Clues to the pathogenesis of fallopian tube carcinoma: a morphological and immunohistochemical case control study.

The purpose of this study was to identify histopathological fallopian tube changes that might be related to the development of fallopian tube carcinoma (FTCA). Each of 14 unilateral cases of the latter was matched with 2 controls for age, hospital, and year of diagnosis. The uninvolved fallopian tube from patients with FTCA, all of which were of serous type, was compared to fallopian tubes from the same side in 28 matched controls. The features evaluated included plical bridging, trapped gland-like structures, inflammation, epithelial stratification, tufting, nuclear atypia, plical atrophy, luminal dilatation, and presence or absence of in situ carcinoma. The significant changes (p < 0.05) in the contralateral tubes of patients with FTCA were luminal dilatation (p = 0.0004), plical atrophy (p = 0.0015), and chronic inflammation (p = 0.0089). FTCA may therefore develop in tubes demonstrating histologic features of chronic healed salpingitis, findings that reflect bilateral tubal disease which apparently antedates the development of the FTCA. p53 stains were strongly positive in 9 of 14 FTCAs and in 5 of 6 foci of in situ carcinoma found in the tubes with unilateral FTCA. No p53 staining was found in any of the contralateral tubes. Serous FTCAs may be etiologically related to antecedent bilateral healed chronic salpingitis and arise from in situ carcinoma in a background of atrophy.

Expression of angiopoietin-2 by human endometrial endothelial cells: regulation by hypoxia and inflammation.

The functional endometrial layer receives the implanting blastocyst, but is sloughed off during menstruation. Angiogenesis regulates growth and repair of cycling human endometrium. While vascular endothelial growth factor initiates angiogenesis, the angiopoietins (Angs) acting via the Tie2 receptor, are key regulators of subsequent angiogenic steps. This study is the first to localize Ang-2 and Tie2 in human endometrium and to study Ang-2 regulation in cultured human endometrial endothelial cells (HEECs). Immunohistochemistry revealed that expression of Ang-2 and Tie2 was absent from the glands, low in stromal cells, and intense in the endothelial cells. In contrast, only weak expression of Ang-1 was detected. The phase of the menstrual cycle did not appear to affect the expression of Ang-2 or Tie2. In vitro studies were carried out utilizing isolated HEECs, the most relevant model for endometrial microvascular biology studies. Both hypoxia and phorbol-myristate-acetate enhanced Ang-2 mRNA levels in HEECs. These results suggest that Ang-2 plays a role in endometrial pathologies complicated by impaired blood flow and inflammation.

Effects of leuprolide acetate on low-grade endometrial stromal sarcoma.

We describe a low-grade endometrial stromal sarcoma coexistent with leiomyoma and adenomyosis treated with leuprolide acetate. We describe its histologic characteristics and clinical significance.

Xanthogranulomatous tubo-ovarian abscess resulting from chronic diverticulitis.

We report a case of xanthogranulomatous tubo-ovarian abscess which was preoperatively suspected to be an adnexal neoplasm. With foreign body material found in the abscess wall and vegetable fiber in the tubal lumen, a previously treated chronic diverticulitis was the presumed cause. Culture studies showed polymicrobial isolates which included Escherichia coli, an enteric pathogen. After surgery, administration of antibiotics, and revision of delayed subcutaneous wound healing, the patient is reportedly well.

Progestin-epidermal growth factor regulation of tissue factor expression during decidualization of human endometrial stromal cells.

Perivascular decidualized human endometrial stromal cells (HESCs) are ideally positioned to prevent peri-implantational hemorrhage during endovascular trophoblast invasion by expressing tissue factor (TF), the primary cellular mediator of hemostasis. Earlier in vivo and in vitro studies have demonstrated enhanced TF expression in estradiol (E2)-primed HESCs during progestin-induced decidualization. However, the absence of estrogen or progesterone response elements from the TF gene promoter suggests that paracrine factor(s) may mediate these effects. We now demonstrate that significant elevation of TF messenger RNA and protein levels in the cultured HESCs require incubation with both epidermal growth factor (EGF) and the progestin medroxyprogesterone acetate (MPA) added, with or without E2. By contrast, no effects were elicited by adding EGF with E2, or by the separate additions of EGF, MPA, or E2 plus MPA. Our finding, that transforming growth factor-alpha, but not transforming growth factor-beta or interleukin 1-beta mimics these EGF effects, indicates that progestin-enhanced TF expression in cultured HESCs requires activation of the EGF receptor (EGFR). Western blot analysis indicated that MPA increased EGFR levels 2-to 3-fold in cultured HESCs. The current results suggest that the progestin up-regulation of TF levels in decidualized HESCs is mediated by enhanced EGFR expression.

Fine-needle aspiration cytology of malignant fibrothecoma of the ovary.

Fibrothecomas are common, but their malignant counterpart is extraordinarily rare. To the best of our knowledge, this is the first report on the cytologic features of malignant fibrothecoma. We had an opportunity to study it because the 70-yr-old woman refused initial surgery until the tumor reached 22 cm in size and weighed 1, 500 gm. A CT-guided fine-needle aspiration biopsy was obtained from a 5 cm left pelvic mass, which was the second recurrence within 5 yr. The smears showed large fragments of tightly packed, small, oval cells with scanty, eccentric blue cytoplasm (Diff-Quik stain), and finely granular chromatin with small central nucleoli (Ultrafast Papanicolaou stain), transected by delicate blood vessels. The tumor resembled well-differentiated carcinoma, low-grade endometrial stromal sarcoma, and other small oval cell gynecologic neoplasms. Cytodiagnosis of nonepithelial ovarian neoplasms can be difficult. However, it is not impossible, especially for recurrent tumors with previously established histodiagnosis. Diagn. Cytopath. 21:284-286, 1999.

Peritoneal cytology in uterine papillary serous carcinoma.

OBJECTIVE: To highlight the significance of positive peritoneal cytology in uterine papillary serous carcinoma (UPSC). STUDY DESIGN: Seventeen consecutive UPSC cases with peritoneal cytology from 1993 to 1997 were reviewed and compared with the original cytologic diagnosis and extent of tumor involvement in tissues. RESULTS: Of the 17 post-menopausal women with UPSC, 11 had early-stage tumors (clinical stage I and II); three cases (27%) with positive peritoneal cytology were upgraded from at least International Federation of Gynecologists and Obstetricians stage IA to IIIA. No change in surgical stage was noted in four of six (67%) advanced cases with positive peritoneal cytology. The review diagnoses of peritoneal cytology did not differ from the original diagnoses. CONCLUSION: The features of UPSC in peritoneal cytology are those of a high grade malignancy and may be shared by tumors with similar histology from other sites. The malignant features are readily identified, but the site of origin may not be completely ensured. Positive peritoneal cytology upgrades the surgical stage of early-stage UPSC cases and helps with prognostication and treatment. One case with positive washings but without residual tumor probably represented early spread and/or multicentric origin of the tumor.

Atypical cellular chorangioma.

We describe an unusual, large atypical cellular chorangioma with abundant mitoses and focal necrosis. Other than premature birth, the prenatal and postpartum clinical course was unremarkable for both the mother and baby. Our case and a few similar cases reported in literature suggest that atypical cellular chorangioma is a benign tumor, despite its worrisome histopathologic features.

MIB-1 expression is useful in distinguishing dysplasia from atrophy in elderly women.

Both atrophic and dysplastic cervical squamous epithelia show lack of maturation, nuclear crowding, and increased nuclear/cytoplasmic ratio. Because of these similarities, distinguishing dysplasia from atrophy in cervical biopsies from elderly patients is often problematic. Because dysplasia shows increased proliferation and atrophy has decreased proliferation, the possible utility of MIB-1 in distinguishing dysplasia from atrophy was evaluated. One or more of the following criteria were present in all nine cases with dysplasia and in none of the 17 cases with atrophy: MIB-1 expression in > 20% of cells in the basal one-third of the epithelium, > 5% of cells in the middle one-third of the epithelium, and > 1% of cells in the upper one-third of the epithelium. MIB-1 immunostaining is useful in distinguishing dysplasia from atrophy.

Immunohistochemical comparison of uterine papillary serous and papillary endometrioid carcinoma: clues to pathogenesis.

Twenty-four predominantly papillary carcinomas of the endometrium, 10 serous and 14 endometrioid, were compared using a variety of immunohistochemical antibodies, including p53, estrogen and progesterone receptors, carcinoembryonic antigen, and E-cadherin. These were selected to attempt to find clues to explain the disparate behavior of these two tumor subtypes. We found that 6 of 8 (75%) serous carcinomas had a p53 reactivity score of 300, whereas 90% of endometrioid tumors had a p53 reactivity score of less than 20 (p = 0.0008). Combined estrogen and progesterone hormone reactivity was positive in 13 (100%) of endometrioid lesions compared with 4 of 8 (50%) of serous lesions (p = 0.0117). The significantly greater p53 expression and its significantly diminished hormone receptor expression indicate that papillary serous carcinomas belong to the type II group of endometrial carcinomas that occur in a background of atrophic endometrium, are high grade, present with high stage disease, and have a poor prognosis. In contrast, papillary endometrioid carcinomas, which belong to type I carcinomas, often arise in a background of estrogen-stimulated endometrial hyperplasia, are usually well-differentiated, and have a good prognosis. Early p53 mutations in papillary serous carcinoma as well as in endometrial intraepithelial serous carcinoma may partially explain their proclivity for early intra-abdominal dissemination. Carcinoembryonic antigen expression was similar in both groups and therefore is not useful to characterize possible differences in the cell of origin. The reactivity scores for E-cadherin were also similar in the two tumor subtypes, thus not supporting the hypothesis that decreased cell to cell adhesion molecules might contribute to early dissemination of serous lesions.

Aborted leiomyosarcoma after treatment with leuprolide acetate.

BACKGROUND: Leuprolide acetate has been used to decrease uterine size and shrink leiomyomata. In carefully selected patients, its treatment benefits are well recognized. However, if leuprolide acetate is inadvertently given to a patient with an unsuspected leiomyosarcoma, complications may occur. CASE: A patient presumed to have leiomyomata was treated with monthly injections of leuprolide acetate. In the third month of treatment, unusual manifestations, including increased bleeding, aborting mass, urinary retention, and severe pain, occurred suggesting a possible malignancy and requiring immediate operation. CONCLUSION: The use of leuprolide acetate can delay the diagnosis and treatment of leiomyosarcoma and thus may increase the risk of morbidity and affect the treatment outcome of patients with leiomyosarcoma. The histologic changes ascribed to leuprolide acetate treatment in leiomyomata also were seen in this leiomyosarcoma.

Immunohistochemistry of vascular changes in leuprolide acetate-treated leiomyomas.

We report two cases of leuprolide acetate-treated leiomyomas with striking vascular changes and histologic features of vasculitis and atherosclerosis. These changes may cause ischemic damage if they occur in other organs. We describe the histologic findings and discuss their clinical implications.