associated with a higher rate of recurrence. The recurrence rate in STGC-positive spinal germinomas is 33% (2/6), whereas it is only 8% in STGC-negative tumors (2/24). We advocate limited volume radiotherapy combined with systemic chemotherapy in patients with high risk of recurrence. To reduce endocrine and neurocognitive side effects, cranio-spinal radiation should be used as a last resort in patients with recurrence.

Recently described and unusual variants of urothelial carcinoma of the urinary bladder

Urothelial carcinoma (UC) of the urinary bladder has a great propensity to undergo divergent differentiation. The resulting subtypes are morphologically unique and have significant prognostic and therapeutic differences. While squamous and glandular subtypes are the most common, a number of other well characterised morphological subtypes were described in the 2004 World Health Organization Classification. More recently additional variants of UC have been described, while others have been more fully characterised. In this review we report the details of recently described and selected unusual variants of UC. Specifically, the pathological and clinical details are discussed, relating to large nested and nested variant of UC, large cell undifferentiated carcinoma, lymphoepithelioma-like carcinoma, osteoclast rich undifferentiated carcinoma, pleomorphic giant cell carcinoma, UC with syncytiotrophoblastic giant cells, lipid cell variant of UC, micropapillary UC, UC with abundant myxoid stroma and plasmacytoid UC.

Germinoma With Syncytiotrophoblastic Giant Cells Arising in the Corpus Callosum -Case Report-

A previously healthy 31-year-old Japanese man presented with a very rare germinoma of the corpus callosum without other intracranial lesions manifesting as transitory speech disturbance. Magnetic resonance (MR) imaging revealed a heterogeneously enhanced mass in the corpus callosum extending into the cavity of the septum pellucidum. A tumor specimen obtained by stereotactic biopsy revealed a two-cell pattern germinoma containing human chorionic gonadotropin (HCG)-beta-positive giant cells. The cerebrospinal fluid and serum levels of HCG and HCG-beta subunit were measurable. The diagnosis was germinoma with syncytiotrophoblastic giant cells. Three cycles of chemotherapy consisting of ifosfamide, cisplatin, and etoposide, followed by radiation therapy achieved complete remission, and 5 cycles of chemotherapy with carboplatin and etoposide were added. MR imaging performed 40 months after the diagnosis showed a cicatricial cyst in the body of the corpus callosum, the original tumor site. All 11 previously reported cases of germinoma in the corpus callosum were associated with synchronous or metachronous intracranial lesions. These patients tended to be older than patients with general intracranial germinoma. Germinoma should be included in the differential diagnosis of corpus callosum tumors, especially in young adult males.

Central Nervous System Germ Cell Tumors: Classification, Clinical Features, and Treatment With a Historical Overview

Central nervous system germ cell tumors are neoplasms that affect children and young adults. They are subclassified into germinoma and nongerminomatous germ cell tumors. The latter include teratoma (mature teratoma, immature teratoma, teratoma with malignant transformation), choriocarcinoma, embryonal carcinoma, yolk sac tumors, and mixtures of these entities. Germinoma with syncytiotrophoblastic giant cells is a variant of germinoma. Germinomas respond well to radiation therapy, but late sequelae due to irradiation have been reported. The results of radiation treatment alone for nongerminomatous germ cell tumor are not satisfactory. Combination radiochemotherapy has been applied, and this yields a good outcome with less toxicity for germinomas and better survival of nongerminomatous germ cell tumors. This article also discusses other issues, including the controversy regarding spinal irradiation and the treatment of recurrent disease.

Mixed germ cell tumor of the midbrain

This 14-year-old boy presented with left hemiparesis, gait disturbance, and multiple cranial nerve palsies. Magnetic resonance imaging revealed a multicystic mass with hemorrhagic fluid-fluid levels in the right midbrain, suggesting the presence of a cavernous malformation. Diffusion tensor imaging showed the mass to be close to the right corticospinal tract and ipsilateral medial lemniscus. Subtotal removal of the mass was performed via a right subtemporal approach. The histopathological diagnosis was of a mixed germ cell tumor (GCT) comprising mature teratoma and germinoma cells with syncytiotrophoblastic giant cells. The patient underwent postoperative chemotherapy and radiotherapy, and no tumor progression was found during 1 year of follow-up. Intracranial GCTs arise mainly in the pineal and the suprasellar area. Germ cell tumors in the brainstem are rare, with only 12 reported cases. Among these, 4 were in the midbrain and histologically were pure germinomas. To the authors' knowledge, this is the first reported case of a mixed GCT in the midbrain combining mature teratoma and germinoma cells.

Fine needle aspiration diagnosis of bilateral dysgerminoma with syncytiotrophoblastic giant cells

Dysgerminoma accounts for only 1–3% of ovarian cancers and about 30–40% of all ovarian germ cell malignant tumors. Literature states that about 2% of nonpregnant patients with dysgerminomas present with elevated serum or urine levels of human chorionic gonadotropin (hCG). Here, we report a 34 year-old multiparous woman presenting with an abdominal lump, ascites, and abdominal pain with elevated urinary and serum hCG levels. An abdominal ultrasound showed bilateral ovarian mass. An ultrasound-guided, transabdominal fine needle aspiration revealed dysgerminoma with syncytiotrophoblastic giant cells. Bilateral oophorectomy was done and the diagnosis was confirmed on histopathology.

Method Validation for Cerebral Spinal Fluid Human Chorionic Gonadotropin Measurement with the Advia Centaur®2

Intracranial germ cell tumors account for 0.4%–3.4% of all brain tumors (1). These tumors can be divided into 2 groups, germinomas and nongerminomatous germ cell tumors. Germinomas, which are fairly treatable, arise from primordial germ cells that fail to migrate correctly in embryogenesis. Nongerminomatous germ cell tumors (including choriocarcinomas), which are more refractory to treatment, are differentiated tumors. Measurement of human chorionic gonadotropin (hCG)1 is an important adjunct method in the diagnosis of germ cell tumors. At high concentrations hCG can be detected in serum, but measurement of hCG concentrations in cerebral spinal fluid (CSF) is a more sensitive and reliable indicator of tumor presence (1). Pure germinomas are associated with very low concentrations of hCG in both serum and CSF. A subset of nongerminomatous germ cell tumors contains syncytiotrophoblastic giant cells. These tumors are associated with moderately increased concentrations of hCG (<1000 IU/L) in the serum, CSF, or both, and the survival rate in patients suffering these tumors is poorer than that for patients with pure germinomas …

Nestin expression in central nervous system germ cell tumors

Central nervous system (CNS) germ cell tumors constitute a unique class of rare tumors that mainly affect children and adolescents. These tumors are believed to originate from displaced primordial germ cells. Recently, results of treatment of germ cell tumors have improved with use of radiotherapy and combination chemotherapy. However, some tumors have proven refractory to intensive treatment with surgery, radiation, and combination chemotherapy. Nestin is an intermediate filament protein expressed in undifferentiated cells during CNS development and in CNS tumors and is used as a marker of immature elements of tumors, including brain tumor stem cells. In this study, we examined for the first time nestin expression in 19 CNS germ cell tumors (nine pure germinomas, five germinomas with syncytiotrophoblastic giant cells, one yolk sac tumor, one choriocarcinoma, one embryonal carcinoma, and two mature teratomas). Nestin was expressed in 14 cases but was not expressed in three pure germinomas and two mature teratomas. Clinically, nestin-negative tumors did not exhibit dissemination, while all tumors that exhibited dissemination also strongly expressed nestin protein. These findings suggest that the detection of nestin expression could be useful in the management of CNS germ cell tumors, as an auxiliary predictor of dissemination and/or progression.

Histologically Pure Stage I Seminoma With an Elevated β-hCG of 4497 IU/l

Approximately 30% of patients with pure seminoma of the testis have mild elevation of human chorionic gonadotropin (hCG) due to the presence of syncytiotrophoblastic giant cells. Levels are usually less than 500 IU/L; however, the occurrence of higher levels is rare. We report a case of a man with a stage I histologically pure seminoma, copious syncytiotrophoblast cells, and a serum beta human chorionic gonadotropin (beta-hCG) of 4497 IU/L. To our knowledge this is the third highest value of beta-hCG reported with a stage I pure seminoma. The patient underwent an orchiectomy and chemotherapy. His beta-hCG level was undetectable by postoperative day 13, and he remains disease free at 30 months.

Mixed testicular germ cell tumor in an adult with cryptorchidism and Down's syndrome

We here present a case of mixed testicular germ cell tumor in an adult with cryptorchidism and Down's syndrome. A 20-year-old Japanese man with a mass in the left inguinal region underwent orchidectomy as a left testicular tumor was suspected. Histology showed a mixed germ-cell tumor with embryonal carcinoma and yolk sac tumor with syncytiotrophoblastic giant cells occurring in a cryptorchid testis. Chromosomal analysis of peripheral lymphocytes disclosed a karyotype of 47,XY,+21[20]. Our case provides further evidence that these three conditions-Down's syndrome, cryptorchidism and testicular germ cell tumor-may be closely associated. To our knowledge this is the first case of mixed germ cell tumor arising in a patient with Down's syndrome and cryptorchidism.

Evaluation of Residual Tissues after Adjuvant Therapy in Germ Cell Tumors

Objective: Germ cell tumors are the tumors sensitive for adjuvant therapy such as radiotherapy and chemotherapy. We evaluated the pathological findings of these heterogeneous tumors to determine the persistence of residual viable tumor cells after adjuvant therapy. Patients and Methods: Between 1988 and 2005, we treated 31 patients with germinoma or germinoma with syncytiotrophoblastic giant cells (STGC) and 15 patients with non-germinomatous malignant germ cell tumors (NGMGCTs). All 46 patients received a combination of chemo- and radiotherapy. A second-look operation was performed in 3 of 31 patients with germinomas or germinomas with STGC and 12 of 15 patients with NGMGCTs. The follow-up period was 2–139 months (median 95) in patients with germinomas or germinomas with STGC (group 1) and 10–202 months (median 65) in NGMGCT patients (group 2). Results: Post-treatment, 3 group 1 and 12 group 2 patients manifested residual tumors. The pathological diagnosis in group 1 patients was mature teratoma, pineal cyst, and fibrous tissue with calcification; in group 2 it was yolk sac tumor (n = 1), immature teratoma (n = 3), mature teratoma (n = 4), and necrosis or fibrous tissue (n = 4). While no group 1 patients manifested tumor cells, MIB-1-positive viable tumor cells were present in resected tissues from one-third of the group 2 patients (3 immature teratomas and 1 yolk sac tumor). Conclusion: The absence of viable tumor cells in residual tissue indicates that the combination of cisplatin-based chemo- and radiotherapy was effective in our germinoma patients. On the other hand, in patients with NGMGCTs, these cells persisted despite this combination therapy.

Oncofetal protein glypican-3 in testicular germ-cell tumor

The expression of an oncofetal protein, the glypican-3 (GPC3), was immunohistochemically evaluated in a wide variety of primary testicular germ-cell tumors (GCTs) in comparison with other markers, alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG)-beta, and OCT3/4. Eighty-nine cases of GCT including 22 cases of mixed GCT were evaluated with reference to each tumor component. GPC3 expression was observed in neoplastic cells of yolk-sac tumor (YST) (25/25), teratoma (2/10), components of syncytiotrophoblastic giant cells (STGCs) (10/14), and choriocarcinoma (1/3), but none in intratubular germ-cell neoplasias, unclassified type (0/33), seminomas (0/61), or embryonal carcinoma (0/19). All cases of YST showed diffuse labeling of neoplastic cells in cytoplasmic and membranous patterns, and the positive area of GPC3 was much larger than that of AFP. Glandular structures in teratomas showed GPC3 immunostaining as well as AFP. Although the number of GPC3-positive cells was smaller in STGC components and choriocarcinoma, there was no diffusion artifact in GPC3 immunostaining, as was frequently encountered in hCG-beta staining. Thus, GPC3 is a unique oncofetal protein, which is useful as an immunohistochemical marker for GCT differentiated to extraembryonic tissue, especially YST.

Podoplanin expression in primary central nervous system germ cell tumors: a useful histological marker for the diagnosis of germinoma

Podoplanin, a mucin-like transmembrane sialoglycoprotein, promotes platelet aggregation and may be involved in cancer cell migration, invasion, metastasis, and malignant progression. Podoplanin/aggrus is highly expressed in testicular seminoma, suggesting that it may be a sensitive marker for testicular seminomas. Here we investigated the expression of podoplanin in central nervous system (CNS) germ cell tumors (GCTs) by immunohistochemical staining of tumor samples from 62 patients. In 40 of 41 (98%) germinomas (including germinomatous components in mixed GCTs), podoplanin was diffusely expressed on the surface of germinoma cells; lymphocytes, interstitial cells, and syncytiotrophoblastic giant cells were negative for podoplanin. Except for immature teratomas (12/17; 71%), podoplanin expression was absent in non-germinomatous GCTs, including seven teratomas, seven embryonal carcinomas, seven yolk sac tumors, and seven choriocarcinomas. In immature teratomas, focal podoplanin staining was observed in fewer than 10% of immature squamous and columnar epithelial cells. Thus, podoplanin expression may be a sensitive immunohistochemical marker for germinoma in CNS GCTs. As such, it may be useful for diagnosis, for monitoring the efficacy of treatment, and as a potential target for antibody-based therapy.

Recurrent intracranial germinoma outside the initial radiation field: A single-institution study

Between 1975 and 2005, we treated 52 newly diagnosed germinoma patients. Until 1991, patients with pure germinomas or germinomas with syncytiotrophoblastic giant cells (STGCs) received whole-brain radiotherapy only. Of the 52 patients, 30 were treated with a reduced radiation volume and combined chemotherapy; seven of these received local irradiation with 24 Gy, two received whole-brain (30 Gy) plus local irradiation (20 Gy), 16 received extended local irradiation delivered to the whole ventricles (30 Gy) plus local (20 Gy) irradiation, and five received extended local irradiation (24 Gy). Of the 30 patients treated with a reduced radiation volume and combined chemotherapy, four experienced tumor recurrence; three patients had been treated with 24 Gy of local radiotherapy and one had received extended local (30 Gy) plus local (20 Gy) irradiation in addition to chemotherapy. In these patients, the delivered radiotherapy was inadequate and the origin of the recurrent tumors was outside the radiation field. None of the patients who had received at least 24 Gy of whole ventricle radiotherapy combined with chemotherapy experienced tumor recurrence. In combination with chemotherapy, the delivery of irradiation covering the ventricles effectively reduced the incidence of tumor recurrence in patients with germinomas or germinomas with STGCs.