Serum alphafetoprotein (AFP) in patients with germ cell tumors of the gonads and extragonadal sites: correlation between endodermal sinus (yolk sac) tumor and raised serum AFP

During the last 6 1/2 years, serum AFP has been determined by radioimmunoassay in 387 patients with germ cell tumors of the gonads and extragonadal sites. The histological appearances of all these neoplasms were carefully reviewed. Highly elevated levels of serum AFP were noted in patients with tumors containing endodermal sinus (yolk sac) tumor elements irrespective of the location of the neoplasm or presence or absence of metastatic disease. There was good correlation between the presence and quantity of endodermal sinus (yolk sac) tumor elements within the primary tumor or its metastases and elevated levels of serum AFP. All patients with tumors composed of pure seminoma or dysgerminoma, and teratoma, had normal serum AFP levels. Slightly elevated levels of serum AFP up to 60 ng/mg (upper limit of normal 20 ng/ml) were noted in a few patients with testicular tumors composed of pure embryonal carcinoma, whereas patients with tumors composed of or containing endodermal sinus (yolk sac) tumor elements had serum AFP levels that could be measured in 100's or 1000's of ng/ml. Serum AFP was elevated only in patients with active disease. Serum AFP was determined in 81 patients with gonadal tumors of non germ cell origin and was normal in all these patients. Serum AFP is a very good tumor marker in patients with germ cell tumors composed of or containing endodermal sinus (yolk sac) tumor, irrespective of their location. Serial serum SFP determinations can be used for diagnostic purposes, for monitoring the results of treatment, and for early detection of metastases and recurrences. Serial serum AFP determination is a useful procedure in all patients with germ cell neoplasms and is highly recommended.     

Alpha-foetoprotein and carcinoembryonic antigen in germ cell neoplasms.

Serum alpha-foetoprotein (AFP) and serum carcinoembryonic antigen (CEA) levels were measured, serially whenever possible, in 70 patients attending the Institute of Radiotherapy, Rotterdam, on account of testicular (65) or ovarian (4) germ cell tumours or, in one case, an endodermal sinus (yolk sac) tumour in the mediastinum. In 15 patients the disease was active; in the others it was in remission. Patients with active disease had raised serum AFP levels which correlated well with disease activity; no patient without evidence of active disease had raised serum AFP levels. None of the patients with active disease was found to have raised serum CEA levels. There was no correlation between serum AFP and CEA levels in patients with germ cell neoplasms, but good correlation between serum AFP levels and disease activity. Serum CEA levels did not correlate with disease activity, and serial determinations would therefore not be useful in monitoring progress in this group of diseases.     

Mediastinal yolk sac tumor in a woman

Primary endodermal sinus tumor (yolk sac tumor) of the mediastinum is uncommon and most patients are young and male. We report a yolk sac tumor with a mature teratoma of the anterior mediastinum in a 28-year-old woman with an intrathoracic mass. Four courses of combination chemotherapy were given and the tumor was resected. The patient's serum alpha-fetoprotein (AFP) level was elevated, to more 100 000 ng/ml. To the best of our knowledge, this is the first report of serum AFP level exceeding 100 000 ng/ml in a yolk sac tumor with a mature teratoma.     

Transformation of ovarian yolk sac tumor to immature teratoma following chemotherapy

The patient, a 28-year-old woman, in her ninth week of pregnancy, was operated on for stage Ia, mixed germ cell tumor (grade 3 immature teratoma + yolk sac tumor) of AFP decreased to the normal level. Eight months later, an intrapelvic mass and raised AFP were found. The extirpated recurrent tumor in the pouch of Douglas was a grade 2 immature teratoma with no yolk sac element. FAM chemotherapy was given again, and the patient is alive and well after taking oral UFT. As in testicular germ cell tumors, ovarian germ cell tumors can be converted to a more differentiated tumor following chemotherapy.     

Immature teratomas: identification of patients at risk for malignant recurrence

We investigated the significance of immature elements in an otherwise benign teratoma in 28 patients with immature teratomas diagnosed and treated at the Childrens Hospital of Los Angeles from 1941 to 1986. Different characteristics, including age, sex, primary tumor site, type of surgery (complete resection vs. partial resection or biopsy), and preoperative levels of alpha-fetoprotein (AFP) were analyzed to evaluate their association with risk of subsequent local malignant recurrence. After a median follow-up of 6 years, 21 patients are alive with no recurrence of the tumor (72% event-free survival). One patient died from infection after surgery and six patients had local malignant tumor recurrence within 1 year from diagnosis. Of the 28 patients, 12 had AFP levels measured at diagnosis. Eight patients had normal levels with no further evidence of tumor recurrence, and four had elevated levels with three tumor recurrences. Our experience demonstrates that only at the time of diagnosis do AFP levels correlate with a subsequent malignant behavior of these tumors (P = .004). Those patients with immature teratomas and elevated AFP levels at diagnosis should receive adjuvant chemotherapy after the initial surgical resection.     

Immunohistochemical Type Distinction of a-Fetoprotein in Various a-Fetoprotein-secreting Tumors

In order to clarify the histogenesis of a -fetoprotein(AFP)-secreting tumor tissues, formalin-fixed, paraffin-embedded serial sections of 148 tumors in various organs were examined by the peroxidase-antiperoxidase method for AFP, and paradoxical concanavalin A staining. Yolk sac-type AFP was found in yolk sac tumors, embryonal carcinomas, solid teratomas, (yolk sac) endodermal cell tumors, adenocarcinomas (stomach, ovary or lung) and metastatic liver cancers. Hepatic-type AFP was demonstrated in hepatocellular carcinomas, hepatoblastomas, solid teratomas and a stomach cancer. Yolk sac-type AFP was observed in the neighboring liver cells of metastatic liver cancers without relation to the type of AFP in primary cancers. The results from serum analyses of preoperative tumor-bearing patients (68 cases) were coincident with those from immunohistochemical stainings.     

Transformation of an AFP-positive yolk sac carcinoma into an AFP-negative neoplasm. Evidence for in vivo cloning of the human parietal yolk sac carcinoma

An alpha-fetoprotein (AFP)-positive ovarian yolk sac carcinoma of typical histologic appearance was surgically removed from a 19-year-old woman. The AFP-positive tumor recurred and was treated with x-rays and cytotoxic drugs to full remission, i.e., until no clinical or biochemical signs of tumor were evident. The second recurrence, which proved to be fatal, was noticed approximately 1 year after the initial diagnosis, but was not associated with elevated levels of serum AFP. At autopsy, the widespread tumor had the histologic appearance reminiscent of murine parietal yolk sac (PYS) carcinoma. The tumor cells did not form the characteristic histologic features of the classical human yolk sac carcinoma, did not secrete AFP, and were surrounded by extensive hyalinous extracellular matrix rich in laminin and collagen. It is thus shown that recurrent human yolk sac carcinomas could change their histologic morphology due to selective outgrowth and cloning of the parietal yolk sac component. Clinical recognition of this cloning is important because the PYS carcinoma cells do not secrete AFP, and the tumor growth cannot be biochemically monitored with this classical tumor marker.     

Alpha-1 antitrypsin (AAT) and alphafoetoprotein (AFP) in sera of patients with germ-cell neoplasms: value as tumour markers in patients with endodermal sinus tumour (yolk sac tumour).

Serum alphafoetoprotein (AFP) and serum alpha-1 antitrypsin (AAT) were determined in 24 patients with germ-cell neoplasms of the gonads and extragonadal sites and in two patients with hepatocellular carcinoma. In the majority of the patients serial determinations were performed. All seven patients with testicular seminoma and four patients without evidence of active disease had normal levels of serum AAT and AFP. The remaining 13 patients with germ-cell neoplasms had tumours containing endodermal sinus tumour (yolk-sac tumour) elemetns. All these 13 patients had elevated levels of serum AFP and the levels were high or very high in most cases. Nine of these 13 patients had raised serum AAT, although the elevation above normal levels was only slight in a number of cases. When serial determinations were performed serum AAT levels frequently followed the pattern of serum AFP levels, but the AAT levels were frequently within normal limits and therefore the interpretation of the results was difficult, and much less reliable as compared with those for serum AFP. The elevation of serum AAT levels following the recurrence of the tumour was found to occur much later and was much less marked than elevation of serum AFP, which occurred early, showed a large rise and was a reliable marker of tumour recurrence in patients with germ-cell neoplasms containing endodermal sinus tumour elements. It is therefore considered that, although there is good evidence that serum AAT is produced by endodermal sinus tumour elements, serum AAT is not a useful monitor of disease activity in these patients, especially when compared with serum AFP, the value of which is well recognized. Serum AAT may be a useful tumour marker in patients with hepatocellular carcinoma, and this aspect should be investigated further.     

Endodermal sinus tumor of the ovary and alpha fetoprotein: a case report.

Yolk sac tumors of the ovary are associated with elevations in serum levels of alpha fetoprotein (AFP). Thus, an antigenic marker is provided for evaluating therapeutic results in selected patients. A patient with a pure endodermal sinus tumor of the ovary is presented who underwent serial determinations of AFP. The effectiveness and limitations of serial AFP levels as demonstrated by this case are discussed in addition to the surgical and chemotherapeutic management of patients with yolk sac tumor of the ovary.     

Tumor markers AFP,CA 125, and CA 19-9 in the long-term follow-up of sacrococcygeal teratomas in infancy and childhood

Given the tendency of a proportion of sacrococcygeal teratomas (SCT) to recur, we evaluated whether serial tumor marker measurements are helpful in the management of these children. Between 1985 and 2006, 32 children with SCT were followed up for 1–15 years, and a total of 344, 197, and 193 serial samples for serum alpha-fetoprotein (AFP), CA 125, and CA 19-9 were analyzed, respectively. Six children with neonatal SCT developed eight recurrences. Serum AFP was elevated in two of two children prior to diagnosis of malignant recurrences (yolk sac tumor and adenocarcinoma), and CA 125 was elevated in one third of mature and one third of immature recurrences. CA 19-9 remained within reference values in relation to recurrences of neonatal SCT. Taken together, serum CA 125 measurements may complement the use of serum AFP in the follow-up of SCT.     

Alpha-fetoprotein (AFP) Elevation Gastric Adenocarcinoma and Importance of AFP Change in Tumor Response Evaluation

Background: Elevated serum alpha-fetoprotein (AFP) levels in adults are considered abnormal. This parameteris used mostly in the diagnosis and follow-up of hepatocellular carcinomas and yolk sac tumors. Among the otherrare tumors accompanied with elevated serum AFP levels, gastric cancer is the most common. In this study, weevaluated the follow-up and comparison of the treatment and marker response of patients with metastatic gastriccancer who had elevated serum AFP levels. Materials and Methods: We performed a retrospective study, includingall consecutive patients with advanced gastric cancer, who received systemic chemotherapy with elevated AFPlevel. Results: Seventeen metastatic gastric cancer patients with elevated AFP levels at the time of diagnosis wereevaluated. Fourteen (82.4%) were males and three (17.6%) were females. The primary tumor localization wasthe gastric body in 8 (76.4%), cardia in 7 (41.2%), and antrum in 2 (11.8%). Hepatic metastasis was observed in13 (76.4%) at the time of diagnosis. When the relationship of AFP levels and carcinoembryonic antigen (CEA)response of the patients with their radiologic responses was evaluated, it was found that the radiologic responsewas compatible with AFP response in 16 (94.1%) patients and with CEA response in 12 (70.6%); however, in 5(29.4%) patients no accordance was observed between radiological and CEA responses. Conclusions: Followupof AFP levels in metastatic gastric cancer patients with elevated AFP levels may allow prediction of earlytreatment response and could be more useful than the CEA marker for follow-up in response evaluation.     

Prognostic value of tumor size, metastases, extension into bone, and increased tumor marker in children with malignant sacrococcygeal germ cell tumors: a prospective evaluation of 71 patients treated in the German cooperative protocols Maligne Keimzelltumoren (MAKEI) 83/86 and MAKEI 89.

PURPOSE: To evaluate the prognostic value of metastases, extension into bone, and alpha-fetoprotein (AFP) elevation in children with malignant sacrococcygeal germ cell tumors (GCTs) prospectively collected in two cooperative Maligne Keimzelltumoren (MAKEI) protocols (83/86 and 89). PATIENTS AND METHODS: Between October 1983 and October 1995, 76 of 210 registered patients with sacrococcygeal primaries presented either with pure yolk sac tumor, embryonal carcinoma (EC), or yolk sac tumor and EC mixed with immature and mature teratoma elements. Stages T1 and T2 disease were diagnosed in 15 and 61 children, respectively, 41 patients had metastases, and 35 children presented with extension into bone. At diagnosis, 22 children had an AFP elevation of less than 10,000 ng/mL. Thirty-six children showed an AFP level between 10,000 and 100,000 ng/mL, and 12 patients had values of greater than 100,000 ng/mL. Five patients died of complication during treatment and were excluded from further evaluation. Seventy-one patients could be analyzed. RESULTS: The 5-year relapse-free survival rate (RFS, Kaplan-Meier) was 0.76 +/- 0.03 (54 of 71 patients; median observation time, 54 months after diagnosis). The RFS of patients with and without metastases was different, but not significantly so (0.71 v 0.82). The outcome of patients with extension into bone (n = 31) and without this extension (n = 40) was 0.71 versus 0.80 (RFS, 5 years). Above-normal AFP level had no prognostic significance (P =.52). CONCLUSION: In children with malignant sacrococcygeal GCTs treated with an intensive, short-interval, platinum-based regimen, the stage, extent of metastases, extension into bone, and AFP level had no prognostic significance.     

Value of five tumor markers (AFP, CEA, hCG, hPL and SP1) in diagnosis and staging of testicular germ cell tumors

Serum levels of AFP, CEA, hCG, hPL and SP1 were measured by specific radioimmunoassays in 111 patients with testicular germ cell tumors. Seminomas, mature teratomas and "pure type" embryonal carcinomas, as well as the latter two types of tumor with seminomatous admixture, do not produce markers unless in advanced stages when they may do so (small amounts of hCP, hPL and SP1). Tumors composed of yolk-sac elements alone or mixed with embryonal carcinoma produce AFP: of syncytiotrophoblastic elements - hCG, hPL or SP1; and teratomas with differentiated structures - CEA. Compound tumors can produce any of the five markers. When present in serum after orchiectomy or lymphadenectomy, the markers are useful both in diagnosis of the tumor elements that metastasized and in staging; whereas their absence does not exclude regional or distant metastases which may contain only marker-negative elements, e.g., due to changes in tumor histology. Measurement of the serum levels of the markers informs about the remaining regional tumor elements or latent metastases and therefore is more useful than immunoperoxidase staining which provides information on the already dissected structures only.     

Primary intracranial germ-cell tumors. A retrospective analysis with special reference to long-term results of treatment and the behavior of rare types of tumors

Thirty cases of primary intracranial germ-cell tumors were reviewed with reference to the effect of treatment. Histologically, there were 23 pure germinomas, while the remaining tumors had more unusual histology; 3 of these were teratomas, and 4 germ-cell tumors with the admixture of yolk sac tumor (YST) or embryonal carcinoma (EMC). Three of these rare cases are presented. The performed surgery and radiotherapy, seemed adequate for pure germinomas, and all these cases lived tumor-free after an observation time of 13 to 139 months although 4 patients developed intellectual retardation or cerebral dullness after radiotherapy. Four cases with YST and EMC elements, indicated by the elevation of AFP and HCG values in serum, were resistant to radio- and chemotherapy and developed, despite surgically total removal of the tumor, intra- or extracranial metastases. A review of the literature is included.     

婴幼儿睾丸卵黄囊瘤11例临床病理分析

  目的  探讨婴幼儿睾丸卵黄囊瘤的临床病理、治疗与预后特点。   方法  回顾性分析海南省人民医院2000年5月~2011年5月间1 1例手术切除的婴幼儿睾丸卵黄囊瘤病例资料, 观察其组织形态特征, 进行Glypican-3、AFP、CK8 & 18、HCG、PLAP、CD99、S-100和CD34免疫组化标记。   结果  患者中位年龄15个月, 右侧占优(9/11), 睾丸单侧无痛性增大为主要临床表现, 术前血清AFP值明显升高。组织学分型: 10例为单纯型卵黄囊瘤, 1例为伴有成熟性畸胎瘤的混合型卵黄囊瘤病例。所有的卵黄囊瘤中, Glypican-3弥漫强阳性表达, 而CK8 & 18、AFP均呈不同程度阳性, 其余的CD99、S-100和CD34等呈阴性。11例睾丸高位切除, 2例瘤旁有血管瘤栓者予以BEP方案辅助化疗。目前患者生存良好, 未见复发和转移。   结论  婴幼儿睾丸卵黄囊瘤以单纯型多见, 混合型罕见。Glypican-3是诊断卵黄囊瘤较特异和敏感的指标。婴幼儿的卵黄囊瘤睾丸高位切除疗效较好, 对于高危的患儿可予以辅助化疗。      

Complete surgical excision is effective treatment for children with immature teratomas with or without malignant elements: A Pediatric Oncology Group/Children's Cancer Group Intergroup Study.

PURPOSE: To determine whether the 3-year event-free survival (EFS) of children with completely resected immature teratomas is greater than 85%. PATIENTS AND METHODS: Patients with immature teratomas treated at Pediatric Oncology Group or Children's Cancer Group institutions were eligible. Pathology was centrally reviewed to confirm diagnosis and tumor grading. Follow-up included physical examination, measurement of tumor markers (alpha fetoprotein and human chorionic gonadotropin), and imaging. All patients were monitored for events, defined as tumor recurrence, second malignancy, or death. RESULTS: Seventy-three children (median age, 7.8 years) with extracranial immature teratomas were enrolled on study. Primary tumor sites included ovarian (n = 44), testicular (n = 7), and extragonadal (n = 22). However, on review, 23 patients had foci of yolk sac tumor (n = 21) or primitive neuroectodermal tumor (n = 2), whereas 50 had pure immature teratomas. Twenty-five patients had increased alpha fetoprotein (n = 18), human chorionic gonadotropin (n = 5), or both (n = 2); nine had foci of yolk sac tumor on review. Pathology review identified 23 patients with grade 1, 29 with grade 2, and 21 with grade 3 immature teratomas. With a median follow-up of 35 months, the overall 3-year EFS was 93% (95% confidence interval, 86% to 98%), with 3-year EFS of 97.8%, 100%, and 80% for patients with ovarian, testicular, and extragonadal tumors, respectively. Only four of 23 patients with immature teratoma and malignant foci developed recurrence, suggesting that surgical resection followed by close observation are effective treatment. Overall, five patients had disease recurrence 4 to 7 months from diagnosis, and four (80%) are disease free after platinum-based therapy. The fifth patient has residual tumor after cisplatin, etoposide, and bleomycin treatment requiring further therapy. CONCLUSION: Surgical excision is safe and effective treatment for 80% to 100% of children with immature teratoma.     

Immunohistochemical localisation of alpha-fetoprotein (AFP) in germ cell tumours: evidence for AFP production by tissues different from endodermal sinus tumour

20 germ cell tumours have been studied with respect to the presence of alpha-fetoprotein (AFP), using the peroxidase-antiperoxidase (PAP) technique. 6 out of 20 tumours contained elements of endodermal sinus tumour (EST) and were AFP positive. 16 tumours were diagnosed either as pure embryonal carcinomas (6) or as mixed germ cell tumours, containing elements of embryonal carcinoma (10). In 3 of these 16 tumours AFP was localised definitely in the embryonal carcinoma cells; in an additional 6, AFP was also detected but it could not be decided whether AFP was present in embryonal carcinoma cells or in EST cells during early differentiation. In 2 of 7 immature teratomas, AFP was shown to be present in cylindric epithelia. All seminomas (4) studied were AFP-negative. These results show that AFP, which occurs regularly in EST, may also be present in embryonal carcinomas as well as in immature teratomas. Thus, it seems that the immunohistochemical demonstration of AFP by the PAP technique is a suitable method of identifying late stages of embryonal carcinoma or early stages of endodermal sinus tumour during the process of differentiation.     

The treatment of cranial germ cell tumours

Germ cell tumours of the central nervous system (CNS) include many subtypes whose response to treatment varies, even though the symptoms and radiological appearances are similar. Five-year survival rates are 96% for germinomas, 100% for mature teratomas, 67% for immature teratomas and 69% for immature teratomas mixed with germinomas; for beta-HCG secreting germinomas the rate is only 38%. Patients with choriocarcinoma, embryonal carcinoma, or yolk sac tumour have the lowest survival rates; patients with germinoma or mature teratoma have longer survival rates.Although a wider resection is associated with a higher rate of survival for patients with non-germinomatous germ cell (NGGC) tumours, to date an aggressive surgical approach has been advocated only for pineal region tumours, but not for hypothalamic/neurohypophyseal tumours. Beside the delayed injury induced by radiotherapy, the late injury induced by chemotherapy is becoming increasingly evident. Cisplatin is considered an indispensable drug, but it may cause renal damage, ototoxicity, peripheral neuropathy and sterility, while etoposide is associated with an excess frequency of second neoplasms.Taking into account all of the published literature, the following therapeutic options are suggested: in pure germinoma tumours (GT) radiotherapy alone will usually ensure adequate control of the disease, and the long-term sequelae may be limited by reducing the dose delivered, as was proposed for germ cell testicular tumours, to 30 Gy to limited fields plus 25-30 Gy to the spinal axis if there is disseminated disease. In cases of recurrence, which should be uncommon, patients may be rescued with both radiotherapy and chemotherapy.In NGGC tumours, the prognosis is more unfavourable and there is often dissemination to the spine at diagnosis; however, the tumour's high chemosensitivity suggests neoadjuvant treatment chemotherapy with cisplatin and etoposide for three cycles followed by consolidation radiotherapy with 40 Gy to the limited fields plus 30 Gy to the spinal axis if disseminated.In our opinion, a higher dose of radiotherapy in cases in which chemotherapy does not achieve a radiological complete remission is not advisable, because very often the residual radiological abnormality does not represent biologically active tumour but differentiated forms such as mature teratoma.The challenge for 2000 is to both cure these patients, and avoid the late and permanent sequelae of radiation and/or chemotherapy that may subsequently impair quality of life.     

Polyembryoma of ovary producing alpha-fetoprotein and HCG: immunoperoxidase and electron microscopic study

Polyembryoma of ovary producing alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) was studied by indirect immunoperoxidase method for AFP and HCG, and electron microscopy. Clinically, this patient showed pseudoprecocious puberty caused by elevated HCG which is synthesized by trophoblastic cells in polyembryoma. She is put under VAC (vincristine, actinomycin-D, cyclophosphamide) chemotherapy after operation and shows no signs of recurrence including reelevation of serum AFP at five months after operation. Embryoid bodies which we studied correspond to normal embryo at 15- or 16-day stage. Immunoperoxidase study showed that AFP is synthesized by yolk sac cells of the embryoid bodies and HCG is synthesized by syncytiotrophoblastic cells. The finding about AFP synthesis suggests that normal embryo at 15- or 16-day stage may begin AFP synthesis. Electron microscopic study showed that each part of the embryoid bodies had some characteristic structures. Most striking features found in the cytodifferentiation of the embryoid bodies were noticed in some special differentiation of plasma membrane and existence of surface coat. Desmosomes were found in endodermal cells and yolk sac cells. Ectodermal cells were attached to each other by zonulae occludentes and adherentes. Microvilli were found in ectodermal cells and yolk sac cells. Two different kinds of surface coat were found in mesodermal cells and lining cells of yolk sac cavity: thin-layered deposit of electron-dense material covering the plasma membrane facing intercellular space of mesodermal cells and endodermal cells, and thick-layered deposit of electron-dense material which covered the plasma membrane facing yolk sac cavity of endodermal cells and yolk sac cells. Presence of similar characteristic material in RER of yolk sac cells led us to speculate that thick deposit was synthesized by yolk sac cells and secreted into yolk sac cavity. Combined with immunoperoxidase study by light microscopy, we assume that this thick-layered deposit has some close relation to AFP.     

Cellular localization of alpha-fetoprotein and human chorionic gonadotropin in germ cell tumors of the testis using and indirect immunoperoxidase technique.

An immunohistologic study of 21 patients with germ cell tumors of the testis with measured serum levels of chorionic gonadotropin (HCG) and alpha-feto protein (AFP) was undertaken to correlate the various types of neoplasms with the presence of these tumor markers in the tissue and serum. AFP was demonstrated in mononuclear embryonal cells within embryonal carcinoma and endodermal sinus tumor. HCG was identified within syncytiotrophoblastic giant cells, frequently in association with embryonal carcinoma, and rarely with endodermal sinus tumor and seminoma, as well as in the syncytiotropho-blastic component of choriocarcinoma. Eighteen of the 21 patients (86%) had elevated tumor markers in their serum; serum HCG alone was elevated in five (24%), AFP alone in five (24%) and both were elevated in eight (38%). There was tissue localization of HCG in 12 of the 13 patients (92%) with elevated serum HCG while AFP was identified in the tumor in eight of the 13 patients (53%) with elevated serum AFP levels. Based on these findings, a tentative immunohistologic classification of germ cell tumors utilizing AFP and HCG is proposed. Thus, embryonal carcinoma, adult type, is frequently associated with both AFP and HCG, endodermal sinus tumor with AFP and choriocarcinoma with HCG, whereas pure seminoma and teratoma are unlikely to be associated with either marker.