Endometrial adenocarcinoma appearing during tamoxifen therapy. Report of a clinical case

Tamoxifen is a non-steroid estrogenic antagonist, used in post-surgical therapy of breast cancer. It interferes with endocrinous promotion of breast cancer. Tamoxifen could determine endometrial, even carcinomatous, alterations. The case of a postmenopausal patient surgically treated for breast cancer and successively treated with tamoxifen (20 mg/die), is reported. She underwent ultrasonographic and hysterosonographic endometrial evaluation and finally a hysterectomy with bilateral annessiectomy. This case seems to confirm tamoxifen possible carcinogenical effects on the endometrium.     

Mammographic changes during postmenopausal hormonal replacement therapy with tibolone

PURPOSE OF INVESTIGATION: To evaluate mammographic changes in postmenopausal women receiving hormonal replacement therapy (HRT) with tibolone. METHODS: 83 postmenopausal women aged 45-62 received the same dose of tibolone for a period of six months to five years without interruption. The women were examined mammographically every six to 12 months during the observation period. RESULTS: There was a low incidence of breast tenderness. Also, we did not observe any significantly increased mammographic density or neoplasmatic disease of the breast. As far as dysplastic changes are concerned, no remarkable aggravation in the mammographic picture was noted. CONCLUSION: The new synthetic steroid tibolone, in contrast to conventional HRT, rarely causes breast pain. At least short-period tibolone therapy (less than 5 years) has good effects on climacteric disorders and does not cause breast changes (dysplasia or cancer). Our study is on-going.     

Endometrial polyp size and polyp hyperplasia

Objective

To assess the correlation between the size of endometrial polyps and the histopathologic diagnosis of hyperplasia or cancer.

Methods

A retrospective study was conducted using databases of the outpatient clinic at Antonio Pedro University Hospital in Niterói, Brazil, and of a private hysteroscopy service. The analysis included 1136 asymptomatic patients with an endometrial polyp identified on hysteroscopy, with pathologic examination, during the period 1999–2012. The polyp size, the patients’ age, the indication for hysteroscopic examination, and the use of hormone medication were compared with the finding of hyperplasia in the pathologic examination.

Results

Only polyp size showed statistical significance among the variables analyzed (P < 0.05). Endometrial polyps greater than 15 mm showed a hyperplasia rate of 14.8%, compared with 7.7% in the group with smaller polyps (P < 0.05).

Conclusion

Endometrial polyps measuring more than 15 mm were associated with hyperplasia.     

Endometrial adenocarcinoma and the Stein-Leventhal syndrome

Six cases of adenocarcinoma of the endometrium associated with the Stein-Leventhal syndrome are presented. The average age of the patients was 27.8 years. All patients were treated surgically; 2 had preoperative intracavitary irradiation, and 1 had postoperative intravaginal cesium-137 application. At follow-up, ranging from 1 to 15 years, all patients are alive and free of disease. Almost 90% of endometrial adenocarcinoma in association with the Stein-Leventhal syndrome is well differentiated, and appropriate treatment is associated with a good prognosis. Conservative therapy carries the risk of progression of the cancer to more advanced stages and has very little to offer for future fertility. It is suggested that these patients be treated as are any other patients with endometrial cancer.     

Endometrial hyperplasia and the risk of carcinoma

Recent reports suggest that atypical endometrial hyperplasia diagnosed by biopsy or curettage is accompanied by a higher than expected risk of coexistent invasive cancer. In order to test this hypothesis we reviewed the pathology and clinical history of all patients at our institution who underwent hysterectomy for endometrial hyperplasia with or without cytologic atypia. We found 24 patients of 45 with a preoperative diagnosis of hyperplasia with cytologic atypia, and 21 with simple or complex hyperplasia without atypia. No cancers were found at surgery in the latter group nor were any significant historical differences found between the two groups. Of the patients with atypia, 12/24 (50%) had an endometrial carcinoma and nine patients (37.5%) were stage IB or greater. This is a significantly greater risk than previously reported in the literature. Endometrial hyperplasia with cytologic atypia may carry a higher risk of coexistent invasive endometrial carcinoma than previously believed. Methods to identify those patients at highest risk should be determined.     

Endometrial survey during phytoestrogens therapy in postmenopausal women

AIM: The aim of this study was to verify the effects on endometrium of short-term phytoestrogens therapy in postmenopausal women. METHODS: This randomized study compared two groups of 50 patients undergone respectively to phytoestrogens therapy or placebo. An endometrial survey was performed on the study groups by ultrasound and hysteroscopy at baseline and at 6 and 12 months. RESULTS: The ultrasonographic findings and the hysteroscopic biopsies in the 47 women submitted to phytoestrogens therapy that completed the follow-up showed an atrophic and/or inactive endometrial mucosa less than in one patients (2.1%) with endometrial thickness and proliferative endometrium bioptical sample after 12 months of treatment; no cases of endometrial hyperplasia were found. CONCLUSION: In the authors' 12 month experience, phytoestrogens therapy in postmenopausal women was safe for endometrial stimulation because did not cause any significant alteration of the mucosa in a short-term administration.     

Loss of heterozygosity alterations associated with progesterone therapy in endometrial hyperplasia and adenocarcinoma

Loss of heterozygosity (LOH) was analyzed in four patients with endometrial hyperplasia (EH) with atypia (two patients) and without atypia (two patients) and in five patients with endometrial adenocarcinoma (EAC) to clarify the clinicopathologic relationship between genetic alterations and hormone therapy. Each patient was initially administered high-dose medroxyprogesterone acetate (MPA) as a uterine-sparing treatment. The five microsatellite markers used to analyze LOH were at chromosomal loci 8p22.1, 8p21, 8p21.3, 8p22, and 8p22. DNA was extracted from paraffin-embedded sections before, during, and after MPA therapy using laser capture microdissection. As a result, LOH was more frequently detected after MPA therapy (overall ratios were 16, 17, and 29% before, during, and after MPA therapy, respectively). LOH is more easily detected in EH loci than in EAC loci before MPA. For EAC, initial LOH detection on chromosome 8 may be related to an incomplete response to MPA, but negative LOH does not guarantee a favorable treatment outcome. For EH or atypical endometrial hyperplasia, it is unknown whether LOH alteration associated with MPA therapy is related to atypia of the disease.     

Endometrial adenocarcinoma and the polycystic ovary syndrome.

While endometrial adenocarcinoma is the second most common female genital malignancy, only four per cent of the cases occur in women less than 40 years of age. The relative rarity of this disease in young women requires that we be especially attuned to those who are at high risk. This paper presents two case reports of women with polycystic ovarian disease who developed endometrial adenocarcinoma at 24 years of age. The pathophysiology ovarian disease and its relationship to the development of endometrial adenocarcinoma are discussed.     

Development of metastatic endometrial endometrioid adenocarcinoma while on progestin therapy for endometrial hyperplasia

BACKGROUND: Conservative treatment with progestins is a reasonable treatment option for endometrial complex atypical hyperplasia and, in the experimental setting, for some women with grade 1 endometrial endometrioid adenocarcinoma. The risk of progression to a high-stage endometrial cancer is quite low, with only two previously reported cases in the English literature. CASE: A 40-year-old woman with endometrial complex atypical hyperplasia diagnosed by dilatation and curettage was managed conservatively with progestin therapy (initially, megesterol acetate; then, a combination oral contraceptive). More than 2 years after her original diagnosis, she developed endometrial endometrioid adenocarcinoma, FIGO grade 2, with lymph node metastasis. The tumor was microsatellite instability-high due to methylation of MLH1 and loss of MLH1 protein. CONCLUSION: Currently, there are no good criteria for predicting which patients with complex atypical hyperplasia/grade 1 endometrioid adenocarcinoma will optimally respond to progestin therapy. There is some evidence that endometrial complex hyperplasia demonstrating loss of MLH1 protein by immunohistochemistry is strongly related to subsequent or concurrent endometrial cancer, especially tumors of higher grade and stage. In a woman with a biopsy diagnosis of endometrial hyperplasia, evaluation of MLH1 protein status by immunohistochemistry may provide useful information when medical management is being considered.