CLINICAL EXPERIENCE WITH YOLK SAC TUMORS AND TERATOMA IN CHILDREN

Between 1971 and 1993, 12 children with testicular germ cell tumors were treated at the Department of Urology, Faculty of Medicine, Kyoto University. Seven patients had yolk sac tumors and 5 had mature teratoma. Of the 7 patients with yolk sac tumors, 6 had stage I and 1 had stage III tumors. Initial management of the stage I tumors consisted of high orchiectomy in 5 patients and high orchiectomy plus retroperitoneal lymph node dissection in 1 patient. Of these 6 patients, 4 were cured by surgery alone but lung metastases developed in the other 2 patients. One of them was salvaged with thoracotomy and chemotherapy but the other died of tumor. The patient with stage III tumor had bulky tumor spread to lung and retroperitoneum, but seems to have been cured by chemotherapy followed by resection of the residual mass although follow-up is still inadequate (14 months). Six of the 7 patients (85.7%) are alive 13 months to 21 years after diagnosis. Five patients with mature teratoma were treated by high orchiectomy or, more recently, enucleation and all are alive 4 months to 22 years after surgery.     

小儿早期睾丸卵黄囊瘤12例报告

目的：提高对小儿早期睾丸卵黄囊瘤的诊断与治疗水平。方法：回顾性分析12例小儿早期睾丸卵黄囊瘤的病例资料。结果：12例患者术前行阴囊B超示睾丸增大，内部回声不均匀，7例可见睾丸内积液改变；甲胎蛋白(AFP)值均明显升高。12例均行根治性睾丸切除术，术后行病理检查确诊。术前、术后均未行化疗，9例随诊5年未见复发，2002年就诊的3例目前未见复发症状。结论：小儿早期睾丸卵黄囊瘤可根据相关检查结果，结合病理检查确诊。治疗方法为行根治性睾丸切除，可不作化疗，预后较好。     

Malignant sacrococcygeal teratoma--endodermal sinus, yolk sac tumor--in infants and children: a 32-year review

Fifteen cases of malignant sacrococcygeal teratoma were treated at our hospital over the last 32 years. These included five cases of endodermal sinus (yolk sac) tumor that arose in otherwise benign or immature teratoma, and ten cases of pure endodermal sinus (yolk sac) tumor. Most were females, and only one was a neonate. The presence of symptoms almost always indicated local extension or distant metastases. According to Altman's classification, all but two of these malignant tumors were Types III and IV. The resectability was low, but with aggressive radiotherapy and chemotherapy, second look operations in five have been possible with increasing optimism for survival. Two of five patients with secondary resections are alive and tumor-free almost two years after therapy was discontinued. So far, only the newborn is a long-term (14 years) cure.     

Perinatal (fetal and neonatal) germ cell tumors

Background/Purpose

Germ cell tumors are relatively common in the fetus and neonate and are the leading neoplasms in some perinatal reviews. The purpose of this study is to focus on the fetus and neonate in an attempt to determine the various ways germ cell tumors differ clinically and morphologically from those occurring in the older child and adult and to show that certain types of tumors have a better prognosis than others.

Methods

The author conducted a retrospective review of perinatal teratomas and other germ cell tumors reported in the literature and of patients treated and followed up at Children’s Hospital San Diego and Children’s Hospital Los Angeles. Only fetuses and infants less than 2 months of age with adequate clinical and pathologic data were accepted for review.

Results

Five hundred thirty-four fetuses and neonates presented with teratomas diagnosed prenatally (n = 226) and at birth (n = 309). The most common initial finding was a mass, noted either by antenatal sonography or by physical examination during the neonatal period, with signs and symtoms referable to the site of origin. Overall polyhydramnios was next followed by respiratory distress and stillbirth. The number of mature and immature teratomas was approximately the same. The incidence of teratoma with yolk sac tumor either at presentation or at recurrence was 5.8%, and the survival rate was 39%. Sacroccoccygeal teratomas had the highest incidence of yolk sac tumor at 10%. Recurrent disease in the form of either teratoma or yolk sac tumor developed in 5% of patients. All individuals with teratomas who survived received surgical resection.

Conclusions

Some germ cell tumors of the fetus and neonate have a better prognosis than others. Neonates with gastric teratomas have the best survival rates, and those with intracranial germ cell tumors the worst. Fetuses with teratomas detected antenatally have 3 times the mortality rate compared with postnatally diagnosed neonates. Although perinatal teratomas have a relatively low recurrence rate of 5%, close follow-up with imaging studies and serum α-fetoprotein determinationsis is strongly recommended. Surgical resection alone may be adequate therapy for teratomas with nonmetastatic, microscopic foci of yolk sac tumor. In the nonteratoma group, patients with pure yolk sac tumor and gonadoblastoma have a much better outcome than those with choriocarcinoma, which has a very low survival of rate of 12%. Currently, the use of platinum-based combination chemotherapy has significantly improved the survival rate of infants with advanced malignant germ cell tumor disease.     

Archenteronoma (yolk sac tumors).

Ten cases of archenteronoma are reviewed with a follow-up between 2 mo and 7 yr. Their presentation was similar to that of rhabdomyosarcoma except for testicular tumors that may present as a hydrocele. A good prognosis was found with tumors amenable to primary resection and chemotherapy. Other tumors are best treated initially with chemotherapy before relatively conservative surgery, radiotherapy being used either pre- or postoperatively.     

小儿睾丸肿瘤的诊疗现状

儿童与成人睾丸肿瘤在病理特点、治疗方案、临床预后上均存在明显差异。由于睾丸肿瘤在儿童中发病率低、病理分析较多、治疗方案差别较大,这要求临床医师要掌握丰富的相关医学知识及临床技能,以便对睾丸肿瘤及早诊断、精准分型及合理治疗。目前国内对小儿睾丸肿瘤的研究不多,患者数量相对较少导致研究的局限性和研究偏倚,因此对小儿睾丸肿瘤的认识有限。本文综述了睾丸肿瘤的诊断与治疗进展。     

Extra embryonic elements in testicular tumours

Extra embryonic elements in germ cell tumours resemble the trophectoderm or yolk sac endoderm which are the extra embryonic membranes of the developing embryo. True chorionic (trophoblastic) differentiation with syncytiotrophoblast and cytotrophoblast, perhaps with a villous pattern, is rare and is associated with a very poor prognosis and with hCG production. Isolated syncytiotrophoblastic cells also produce hCG but are prognostically less sinister. Yolk sac elements occur in two thirds of non seminomatous germ cell tumours, and affect all age groups. Pure forms of yolk sac tumour (YST) occur but are not common except in infants. They are often associated with AFP production but AFP is not a specific marker for YST. Yolk sac tumours have a similar prognosis to malignant teratoma undifferentiated (MTU: embrvonal carcinoma).     

Experience with testis sparing surgery for testicular teratoma

PURPOSE: Testicular teratoma is a rare neoplasm affecting the pediatric population and has classically been reported to be the second most common testis tumor in children behind yolk sac tumors. Testicular teratomas are benign and partial orchiectomy may be considered. We describe our single institution experience with testicular teratoma and definitive treatment with testis preserving surgery. MATERIALS AND METHODS: We reviewed the pathology records at our institution for all testicular and paratesticular tumors diagnosed between 1976 and November 2002 in males younger than 18 years. We specifically examined the prepubertal incidence of teratoma, including epidermoid cysts, and our experience with testis preserving surgery. Preoperative and postoperative ultrasonography images were used to calculate the atrophy index following surgery. Patients were contacted for long-term followup. RESULTS: Of 77 primary testicular and paratesticular tumors 38 were diagnosed in prepubertal boys (age younger than 13 years) including 11 mature teratomas and 5 epidermoid cysts. Mean patient age at treatment was 34.4 months (range 4 months to 10 years). All boys presented with a painless scrotal mass, cystic foci within an intratesticular mass on ultrasound and a normal alpha-fetoprotein level. Of the 16 boys with benign teratomas 13 (81%) were treated with a testis sparing procedure. At a mean 7-year followup no patient has presented with recurrent tumor in the ipsilateral or contralateral testicle. Postoperative physical examination and scrotal ultrasound were obtained in 9 patients at a median followup of 10.2 months, and there was no evidence of testicular atrophy or persistent discomfort. CONCLUSIONS: Unlike previously published series based on tumor registries, benign teratoma was the most common pediatric testicular tumor treated at our institution. Our single institution experience with testis preservation and long-term followup confirms the role and safety of this technique. Testis sparing surgery remains our technique of choice for testicular teratoma.     

Endodermal sinus (yolk sac) tumors in infants and children.

Endodermal sinus tumors, as a specific entity, were first proposed and described by Teilum on the basis of morphological and histogenetic features. Recent work utilizing tumor markers (alpha-fetoprotein), immunofluorescent and electron microscopic studies have supported Teilum's original concept as to the origin of these tumors. Five typical presentations of endodermal sinus tumors seen in the pediatric age group were reviewed with reference to the original presentation, the utilization of tumor markers (alpha-fetoprotein) and the prognostic implications of this neoplasm.     

小儿睾丸卵黄囊瘤合并鞘膜积液诊治分析(附7例报告)

目的:提高小儿睾丸卵黄囊瘤的诊治水平,探讨小儿睾丸卵黄囊瘤合并鞘膜积液的临床特点及其中关联。方法:回顾性分析2008年9月至2012年4月收治7例睾丸卵黄囊瘤合并大量鞘膜积液患儿的临床资料。7例均初步诊断为睾丸卵黄囊瘤,临床Ⅰ期。术中快速病理证实为卵黄囊瘤后,行根治性高位精索睾丸切除术。7例术后随访时间3⁴1个月,按术后第1年每个月;第2年每3个月;第3年每6个月随访。内容包括常规体检、血清甲胎蛋白(AFP)、胸片、B超及CT。结果:7例术后病理均证实为睾丸卵黄囊瘤,未累及精索切缘端。6例术后1个月内血清AFP降至正常,诊断为临床Ⅰ期,未行化疗,无复发、转移;1例术后1个月血清AFP116μg/L,诊断为临床Ⅱ期,予PVB方案化疗,术后3个月失访。结论:小儿睾丸卵黄囊瘤合并鞘膜积液易于误诊,应常规检查B超。Ⅰ期患儿可单纯行根治性高位精索睾丸切除术,术后需密切随访;Ⅱ期患儿术后辅以联合化疗。目前尚无证据支持小儿睾丸卵黄囊瘤与鞘膜积液存在关联,其预后与同期病例相仿。     

Clinical and pathological features associated with the testicular tumor of the adrenogenital syndrome

PURPOSE: Testicular tumor of the adrenogenital syndrome is a rare clinical entity found in young men with endocrine disorders. Histologically it resembles Leydig cell tumor. We 1) reviewed the clinical features of testicular tumor of the adrenogenital syndrome and 2) determined if special histopathological features of the tumor and synaptophysin reactivity could distinguish testicular tumor of the adrenogenital syndrome from Leydig cell tumor. MATERIALS AND METHODS: We reviewed the medical and pathological records for all patients with testicular tumor of the adrenogenital syndrome seen at our institution from 1978 to 2004. These tumors were examined by histological and immunophenotypic methods for comparison to Leydig cell tumor. RESULTS: A total of 14 males with an endocrine disorder had pathological evidence of testicular tumor of the adrenogenital syndrome. These tumors were often bilateral (93% or 13 of 14 cases), associated with pain (92% or 12 of 13) and refractory to medical management with high dose exogenous steroids (93% or 13 of 14). Testicular tumor of the adrenogenital syndrome was managed by tumor enucleation in 7 patients (54%) and by radical orchiectomy in 6 (46%). All patients had resolution of pain at 3-month followup. Upon histological review features found to be more common to testicular tumor of the adrenogenital syndrome compared with Leydig cell tumor were nuclear pleiomorphism, low mitotic activity, extensive fibrosis, lymphoid aggregates, adipose metaplasia and prominent lipochrome pigment. Synaptophysin (ICN, Costa Mesa, California) reactivity was strong in testicular tumor of the adrenogenital syndrome but rarely observed in Leydig cell tumor. CONCLUSIONS: In our series medical treatment failed in patients with testicular tumor of the adrenogenital syndrome and conservative surgical therapy was possible in select individuals. We identified special histopathological and immunophenotypic features, including synaptophysin staining, which distinguish testicular tumor of the adrenogenital syndrome from Leydig cell tumor.     

Tumor marker levels in post-chemotherapy cystic masses: clinical implications for patients with germ cell tumors

PURPOSE: Increased tumor markers after induction chemotherapy for patients with germ cell tumor usually represent systemic disease and consequently second line chemotherapy is instituted, while retroperitoneal lymph node dissection (RPLND) is reserved for patients with marker normalization. We report the concentration of alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) in the fluid of post-chemotherapy cystic masses to evaluate this as a potential source for serum marker elevation. MATERIALS AND METHODS: From March 2002 to December 2002, 11 consecutive patients with post-chemotherapy cystic masses underwent RPLND. Following resection, aspirated fluid was analyzed for AFP and HCG. Only 5 post-chemotherapy RPLNDs were performed in patients with increased serum tumor markers, including the 3 patients in our study. Patients with increasing tumor markers and/or multifocal disease with noncystic residual masses after induction chemotherapy underwent salvage chemotherapy despite teratomatous elements in the primary tumor. RESULTS: All 11 patients had teratoma in the orchiectomy specimen and retroperitoneum, including one with malignant transformation. Cystic fluid markers were increased in all patients, 9 of 9 with HCG (range 7.0 to 6,880) and 9 of 11 with AFP (27.5 to 521.2). Two patients with an increased serum AFP before surgery (47.9 and 31.6) had cyst levels of 73.5 and 790.4 respectively. Both serum markers normalized postoperatively. One patient with increased pre-RPLND serum HCG (11.6) had a cyst level of 233. HCG continued to increase postoperatively and the patient died of disease. The remaining 10 patients remain disease free. CONCLUSION: Fluid from cystic teratoma contains variably elevated levels of HCG and AFP in all patients and appears to be independent of serum marker level or pathology. It is possible that a "slow leak" of fluid from cystic teratoma may explain elevated serum markers in selected patients with teratoma and thus may potentially avoid second line chemotherapy.     

Clinical stage I pure yolk sac tumor of the testis in adults has different clinical behavior than juvenile yolk sac tumor

PURPOSE: We evaluated the clinical behavior of clinical stage I pure yolk sac tumor of the testis in adults to determine whether the behavior of this entity is different than that of clinical stage 1 nonseminoma. MATERIALS AND METHODS: We searched the testis cancer database at our institution for adults with clinical stage I pure yolk sac tumor of the testis who underwent retroperitoneal lymph node dissection. We identified 12 such patients and reviewed the database and hospital charts to determine clinical behavior. RESULTS: Disease was pathological stage I in 8 of the 12 patients (66%), including 1 with recurrence after retroperitoneal lymph node dissection. Disease was pathological stage II in 14 patients (33%), including 1 who remains disease-free after electing adjuvant bleomycin, etoposide and cisplatin. Of the 3 patients who elected observation after retroperitoneal lymph node dissection only 1 has had recurrence, while 2 (66%) were cured by retroperitoneal lymph node dissection only. CONCLUSIONS: Contrary to juvenile yolk sac tumor, which has a strong tendency toward hematogenous metastasis, the behavior of clinical stage I adult pure yolk sac tumor is similar to that of all other stage I nonseminomas in adulthood.     

Resection of pulmonary metastases following chemotherapy for high stage testicular tumors

BACKGROUND: Our objective was to analyze retrospectively our experience with 19 patients who had metastatic germ cell testicular tumor and had undergone resection of pulmonary metastases following chemotherapy. We wished to determine the necessity of thoracic surgery on these patients. METHODS: Of 103 patients in need of postchemotherapeutic surgery for metastatic germ cell testicular tumors, 19 patients (mean age 31) underwent surgery for thoracic masses following cis-platin based chemotherapy. Resection of pulmonary metastases was performed on patients with normal tumor markers after chemotherapy, who did not achieve complete radiological remission. Histopathological findings, correlation with the pathology of abdominal surgery and probable prognostic factors for disease-free and overall survivals were evaluated. RESULTS: Disease-free and overall survival rates were 14/19 (73%) and 16/19 (84%), respectively, within a median follow-up time of 30 months (15-212 months). Patients with and without viable tumor cells in their thoracic histopathological specimen had 40% and 85% disease-free survival rates, respectively (P < 0.05). Eight patients had both abdominal and thoracic postchemotherapy surgery. Only two (25%) of these patients had the same histopathological features at both sites. CONCLUSIONS: All patients with residual thoracic masses must be considered candidates for surgery, because there are no predictive factors to determine the thoracic pathology without surgery. With the resection of the pulmonary metastases only, surgery can be performed without significant morbidity and is essential to select patients for further chemotherapy, to remove all visible masses and to provide histopathological confirmation. Patients with viable tumor cells in the thoracic surgical specimen have a poor prognosis.     

Different transformation of mature teratoma in a patient with mixed germ cell tumor of the testis

A 44-year-old male was referred with a left supraclavicular lymphadenopathy. A biopsy of the lymph node showed metastatic embryonal carcinoma. Tumor markers were present at high levels: alpha-fetoprotein 253.9 ng/mL, beta-human chorionic gonadotrophin 62 ng/mL. Computed tomography (CT) showed retroperitoneal adenopathy. High orchiectomy was done. The patient was treated with three cycles of etoposide plus cisplatin, achieved normalization of the serum tumor markers and underwent retroperitoneal lymph node dissection. Pathological findings of multiple lymph nodes showed teratomatous glands without viable cells. At follow-ups performed every 3 months, tumor markers remained within normal limits and no evidence of recurrence was observed. Eight years after first admission a CT scan revealed a cystic tumor 1 cm in diameter in the para-aortic region. The cystic tumor continued to slowly grow, expanding by 1 cm in diameter per year without elevation of tumor markers. The para-aortic tumor had grown to 4 cm in diameter and a left supraclavicular lymphadennopathy recurred. A resection of the supraclavicular cystic tumor showed mucinous cystadenocarcinoma, but a cystic tumor in the para-aortic region revealed mature teratoma. Here we report a case of mature teratoma with metastases at supraclavicular and para-aortic lymph nodes which had different transformations in spite of both regions consisting of cystic tumors.     

Identification and validation of a five apoptosis-related genes signature for prediction of disease-free survival for testicular germ cell tumors

BackgroundMore and more studies have paid attention to the role of apoptosis in tumorigenesis. A variety of apoptosis-related genes (ARGs) are related to tumor progression and resistance to chemotherapy drugs. Therefore, this study aims to establish a prognostic marker for ARG-based testicular germ cell tumors (TCGT).MethodsTCGT sequencing data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) database and GEO database. The sequencing data of normal tissues came from the GTEx database. Through univariate COX, LASSO, and multiple COX regression analyses, we screened out key ARGs related to prognosis and constructed a risk signature and a prognostic nomogram. Finally, we performed internal and external verification to verify the signature we have established.ResultsFive ARGs, including CHGA, LPCAT1, PPP1CA, PSMB5, UBR2 were selected out and utilized to establish a novel signature. Based on this signature, TCGT patients were divided into high-risk groups and low-risk groups. The results showed that the disease-free survival (DFS) of patients in the high-risk group was lower than that in the low-risk group (P=0.02268). The subsequent univariate and multivariate Cox regression analysis further proved that the features we established are valuable independent prognostic factors (P<0.05). Also, a prognostic nomogram was created to visualize the relationship between various prognostic-related factors and the 1-, 3-, and 5-year DFS of TCGT in the TCGA cohort.ConclusionsWe constructed a new nomogram based on ARGs to predict the risk of testicular tumor recurrence. It can help clinicians better and more intuitively predict the survival of patients.     

Lactate dehydrogenase isoenzyme-1 in the mediastinal yolk sac tumor

LDH isozymes in both the serum and tumor tissues of 4 patients with mediastinal yolk sac tumors, and in the cystic content of tumors transplanted into nude mice was examined. Our findings suggested that LDH-1, along with AFP, is an important marker of this tumor, and that LDH isozyme study is necessary for its diagnosis.     

Bilateral testicular tumors: A report of nine cases with long-term follow-up

BACKGROUND: The incidence and clinical features of bilateral germ cell testicular tumor (GCTT) in the Japanese population are not fully characterized. We examined the incidence, clinical features, management and outcome, sexual status, hormonal environment, implication of androgen replacement, and human leukocyte antigen (HLA) typing of bilateral GCTT. METHODS: We treated nine consecutive patients with bilateral GCTT from 1980 through to 1999, and reviewed their hospital and clinic charts. Testosterone, luteinizing hormone, follicle stimulating hormone, dehydroepiandrosterone, and dehydroepiandrosterone-sulfate were measured in bilateral orchiectomized patients. Human leukocyte antigen typing was assessed with peripheral lymphocyte. RESULTS: The incidence of bilateral GCTT against the total number of patients with GCTT was 9/274 (3.3%). The median age of the first tumor was 29 (range 21-75) years. Three cases were synchronous and the remaining six cases were metachronous. In the case of metachronous tumor, the median interval between first and contralateral tumor was 8 (range 2-25) years. Standard treatment was defined as surveillance policy in stage I, chemotherapy for higher stages of non-seminoma, and radiotherapy for stage II seminoma. Human leukocyte antigen typing was examined for seven cases. Five cases were positive for HLA-A24. The incidence of HLA-A24 in bilateral GCTT was identical to that of the Japanese population. The relapsing incidence of stage I disease with surveillance policy was almost identical to unilateral GCTT. A 74-year-old patient with stage II seminoma died of the disease at 1.3 years. The other eight patients remained well without any evidence of recurrence at a median follow-up period of 78 (range 12-204) months. Four patients with bilateral orchiectomy did not require androgen replacement without easy fatigability. Sexual status was conserved using androgen replacement. CONCLUSIONS: Long-term follow-up, as long as 25 years, is recommended for contralateral relapse. Some patients with bilateral orchiectomy do not require androgen replacement. The significance of HLA-A24 for bilateral testicular tumor is equivocal in the Japanese population.