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The Nature and Classification of Ovarian Neoplasms M Canad. Med. Ass. J. 1102 Current Progress: Ovarian Neoplasms May 21, 1966. vol. 94 1lljf83J^ll£*#^^ The Nature and Classification of Ovarian Neoplasms M. R. ABELL, M.D., Ph.D., Ann Arbor, Mich., U.S.A. ABSTRACT SOMMAIRE The classification of ovarian neoplasms on L'auteur etudie la classification des neo- a histogenetic basis according to present- plasmes ovariens d'apres des criteres histo- day concepts of development and structure genetiques bases sur nos connaissances of the ovary is considered. There are four actuelles du developpement et de la struc¬ histogenetic categories of primary ovarian ture de l'ovaire. II admet quatre categories tumours: neoplasms of germ cell origin, neo¬ histogenetiques des tumeurs ovariennes plasms of celomic (germinal) epithelium and primaires: les neoplasmes des cellules ger- its derivatives, neoplasms of specialized minales, les neoplasmes de Tepithelium gonadal stroma (sex cords and mesen- ccelomique (crete ge*nitale) et de ses de- chyme), and neoplasms of non-specialized rives, les tumeurs du stroma gonadique dif- gonadal stromal and heterotopic elements. ferencie (cordons sexuels et mesenehyme) et In patients of all ages, 70% of ovarian neo¬ les neoplasmes des cellules du stroma gona¬ plasms were of celomic epithelial origin, dique nos differenciees (gonocytes) et des 16% of germ-cell origin, 5% of specialized elements heterotypiques. Chez l'ensemble gonadal stromal origin, and 9% arose from des patientes, considerees independamment the non-specialized stroma and heterotopic de Tage, 70% des neoplasmes ovariens elements. Before 20 years of age, 59% of avaient leur origine dans Tepitheiium ccelo¬ ovarian neoplasms were of germ cell origin mique, 16% dans les cellules germinales, and before puberty they accounted for 90% 5% dans les cellules differenciees du stroma of all ovarian tumours. The different struc¬ gonadique et 9% provenaient du stroma non tural types of neoplasms within the four differencie et d'el&nents heterotypiques. categories are described. Accurate classifica¬ Chez les femmes agees de moins de 20 ans, tion of ovarian neoplasms on a histogenetic les neoplasmes ovariens avaient comme basis is stressed if proper treatment is to origine les cellules germinales et, avant la be given and intelligent assessment of end puberte, ils expliquaient 90% de toutes les results is to be made. tumeurs ovariennes. L'auteur decrit les divers types structuraux des neoplasmes des quatre categories. II souligne la necessite de classifier les neoplasmes ovariens d'apres une base histogenetique. Si on veut donner A BEWILDERING variety of structurally differ- le traitement convenable, il importe ¦"¦ ent neoplasms, benign and malignant, occur in d'evaluer intelligemment les resultats the ovary. The majority of these (75% ) are benign ultimes. when discovered but many have the potential of becoming malignant if they are not removed or of behaving so if they escape the confines of the ovary. The latter lesions are malignant by virtue of posi¬ is about 15%. The overall survival rates for pa¬ tion rather than of cytological structure. In roughly tients with frankly malignant ovarian neoplasms are 20% of patients with ovarian neoplasms there are low, but there is considerable variation according bilateral autochthonous lesions, usually synchronous. to histological type. These aspects of ovarian neo¬ The percentage is somewhat higher for malignant plasms, together with the apparent two- to three- neoplasms, but it is often difficult to separate bi¬ fold increase in their occurrence since 1930,2 make lateral primary lesions from single unilateral this problem both interesting and vitally important. primaries with metastases. The ovary ranks third Most pathologists, and I am no exception, are as the primary site of gynecological cancers follow¬ collectors of things and thoughts. In this instance ing the uterine cervix and corpus uteri. In our ma¬ the things are ovarian neoplasms and the thoughts terial ovarian lesions account for 9% of female are observations on pathogenesis, structure and genital cancers1 but in other series the percentage natural course. It is inevitable that such a collec¬ tion be put in order and that a classification evolve. From the Department of Pathology, The University of Many of the classifications that have been offered Michigan, Ann Arbor, Michigan, U.S.A. are either and too cumbersome for Presented at the Clinical Conference on Cancer of the Ovary illogical practi¬ sponsored by the Ontario Cancer Treatment and Research cal use or are far too and fail to recognize Foundation. University of Windsor, Windsor, Ontario, simple November 5, 1965. neoplasms that have distinctive clinical and histo- Canad. Med. Ass. J. Progress: Ovarian Neoplasms 1103 May 21, 1966, vol. 94 Current Pig. -j..Section of a normal ovary from a prepubertal child. The surface is covered by a single layer of flattened epithelial (celomic) cells. Groups of ova surrounded by single layers of follicular (granulosa) cells are scattered throughout the cortex. One developing follicle deep in the cortex consists of proliferating granulosa cells about an ovum with a surrounding in- distinct zone of pale fibroblastic cells representing a developing theca. (H & E X 125.) logical features. The ideal classification, if there be sex cord cells persist as supportive elements about such, should be basically simple, yet accurate, the ova. Remnants of the sex cords may be found systematic, and capable of quick expansion and in the medulla and are a constant finding in the modification as questionable lesions are more cor¬ hilum in the form of the rete ovarii.4 rectly defined and new entities delineated. These At birth the surface of the ovary is covered by requirements are best met by a classification that is a single layer of flattened cuboidal cells represent¬ based on histogenesis according to our present-day ing a modified peritoneum and referred to as understanding of the development and structure of celomic or germinal epithelium (Fig. 1). These the ovary. cells often become hyperplastic during the repro- ductive years and may take on the characteristics Aspects of Normal Development and of epithelial cells of the fallopian tube (endo- Structure of Ovary salpingiosis), endometrium (endometriosis) or endocervix. As a result of of Before discussing the components of a histo¬ repeated rupture genetic classification of ovarian neoplasms, it is follicles and following inflammatory changes in the essential to consider certain aspects of normal de¬ area, pieces of this surface epithelium become and structure. The first sequestered and form small cortical inclusion cysts. velopment gonads appear of as condensations of mesenchyme, the gonadal These are commonly encountered near the end ridges (folds), beneath the posterior celom into the reproductive period and thereafter. which migrate primordial germ cells from the endo- Numerous germ cells are present in the ovarian derm of the yolk sac.3 Shortly thereafter, differentia- cortex at birth and remain prominent but decrease tion begins and cords of cells grow down from the in numbers during childhood (Fig. 1). They are covering celomic (germinal) epithelium. These are absent at the end of the reproductive period. Most clearly visible by the sixth week of gestation. If of these cells can be recognized as ova but others the gonad is destined to become a testis, the sex are smaller and less mature in appearance. The cords persist and form seminiferous tubules, where¬ immature cells are more easily identified in dys- as if the call is for an ovary, the cords disintegrate genetic ovaries. During the reproductive period and largely disappear. Some workers believe that (Figs. 2 and 3), developing and atretic follicles Canad. Med. Ass. J. 1104 Current Progress: Ovarian Neoplasms May 21, 1966, vol. 94 Fig. 2..A developing follicle. The wall is formed by granulosa cells which, at one pole. encase the ovum and form the cumulus oophorus. Surrounding the granulosa cells is the thecal zone consisting of two ill-defined layers, the theca interna and the theca externa. (H & E X 66.) ****** Fig. 3..This is a higher magnification of the follicle shown in Fig. 2. Scattered division figures can be seen among the proliferating granulosa and theca cells. (H & E X 320.) Canad. Med. Ass. J. Current Progress: Ovarian Neoplasms 1105 May 21, 1966, vol. 94 Fig. 4..Section from the hilum of a normal ovary. The irregular-shaped tubule is part of the rete ovarii Small polvgonal hilus (Leydig) cells form an ill-defined mass adjacent to this tubule. (H & E X 160.) are found in the cortex, and corpora lutea, formed by pale or vacuolated cuboidal cells albicantia and fibrosa are located in the adjacent supported by a basement membrane and a muscular medulla. wall. Accessory adrenal tissue is present in the The stroma is a region of the ovary in 10 to 20% of patients (Fig. cortical specialized mesenchyme cortical that varies considerably in structure with age. It 5). These adrenals of Marchand consist of masses contained is scant in infants and very prominent in women cells only and are sharply defined near the and for there¬ within a definite fibrous capsule. This arrangement menopause varying periods col¬ after. It forms a thin outer zone of relatively hyaline contrasts with the scattered, non-encapsulated fibrous tissue, the tunica albuginea. Beneath this is lections of hilus cells with which they have been the cellular functioning cortex which gives rise to confused. theca and lutein cells, and possibly granulosa cells, although the latter may be derived from the sex A Histogenetic Classification cords. In the histogenetic classification of ovarian neo¬ Certain structures are present in the hila and/or plasms that we employ, there are four basic cate¬ adjacent mesovarii of ovaries and are important in gories (Table I). In the germ-cell category, all neo¬ the pathogenesis of some neoplasms. The retia plasms are included that are thought to arise from ovarii are always present, and if the work of Gill- primitive germ cells and those that may develop in man4 is accepted, they represent remnants of the these tumours as secondary cancers, such as a primitive sex cords from the celomic epithelium.
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