Malignant ovarian tumours in childhood in Britain, 1962-78

The files of the Childhood Cancer Research Group and of the Oxford Survey of Childhood Cancers were scrutinized for all the ovarian neoplasms registered in England, Scotland and Wales in children under age 15 years throughout the period 1962-78. Among 172 cases confirmed as malignant ovarian tumours, 145 (84%) were tumours of germ cell origin (54 dysgerminomas, 36 malignant teratomas, 26 endodermal sinus tumours, 4 embryonal carcinomas, 2 pure choriocarcinomas, 20 mixed germ cell neoplasms, 3 gonadoblastomas), 13 (8%) were epithelial carcinomas (3 serous or undifferentiated, 10 mucinous), 9 (5%) were sex-cord stromal tumours (3 granulosa cell, 3 Sertoli-Leydig, 3 unclassified) and 5 (3%) were other miscellaneous tumour types. Less than 10% of the neoplasms occurred at age less than 5 years, approximately 20% from 5-9, and greater than 70% from 10-14 years. Germ cell neoplasms of greater malignancy (immature teratomas, endodermal sinus tumours) occurred in a significantly higher proportion at younger age (less than 10 years) than dysgerminomas (P = 0.01). The overall incidence (approximately 1.7 cases per 10(6) per annum) did not show any noticeable trend over the 17-year period considered. The clustering of two confined cases and, possibly, a third case, of germ cell neoplasms in three generations of the same family pointed to a genetic component in the aetiology of some of these neoplasms. A large number of sex related and mental or neurological abnormalities was also reported in case children. The 10-year survival rates, determined by the life-table method were: epithelial carcinomas 73%, sex-cord stromal tumours 44%, dysgerminomas 73%, malignant teratomas 33%, endodermal sinus tumours 39%, embryonal carcinomas 25%, other germ cell neoplasms 30% and gonadoblastomas 100%. Apart from cell-type, factors associated with prognosis were clinical stage (in all types), size and degree of histological differentiation (in malignant teratomas, but only when stage was not allowed for). The adoption of efficacious polychemotherapy regimens completely changed the prognosis of germ cell tumours other than dysgerminomas (from 29% to greater than 85% disease-free survivors in the present series).     

Cultured stem-cells from human testicular teratomas: the nature of human embryonal carcinoma, and its comparison with two types of yolk-sac carcinoma

The understanding of differentiation in human teratomas requires a better definition of the phenotype and developmental potential of the stem cells in these tumours. We describe the characterization of 6 new cell lines from human testicular teratomas which are representative of 3 distinct cell types. Cell lines GCT 27, GCT 35, and GCT 48, identified as embryonal carcinoma, comprise epithelial cells which express cytokeratin intermediate filaments and desmoplakins, as determined by indirect immunofluorescence microscopy. A minority of the cells also express vimentin. Most cells in these cultures show surface staining with monoclonal antibodies (MAbs) to stage-specific embryonic antigens SSEA 3 and SSEA 4 but not SSEA 1. Staining with MAb W6/32, which recognizes HLA A,B and C chains in the presence of beta-2 microglobulin, is not above background level. When injected into nude mice, GCT 27 cells form tumours consisting of embryonal carcinoma, somatic tissues, and cells positive in immunocytochemical assays for alphafoetoprotein (AFP) and human chorionic gonadotrophin (HCG); GCT 35 cells form embryonal carcinomas with foci of AFP and HCG-positive cells; and GCT 48 cells form embryonal carcinoma only. A second type of cell (GCT 72) displays some properties of rodent visceral endoderm. GCT 72 cells contain cytokeratin intermediate filaments, but not vimentin, and show very strong staining at cell borders with anti-desmoplakin I + II antibody. At the cell surface, GCT 72 cells express the epitopes recognized by antibodies to SSEA 3, SSEA 4, and SSEA 1; staining with W6/32 is negligible. Levels of AFP in supernatants from GCT 72 cultures are in excess of 500 KIU/I. The tumours formed following inoculation of nude mice with GCT 72 cells are solid yolk-sac tumours, with all cells strongly positive for AFP. A third cell type (GCT 44 and GCT 46), resembles in some ways rodent parietal endoderm. These cells uniformly coexpress keratin and vimentin intermediate filaments, but not desmoplakins. The determinants recognized by MAbs to SSEA 3, 4, or 1 are not detected on the majority of cells in these cultures. In striking contrast to the other teratoma lines, these cells can attach to untreated tissue culture plastic in serum-free medium and may be serially cultivated under these conditions. The tumours formed in nude mice by these 2 cell lines are yolk-sac carcinomas with endodermal sinus tumour histology. Thus, human testicular teratomas consist of epithelial cells which may be nullipotent, pluripotent or committed to extraembryonic endodermal differentiation.(ABSTRACT TRUNCATED AT 400 WORDS)     

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.     

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.     

Serum alpha1-foetoprotein levels in 153 male patients with germ cell tumours.

--alpha1-Foetoprotein (AFP) levels have been measured by radioimmunoassay in the serum of 153 male patients with gonadal and extragonadal germ cell tumours. Thirty-five patients with pure seminoma, and 34 patients with teratoma but without any postoperative evidence of residual or recurrent tumour, consistently had normal serum AFP levels (less than 25 ng/ml). Of 84 patients with active teratomas, 56 (67%) had serological evidence of AFP production. Ten patients with histological evidence of pure yolk sac (endodermal sinus) tumours all had raised levels. Teratomas containing yolk sac (elements may or may not be associated with raised serum levels. Trophoblastic (choriocarcinomatous) elements in a teratoma were not normally associated with high values. Fourteen patients with teratomas had elevated levels in the absence of histologically detectable yolk sac elements. Serum AFP levels often became elevated before clinical evidence of recurrence, so that AFP can act as an effective marker of the course of the disease and its response to therapy in many patients, but recurrent or progressive disease may be present in the absence of raised levels.     

Management of primary intracranial germ cell tumors

Primary intracranial germ cell tumors are rare and usually localized in the pineal and the suprasellar regions. They are divided into the following histologic types: germinoma, teratoma (mature, immature, malignant), choriocarcinoma, embryonal carcinoma, endodermal sinus tumor (yolk sac tumor), and mixed tumors. Clinically, they are manifested with ocular signs or signs of obstructive hydrocephalus. Localized germinomas are treated with radiation therapy and exhibit a relatively good prognosis. Chemotherapy is reserved for disseminated germinomas. Mature teratomas are treated with surgery. The rest of germ cell tumors are managed with various combinations of surgery, chemotherapy, and radiotherapy depending on the tumor type. If the tumors secrete beta-human chorionic gonadotrophin (hCG) or alpha-fetoprotein (FP), these tumor markers can be used to accurately monitor response to treatment. Prognosis is best for germinomas and mature teratomas and worst for choriocarcinomas and embryonal carcinomas.     

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.     

Treatment of malignant ovarian germ cell tumors: response to vincristine, dactinomycin, and cyclophosphamide (preliminary report)

From November 1971 to November 1975, 27 patients with malignant germ cell tumors of the ovary (excluding pure dysgerminoma and tumors containing trophoblastic elements) were treated with vincristine, dactinomycin, and cyclophosphamide; 12 patients received other therapy. Fourteen tumors were pure endodermal sinus tumors, two were embryonal carcinomas, 11 were mixed germ cell tumors and 12 were immature teratomas. Of 23 patients with surgically resected disease (Stages I-IIA) only seven have failed. Median follow-up for 16 patients remaining free of disease is 24.5 months. Restaging (second-look) laparotomies were done in 15 patients. Eight were negative. Fifteen of the patients had tumors with endodermal sinus elements. Six of these have failed. Of 16 patients with advanced disease (Stage IIB, III and recurrent), eight have responded to chemotherapy, eight have failed. Median follow-up period for those remaining free of disease is 26.5 months. Six have had negative second-look surgery and one had mature teratoma. Four of eight cases which contained endodermal sinus elements responded to chemotherapy and remain disease-free. Grade 3 hematologic toxicity was seen in eight patients, dose-limiting gastrointestinal toxicity in five patients, dose-limiting neurotoxicity in five patients.     

Embryonal carcinoma of the ovary: a clinicopathologic entity distinct from endodermal sinus tumor resembling embryonal carcinoma of the adult testis.

The clinical and pathologic features of 15 examples of a hitherto undescribed germ cell tumor of the ovary are delineated. This tumor resembles the embryonal carcinoma of the adult testis and may be distinguished from the endodermal sinus tumor on the basis of its histologic and immunohistochemical characteristics. An indirect immunoperoxidase method for the localization of human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP) was done on formalin-fixed paraffin-embedded tissue from 10 neoplasms; HCG was present in all 10 neoplasms, and AFP was found in seven. HCG was indentified only in cells resembling syncytiotrophoblast, whereas AFP was present only in mononuclear embryonal cells, indicating that the two protein antigens were localized in different cell types. Abnormal hormonal manifestations, consisting of precocious puberty, irregular bleeding, amenorrhea, or hirsutism, were present in nine (60%) of the patients. The actuarial survival for the entire group was 39%; for those with stage I tumors, 50%. We are proposing the term "embryonal carcinoma" for this neoplasm in order to distinuish it from the more common endodermal sinus tumor of the ovary and to emphasize the histologic similarity to embryonal carcinoma of the adult testis.     

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.     

General concepts of alpha-fetoprotein (AFP)-secreting tumors, with special reference to the histogenesis

Recently, in addition to yolk sac tumors (YST) and hepatocellular carcinomas, many AFP-secreting tumors have been reported. A comparative morphological study of YST to the human yolk sac has revealed tumor cells mimicking the behavior of the human yolk sac endodermal cells (HYSEC). Another investigation suggests that an embryonal carcinoma (adult type), a gastric adenocarcinoma, or an ovarian adenocarcinoma, each showing no histologic features specific for YST, have a selective differentiation to HYSEC which can secrete an increased serum AFP. These tumors might well be called endodermal cell tumors. The histogenesis of AFP-secreting tumors can be attributed to the endodermal origin (or retrodifferentiation to the HYSEC).     

Vincristine, dactinomycin, and cyclophosphamide in the treatment of malignant germ cell tumors of the ovary. A Gynecologic Oncology Group Study (a final report)

Seventy-six patients with malignant germ cell tumors of the ovary received vincristine, dactinomycin, and cyclophosphamide (VAC) postoperatively. Fifty-four were treated after removal of all gross disease. The majority of these remain disease-free. Indeed, only 15 (28%) have failed, including 11 of 24 with pure endodermal sinus tumor, 3 of 11 (27%) with mixed germ cell tumor containing endodermal sinus elements, and only 1 of 20 with immature teratoma grade 2 or 3, a patient seen initially with recurrent disease. Postoperative VAC therapy, however, did not appear to be effective in patients with unresectable or incompletely resected germ cell tumors of the ovary. Fifteen of 22 patients (68%) with incompletely resected germ cell tumors failed VAC therapy, including 4 of 7 with pure endodermal sinus tumor, 5 of 5 with mixed germ cell tumors containing endodermal sinus elements, 2 of 2 with embryonal carcinoma, and 4 of 8 with immature teratoma. In failing, patients' median time to progression was 8 months. Dose-limiting toxicity was seen in 30% of the entire group. Combined cisplatin, vinblastine and bleomycin therapy now is being tested in this group of tumors.     

Evaluation of five tumor markers (AFP, CEA, hCG, hPL and SP1) in monitoring therapy and follow-up of patients with testicular germ cell tumors

61 patients with seminoma and 113 with nonseminomatous germ cell tumors of the testis were treated according to the histology, stage of disease, and serum levels of tumor markers (CEA, AFP, hCG, hPL and SP1). 33 were stage I, 63 stage II, and 78 stage III patients. Most patients with seminoma, mature teratoma, immature teratoma, and 'pure type' embryonal carcinoma, as well as the latter three types with seminomatous admixture, had normal serum levels of the markers. Sometimes, slightly elevated levels of hCG suggested the presence of metastases. But, serial measurements of the markers were seldom useful in monitoring therapy. The 5-year tumor-free survival rates were favorable: 100% for stage I and II disease; and 57 or 44% for, respectively, stage III seminoma or the other tumors amounting to 10% of the nonseminomatous group. The role of the five markers was significant in patients with teratoma with malignant transformation, choriocarcinoma, endodermal sinus tumor (EST), and embryonal carcinoma or teratocarcinoma with an admixture of EST or choriocarcinoma or both. Elevation of a marker was a grave prognostic sign. The 5-year survival rates were 100, 16, and 4% for stages I, II and III disease, respectively. An elevated level of one or more of the markers assayed was always useful for monitoring therapy. Decreasing level indicated regression. However, return of an elevated level to normal did not indicate eradication of all tumor and called for diagnosis by imaging modalities. Constantly elevated or increasing marker levels during treatment indicated resistance to therapy. An increasing level from any nadir during remission indicated recurrence. Elevated levels of any of the five markers tested were as important as imaging modalities, and often more sensitive.     

Teratocarcinoma stem cells

Human teratocarcinomas or mixed germ cell tumours are histologically composed of diverse tissues corresponding to somatic and extraembryonic (trophoblastic and yolk sac) like cells, as well as malignant stem cells. In typical teratocarcinomas these stem cells correspond to embryonal carcinoma cells, ie developmentally pluripotent cells equivalent to embryonic cells from the early stages of development. These cells have the capacity to differentiate and give rise to non-proliferating terminally differentiated tissue. Occasionally embryonal carcinoma cells can give rise to more differentiated stem cells which have the phenotype and the restricted developmental potential of choriocarcinoma and yolk sac carcinoma cells, or less commonly to somatic cell malignancies, indistinguishable from typical carcinomas, sarcomas, melanoma or lymphomas. Malignant transformation of benign somatic tissues in teratomas can also give rise to malignant stem cells, which all have a somatic cell phenotype. The biology and the clinical presentation as well as the response to chemotherapy of germ cell tumours depend on the nature of stem cells that form their proliferative compartment and account for the malignancy of these tumours.     

Testicular Germ Cell Tumours in Denmark 1976-1980 Pathology of 1058 Consecutive Cases

In the first five-year period of the Danish Testicular Carcinoma Study (DATECA) 1058 consecutive testicular germ cell tumours were examined. Of these, 554 were seminomas comprising 515 of typical type, 26 anaplastic and 13 spermatocytic; 497 were non-seminomas comprising 145 pure tumours and 352 mixed tumours of various types. Among the various subtypes of non-seminomas embryonal carcinoma (EC) was recorded in 87 per cent, endodermal sinus tumour (yolk sac tumour; EST) in 22 per cent, teratoma (T) in 55 per cent and choriocarcinoma (CC) in 17 per cent. Only very few tumours were pure EST or pure CC. Five tumours were recorded as 'others or uncertain'. The tumours were graded with regard to various histologic features. Moderate and severe necrosis, bleeding, and a large number of mitoses were significantly more frequent in non-seminomas. The presence of tumour tissue at the resection margin was also more frequent in non-seminomas. Tumours with a largest diameter of less than 2.5 cm had already caused metastases in 16 per cent of the seminomas and 29 per cent of the non-seminomas. Increasing size of the tumours was associated with increasing frequency of metastatic disease but this association was not directly proportional. Distribution of the various histologic types according to the stage of disease varied. Thus, 78 per cent of the seminomas presented in stage 1 while 54 per cent of the non-seminomas had localized disease. Anaplastic seminomas were distributed similarly to the non-seminomas while all spermatocytic seminomas, with one exception, were recorded as stage I. Of non-seminomatous subtypes pure EC was associated with the highest frequency of stage III, followed by mixed tumours containing CC components. Although the present series is large the heterogeneity of germ cell tumours demands further investigation of larger numbers to confirm some of the findings.     

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.     

Glutathione sulfhydryl transferase-pi expression in testicular germ-cell tumors - an immunohistochemical study of 30 cases

Glutathione sulfhydryl transferase (GST) is believed to play a major role in the detoxification of chemotherapeutic agents and therefore is thought to be important in chemoresistance. Thirty primary testicular germ cell tumors were stained immunohistochemically for GST pi using a rabbit polyclonal antibody and formalin-fixed paraffin-embedded tissue. There were 12 pure seminomas and 18 mixed germ cell tumors (GCTs). Immunostaining of each element present was graded as negative (-), weakly positive (+), or strongly positive (++). The results were as follows: seminoma (8/17 +, 9/17 ++); embryonal carcinoma (1/13 -, 7/13 +, 5/13 ++); mature teratoma (9/9 ++); immature teratoma (7/7 +); endodermal sinus tumor (7/8 +, 1/8 ++); and choriocarcinoma (1/1 -). These results show that variability exists in the expression of GST pi between different tumor types and between different examples of the same tumor type. Strongest expression was seen in seminomas and mature teratomas while other germ cell elements tended to show weaker staining. The staining patterns showed no apparent correlation with stage or response to therapy.     

Serum alphafetoprotein (AFP) in diagnosis and management of endodermal sinus (yolk sac) tumor and mixed germ cell tumor of the ovary.

Serum AFP was determined serially by radioimmunoassay in 13 patients with ovarian germ cell tumors and in one patient with bilateral pure gonadoblastoma. There were 4 patients with pure dysgerminoma, one with pure endodermal sinus tumor (EST) and 8 with mixed germ cell tumors, all containing EST. The patients with dysgerminoma and gonadoblastoma had normal serum AFP at all times. All patients with tumors containing EST had raised serum AFP, although in most cases it was first determined between 1 and 3 weeks after operation and there was no evidence of metastases. Serum AFP became normal 5 to 7 weeks after operation and began to rise when disease recurred. Serum AFP determinations detected presence of recurrent disease long before it became detectable by other methods. Serum CEA was determined serially by radioimmunoassay in 8 of these patients, including 2 who dies with metastases, and was normal on all occasions.     

Alpha-fetoprotein-producing non-germ cell tumours of the female genital tract

Elevated levels of alpha-fetoprotein (AFP), a foetal serum protein, occur mainly on the development of hepatocellular carcinoma (HCC) or germ cell tumours, including yolk sac tumour (YST) and embryonal carcinoma of the ovary. Rarely, other tumours of the female genital tract produce AFP. This article reviews the AFP-producing non-germ cell tumours reported in different parts of the female genital tract to date. These include different types of carcinomas and carcinosarcomas of the uterus, ovary and cervix and sex cord stromal tumours of the ovary. It is important for both pathologists and oncologists to be aware of such cases and the clinicopathological distinction from germ cell tumours, as the diagnosis would affect the management plan for the patient. The reviewed cases suggest that regardless of the patient’s age when no lesion is detected in the liver and stomach of a woman whose serum AFP level is abnormally high, the female reproductive system should be examined as a possible site of AFP-producing tumour. Biochemical, physiological and pathological features of AFP are briefly presented.