Immunohistochemical evaluation of PTEN protein in patients with endometrial intraepithelial neoplasia compared to endometrial adenocarcinoma and proliferative phase endometrium

OBJECTIVE: The aim of this study was to reclassify endometrial hyperplasia cases and examine PTEN protein immunoreactivity compared to cases with endometrial adenocarcinoma and proliferative endometrium. DESIGN: Endometrial samples from 37 women with endometrial hyperplasia with atypia were reclassified as endometrial intraepithelial neoplasia (EIN). Eighteen were complex and 19 were simple endometrial hyperplasia. Twenty-our cases of EIN, ten endometrial adenocarcinoma cases and ten proliferative phase endometrium sections were immunostained for PTEN expression. PTEN expression was documented according to the degree of immunoreactivity as complete loss, partial loss and present. RESULTS: Twenty-four of 37 (64%) women with endometrial hyperplasia were reclassified as EIN. Complete loss of PTEN immunoreactivity was found in only one of the 24 EIN patients (4.2%), partial loss in eight of 24 (33.3%) and present in 15 of 24 (62.5%). There were no difference in PTEN immunoreactivity between EIN, endometrial adenocarcinoma and endometrial proliferation (p = 0.342). PTEN immunoreactivity was partially lost in seven and present in three of the patients with endometrial adenocarcinoma. None of the patients expressed complete loss of PTEN immunoreactivity in this group. CONCLUSION: EIN classification may provide a better and more objective assessment of endometrial hyperplasia cases. PTEN expression showed no differences among the cases of EIN, endometrial carcinoma and proliferative phase endometrium.     

Endometrial hyperplasia and carcinoma in endometrial polyps: clinicopathologic and follow-up findings.

The objectives of this study were: 1) to evaluate findings in follow-up hysterectomy specimens after a diagnosis of complex atypical hyperplasia or carcinoma in endometrial polyps (EMPs) for possible significance in management strategies; and 2)to identify features in these polyps, that are predictive of the presence of endometrial hyperplasia or carcinoma in subsequent hysterectomy. Records of all cases of EMPs with endometrial hyperplasia were retrieved from the files of New York University Medical Center from 1993 to 2005. Those cases with follow-up hysterectomy were selected for the study. Of the 29 patients with complex atypical hyperplasia within the polyp, 19 out of 29 (66%) patients had hyperplasia of the non-polyp endometrium, and adenocarcinoma was observed in 9 out of 29 (31%) patients on follow-up hysterectomy. The percentage of polyp area involved by the hyperplasia was predictive of finding endometrial disorder in subsequent hysterectomy (P = 0.005). Of the 8 patients with adenocarcinoma in situ (AIS) within the polyp 3 (38%) had myoinvasive adenocarcinoma. In contrast, in cases without AIS, 4 out of 21 (19%) had myoinvasive adenocarcinoma in follow-up hysterectomy. Eight of the nine cases with carcinoma in endometrial polyp had endometrial pathology on hysterectomy. Approximately two thirds of the patients with hyperplasia and 90% of patients with adenocarcinoma in endometrial polyps show endometrial pathology on subsequent hysterectomy. The above findings reinforce the need for hysterectomy especially in postmenopausal women with atypical complex hyperplasia or carcinoma in endometrial polyps even if these changes appear confined to the polyp in initial sampling.     

Preoperative and postoperative correlation of histopathological findings in cases of endometrial hyperplasia

OBJECTIVES: To determine the preoperative and postoperative correlation of histopathological findings in cases of endometrial hyperplasia. MATERIAL AND METHODS: One hundred and three patients with endometrial hyperplasia detected by surgical curettage performed due to various gynecologic pathologies were treated by hysterectomy. We compared retrospectively the histopathological diagnoses found on curettage with those found on hysterectomy specimens. The classification scheme endorsed by the International Society of Gynecological Pathologists was used to classify the endometrial hyperplasia. The histologic findings found on the endometrial tissue of curettage specimens were correlated with those from hysterectomy specimens. Histopathologic evaluation was performed by a single skilled gynecologic pathologist. RESULTS: A total number of 103 women--76 (73.8%) premenopausal and 27 (26.2%) postmenopausal--were determined to have endometrial hyperplasia on histopathological evaluation of endometrial tissues obtained by endometrial curettage performed for evaluation of various bleeding abnormalities. These included 94 patients with simple hyperplasia without atypia (91.3%), two patients with simple hyperplasia with atypia (1.9%), five patients with complex hyperplasia without atypia (4.9%), and two patients with complex hyperplasia with atypia (1.9%). Histopathological evaluation of endometrial tissue obtained from hysterectomy specimens (of patients diagnosed with hyperplasia on curettage) revealed a total number of 65 cases (63.1%) with endometrial hyperplasia, and 38 cases (36.9%) with various histopathological findings. The correlation between preoperative and postoperative endometrial histologic findings was found to be statistically insignificant (r = 0.105, p = 0.29). Among 94 patients who were found to have simple hyperplasia without atypia on curettage specimens, 55.3%, were found to have simple hyperplasia without atypia, 1.1% simple hyperplasia with atypia, 5.3% complex hyperplasia without atypia, 9.6% secretory endometrium, 4.3% proliferative endometrium, 21.3% disorganized proliferative endometrium, 1.1% corpus luteum persistency, 1.1% basal endometrium, and 1.1% endometrium cancer on final hysterectomy specimens. CONCLUSION: Postoperative diagnosis of endometrial pathology might be different from that of preoperative especially in cases with simple endometrial hyperplasia without atypia.     

Natural history of endometrial hyperplasia

Seventy-seven patients with endometrial hyperplasia, 48 with simple hyperplasia without atypia (SH), 17 with complex hyperplasia without atypia (CH), one with simple hyperplasia with atypia (SHA), and 11 with complex hyperplasia with atypia (CHA) were prospectively followed-up by total curettage every 12 months for 3 years. Progression to carcinoma occurred in only one of the 77 patients; she showed grade 1 adenocarcinoma. The overall regression rates were 79% for SH, 100% for SHA, 94% for CH, and 55% for CHA, respectively. In patients with CHA whose disease reverted to normal endometrium, regression was most likely to occur within the first year. Received: 28 August 2000 / Accepted: 19 October 2000     

Liquid-based endometrial cytology: its possible value in postmenopausal asymptomatic women

The incidence of endometrial adenocarcinoma in asymptomatic women is low. Nevertheless, some of these women might require endometrial surveillance. In this study, we evaluated the accuracy of liquid-based endometrial cytology compared to biopsy in asymptomatic postmenopausal women. Three hundred twenty women scheduled for hysteroscopy were enrolled for this study. After hysteroscopy, patients were submitted to endometrial cytology and to biopsy. Two hundred ninety-three (92%) women had sonographically thickened endometrium (>5 mm), 53 (17%) were on tamoxifen, and 16 (5%) were on hormonal substitutive treatment. The evaluation of the biopsies determined that six (2%) women had adenocarcinoma, one (<1%) had adenomatous atypical hyperplasia, and eight (3%) had simple nonatypical hyperplasia. Endometrial cytology evidenced 5 (2%) neoplastic cases, 2 (<1%) hyperplastic with atypia cases, and 25 (8%) hyperplastic without atypia cases. Two hundred twenty-two biopsies (69%) and 17 (5%) cytologies were inadequate. One adenocarcinoma and one simple nonatypical hyperplasia were underrated by cytology resulting, respectively, as atypical hyperplasia and as negative. Four cases were false positive (simple nonatypical hyperplasias on cytology, negative on biopsy). The sensitivity and specificity were estimated, respectively, at 94% and 95%; the positive and negative predictive value were estimated, respectively, at 80% and 99%. Endometrial cytology provided sufficient material more often than biopsy (P < 0.01). We suggest to introduce liquid-based endometrial cytology in the management of some subpopulations of asymptomatic postmenopausal women. Particularly, the combination of liquid-based endometrial cytology and transvaginal sonography may improve their diagnostic accuracy and reduce unnecessary more invasive and expensive procedures.     

Significance of "normal" endometrial cells in cervical cytology from asymptomatic postmenopausal women receiving hormone replacement therapy

OBJECTIVE: The aim of this study is to assess the significance of normal endometrial cells identified in screening Pap smears from asymptomatic postmenopausal women taking hormone replacement therapy (HRT). METHODS: Endometrial histology reported from 93 asymptomatic postmenopausal women receiving HRT noted to have normal endometrial cells on a screening Pap smear was reviewed. Information regarding HRT, endometrial sampling, and interval between the sentinel Pap and sampling was extracted from the record. RESULTS: Endometrial biopsies were obtained an average of 1.7 months after the Pap smears. Eighteen of the ninety-three histology specimens (19%, 95% CI: 12--27%) identified abnormalities, in four cases precancerous or cancerous lesions. These 18 abnormalities included 7 endometrial polyps; 7 cases of simple hyperplasia, 1 with atypia; 3 cases of complex hyperplasia, 1 with atypia; and 1 endometrial adenocarcinoma. CONCLUSION: Normal endometrial cells identified on a screening Pap smear in this population may be an indication of endometrial disease.     

Implementation of assisted reproductive technologies following conservative management of FIGO grade I endometrial adenocarcinoma and/or complex hyperplasia with atypia

OBJECTIVE: The objective was to report a series of infertility therapy outcomes following conservative management of endometrial adenocarcinoma and/or complex hyperplasia with atypia. METHODS: A retrospective review of the University of Iowa assisted reproductive technology database was performed. All women presenting with International Federation of Obstetrics and Gynecology (FIGO) grade I uterine adenocarcinoma and/or complex hyperplasia with atypia were assessed for type and duration of medical management, initial, interim treatment, and preinfertility treatment endometrial biopsy (BX) findings. Assessment of infertility treatment outcomes and postinfertility endometrial biopsy findings were performed. All of the pathology samples were re-reviewed at the Gynecologic Oncology Tumor Board to confirm the diagnosis by a pathologist with a particular expertise in gynecologic pathology. RESULTS: Four infertile women, three nulligravid and one primigravid, were evaluated with the diagnosis of FIGO grade 1 endometrial adenocarcinoma and/or complex hyperplasia with atypia desiring to preserve fertility. Two women with FIGO grade 1 endometrial adenocarcinoma were successfully treated with high-dose progestational agents resulting in normal proliferative endometrium. In addition, both women with complex hyperplasia with atypia were successfully treated with progestins and/or ovulation induction. Successful pregnancy outcomes were achieved for three of the four women with assisted reproductive technology. A total of five successful pregnancies and eight healthy live-born infants were achieved among three women. One of the four women was unable to conceive despite three cycles of in vitro fertilization. Hysterectomy was performed for recurrent complex hyperplasia with atypia. In our series, we found it can take 3-10 months (mean, 6.25 months; median, 6 months) to obtain benign endometrium preceding infertility therapy. CONCLUSION: This report demonstrates that conservative management of well-differentiated endometrial adenocarcinoma and/or complex hyperplasia with atypia followed by aggressive assisted reproduction is an option to highly motivated and carefully selected women.     

Significance of atypical endometrial cells detected by cervical cytology

A retrospective study was conducted to assess the histologic significance of atypical endometrial cells identified on routine cervical cytology. One hundred seventy-seven women had Papanicolaou smears demonstrating atypical endometrial cells. The histology of the endometrium was available from endometrial sampling and/or hysterectomy in 134 of the patients within 12 months of their abnormal cytologic evaluation. Fifty-six women (42%) had endometrial disease, including 14 cases (10%) of endometrial polyp, 15 cases (11%) of endometrial hyperplasia, and 27 cases (20%) of adenocarcinoma. The frequency and nature of the endometrial changes depended on the age of the patient (P less than .001) and the degree of cytologic atypia (P less than .05). In 21 women over 59 years who had atypical endometrial cells suspicious for adenocarcinoma, 12 (57%) had adenocarcinoma. Using this information, we have estimated the risk of adenocarcinoma in various groups of women with atypical endometrial cells.     

Descriptive epidemiology of endometrial hyperplasia in patients with abnormal uterine bleeding

PURPOSE OF INVESTIGATION: To evaluate the prevalence and epidemiologic characteristics of endometrial hyperplasias in women with abnormal uterine bleeding. METHODS: We performed a retrospective analysis on data gained from 294 patients with histologically documented endometrial hyperplasia (with or without atypia), detected among 1,469 women who underwent fractional dilatation and curettage in our department due to abnormal uterine bleeding from 1986 to 1998. Epidemiologic characteristics were abstracted from the patients' medical charts. RESULTS: 294/1469 women were found with endometrial hyperplasia (258 without atypia and 36 atypical hyperplasias). Thirty-six of them were under 40 years of age. Four of the detected endometrial hyperplasias progressed to endometrial carcinoma (one with simple hyperplasia, two with complex and one with atypical hyperplasia). Obesity and hypertension were justified as risk factors in our study population. CONCLUSIONS: The prevalence of endometrial hyperplasia according to our data was 20%. There were statistically significant differences in most epidemiologic parameters between the two types of hyperplasia. The progression of four endometrial hyperplasias to endometrial adenocarcinoma indicates the need for intense follow-up even in cases where patients undergo conservative therapy.     

Resectoscopic surgery may be an alternative to hysterectomy in high-risk women with atypical endometrial hyperplasia

STUDY OBJECTIVE: Endometrial hyperplasia is found in 2% to 10% of women with abnormal uterine bleeding (AUB). Up to 43% of patients with cytologic atypia harbor coexisting adenocarcinoma, and approximately 20% to 52% of atypical hyperplasias, if untreated, progress to cancer. The objective of this study was to estimate the incidence of atypical endometrial hyperplasia encountered during routine resectoscopic surgery in women with AUB and to evaluate the role of resectoscopic surgery in the management of women with AUB and atypical endometrial hyperplasia who refused and/or were at high risk for hysterectomy. DESIGN: Prospective cohort study (Canadian Task Force classification II-3). SETTING: University-affiliated teaching hospital. PATIENTS: From January 1990 through December 2005, the senior author (GAV) performed primary resectoscopic surgery in 3401 women with AUB. Among these, there were 22 women with atypical (17 complex, 5 simple) endometrial hyperplasia. INTERVENTIONS: All women underwent hysteroscopic evaluation and partial (n = 3) or complete (n = 19) endometrial electrocoagulation and/or resection. Subsequently, 6 women had hysterectomy and bilateral salpingo-oophorectomy (BSO). MEASUREMENTS AND MAIN RESULTS: The median (range) for age, parity, and body mass index were 55 years (24-78 years), 2 (0-4), and 30.1 kg/m2 (22.5-52.2 kg/m2), respectively. Among the 3401 women, there were 22 cases of atypical endometrial hyperplasia, 12 of which were incidentally diagnosed at the time of hysteroscopy (complex 10, simple 2, incidence 0.35%). After hysteroscopic diagnosis or confirmation of diagnosis, 6 women underwent hysterectomy and BSO. Of the remaining 16 women, followed for a median of 5 years (range 1.5-12 years), 1 was lost to follow-up, 1 had only a biopsy to preserve fertility, 1 died from lung cancer after 4 years, and 1 died from colon cancer after 5 years. One patient developed endometrial cancer after 10.5 years with postmenopausal bleeding. She remains alive and well 3.5 years after hysterectomy and BSO. The remaining 11 patients are amenorrheic at a median follow-up of 6 years (range 1.5-12 years). CONCLUSIONS: Resectoscopic surgery in 3391 women with AUB detected 12 incidental cases of atypical endometrial hyperplasia (incidence 0.35%). Skillful resectoscopic surgery may be an alternative to hysterectomy in women with AUB and atypical endometrial hyperplasia, who refuse or are at high-risk for hysterectomy and who are compliant with regular and long-term follow-up.     

Analysis of the frequency of prevalence of endometrial hyperplasia and endometrial adenocarcinoma based on own material in the year 1975, 1985 and 1995

We analysed the frequency of prevalence of endometrial hyperplasia and endometrial adenocarcinoma in the years 1975, 1985 and 1995. Significant differences between endometrial simple hyperplasia and complex hyperplasia with atypia was found. There were no statistic differences in the frequency of the prevalence of endometrial adenocarcinoma between analysed years.     

Atypical endometrial hyperplasia: grounds for possible misdiagnosis of endometrial adenocarcinoma

OBJECTIVE: The diagnoses of atypical hyperplasia and well-differentiated adenocarcinoma imply totally different approaches because of clinical and patient-oriented ramifications, especially when morphological differences are not entirely conclusive. The purpose of this study was to examine the relationship between the diagnosis of atypical hyperplasia during curettage or endometrial biopsy and the definitive histological findings from hysterectomy material. STUDY DESIGN: 23 patients were found fit for the current study and subsequently their clinical histories were reviewed for relevant clinical data, histopathological profiling and type of therapeutic interventions. RESULTS: Adenocarcinoma was observed in 12 (52.17%) of 23 hysterectomy cases. The hyperplasia was found in 10 (43.47%) cases, although 4 of them lacked atypia and 1 case proved to be hyperplasia-free. CONCLUSION: Hysterectomy was prescribed as the next step in the diagnosis of atypical endometrial hyperplasia. Other wait-and-see approaches could have easily forfeited the chances of providing an adequate treatment for an operable and curable cancer in approximately half of the studied cases.     

Significance of benign endometrial cells in Pap smears from postmenopausal women

OBJECTIVE: To assess the significance of benign exfoliated endometrial epithelial or stromal cells on cervicovaginal Pap smears obtained from postmenopausal women not receiving exogenous hormones. STUDY DESIGN: A computerized search of the cytology database at two institutions was performed for a five-year period, and all cervical cytology cases from postmenopausal patients diagnosed with benign endometrial cells were identified. Those cases with histologic follow-up within 12 months of the original cytologic evaluation were selected for analysis, and their cytology and surgical pathology slides were reviewed. RESULTS: A total of 227 postmenopausal women with benign endometrial cells were identified. Of the 61 patients with histologic follow-up, 25 (41%) had significant endometrial diseases, including hyperplasia without atypia (11), atypical endometrial hyperplasia (5), well-differentiated adenocarcinoma (8) and high grade serous carcinoma (1). Benign diagnoses, including atrophy (15), weakly proliferative endometrium (9) and proliferative endometrium (6), were noted in 30 patients (49%). Endometrial polyp was identified in three patients (5%). There were three cases of nondiagnostic histologic specimens that lacked endometrial tissue (5%). Two of nine women (22%) with proven carcinoma were asymptomatic. CONCLUSION: The diagnosis of endometrial cells, cytologically benign, in a postmenopausal woman not receiving hormone on Pap smears is associated with a significant number of cases of endometrial hyperplasia, atypical hyperplasia and carcinoma.     

c-Kit proto-oncogene expression in endometrial hyperplasia and endometrial cancer

Purpose

To evaluate the expression of c-kit (CD117) in endometrial hyperplasia and endometrial cancer.

Methods

Expression of c-kit in 10 normal endometrium, 18 simple endometrial hyperplasia, 16 complex endometrial hyperplasia (10 cases with atypia and 6 cases without atypia), and 6 endometrial cancer were investigated by immunohistochemistry.

Results

c-Kit expression decreased as the lesion progressed to endometrial cancer. Immunostaining was mostly focal and weak in the normal endometrium and was mostly diffuse and strong in the simple and complex endometrial hyperplasia.

Conclusions

Simple and complex hyperplastic endometrial tissues express diffuse cytoplasmic staining for c-kit and the expression decreases with the progression of the lesion.     

Concurrent endometrial carcinoma following hysterectomy for atypical endometrial hyperplasia

Objective

To evaluate the prevalence of concurrent endometrial carcinoma in women diagnosed with atypical endometrial hyperplasia (AEH) by endometrial biopsy.

Study design

We retrospectively analyzed the medical records of 126 patients who underwent hysterectomies for AEH diagnosed by endometrial biopsy from 1999 to 2008. AEH was initially diagnosed by dilatation and curettage (98 cases) or endometrial biopsy with a Z-sampler (24 cases). The remaining four cases were diagnosed by hysteroscopic polypectomy. The results of the endometrial biopsies were graded on an ordinal scale and were compared with pathologic features obtained at the hysterectomy.

Results

In patients preoperatively diagnosed with AEH by biopsy, hysterectomy specimens revealed a rate of simple or complex endometrial hyperplasia without atypia of 27% with AEH and normal proliferative phases found in 54.7 and 7.9% of specimens, respectively. The incidence of endometrial carcinoma was considerably high (13/126, 10.3%). Eleven of 13 cases were confined to the endometrium and the remaining two were located at the adenomyosis without myometrial invasion. All patients with endometrial carcinoma displayed coexisting atypical complex hyperplasia following hysterectomy.

Conclusions

Biopsy specimens showing AEH, particularly atypical complex hyperplasia, are associated with a risk of coexisting endometrial carcinoma. When considering management strategies for women with a biopsy diagnosis of AEH, clinicians should take into account the considerable rate of concurrent endometrial cancer and the discrepancy with pathologic diagnosis. Treatment modalities may differ depending on population as the rates of concurrent endometrial cancer with AEH and myometrial invasion vary by geographical location.     

Prevalence of underlying adenocarcinoma in women with atypical endometrial hyperplasia.

There is controversy regarding the prevalence of underlying endometrial adenocarcinoma among women with a diagnosis of atypical endometrial hyperplasia. This study further defines that risk. At our institution atypical endometrial proliferations non-diagnostic for invasive adenocarcinoma are diagnosed as either atypical endometrial hyperplasia (ATHY) or as an "atypical proliferative lesion of the endometrium, suggestive but not diagnostic of atypical endometrial hyperplasia" (APL). Between 1996 and 2003, these diagnoses were made on either endometrial biopsy or endometrial curettings in 60 women who subsequently received a hysterectomy. Endometrial adenocarcinoma was identified in 48% (29/60) of the hysterectomy specimens. Age and sampling method had no significant impact on the prevalence of adenocarcinoma. Adenocarcinoma was no more likely to be subsequently identified when a woman had a preoperative diagnosis of ATHY (24 of 52, 46%) compared to APL (5 of 8, 63%). In some women with a diagnosis of ATHY a comment was made in the report that "carcinoma cannot be ruled out". These cases had a significantly higher prevalence of underlying adenocarcinoma (16 of 25, 64%) compared to cases of ATHY in which such a comment was not made (8 of 27, 30%) (p = 0.025). In conclusion, there is a high prevalence of underlying endometrial adenocarcinoma among women undergoing hysterectomy for any of atypical endometrial proliferation.     

Endometrial Hyperplasia: A Clinicopathological Study in a Tertiary Care Hospital

Objective

To evaluate the clinical as well as histomorphologic features in different cases of endometrial hyperplasia along with its relative occurrence.

Materials and Methods

A one-and-a-half-year prospective study was conducted on histopathologically diagnosed cases of endometrial hyperplasia in a tertiary care hospital. Apart from relevant clinical findings, histomorphologic details were noted and statistically analyzed.

Observations

Maximum number (46.5 %) of endometrial hyperplasia occurred in patients of 41–50 years age group. Majority (55.2 %) of the patients were found to be premenopausal. Menorrhagia was the most common (49.6 %) clinical presentation followed by postmenopausal bleeding (30.8 %). Simple hyperplasia without atypia was the most common type (95.6 %) followed by complex hyperplasia without atypia (3.6 %) and complex hyperplasia with atypia (0.8 %), respectively. The study of gland–stroma ratio revealed 65:35 to be the most frequent (34 %) ratio; variable-sized glands with cystic dilatation (60.4 %) was the commonest gland architecture and most of the cases (99.2 %) showed the absence of atypia. Associated histopathological findings included a case each of endometrial adenocarcinoma and undifferentiated endometrial stromal sarcoma along with the common leiomyoma and progesterone effects.

Conclusion

Menorrhagia was the most common presenting complaint in cases of endometrial hyperplasia. The cases were mostly in the premenopausal age group. Simple endometrial hyperplasia without atypia was the commonest type diagnosed histopathologically. Histopathological examination along with clinical details is essential to give the final opinion regarding the diagnosis.     

The management of endometrial hyperplasia: an evaluation of current practice

OBJECTIVE: To identify current management practices and evaluate subsequent outcomes of treatment for women diagnosed with endometrial hyperplasia. STUDY DESIGN: All women with a histological diagnosis of endometrial hyperplasia at the Birmingham Women's Hospital were identified between October 1998 and September 2000. A retrospective case note review was performed for each woman using a standardised data abstraction sheet. Baseline characteristics including clinical presentation and treatment strategy were obtained. Results of subsequent endometrial tissue examinations were used to assess histological response to treatment and the need and indication for hysterectomy was used to assess clinical response. RESULTS: There were 351 women diagnosed with endometrial hyperplasia during the study period of which 84% presented with symptoms of abnormal uterine bleeding and 54% were postmenopausal. Complex endometrial hyperplasia was the most common diagnosis accounting for 60% of all cases. Eighty percent of women with atypical endometrial hyperplasia were treated by hysterectomy compared with 30% without evidence of cytological atypia (relative hysterectomy rate of 2.6, 95% CI 2.0-3.3). Hysterectomy was avoided in 138/172 (80%, 95% CI 74-86%) women managed conservatively during the study period. Overall 35/108 (36%, 95% CI 27-46%) of women managed conservatively had persistent or progressive disease identified (mean follow up 36 months). 20/143 (14%) women initially diagnosed with endometrial hyperplasia who subsequently underwent hysterectomy were found to have endometrial cancer, the majority of whom had been diagnosed with atypical disease (14/20, 70%). CONCLUSION(S): The majority of women with atypical endometrial hyperplasia were managed by hysterectomy and the substantial risk of diagnostic under-call supports this approach to treatment. In contrast, there is no consensus regarding the initial management of women with endometrial hyperplasia without cytological atypia.     

Histopathologic behavior of endometrial hyperplasia during tamoxifen therapy for breast cancer

OBJECTIVE: The purpose of the present study is to prospectively evaluate the effects of tamoxifen on the pathological behavior of endometrial hyperplasias without atypia, diagnosed before the start of adjuvant endocrine therapy, in menopausal patients suffering from breast cancer. METHODS: Twenty-six patients suffering from estrogen-receptor positive breast cancer and candidate to receive adjuvant tamoxifen, were found to be affected by endometrial hyperplasias before the start of endocrine therapy. All women showed a baseline endometrial stripe, measured by transvaginal ultrasonography, thicker than 4 mm and the diagnosis of endometrial hyperplasia was made by hysteroscopy and endometrial biopsy. Two patients showing complex atypical hyperplasia underwent vaginal hysterectomy, whereas the remaining 24 patients, suffering from endometrial hyperplasia without atypia, were followed on a yearly basis during the period of tamoxifen intake, by hysteroscopy and endometrial biopsy. RESULTS: Baseline histopathology showed simple and complex hyperplasia in 20 and in 4 patients, respectively. The median follow-up period was 38 months; in particular, all patients underwent endometrial assessment after 12 months, while 22, 16, 10 and 4 patients were followed-up after 24, 36, 48 and 60 months of tamoxifen therapy, respectively. Progression from complex hyperplasia to complex atypical hyperplasia (1 patient) and from complex and simple hyperplasia to adenocarcinomas (2 patients) was found within 24 months of tamoxifen intake in 3 patients (12.5%). In 2 patients (8.3%), a progression from simple to complex hyperplasia was detected within 36 months of tamoxifen treatment. In 13 patients (54.1%), stable histology of simple or complex hyperplasia was found, whereas 6 patients (25.0%), with focal hyperplasia harbored in an endometrial polyp, showed a normalization of endometrial histology after polyp resection. CONCLUSIONS: Endometrial hyperplasias without atypia diagnosed before endocrine therapy for breast cancer in menopausal patients show an early and high progression-rate to atypical lesions under tamoxifen influence.     

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.