Prostitution, condom use, and invasive squamous cell cervical cancer in Thailand.

Cervical cancer is probably caused by a sexually transmitted agent. A case-control study was conducted in three hospitals in Thailand to investigate further the role of male sexual behavior, particularly regarding sexual contacts with prostitutes, in the development of this disease. Data were obtained from interviews with 225 married women with invasive squamous cell cervical carcinoma and 791 hospitalized controls, all of whom reported having only one sexual partner, and from interviews with their husbands. Risk of cervical cancer was strongly related to the women's husbands having visited prostitutes without using a condom when the husbands were less than 30 years old. A strong increasing trend in risk in relation to decreasing frequency of the husbands' condom use with prostitutes was observed, and a weaker increasing trend in risk with husbands' estimated lifetime total number of visits to prostitutes was found. The average latent period between the women's likely initial exposure to a sexually transmitted oncogenic agent and her diagnosis of invasive cervical cancer was about a quarter of a century. Regular use of condoms by customers of prostitutes could reduce the number of invasive cervical cancer cases in the general population of Thailand by at least one fourth.

PIP: Researchers compared data on 225 Thai married women with invasive squamous cell cervical cancer admitted to Siriraj and Chulalongkorn hospitals in Bangkok and at Maharaj Nakorn Chiang Mai Hospital during October 1979-September 1998 with data on 791 hospitalized Thai controls to examine the role of male sexual behavior and prostitution in the development of cervical cancer and the likely protective effect of condom use against cervical cancer. All the cases and controls claimed to have had only one sexual partner. Interviews were conducted with the husbands of all the cases and controls. There was a significant trend of increasing risk of cervical cancer as the frequency of husband's condom use with prostitutes declined (p = 0.004) (relative risk [RR] = 2.05 for rarely or never, 1.24 for sometimes, and 0.96 for always or frequently). The increasing risk of cervical cancer associated with little or no condom use with prostitutes was highest when the husbands were less than 30 years old (RR = 2.11 vs. 1.56-1.81 for age 20 or older). There was a weaker trend of increasing risk of cervical cancer with the husband's estimated lifetime total number of visits to prostitutes (p = 0.12). On average, the latent period between the wife's likely first exposure to a sexually transmitted oncogenic agent (i.e., date of their marriage) and her diagnosis of invasive cervical cancer was 24 years. These findings indicate the condom use with prostitutes would reduce the risk of cervical cancer.

Steroid related neoplasia in human liver.

Prior to the early 1970's, benign liver neoplasms were among the rarest of tumors. The seemingly rapid increase, especially in young females ingesting oral contraceptives, as well as the catastrophic presentation of many of the tumors resulting from liver rupture and hemoperitoneum, stimulated studies by several investigators. In the Liver Tumor Registry at the University of Louisville, we have examined the histologic material, and finalized the data on 227 tumors, the majority in young women. With few exceptions, they had used oral contraceptives or were either pregnant or immediately post-partum and presumably in a hyperestrogenic state. There have been 82 hepatocellular adenomas (HCA), 105 cases of focal nodular hyperplasia (FNH), and 31 hepatocellular carcinomas. The hepatocellular carcinomas occurred in non-cirrhotic livers, and 14 of the 31 cases were of a distinct, but rare type, polygonal cell carcinoma with lamellar fibrosis. While it seems reasonable to believe steroids play a role in adenomas and in FNH it is less certain that they produce hepatocellular carcinomas since malignant liver tumors are not uncommon in this age group without the use of oral contraceptives. With an estimated 50 million women either currently using or who have used oral contraceptives the risk must be very slight.

The significance of the pathologic findings in endometrial cancer.

Endometrial carcinoma includes several specific subtypes which have differing prognostic implications. The two most common subtypes are adenocarcinoma, not otherwise specified (NOS), and adenoacanthoma. Also included in the adenocarcinoma NOS are secretory carcinoma and mucinous carcinoma which have the same natural history as do adenocarcinomas without these features. Fortunately, the above types have the best prognosis and constitute approximately 80% of all endometrial carcinomas. They also present the major diagnostic problem for the pathologist in distinguishing atypical hyperplasia and some of the metaplasias from well-differentiated carcinoma. The tendency would appear to be the over-interpretation of these hyperplastic lesions. Other subtypes have a much less favorable outlook. They include papillary carcinoma, adenosquamous carcinoma, glassy cell carcinoma and clear cell carcinoma. There are two distinct types of papillary carcinoma, the papillary clear cell and the papillary nonclear cell carcinoma. These can readily be separated, and should be, on the basis of prognostic implications. Other pathologic parameters play a significant role in patient management and in the estimation of prognosis. These include postsurgical pathological staging, measurement of depth of myometrial invasion, lymphatic and blood-vascular invasion, serosal involvement, local spread and, perhaps most importantly, tumor grade. Nuclear grading proved to be a better predictor of treatment outcome than did either the FIGO or WHO grading systems. This was especially true in adenocarcinoma NOS, adenoacanthoma and papillary carcinoma.

Primary duodenal choriocarcinoma.

We report a case of nongestational extragenital choriocarcinoma arising in the duodenum of a 29-year-old woman. Immunohistochemical stains of the tumor were positive for human chorionic gonadotropin and human placental lactogen.

Malignant trophoblastic tumors with massive hemorrhage presenting as liver primary. A report of two cases.

Two women, aged 29 and 27, presented with evidence of recent hemorrhage and large tumors of the liver. One tumor was successfully resected; the other patient died of blood loss. Both lesions were almost identical and were indistinguishable from choriocarcinoma. Both patients had markedly elevated serum human chorionic gonadotropin (hCG) levels and positive pregnancy tests. Examination of the endometrium showed only proliferative endometrium, and the pelvic organs were found to be normal. Immunoperoxidase stains of the liver tumors were strongly positive for hCG and human placental lactogen. Alpha-1-antitrypsin and alpha-fetoprotein tests were weakly positive, and one patient tested positive for carcinoembryonic antigen.

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 1 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.

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.

Human liver tumors in relation to steroidal usage.

Since 1973 a number of investigators have reported an association between liver neoplasia and steroid usage. Through referral material we have examined the histology of over 250 cases of hepatic neoplasia, most in patients receiving steroid medications. The majority have been benign, predominantly focal nodular hyperplasia (55%) and hepatocellular adenoma (39%). The average age was 31.4 years; 83% had significant steroid exposure with an average duration of 71 months for focal nodular hyperplasia and 79.6 months for hepatocellular adenoma. The type of estrogenic agent was predominantly mestranol; however, during the period mestranol was the most frequently used synthetic steroid. A distinct clinical entity of life threatening hemorrhage from the lesion occurred in 31% of patients with hepatocellular adenoma and 9% of patients with focal nodular hyperplasia. Recurrence of benign tumors has occurred in some patients who continued using steroids and regression has been observed in patients who had incomplete tumor removal but discontinued steroid medication. Medial and intimal vascular changes have been present in a large number of the benign tumors. The relationship of these vascular changes to oncogenesis is unclear, but similar lesions have been described in the peripheral vasculature associated with steroid administration. A number of hepatocellular carcinomas have also been seen. Of significance is the young age of these patients and lack of abnormal histology in adjacent nonneoplastic liver. A striking number of the malignant hepatocellular tumors have been of the uncommon type described as "eosinophilic hepatocellular carcinoma with lamellar fibrosis." The epidemiology of liver lesions within this series is difficult to assess, since the material has been referred from very diverse locations.

PIP: Since 1973, a number of investigators have reported an association between liver neoplasia and steroid usage. Through referral material, we have examined the histology of over 250 cases of hepatic neoplasia, mostly in patients receiving steroids. The majority have been benign, predominantly focal nodular hyperplasia (55%) and hepatocellular adenoma (39%). The average age was 31.4 years; 83% had significant steroid exposure with an average duration of 71 months for nodular focal hyperplasia and 79.6 months for hepatocellular adenoma. The type of estrogenic agent was predominantly mestranol; however, during the period mestranol was the most frequently used synthetic steroid. A distinct clinical entity of life threatening hemorrhage from the lesion occurred in 31% of the patients with hepatocellular adenoma and 9% of patients with focal nodular hyperplasia. Recurrence of benign tumors has occurred in some patients who continued using steroids and regression has been observed in those who had incomplete tumor removal but discontinued steroid medication. Medial and intimal vascular changes have been present in a large number of the benign tumors. The relationship of these vascular changes to oncogenesis is unclear, but similar lesions have been described in the peripheral vasculature associated with steroid administration. A number of hepatocellular carcinomas have also been seen. Significant is the young age of these patients and the lack of abnormal histology in adjacent nonneoplastic liver. A striking number of the malignant hepatocellular tumors have been of the uncommon type described as "eosinophillic hepatocellular carcinoma with lamellar fibrosis." The epidemiology of liver lesions within this series is difficult to assess, since the material has been referred from very diverse locations.

Carcinoma of the endometrium. IV. Mixed adenosquamous carcinoma. A clinical-pathological study of 68 cases with long-term follow-up.

In a histologic review of 989 cases of invasive endometrial carcinomas there were 68 mixed adenosquamous carcinomas. Sixty were followed for at least five years, or until death. The other eight were diagnosed in 1976 and were ineligible for five-year status evaluation. Twenty-eight of the 60 patients or 46.7% were alive at five years. Twenty-five or 41.7% died of their cancer. Stage of disease, depth of myometrial invasion, vascular invasion, age, and method of treatment all had an impact on end results. By comparison, the absolute five-year survival rate for 200 women with adenocanthoma was 87.0%. Thirty patients with atypia of the squamous portion of the adenoacanthoma had an identical survival rate as those without atypia. Combined irradiation and hysterectomy end results were superior to hysterectomy only, or to radiation therapy only. Although one examination of time trends revealed a significant increase in the percentage of all tumors that were diagnosed as adenoacanthoma, there was no increase in the relative frequency of mixed adenosquamous carcinoma.

Carcinoma of the endometrium. II. Papillary adenocarcinoma: a clinical pathological study, 46 cases.

Forty-six patients with papillary carcinoma of the endometrium were studied. Forty-five were followed for at least five years or until death, and 41 were followed for 10 years. The remaining patient was alive at four years. The survival rate was 51.1% at five years and 46.3% at 10 years. At five years one-third had died of their disease. The median age at time of diagnosis was 63 years, and the age at diagnosis was an important determinant of survival. None of the seven black women survived for five years. Tumor grade was an important predictor of the course of disease and nuclear grading was a significantly more accurate indicator than was the histologic grading of the World Health Organization. Papillary carcinoma should be distinguished from the papillary type of clear cell carcinoma of the endometrium. While it has a somewhat better prognosis than mixed adenosquamous carcinoma or clear cell carcinoma, it appears to be more aggressive with a lower survival rate and higher rate of death from disease than the usual type of endometrial adenocarcinoma or adenoacanthoma.

Glassy cell carcinoma of the endometrium.

A variant of mixed adenosquamous carcinoma of the endometrium was encountered in 5 of 68 patients (7.4 per cent) with mixed adenosquamous carcinomas of the endometrium. A sixty patient had an isolated area of glassy cell carcinoma in an otherwise typical adenosquamous carcinoma. The ground-glass appearance of the cytoplasm, the distinctive nucleus with prominent nucleoli, the numerous mitoses, and the similarity of this tumor to previously described glassy cell cervix cancers all suggest that the tumor is glassy cell carcinoma. Four of the five tumors behaved in an aggressive manner.

Carcinoma of the endometrium. III. Analysis of 865 cases of adenocarcinoma and adenoacanthoma.

Eight hundred sixty-five patients with confirmed adenocarcinoma of the endometrium were studied. Eight hundred eleven were followed up for at least 5 years or until death, and 537 were followed up for 10 years. The survival rate was 77.1% at 5 years and 61.0% at 10 years. Age at diagnosis was the single most important clinical determinant of survival. Tumor grade was an important predictor of the course of disease, and nuclear grade was a significantly more accurate indicator than was histologic grade. Stage and depth of invasion were also important predictors of survival. The 5-year survival rate for black women was only 41.9%. Stage for stage and grade for grade, women undergoing hysterectomy alone and with radiation had similar survival rates. Adenoacanthoma had a better prognosis that did adenocarcinoma without squamous metaplasia; there were no deaths at 5 to 10 years in women diagnosed before age 50. The subtype of carcinoma was found to be a highly significant predictor of prognosis.

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 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.