Detection of AFP and HCG in metastatic testicular cancer after treatment with chemotherapy or radiation therapy

We used an indirect immunoperoxidase technique to detect alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) in tissue sections of nine metastatic germ cell tumors excised after treatment with chemotherapy or radiation therapy, and correlated the results with the serum levels of AFP and HCG. In all but 1 case yolk sac tumor (YST) was the only histologic type that reacted for AFP (AFP+) and syncytiotrophoblasts (STB) were the only histologic type that reacted for HCG (HCG+). Among 5 cases with normalization of the serum AFP before surgery, 3 were associated with YST-/AFP-, 1 with YST+/AFP+, and 1 with YST+/AFP- metastases; and among 4 cases with normalization of the serum HCG all were associated with STB-/HCG- metastases. Among 3 cases with persistent elevation of the serum AFP, 1 was associated with YST+/AFP+, 1 with YST+/AFP-, and 1 with YST-/AFP- metastases; and of 2 cases with persistent elevation of the serum HCG, 1 was associated with STB-/HCG- and 1 with STB+/HCG+ metastases. These data suggest that marker normalization in the face of persistent tumor results primarily from eradication of YST and STB, but also from treatment-induced inhibition of AFP and HCG synthesis or secretion.     

Induction chemotherapy and radical resection for primary nonseminomatous mediastinal germ cell tumor (NSGCT); report of a case

A 15-year-old male was admitted to our hospital for treatment of an anterior mediastinal tumor. The tumor was visualized by chest radiography 3 months prior to admission. Computed tomography (CT) revealed a heterogeneous solid tumor located in the anterior mediastinum. Although CT-guided needle biopsy had been performed twice, histologic diagnosis could not be confirmed. We believed this tumor to be nonseminomatous mediastinal germ cell tumor (NSGCT) and started intensive chemotherapy with cisplatin (CDDP) without histologic diagnosis because his serum AFP level was rapidly increasing. After 2 courses of chemotherapy, his serum AFP level returned to the normal range and surgical resection of the tumor with part of right lung was performed. Histopathological examination revealed that the tumor consisted of mature teratoma and yolk sac tumor. He underwent 1 course of chemotherapy post-operatively because a small number of viable cells were histopathologically recognized in the yolk sac component. At the time of writing, the patient is alive without any evidence of recurrence.     

Clinical features of testicular tumors in children

AIM: Testicular tumors are not common pediatric solid tumors, especially in Asian children. There have been few reviews of cases in Japan to date. We present the clinical features of 14 pediatric testicular tumor patients. METHODS: Clinical features of 14 testicular tumor patients, such as chief complaints, age at diagnosis, pathology, stages, treatments and prognosis, were examined from medical records. Two patients had their semen tested at adolescence. RESULTS: Of the 14 prepubescent patients, 12 (85.7%) patients were diagnosed before 3 years of age. Ten cases (71.4%) were diagnosed as yolk sac tumors, three (21.4%) as mature teratomas and one case as an epidermoid cyst. Nine cases (90.0%) among the 10 cases of yolk sac tumor were diagnosed as stage I and one case was stage IV. One stage I yolk sac tumor patient developed lung metastasis later. Eventually, two yolk sac tumor patients died, despite chemotherapy. While all the cases with a diagnosis before 2 years of age survived, 67% (2/3) of cases with a diagnosis after the age of 2 died of tumors. Semen analysis in two patients showed normospermia. CONCLUSION: In the present study, the most common testicular tumors were yolk sac tumors and the patients diagnosed before 2 years of age showed favorable results. Age could be a relapse risk factor in yolk sac tumors. Guidelines for handling testicular tumors in children is not yet well established in Japan. An organized system seems necessary to gather and accumulate the results of the cases in Japan in order to develop better guidelines for treatment.     

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。     

A study on alpha-fetoprotein and endodermal sinus tumor.

The phenomenon of alpha-fetoprotein production by testicular, ovarian, or sacrococcygeal teratocarcinomas is frequently observed but has not been well explained. This paper includes clinicopathologic studies of 19 cases of teratocarcinoma with positive AFP reactions. Sixteen of the 19 showed typical histologic features of endodermal sinus tumor (yolk sac tumor) of Teilum and one other was compatible with this diagnosis.^6,7 The occurrence of AFP in these tumors is best explained by the concept of endodermal sinus tumor; because it is known that large amounts of AFP are synthesized not only by the fetal liver but also by the yolk sac during early embryonic life, and because the diagnosis of endodermal sinus tumor itself implies that the tumor is of yolk sac origin morphologically.¹³More direct evidence of AFP synthesis was demonstrated by immunofluorescent technique in one of our cases. Immunofluorescence was seen only in that cell layer long defined as of yolk sac origin morphologically.Alpha-fetoprotein studies are valuable in following such patients, unless they are 1 mo of age or younger.     

The UK Children's Cancer Study Group: testicular malignant germ cell tumours 1979-1988.

The United Kingdom Children's Cancer Study Group (UKCCSG) malignant germ cell tumour (MGCT) studies were undertaken to establish standard protocols of investigation, staging, and treatment. The efficacy of new drug combinations and the value of serial measurements of serum alphafetoprotein (AFP) and human chorionic gonadotrophin (HCG) were evaluated. Following the initial surgery, staging of the tumour was performed using a variety of investigative approaches. In stage 1 testicular tumours, orchidectomy was performed. In more advanced tumours, and in stage 1 tumours that failed to show the expected decline in AFP or recurred, chemotherapy was used after appropriate surgery. Seventy-three boys, under 14 years of age, with testicular MGCTs have been entered into the UKCCSG studies since 1979. Serum AFP was measured preoperatively, or within 2 weeks of operation, in 70 boys. It was unequivocally elevated in 69. Monitoring by serial AFP measurement proved valuable in assessing response and in early detection of recurrence. HCG was measured in 46 boys, and was raised in three. Sixty-seven (91%) of the tumours were yolk sac (Teilum) tumours, four were immature teratoma, and two were mixed MGCTs. The only non-AFP producing tumour was an immature polydermal teratoma in a 1-year-old boy. Serum HCG was raised in three boys with yolk sac tumours, one with a mixed teratoma, and one 14-year-old boy who had a mixed MGCT. The results of treatment were assessed on April 1, 1989 (median time from diagnosis, 3 years 4 months). Seventy-one boys were alive, 48 of whom had been cured by orchidectomy alone. The remaining 25 patients received chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Juvenile granulosa cell tumor of the testis:: contemporary clinical management and pathological diagnosis

PURPOSE: Juvenile granulosa cell tumor (JGCT) of the testis is a rarely diagnosed subset of testicular stromal tumors. Although this variant of testicular stromal tumor is predominantly a benign entity in prepubertal patients, limited experience precludes a complete understanding of its clinical presentation and pathological diagnosis. MATERIALS AND METHODS: We reviewed all cases of testicular tumors at Children's Hospital of Philadelphia between 1976 and 2002 in males younger than 18 years. We specifically reviewed our experience with JGCT in terms of presentation, surgical treatment and long-term outcome. We also reviewed the microscopic findings and histochemical techniques used to confirm the diagnosis. RESULTS: We identified 77 tumors during the defined interval, of which 3 (3.9%) were JGCTs. All 3 patients with JGCT were first noted to have a testis mass soon after birth. All presented with a firm, unilateral testicular mass. Ultrasonographic findings were consistent with a complex, multiseptated, hypoechoic mass. Two of the 3 patients underwent radical orchiectomy. Testis sparing mass excision was performed in 1 patient. Grossly the tumors were partially cystic masses. Histologically positive immunostaining with inhibin-alpha and negative staining for alpha-fetoprotein (AFP) reliably differentiated JGCTs from yolk sac tumors. At a mean followup of 8.5 years (range 5 to 14) no metastases or local tumor recurrences have been diagnosed. CONCLUSIONS: To our knowledge we report the first case of testis sparing enucleation of a JGCT with a 5-year recurrence-free followup. Testis sparing enucleation is now our procedure of choice for tumors in neonates and prepubertal children with serum AFP in the normal range for age. JGCT should be suspected in neonates presenting at birth with a complex, cystic mass of the testis. Positive immunostaining for inhibin-alpha and a lack of AFP staining have consistently corroborated the pathological diagnosis in our experience and they should be applied for pediatric testis tumors that may mimic yolk sac tumor pathology.     

Glypican 3: a novel marker in testicular germ cell tumors

Glypican 3 (GPC3), a membrane-bound heparin sulfate proteoglycan, may play a role in promoting embryonic cell growth and differentiation. GPC3 is mutated in Simpson-Golabi-Behmel syndrome, characterized by tissue overgrowth and an increased risk of embryonal malignancies. Recently, GPC3 was reported to be one of the over-expressed genes in testicular yolk sac tumors by gene expression microarray analysis. However, the presence of the GPC3 protein in germ cell tumors has never been investigated. The purpose of the study was to investigate the GPC3 expression in various histologic components of testicular germ cell tumors using immunohistochemistry and to assess its possible utility as a diagnostic marker. Tumors from 71 patients were examined, including components of 42 seminomas, 37 embryonal carcinomas, 24 yolk sac tumors, 20 teratomas with mature elements, 16 teratomas with immature elements, and 7 choriocarcinomas. Cytoplasmic and membranous immunoreactivity was semiquantitatively evaluated. All yolk sac tumor (24/24) and choriocarcinoma (7/7) components were immunoreactive for GPC3, whereas only 38% of teratomas with immature elements and 8% of embryonal carcinomas expressed GPC3. There was no immunoreactivity in benign testicular tissue, intratubular germ cell neoplasia, seminomas (0/42), or teratomas with mature elements (0/20). We conclude that the oncofetal protein GPC3 is a novel immunohistochemical marker in testicular germ cell tumors with differential expression in defined histologic subtypes. Our findings suggest a possible role of GPC3 in tumor cell differentiation. Furthermore, GPC immunostaining may be useful in the pathologic diagnosis of nonseminomatous germ cell tumors, particularly yolk sac tumor, and choriocarcinoma.     

A case of mediastinal yolk sac tumor successfully treated with chemotherapy and surgery

A 28-year-old man was admitted due to increasing respiratory symptoms. X-ray examination of the chest showed a tumor mass in the anterior mediastinum with possible invasion into the chest wall and upper lobe of right lung. No tumor was found in the testis. Serum alpha-fetoprotein (AFP) concentration was 6400 ng/ml. Serum levels of CEA and HCG were within normal limits. Percutaneous biopsy of the tumor strongly suggested yolk sac tumor with an evidence of AFP by an immunoenzyme labelling technique. The serum AFP rapidly decreased after two courses of combination chemotherapy. En bloc resection of the tumor was successfully performed and third chemotherapy was added. Mediastinal yolk sac tumors should be treated with combination chemotherapy and surgical resection.     

A case of recurrent yolk sac tumor of the testis in childhood: bulky retroperitoneal metastatic tumors cured by tumor resection and chemotherapy

We carried out only high orchiectomy for a 1-year and 7-month-old boy with stage 1 yolk sac tumor of the testis, after 13-months a bulky retroperitoneal metastatic tumor was found. Following chemotherapy with CDDP, ACD, VBL, PLM and CTX two times after tumor resection, elevated serum AFP was normalized. He has been in continuous complete remission with no evidence of disease for 3 years and 2 months. Combination chemotherapy with CDDP has a dramatic effect on the yolk sac tumor of infantile testis. We believe that "watchful waiting" after high orchiectomy alone is the best modality for all cases of stage 1 yolk sac tumor of the infantile testis.     

A case report of infantile testicular cancer: dissection of paraaortic lymph node involvement indicated by gradual rise in serum alpha-fetoprotein after orchiectomy

We present a case of a 32-month-old boy with teratoma accompanied by yolk sac carcinoma and embryonal carcinoma of the right testicle. To treat the gradual rise in serum AFP value 3 months postoperatively, he received combined chemotherapy including VCR, CPM and ADM followed by bilateral retroperitoneal lymph node dissection. The preaortic lymph node disclosed, pathologically, yolk sac carcinoma and embryonal carcinoma, which demonstrated neither degeneration nor necrosis despite remarkable decrease in serum AFP value after the chemotherapy. The patient had normal AFP value and no evidence of recurrent disease 36 months after the lymph node dissection. We emphasize the discrepancy between the response of the tumor marker after the chemotherapy and the histologic alteration. Furthermore, the management of infantile testicular cancer is discussed.     

函数法分析AFP和β-hCG在睾丸肿瘤中的变化

目的:建立一种函数法分析AFP和β-hCG在睾丸肿瘤中变化的方法。方法:首先在睾丸根治术后复查AFP和β-hCG并计算其实测值坐标:以癌标实测值的半衰期个数为横坐标,癌标实测值的对数值为纵坐标。其次计算预测值坐标:设术前癌标实测值为a,半衰期个数为x,经过x个半衰期后预测值的对数值为y(以2为底取对数):y=log22axx+y=log2a(公式1),根据公式推导预测值坐标。最后比较癌标实测值与预测值坐标,了解是否有睾丸肿瘤残留或转移。结果:病例1为卵黄囊瘤和合体滋养层细胞的混合性生殖细胞瘤。其AFP和β-hCG在术后第10天的实测值坐标分别为(2.22,6.21)和(10,8.38),预测值坐标分别为(2.22,6.34)和(10,4.41)。该结果提示卵黄囊瘤尚未出现转移,合体滋养层细胞已出现转移。病例2为恶性畸胎瘤和卵黄囊瘤的混合性生殖细胞瘤,其AFP和β-hCG在术后第12天的实测值坐标分别为(2.67,-1.03)和(12,-3.32),预测值坐标分别为(2.67,1.41)和(12,-5.80)。但复查AFP和β-hCG的时间分别为2.67和12个半衰期,超过半衰期有效区间,此时癌标实测值均小于其正常值,可认为肿瘤无残留或转移。病例3为胚胎癌,其AFP在术后第1天的实测值坐标为(0.22,9.25),预测值坐标为(0.22,9.55),该结果提示胚胎癌尚未出现转移。结论:该方法预测的3例患者癌标变化均与实际病程吻合,睾丸根治术后如癌标实测值坐标与预测值坐标吻合,提示肿瘤尚未转移;如不吻合,则提示睾丸肿瘤残留或转移可能。     

Primary testicular tumors in children

Twenty-six primary testicular tumors in children (less than 15 years old) seen within a period of nine years (1978-1986) were analyzed. Of these, 16 (61.5%) were benign mature or immature teratomas and ten (38.5%) malignant. This is obviously different from most of the western series in which a 75-80% rate of malignancy has usually been reported. Sixteen benign testicular tumors, which were either mature or immature teratomas, showed no evidence of tumor one to nine years after high inguinal orchiectomy. Serum alpha-fetoprotein (AFP) levels were available in 14 of these patients and all of them were below 50 ng/ml. In the ten malignant tumors, eight were yolk sac tumors and two embryonal rhabdomyosarcomas. High inguinal orchiectomy only was performed for stage I disease with sequential monitoring of AFP level for two years. For stage II or III tumors, chemotherapy and/or irradiation were added in the treatment regimen. Retroperitoneal node dissections were not performed in this series. Eight out of these ten cases were alive without evidence of disease after one to seven years, one expired for an unknown cause and one was lost to follow-up. We advocate this conservative approach to childhood testicular tumors which have a better outcome than adult tumors.     

Treatment of nonseminomatous testicular tumor with liver metastases

Therapeutic course of 2 cases of nonseminomatous testicular tumor with liver metastasis is reported. One case had mixed tumors including embryonal carcinoma, choriocarcinoma and yolk sac carcinoma, and was positive pulmonary metastasis already at the initial examination. In the other case having mixed tumors of embryonal carcinoma and choriocarcinoma, metastasis to the supraclavicular lymph node was detected at the initial examination. In both cases liver metastasis occurred after complete response could be obtained by treatment chiefly consisting of PVB therapy. For liver metastasis four-drug combination treatment using cisplatin, vinblastine, adriamycin and actinomycin D was performed with partial response. However, this patient eventually died. The other case received VAB-6 therapy with complete response for liver metastasis. It is advisable to consider other modalities therapy in addition to conventional chemotherapy in cases of testicular tumor with liver metastasis since the prognosis is poor in these cases.     

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。     

Profiles of epitope-defined markers in sera from patients with testicular germ cell tumors

Summary Epitope-defined tumor markers of AFP (FA), HCG (PM), PLAP (H7) and CEA (D/AH) were determined by monoclonal antibodies in sera of patients with germ cell tumors of the testis. Characteristic profiles of PLAP (H7) were seen in localized and metastatic seminoma and in sera of patients with mixed tumors with seminoma components. PLAP (H7) levels started to rise 10 months before clinical detection of recurrence in one case. Persisting elevated levels of PLAP (H7) in several cases were indicative of metastafic seminoma. PLAP (H7) occurred rarely in sera of patients with metastasing non-seminomatous tumors. AFP (FA) detected in seminoma sera led to identification of non-seminomatous disease in one case. High AFP (FA) alone occurred in yolk sac tumors, HCG (PM) with AFP (FA) or PLAP (H7) in patients where the tumors had components of teratoma and/orembryonal carcinoma, moderately elevated levels of AFP (FA) and sometimes also HCG (PM) occurred.     

睾丸内胚窦瘤(附10例报告)

目的 提高睾丸内胚窦瘤的诊治水平。方法 对我院1987年11月～2002年11月收治10例睾丸内胚窦瘤的诊治资料进行分析。结果 10例均行患侧睾丸肿瘤根治术，术后辅以化疗。随诊1～15年，6例Ⅰ期患者均无局部复发及转移。结论 Ⅰ期患者不必常规行腹膜后淋巴结清扫术；早期诊断，睾丸肿瘤根治术加化、放疗能明显提高睾丸内胚窦瘤的治愈率。AFP的动态观察可判断肿瘤是否复发和转移。     

Importance of alpha-fetoprotein in patients with seminoma

Since one third of the patients who die of seminoma have unsuspected nonseminomatous metastases, testicular histology alone does not establish the diagnosis of “pure seminoma.” The serum protein markers alpha fetoprotein and the beta subunit of human chorionic gonadotropin are rarely, if ever, elevated in pure seminoma. An illustrative case is reported in which an elevated alpha fetoprotein led to the diagnosis of unsuspected yolk sac tumor in a patient with seminoma. Persistent elevation of alpha fetoprotein in a patient with seminoma is an indication of nonseminomatous disease and should be managed accordingly.     

Histological patterns of treatment failures in testicular neoplasms

We reviewed 77 consecutive autopsies performed between 1965 and 1982 on patients who had been treated for germ cell tumors of the testis at our institute. Identifiable germ cell tumor was present at autopsy in 64 cases. On review, a single pattern was seen at autopsy in the majority of the cases (69.7 per cent) compared to the primary tumors, in which single patterns were seen in only 45 per cent. The occurrence of yolk sac tumor as the sole element in 6 of 29 autopsy specimens of nonseminomatous tumors after the introduction of the current standard 3-drug therapy and only once in 32 autopsies before 1976 appears significant. A possible explanation for this finding is that the yolk sac element was obscured by more aggressive and rapidly growing varieties of tumor in the earlier years but proved less responsive to chemotherapy.