Liane Deligdisch

The spectrum of endometrial pathology induced by progesterone receptor modulators

Progesterone receptor modulators (PRM) are hormonally active drugs effective in the management of endometriosis and uterine leiomyomata. The endometrial effects of progestin blockade by PRMs in premenopausal women are currently being evaluated in several clinical trials, but few pathologists have had access to these materials and published information of the histological changes is scanty. Eighty-four endometrial specimens from women receiving one of four different PRMs were reviewed by a panel of seven experienced gynecologic pathologists to develop consensus observations and interpretive recommendations as part of an NIH-sponsored workshop. Although the pathologists were blinded to agent, dose, and exposure interval, the review was intended to provide an overview of the breadth of possible findings, and a venue to describe unique features. Endometrial histology included inactive and normal-appearing cycling endometrium. Overtly premalignant lesions (atypical hyperplasia or EIN) were not seen. In a subset of cases, asymmetry of stromal and epithelial growth resulted in prominent cystically dilated glands with admixed estrogen (mitotic) and progestin (secretory) epithelial effects of a type not encountered in contemporary clinical practice. The variety of endometrial appearances suggested that findings might differ by agent and dose over time according to relationships that must be specified for each agent. The constellation of changes seen in those endometria with cystically dilated glands is so novel that new terminology and diagnostic criteria are required for pathologists to recognize them. The panel has designated these changes as PRM-associated endometrial changes (PAEC). Additional follow-up studies will be needed to fully define their natural history and relationship to specific agents and administration regimens.

Ovarian intraepithelial neoplasia demonstrated in patients with stage I ovarian carcinoma

Retrospective review of sections of ovary from 50 patients with stage I, grade 1-3, epithelial ovarian carcinoma was performed to assess presence of cellular and nuclear atypia in noncancerous tissue adjacent to the primary tumor; ovarian tissue from 50 patients undergoing incidental oophorectomy was reviewed as well. Atypia was more common in cancer patients, and finding the combination of nuclear atypia, defined as presence of pleomorphism or irregular chromatin distribution, with cellular atypia, defined as presence of stratification or loss of polarity, allowed separation of cancer and control groups with 98% sensitivity and 100% specificity. Presence of nuclear and cellular atypia was used to define ovarian intraepithelial neoplasia (OIN). If OIN is demonstrated to precede ovarian carcinoma, then it may offer insights into the development of ovarian cancer and may eventually increase the feasibility of screening for this disease.

Histologic correlates and virulence implications of endometrial carcinoma associated with adenomatous hyperplasia

The association of endometrial carcinoma (EC) with endocrinopathies manifested by obesity, nulliparity, and/or increased estrogen levels of exogenous or endogenous estrogens is now well‐known. EC is also seen in patients without these findings. Are these different cancers? Seventy‐four cases of EC were reviewed and classified into two groups: group I, with associated adenomatous hyperplasia (AH), 31 cases; and group II, without associated AH, 43 cases. Group I included more well‐differentiated and less invasive carcinomas; histologically, the pattern was glandular in all cases. In Group II, the EC were less well‐differentiated, more invasive, and included, besides adenocarcinomas, clear‐cell, papillary, and anaplastic carcinomas with giant tumor cells. Squamoid features were found in both groups. The possible existence of two types of EC, a hormonal‐dependent EC associated with AH (which is believed to result from hyperestrogenism, and to have a better clinical prognosis), and an “independent” EC, not associated with AH, is discussed.

Ovarian dysplasia. A Study of identical twins

The normal, identical twin sisters of patients who had been the subjects of ovarian cancer were subjected to prophylactic oophorectomy after the menopause. The finding of epithelial abnormality suggests a precancerous change similar to other genital epithelial dysplasia.

Prophylactic oophorectomy: a morphologic and immunohistochemical study.

The tumorigenesis of ovarian carcinoma is poorly understood. The authors studied morphologic features and immunohistochemical expression patterns of neoplasia‐associated markers in prophylactically removed ovaries, normal ovaries, and papillary serous ovarian carcinomas to identify possible preneoplastic changes in ovarian surface epithelium.

Pathologic changes in gonadotropin releasing hormone agonist analogue treated uterine leiomyomata

OBJECTIVE To define the pathologic changes underlying the mechanism of shrinkage of uterine leiomyomata in patients treated with luprolide acetate. DESIGN Retrospective study of pathologic changes seen in leiomyomata removed by hysterectomy or myomectomy in treated and untreated patients, matched by age and size of uteri and leiomyomata. PATIENT(S) Gross description and histologic slides of 30 treated and 30 untreated patients. INTERVENTION(S) Histologic examination performed blindly (without knowledge of treatment). Statistical work-up using chi 2 analysis with 1 df. MAIN OUTCOME MEASURE(S) Degree of hyaline and hydropic degeneration, cellularity, nuclear atypia, necrosis, and obliteration of interface. RESULT(S) Confluent nodular hyaline degeneration representing a scarlike retraction, geographic hydropic degeneration necrosis and obliteration of the interface between myoma and myometrium were found in higher proportions in the treated patients; differences in cellularity, nuclear atypia, and edema were not statistically significant. CONCLUSION(S) The decrease in size of the treated leiomyomata occurs as an accelerated postmenopausal shrinkage because of the antiestrogenic effect of the therapy. Obliterated cleavage planes may explain the difficult enucleation of myomatous nodules in some of the treated patients.

Characterization of ovarian dysplasia by interactive morphometry

This study defines, by morphometric analysis, criteria for the diagnosis of ovarian dysplasia. Areas of surface epithelium, adjacent to Stage I ovarian serous papillary adenocarcinoma, were diagnosed as dysplastic and evaluated for architectural and cytologic changes by means of two specially designed interactive morphometric procedures. Statistical evaluation was based on stepwise discriminant analysis of multiple quantitative descriptors. A data base was generated by analyzing histologic slides from eight normal (control), and 13 malignant ovarian tissues. Confirmation of the diagnosis was achieved in each case. The histologic criteria for ovarian dysplasia differ from those used for ovarian borderline malignancy. Interactive morphometric image analysis offers an objective method for delineating cancer precursors that could be used in ovarian biopsies taken by laparoscopy or during incidental abdominal surgery. It could be applied to cancer precursors in other locations.

Clinical features of advanced ovarian mixed mesodermal tumors and treatment with doxorubicin- and cis-platinum-based chemotherapy

Records of 15 patients with stage III and IV malignant mixed mesodermal tumors of the ovary treated between 1977 and 1988 were reviewed. All patients had primary surgery; 13 were given postoperative chemotherapy including doxorubicin and cis-platinum. Median survival for patients receiving chemotherapy is 16 months; 62% were alive at 12 months and 31% at 24 months. Progression-free responses were seen in 85% of treated patients and 55% of these recurred. All recurrences involved the pelvis and were predominantly mesenchymal. Serum CA-125 values accurately reflected tumor presence in 82% of tested patients. Cytoreductive surgery followed by treatment including doxorubicin- and cis-platinum-based chemotherapy is effective in treatment of disseminated ovarian mixed mesodermal tumors, but additional components must be added to achieve durable responses and consistently prolonged survivals.

Endometrial Adenocarcinoma Associated With Intrauterine Pregnancy A Report of Five Cases and a Review of the Literature

SummaryEndometrial adenocarcinoma associated with pregnancy is a rare lesion; only 14 acceptable examples have been reported in the literature. This study describes five additional examples with a critical review of the previously published cases. Four of the five women were nulliparous and three had sought medical intervention for infertility. The tumors were all well-differentiated endometrioid adenocarcinomas; three had a focal to extensive papillary pattern and three had focal to extensive squamous differentiation. Four were diagnosed at the time of dilatation and curettage and one at the time of cesarean section for a 28-week, live infant. Follow-up was available for four of the five women. Two women underwent hysterectomy with bilateral oophorectomy and were alive and well 12 and 48 months after diagnosis. The woman who had the live birth and the remaining woman were treated by repeat curettage with or without progesterone therapy, and each woman has had two subsequent full-term pregnancies with live births. These women are alive and well 57 and 58 months after diagnosis. Women with focal, well-differentiated carcinomas can successfully maintain their fertility if followed by repeat curettage with or without progesterone therapy.

Chemotherapy for Angiosarcoma of the Breast: Case Report of 30-Year Survival and Analysis of the Literature

Angiosarcoma of the breast is a rare and highly malignant neoplasm with few long-term survivors. Little is known about the effects of chemotherapy for patients with disseminated disease or its role in the adjuvant setting. We report the case of a patient with metastatic angiosarcoma of the breast who achieved a long-term clinical and pathological remission after treatment with methotrexate. The 30-year course of her disease is the longest reported survival with documented metastatic angiosarcoma of the breast. Analysis of the role of chemotherapy in the adjuvant setting and its effects in relation to histological subtype is undertaken. Adjuvant chemotherapy for patients with poorly differentiated angiosarcoma of the breast results in a higher proportion of patients relapse-free (29.2%) compared to patients not receiving adjuvant chemotherapy (4.4%) (p < 0.05). Patients with well-differentiated tumors do not appear to derive benefit from adjuvant chemotherapy. The effects for patients with disseminated disease are reported.