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Context: Endometrial tissue specimens are commonly encountered in daily practice. It is well known that a number of problematic diagnostic scenarios occur relative to these specimens., Objective: To emphasize practical aspects of endometrial specimen handling and reporting, with selected comments on common diagnostic pitfalls, including (1) the diagnosis of endometrial intraepithelial carcinoma in atrophic endometrial biopsy specimens, (2) evaluation of adequacy of endometrial sampling specimens, (3) problems in diagnosing and measuring the depth of myometrial invasion in endometrial carcinoma, (4) the question of metastasis versus independent primaries in concurrent carcinomas of endometrium and one or both ovaries, (5) the problematic differential diagnoses between type 1 (primarily endometrioid) and type 2 (primarily serous) adenocarcinomas, and (6) atypical hyperplasia and proposed classification systems for its replacement., Data Sources: Published literature, consensus statements, and personal experience., Conclusions: A systematic approach to the handling and reporting of endometrial specimens reduces the potential for omission and error. Recognition of diagnostic pitfalls and practical approaches to their resolution help improve quality.

Context: The endometrium is an intrinsically dynamic tissue with great capability for regeneration and proliferation; consequently, there is some overlap between features seen in benign, premalignant, and malignant lesions. This leads to marked intrabiopsy, interbiopsy, and interobserver variability., Objective: We studied the specificity and sensitivity of computerized image analysis of molecular markers to evaluate its potential use as a diagnostic tool., Design: Specimens from 100 patients were examined and the following histologic diagnoses were assigned: proliferative endometrium (n = 10), secretory endometrium (n = 10), endometrial hyperplasia (n = 40; 30 with no atypia, 10 with atypia), and carcinoma (n = 40; 20 endometrioid, 10 serous, and 10 clear cell). All cases were evaluated immunohistochemically for p53 and proliferating cell nuclear antigen (PCNA) expression. Computerized image analysis was performed with a CAS 200 digital analyzer., Results: Expression of p53 was found only in carcinomas (65%) and endometrial hyperplasia with atypia (30%). Expression of p53 was higher in the poor prognostic categories (serous carcinoma and clear cell carcinoma) than in endometrioid carcinoma. In endometrioid carcinoma, p53 expression correlated with grade. Proliferating cell nuclear antigen showed a similar pattern of results to p53 in the various carcinoma subtypes and endometrioid carcinoma grades. Endometrial hyperplasia PCNA values were the lowest among all the groups. Both carcinomas and proliferative endometrium showed higher glandular and stromal PCNA values, significantly different from endometrial hyperplasia with atypia. In proliferative endometrium, stromal PCNA was the highest among all of the groups. The p53 and PCNA results correlated with each other for carcinoma., Conclusions: Computerized image analysis correlates well with the established morphologic groups of endometrial pathology and yields results consistent with previous studies. Owing to its higher degree of sensitivity, computerized image analysis is of potential use in cases of diagnostic dilemmas and can help objectively allocate the case in the correct category (e.g., proliferative endometrium vs. endometrial hyperplasia, endometrial hyperplasia with atypia vs. endometrioid carcinoma). It is particularly useful in the evaluation of stromal changes.

Currently, molecular pathology plays a limited role in improving patient outcome in gynecologic oncology. However, molecular investigation is providing important insights into the epidemiology, pathogenesis, and progression of female genital cancers. Future roles should include prediction of poor outcome in low-risk cases, more accurate staging of multifocal tumors, identification of new precursor lesions, and prediction of response to specific therapeutic regimens. Gene therapy of some malignant tumors may become important in the near future. In the immediate future, however, the most significant role of molecular pathology may be in the screening and triage of putative cervical cancer precursors and in the possible prophylaxis of these lesions by means of a vaccine or vaccines against human papillomaviruses.

To determine the prognostic significance of signet ring cells in infiltrating lobular carcinomas, the percentage of signet ring cells in 99 infiltrating lobular carcinomas was correlated with the patients' clinical outcomes (mean follow-up interval of 4.8 years). When the carcinomas were divided into those with 0%, 1-9%, and 10% or more signet ring cells, 57% (26/46) of patients with 10% or more signet ring cells had experienced recurrences or metastases compared with 40% (2/5) and 31% (15/48) with 0% and 1-9%, respectively. A similar analysis performed with breakpoints at 20% or 30% failed to yield any statistically significant associations. When patients were stratified by pathologic stage, patients with stage I disease and 10% or more signet ring cells were more likely to have recurrences or metastases than those patients with stage I tumors and fewer than 10% signet ring cells. There was no relationship between signet ring cells and disease progression in stages II, III, and IV. These results indicate that the presence of 10% or more signet ring cells represents a poor individual prognostic factor in stage I infiltrating lobular carcinomas.

As a quality assurance measure, the usefulness of transmission electron microscopy (EM) and immunohistochemistry (IHC) in our surgical pathology laboratory was compared. The surgical pathology reports from 150 consecutive neoplasms that were examined by both EM and IHC were reviewed. Based on the reported clinical histories, final diagnoses, light microscopy results, and the findings by EM or IHC, the contributions of EM and IHC were classified as "helpful" or "not helpful" for each specimen. Electron microscopy was helpful (92%) more often than was IHC (73%). Electron microscopy was most useful in further classifying poorly differentiated carcinomas, while IHC was particularly useful in classifying poorly differentiated neoplasms. Electron microscopy and IHC were of limited value in identifying the origin of metastatic carcinomas of an uncertain primary. All cases determined to be "not helpful" by either modality were further analyzed to establish a reason for the lack of information provided in each case. This analysis demonstrated a need for improved technical quality and ordering patterns of immunohistochemical stains in our laboratory.

Ten granulosa cell tumors of the ovary were investigated using clinicopathologic and flow cytometric parameters. Three of the patients had recurrent or metastatic lesions 3 to 9 years after resection of the primary ovarian tumor. These three cases demonstrated diploidy in both the primary tumor and metastatic or recurrent lesions. Among the seven cases without recurrence, five had diploid DNA indexes. One case was characterized by a high degree of cytologic atypia and tetraploidy (DNA index, 1.98); this patient died of metastatic breast cancer 4 years after resection of the ovarian tumor. Another case demonstrated a high mitotic rate and exhibited aneuploidy (DNA index, 1.33); this woman was alive and well at 5 years of follow-up. In this study, no correlation was found between the recurrence rate and ploidy but, in view of the small numbers and limited follow-up, we cannot definitively analyze these prognostic factors. It does not appear feasible to predict the clinical course of granulosa cell tumors by DNA flow cytometry. However, it can be concluded that: (1) most granulosa cell tumors have diploid DNA content and (2) DNA ploidy correlates well with histologic factors, such as cellular anaplasia and high mitotic activity, which may have predictive prognostic value for granulosa cell tumors.

Primary oncocytic carcinoma of the breast was diagnosed in a 76-year-old man. The histologic and electron microscopic features are characteristic of oncocytic neoplasms that occur at other sites, such as salivary glands and endocrine organs. The pathologic features and the presence of estrogen receptors biochemically are distinct from apocrine carcinoma. The patient is alive 7 years after modified radical mastectomy without additional chemotherapy or radiotherapy.

The autopsy plays an important role in neoplastic disease. Over one third of all adult autopsies disclose cancer, and clinical diagnostic errors are disclosed in approximately 40% of these. There is no evidence that diagnostic accuracy has improved in recent years. In addition to monitoring diagnostic accuracy--particularly with reference to new technologies--the autopsy is also important in detecting both new types of cancer and new causative agents and patterns of incidence and behavior in "old" types of cancer. It also plays a major role in characterizing the toxic effects of new therapeutic regimens and in establishing true causes of death (including accurate primary cancer sites) for setting local, national, and international research and health care priorities.

The lectin binding properties of ten cases each of adenomatoid nodule, follicular adenoma, and papillary carcinoma and five cases of microinvasive follicular carcinoma were examined histochemically and compared with adjacent normal thyroid tissue. Wheat germ agglutinin, concanavalin A, Ulex europaeus agglutinin I, peanut agglutinin, soybean agglutinin, Dolichos biflorus agglutinin, Ricinus communis agglutinin, and Helix pomatia agglutinin were employed. All the lectins but Ulex europaeus agglutinin I, peanut agglutinin, and Helix pomatia agglutinin were bound to thyroid parenchymal cells, colloid and stromal cells, but none uniquely to thyroid parenchymal cells. Helix pomatia agglutinin binding was present in stromal cells but not in parenchymal cells. Ulex europaeus agglutinin I binding to parenchymal cells was weakly positive only in five cases of papillary carcinoma. The binding in adenomatoid and neoplastic cells and their colloid was stronger than in adjacent normal thyroid tissue in all cases examined. Wheat germ agglutinin and concanavalin A binding was most intense among the lectins examined. In papillary carcinoma, lectin binding was observed mostly in the apical cytoplasm of carcinoma cells, whereas a diffuse surface binding pattern was predominant in follicular adenoma and carcinoma, adenomatoid nodules and normal thyroid gland. No consistent differences in lectin binding were found between follicular adenoma and carcinoma, or between adenomatoid nodules and follicular neoplasia.