William M. Christopherson

Carcinoma of the endometrium: I. A clinicopathologic study of clear‐cell carcinoma and secretory carcinoma

In a pathologic review of 1224 cases of endometrial carcinoma, 1023 were confirmed cases of endometrial carcinoma. Fifty‐six (5.5%) were clear‐cell adenocarcinoma (CCE). Fifteen cases of “secretory carcinoma” (SCE) were examined for comparison. Fifty‐five patients with CCE and all with SCE were followed for at least five years or until death. There were only 19 survivors among those with CCE. No five‐year survivor subsequently died of disease. Of the 15 patients with SCE, 13 survived for five years although two additional patients died of recurrent disease at 5.4 and seven years. All survivors of CCE were Stage I patients at the time of diagnosis. All were postmenopausal, and had a median age of 67 years compared with 58 years for patients with SCE. Unlike SCE, the morphology of CCE was preserved in the subsequent hysterectomy specimen, in the recurrent disease, and in the metastases. CCE was proportionately more common in black women and the five‐year survival was only 12.5% as compared with 39.1% for white women. In contrast to endometrial carcinoma in general, most women who failed treatment died of disease. There was no increase in the relative frequency over the 23‐year time period of the study. Age at time of diagnosis seemed to be an important prognosticator. Prognosis also correlated well with stage of disease and depth of myometrial invasion. It correlated to a somewhat lesser extent with the method of treatment and had a poor correlation with the histologic pattern or degree of cellular differentiation: however, essentially all tumors were considered to be poorly differentiated. Finally, a histologic tissue marker in the form of hyalin‐like, PAS‐positive, diastase‐resistant bodies was found in the 64% of the women with CCE.

Carcinoma of the endometrium V. An analysis of prognosticators in patients with favorable subtypes and stage I disease

A review of the pathologic material from patients in our population based uterine cancer registry in Louisville, Kentucky identified three subtypes of endometrial carcinoma with a favorable prognosis: adenoacanthoma, adenocarcinoma with no specific features, and secretory carcinoma. Three subtypes with a much less favorable prognosis were papillary carcinoma, mixed adenosquamous carcinoma, and clear cell carcinoma. The other important determinants of treatment results were: stage of disease, age, race, nuclear grade, and depth of myometrial invasion. This study evaluated these prognostic determinants for the favorable subtypes with Stage I disease that were fully treated. There were 595 patient eligible for five‐year and 380 for ten‐year vital status evaluation. Only three patients were lost to follow‐up at five years and four at ten years. The five‐year survival was 88.1% and the ten‐year 74.5%. At five years 4.4% were dead of disease and at ten years 6.3%. There were 115 women younger than age 50. Their five‐year survival was 98.3% and at ten years 94.6%. None was dead of disease at five years and only one at ten years. Black women had a significantly lower survival than did white women, but no black woman younger than age 50 died of disease. Nuclear grade was the most important histologic determinant of survival, followed by depth of myometrial invasion. Recommendations for treatment planning were formulated based on these prognosticators.

Cervical cancer control. A study of morbidity and mortality trends over a twenty‐one‐year period

Data from a 21‐year period are presented to evaluate the effects of a mass cytologic screening program on uterine cancer morbidity and mortality in Louisville, Jefferson County, Kentucky. The success of screening was greatest in the younger age groups. There was a fall‐off after age 45 years, especially in those age 60 years or older. Women at highest risk for cervical cancer, in the low socioeconomic quartile, had a better initial screening rate than the two middleincome quartiles, and had the highest rate of all women for subsequent rescreening. The greatest decrease in both morbidity and mortality was in women under the age of 50 years. Women age 30–39 and 50–59 years benefitted the most, as measured by mortality, with a decrease of 70.8 and 69.0%, respectively. There was no change in mortality rates for those age 70 years or older. Although there was individual benefit among the screenees with endometrial carcinoma, the average annual age‐adjusted rate increased from 13.2 to 15.3/100,000 women over the 21‐year period.

Cervix cancer death rates and mass cytologic screening.

Death rates for cervix cancer and total uterine cancer among women 20 years old and older have decreased significantly in Jefferson County, Ky., from 1953‐1967. Death rates have not changed significantly in Kentucky outside of Jefferson County during this time period. The average age at time of death from cervix cancer is 7.6 years greater for Jefferson County residents during the last 3 years of the study compared to the first 3 years. The only known factor which could account for these observations is a mass cytologic screening program for cervix cancer in Jefferson County; there was no such mass screening effort in the rest of the state.

Clinical and morphologic features of hepatic angiosarcoma in vinyl chloride workers

Fifteen male workers exposed to vinyl chloride developed angiosarcoma of the liver. Thirteen died of disease and two are currently living for short periods after diagnosis. Their ages ranged from 36 to 58 years (average 47.5 years). Their exposure time ranged from 4 to 27.8 years (average 16.9 years). The most common presenting symptoms were fatigue, weight loss, and abdominal pain. Hepatomegaly followed by splenomegaly were the most common physical findings. Biochemical profiles yielded variable results and proved to be of little value in the detection or diagnosis. Of eight patients autopsied, distant organ involvement was present in two cases, duodenal involvement in one, and direct extension of tumor to adjacent organs or tissues in four additional ones. The remainder, diagnosed by open liver biopsy, revealed no tumor extension. The gross features of the tumors were hemorrhagic necrosis, cystic degeneration, fibrosis, and apparent multicentricity. The histologic features were those of the typical angiosarcoma found in a variety of sites with a wide range of cellular differentiation. The histologic diagnosis was often impaired by the extensive tumor necrosis. Elsewhere in the liver subcapsular fibrosis, a distinct type of portal fibrosis, and endothelial cell hyperplasia with or without sinusoidal dilatation were noted. The reduction of industrial chemical exposure has already been achieved and will hopefully eliminate this chemically related tumor in the future. There is, however, a significant group of previously exposed workers who will require careful monitoring to detect functional abnormalities of the liver and possible early neoplastic changes.

Cervix cancer control in Louisville, Kentucky

The results of 12 years of mass cytologic screening of a community for protection from uterine cancer are reported, and the effects upon incidence rates of the various component cancers are analyzed. A preceding 3‐year period during which no screening was performed was used to calculate the expected rates. Total cancers of the uterus, including carcinoma in‐situ, had an average annual rate of 125.5 per 100,000 women 20 years of age and older during the 15‐year period. During the last 3‐year period, carcinoma of the cervix was diagnosed at an earlier stage, and the rates decreased by one third. Carcinoma in‐situ increased in proportion to screening activity. There was an increase in the rate for endometrial carcinoma. The greatest response to screening was in women under 50 years of age. This group showed the greatest decrease in rates and was, for the most part, diagnosed at an earlier stage of the disease. On the other hand, older women were less inclined to avail themselves of cytologic screening.

Carcinoma of the endometrium: A study of changing rates over a 15-year period

A 15‐year study of endometrial carcinoma in Louisville‐Jefferson County, Kentucky, revealed an increase of 26.3% in average yearly rates when the first 3 years, 1953‐1955, were compared with the last 3 years, 1965‐1967. An increase of 15.9% persisted when the rates were corrected for aging of the population; this was not statistically significant. Thus the mass cytologic screening program which had a beneficial effect on the rates for invasive cervix cancer, failed to have such an effect on endometrial carcinoma.

Atypical endometrial changes associated with carcinoma

Abstract Attempts to identify precursors of endometrial carcinoma have been made sporadically over the past 25 yr. This summary includes additional material on the subject.

Lucy wortham james award. Cytologic detection and diagnosis of cancer. Its contributions and limitations

The use of cytology for the detection and diagnosis of cancer has been a rapidly developing area of pathology. Cytology has been used for mass screening of asymptomatic people, for selective screening of individuals at high risk, and for diagnosis in patients suspected of having cancer. The only area in which mass screening has proved to be cost effective in reducing morbidity and mortality rates is cancer of the uterine cervix. Selective high risk screening has been proposed for endometrium, lung, urinary tract, gastrointestinal tract and oral cavity. Field trials have been performed for each site and some are still operational While a degree of success has been achieved in identifying patients with early and asymptomatic cancer, cost effectiveness has not as yet been demonstrated and it seems unlikely that it will be. The cytologic diagnosis of cancer of these sites in symptomatic patients is highly effective for lung and bladder cancer. It has been somewhat less effective for gastrointestinal cancer. It is also of value in identifying cancer cells in effusions and for cancer staging. Fine‐needle aspiration biopsy for the diagnosis of cancer has been used for over half a century, but in more recent years it has gained wider usage and is now used to diagnose tumors of almost any organ. It is highly cost effective, does not require hospitalization or anesthetic, and is rapid and accurate. Some of the indications and limitations of cellular diagnosis of cancer are presented.

Dysplasia, carcinoma in situ, and microinvasive carcinoma of the uterine cervix

Carcinoma in situ is defined as the early stage of cancer and must therefore be initiated by an as yet unknown carcinogen(s). Progression of the lesion to invasive carcinoma is reported to occur in a high proportion of nontreated cases. Reserve cell proliferations are frequently associated with both dysplasia and carcinoma in situ, and it is suggested that these are the cells from which both lesions arise. Dysplasia may result from both carcinogenic and noncarcinogenic stimuli. Since dysplasia usually either regresses or remains stabilized over a prolonged period, it is suggested that it is more frequently associated with noncarcinogenic stimuli. Microinvasive carcinoma is limited to lesions with no more than 5 mm. of stromal invasion as measured from the surface. Confluence of growth and lymphatic-like space invasion should not interdict the diagnosis. Microinvasive carcinoma thus defined rarely gives rise to lymph node metastasis or eventuates in death. The diagnosis cannot be made from punch biopsy specimens. Only if pathologists adhere to a standard nomenclature can follow-up studies be used successfully to identify the natural behavior of each type of lesion in this spectrum.