Novel heterozygous mutation in the PTEN gene associated with ovarian germ cell tumor complicated by growing teratoma syndrome and overgrowth in a two‐year‐old female

Growing teratoma syndrome (GTS) is a condition in which mature teratoma with negative tumor markers arises at the site of a treated malignant germ cell tumor. Pathogenic variants in PTEN have been reported to cause autosomal dominant cancer predisposition syndromes and are associated with germ cell tumors. We report the association of a novel heterozygous pathogenic variant in PTEN and very early onset ovarian germ cell tumor complicated by GTS as well as overgrowth syndrome. This marks the youngest reported patient to have developed GTS following treatment of her primary malignant ovarian germ cell tumor.     

High‐dose chemotherapy followed by autologous peripheral blood stem cell transplantation for recurrent primary mediastinal malignant germ cell tumor: A case report

A 15‐yr‐old boy presented with an anterior mediastinal mass, multiple lung metastases and obstruction of the left brachiocephalic vein, the superior vena cava and the subclavian vein. Tumor biopsy by CT guidance confirmed a diagnosis of GCT. Five courses of BEP therapy were performed, and CT of the chest revealed reduction in the anterior mediastinal mass and disappearance of the multiple lung metastases. We performed the anterior mediastinal mass extraction followed by adjuvant chemotherapy consisting of ICE and TIP. However, the AFP levels became elevated soon after. Abnormal accumulation was observed in the right upper lung by DW‐MRI. After the operation, two courses of TI chemotherapy and two courses of HDCT followed by auto‐PBSCT were performed. He was complicated with auditory disorder and renal dysfunction. Although HDCT followed by auto‐PBSCT was effective for the relapsed primary mediastinal GCT, a treatment strategy avoiding late complications is warranted.     

The challenges of high‐dose chemotherapy in CNS tumors

High‐dose, myeloablative chemotherapy with hematopoietic stem cell rescue is used in children and young adults with brain tumors for which conventional therapy is either excessively toxic (e.g., radiotherapy in infants) or ineffective. Thus, the aims of such strategies are to improve both quantity and quality of life. Whether high‐dose chemotherapy is less neurotoxic and more effective than other therapeutic approaches is still controversial. We will consider the difficulties in analyzing published data and the challenges of designing effective clinical trials that test high‐dose chemotherapy in patients with brain tumors. Pediatr Blood Cancer 2010;54:652–653. © 2010 Wiley‐Liss, Inc.     

Management of pineal non-germinoma germ cell tumor with residual teratoma and normal alpha-fetoprotein

A 16-year-old white male presented with multiple abnormal extraocular movements secondary to an enhancing pineal tumor. Subtotal resection of the lesion revealed a mixed malignant germ cell tumor. The pre-operative serum alpha-fetoprotein (AFP) was markedly elevated at 155 IU/L. The patient subsequently received radiotherapy and adjuvant chemotherapy consisting of cisplatin rotating monthly with vincristine and cyclo-phosphamide, with dramatic tumor regression and return of AFP to normal. Eighteen months later the persistence of a substantial tumor mass despite a normal AFP raised concern for residual active tumor. Histological examination of the resected lesion revealed benign teratoma and fibrous tissue. Repeat surgical intervention may contribute to the management of mixed malignant germ cell tumors, which demonstrate a persistent mass following an initial response to treatment. © 1994 Wiley-Liss, Inc.     

Ovarian germ cell tumors in children: a clinical study of 66 patients

BACKGROUND: Ovarian germ cell tumors are rare in childhood. The aim of this study is to review clinical presentation, management, and outcome in a two-center series of girls with ovarian germ cell tumor. PROCEDURE: The records of 66 patients (median age 9 years) with histologically proven ovarian germ cell tumor (either benign or malignant), treated over a 44-year-span, were reviewed. RESULTS: Pain and an abdominal mass were the most frequent symptoms. The tumors were right-sided in 35, left-sided in 28, and bilateral in 3. Most patients (52) were stage I, 4 were stage II, 6 stage III, and 1, with liver metastases, stage IV. Sixteen patients had an emergency operation for tumor torsion. Unilateral salpingo-oophorectomy was the most frequently performed procedure (n = 46), and ovarian-sparing tumorectomy was performed in 9 patients (one bilaterally). Histologically, teratomas were found most frequently (mature: 45, immature: 9), followed by mixed tumors (n = 7), yolk sac tumors (n = 3), dysgerminoma (n = 2), gonadoblastoma (n = 2), and embryonal carcinoma (n = 1). Surgical removal of the tumor with or without the ovary and/or adnex was the sole treatment in 55 patients, chemotherapy was administered in 10 and radiotherapy + chemotherapy in one. Intra-operative spillage of tumoral fluid occurred in six; this did not influence outcome in five. Recurrence was observed in three patients. Two patients, with malignant disease, died. The 64 survivors are now between 8 months and 44 years after treatment. CONCLUSIONS: With a recurrence rate of 4.5% and a mortality rate of 3%, this series confirms the excellent prognosis for girls with ovarian germ cell tumor (GCT).     

自体外周血干细胞移植治疗实体瘤中不良反应研究

目的 探讨小儿自体外周血干细胞移植(auto-PBSCT)预处理的不良反应及防治.方法 观察30例实体瘤患儿接受auto-PBSCT的急性相关不良反应.30例中男22例,女8例;其中神经母细胞瘤20例,横纹肌肉瘤3例,原发性神经外胚层瘤(PNET)2例,肝母细胞瘤1例,视网膜母细胞瘤3例,肾母细胞瘤1例.结果 外周血造血干细胞回输后+3～+14 d内不良反应表现为1级21例,Ⅱ级6例,Ⅲ级1例,Ⅳ级2例(死亡1例);经对症处理后于预处理+15～+22 d 25例无不良反应;2例1级,2例Ⅱ级.30例患儿均有不同程度口腔溃疡、呕吐、腹泻及离子紊乱,有心肌损伤、心律不齐及心衰表现5例,出血性膀胱炎Ⅰ例,肝转氨酶升高改变15例,消化道大出血低血容量休克1例,多脏器功能衰竭死亡1例.经过规律抗感染及对症治疗后,30例患儿中+22 d不良反应好转率为86.7%(26/30),+30～+40 d不良反应除2例因病情进展外均好转,移植后1年无病生存率为70.0%(21/30),移植2年后无病生存率为53.3%(16/30).29例患儿于+15～+40 d脏器损伤恢复正常.结论 虽然auto-PBSCT预处理可引起各系统的不良反应,但多可在短期内恢复,对患儿生活质量影响较小.在治疗过程中防治上述不良反应,可有效地提高实体瘤缓解率.     

C-PEB方案联合手术治疗儿童恶性生殖细胞瘤3例并文献复习

目的探讨儿童恶性生殖细胞瘤的临床特点及治疗方法。方法回顾性分析我中心收治的3例恶性生殖细胞瘤病例,均经C-PEB方案联合手术治疗。结果目前3例随访时间分别达2年、2年半、3年,均为完全缓解。结论 C-PEB方案联合手术治疗恶性生殖细胞瘤安全有效。     

Immunotherapy with autologous dendritic cells and tumor antigens for children with refractory malignant solid tumors

Abstract:  Immature DCs were generated from the peripheral blood monocytes from five children with refractory solid tumors (Ewing sarcoma, synovial sarcoma, neuroblastoma) using GM-CSF and IL-4. These DCs were then pulsed with tumor-specific synthetic peptides or tumor lysates in the presence of the immunogenic protein KLH for 12 h. Pulsed DCs were administered subcutaneously every one or two weeks in an outpatient setting without any toxicity. In one patient with Ewing sarcoma, the residual tumor disappeared following autologous PBSCT and DC therapy, and a complete remission has been maintained for 77 months. In two patients with synovial sarcoma or with neuroblastoma, growth of the tumors was temporally suppressed for one and 10 months, respectively, followed by their exacerbation. A DTH response was detected against KLH in all five patients and against the tumor lysate in one patient. In the patients with a possible DC-mediated anti-tumor effect, the number of CD8⁺ HLA-DR⁺ lymphocytes and INF-γ⁺CD8⁺ lymphocytes increased and an elevation of the NK cell cytotoxic activity was observed during and/or after DC therapy. DC-based immunotherapy may therefore be a feasible, well-tolerated and promising approach in the treatment of children with refractory malignant tumors.     

Multimodal treatment including tandem high‐dose chemotherapy and autologous stem cell transplantation in children with anaplastic ependymomas

In this study, we evaluated the results of multimodal treatment that included tandem HDCT/auto‐SCT in children with anaplastic ependymomas. Fourteen patients with anaplastic ependymomas were enrolled from 2006 to 2014. Six cycles of induction chemotherapy were administered to all patients before they underwent tandem HDCT/auto‐SCT. Patients who were older than 3 years of age were administered RT after two cycles of induction chemotherapy. In patients under 3 years of age, RT was either omitted or delayed until they reached 3 years of age, if the patients experienced CR after tandem HDCT/auto‐SCT. All patients, including two who experienced disease progression during induction treatment, underwent the first HDCT/auto‐SCT, and 13 subsequently underwent the second HDCT/auto‐SCT. One patient died from hepatic VOD during the second HDCT/auto‐SCT; other toxicities occurring during tandem HDCT/auto‐SCT were manageable. Relapses or progression occurred in seven patients, and five of seven of them remain alive till date after salvage treatment, including surgery and RT. The 5‐year overall and event‐free survival rates were 85.1% ± 9.7% and 50.0% ± 13.4%, respectively. These findings suggest that multimodal treatment including tandem HDCT/auto‐SCT could be a feasible option for improving survival in children with anaplastic ependymomas.