James W. Reagan

Definition of precursors

Abstract In this retrospective study of 100 cases of cervical intraepithelial abnormalities, the nuclear DNA content was correlated with the histologic findings and follow-up data. All cases had initial biopsies and were followed for more than a year with cytologie and/or histologic examinations. Of the 34 cases having a subsequent normal follow-up, 29 (85%) had a euploid or polyploid pattern and 5 (15%) had an aneuploid distribution. Of the 58 cases persisting as cervical intraepithelial neoplasia (CIN), 3 (5%) had a polyploid pattern and 55 (95%) had an aneuploid distribution. Of the 8 cases which progressed to invasive carcinomas, all had an aneuploid pattern. These findings suggest that euploid or polyploid lesions are more likely to have normal follow-up studies (91%) and rarely persist (9%). Of the aneuploid lesions, 81% persisted as CIN, 12% progressed to invasive carcinoma, and 7% had a normal follow-up. The presence of abnormal mitoses was the most reliable histologic criterion for aneuploidy. By using nuclear DNA analysis and histologic features, as defined in this study, it is possible to distinguish aneuploid precursors from less significant euploid or polyploid lesions.

DYSPLASIA OF THE UTERINE CERVIX

The term dysplasia can be used to designate a group of hetcroplastic lesions involving the surface epithelium of the uterine cervix that are basically characterized by a relative or an absolute increase in the number of immature cells and by certain manifestations of abnormal differentiation. Similar or related changes have been described in the medical literature under a varied terminology including atypia,12 l o atypical,s* or irregular e p i t h e l i ~ m , ~ , l9 anap la~ ia ,~” precancerous metapIasia,2 dissociated intraepithelial anaplasia,17 basal cell hyperplasia5r I4 or hype rac t i~ i ty ,~ atypical hyperplasia,13 dyskaryo~is,’~ leukohyperkeratosis,’” and leukoparakeratosis The literature also includes numerous lesions ( lassified as carcinoma iiz sifu whose histopathological changes are similar to those under i onsideration. The dysplastic lesions vary not only in regard to their tontent of abnormal or primitive cells, hut also as to the relative degree of immaturity of these elements. This, in part, explains the multiplicity of terms that have been applied to these changes. IVhen the magnitude of the dysplasia is great, the changes approach those observed in carcinoma i?z situ and warrant a more serious consideration. On the basis of our present knowledge, a slight degree of dysplasia is relatively unimportant, being more analogous to lesions categorized as “metaplasia with atypicality”” or even so-called. “basal cell hyperplasia.”5j 7 , l 4 This study is based on 100 cases of hist opathologically proved dysplasia. Cellular preparations were obtained hy scraping the uterine cervix and aspirating the contents of the cervical (anal. Using a systematic meander scanning pattern designed to cover the entire slide, the features and measurements of altered cells were recorded a t regular intervals in an attempt to pro\7ide a random sample of the cellular specimen. The entire 4 d e i fas studied in order to count the number of altered cells present and to record and identify the groupings of the cellular elements. Similar st udies were made on 100 cases of in si/u cancer and 100 cases of invasive cancer, all of which were verified by biopsy.

Fibrosarcoma Arising at the Site of Bone Infarcts

Two patients were studied with multiple, idiopathic bone infarcts secondarily complicated by the development of fibrosarcoma at the site of infarction. Similar association of these lesions has not been reported in the literature. A brief review is presented of the pathophysiology of caisson disease and bone infarcts. An analysis of other known causes of bone infarcts failed to provide an explanation for the multiple bone infarcts present in these two patients, and similarly no direct relation was found in these cases to other benign bone lesions complicated by malignant-tumor formation.

Adenocarcinoma and mixed carcinoma of the uterine cervix: I. A clinicopathologic study

Ninety-two primary glandular neoplasms of the uterine cervix, including 51 endocervical adenocarcinomas, four endometrioid carcinomas, and 37 mixed carcinomas, were reviewed to define the biologic significance of pathologic features. Pure adenocarcinomas were found to have a better prognosis from mixed carcinomas of comparable stage (overall five-year survival rate, 49 vs. 36%). Endocervical adenocarcinomas with glandular and papillary patterns had a better prognosis than mucinous adenocarcinomas. When mixed carcinomas were separated into mature, signet-ring, and glassy-cell types, patients with the glassy-cell type had a better five-year survival rate than patients with the other types. However, the long-term prognosis was equally poor. The degree of differentiation as determined by the nuclear features was useful in predicting the outcome in patients with adenocarcinomas. Although the number of cases was small, combined surgery and radiotherapy achieved the best long-term survival for patients with pure adenocarcinomas. This was less apparent for mixed carcinomas.

Adenocarcinoma and mixed carcinoma of the uterine cervix: II. Prognostic value of nuclear dna analysis

The prognosis of the glandular neoplasms of the uterine cervix is related to the clinical stage and, to a lesser extent, to the histologic type, growth pattern, and degree of differentiation of the neoplasms. To determine further the prognostic significance of the stem cell ploidy levels as determined by nuclear DNA quantitation, the authors separated the tumors into low ploidy (less than 3N) and high ploidy (greater than 3N) groups. Of the clinical Stage I and II neoplasms, low ploidy tumors had a better prognosis than high ploidy tumors of comparable stage. Low ploidy tumors had a better prognosis than high ploidy tumors irrespective of the degree of differentiation. Mixed carcinomas had a poorer prognosis than pure adenocarcinomas of comparable clinical stage. This might be explained by the greater proportion of high ploidy stem cells in mixed carcinomas than in pure adenocarcinomas. Although advanced clinical Stage III and IV neoplasms had a poor outlook regardless of the DNA ploidy level, there was a proportional increase of high ploidy tumors with increasing clinical stage. These findings suggest that cervical glandular neoplasms having high ploidy stem cell lines are biologically more aggressive than those with low ploidy stem cell lines.

The ovarian brenner tumor; Its gross and microscopic pathology

Abstract The Brenner tumor is an uncommon benign ovarian neoplasm which is usually unilateral in location. The solid or cystic tumors are variable in size, usually firm, pale yellowish-gray, and well circumscribed. A study of their histopathology reveals polyhedral cells arranged in masses and columns frequently surrounded by degenerate and hyalinized connective tissue. When cysts occur, they are lined by flattened, cuboidal, or columnar epithelium containing glycogen and secretory granules staining with mucicarmine. In this study of 23 cases, serial sections of a small subcortical tumor revealed definite continuity between superficial inclusions and the tumor. A second tumor studied did not reveal conclusive evidence of such an origin.

Histologic types and prognosis of cancers of the uterine cervix

Cancer of the cervix is a model for the successful management of an adult cancer. With the widespread utilization of the Papanicolau smear, and the automation of cytoanalysis, cancer of the cervix has been transformed from a dreaded disease detected in advanced stages to one which is most frequently, particularly in this country, seen as a non-invasive or microinvasive malignancy. The value of early detection by means of simple, accurate and inexpensive screening procedures is evident in the change in stage distribution over the decades in major university and cancer centers. The increasing percentage of Stages 0 and 1A patients in proportion to the whole population of cervical cancer patients has accentuated the interest in the entire process of malignant transformation. Although the pathologist has long been concerned with the dysplastic process as a precursor for malignancy, it is in this site more than any other that the clinician has fine tuned his clinical awareness and judgement as to cellular changes that predict or indeed are precursors for malignancy. The task of the pathologist is to distinguish atypical proliferation which is en route to carcinoma in situ from benign states due to non-carcinogenic causes. Christopherson analyses the stages of initial pathogenesis from metaplasia to dysplasia to carcinoma in

Clinical significance of postirradiation dysplasia of the uterine cervix

Abstract The cytologic and histologic characteristics of postirradiation dysplasia are presented and described. Results of an analysis of the records and survival of 84 patients with postirradiation dysplasia encountered in the follow-up after treatment for carcinoma of the uterine cervix are presented. A significant variation in survival was observed in patients with postirradiation dysplasia as compared to patients with identical clinical stage and histologic grade in the absence of this lesion. Postirradiation dysplasia within 3 years after treatment for cervical carcinoma was associated with a poor prognosis.

The changing nature of endometrial cancer

Abstract Over three decades there was a progressive decrease in the number of cervical squamous cell cancers detected and an increase in the number of precancerous changes. Over this period of time there was a progressive increase in the number of glandular neoplasms detected in the uterus. Endometrial cancer accounted for most of the increase. One type of endometrial cancer, the adenosquamous cancer, was detected more commonly in the last decade. The emergence of this neoplasm is of some importance because of the short duration of symptoms and the poor response to ionizing radiation.

Significance of squamous components in endometrioid carcinoma of the ovary.

Forty‐nine cases of ovarian endometrioid carcinoma with squamous foci were reviewed. Of particular interest was the biologic behavior of the neoplasms in relation to the appearance of the epithelium. As previously noted for the analogous uterine endometrial tumors, the ovarian adenosquamous lesions occurred later in life, were more advanced, were associated with less differentiated adenocarcinomatous components, and had a poorer prognosis. The five‐year survival rate for patients with adenosquamous endometrioid ovarian carcinoma was 21% in comparison with the 90% survival found in patients with ovarian endometrioid adenoacanthoma. Cancer 44:614‐621, 1979.