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.
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.
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.
To the Editor: The article titled “The Pathology of Uterine Smooth Muscle Tumors and Mixed Endometrial Stromal-Smooth Muscle Tumors: A Selective Review and Emphasis on Recent Advances” (Int J Gynecol Pathol 2000; 19: 39–55) is both comprehensive and instructive. This letter is in response to the valid observation that most or all of the publications on the effects of gonadotropin-releasing hormone (GnRH) agonists on leiomyomata neglected to include an evaluation of the mitotic activity in these tumors. All of the patients in our study (1) had surgery within 4 weeks of the last injection of leuprolide acetate. We did not mention the mitotic count because we saw no mitoses or less than 1 mitosis/10 high-power fields in our cases (1,2). We believed that the absence of mitoses resulted from chronic hypoestrogenic effects of GnRH agonists. Interestingly, we have observed a paucity of mitoses, less than 1 mitosis/10 high-power fields in a case of a GnRH agonist-treated cellular low-grade endometrial stromal sarcoma with focal smooth muscle differentiation, which made diagnostic interpretation difficult (3). We are continuing to explore the effects of medications such as GnRH agonists on uterine spindle cell neoplasms. The focus of the first two referenced studies was primarily on the vascular changes that occurred in GnRH agonist-treated leiomyomata. It has not been our custom to report the mitotic count on benign smooth muscle tumors. Rita I. Demopoulos M.D. Augusto F. Mesia M.D.
To the Editor.—Gonadotropin-releasing hormone (GnRH) agonists (ie, leuprolide acetate [Lupron]) have hypoestrogenic properties that result in the shrinkage of uterine leiomyomas. With well-tolerated and generally reversible side effects, the use of GnRH agonists in uterine leiomyomas is related to its ability to cause regression and thus decrease operative bleeding.In a recent study by Kalir et al1 the histologic effects of GnRH agonists on uterine leiomyomas included hyalinization, greater cell density, slightly smaller cell size, and larger collagen fibrils than those of age-matched control patients and post-menopausal women.1 These findings are significant because some investi-gators reported minimal or insignificant histologic changes in their studies.23 However, a matched case-control study by Demopoulos and co-authors 4 revealed significant hy-alinization, fibrosis, and vascular changes in GnRH agonist-treated uterine leiomyomata. These vascular changes, mainly in the form of thickened blood vessel walls and narrowed lumina, are important findings because they explain why uterine leiomyomas decreased in size,hyalinized, and showed other morphologic alterations when subjected to this type of medication. Furthermore, thrombotic occlusions and even accelerated atherosclerotic changes were seen in a few treated leiomyomas. The probable mechanisms of action that resulted in these changes have been described.5 Al-though vascular changes were not the overall focus of the study by Kalir et al, their findings certainly provide valuable electron microscopic and histologic clarification on the effects of GnRH agonists on leiomyomas.In Reply.—I thank Drs Mesia and Popiolek for their kind words and interesting thoughts on the mechanism of action of Lupron in uterine myomas. The cited work of Demopoulos et al, who found vascular changes in Lupron-treated myomas in the form of thickened vessel walls, narrowed lumina, and thrombotic occlusions is interesting. If receptors for estrogen and progesterone are indeed present in blood vessels, it is logical that a low estrogenic state, including that induced by Lupron treatment, might directly affect the vessels and, in turn, that low blood flow might lead to the changes we and others have reported in myomas after Lupron treatment. However, uterine smooth muscle cells also produce estrogen receptors and, reportedly, gonadotropin-releasing hormone (GnRH) receptors. Is it also possible that Lupron directly affects these cells, and that because of lower cellular metabolism there might be decreased blood flow with ensuring secondary vascular changes? Or, alternatively, is it possible that Lupron acts simultaneously on all the tissue components to cause the various changes reported? The 3 possible scenerios are summarized as follows:It would be difficult to test these hypotheses, but Mesia and Popiolek’s letter has sparked our interest in measuring the vascular changes that have been reported by qualitative assessment. We look forward to reporting our results in the future.
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.
Introduction: Pulmonary arteriovenous malformation (PAVM) is a rare cardiovascular anomaly and represents direct communications between the branches of pulmonary artery and pulmonary veins, without an intervening pulmonary bed. The incidence of PAVM is 2–3 per 100,000 population. The male to female ratio varies from 1:1.5 to 1.8. A clinical manifestation may be from asymptomatic to severe hypoxia. Case presentation: A ten years old boy was admitted to a regional hospital because the mother noticed that the boy was slower in the game at the teacher noticed that the boy was slower and could not lift his eyes up of clinical and laboratory examinations have been shown polycythemia, and cyanosis, bat-like appearance of the fingers and polycythemia, RTG chest and CT have claimed AV malformation of the lower left lobes with the feeding artery Neurologic symptoms may be the presenting symptoms in up to 40% of patients. The patient was successfully treated with left lower lobectomy. Early post-operative recovery has been successful. Later checkups showed better blood saturation with oxygen, the same polycythemia, and a better clinical condition. Discussion and Conclusion: If the etiology of the hypoxemia often remains unclear pulmonary AVM should be considered. The diagnosis needs to be confirmed with a CT scan that should identify the food artery. If the AV malformation occupies large part of the lobe, a reasonable treatment options should be lobectomy. Longterm follow up, including chest CT examinations every 1 to 2 years, is recommended.
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