Subject(s)
Brain Neoplasms/genetics , Brain Neoplasms/pathology , Carcinoma, Embryonal/genetics , Carcinoma, Embryonal/pathology , Carrier Proteins/genetics , Membrane Proteins/genetics , Neoplasm Proteins/genetics , Nuclear Proteins/genetics , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Brain Neoplasms/therapy , Carcinoma, Embryonal/therapy , Cerebral Intraventricular Hemorrhage/etiology , Cerebral Intraventricular Hemorrhage/mortality , Cisplatin/administration & dosage , Combined Modality Therapy/methods , Cyclophosphamide/administration & dosage , Fatal Outcome , Female , Humans , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/surgery , Neurosurgical Procedures , Oncogene Fusion/genetics , Vincristine/administration & dosageABSTRACT
PURPOSE: Active surveillance (AS) for testicular nonseminomatous germ cell tumors (NSGCT) is widely used. Although there is no consensus for optimal treatment at relapse on surveillance, globally patients typically receive chemotherapy. We describe treatment of relapses in our non-risk-adapted NSGCT AS cohort and highlight selective use of primary retroperitoneal lymph node dissection (RPLND). METHODS: From December 1980 to December 2015, 580 patients with clinical stage I NSGCT were treated with AS, and 162 subsequently relapsed. First-line treatment was based on relapse site and extent. Logistic regression was used to explore factors associated with need for multimodal therapy on AS relapse. RESULTS: Median time to relapse was 7.4 months. The majority of relapses were confined to the retroperitoneum (66%). After relapse, first-line treatment was chemotherapy for 95 (58.6%) and RPLND for 62 (38.3%), and five patients (3.1%) underwent other therapy. In 103 (65.6%), only one modality of treatment was required: chemotherapy only in 58 of 95 (61%) and RPLND only in 45 of 62 (73%). Factors associated with multimodal relapse therapy were larger node size (odds ratio, 2.68; P = .045) in patients undergoing chemotherapy and elevated tumor markers (odds ratio, 6.05; P = .008) in patients undergoing RPLND. When RPLND was performed with normal markers, 82% required no further treatment. Second relapse occurred in 30 of 162 patients (18.5%). With median follow-up of 7.6 years, there were five deaths (3.1% of AS relapses, but 0.8% of whole AS cohort) from NSGCT or treatment complications. CONCLUSION: The retroperitoneum is the most common site of relapse in clinical stage I NSGCT on AS. Most are cured by single-modality treatment. RPLND should be considered for relapsed patients, especially those with disease limited to the retroperitoneum and normal markers, as an option to avoid chemotherapy.
Subject(s)
Carcinoma, Embryonal/therapy , Neoplasm Recurrence, Local/therapy , Neoplasms, Germ Cell and Embryonal/therapy , Retroperitoneal Neoplasms/therapy , Testicular Neoplasms/therapy , Adult , Carcinoma, Embryonal/pathology , Chemotherapy, Adjuvant , Combined Modality Therapy , Follow-Up Studies , Humans , Lymph Node Excision , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Neoplasms, Germ Cell and Embryonal/pathology , Recurrence , Regression Analysis , Retroperitoneal Neoplasms/pathology , Retroperitoneal Space , Retrospective Studies , Risk , Testicular Neoplasms/pathology , Treatment Outcome , Young AdultABSTRACT
The paternally-imprinted genes insulin-like growth factor 2 (IGF2), H19, delta-like homologue 1 (DLK1), and maternally-expressed gene 3 (MEG3) are expressed from the tandem gene loci IGF2-H19 and DLK1-MEG3, which play crucial roles in initiating embryogenesis and development. The erasure of imprinting (EOI) at differentially methylated regions (DMRs) which regulate the expression of these genes maintains the developmental quiescence of primordial germ cells (PGCs) migrating through the embryo proper during embryogenesis and prevents them from forming teratomas. To address the potential involvement of the IGF2-H19 and DLK1-MEG3 loci in the pathogenesis of embryonal carcinoma (EC), we investigated their genomic imprinting at DMRs in the human PGC-derived EC cell line NTera-2 (NT2). We observed EOI at the IGF2-H19 locus and, somewhat to our surprise, a loss of imprinting (LOI) at the DLK1-MEG3 locus. As a result, NT2 cells express imprinted gene ratios from these loci such that there are i) low levels of the proliferation-promoting IGF2 relative to ii) high levels of the proliferation-inhibiting long noncoding RNA (lncRNA) H19 and iii) high levels of proliferation-promoting DLK1 relative to iv) low levels of the proliferation-inhibiting lncRNA MEG3. Consistent with this pattern of expression, the knockdown of DLK1 mRNA by shRNA resulted in decreased in vitro cell proliferation and in vivo tumor growth as well as decreased in vivo organ seeding by NT2 cells. Furthermore, treatment of NT2 cells with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-azaD) inhibited their proliferation. This inhibition was accompanied by changes in expression of both tandem gene sets: a decrease in the expression of DLK1 and upregulation of the proliferation-inhibiting lncRNA MEG3, and at the same time upregulation of IGF2 and downregulation of the lncRNA H19. These results suggest that the DLK1-MEG3 locus, and not the IGF2-H19 locus, drives the tumorigenicity of NT2 cells. Based on these results, we identified DLK1 as a novel treatment target for EC that could be downregulated by 5-azaD.
Subject(s)
Carcinoma, Embryonal , Genetic Loci , Genomic Imprinting , Insulin-Like Growth Factor II , Intercellular Signaling Peptides and Proteins , Membrane Proteins , Neoplasm Proteins , RNA, Long Noncoding , RNA, Neoplasm , Calcium-Binding Proteins , Carcinoma, Embryonal/genetics , Carcinoma, Embryonal/metabolism , Carcinoma, Embryonal/pathology , Carcinoma, Embryonal/therapy , Cell Line, Tumor , Humans , Insulin-Like Growth Factor II/genetics , Insulin-Like Growth Factor II/metabolism , Intercellular Signaling Peptides and Proteins/genetics , Intercellular Signaling Peptides and Proteins/metabolism , Membrane Proteins/genetics , Membrane Proteins/metabolism , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , RNA, Neoplasm/genetics , RNA, Neoplasm/metabolismSubject(s)
Carcinoma, Embryonal/diagnosis , Lung Neoplasms/diagnosis , Testicular Neoplasms/diagnosis , Adult , Antineoplastic Combined Chemotherapy Protocols , Bronchoscopy , Carcinoma, Embryonal/diagnostic imaging , Carcinoma, Embryonal/secondary , Carcinoma, Embryonal/therapy , Diagnosis, Differential , Dyspnea/etiology , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/secondary , Lung Neoplasms/therapy , Male , Neoplasm Metastasis , Orchiectomy , Testicular Neoplasms/diagnostic imaging , Testicular Neoplasms/pathology , Testicular Neoplasms/therapyABSTRACT
OBJECTIVE: To determine the pathologic findings and clinical outcome of patients with pure embryonal carcinoma (EC) of the testis who were diagnosed with testis cancer from January 1989 to January 2013 who underwent an orchiectomy, cisplatin-based chemotherapy and a postchemotherapy retroperitoneal lymph node dissection (PC-RPLND). METHODS: We compared those patients with 100% EC with those with mixed nonseminomatous germ cell tumor pathology who underwent a PC-RPLND. RESULTS: Of 1105 patients who underwent a PC-RPLND, 145 had pure EC. Twenty-six percent of patients presented with metastatic disease outside the retroperitoneum. Patients with mixed histologies tended to have worse International Germ Cell Cancer Collaborative Group risk compared to those with EC at orchiectomy (P = .037). Histology at PC-RPLND revealed fibrosis or necrosis in 76%, mature teratoma in 19% and viable cancer in 4%. Over one-third of the patients had a residual mass of <1 cm prior to RPLND; of whom 15% harbored mature teratoma in PC-RPLND histology. The Kaplan-Meier estimated probability of recurrence at 5 years of follow-up was 3.1% (95% CI 1.2%, 8.0%) for EC histology, 7.3% lower than mixed histology. For cancer-specific mortality, the Kaplan-Meier estimated probability at 5 years was 4.6% (95% CI 3.3%, 6.3%) and 1.7% (95% CI 0.4%, 6.8%) for mixed and pure EC histologies, respectively. CONCLUSION: Approximately 20% of patients with pure EC had teratoma at PC-RPLND. We have shown that those with a maximum node size of <1 cm should not be precluded from RPLND.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Embryonal/therapy , Lymph Node Excision , Lymph Nodes/pathology , Neoplasms, Complex and Mixed/therapy , Neoplasms, Germ Cell and Embryonal/therapy , Teratoma/therapy , Testicular Neoplasms/therapy , Adult , Carcinoma, Embryonal/secondary , Chemotherapy, Adjuvant , Cisplatin/administration & dosage , Disease Progression , Disease-Free Survival , Fibrosis , Humans , Kaplan-Meier Estimate , Lymphatic Metastasis , Male , Middle Aged , Necrosis , Neoplasm, Residual , Neoplasms, Complex and Mixed/secondary , Neoplasms, Germ Cell and Embryonal/secondary , Orchiectomy , Retroperitoneal Space , Retrospective Studies , Survival Rate , Teratoma/secondary , Testicular Neoplasms/pathology , Testicular Neoplasms/secondarySubject(s)
Carcinoma, Embryonal/therapy , Homeopathy , Teratoma/therapy , Biopsy , Carcinoma, Embryonal/complications , Carcinoma, Embryonal/pathology , Carcinoma, Embryonal/surgery , Child, Preschool , Female , Humans , Plant Extracts/therapeutic use , Pulsatilla/chemistry , Skin/pathology , Teratoma/complications , Teratoma/pathology , Teratoma/surgery , Treatment OutcomeABSTRACT
Resumen Introducción: El hematoma retroperitoneal (HR) es una enfermedad infrecuente con una elevada morbimortalidad, siendo complicado cuando se presenta con dolor y shock hipovolémico. Presentación del caso: Paciente del sexo masculino, de 20 años de edad, sin antecedentes mórbidos. Ingresa en Urgencias por dolor abdominal en el flanco izquierdo, irradiado a dorso y testículo ipsilateral, de 6 h de evolución, de inicio súbito e intensidad severa; el paciente está pálido, hemodinámicamente estable, sin signos de irritación peritoneal. Se solicita pielo-TC por sospecha de litiasis ureteral, que muestra un extenso HR, probable aneurisma aórtico roto. Una angio-TC informa HR adyacente y anterior a psoasilíaco izquierdo, de20 × 11 × 8,5 cm, volumen 972 cc, adenopatías retroperitoneales paraaórticas bilaterales sangrantes y múltiples nódulos pulmonares bilaterales indicativos de diseminación secundaria. Se constata testículo derecho duro, de tamaño normal, eco testicular con masa sólida quística, que indica de lesión orgánica. Discusión: Trauma y enfermedad tumoral son las principales causas de HR. El cáncer testicular suele presentarse en pacientes jóvenes, requiriendo una pronta derivación y estudio debido a su rápida progresión. En nuestro caso, el HR fue un hallazgo imagenológico, destacando que el sangrado de un conglomerado de adenopatías es anecdótico.
Abstract Introduction: Retroperitoneal hematoma (RH) is a rare disease with high morbidity, being complicated when presented with pain and hypovolemic shock. Case report: Male, 20 years old, no morbid history. Arrive to Emergency Service for abdominal pain in the left flank radiating to the back and ipsilateral testis, 6 h of evolution, sudden onset, high intensity; pacient pale, hemodynamically stable without signs of peritoneal irritation. Pielo-TC is requested on suspicion of ureteral stones showing extensive RH, likely ruptured aortic aneurysm. CT angiography reports RH and adjacent preceding left iliopsoas, 20 × 11 × 8.5 cm, volume 972 cc, retroperitoneal bleeding bilateral para-aortic lymphadenopathy and multiple bilateral pulmonary nodules suggestive of secondary spread. Hard right testicle with normal size, testicular ultrasound pointing solid cystic mass, suggestive of organic lesion. Discussion: Trauma and tumor pathology are the main causes of RH. Testicular cancer usually occurs in young patients, requiring early referal and study because of its rapid progression. In our case, the HR was an imaging finding, highlighting that the bleeding of a cluster of lymph nodes is anecdotal.
Subject(s)
Humans , Male , Young Adult , Retroperitoneal Space , Testicular Neoplasms/complications , Carcinoma, Embryonal/complications , Hematoma/etiology , Hematoma/diagnostic imaging , Testicular Neoplasms/therapy , Testicular Neoplasms/diagnostic imaging , Abdominal Pain/etiology , Carcinoma, Embryonal/therapy , Carcinoma, Embryonal/diagnostic imaging , Computed Tomography AngiographyABSTRACT
BACKGROUND AND OBJECTIVE: Pediatric basal ganglia germ cell tumors (GCTs) represent a rare subset of tumors about which little is known. We aimed to summarize the clinical features and radiological findings of this special subgroup of GCTs. METHODS: From January 2010 to January 2015, 12 pediatric patients with basal ganglia GCTs were treated in our hospital. The clinical features, radiologic findings, diagnosis, treatment, and outcome of these patients were analyzed retrospectively. Our institutional diagnostic principle and treatment strategy of this disease were discussed. RESULTS: GCTs accounted for 25.5% of all the pediatric basal ganglia tumors treated in our hospital. There were 9 male and 3 female patients with a mean age of 11.5 ± 2.1 years. The most common symptom was progressive hemiparesis (n = 9, 75%). The radiologic findings showed that the lesions predominately located in caput of caudate nucleus (n = 9, 75.0%), followed by lenticular nucleus (n = 3, 25.0%). Hemiatrophy was commonly observed (n = 8, 66.7%). Eight patients were diagnosed as having germinomas, and 4 patients as having nongerminomatous germ cell tumors. During the follow-up period, preoperative neurologic dysfunctions improved in 7 patients and remained stable in 3. Two patients developed new onset of neurologic dysfunction after the treatment. Two patients suffered from tumor recurrence. CONCLUSIONS: GCTs are not as rare as considered in pediatric basal ganglia tumors. They bear some distinctive clinical and radiologic features, which can help with the accurate diagnosis and successful management of such tumors.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Basal Ganglia Diseases/therapy , Brain Neoplasms/therapy , Neoplasms, Germ Cell and Embryonal/therapy , Adolescent , Aftercare , Basal Ganglia Diseases/complications , Basal Ganglia Diseases/diagnostic imaging , Basal Ganglia Diseases/metabolism , Brain Neoplasms/complications , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/metabolism , Carboplatin/administration & dosage , Carcinoma, Embryonal/complications , Carcinoma, Embryonal/diagnostic imaging , Carcinoma, Embryonal/metabolism , Carcinoma, Embryonal/therapy , Caudate Nucleus/diagnostic imaging , Caudate Nucleus/surgery , Child , Choriocarcinoma, Non-gestational/complications , Choriocarcinoma, Non-gestational/diagnostic imaging , Choriocarcinoma, Non-gestational/metabolism , Choriocarcinoma, Non-gestational/therapy , Chorionic Gonadotropin, beta Subunit, Human/metabolism , Cisplatin/administration & dosage , Cognitive Dysfunction/etiology , Corpus Striatum/diagnostic imaging , Corpus Striatum/surgery , Cranial Irradiation , Diffusion Tensor Imaging , Endodermal Sinus Tumor/complications , Endodermal Sinus Tumor/diagnostic imaging , Endodermal Sinus Tumor/metabolism , Endodermal Sinus Tumor/therapy , Etoposide/administration & dosage , Female , Germinoma/complications , Germinoma/diagnostic imaging , Germinoma/metabolism , Germinoma/therapy , Humans , Magnetic Resonance Imaging , Male , Neoadjuvant Therapy , Neoplasms, Germ Cell and Embryonal/complications , Neoplasms, Germ Cell and Embryonal/diagnostic imaging , Neoplasms, Germ Cell and Embryonal/metabolism , Neurosurgical Procedures , Paresis/etiology , Retrospective Studies , Second-Look Surgery , Seizures/etiology , Tomography, X-Ray ComputedABSTRACT
We report a 33-year-old male with a left advanced non-seminomatous testicular germ cell tumor (NSGCT) accompanied panic disorder. He had experienced palpitation and hyperpnea in crowds in his twenties. He was admitted to the Department of Otorhinolaryngology with the chief complaint of left neck swelling. 18F-fluorodeoxy glucose positron emission tomography/computed tomography (FDG-PET/CT) demonstrated left neck, left supraclavicular, left axillary, and paraaortic lymph node (LN) swelling and left testicular swelling. He was referred to our department. The left testis had enlarged to the size of a fist. He rejected admission at that time, but next day, he was taken to our hospital by an ambulance because he lost consciousness at home. No abnormalities were found in the brain CT and electrocardiogram. He was admitted and left high orchiectomy was performed. The human chorionic gonadotropin (HCG) level had elevated to 9,717 IU/L and alpha fetoprotein level (AFP) had elevated to 427 ng/ml. The histopathological diagnosis was tumors of more than one histological type, mixed forms: seminoma and embryonal carcinoma.He had palpitation and hyperpnea after admission and was diagnosed with panic disorder by a psychiatrist. Psychotropic drugs (fluvoxamine maleate 50 mg/day, alprazolam 0.8 mg/day) were prescribed and the panic attacks disappeared afterwards. The psychiatric social worker supported his mind side. Bleomycin, etoposide, and cisplatin (BEP) therapy was performed for 4 courses. He put on a blanket to his face and came to avoid a conversation with other people during the chemotherapy. He was diagnosed with depression and psychotropic drugs were increased (fluvoxamine maleate 50â75 mg/day, alprazolam 0.8â1.2 mg/day) in quantity.Lymphadenectomies for LN metastases were performed and their histopathological examination revealed the existence of viable embryonal carcinoma in the supraclavicular LN. Etoposide, ifosfamide, and cisplatin (VIP) therapy was performed for 2 courses.The pateint has remained alive without tumor recurrence. Psychotropic drugs were reduced and the recent drug is fluvoxamine maleate 25 mg/day.
Subject(s)
Carcinoma, Embryonal/complications , Carcinoma, Embryonal/therapy , Neoplasms, Germ Cell and Embryonal/complications , Neoplasms, Germ Cell and Embryonal/therapy , Neoplasms, Multiple Primary , Panic Disorder/complications , Testicular Neoplasms/complications , Testicular Neoplasms/therapy , Adult , Alprazolam/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/blood , Carcinoma, Embryonal/diagnosis , Chorionic Gonadotropin/blood , Combined Modality Therapy , Fluvoxamine/administration & dosage , Humans , Lymph Node Excision , Male , Neoplasms, Germ Cell and Embryonal/diagnosis , Orchiectomy , Panic Disorder/drug therapy , Positron Emission Tomography Computed Tomography , Psychotropic Drugs/administration & dosage , Testicular Neoplasms/diagnosis , Treatment Outcome , alpha-FetoproteinsABSTRACT
A 50-year-old man with a history of smoking of 45 pack-years underwent right lower lobectomy after neoadjuvant chemoradiotherapy for locally advanced non-small cell lung cancer diagnosed on a bronchial biopsy and standard imaging examinations, including chest-abdominal contrast-enhanced computed tomography (CT) and whole-body F-18 fluorodeoxyglucose positron emission tomography/CT. Left orchiectomy was performed simultaneously to treat the slightly swollen left testis, which had remained unchanged for over five years. The thoracic tumor was proven to be in pathological complete remission and the testicular lesion was pathologically diagnosed as an embryonal carcinoma. Furthermore, a pathological reevaluation of the preoperative bronchial biopsy specimen revealed the lung tumor to be a metastatic embryonal carcinoma.
Subject(s)
Carcinoma, Embryonal/pathology , Carcinoma, Embryonal/secondary , Lung Neoplasms/pathology , Lung Neoplasms/secondary , Testicular Neoplasms/pathology , Biopsy , Carcinoma, Embryonal/diagnosis , Carcinoma, Embryonal/therapy , Carcinoma, Non-Small-Cell Lung/pathology , Chemoradiotherapy , Diagnosis, Differential , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/therapy , Male , Middle Aged , Neoplasm Staging , Orchiectomy , Positron-Emission Tomography , Testicular Neoplasms/surgery , Tomography, X-Ray ComputedSubject(s)
Abdominal Wall , Carcinoma, Embryonal/pathology , Neoplasms, Multiple Primary/pathology , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/pathology , Pelvic Neoplasms/pathology , Teratoma/pathology , Adult , Carcinoma, Embryonal/therapy , Female , Humans , Neoplasms, Multiple Primary/therapy , Ovarian Neoplasms/therapy , Pelvic Neoplasms/therapy , Teratoma/therapyABSTRACT
We report the case of a 19-year-old woman experiencing lower abdominal distension and pain. Laboratory tests indicated elevated serum levels of Alpha-Fetoprotein (AFP) and human Chorionic Gonadotropin (hCG). A large mass was detected in the abdomen by physical examination and by transvaginal ultrasonography. Exploratory laparotomy was performed, and a smooth-surfaced, spherical, solid tumor was found on the left ovary, measuring 11.5 x 9.9 x 6.9 cm. Histological evaluation revealed that the tumor consisted of a combination of immature teratoma, Yolk Sac Tumor, and embryonal carcinoma; this is a very rare combination in mixed germ cell tumors.
Subject(s)
Carcinoma, Embryonal/pathology , Endodermal Sinus Tumor/pathology , Neoplasms, Complex and Mixed/pathology , Neoplasms, Germ Cell and Embryonal/pathology , Ovarian Neoplasms/pathology , Teratoma/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bleomycin/therapeutic use , Carcinoma, Embryonal/blood , Carcinoma, Embryonal/therapy , Chemotherapy, Adjuvant/methods , Chorionic Gonadotropin/blood , Cisplatin/therapeutic use , Endodermal Sinus Tumor/blood , Endodermal Sinus Tumor/therapy , Etoposide/therapeutic use , Female , Humans , Laparotomy , Neoplasms, Complex and Mixed/blood , Neoplasms, Complex and Mixed/therapy , Neoplasms, Germ Cell and Embryonal/blood , Neoplasms, Germ Cell and Embryonal/therapy , Ovarian Neoplasms/blood , Ovarian Neoplasms/therapy , Ovariectomy , Salpingostomy , Teratoma/blood , Teratoma/therapy , Treatment Outcome , Young Adult , alpha-Fetoproteins/analysis , alpha-Fetoproteins/metabolismABSTRACT
Mediastinal embryonal carcinoma is rare, and the life prognosis of this disease is assumed to be relatively short. We encountered a case of mediastinal embryonal carcinoma for which we could perform radical surgical resection. The patient was male, aged 16 years, and acutely aware of back pain. Because the pain increased during the same year, he visited a local doctor, and an expanding neoplastic lesion was detected in the right thoracic wall by computed tomography (CT). Then he was referred to our institution. Magnetic resonance imaging (MRI) showed a dumbbell type tumor (Eden type 3) at the Th7/8 level. Malignant disease was suspected, so the authors planned and performed CT-guided biopsy. The result showed that this tumor pathologically corresponded to malignant peripheral nerve sheath tumor (MPNST). Therefore, chemotherapy was considered the main treatment. After 2 courses of chemotherapy, the tumor size decreased dramatically. The authors thought that radical resection is possible if there is no intrathoracic tumor dissemination as a result of a favorable response to chemotherapy. We thus perfomed surgical resection after we confirmed by a thoracoscopic exploratory thoracotomy that there was no intrathoracic tumor dissemination. Pathological findings were consistent with an embryonal carcinoma. Both the cutting ends of the thoracic wall and the epidural lateral sides of the excised lesion were negative for tumor cells. There is no image finding from the MRI and PET-CT suggesting metastasis or recurrence in the MRI and PET-CT 18 months after surgical resection. Therefore, the long-term vital prognosis can be expected in this patient.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Embryonal/therapy , Mediastinal Neoplasms/therapy , Neoadjuvant Therapy , Thoracic Surgical Procedures , Adolescent , Back Pain/etiology , Biopsy , Carcinoma, Embryonal/complications , Carcinoma, Embryonal/pathology , Chemotherapy, Adjuvant , Cisplatin/administration & dosage , Doxorubicin/administration & dosage , Etoposide/administration & dosage , Humans , Ifosfamide/administration & dosage , Magnetic Resonance Imaging , Male , Mediastinal Neoplasms/complications , Mediastinal Neoplasms/pathology , Positron-Emission Tomography , Time Factors , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
Malignant germ cell tumors of the ovary are very rare and account for about 2-5% of all ovarian tumors of germ origin. Most patients are adolescent and young women, approximately two-thirds of them are under 20 years of age, occasionally in postmenopausal women. But clear cell carcinoma usually occurs in older patients (median age: 57-year old), and closely related with endometriosis. Here we report a case of a 55-year old woman with right ovarian mass that discovered by B ultrasonic. Her serum levels of human chorionic gonadotropin (hCG) and α-fetoprotein (AFP) were elevated. Pathological examination revealed the tumor to be a mixed germ cell tumor (yolk sac tumor, embryonal carcinoma and mature teratoma) with clear cell carcinoma in a background of endometriosis. Immunohistochemical staining showed SALL4 and PLAP were positive in germ cell tumor area, hCG, CD30 and OCT4 were positive in epithelial-like cells and giant synctiotrophoblastic cells, AFP, AAT, CD117 and Glyp3 were positive in yolk sac component, EMA and CK7 were positive in clear cell carcinoma, CD10 was positive in endometrial cells of endometriotic area. She was treated with surgery followed by seven courses of chemotherapy. She is well and serum levels of hCG and AFP have been decreased to normal levels.
Subject(s)
Carcinoma, Embryonal/pathology , Endodermal Sinus Tumor/pathology , Neoplasms, Complex and Mixed/pathology , Ovarian Neoplasms/pathology , Postmenopause , Teratoma/pathology , Biomarkers, Tumor/blood , Biopsy , Carcinoma, Embryonal/blood , Carcinoma, Embryonal/chemistry , Carcinoma, Embryonal/diagnostic imaging , Carcinoma, Embryonal/therapy , Chorionic Gonadotropin/blood , Endodermal Sinus Tumor/blood , Endodermal Sinus Tumor/chemistry , Endodermal Sinus Tumor/diagnostic imaging , Endodermal Sinus Tumor/therapy , Endometriosis/pathology , Female , Humans , Immunohistochemistry , Middle Aged , Neoplasms, Complex and Mixed/blood , Neoplasms, Complex and Mixed/chemistry , Neoplasms, Complex and Mixed/diagnostic imaging , Neoplasms, Complex and Mixed/therapy , Ovarian Neoplasms/blood , Ovarian Neoplasms/chemistry , Ovarian Neoplasms/diagnostic imaging , Ovarian Neoplasms/therapy , Teratoma/blood , Teratoma/chemistry , Teratoma/diagnostic imaging , Teratoma/therapy , Treatment Outcome , Ultrasonography , alpha-Fetoproteins/metabolismABSTRACT
Testicular germ cell tumors (GCTs) commonly metastasize to the retroperitoneal lymph nodes (RPLNs). We evaluated 100 cases of RPLN dissection specimens with viable GCTs after chemotherapy and compared them with their corresponding orchiectomy specimens. The mean age of patients was 28 years (range, 15-58 years). The testicular tumors consisted of mixed GCT (n = 72), teratoma (n = 18), seminoma (n = 4), embryonal carcinoma (n = 3), yolk sac tumor (n = 1), and no viable tumor (n = 2). Somatic malignant components were found in 5 cases. The metastatic tumors in the RPLNs consisted of only teratoma (n = 77) and non-teratomatous GCT (n = 23). Twenty-one patients had only teratoma in the RPLNs but not in the testis, and 10 patients had metastatic non-teratomatous GCT components that were not observed in the testis. Six patients had somatic malignant components in the RPLNs, but only one of them had such a component in the testis. Overall, 13 patients died of disease in a mean of 42 months, and the patients with only teratoma in the RPLNs had a lower mortality rate (9%) than those with non-teratomatous components (26%) (P = .044). One patient with somatic components in the primary GCT and 3 patients with somatic components in the metastases died of disease. Our study demonstrates that there is frequent discordance of histologic composition between primary and metastatic testicular GCTs. Teratoma is the most common component in treated GCTs and is usually associated with a more favorable clinical outcome than non-teratomatous GCTs. The presence of somatic components in the RPLNs metastasis indicates a poor prognosis.
Subject(s)
Neoplasms, Germ Cell and Embryonal/secondary , Testicular Neoplasms/pathology , Adolescent , Adult , Carcinoma, Embryonal/mortality , Carcinoma, Embryonal/pathology , Carcinoma, Embryonal/therapy , Combined Modality Therapy , Endodermal Sinus Tumor/mortality , Endodermal Sinus Tumor/pathology , Endodermal Sinus Tumor/therapy , Humans , Lymph Nodes/pathology , Male , Middle Aged , Neoplasms, Germ Cell and Embryonal/mortality , Neoplasms, Germ Cell and Embryonal/therapy , Orchiectomy , Retroperitoneal Space , Retrospective Studies , Seminoma/mortality , Seminoma/pathology , Seminoma/therapy , Survival Rate , Teratoma/mortality , Teratoma/secondary , Teratoma/therapy , Testicular Neoplasms/mortality , Testicular Neoplasms/therapy , Young AdultABSTRACT
PURPOSE: Some nonseminomatous germ cell tumors are resistant to any type of chemotherapy. Control of embryonal carcinoma cells is crucial to manage nonseminomatous germ cell tumors. We established SOX2 targeting therapy in an embryonal carcinoma model. MATERIALS AND METHODS: SOX2 expression was evaluated in a series of testicular germ cell tumor tissue samples. The antitumor effect of SOX2 knockdown was analyzed in vitro and in vivo using an embryonal carcinoma model. RESULTS: In testicular germ cell tumor tissue SOX2 was expressed in the foci of embryonal carcinoma but negative in seminoma and yolk sac tumors. In an embryonal carcinoma model SOX2-siRNA induced apoptotic cell death in vitro and significant growth suppression in vivo. CONCLUSIONS: This study shows the therapeutic potential of SOX2 silencing for embryonal carcinoma. However, further improvements are needed in SOX2-siRNA delivery to the tumor.
Subject(s)
Carcinoma, Embryonal/metabolism , Carcinoma, Embryonal/therapy , SOXB1 Transcription Factors/antagonists & inhibitors , SOXB1 Transcription Factors/metabolism , Testicular Neoplasms/metabolism , Testicular Neoplasms/therapy , Animals , Carcinoma, Embryonal/pathology , Cell Death , Cell Line, Tumor , Disease Models, Animal , Gene Silencing , Immunohistochemistry , Male , Mice , Mice, Inbred Strains , RNA, Small Interfering/therapeutic use , Seminoma/metabolism , Seminoma/pathology , Testicular Neoplasms/pathology , TransfectionABSTRACT
T-cell factor 3 (TCF3), a downstream effector of Wnt signaling in embryonic stem (ES) cells, plays an important role in pluripotent self-renewal and proliferation. Loss of TCF3 delays the differentiation of mouse ES cells. The purpose of this study was to investigate the effect of TCF3 on embryonal carcinoma (EC). The mouse F9 EC cell line and a tumor-bearing mouse model were used to evaluate the anti-EC tumor effects of TCF3 in vitro and in vivo, respectively. The overexpression of TCF3 significantly inhibited proliferation, colony-forming and migration in F9 EC cells by approximately 30, 45 and 30%, respectively. The in vivo mouse model showed that the overexpression of TCF3 significantly reduced tumor volume (36.4%) and tumor weight (34.8%), malignancy progression and local infiltration and prolonged the life span of tumor-bearing mice. Overexpression of TCF3 significantly down-regulated Oct4 expression in the F9 EC cells. The results indicate that TCF3 is an inhibitor of the malignant phenotypes of embryonal carcinoma through the regulation of Oct4 expression.
Subject(s)
Carcinoma, Embryonal/metabolism , Carcinoma, Embryonal/pathology , Embryonal Carcinoma Stem Cells/metabolism , Embryonal Carcinoma Stem Cells/pathology , Octamer Transcription Factor-3/metabolism , Transcription Factor 7-Like 1 Protein/biosynthesis , Animals , Carcinoma, Embryonal/genetics , Carcinoma, Embryonal/therapy , Cell Differentiation/physiology , Down-Regulation , Female , Genetic Therapy , HeLa Cells , Humans , Male , Mice , Mice, Inbred BALB C , NIH 3T3 Cells , Signal Transduction , Transcription Factor 7-Like 1 Protein/genetics , Transcription Factor 7-Like 1 Protein/metabolismSubject(s)
Androgens/metabolism , Carcinoma, Embryonal/metabolism , Hyperandrogenism/etiology , Mixed Tumor, Malignant , Neoplasms, Germ Cell and Embryonal/metabolism , Seminoma/metabolism , Teratoma/metabolism , Testicular Neoplasms/metabolism , Adult , Androgens/blood , Carcinoma, Embryonal/complications , Carcinoma, Embryonal/pathology , Carcinoma, Embryonal/therapy , Chemotherapy, Adjuvant , Gynecomastia/etiology , Humans , Hyperandrogenism/blood , Male , Middle Aged , Neoplasm Staging , Neoplasms, Germ Cell and Embryonal/complications , Neoplasms, Germ Cell and Embryonal/pathology , Neoplasms, Germ Cell and Embryonal/therapy , Orchiectomy , Positron-Emission Tomography , Seminoma/complications , Seminoma/pathology , Seminoma/therapy , Teratoma/complications , Teratoma/pathology , Teratoma/therapy , Testicular Neoplasms/complications , Testicular Neoplasms/pathology , Testicular Neoplasms/therapy , Tomography, X-Ray Computed , Treatment Outcome , Up-RegulationABSTRACT
OBJECTIVE: Vulvar cancer is rare in Eastern females, especially in pre- and peripubertal girls. The prognosis of vulvar cancer is poor and treatment is variable. CASE REPORT: A 14-year-old girl suffered from a left vulvar tenderness mass and underwent excision of the mass. The diagnosis of the pathology was vulvar yolk tumor with an embryonal carcinoma. After the vulvectomy, inguinal area lymph node dissection, chemotherapy (bleomycin, etoposide and cisplatin) treatment and radiotherapy, metastasis to lung was also noted after eight months. Resection of lung tumor was performed. She received chemotherapy with a combination of paclitaxel, ifosphamide and cisplatin (TIP) and received peripheral blood stem cell transplantation (PBSCT) twice and chemotherapy treatment of gemitabine and oxaliplatin (GEMOX). Up until now, the patient has been free of disease. CONCLUSION: High-dose TIP and GEMOX chemotherapy plus PBSCT for bone marrow rescues could be considered to treat patients with metastatic malignant vulvar germ cell tumor after failed first-line chemotherapy and radiation.