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Apurinic/apyrimidinic endonuclease expression in pediatric yolk sac tumors.

BACKGROUND: The enzyme apurinic/apyriminidic endonuclease/redox factor 1 (Ape1/ref1), a key protein in the base excision repair pathway, displays repair and redox activity. We examined the role of Ape1/ref1 and a protein it regulates, hypoxia inducible factor 1 alpha (HIF-1 alpha) in pediatric yolk sac tumors. PATIENTS AND METHODS: Using an immunohistochemical evaluation, 16 pediatric yolk sac tumors were evaluated for Ape1/ref1 and HIF-1 alpha expression. Samples were obtained from archival tissue. RESULTS: We demonstrated high levels of expression of Ape1/ref1 in 14/16 of the tumors. This expression was limited to the nucleus of the viable portion of each tumor. High levels of HIF-1 alpha expression was noted in half of the same tumors and localized to both the nucleus and cytoplasm of the viable tumor. CONCLUSIONS: The high levels of expression of Ape1/ref1 in this group of chemosensitive tumors may be related to the subcellular location or redox regulatory activity of one of the other factors controlled by Ape1/ref1.

Carbon-Oxygen Lyases↗

Insulin-like growth factor II messenger ribonucleic acid expression in Wilms tumor, nephrogenic rest, and kidney.

BACKGROUND: Wilms tumors (WTs) are embryonic neoplasms of the kidney that are believed to arise from primitive metanephrogenic blastema. Our previous reports and those of others indicate that WTs show an increased expression of insulin-like growth factor II (IGF-II) mRNA. However, the precise role of IGF-II on Wilms tumorigenesis is not known. A central question is to determine whether the increased IGF-II expression in WTs simply reflects the fetal nature of WTs (effect), or is induced by specific changes in gene expression (cause). EXPERIMENTAL DESIGN: This study included 31 sporadic WTs, 7 fetal and 3 adult kidneys and 1 yolk sac tumor. Clinical and histologic summaries of WT cases are shown in Table 1. In WTs, the relative area of blastemal, epithelial, poorly differentiated spindle cell and heterologous cell components were assessed. Dot and Northern blot hybridization, using cDNA probes, were done to assess the level of IGF-II mRNA expression. In situ RNA hybridization was employed to localize IGF-II transcripts. Immunohistochemistry was applied to frozen sections to demonstrate cytokeratin and type-IV collagen. These results were then correlated with the histology of WTs and their precursor lesions, i.e., nephrogenic rests (NRs). RESULTS: Dot blot hybridization indicated that IGF-II transcripts were 32- to 64-fold more abundant in WTs than in the adjacent uninvolved kidneys. In situ hybridization showed that WTs, NRs, and fetal kidney shared a common feature in which IGF-II transcripts were predominantly associated with blastema. However, WTs and NRs differed from fetal kidney in that occasional epithelial structures and dense blastema showed aberrant, sustained IGF-II expression. CONCLUSIONS: The data indicate two points. 1) There is an inverse correlation between nephroblastic differentiation and IGF-II expression in developing fetal kidney. 2) The IGF-II expression in WTs and NRs does not simply reflect the embryonal nature of the tumor but is rather significantly altered, suggesting a role as a transforming growth factor in Wilms tumorigenesis.

Adolescent↗

Primary intracranial germ cell tumors: a clinical analysis of 153 histologically verified cases.

The authors analyzed 153 cases of histologically verified intracranial germ cell tumors. The histological diagnosis was germinoma in 63 patients (41.2%), teratoma in 30 (19.6%), and other types of tumors in 60 patients (39.2%). The patients were treated by a consistent policy of surgical removal with histological verification followed by radiation therapy with or without chemotherapy. The 10- and 20-year survival rates of patients with pure germinoma were 92.7% and 80.6%, respectively. The 10-year survival rates of patients with mature teratoma and malignant teratoma were 92.9% and 70.7%, respectively. Patients with pure malignant germ cell tumors (embryonal carcinoma, yolk sac tumor, or choriocarcinoma) had a 3-year survival rate of 27.3%. The mixed tumors were divided into three subgroups: 1) mixed germinoma and teratoma; 2) mixed tumors whose predominant characteristics were germinoma or teratoma combined with some elements of pure malignant tumors; and 3) mixed tumors with predominantly pure malignant elements. The 3-year survival rates were 94.1% for the first group, 70% for the second group, and 9.3% for the third group, and the differences were statistically significant. Twenty-six patients with malignant tumors received chemotherapy that consisted of cisplatin and carboplatin combinations with or without radiation therapy. However, chemotherapy was not significantly more effective than radiation therapy alone. From these treatment results, the authors classified tumors into three groups with different prognoses and proposed a treatment guideline appropriate for the subgroups.

Adolescent↗

[Endodermal pulmonary tumor resembling a fetal lung].

We report a case of a 56-year-old man who developed a flu-like syndrome associated with weight loss. Chest X-ray revealed a homogeneous round lesion of the lung with sharply defined margins in the central lobe. At pathology, the tumor was found to be an endodermal pulmonary tumor resembling a fetal lung. This uncommon tumor is generally a fortuitous chest X-ray finding seen as a rounded peripheral opacity. Diagnosis is based on pathology examination of the surgical specimen. Complementary investigations are not contributory. Unlike blastoma, a differential diagnosis, prognosis is generally good.

Diagnosis, Differential↗

Yolk sac tumor and testicular microlithiasis.

Yolk sac tumor (YST) of prepubertal testis is a peculiar neoplasm with overall good prognosis. There are no known conditions associated with the development of this tumor. The case of a 2-year-old boy with testicular YST and presence of testicular microlithiasis (TM) in the adjacent-still-recognizable testicular tissue is reported. Concentrically laminated microliths were clearly extratubular structures. Ultrasound of the remaining testis revealed microlithiasis. Bilateral TM is being recognized with increasing frequency due to the extensive use of ultrasound. The exact meaning of its finding has not been definitively elucidated, but the association of TM with cryptorchidism, intratubular germ cell neoplasia and germ cell tumors either of the testis or mediastinum is on record. The combination of prepubertal YST and bilateral TM has not been reported previously. Finding of TM at this early age suggests a congenital deranged Sertoli cell function and/or an abnormal gonadal embryogenesis in its pathogenesis.

Calcium↗

[Testis yolk sec tumor--a case report].

A 16-months old normal boy, a right testicular mass was discovered incidentally by his grandmother. Right inguinal orchiectomy was performed. Histological examination showed yolk sac tumor of testis. A preoperative alpha-fetoprotein level was markedly elevated at 13568.9 ng/ml, by the end of the twelve postoperative months, the serum alpha-fetoprotein levels was 118 ng/ml. The patient is doing well one-year postoperatively.

Endodermal Sinus Tumor↗

CT and MRI features of intracranial germ cell tumors.

The computed tomographic (CT) and magnetic resonance imaging (MRI) features of 73 histologically proven primary intracranial germ cell tumors were analysed. CT images were available for all 73 patients, and 22 of them were also examined by MRI. The tumors were classified as germinoma, mature teratoma, immature or malignant teratoma, yolk sac tumor, choriocarcinoma, embryonal carcinoma and mixed type. Germinoma was revealed as a high- or slightly high-density area on plain CT scan, and was enhanced homogeneously. MRI revealed iso- or slightly low signal intensity on T1-weighted images, and iso- or high intensity on T2-weighted images. Mature teratoma, which had a clear margin on neuroradiological images, was characterized by mixed density on CT scans, often showing large cysts and area of calcification. Immature or malignant teratoma had a similar pattern to that of mature teratoma, but the cystic components and area of calcification tended to be less and smaller respectively. The tumor margin was obscure in malignant teratoma, and perifocal edema was observed in some cases. The shape of yolk sac tumors was irregular. Plain CT scan revealed an iso- or low-density mass with good heterogeneous enhancement. Perifocal edema was observed in some cases. In mixed germ cell tumors, MRI imaging was useful for detecting teratomatous components, particularly fatty components. Although definite histological diagnosis cannot be achieved by CT and/or MRI alone, detailed analysis of neuroradiological images are useful for predicting the histological diagnosis.

Brain Neoplasms↗

Familial clustering of malignant germ cell tumors and Langerhans' histiocytosis.

Three sisters in a family with seven children whose grandmother had an ovarian embryonal carcinoma experienced development of malignant and a malignant-like situation in childhood. Two were diagnosed as having malignant germ cell tumors of the ovary, and the third was found to have Langerhans' histiocytosis. The two girls with germ cell tumor shared an identical human leukocyte antigen, whereas the sister with histiocytosis shared one identical haplotype with them. All three children have been treated successfully with chemotherapy and are doing well off of treatment.

Aged↗

Hematologic disorders associated with primary mediastinal nonseminomatous germ cell tumors.

BACKGROUND: The association between primary germ cell tumors of the mediastinum (the space between the lung pleura that contains the heart and other chest viscera) and hematologic malignancies has been described by retrospective analysis of patients treated at individual clinical centers. To better characterize the risk of hematologic disorders in patients with extragonadal germ cell tumors and to describe the clinical and biologic features of the disorders, we studied an unselected population in a large, international, multicenter database. METHODS: Six hundred thirty-five patients treated at 11 centers in the United States and Europe from 1975 through 1996 were evaluated retrospectively. RESULTS: A hematologic disorder was observed in 17 patients with germ cell tumors. All cases developed among the 287 patients with primary mediastinal nonseminomatous germ cell tumors, giving an incidence rate in this group of 2.0% (95% confidence interval [CI] = 1.1%-3.1%) per year over a median follow-up time of 3 years. The risk of developing hematologic disorders was statistically significantly increased in patients with primary mediastinal nonseminomatous germ cell tumors in comparison with the age-matched general population (standardized incidence ratio = 250; 95% CI = 140-405). The median time to onset of hematologic neoplasia was 6 months (range, 0-47 months), and the median survival after diagnosis of the hematologic disorder was 5 months (range, 0-16 months) (two-sided P<.0001, comparing survival from the time of diagnosis of the germ cell tumor of patients with and without hematologic disorders). CONCLUSION: In our study, approximately one in 17 patients with primary mediastinal nonseminomatous germ cell tumors was affected by a hematologic disorder, whereas no cases were seen among 334 patients with other extragonadal germ cell tumors. The hematologic disorder had a statistically significant impact on prognosis, with none of the 17 reported patients surviving for more than 2 years.

Adolescent↗

Treatment of a pineal yolk sac tumor: report of one case.

Pineal yolk sac tumors are rare. We present a case of pineal yolk sac tumor in a 15-year-old boy with hydrocephalus and possible cerebrospinal dissemination. He was treated by surgical excision, craniospinal axis irradiation, PVBE (cisplatin, vinblastine, bleomycin, and etoposide) chemotherapy, and intrathecal methotrexate chemotherapy. There was no tumor recurrence at follow-up 2.5 years after treatment.

Adolescent↗

[Ovarian tumors in children].

Ovarian tumors in children are uncommon. We reviewed all cases of ovarian tumors treated at the Department of Pediatric Surgery of Vicenza Regional Hospital from 1979 to 1994. They include 6 cases of cystic teratoma and 1 gonadoblastoma; the malignant lesions included 1 immature teratoma, 1 dysgerminoma, 1 yolk-sac tumors and 1 patient with ovarian infiltration from malignant leukemia. Only the patient with leukemia died of progression of the disease. These data show that most ovarian masses are benign. Germ-cell tumors are the most common malignancy and epithelial cell tumors are less likely. Epithelial cyst and teratomas are the most common benign lesions. Although ultrasound was 100% accurate in the diagnosis of ovarian pathology, the ultrasonogram could not distinguish between benign and malignant lesions.

Adolescent↗

Malignant müllerian mixed tumor of the uterus with a prominent alpha-fetoprotein-producing component of yolk sac tumor.

We describe a case of a 64-year-old woman with a malignant müllerian mixed tumor of the uterus containing a prominent component of yolk sac tumor, which was associated with high serum levels of alpha-fetoprotein. The neoplasm pursued an aggressive course and the patient died 2 months postoperatively. This is the first case of this type and only the ninth alpha-fetoprotein-secreting endometrial cancer in the literature.

Adult↗

Sustained complete remission in a patient with platinum-resistant ovarian yolk sac tumor.

BACKGROUND: Yolk sac tumors of the ovary are generally very responsive to chemotherapy; however, they are difficult to manage in the setting of platinum resistance where treatment options are limited and outcomes are poorer. CASE: We present a 39-year-old woman who had a platinum-resistant yolk sac ovarian tumor. She achieved complete remission on an innovative regimen of docetaxel, gemcitabine, and thalidomide. CONCLUSION: The combination of docetaxel, gemcitabine, and thalidomide might be an active regimen for platinum-resistant ovarian nondysgerminomas and further investigation of this combination is warranted.

Adult↗

The pathology of late recurrence of testicular germ cell tumors.

A total of 91 men had histologically documented late recurrences of testicular germ cell tumors characterized by a complete response to treatment with a subsequent disease-free interval of at least 2 years and no evidence of a second primary lesion. Ninety percent of the patients for whom information was available received chemotherapy shortly after their initial diagnosis of testicular germ cell tumors; most of the other patients were known to have stage I disease initially. Overall, 60% of patients had teratoma in their late recurrences, including 20 patients (22%) in whom teratoma was the only element. Thus, teratoma was the most common type of neoplasm in late recurrences. Excluding teratoma coexisting with other types of neoplasms, yolk sac tumor was the most frequent type of tumor in patients with late recurrence. It occurred in 47% of patients, either alone or with teratoma, another nonteratomatous germ cell tumor type, or a "nongerm cell malignant tumor." Unusual types of yolk sac tumor, including glandular, parietal, clear cell, and pleomorphic patterns, were seen frequently in late recurrences and often raised differential diagnostic problems with "nongerm cell" carcinomas. A smaller number of late recurrences consisted of other types of neoplasms. Twenty percent of patients with late recurrence had a nonteratomatous germ cell tumor other than yolk sac tumor, either alone, with yolk sac tumor, or with a "nongerm cell malignant tumor." Most of these nonteratomatous germ cell tumors other than yolk sac tumor were embryonal carcinoma, although rarely seminoma and choriocarcinoma were encountered. "Nongerm cell malignant tumors," including both sarcomas and carcinomas of various types, occurred in 23% of late-recurrence patients, either alone or with a nonteratomatous germ cell tumor. Late recurrences were seen in many different sites in these patients, including the retroperitoneum, abdomen, pelvis, liver, mediastinum, lung, bone (femur, vertebra, and rib), lymph nodes outside the retroperitoneum and mediastinum (supraclavicular, neck, and axillary regions), scrotum and inguinal regions, adrenal gland, chest wall, and buttocks. Follow-up data were available for 79 of the 91 patients studied. Duration of follow-up ranged from 2 months to 13 years after the patient's first late recurrences; the mean length of follow-up was 4.8 years. Patients whose late recurrences consisted of teratoma only had the most favorable outcomes, with 79% having no evidence of disease at last follow-up. Patients whose late recurrences consisted of pure "nongerm cell malignant tumor" or pure germ cell tumor (yolk sac tumor or other types) had a much worse prognosis: Only 36% to 37% were alive with no evidence of disease. Patients with two different types of nonteratomatous malignancies in their late recurrences had a dismal clinical course: Only 17% with both yolk sac tumor and other nonteratomatous germ cell tumor had no evidence of disease, whereas no patient with both nonteratomatous germ cell tumor and "nongerm cell malignant tumor" was disease free. Late recurrences consisting of teratoma alone often have a favorable outcome, but the prognosis in all other patients is poor. Furthermore, late recurrence is not likely to respond to chemotherapy and is best treated by surgical excision when possible.

Adolescent↗

Primary yolk sac tumor in the spinal cord.

A case of a primary yolk sac tumor of the spinal cord is reported. The patient was a 17-month-old Japanese girl, who was found to have an intramedullary mass at the upper thoracic level. The preoperative diagnosis was primary glioma, but histological examination of the surgical specimen revealed a yolk sac tumor. As there were no other lesions, the spinal cord lesion was considered to be the primary tumor. Based on our previous experience, we treated this patient with low-dose irradiation followed by combination chemotherapy with cisplatin, vinblastine and bleomycin. However, the effectiveness of this therapy was poor in this particular case, and the patient died of pyelonephritis with uncontrollable imbalance of serum electrolytes.

Combined Modality Therapy↗

[Malignant germ cell tumours. Multicenter prospective trial in Polish Pediatric Group for Solid Tumours (years 1998-2000)].

UNLABELLED: Germ cell tumors constitute about 3% of all pediatric malignancies. Since 1998 the multicenter trial was initiated in Poland. MATERIAL AND METHODS: 95 children (aged from 1 month to 17 years--mean 9.2 years) were registered. There were 38 boys and 57 girls. Diagnosis was made on histopathological examination in 88% patients (pts) and in 12% was established on imaging and biochemical findings (elevated AFP). Mixed germ cell tumor and yolk sac tumor prevelaged. AFP was elevated in 72% pts; in 26% it was over 15.000. Primary tumor was localized in gonads (59%) and in sacrococcygeal region (30%). Following disease stages were identified: I and II--41% pts, III--34%, IV--25%. All patients were treated according to French TGM'95 protocol. 43 belonged to high risk and 52 to standard risk group. 77 children completed therapy, 15 continue treatment and 3 were lost from follow-up. RESULTS: Among children who were off therapy, 70 (91%) are alive in a complete remission (second remission in 3 cases). Survival in high risk group is 89%, while in standard risk group is 93%. Median time of follow-up is 31 months from the beginning of treatment and 25 months after completion of therapy. 7 children died; all had progressive disease. CONCLUSION: The outcome of malignant germ cell tumors treatment in Poland is favourable and comparable to results showed by other study groups in the world.

Adolescent↗

[Yolk sac tumor resected by transverse sternotomy: a case report].

Transverse sternotomy was performed in a 39-year-old man having bilateral lung metastatic lesions of yolk sac tumor. This approach provided an excellent operative field. Bilateral partial lobes including parietal pleura and diaphragma were readily resected. As described in this paper, transverse sternotomy is one of the beneficial method in the thorough surgical treatment for metastatic bilateral lung lesion.

Adult↗