Fig. 1.1
The relative incidence of testicular tumors in the study of Friedman and Moore [11] (Reproduced with permission of the publisher)
Fig. 1.2
Schematic drawing illustrating the developmental potential of embryonal carcinoma according to Friedman and Moore [11] (Reproduced with the permission of the publisher)
The original classification of Friedman and Moore [11] was first modified by Dixon and Moore and printed in the first edition of atlases of the Armed Forces Institute of Pathology [AFIP] in 1952 [16]. In that treatise, Dixon and Moore have in de facto divided testicular germ cell tumors in two groups: seminomas and all others, stating that embryonal carcinoma, choriocarcinoma, and teratomas are closely related tumors, as indicated in their drawing (Fig. 1.3). They also stated that there are numerous mixed forms, calculating at least 15 possible varieties and combinations which could be encountered in various tumors. To simplify the matters and to make the classification as clinically relevant as possible, Dixon and Moore [16] divided the germ cell tumors in five groups: (I) seminoma, pure; (II) embryonal carcinoma, pure or with seminoma; (III) teratoma, pure or with seminoma; (IV) teratoma with either embryonal carcinoma or choriocarcinoma or both and with or without seminoma; and (V) choriocarcinoma, pure or with either seminoma or embryonal carcinoma or both.
Fig. 1.3
Histogenesis of testicular tumors according to Dixon and Moore [16] (Reproduce with the permission of the publisher)
The classification proposed by Dixon and Moore [16] was modified several times over the last 60 some years [17–19], resulting in a clinically useful approach combined with an easily reproducible microscopic subdivision of testicular tumors. The 2004 classification sponsored by the World Health Organization [WHO] and recommended by the panel of WHO experts for general use has been further disseminated in the widely circulated in the AFIP series of atlases of pathology [19]. Even though this classification is primarily based on microscopic morphology of tumors [Table 1.1], it correlates well with the clinical requirements for subdividing testicular germ cell tumors into two major groups: seminomas and nonseminomas, also known as nonseminomatous germ cell tumors [NSGCT]. It also incorporates some of the basic histogenetic tenets and discoveries that were made over the years since the WWII. For epidemiologic research, for international studies, and for billing purposes, the International Classification of Diseases has produced its ICD-10 listing of testicular tumors, which is for completeness’ sake included as Table 1.2.1
Table 1.1
WHO 2004-based classification of testicular germ cell tumors
Testicular germ cell tumors |
|---|
Precursor lesions |
Intratubular germ cell neoplasia, unclassified |
Intratubular germ cell neoplasia, specific types |
Germ cell tumors of one histologic type |
Seminoma |
Spermatocytic seminoma |
Embryonal carcinoma |
Yolk sac tumor |
Trophoblastic tumors |
Teratoma |
Germ cell tumors of more than one histologic type |
Mixed germ cell tumors |
Polyembryoma |
Diffuse embryoma |
Regressed (“burnt-out”) germ cell tumors |
Germ cell sex cord-stromal tumors |
Gonadoblastoma |
Unclassified |
Table 1.2
Classification of testicular germ cell tumors
2014 ICD-10-CM diagnosis code C62.90 |
|---|
Malignant neoplasm of testis NOS |
Cancer of the testis |
Cancer of the testis, choriocarcinoma |
Cancer of the testis, nonseminomatous germ cell |
Cancer of the testis, seminoma |
Choriocarcinoma of testis |
Mixed germ cell tumor of testis |
Nonseminomatous germ cell neoplasm of testis |
Primary malignant neoplasm of testis |
Seminoma of testis |
Testicular cancer |
Testis, mixed germ cell tumor |
The limitations of space do not allow me to enumerate all the major figures who have played a critical role in advancing our knowledge about germ cell tumors during the last few decades. Thus, by necessity I will mention only five physician-scientists, realizing that this is a rather subjective choice, with a strong personal bias. Nevertheless, I feel that I would be remiss for not mentioning the comparative studies of Gunnar Teilum, which led to the better understanding of the similarities between ovarian and testicular germ cell tumors and the recognition of yolk sac carcinoma as a distinct entity [20]. Robert E. Scully was a true giant of urogenital and gynecologic pathology, whose contributions were recently lovingly reviewed by Oliva and Young [21–23]. His contributions are too many to list, but in essence his work over half a century helped us all to conceptualize and delineate some of the basic aspects of testicular and ovarian pathology. F. K. Mostofi was instrumental in defining the basic approaches to classifying testicular and other urogenital tumors promoting worldwide discussions under the aegis of the WHO [17, 24, 25]. The astute observations and persistence of Niels E. Skakkebæk led to the recognition of intratubular germ cell neoplasia [26]. G. Barry Pierce, my mentor and longtime friend, performed some of the fundamental experiments on mouse germ cell tumors and provided a new insight into the basic biology of human germ cell tumor based on sound scientific principles [13].
1.3 Classification of Ovarian Germ Cell Tumors
Ovarian germ cell tumors are basically equivalent to those originating from male germ cells. Yet there are some important biological and clinical differences between these two groups of tumors [27–29]. For example, in contrast to the malignant nature of the vast majority of testicular tumors, most ovarian tumors are benign, presenting clinically as mature teratomas.
Experimental data obtained in mice indicate that ovarian teratomas are formed from parthenogenetically activated ovarian germ cells [30]. Human parthenotes isolated from the ovaries can rise to embryonic stem cells [31], and thus by extrapolation, one can assume that these cells could give rise to teratomas and other germ cell tumors as well.
The histogenesis of teratoma can be readily explained by parthenogenetic activation of ovarian germ cells. The histogenesis of malignant ovarian germ cell tumors is a bit more complicated, and several histogenetic schemes have been proposed, as reviewed by J. Prat in the monograph which he has edited with G. Mutter [31]. Despite many attempts to modify our understanding of malignant ovarian germ cell, histogenesis is still incomplete. The panel of experts of WHO has thus decided to base the latest WHO classification of malignant germ cell tumors on the most popular model of histogenesis of these tumors dating back to the work of Teilum [20]. According to this scheme, the malignant germ cell can form either dysgerminoma or embryonal carcinomas, which in turn could give rise to choriocarcinoma, yolk sac carcinoma, or teratoid tumors. In the expanded histogenetic algorithm presented here (Fig. 1.4), we propose that the tumor formation depends in all cases on parthenogenetic activation of the ovarian germ cells [ova], which may give rise as such to benign tumors, i.e., teratomas. Alternatively, if the germ cells undergo malignant transformation, they may give rise to dysgerminoma or form embryonal carcinoma cells. EC cells may form either a monotypic tumor-embryonal carcinoma or by differentiating into somatic and extrasomatic cells and tissues form the malignant stem cells of a malignant mixed germ cell tumor. Even monotypic EC tumors contain syncytiotrophoblastic cells, which may be present in most of such tumors. EC cells can sometimes differentiate into yolk sac or choriocarcinoma cells, which as such may form tumors of the same name, overgrowing the EC component, which may be hard to find. Alternatively, EC cells may remain part of the mixed germ cell tumors which in such cases will contain several other distinct components: EC cells, teratomatous tissues, yolk sac tumor, and choriocarcinoma, or various combinations of these elements. There is also some evidence that dysgerminomas may give rise to embryonal carcinoma, but there is no doubt that they can be part of mixed germ cell tumors. An abbreviated most recent classification of all these ovarian germ cell tumors is presented in Table 1.3.
Fig. 1.4
Hypothetical histogenesis of ovarian germ cell tumors, based on the original concepts of Gunnar Teilum [20]. The key processes in the formation of various germ cell tumors, such as parthenogenetic activation of the oocytes, and the malignant transformation of their descendants (marked in red) remain still incompletely understood
Table 1.3
WHO 2014 histologic classification of ovarian germ cell tumors
Dysgerminoma |
Yolk sac tumor (primitive endodermal tumor) |
Embryonal carcinoma |
Polyembryoma |
Non-gestational choriocarcinoma |
Teratomas |
Immature |
Mature |
Solid |
Cystic |
With secondary tumor |
Monodermal |
Struma ovarii |
Carcinoid tumor
 Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
Get Clinical Tree app for offline access
|