scholarly journals NI-11 Clinical significance of intracystic diffusion hyperintensity lesions remaining after treatment of intracranial germ cell tumor

2020 ◽  
Vol 2 (Supplement_3) ◽  
pp. ii14-ii14
Author(s):  
Motoki Takano ◽  
Takeshi Takayasu ◽  
Ushio Yonezawa ◽  
Akira Taguchi ◽  
Kazuhiko Sugiyama ◽  
...  
Keyword(s):  
Germ Cell ◽  
Clinical Significance ◽  
Cyst Wall ◽  
High Intensity ◽  
Mature Teratoma ◽  
Germ Cell Tumors ◽  
Residual Tumor ◽  
Cystic Tumor ◽  
Intracranial Germ Cell Tumor ◽  
Intensity Lesion

Abstract Background and purpose: About 30% of intracranial germ cell tumors are mixed germ cell tumors and teratomas are often found as those components. Intense chemoradiotherapy is performed according to the malignancy of the histopathology, but high-intensity lesion inside the cystic tumor on diffusion weighted imaging (DWI) sometimes remains after completion of the chemoradiotherapy. In this study, we examined the clinical significance of the DWI high-intensity lesion remaining in the cyst. METHODS: Five patients after initial chemoradiotherapy were resected residual tumor by craniotomy at our hospital from 2009 to 2019. Preoperative gadolinium-enhanced MRI defined the non-contrast-enhanced part of the tumor as intracystic, and DWI intensity was classified by its look as low-intensity, equal-intensity, and high-intensity compared to the cortex of the same slice. DWI signals in the solid area, cyst wall, and cyst were evaluated. Results: All cases were mature teratoma in histopathology, and no other tumor components were observed. On DWI, the cyst wall and solid part were visualized with low signal. High-intensity lesions and equal-intensity lesions in the cyst cavity were found in 3 and 1 cases, respectively. In these cases, pathological findings revealed a keratin-like substance in the cyst. Discussion: The intracystic high and equal intensity lesions on DWI removed after completion of chemoradiotherapy are considered to reflect the keratin-like component of mature teratoma. If DWI- high intensity and equal intensity lesions remain in the cyst of the tumor after the completion of chemoradiotherapy, tumor shrinkage cannot be expected even if the chemotherapy is strengthened. In such cases, we should consider to removing them by surgery. Conclusion: When DWI high and equal intensity lesions are found in the cysts of tumors remaining after chemoradiotherapy for intracranial germ tumors, it is possible that mature teratoma remains.

scholarly journals MPC-08 CLINICOPATHOLOGICAL ANALYSIS OF 12P GAIN IN INTRACRANIAL GERM CELL TUMORS

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii23-ii23
Author(s):  
Kaishi Satomi ◽  
Hirokazu Takami ◽  
Shintaro Fukushima ◽  
Yoichi Nakazato ◽  
Shota Tanaka ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumor ◽  
Copy Number ◽  
Mature Teratoma ◽  
Methylation Status ◽  
Germ Cell Tumors ◽  
Copy Number Variations ◽  
Cell Tumor ◽  
Testicular Germ Cell ◽  
Intracranial Germ Cell Tumor

Abstract BACKGROUND Gain of short arm of chromosome 12 (12p) is commonly observed in testicular germ cell tumors (tGCTs). 12p gain is also frequently seen in intracranial GCTs (iGCTs). However, little is known about the clinical significance of 12p gain in iGCTs. MATERIALS AND METHODS We have collected over 200 fresh frozen tissue samples of iGCTs through the Intracranial Germ Cell Tumor Genome Analysis Consortium in Japan. Firstly, we analyzed DNA methylation status in 83 iGCTs, 3 seminomas and 6 normal control samples using Infinium Human Methylation 450K BeadChip array (Illumina, CA). Idat files were processed using R (Version 3.5.3) and minfi package (1.30.0) to generate copy number variations. Compared with average genome-wide copy number level, 12p gain was determined. Then, 58 iGCTs with clinicopathological information were analyzed for progression-free survival (PFS) and overall survival (OS). Those tumors that consist of only either germinoma and/or mature teratoma components were classified as Favorable Histology (FH) and all the others that contains malignant histological components were classified as Unfavorable Histology (UFH). RESULT 12p gain was observed in 100% (3/3) of seminoma, 13.6% (3/22) of germinoma, 16.7% (1/6) of mature teratoma, 25% (1/4) of immature teratoma, 55% (11/20) of mixed germ cell tumor, 100% (4/4) of yolk sac tumor, 100% (1/1) of embryonal carcinoma, and 100% (1/1) of choriocarcinoma. In total, 44.6% (37/83) of iGCT showed 12p gain. Regarding histological classification, the 12p gain rate in UFH (72%, 18/25) was significantly higher than that in FH (12.1%, 4/33, P<0.01). Both PFS and OS were significantly worse in iGCTs with 12p gain (PFS: P=0.027, OS: P=0.0012). DISCUSSION 12p gain can be a molecular marker to predict prognosis and histological malignancy in iGCTs.

Second-Look Surgery for Intracranial Germ Cell Tumors

Neurosurgery ◽  
2015 ◽  
Vol 76 (6) ◽  
pp. 658-662 ◽  
Author(s):  
Hideki Ogiwara ◽  
Chikako Kiyotani ◽  
Keita Terashima ◽  
Nobuhito Morota
Keyword(s):  
Germ Cell ◽  
Tumor Markers ◽  
Mature Teratoma ◽  
Germ Cell Tumors ◽  
Residual Tumor ◽  
Complete Response ◽  
Mixed Germ Cell Tumor ◽  
Second Look ◽  
Intracranial Germ Cell Tumors ◽  
Atypical Cells

Abstract BACKGROUND: The role of second-look surgery in intracranial germ cell tumors (GCTs) needs to be reviewed. OBJECTIVE: To present our experience of second-look surgery in patients with intracranial GCTs who showed less than complete response despite normalizing or decreasing tumor markers after chemotherapy. METHODS: Retrospective review of 7 patients who underwent second-look surgery for an intracranial GCT was performed. RESULTS: Of 23 consecutive patients with newly diagnosed intracranial GCTs treated between August 2003 and August 2013, 7 patients (30%) underwent second-look surgery. The mean age was 9.4 years. The initial diagnoses were mixed germ cell tumor in 5 and immature teratoma in 2. Second-look surgery was performed after 1 to 3 courses of chemotherapy. Magnetic resonance imaging at the surgery demonstrated increasing residual tumor in 4 and stable residual tumor in 3. Tumor markers were normalized in 5 and nearly normalized in 2. Gross total resection was achieved in all patients. Histopathology at second-look surgery revealed mature teratoma in 5, fibrosis with atypical cells in 1, and fibrosis in 1. All patients subsequently underwent additional chemoradiation therapy according to the initial diagnosis. All patients are alive with no evidence of recurrence, with a mean follow-up of 48 months. CONCLUSION: Second-look surgery plays an important role in the treatment of intracranial GCTs. Surgery may be encouraged at a relatively early phase after chemotherapy when the residual tumor increases or does not change size despite normalized or nearly normalized tumor markers in order to achieve complete resection and improve outcome.

scholarly journals GCT-70. INTRACRANIAL GROWING TERATOMA SYNDROME IN CHILDREN

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii342-iii342
Author(s):  
Maria Carter Febres ◽  
Carol S Bruggers ◽  
Holly Zhou ◽  
Arie Perry ◽  
John Kestle ◽  
...  
Keyword(s):  
Germ Cell ◽  
Obstructive Hydrocephalus ◽  
Mature Teratoma ◽  
Germ Cell Tumors ◽  
Residual Tumor ◽  
Complete Resection ◽  
Pineal Tumor ◽  
Tumor Biopsy ◽  
Growing Teratoma Syndrome ◽  
Multiagent Chemotherapy

Abstract Germ cell tumors account for less than 5% of all intracranial malignancies in children. Intracranial growing teratoma syndrome (GTS) is a rare pathophysiologic process characterized by growth of mature teratoma elements of a non-germinomatous germ cell tumor (NGGCT) during or following treatment with chemotherapy, in addition to normalization of or declining AFP/βHCG of the cerebral spinal fluid (CSF)/serum. A 13-year-old male presented with headache, emesis, and diplopia. MRI of the brain/spine revealed a localized 3.1 x 3.1 x 3.2 cm pineal tumor. Biopsy confirmed NGGCT (germinoma, immature and mature teratoma). Serum AFP (227ng/ul) and βHCG (12 IU/L) and CSF AFP (21ng/ul) and βHCG (31 IU/L) were elevated. Prior to cycle two of chemotherapy, he developed unstable gait and moderate hearing loss. Repeat MRI brain demonstrated tumor enlargement (4.4 x 5.2 x 5.1 cm) and obstructive hydrocephalus, although serum AFP/βHCG had normalized. Gross total resection of tumor confirmed GTS, without residual immature/malignant elements. Following six cycles of multiagent chemotherapy (carboplatin, etoposide, ifosfamide) and proton beam craniospinal irradiation (36 Gy with 18 Gy boost), he remains free of disease at eleven months since diagnosis. The pathogenesis of GTS remains unclear. Care must be taken to avoid misdiagnosing GTS as progressive NGGCT, as treatment and prognosis differ significantly. Second-look surgery, with a goal of complete resection, should be considered in cases of NGGCT when residual tumor grows during or following therapy, as this may represent GTS. Although histologically benign, GTS can be fatal. In patients with GTS, complete resection is usually curative.

scholarly journals Immature Teratoma and Mature Cystic Teratoma

2021 ◽  
Vol 5 (2) ◽  
pp. 139-147
Author(s):  
Nova Fenita Sari ◽  
RZ Nizar
Keyword(s):  
Germ Cell ◽  
Mature Teratoma ◽  
Relevant Literature ◽  
Primordial Germ Cells ◽  
Germ Cell Tumors ◽  
Cystic Teratoma ◽  
Residual Tumor ◽  
Scientific Paper ◽  
Immature Teratoma ◽  
Mature Cystic Teratoma

Introduction : Germ cell tumors arise from primordial germ cells and account for about 30% of all ovarian tumors. More than 95% of this group are benign dermoid cysts (mature cystic teratoma) and the remaining 5% are malignant. Ovarian teratomas represent 15% to 20% of ovarian germ cell tumors. Teratomas are classified as mature or immature and often consist of several embryological layers. While the mature type is benign, the immature type is more aggressive.Objective : Based on the above, this article will review about immature teratoma and mature cystic teratoma of the ovary. Material and methods : The method of writing this scientific paper is a literature review. The data used are sourced from relevant literature and in accordance with the topics discussed.Result : Teratomas are a common form of germ cell tumors. Teratomas are histologically defined as tumors containing tissue derived from all germ cell layers: ectoderm, mesoderm, and endoderm. Teratomas are classified as immature teratoma, mature teratoma and monodermal teratoma. Conclusion : Teratomas are usually asymptomatic and if there are symptoms, they tend to be non-specific. In patients with no residual tumor after surgery, the survival rate is 90-100%.Keywords: Teratoma, Immature Teratoma, Mature Cystic Teratoma

scholarly journals GCT-14. SECOND-LOOK SURGERY FOR INTRACRANIAL GERM CELL TUMORS

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii330-iii330
Author(s):  
Hideki Ogiwara
Keyword(s):  
Germ Cell ◽  
Tumor Markers ◽  
Mature Teratoma ◽  
Germ Cell Tumors ◽  
Residual Tumor ◽  
Complete Response ◽  
Immature Teratoma ◽  
Total Resection ◽  
Mixed Germ Cell Tumor ◽  
Second Look

Abstract OBJECTIVE The authors present their experiences of second-look surgery in patients with intracranial GCTs who showed less than complete response despite normalizing or decreasing tumor markers after chemotherapy. METHODS Retrospective review of 14 patients who underwent second-look surgery for an intracranial GCT was performed. RESULTS Of 40 consecutive patients with newly diagnosed intracranial GCTs treated between August 2003 and 2019, 14 patients (35%) underwent second-look surgery. The mean age was 9.2 years. The initial diagnoses were mixed germ cell tumor in 6, immature teratoma in 4, yolk sac tumor in 2, and germinoma 2. Second-look surgery was performed after 1–3 courses of chemotherapy. Magnetic resonance imaging (MRI) at the surgery demonstrated increasing residual tumor in 8 and stable residual tumor in 6. Tumor markers were normalized in 10 and nearly-normalized in 4. Gross total resection was achieved in 12 patients and near-total resection in 2. Histopatholgy at second-look surgery revealed mature teratoma in 6, immature teratoma in 3, fibrosis with atypical cells in 2, and fibrosis in 3. Eleven patients subsequently underwent additional chemo-radiation therapy according to the initial diagnosis. All patients are alive with no evidence of recurrence with a mean follow-up of 69 months. CONCLUSIONS Second-look surgery plays an important role in the treatment of intracranial GCTs. Surgery may be encouraged at a relatively early phase after chemotherapy when the residual tumor increases or does not change the size despite normalized or nearly-normalized tumor markers in order to achieve complete resection and improve the outcome.

Serum AFP, hCG and CEA in the Management of Patients with Testicular, Ovarian and Extragonadal Germ Cell Tumors

1992 ◽  
Vol 7 (2) ◽  
pp. 80-86 ◽  
Author(s):  
M.S. Motawy ◽  
J.J. Szymendera ◽  
H. Al-Jazzaf ◽  
A.E. Behbehani ◽  
M.O. Foudeh ◽  
...  
Keyword(s):  
Germ Cell ◽  
Tumor Cells ◽  
Mature Teratoma ◽  
Germ Cell Tumors ◽  
Residual Tumor ◽  
Serum Levels ◽  
Normal Serum ◽  
Testicular Germ Cell ◽  
Monitoring Therapy ◽  
Extragonadal Germ Cell Tumors

Serum levels of AFP, hCG and CEA were initially and serially measured in 59 patients with testicular germ cell tumors, and serially in 37 with ovarian and 3 with extragonadal germ cell tumors. Patients with seminoma/dysgerminoma or mature teratoma had normal serum AFP and sporadically slightly elevated hCG. Some patients with embryonal carcinoma, pure or with admixture of seminoma, had serum AFP elevated to maximum 100 U/ml, yet its use for monitoring therapy was limited. Patients with yolk sac tumors had elevated AFP and sometimes CEA levels, those with choriocarcinoma had elevated hCG, and those with compound tumors had one or more of the markers highly elevated. High AFP and/or hCG levels indicated the presence of the relevant tumor cells both in the primary and in residual tumor and/or metastases, also those missed in histological material, and thus were useful in restaging. Unfortunately, their absence in serum did not exclude the presence of marker-negative subpopulations of tumor cells. Changes in marker values paralleled the effects of treatment: the level increasing from any nadir heralded recurrence in patients in remission; elevated or increasing levels during therapy implied resistance to the therapy; decreasing levels indicated regression even though a return to the normal range did not mean eradication of all tumor cells.

scholarly journals GCT-43. GAIN OF SHORT ARM OF CHROMOSOME 12 IS A MOLECULAR MARKER TO PREDICT PROGNOSIS AND REPRESENTS AN EARLY EVENT IN TUMORIGENESIS IN INTRACRANIAL GERM CELL TUMORS

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii336-iii336
Author(s):  
Kaishi Satomi ◽  
Hirokazu Takami ◽  
Shintaro Fukushima ◽  
Yoichi Nakazato ◽  
Shota Tanaka ◽  
...  
Keyword(s):  
Molecular Marker ◽  
Germ Cell ◽  
Germ Cell Tumor ◽  
Mature Teratoma ◽  
Germ Cell Tumors ◽  
Cell Tumor ◽  
Chromosome 12 ◽  
Early Event ◽  
Testicular Germ Cell ◽  
Intracranial Germ Cell Tumor

Abstract Gain of short arm of chromosome 12 (12p) is commonly observed in testicular germ cell tumors (tGCTs) and also seen in intracranial GCTs (iGCTs). However, little is known about the clinical significance of 12p gain in iGCTs. We have collected over 200 fresh frozen tissue samples of iGCTs through the Intracranial Germ Cell Tumor Genome Analysis Consortium in Japan. Firstly, we analyzed DNA methylation profile in 83 iGCTs, 3 tGCTs (seminomas) and 6 normal control samples using Infinium Human Methylation 450K BeadChip array (Illumina, CA, USA) in order to determine 12p gain status. Then, fluorescence in situ hybridization (FISH) study was carried out on 3 mixed iGCT cases using 12p/CEP12 probe (Abbott Molecular, Abbott park, IL, USA). Lastly, 58 iGCTs with clinicopathological information were analyzed for progression-free survival (PFS) and overall survival (OS). Gain of 12p was observed in 100% (3/3) of seminoma, 14% (3/22) of germinoma, 17% (1/6) of mature teratoma, 25% (1/4) of immature teratoma, 55% (11/20) of mixed germ cell tumor, 100% (4/4) of yolk sac tumor, 100% (1/1) of embryonal carcinoma, and 100% (1/1) of choriocarcinoma. In total, 45% (37/83) of iGCT showed 12p gain. Different histological components in each mixed GCT shared the same 12p copy number status within each mixed GCT case. Both PFS and OS were significantly worse in iGCTs with 12p gain (PFS: P=0.027, OS: P=0.0012). Gain of 12p can be a molecular marker to predict prognosis and represents an early event in tumorigenesis prior to histological differentiation in iGCTs.

scholarly journals GCT-15. INTEGRATED CLINICAL, HISTOPATHOLOGICAL, AND MOLECULAR DATA ANALYSIS OF 190 CENTRAL NERVOUS SYSTEM GERM CELL TUMORS FROM THE IGCT CONSORTIUM

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii330-iii331
Author(s):  
Hirokazu Takami ◽  
Koichi Ichimura ◽  
Kohei Fukuoka ◽  
Akitake Mukasa ◽  
Nobuhito Saito ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Basal Ganglia ◽  
Pineal Gland ◽  
Germ Cell ◽  
Prognostic Significance ◽  
Germ Cell Tumors ◽  
Molecular Data ◽  
Molecular Heterogeneity ◽  
Intracranial Germ Cell Tumor

Abstract BACKGROUND We integrated clinical, histopathological, and molecular data of central nervous system germ cell tumors to provide insights into their management. METHODS Data from the Intracranial Germ Cell Tumor Genome Analysis Consortium were reviewed. A total of 190 cases were classified as primary GCTs based on central pathological reviews. RESULTS All but one of the cases that were bifocal (neurohypophysis and pineal glands) and cases with multiple lesions including neurohypophysis or pineal gland were germinomas (34 of 35). Age was significantly higher in patients with germinoma than other histologies. Comparison between tumor marker and histopathological diagnoses showed that 18.2% of histopathologically diagnosed germinomas were marker-positive and 6.1% of non-germinomatous GCTs were marker-negative, suggesting a limitation in the utility of markers or histopathology alone using small specimens for diagnosis. Comparison between local and central histopathological diagnoses revealed a discordance of 12.7%. Discordance was significantly less frequent in biopsy cases, implying difficulty in detecting all histopathological components of heterogeneous GCTs. Germinomas at the typical sites (neurohypophysis or pineal gland) showed a better PFS than those at atypical sites (p=0.03). A molecular-clinical association study revealed frequent MAPK pathway mutations in males (51.4 vs 14.3 %, p=0.007), and PI3K/mTOR pathway mutations in basal ganglia cases (p=0.004). Basal ganglia cases also had frequent chromosomal losses. Some chromosomal aberrations (2q, 8q gain, 5q, 9p/q, 13q, 15q loss) showed potential prognostic significance. CONCLUSIONS These in-depth findings of this study regarding the clinical and molecular heterogeneity will increase our understanding of the pathogenesis of this enigmatic tumor.

scholarly journals Integrated clinical, histopathological, and molecular data analysis of 190 central nervous system germ cell tumors from the iGCT Consortium

2019 ◽  
Vol 21 (12) ◽  
pp. 1565-1577 ◽  
Author(s):  
Hirokazu Takami ◽  
Kohei Fukuoka ◽  
Shintaro Fukushima ◽  
Taishi Nakamura ◽  
Akitake Mukasa ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Basal Ganglia ◽  
Pineal Gland ◽  
Germ Cell ◽  
Prognostic Significance ◽  
Germ Cell Tumors ◽  
Molecular Data ◽  
Molecular Heterogeneity ◽  
Intracranial Germ Cell Tumor

Abstract Background We integrated clinical, histopathological, and molecular data of central nervous system germ cell tumors to provide insights into their management. Methods Data from the Intracranial Germ Cell Tumor Genome Analysis (iGCT) Consortium were reviewed. A total of 190 cases were classified as primary germ cell tumors (GCTs) based on central pathological reviews. Results All but one of the cases that were bifocal (neurohypophysis and pineal glands) and cases with multiple lesions including neurohypophysis or pineal gland were germinomas (34 of 35). Age was significantly higher in patients with germinoma than other histologies. Comparison between tumor marker and histopathological diagnoses showed that 18.2% of histopathologically diagnosed germinomas were marker positive and 6.1% of non-germinomatous GCTs were marker negative, suggesting a limitation in the utility of markers or histopathology alone using small specimens for diagnosis. Comparison between local and central histopathological diagnoses revealed a discordance of 12.7%. Discordance was significantly less frequent in biopsy cases, implying difficulty in detecting all histopathological components of heterogeneous GCTs. Germinomas at the typical sites (neurohypophysis or pineal gland) showed a better progression-free survival than those at atypical sites (P = 0.03). A molecular clinical association study revealed frequent mitogen-activated protein kinase (MAPK) pathway mutations in males (51.4% vs 14.3%, P = 0.007), and phosphatidylinositol-3 kinase/mammalian target of rapamycin (PI3K/mTOR) pathway mutations in basal ganglia cases (P = 0.004). Basal ganglia cases also had frequent chromosomal losses. Some chromosomal aberrations (2q, 8q gain, 5q, 9p/q, 13q, 15q loss) showed potential prognostic significance. Conclusions The in-depth findings of this study regarding clinical and molecular heterogeneity will increase our understanding of the pathogenesis of this enigmatic tumor.

Residual Tumor Resection After High-Dose Chemotherapy in Patients With Relapsed or Refractory Germ Cell Cancer

2004 ◽  
Vol 22 (18) ◽  
pp. 3713-3719 ◽  
Author(s):  
O. Rick ◽  
C. Bokemeyer ◽  
S. Weinknecht ◽  
J. Schirren ◽  
T. Pottek ◽  
...  
Keyword(s):  
Germ Cell ◽  
Mature Teratoma ◽  
Univariate Analysis ◽  
Cell Cancer ◽  
Tumor Resection ◽  
Residual Tumor ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Incomplete Resection ◽  
Residual Tumor Resection

Purpose To assess the role of residual tumor resection performed after high-dose chemotherapy (HDCT) in patients with relapsed or refractory germ cell tumors (GCT). Patients and Methods Between July 1987 and October 1999, postchemotherapy resections of residual tumors were performed in 57 patients who had been treated with HDCT for relapsed or refractory GCT and who had achieved a partial remission to this treatment. Results Complete resections of residual masses were achieved in 52 (91%) of 57 patients who were rendered disease free; in five (9%) of 57 patients, the resections were incomplete. Resection of a single site was performed in 39 (68%) of 57 patients, and the remaining 18 (32%) of 57 patients required interventions at two or more residual tumor sites. Necrosis was found in 22 (38%) of 57 patients, mature teratoma with or without necrosis was found in nine (16%) of 57 patients, and viable cancer with or without additional necrosis or mature teratoma was found in 26 (46%) of 57 patients. Viable cancer consisted either of residual germ cell or undifferentiated cancer in 22 (85%) of 26 patients, with additional non-GCT histologies in the remaining four patients. Patients with viable cancer had a significantly inferior outcome after surgery compared with patients with necrosis and/or mature teratoma even if all cancer was completely resected. Pulmonary lesions with a diameter of more than 2 cm were the only predictive variable for viable cancer in univariate analysis. Conclusion Resections of all residual tumors should be attempted in patients with relapsed or refractory GCT and partial remissions after HDCT.

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