The enigma of bifocal germ cell tumors in the suprasellar and pineal regions: synchronous lesions or metastasis?

Object Intracranial germ cell tumors (GCTs) frequently present with bifocal lesions in both the suprasellar and pineal areas. The pathogenesis of these bifocal GCTs has been the subject of controversy. Bifocal GCTs may be caused by synchronous tumors or by metastatic spread of tumor cells from one site to the other. The prognosis associated with bifocal GCTs has also been a cause of concern. Methods The authors constructed a single-institution patient cohort comprising 181 patients with intracranial GCTs. The clinical characteristics of bifocal GCTs were compared with those of suprasellar and pineal GCTs. Results Bifocal GCTs were observed in 23 patients (12.8%). Eighteen patients presented with bifocal GCTs that were diagnosed as germinomas, but 5 patients exhibited mixed GCTs. Analyses of age distributions and comparisons of tumor sizes were compatible with a model of a metastatic origin of bifocal GCTs. Eleven patients (47.8%) presenting with bifocal GCTs exhibited tumor seeding at presentation. Tumor seeding was significantly associated with bifocal lesions (p < 0.001). Patients with bifocal germinomas showed significantly shorter event-free survival and overall survival than did those presenting with germinomas from a single site of origin. Conclusions Bifocal GCTs are not restricted to germinomas, as had been previously reported, but do include mixed GCTs. The authors hypothesize that bifocal GCTs may result from the metastatic spread of suprasellar or pineal GCTs. The bifocal presentation of germinomas may be a poor prognostic sign and should alert clinicians to the possibility of a disseminated disease.

Download Full-text

Malignant Sacrococcygeal Germ Cell Tumors in Children: A 30-year Experience from a Single Institution

Tumori Journal ◽

10.1177/030089161309900109 ◽

2013 ◽

Vol 99 (1) ◽

pp. 51-56 ◽

Cited By ~ 2

Author(s):

Münevver Büyükpamukcu ◽

Ali Varan ◽

Serhan Küpeli ◽

Saniye Ekinci ◽

Sule Yalcin ◽

...

Keyword(s):

Germ Cell ◽

Univariate Analysis ◽

Survival Rates ◽

Germ Cell Tumors ◽

Patient Characteristics ◽

Tumor Stage ◽

Event Free Survival ◽

Treatment Results ◽

Free Survival ◽

Chemotherapy Protocol

Background Our aim was to analyze treatment results and survival characteristics of our patients with malignant sacrococcygeal germ cell tumors. Procedure Patient files of children with malignant sacrococcygeal germ cell tumors, treated at our institution between 1979 and 2009, were searched. Patient characteristics, histopathological subtypes, extension of disease, alpha-fetoprotein (AFP) level at the time of diagnosis and relapse, extent of surgical resection, chemotherapy protocols, details of radiotherapy and survival characteristics were recorded. Results A total of 58 patients (M/F = 20/38) with malignant sacrococcygeal germ cell tumor was included in analysis. With a mean follow-up of 156 months (range, 26 days to 288.8 months) overall and event-free survival rates of the 58 patients were 50.9% and 43.8%, respectively. AFP status of the patients (37% in patients with <10,000 ng/ml, 68.9% in patients with ≥10,000 ng/ml), type of resection (total vs others), coccygeal resection, chemotherapy protocol (PEB vs others) and number of chemotherapy courses had an impact on event-free survival in univariate analysis. In multivariate analysis, AFP status had the greatest effect on prognosis. Conclusions Our treatment results are worse than those reported in the literature. Elevated AFP level at the time of diagnosis had a beneficial effect on prognosis, but year of diagnosis, tumor stage, presence of metastasis, tumor size and histopathological subtype had no impact on survival in patients with malignant sacrococcygeal germ cell tumors.

Download Full-text

A pragmatic diagnostic approach to primary intracranial germ cell tumors and their treatment outcomes

CNS Oncology ◽

10.2217/cns-2021-0012 ◽

2021 ◽

Vol 10 (4) ◽

Author(s):

Jeyaanth Venkatasai ◽

Rajesh Balakrishnan ◽

Balakrishnan Rajkrishna ◽

Patricia Sebastain ◽

Rikki Rorima John ◽

...

Keyword(s):

Overall Survival ◽

Germ Cell ◽

Germ Cell Tumors ◽

Progression Free Survival ◽

Cell Tumor ◽

Distinct Entity ◽

Intracranial Germ Cell Tumor ◽

Free Survival ◽

Intracranial Germ Cell Tumors ◽

Significant Difference

Background: Primary intracranial germ cell tumors (ICGCT) are often diagnosed with tumor markers and imaging, which may avoid the need for a biopsy. An intracranial germ cell tumor with mild elevation of markers is seldom stratified as a distinct entity. Methods: Fifty-nine patients were stratified into three groups: pure germinoma (PG), secreting germinoma (SG) and non-germinomatous germ cell tumors (NGGCTs). Results: At 5 years, progression-free survival and overall survival of the three groups (PG vs SG vs NGGCT) were 91% versus 81% versus 59%, and 100% versus 82% versus 68%, respectively. There was no statistically significant difference in outcome among histologically and clinically diagnosed germinomas. Conclusion: A criterion for clinical diagnosis when a biopsy is not feasible is elucidated, and comparable outcomes were demonstrated with histologically diagnosed germinomas.

Download Full-text

PITUITARY DYSFUNCTION IN PATIENTS WITH INTRACRANIAL GERM CELL TUMORS TREATED WITH RADIOTHERAPY

Endocrine Practice ◽

10.4158/ep-2020-0192 ◽

2020 ◽

Vol 26 (12) ◽

pp. 1458-1468

Author(s):

Boni Xiang ◽

Xiaoming Zhu ◽

Min He ◽

Wei Wu ◽

Haopeng Pang ◽

...

Keyword(s):

Germ Cell ◽

Diabetes Insipidus ◽

Adrenal Insufficiency ◽

Germ Cell Tumors ◽

Central Diabetes Insipidus ◽

Central Hypothyroidism ◽

Free Survival ◽

Sellar Lesions ◽

Intracranial Germ Cell Tumors

Objective: To evaluate the endocrine abnormalities in intracranial germ cell tumors (iGCTs) treated with radio-therapy (RT), and to discuss the effects of RT on pituitary functions. Methods: Seventy-seven patients diagnosed with iGCTs who had received RT and endocrine follow-up in Huashan Hospital between January 2010 and July 2017 were retrospectively analyzed, consisting of 49 germinomas and 28 NGGCTs. The median follow-up period was 50.0 months. Fifty-one patients had radiologically proved suprasellar/sellar lesions. Results: The male to female ratio was 62/15. The median endocrine follow-up period was 19 (4, 42) months. The median age at the last endocrine visit was 18 (16, 20) years old. The 5-year overall and recurrence-free survival were both 98.7%. The overall prevalence of central adrenal insufficiency (CAI), central hypothyroidism (CHT), central hypogonadism (CHG), hyperprolactinemia, and central diabetes insipidus (CDI) was 57.3%, 56%, 56.6%, 35.3%, and 52.1%, respectively, after RT. Patients having suprasellar/sellar lesions showed significantly higher post-therapeutic prevalence of hypopituitarism than those who didn’t. Compared to that before RT, CAI, CHT, and CHG weren’t significantly improved while the levels of prolactin and the prevalence of CDI declined significantly ( P = .03 and .001). The radiation doses to pituitary and hypothalamus between those with and without CAI, CHT, and CHG weren’t significantly different. Conclusion: The prevalence of hypopituitarism was high in iGCTs, especially in those with suprasellar/sellar involvement. The levels of prolactin and the prevalence of CDI declined significantly after RT. The hypopituitarism in iGCTs was mainly induced by tumor effects, and RT showed no additional damage to pituitary functions in our study. Abbreviations: AFP = alpha-fetoprotein; CAI = central adrenal insufficiency; CDI = central diabetes insipidus; CHG = central hypogonadism; CHT = central hypothyroidism; CT = computed tomography; DA = dopamine; GH = growth hormone; βHCG = beta-human chorionic gonadotropin; HPA = hypothalamus-pituitary-adrenal; HPG = hypothalamus-pituitary-gonadal; HPL = hyperprolactinemia; HPT = hypothalamus-pituitary-thyroid; iGCT = intracranial germ cell tumor; IGF-1 = insulin-like growth factor 1; NGGCT = nongerminomatous germ cell tumors; OS = overall survival; PFS = progression-free survival; PRL = hypothalamus-pituitary-prolactin; RT = radiotherapy

Download Full-text

A randomized trial of etoposide + cisplatin versus vinblastine + bleomycin + cisplatin + cyclophosphamide + dactinomycin in patients with good-prognosis germ cell tumors.

Journal of Clinical Oncology ◽

10.1200/jco.1988.6.8.1231 ◽

1988 ◽

Vol 6 (8) ◽

pp. 1231-1238 ◽

Cited By ~ 176

Author(s):

G J Bosl ◽

N L Geller ◽

D Bajorin ◽

S P Leitner ◽

A Yagoda ◽

...

Keyword(s):

Germ Cell ◽

Randomized Trial ◽

Mature Teratoma ◽

Germ Cell Tumors ◽

Good Prognosis ◽

Event Free Survival ◽

Free Survival ◽

Acute And Chronic Effects ◽

Related Mortality

Standard chemotherapy for disseminated germ cell tumors (GCT) cures most patients but causes considerable acute toxicity, including treatment-related death due to septicemia during neutropenia and pulmonary fibrosis. In addition, chronic and delayed toxicities, particularly Raynaud's phenomenon, have been reported in 6% to 37% of treated patients. In an attempt to minimize the acute and chronic effects of treatment which are related primarily to vinblastine and bleomycin, a randomized trial comparing the efficacy and toxicity of vinblastine + bleomycin + cisplatin + cyclophosphamide + dactinomycin (VAB-6) and etoposide + cisplatin (EP) was conducted on 164 eligible patients with good-prognosis GCT. Seventy-nine of 82 (96%) patients receiving VAB-6 and 76/82 (93%) receiving EP achieved a complete remission (CR) with or without adjunctive surgery. Similar proportions of patients in both arms were found at surgery to have necrosis/fibrosis or mature teratoma. With a median follow-up of 24.4 months in the VAB-6 arm and 25.9 months in the EP arm, the total, relapse-free, and event-free survival distributions were similar in the two arms. Patients receiving EP experienced less emesis (P = .05), higher nadir WBC (P = .06) and platelet counts (P = .01), less magnesium wasting (P = .0001), less mucositis (P = .09), and no pulmonary toxicity. No treatment-related mortality was observed. EP is an efficacious and less toxic regimen and is recommended for good-prognosis patients with disseminated GCT.

Download Full-text

Results of treatment of malignant germ cell tumors in 93 children: a report from the Childrens Cancer Study Group.

Journal of Clinical Oncology ◽

10.1200/jco.1991.9.10.1782 ◽

1991 ◽

Vol 9 (10) ◽

pp. 1782-1792 ◽

Cited By ~ 72

Author(s):

A R Ablin ◽

M D Krailo ◽

N K Ramsay ◽

M H Malogolowkin ◽

H Isaacs ◽

...

Keyword(s):

Germ Cell ◽

Treatment Plan ◽

Germ Cell Tumors ◽

Event Free Survival ◽

Histologic Subtype ◽

Free Survival ◽

Results Of Treatment ◽

Second Look ◽

Incomplete Removal ◽

Malignant Germ Cell Tumors

We report treatment results in 93 children entered on study from 1978 to 1984 with malignant germ cell tumors (MGCTs), excluding dysgerminoma and tumors of the testis or brain. The estimated 4-year survival and event-free survival (EFS) for all 93 patients were 54% and 49%, respectively. For 30 children with ovarian tumors, the estimated 4-year survival was 67% and EFS was 63%. For 63 children with nongonadal tumors, survival and EFS were 48% and 42%, respectively. The comparison of EFS between ovarian and nongonadal tumors was significant at P = .03. The treatment plan included a second-look surgical procedure after 18 weeks of chemotherapy. Over half of 36 patients evaluated as having a residual mass present immediately before second-look surgery had no malignant tumor after review of surgical specimens. Age greater than 11 years at diagnosis, incomplete removal of tumor at first surgery, and more than one structure or organ involved at diagnosis increased the risk for adverse event. The histologic subtype of the primary tumor was not related to outcome. Diagnosis was verified by independent pathologic review, and treatment was uniform. Seventeen percent of all registered patients (21 of 127) were excluded because of ineligible pathologic diagnoses; sixty percent (13 of 21) were immature teratomas.

Download Full-text

Primary Chemotherapy for Intracranial Nongerminomatous Germ Cell Tumors: Results of the Second International CNS Germ Cell Study Group Protocol

Journal of Clinical Oncology ◽

10.1200/jco.2004.07.006 ◽

2004 ◽

Vol 22 (5) ◽

pp. 846-853 ◽

Cited By ~ 87

Author(s):

Stewart J Kellie ◽

Hayden Boyce ◽

Ira J Dunkel ◽

Blanca Diez ◽

Marc Rosenblum ◽

...

Keyword(s):

Complete Remission ◽

Partial Response ◽

Germ Cell ◽

Germ Cell Tumors ◽

Initial Therapy ◽

Primary Objective ◽

Event Free Survival ◽

Free Survival ◽

Cell Study

Purpose The optimum therapy for intracranial nongerminomatous germ cell tumors (NGGCT) remains controversial. The primary objective of this study was to determine whether intensive cisplatin and cyclophosphamide-based combination chemotherapy was effective in patients with intracranial NGGCT. Patients and Methods Twenty patients were enrolled, aged 5 to 41 years (median, 13 years). Initial therapy included two courses of Regimen A (cisplatin, etoposide, cyclophosphamide, and bleomycin). Patients achieving a complete remission (CR) then received two courses of Regimen B (carboplatin, etoposide, and bleomycin). Those in CR after four courses of treatment received one additional course of Regimen A and Regimen B, while those not in CR after four treatment courses underwent second-look surgery and/or irradiation. Results Sixteen of 17 patients assessable for response after two courses of treatment achieved a CR or partial response (CR + partial response, 0.94; 95% CI, 0.73 to 1.0). With a median follow-up of 6.3 years, 14 of 20 patients are alive without disease; eight patients were without relapse or progression, of whom three received local irradiation in first complete remission in violation of protocol, and six patients were in durable second or third complete remission after further chemotherapy and/or irradiation. The 5-year overall survival and event-free survival were 0.75 (95% CI, 0.56 to 0.94) and 0.36 (95% CI, 0.13 to 0.59), respectively. Conclusion Intensive chemotherapy was effective in one-third of patients in this study. Salvage therapy, including irradiation, was feasible in patients with recurrent disease.

Download Full-text

c-Kit gene mutations in intracranial germ cell tumors

Klinische Pädiatrie ◽

10.1055/s-0030-1254480 ◽

2010 ◽

Vol 222 (03) ◽

Author(s):

B Steiger ◽

O Schmidt ◽

T Pietsch

Keyword(s):

Germ Cell ◽

Germ Cell Tumors ◽

Gene Mutations ◽

Intracranial Germ Cell Tumors ◽

Kit Gene

Download Full-text

Sonographic Diagnosis of Unilateral Synchronous Testicular Tumors

American Journal of Sonography ◽

10.25259/ajs-3-2019 ◽

2019 ◽

Vol 2 ◽

pp. 2

Author(s):

Allison Forrest ◽

Numbereye Numbere ◽

Jerome Jean-Gilles ◽

Thomas Frye ◽

Vikram Dogra

Keyword(s):

Testicular Cancer ◽

Germ Cell ◽

Germ Cell Tumors ◽

Histological Type ◽

Synchronous Tumors ◽

Testicular Tumors ◽

Sonographic Diagnosis ◽

Histological Types ◽

Common Cancer

Testicular cancer accounts for 1% of all male cancers yet is the most common cancer affecting men aged 15–44 years. Most testicular cancers are seminomas or non-seminomatous germ cell tumors. Rarely, multiple testicular cancers may occur simultaneously, most often of the same histological type. However, synchronous tumors of different histological types may occur, although rarely. In this case study, we present the sonographic features with histopathologic correlation in a case of unilateral synchronous testicular tumors of discordant histology.

Download Full-text