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Malignant Germ Cell Tumors of the Ovary and Testis an Immunohistologic Study of 69 Cases R

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Malignant Germ Cell Tumors of the Ovary and Testis an Immunohistologic Study of 69 Cases R ANNALS OF CLINICAL AND LABORATORY SCIENCE, Vol. 9, No. 6 Copyright © 1979, Institute for Clinical Science, Inc. Malignant Germ Cell Tumors of the Ovary and Testis An Immunohistologic Study of 69 Cases R. J. KURMAN, M.D.,* P. T. SCARDINO, M.D.,t K. R. McINTIRE, M.D.J T. A. WALDMANN, M.D.J N. JAVADPOUR, M.D.J and H. J. NORRIS, M.D.§ * Department of Pathology, U.S.C. School of Medicine and LAC-USC Medical Center, Los Angeles, CA 90033 f Department of Urology, U.C.L.A. Medical Center, Los Angeles, CA 90024 | National Cancer Institute, N.I.H., Bethesda, MD 20014 § Division of Gynecologic Pathology, Armed Forces Institute of Pathology, Washington, DC 20007 ABSTRACT An immunohistologic study of 21 patients with germ cell tumors of the testis with measured serum levels of human chorionic gonadotropin (HCG) and alpha fetoprotein (AFP) was undertaken to correlate the various types of neoplasms with the presence of these tumor markers in the tissue and serum. The same immunoperoxidase technique was applied to 48 patients with malignant germ cell tumors of the ovary in whom serum was not available. In the testicular tumor group, 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 syncytiotrophoblastic component of choriocarcinoma. Eighteen of the 21 patients (86 percent) had elevated tumor markers in their serum; serum HCG alone was elevated in 5 (24 percent), AFP alone in 5 (24 percent) and both were elevated in 8 (38 percent). There was tissue localization of HCG in 12 of 13 patients (92 percent) with elevated serum HCG while AFP was identified in the tumor in eight of the 13 patients (53 percent) with elevated serum AFP levels. In the ovarian tumor group, all 15 endodermal sinus tumors examined were positive for AFP and negative for HCG. Seven of 10 embryonal car­ cinomas were positive for AFP and all 10 were positive for HCG. The two cases of choriocarcinoma were both positive for HCG and negative for AFP. In contrast, the 11 dysgerminomas and 10 teratomas were negative for both AFP and HCG. The results parallel those for malignant germ cell tumors of the testis, affording additional evidence of the analogous nature of germ cell tumors of the gonads. Based on these findings a tentative immunohisto­ logic classification of germ cell tumors utilizing AFP and HCG is proposed. Thus, embryonal carcinoma is frequently associated with both AFP and HCG, endodermal sinus tumor with AFP and choriocarcinoma with HCG, whereas pure seminoma, dysgerminoma and teratoma are unlikely to be associated with either marker. * Present Address: Georgetown University, School of Medicine, Department of Pathology, 3800 Reservoir Road, Washington, DC 20007. 462 0091-7370/1100-0462 $00.90 © Institute for Clinical Science, Inc. MALIGNANT GERM CELL TUMORS OF OVARY AND TESTIS 463 Introduction have been confused because terms such as embryonal carcinoma, teratocarcinoma, The value of alpha-fetoprotein (AFP) malignant teratoma, teratoblastoma, en- and human chorionic gonadotropin dodermal sinus tumor, yolk sac tumor, (HCG) as tumor markers in the diagnosis embryonal carcinoma of the infant testis and management of germ cell tumors of have been used interchangeably.9 the testis is now well established.1’2,10,11,14 Clinically, determination of these mar­ 2. Until recently, histopathologic studies of germ cell tumors have not kers has merit for several reasons as fol­ lows: paralleled the advances in tumor immu­ nology. Consequently, a contemporary 1. Successful treatment of patients with hypothesis of AFP and HCG synthesis by germ cell tumors depends on accurate germ cell tumors is compromised by out­ clinical staging. Occult metastasis not de­ moded concepts of histopathology. For tectable by lymphangiography can be example, the presence of HCG in the identified by the presence of elevated serum of patients with germ cell tumors levels of AFP and/or HCG in the serum has been regarded as evidence of the using highly sensitive and specific radio­ presence of choriocarcinoma. However, immunoassays (RIA).11,14 the rarity of choriocarcinoma arising in the 2. Chemotherapy is most effective male testis (only 18 cases of pure chorio­ when used for the eradication of micro­ carcinoma among 6,000 testis tumors on scopic rather than gross disease.16 The RIA for AFP and HCG has been shown to file in the American Testicular Tumor be effective in detecting early “occult” Registry at the Armed Forces Institute recurrence before tumor can be identified of Pathology and only 5 percent of mixed by clinical examination and can therefore germ cell tumors contain chorio­ be used to direct chemotherapy.11,14 carcinoma)9 is inconsistent with the fact 3. Since certain tumor markers are as­ that approximately 70 percent of non- sociated with particular histologic types, seminomatous testicular germ cell tumors determination of these markers may have are associated with elevated serum levels prognostic import.14 of HCG as measured by RIA.24 4. Similarly, tumor markers, by iden­ 3. F inally, since 40 percent of testicular tifying specific tumor types, may be sig­ germ cell tumors9 and almost 10 percent of nificant in the selection of appropriate ovarian germ cell tumors7 are composed of therapeutic agents.17,25 combinations of two or more histologic For these reasons it is apparent that a patterns, it is manifestly impossible to de­ correlation of the histologic type with the termine which element in the tumor is tumor markers is vital for a rational ap­ responsible for the synthesis of a particu­ proach to accurate diagnosis and man­ lar tumor marker in the serum using or­ agement of ovarian and testicular germ thodox histologic techniques. In view of cell tumors. Also, a correlative histopatho­ this limitation an investigation was under­ logic and tumor marker study might be taken to identify the specific cellular helpful in shedding light on the histo­ components responsible for the synthesis genesis of this poorly understood group of of AFP and HCG using an immuno- neoplasms. Factors that must be consid­ histologic method. ered in this type of study and problems encountered in the past are the following: Methods 1. In view of their rarity, much of the The analysis of testicular tumors8 was confusion regarding germ cell tumors has based on 21 patients for whom paraffin resulted from a lack of a uniform terminol­ blocks of tissue were available. Serum de­ ogy. Neoplasms with distinctive his­ terminations of AFP and HCG were per­ tologic patterns and biologic behavior formed either prior to or within 30 days of 464 KURMAN, SCARDINO, MCINTIRE, WALDMANN, JAVADPOUR AND NORRIS tissue acquisition, thereby permitting a tile type, characterized by a distinctive correlation of the various histologic pat­ reticular-papillary pattern was found in terns together with the cellular localiza­ four instances. tion of AFP and HCG and the levels of Trophoblast was present in two forms in these markers in the serum. An indirect this group of tumors. One type, corre­ immunoperoxidase technique for the sponding to choriocarcinoma, contained localization of AFP and HCG, previously an intimate admixture of cytotrophoblast reported by Kurman and Norris,5,6 was and syncytiotrophoblast and was found in selected since this method can be used in two cases. The other form was comprised a retrospective fashion to study tumors in of syncytiotrophoblastic giant cells exclu­ paraffin blocks,—frozen tissue not being sively. These were typically multi­ necessary. The tumors were classified in nucleated with abundant eosinophilic or accordance with the classification of tes­ amphophilic cytoplasm containing one or ticular neoplasms proposed by Mostofi more vacuoles of varying size. These cells and Price.9 were found in association with areas of A double antibody RIA developed by embryonal carcinoma in 11 instances, Vaitukaitis and associates, specific for the with endodermal sinus tumor in one case /3 subunit,22 was utilized for the quantita­ and with seminoma in another. tion of the serum level of HCG and a dou­ With the immunoperoxidase technique, ble antibody RIA developed by HCG was found only in the syncytiotro­ Waldmann and Mclntire23 was used for phoblastic element of choriocarcinoma quantitation of AFP in the serum. (two cases) or in syncytiotrophoblastic Serum samples were not available for giant cells (13 cases). the patients with ovarian tumors. Con­ sequently, this part of the study was lim­ AFP was identified in the mononuclear ited to an immunohistologic analysis of 48 embryonal carcinoma cells of embryonal pure malignant germ cell tumors using an carcinoma in seven of the eleven cases (47 immunoperoxidase technique identical to percent) and within similar type cells in that utilized for the testicular study. The two of the four areas of endodermal sinus ovarian neoplasms were classified in ac­ tumor (50 percent). Cells in which HCG cordance with the WHO classification for was localized did not contain AFP and ovarian tumors adopted in 1973.15 similarly those in which AFP was localized did not contain HCG. Thus, it Results appears that AFP and HCG are found in and probably synthesized by two dis­ T e s t ic u l a r G e r m C e l l T u m o r s tinctly different cell lines. The cellular (21 c a s e s ) constituents of seminoma, teratoma, and Areas of typical seminoma were found the cytotrophoblastic element of chorio­ in seven instances. carcinoma were negative for both AFP Areas of teratoma containing elements and HCG. derived from all three germ cell layers Elevated serum levels of AFP alone were encountered in eight instances.
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