Gynecologic oncology: changing perspectives.

As knowledge grows and our experience is tabulated and analyzed, there must occur modifications in our management of disease and in the principles and policies that direct our decisions. In gynecologic oncology, some degree of change in perspective has taken place in almost every aspect, in prevention, screening, detection, diagnostics, and therapeutics, as well as in the attention devoted to the sociologic, emotional, and political implications of cancer in women. The specialty is now 50 years old and was established and fostered by physicians who thought in surgical terms and who were willing and competent to extend their technical arena as far and as fast as continuous improvements in anesthesia and other support measures permitted. The textbooks and journal publications of that era clearly mirror this emphasis. A new generation of gynecologic oncologists has assumed leadership. Their training is broad, and their knowledge and competence extends far beyond technical surgery. This is well illustrated by the program of this conference. And comparison of this program with that of the last session five years ago clearly demonstrates how far we have come from a time of preoccupation with morphology and technique.

The stilbestrol disorders in historical perspective.

In the late 1960's when a series of adolescent girls with adenocarcinoma of the vagina presented themselves to our hospital, we did not immediately suspect the cause. Previous experience with radical hysterectomy and with vaginal reconstruction had prepared us technically to treat them sucessfully. Then a clue to etiology from one mother's observation regarding DES as a pregnancy supportive medication was quickly and conclusively converted into fact by an investigation with case controls. Rapid expansion of our knowledge came about through information accumulated in a Registry, and untoward effects other than cancer soon came to notice as young asymptomatic women presented themselves for examination because of known fetal exposure. The dominant event is clearly recognizable ss teratogenic, resulting in anomalous development of the vagina and cervix. Although the appearance of clear cell adenocarcinoma in a small fraction of DES-daughters is a consequence, the role of DES in its carcinogenesis is still unproved.

The embryologic development of the human vagina.

Our present understanding of the sequence and mechanisms of human genital organogenesis is reviewed. Current theories about the derivation of the vaginal epithelium are examined and tested against two anomalous circumstances, congenital androgen insensitivity and agenesis of the lower vagina, which are presented as examples demonstrating the respective participation of the urogenital sinus or of the Müllerian ducts alone in the developmental process. The abnormalities recently described in the vagina and cervix of girls exposed in utero to diethylstilbestrol (DES) correspond remarkably with those encountered in lower vaginal agenesis, particularly with regard to the presence of vaginal adenosis, the deficiency of glycogen in the squamous cells (squamous metaplasia), and the abnormal response of the squamous epithelium to Schiller's iodine test. It is concluded that the development of the human vagina is best explained by the theory which holds that the Müllerian ducts in fetal life extend caudally to the level of the future hymen. After fusion of these ducts, squamous cells arising in the epithelium of the urogenital sinus invade from below, advance, and replace completely the Müllerian mucosa up to the level of the external os of the cervical canal.

PIP: The course of development of the human genital tract is undifferentiated up to the 9th week (32 mm). At this time both Wolffian (mesonephric) and Mullerian (paramesonephric) ducts are present as symmetric paired structures. These, together with the urogenital sinus and the metanephric ducts, provide the tissue sources for the internal genital and urinary apparatus, exclusive of the gonads and kidneys. Configuration of the oviducts varies among species. Most human anomalies may be represented in other species so that some authors consider them to be atavistic reversions. The gonad of the developing male fetus plays a critical role in the formation of the genital tract. It elaborates androgenic steroids and a polypeptide, a Mullerian inhibiting substance, which induced suppression and resorotion of the Mullerian ducts. In the female the Mullerian ducts grow and develop into their adult morphology while the Wolffian ducts persist only as microscopic islands. The development of the external genitals and secondary sex characteristics depends upon further exposure to androgenic or estrogenic hormone milieu. a case is reported of an instance of congenital absence of the upper vagina. At laparotomy normal sized uterus, tubes, and ovaries were found. Further plastic surgery via the vagina corrected the condition. 15 years later (age 32) it was learned that she had been married and had 3 pregnancies. The adenosis, areas of squamous metaplasia, and deformities of the cervix of girls exposed in utero to diethylestibestrol are examples of deranged development. The shallow depth or absence of the vaginal canal of individuals with testicular feminization are also due to faulty development. Both Mullerian tissue and that of the urogenital sinus origin normally participate in the development of the vagina. In the normal adult the squamous cells that line the vagina contain abundant glycogen indicating urogenital origin. Glycogen-deficient squamous cells and adenosis are thought to be of Mullerian origin. In an accompanying discussion additional details of development are mentioned. It was noted that 7 cases of adenocarcinoma of the prostatic utricle in males have been reported as resembling endometrial carcinoma. The prostatic utricle is a homologue of the uterus and upper vagina and may be involved in similar deranged developments

The stilbestrol-adenosis-carcinoma syndrome.

This disease complex is one of the few entirely new and previously unsuspected discoveries of the recent past. The first case, seen in 1966, ushered in an era of suspicion. A study and report on the first seven cases published in 1970 inaugurated the era of hot pursuit which culminated in 1971 in an epidemiologically structured and controlled investigation of possible etiologic factors. With the establishment of the stilbestrol association a Registry of Cases was initiated. , heralding the era of verification. This Registry, while accelerating and embossing confirmation of the suspected relationship, served an even more useful purpose by collecting under one roof and in front of one cluster of observers all the necessary and relevant data on a sufficiently large number of cases to enable rapid (1973-1974) wide dissemination of knowledge about the occurrence and behavior of the disease and its response to treatment. The behavior of these tumors is comparable to that of other cancers at this location. When they are still localized, cure is possible by either surgery or radiation therapy. Since all the individuals at risk can be identified by their clinical history, screening examination for presymptomatic cancer is entirely feasible. At the same time we can and should note the presence and nature of any morphologic anomalies of the kind, which are seen in a very high proportion of the women exposed before the 18th week of fetal life.

Glassy cell carcinoma of the cervix.

A clinicopathologic analysis of 13 cases of glassy cell carcinoma of the uterine cervix is presented. The glassy cell carcinoma is considered to be a poorly differentiated mixed adenosquamous carcinoma. Its histologic appearance is distinctive, being characterized by cells with a moderate amount of cytoplasm having a ground glass or finely granular appearance, a distinct cell wall that stains with eosin and PAS, and enlarged nuclei with prominent nucleoli. In the present study this tumor was associated with extrapelvic spread in 6/13 cases at diagnosis. Results were poor with either surgery and/or radiotherapy. Only four of 13 patients survived 5 years. The glassy cell carcinoma appears to be a distinct clinicopathologic entity which warrants a place in the classification of carcinoma of the cervix.