Benign prostatic hyperplasia: diagnosis and treatment. Benign Prostatic Hyperplasia Guideline Panel. Agency for Health Care Policy and Research.
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Adrenergic alpha-Antagonists↗
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Results for “HYPERPLASIA”
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p53 expression in intraductal epithelial hyperplasia, atypical intraductal hyperplasia, and intraductal carcinoma of the breast.
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Adenoma, Sweat Gland↗
[Recommendations for billing alternative therapy of benign prostatic hyperplasia. Laser therapy of benign prostatic hyperplasia].
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Complementary Therapies↗
[Bowen's disease (pure hyperplasia, simple hyperplasia, Queyrat's erythroplasia].
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Carcinoma, Squamous Cell↗
A multicentric European study testing the reproducibility of the WHO classification of endometrial hyperplasia with a proposal of a simplified working classification for biopsy and curettage specimens.
This study was designed to assess intraobserver and interobserver agreement in the diagnosis of 56 endometrial specimens by five European expert gynecologic pathologists using the WHO classification and to establish which histologic features are significantly associated with each classification category. The seven categories were simple hyperplasia, complex hyperplasia, atypical hyperplasia, well-differentiated adenocarcinoma, proliferative endometria, secretory endometria, and other. Slides were reviewed twice for diagnosis, with accompanying evaluation of a checklist of histologic features. These seven categories were eventually reduced to four and three for the purposes of data analysis. The four modified diagnostic categories consisted of hyperplasia (previously simple hyperplasia and complex hyperplasia), atypical hyperplasia, well-differentiated adenocarcinoma, and cyclical endometrium (previously proliferative, secretory, and other). The three diagnostic categories consisted of hyperplasia, endometrioid neoplasia (previously atypical hyperplasia and well-differentiated adenocarcinoma), and cyclical endometrium. Intraobserver and interobserver agreement was assessed using the percentage agreement and kappa statistics. The associations among the various histologic features and diagnoses was analyzed using multiple logistic regression to identify those features that were useful for distinguishing diagnostic categories. When using seven categories, kappa values ranged from 0.53 to 0.74 (percentage agreement, 61-79%) and from 0.33 to 0.59 (percentage agreement, 43-63%) for intraobserver and interobserver agreement, respectively. When using four categories, kappa values ranged from 0.68 to 0.73 (percentage agreement, 77-80%) and from 0.39 to 0.64 (percentage agreement, 54-73%) for intraobserver and interobserver agreement, respectively. When using three categories, kappa values ranged from 0.70 to 0.83 (percentage agreement, 80-89%) and from 0.55 to 0.73 (percentage agreement, 70-82%) for intraobserver and interobserver agreement, respectively. Data were analyzed in each diagnostic category. When using four or three diagnostic categories, the mean intraobserver and interobserver agreements varied less between categories and achieved higher values, with smaller 95% confidence intervals. The mean percentage agreement was lowest for complex hyperplasia and for atypical hyperplasia. For distinguishing cyclical endometrium versus hyperplasia, the useful histologic feature was glandular crowding. For hyperplasia versus atypical hyperplasia and for hyperplasia versus endometrioid neoplasia, the useful features were nuclear enlargement, nuclear pleomorphism, vesicular chromatin, and nucleoli, but of these, only nuclear pleomorphism achieved substantial mean intraobserver and interobserver agreements. For discriminating atypical hyperplasia from well-differentiated adenocarcinoma, the only useful feature was stromal alterations, which achieved only fair mean intraobserver and interobserver agreements. In summary, in endometrial biopsy or curettage specimens, the lack of agreement in the diagnoses of complex hyperplasia and atypical hyperplasia and the lack of reproducibility in the recognition of the histologic feature of stromal alterations to differentiate atypical hyperplasia from well-differentiated adenocarcinoma suggest that the histologic classification should be simplified by including a combined category for simple and complex hyperplasia, called hyperplasia, and a combined category for atypical hyperplasia and well-differentiated adenocarcinoma, called endometrioid neoplasia. Diagnoses of hyperplasia and endometrioid neoplasia are highly reproducible between observers from different institutions. Glandular crowding is the best histologic feature to differentiate cyclical endometrium from hyperplasia, whereas nuclear pleomorphism is the reproducible cytologic feature to differentiate hyperplasia from endometrioid neoplasia.
Biopsy↗
The value of curettage in diagnosis of endometrial hyperplasia.
OBJECTIVES: The aim of this study was to assess the value of diagnosis of endometrial hyperplasia by curettage and to determine the results of proliferating cell nuclear antigen (PCNA) immunostaining in differentiating endometrial carcinoma from endometrial hyperplasia. METHODS: According to Kurman's criteria, we treated 150 patients with endometrial hyperplasia detected by curettage and compared retrospectively the diagnosis by curettage with that by hysterectomy. PCNA expression was examined using immunohistochemostaining on 60 patients with complex atypical hyperplasia detected by curettage. RESULTS: Simple hyperplasia was found by curettage in 53 patients, complex hyperplasia in 11, simple atypical hyperplasia in 26, and complex atypical hyperplasia in 60. All patients were rediagnosed after hysterectomy. As a result, 65 were found to have simple hyperplasia, 7 complex hyperplasia, 15 simple atypical hyperplasia, 29 complex atypical hyperplasia, and 34 endometrial carcinoma. The accuracy of histological diagnosis by curettage was 76.7-92.0% and was dependent on different types of hyperplasia. Simple atypical hyperplasia and complex atypical hyperplasia were more likely to coexist with endometrial carcinoma than both simple hyperplasia and complex hyperplasia (chi2 = 26.3, P < 0.001), and complex atypical hyperplasia was more likely to coexist with endometrial carcinoma than simple atypical hyperplasia (chi2 = 9.78, P < 0.005). In complex atypical hyperplasia patients, coexistence with endometrial carcinoma was more common after menopause than before menopause (chi2 = 3.93, P < 0.05). In complex atypical hyperplasia patients, the expression of PCNA in cases associated with endometrial carcinoma was higher or stronger than in cases associated without endometrial carcinoma (chi2 = 7.68, P < 0.01, or U = 252.00, P < 0.01). Conclusions. Curettage tends to be more highly accurate in diagnosing simple hyperplasia than complex atypical hyperplasia, which is often found by hysterectomy to be associated with endometrial carcinoma. The expression of PCNA may be helpful in differentiating complex atypical hyperplasia from endometrial carcinoma.
Adult↗
Accuracy of hysteroscopic diagnosis of endometrial hyperplasia: a retrospective study of 323 patients.
STUDY OBJECTIVE: To evaluate the diagnostic accuracy of hysteroscopic view in endometrial hyperplasia. DESIGN: Retrospective study (Canadian Task Force classification II-2). SETTING: Public hospital in northern Italy. PATIENTS: Three hundred twenty-three patients suffering from endometrial hyperplasia out of 2251 women (1119 premenopausal and 1132 postmenopausal) who underwent office-based hysteroscopy from January 1996 through May 2004. INTERVENTION: Review of 2251 outpatient hysteroscopies carried out with 5- to 6-mm sheathed hysteroscopes and accomplished with blind or hysteroscopically targeted endometrial biopsies. MEASUREMENTS AND MAIN RESULTS: The pathologic report was considered the reference test. Hysteroscopic detection of focal or extensive endometrial thickening, irregular vascular network, architectural distortion and crowding of gland openings, and gland cyst formation were considered endoscopic features consistent with hyperplasia. Overall sensitivity, specificity, negative predictive values (NPV), and positive predictive values (PPV) of hysteroscopy in order to foresee a diagnosis of hyperplasia were calculated. These figures were calculated both in premenopausal and postmenopausal patients. Histopathology yielded a diagnosis of simple, complex, and atypical hyperplasia in 247, 51, and 25 patients, respectively. Hysteroscopy foresaw hyperplasia in 38.4% of patients with simple hyperplasia and in 58.9% of patients with complex or atypical hyperplasia. Normal hysteroscopic findings underestimated simple hyperplasia in 34 patients (13.7%) and complex or atypical hyperplasias in 1 patient (1.3%) (p <.01). To predict the diagnosis of hyperplasia, hysteroscopy showed an overall sensitivity, specificity, NPV, and PPV of 63.7%, 91.7%, 91.3%, and 64.7%, respectively. Among premenopausal patients, hyperplasia was diagnosed in 134 women (11.9%); in this group, hysteroscopy showed sensitivity, specificity, NPV, and PPV of 65.6%, 88.5%%, 93.5%, and 50.5%, respectively. In postmenopausal patients, we found endometrial hyperplasia in 189 women (16.6%); sensitivity, specificity, NPV, and PPV of hysteroscopic view to anticipate hyperplasia were 61.6%, 95.2%, 89.3%, and 79.4%, respectively. A significantly better PPV to foresee hyperplasia was found in postmenopausal women compared with premenopausal patients (p <.01). CONCLUSIONS: Current hysteroscopic criteria suggesting endometrial hyperplasia are inaccurate; in order to exclude hyperplasia, a pathologic assessment is warranted in all hysteroscopies showing an irregularly lined or thick endometrium.
Adult↗
Basal cell hyperplasia in the peripheral zone of the prostate.
Basal cell hyperplasia in the prostate is often viewed as a transition zone proliferation, related to usual, nodular glandular, and stromal hyperplasia. Basal cell hyperplasia in the prostatic peripheral zone, the most common site for development of prostatic intraepithelial neoplasia and carcinoma, has not been previously characterized. We characterized the incidence and histomorphological attributes of basal cell hyperplasia in a series of 500 consecutive sextant needle core biopsy samples and in 26 completely embedded prostate glands from radical prostatectomy specimens. Comparative proliferation indices (by MIB-1 staining) and apoptotic indices (by TUNEL labeling) were quantitated for peripheral zone versus transition zone basal cell hyperplasia versus normal basal cells. The incidence of basal cell hyperplasia in prostate needle biopsy tissue was 10.2% (51 of 500 cases). Usual basal cell hyperplasia was detected in 8.2% of the 500 cases, and basal cell hyperplasia with prominent nucleoli, in 2.0% of cases. Basal cell hyperplasia in needle biopsy tissue was typically focal and associated with inflammation, which was usually lymphocytic, in 84% of cases. Peripheral zone basal cell hyperplasia was found in 23% of whole prostate glands. Peripheral zone basal cell hyperplasia was not observed to be in direct physical continuity with intraepithelial or invasive neoplasia. Peripheral zone and transition zone basal cell hyperplasia exhibited similar mean proliferation and apoptotic indices, at 1% and 0.07%, respectively. This proliferation index was elevated, and apoptotic index was decreased, relative to normal basal cells (P = 1 x 10(-7)). Basal cell hyperplasia in the peripheral zone is present in a significant minority of prostate needle biopsy samples and whole prostate glands. The presence of prominent nucleoli in basal cell hyperplasia may cause diagnostic concern for a neoplastic proliferation. The increase in cell number in basal cell hyperplasia appears to be due to a coordinate increase in proliferation index coupled with a diminished apoptotic index. The presence of inflammation in the majority of basal cell hyperplasia foci suggests that peripheral zone basal cell hyperplasia in untreated patients may represent a stereotyped response to injury such as that sustained because of inflammation.
Adult↗
Proliferative potential and K-ras mutation in epithelial hyperplasia of the gallbladder in patients with anomalous pancreaticobiliary ductal union.
BACKGROUND: Recent studies have shown that anomalous pancreaticobiliary ductal union (APBD) is an important risk factor for the development of gallbladder carcinoma. Epithelial hyperplasia of the gallbladder is one of the characteristic changes, but it is not clear whether epithelial hyperplasia is a premalignant lesion that could lead to cancer in APBD patients. METHODS: Twenty-four APBD patients were classified into two types: patients with bile duct dilation (dilated type) (n 13) and patients without dilation (undilated type) (n = 11). Resected gallbladders obtained from APBD patients and control patients without APBD were examined histologically and with immunohistochemical techniques for the detection of p53 and Ki-67 (as a cell proliferation marker). K-ras mutations were examined using polymerase chain reaction-restriction fragment length polymorphism and direct DNA sequence analysis. The patients were also classified, according to extent of epithelial hyperplasia, as having high grade or low grade hyperplasia. RESULTS: Fifteen (63%) of 24 APBD patients had epithelial hyperplasia of the gallbladder, whereas no patients without APBD exhibited this lesion. The incidence of epithelial hyperplasia was significantly higher in the gallbladders of undilated-type APBD patients (91%) than in those of dilated-type patients (38%) (P < 0.01). Three of 24 APBD patients (13%) had gallbladder carcinoma, and 2 of the 3 gallbladder carcinomas (67%) were accompanied by diffuse epithelial hyperplasia of the gallbladder. Among 21 nonneoplastic gallbladders, diffuse epithelial hyperplasia was observed in all (100%) of the undilated-type APBD and in 4 (33%) of 12 dilated-type APBD (P < 0.001). High grade hyperplasia was observed in 7 of 11 patients (64%) with undilated-type APBD and 2 of 13 patients (15%) with dilated-type APBD (P < 0.05). The incidence of high grade hyperplasia increased with age among patients older than 35 years. Ki-67 labeling index (LI) was significantly higher in hyperplastic mucosa than in control gallbladder mucosa. High grade hyperplasia had a significantly higher Ki-67 LI than low grade hyperplasia (P < 0.001). Two (22%) of 9 high grade hyperplasia cases had K-ras mutations, whereas none of 6 low grade hyperplasia cases had. The types of K-ras mutations in codon 12 were GTT (Val) and GAT (Asp) in each case of hyperplasia; these were identical to those of concomitant carcinomas. Neither hyperplastic nor normal mucosa exhibited p53 overexpression. CONCLUSIONS: The results of this study suggest that hyperplasia of the gallbladder mucosa in APBD patients is an early change that, because of the increased proliferative activity and presence of K-ras mutations, could be considered a premalignant lesion of the gallbladder. An increased cell population of epithelial hyperplasia may predispose the mucosa to mutational events, resulting in an increased risk for the development of gallbladder carcinoma in APBD patients.
Adolescent↗
Increased connexin43 expression in human saphenous veins in culture is associated with intimal hyperplasia.
OBJECTIVE: Intimal hyperplasia is a vascular remodelling process that occurs after a vascular injury. The mechanisms involved in intimal hyperplasia are proliferation, dedifferentiation, and migration of medial smooth muscle cells towards the subintimal space. We postulated that gap junctions, which coordinate physiologic processes such as cell growth and differentiation, might participate in the development of intimal hyperplasia. Connexin43 (Cx43) expression levels may be altered in intimal hyperplasia, and we therefore evaluated the regulated expression of Cx43 in human saphenous veins in culture in the presence or not of fluvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity. METHODS: Segments of harvested human saphenous veins, obtained at the time of bypass graft, were opened longitudinally with the luminal surface uppermost and maintained in culture for 14 days. Vein fragments were then processed for histologic examination, neointimal thickness measurements, immunocytochemistry, RNA, and proteins analysis. RESULTS: Of the four connexins (Cx37, 40, 43, and 45), we focused on Cx43 and Cx40, which we found by real-time polymerase chain reaction to be expressed in the saphenous vein because they are the predominant connexins expressed by smooth muscle cells and endothelial cells. After 14 days of culture, histomorphometric analysis showed a significant increase in the intimal thickness as observed during the process of intimal hyperplasia. A time-course analysis revealed a progressive upregulation of Cx43 to reach a maximal increase of sixfold to eightfold at both transcript and protein levels after 14 days in culture. In contrast, the expression of Cx40, abundantly expressed in the endothelial cells, was not altered. Immunofluorescence showed a large increase in Cx43 within smooth muscle cell membranes of the media layer. The development of intimal hyperplasia in vitro was decreased in presence of fluvastatin and was associated with reduced Cx43 expression. CONCLUSIONS: These data show that Cx43 is increased in vitro during the process of intimal hyperplasia and that fluvastatin could prevent this induction, supporting a critical role for Cx43-mediated gap-junctional communication in the human vein during the development of intimal hyperplasia. CLINICAL RELEVANCE: Stenosis due to intimal hyperplasia is the most common cause of failure of venous bypass grafts. To better understand the development of intimal hyperplasia, we used an ex vivo organ culture model to study saphenous veins harvested from patients undergoing a lower limb bypass surgery. In this model, the morphologic and functional integrity of the vessel wall is maintained and significant intimal hyperplasia development occurs after 14 days in culture. We have postulated that gap junctions, which coordinate physiologic processes such as cell growth and differentiation, may participate in the development of intimal hyperplasia. Indeed, intimal hyperplasia consists of proliferation and migration of smooth muscle cells into the subendothelial space. Intercellular communication is responsible for the direct transfer of ions and small molecules from one cell to the other through gap-junction channels found at cell-cell appositions. No study to date has evaluated whether gap junctional communication is involved in the process of intimal hyperplasia in humans. This assertion was investigated by using the aforementioned organ culture model of intimal hyperplasia in human saphenous veins, and our data support a critical role for Cx43-mediated gap junctional communication in human vein during the development of intimal hyperplasia.
Blotting, Western↗
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.
Adult↗
Hormone replacement therapy in postmenopausal women: endometrial hyperplasia and irregular bleeding.
BACKGROUND: The decline in circulating oestrogen around the time of the menopause often induces unacceptable symptoms that affect the health and well being of women. Hormone replacement therapy (both unopposed oestrogen and oestrogen and progestogen combinations) is an effective treatment for these symptoms. In women with an intact uterus, unopposed oestrogen may induce endometrial stimulation and increase the risk of endometrial hyperplasia and carcinoma. The addition of progestogen reduces this risk but may cause unacceptable symptoms, bleeding and spotting which can affect adherence to therapy. OBJECTIVES: The objective of this review is to assess which hormone replacement therapy regimens provide effective protection against the development of endometrial hyperplasia and/or carcinoma with a low rate of abnormal vaginal bleeding. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (searched January 2003), The Cochrane Library (Issue 2, 2003), MEDLINE (1966 to January 2003), EMBASE (1980 to January 2003), Current Contents (1993 to January 2003), Biological Abstracts (1969 to 2002), Social Sciences Index (1980 to January 2003), PsycINFO (1972 to February 2003) and CINAHL (1982 to January 2003). The search strategy was developed by the Cochrane Menstrual Disorder and Subfertility Group. Attempts were also made to identify trials from citation lists of review articles and drug companies were contacted for unpublished data. In most cases, the corresponding author of each included trial was contacted for additional information. SELECTION CRITERIA: The inclusion criteria were randomised comparisons of unopposed oestrogen therapy, combined continuous oestrogen-progestogen therapy and sequential oestrogen-progestogen therapy with each other and placebo administered over a minimum treatment period of six months. Trials had to assess which regimen was the most protective against the development of endometrial hyperplasia/carcinoma and/or caused the lowest rate of irregular bleeding. DATA COLLECTION AND ANALYSIS: Sixty RCTs were identified. Of these 23 were excluded and seven remain awaiting assessment. The reviewers assessed the thirty included studies for quality, extracted the data independently and odds ratios for dichotomous outcomes were estimated. Outcomes analysed included frequency of endometrial hyperplasia or carcinoma, frequency of irregular bleeding and unscheduled biopsies or dilation and curettage, and adherence to therapy. MAIN RESULTS: Unopposed moderate or high dose oestrogen therapy when compared to placebo was associated with a significant increase in rates of endometrial hyperplasia with increasing rates at longer duration of treatment and follow up. Odds ratios ranged from (1 RCT; OR 5.4, 95% CI 1.4 to 20.9) for 6 months of treatment to (4 RCTs; OR 9.6, 95% CI 5.9 to 15.5) for 24 months treatment and (1 RCT; OR 15.0, 95% CI 9.3 to 27.5) for 36 months of treatment with moderate dose oestrogen (in the PEPI trial, 62% of those who took moderate dose oestrogen had some form of hyperplasia at 36 months compared to 2% of those who took placebo). Irregular bleeding and non adherence to treatment were also significantly more likely under these unopposed oestrogen regimens that increased bleeding with higher dose therapy. Although not statistically significant, there was a 3% incidence (2 RCTs) of hyperplasia in women who took low dose oestrogen compared to no incidence of hyperplasia in the placebo group. The addition of progestogens, either in continuous combined or sequential regimens, helped to reduce the risk of endometrial hyperplasia and improved adherence to therapy. At longer duration of treatment, continuous therapy was more effective than sequential therapy in reducing the risk of endometrial hyperplasia. There was evidence of a higher incidence of hyperplasia under long cycle sequential therapy (progestogen given every three months) compared to monthly sequential therapy (progestogen given every month). No increase in endometrial cancer was seen in any of t in any of the treatment groups during the duration (maximum of six years) of these trials. During the first year of therapy irregular bleeding and spotting was more likely in continuous combined therapy than sequential therapy. However, during the second year of therapy bleeding and spotting was more likely under sequential regimens. REVIEWERS' CONCLUSIONS: There is strong and consistent evidence in this review that unopposed oestrogen therapy, at moderate and high doses, is associated with increased rates of endometrial hyperplasia, irregular bleeding and consequent non adherence to therapy. The addition of oral progestogens administered either sequentially or continuously is associated with reduced rates of hyperplasia and improved adherence to therapy. Irregular bleeding is less likely under sequential than continuous therapy during the first year of therapy but there is a suggestion that continuous therapy over long duration is more protective than sequential therapy in the prevention of endometrial hyperplasia. Hyperplasia is more likely when progestogen is given every three months in a sequential regimen compared to a monthly progestogen sequential regimen.
Endometrial Hyperplasia↗
The molecular genetics and morphometry-based endometrial intraepithelial neoplasia classification system predicts disease progression in endometrial hyperplasia more accurately than the 1994 World Health Organization classification system.
BACKGROUND: The objective of this study was to compare the accuracy of disease progression prediction of the molecular genetics and morphometry-based Endometrial Intraepithelial Neoplasia (EIN) and World Health Organization 1994 (WHO94) classification systems in patients with endometrial hyperplasias. METHODS: A multicenter, multivariate analysis was conducted on 477 patients with endometrial hyperplasia who were required to have a 1-year minimum disease-free interval from the time of the index biopsy (1-18 years of follow-up). The results from that analysis were compared with the results from 197 patients who had < 1 year of follow-up. RESULTS: Twenty-four of 477 hyperplasias (5.0%) progressed to malignant disease over an average of 4 years (maximum, 10 years). According to the WHO94 classification, 16 of 123 atypical hyperplasias (13%) and 8 of 354 nonatypical hyperplasias (2.3%) progressed (hazard ratio [HR] = 7). Twenty-two of 118 EINs (19%) and 2 of 359 non-EINs (0.6%) progressed (HR = 45). EIN was prognostic within each WHO94 subcategory. Progression rates were 3% in simple hyperplasias, 22% in complex hyperplasias, 17% in simple atypical hyperplasias, and 38% in complex atypical hyperplasias with EIN, compared with progression rates of 0.0-2.0% in all hyperplasias if EIN was absent. EIN detected precancerous lesions (sensitivity, 92%) better than WHO94 atypical hyperplasias collectively (67%) or complex atypical hyperplasias alone (46%). In a Cox regression analysis, EIN was the strongest prognostic index of future endometrial carcinoma. The same was true for patients with < 1 year of follow-up (HR for EIN, atypical hyperplasia, and complex atypical hyperplasia: 58, 7, and 8, respectively). CONCLUSIONS: The EIN classification system predicted disease progression more accurately than the WHO94 classification and identified many women with benign changes that would have been regarded as high risk according to the WHO94 classification system.
Adult↗
Adenomatous hyperplasia in the vicinity of small hepatocellular carcinoma.
The nodular lesions seen in the noncancerous areas of the 80 consecutively resected small hepatocellular carcinoma associated with cirrhosis were pathomorphologically studied. A total of 51 nodular lesions were found, and they were classified into the following four groups: large regenerative nodule (30 nodules), adenomatous hyperplasia (12 nodules), atypical adenomatous hyperplasia (4 nodules) and adenomatous hyperplasia containing cancerous foci (5 nodules). Grossly, all large regenerative nodules were well demarcated, but some of the adenomatous hyperplasia group were vaguely nodular. Atypical adenomatous hyperplasia and adenomatous hyperplasia containing cancerous foci accounted for 43% of the adenomatous hyperplasia group found in the vicinity of the 16 resected hepatocellular carcinoma (20%) out of 80 cases. The mean size (+/- S.D.) of the adenomatous hyperplasias containing cancerous foci, 15.8 +/- 2.2 mm, was significantly larger than 10.1 +/- 2.6 mm of the adenomatous hyperplasias p less than 0.01). All adenomatous hyperplasias containing cancerous foci and 75% of the atypical adenomatous hyperplasias demonstrated a marked fatty change, but none of the large regenerative nodules were accompanied by any fatty changes. This study demonstrated the morphological transition from adenomatous hyperplasia to hepatocellular carcinoma that was suggestive of multistep hepatocarcinogenesis. As a result, it is predicted that approximately 20% of all hepatocellular carcinomas may have the potential for being of multicentric origin and that approximately 40% of adenomatous hyperplasias may undergo malignant transformation, but it is difficult to estimate the exact number of incidences. The presence of varying degrees of fatty change may be one of the significant morphological markers for a malignant transformation from adenomatous hyperplasia to hepatocellular carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenoma↗
Down-regulation of bcl-2 is a potential marker of the efficacy of progestin therapy in the treatment of endometrial hyperplasia.
OBJECTIVE: The objective of this study was to evaluate the expression of bcl-2, a regulatory protein in programmed cell death, in endometrial hyperplasia before and after progestational therapy. METHODS: Pre- and posttreatment paraffin-embedded endometrial tissue samples from 20 women with an initial diagnosis of endometrial hyperplasia were obtained from archived files. Cases were evaluated and classified as either complete resolution of hyperplasia or persistent hyperplasia in response to progestin treatment. Sections were examined for bcl-2, estrogen receptor, and progesterone receptor expression using immunohistochemistry and compared within the treatment response groups. RESULTS: Among the 20 women studied, 13 had complete regression of their hyperplasia with progestin treatment and 7 had evidence of persistent disease after therapy. Bcl-2 expression was significantly decreased after treatment from a mean reactivity score of 2.08 to 0.31 (P = 0.0005) in the group of patients whose hyperplasia completely regressed with progestin administration. Among the women who had persistent hyperplasia after therapy, no significant change was observed between pre- and posttreatment bcl-2 expression, with a mean reactivity of 1.86 to 1. 29, respectively (P = 0.075). Progestational therapy significantly decreased the status of estrogen receptors from a mean score of 2.08 to 0.46 (P = 0.0005) in completely resolved cases of hyperplasia and from 2.00 to 0.43 (P = 0.0025) in persistent hyperplasias. Treatment also significantly decreased the status of progesterone receptors from a mean reactivity score of 1.92 to 0.31 (P = 0.0005) in cases of regressed hyperplasia and from a mean reactivity of 1.86 to 0.29 (P = 0.005) in persistent cases of hyperplasia. CONCLUSIONS: Bcl-2 expression decreases following successful progestin treatment of endometrial hyperplasias, whereas it remains expressed in hyperplasias which persist despite progestational therapy. This suggests that bcl-2 expression may represent a component of the therapeutic effects exerted in the endometium during progestational therapy in the treatment of hyperplasia. The activity of the oncoprotein may be a potential measure of the progress of treatment.
Adult↗
Simple hyperplasia of the endometrium: an evaluation of proliferative activity by Ki-67 immunostaining.
As endometrial hyperplasia has been characterized over the past 100 years, some investigators have questioned the hyperplastic nature of nonatrophic cystic glands associated with an increase in gland-to-stroma ratio, which is currently considered to represent simple endometrial hyperplasia. In the current study, the proliferative activity of simple endometrial hyperplasia was examined using an antibody to Ki-67 protein, a well-established marker of proliferative activity, and compared with the results of activity in inactive/atrophic endometrium, proliferative endometrium, and other forms of endometrial hyperplasia. In an evaluation of 68 endometrial biopsy specimens showing 110 histologic patterns, the mean Ki-67 index (percentage of Ki-67 positive nuclei) was 2.8% in inactive/atrophic endometrium, 23.2% in proliferative endometrium, 9.8% in simple hyperplasia, 12.7% in complex hyperplasia, and 10% in atypical complex hyperplasia. In simple hyperplasias, the mean Ki-67 index was 3.9% in dilated glands without infolding or outbranching, 14.6% in nondilated glands showing outbranching or slight crowding, and 6.9% in dilated glands with infolding or outbranching. Ki-67 indices for dilated glands were most similar, therefore, to atrophic/inactive endometrium with no statistical significant difference in the percentage of these cells staining between these two groups. In contrast, statistically significant differences were seen in staining between cystic patterns of simple hyperplasia and proliferative endometrium, simple hyperplasia showing outbranching and/or slight crowding but no dilation, complex hyperplasia, and atypical hyperplasia. The findings in the current study suggest that nonatrophic cystic glands with an increase in the gland-to-stroma ratio in the endometrium should not be considered a hyperplastic process and in the absence of other findings such as excessive bleeding or coexistent noncystic simple hyperplasia, treatment with progestin therapy, a widely used practice, is unnecessary. As discussed, the findings also suggest that these cystic forms of simple hyperplasia are precursors of cystic atrophies. Confirmation of these results on a larger population by a different research team appears desirable.
Biopsy↗
Endometrial hyperplasia: a review.
UNLABELLED: Endometrial hyperplasia is a precursor to the most common gynecologic cancer diagnosed in women: endometrial cancer of endometrioid histology. It is most often diagnosed in postmenopausal women, but women at any age with unopposed estrogen from any source are at an increased risk for developing endometrial hyperplasia. Hyperplasia with cytologic atypia represents the greatest risk for progression to endometrial carcinoma and the presence of concomitant carcinoma in women with endometrial hyperplasia. Abnormal uterine bleeding is the most common presenting symptom of endometrial hyperplasia. Specific Pap smear findings and endometrial thickness per ultrasound could also suggest the diagnosis. Unopposed estrogen in women taking hormone replacement therapy increases the risk of endometrial hyperplasia. Tamoxifen has demonstrated its efficacy in treating women at risk for breast cancer, but it increases the risk of endometrial hyperplasia. The choice of treatment for endometrial hyperplasia is dependent on patient age, the presence of cytologic atypia, the desire for future childbearing, and surgical risk. Endometrial hyperplasia without atypia responds well to progestins. However, women with atypical hyperplasia should be treated with hysterectomy unless other factors preclude surgery. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to describe the definition and classification of endometrial hyperplasia, to outline the clinical features of a patient with endometrial hyperplasia, to point out the natural history of endometrial hyperplasia, and to summarize the diagnostic options for patients with endometrial hyperplasia.
Algorithms↗
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.
Antineoplastic Agents, Hormonal↗