Contraception: Endometrial microvascular density during the normal menstrual cycle and following exposure to long-term levonorgestrel

The mechanisms that underlie progestogen-induced endometrialbreakthrough bleeding are poorly understood. The aim of thepresent study was to quantify endometrial microvascular densityin 54 controls and 42 women with 3–12 months' exposureto Norplant (levonorgestrel subdermal contraceptive implant)and to correlate it with bleeding pattern, endometrial histology,and peripheral plasma oestradiol and progesterone concentrations.Endometrial biopsies were processed routinely and sections immunostainedusing anti-CD34 antibody to identify vascular endothelial cells.Menstrual record card data were analysed using World HealthOrganization definitions. The mean microvascular density (±SEM) for control samples was 186 ± 8 vessels/mm², andthere were no significant differences across the cycle. Norplantuser's endometrial microvascular density was significantly elevatedabove controls (294 ± 18 vessels/mm², P = 3.36 x 10^–8).Endometrial microvascular density in Norplant users did notcorrelate with oestrogen concentrations prior to biopsy, bleedingpatterns or endometrial histology. The results from this studyshow that women receiving Norplant have significantly increasedendometrial microvascular density compared to controls. Anotherfinding from this study was that bleeding in Norplant usersoften occurred from thin atrophic endometrium. These resultsprovide new insights into the physiological mechanisms thatmay be involved in progestogen-induced endometrial bleeding.     

Contraception: Endometrial endotheial cell proliferation in long-term users of subdermal levonorgestrel

The aim of the oresent study was to quantity endothelial cellproliferation (a component of angiogenesis) using immunohistochemistry,in the endometrium of users of subdermal levonorgestrel (Norplant®).It was postulated that the increased endometrial microvasculardensity seen in Norplant users, compared to normally cyclingwomen, was associated with an increased rate of endothelialcell proliferation. The results, however, showed that the endometrialendothelial cell proliferative index of Norplant users (0.39±0.16%mean ±SEM) was significantly reduced compared to thatseem in normally cycling women (8.99±1.64). At the sametime, total numbers of endometrial endothelial cells permm2in Norplant users (317.40±13.88) were significantly higherthan in normally cycling women (223.25 ±10.31). It ispossible that in the endometrium with levonorgestrel use, thereis either a reduced rate of regression of the blood vesselsrelative to the rest of the tissue, or there is a reduced rateof endothelial cell death or turnover, Peripheral oestrogenand progesterone concentrations, bleeding pattern over the previous90 days, and the histological appearance of the endometriumdid not appear to be associated with the endithelial cell proliferstiveindex. The results suggest that subdermal levonorgestreo useaffects the mechanisms that dictate the normal relationshipbetween endometrial blood vessel growth and regression, andthe surrounding non-vascular tissue.     

Investigation of the infertile couple: hysteroscopy with endometrial biopsy is the gold standard investigation for abnormal uterine bleeding

During the last decade hysteroscopy has become the tool of choice for the evaluation of the endometrial cavity, including for assessment of abnormal uterine bleeding (AUB). Many clinicians would consider that, in most patients, the combination of transvaginal sonography and out-patient endometrial biopsy with diagnostic hysteroscopy could replace the need for dilation and curettage. Hysteroscopy was reported to have sensitivity, specificity, negative predictive value and positive predictive value of 94.2, 88.8, 96.3 and 83.1% respectively, in predicting normal or abnormal endometrial histopathology. The highest accuracy of hysteroscopy was in diagnosing endometrial polyps, whereas the worst result was in estimating hyperplasia. Therefore, since the incidence of focal lesions in patients with AUB is high, it seems that the most beneficial approach is to proceed with hysteroscopy complemented by endometrial biopsy early in the assessment of AUB. Nevertheless, the usage of distension media to flush the uterine cavity raises the concern that when the endometrium harbours pathology, there is the potential risk of retrograde dissemination of malignant cells into the peritoneal cavity. The clinical significance of the dissemination of endometrial cells during hysteroscopy is still undetermined.     

Endometrial breakdown in women using Norplant is associated with migratory cells expressing matrix metalloproteinase-9 (gelatinase B)

Norplant, subdermally implanted slow-release levonorgestrel, is an effective and widely used contraceptive agent but has a high rate of discontinuation due to unacceptable abnormal uterine bleeding. Matrix metalloproteinases (MMPs) are expressed in normal cycling endometrium and are postulated to be responsible for the tissue breakdown at menstruation. We have compared the immunolocalization of MMP-9 and migratory cells in endometrium from Indonesian women using Norplant with normal controls. Positive MMP-9 immunostaining was observed intracellularly within stromal and intravascular leukocytes and extracellularly in areas of tissue lysis adjacent to these migratory cells. The MMP-9 positive cells were identified as neutrophils, eosinophils, CD3+ T-cells and macrophages. Quantitative assessment revealed that the number of MMP-9 positive cells, neutrophils and eosinophils were significantly increased in those endometrial biopsies from Norplant users displaying a shedding morphology and in normal controls at menstruation. There was no correlation between the number of MMP-9 positive cells and the number of bleeding days reported. Endometrial immunostaining for tissue inhibitor of metalloproteinases was similar in Norplant users and normal controls. These results suggest that MMP-9, an enzyme capable of degrading basement membrane components, may be involved in endometrial breakdown in women using Norplant.     

Uterus and endometrium: The effect of local intrauterine levonorgestrel administration on endometrial thickness and uterine blood circulation

To evaluate non-invasively the role of levonorgestrel releasingdevices in direct contact with the endometrium on menstrualspotting and endometrium inactivation, we inserted levonorgestrelreleasing devices (20 µg/24 h) either into the cervicalcanal or the uterine cavity of 30 fertile women. Both beforeinsertion and over the following 3 months, we used transvaginalsonography to measure the endometrial thickness in 20 of thewomen and Doppler flow to measure the uterine blood flow inthe remaining 10 women. The women were asked to keep recordsof menstrual bleeding and they gave blood samples for the measurementof serum oestradiol, progesterone and levonorgestrel. By 10weeks after insertion there was a significant decrease in endometrialthickness in both groups. Intracervical levonorgestrel releaseallowed the endometrium to maintain cyclic changes, whereasdirect intrauterine levonorgestrel release eliminated the cyclicalchanges. The total number of spotting days was significantlyless (P = 0.0249) in the intracervical release group at 3 months;1.2 ± 0.6 versus 8.1 ± 1.8 (mean ± SE).There were no significant differences in hormone concentrationsbetween the groups. The pulsatility index did not change significantlyduring the study. We concluded that the inactivation processof the endometrium can be monitored by transvaginal sonographyand that locally administered levonorgestrel does not changecirculatory conditions detectable by Doppler flow. Our resultsalso suggest that the inactivation process of the endometriumis different between intracervical and intrauterine levonorgestreladministration and may explain the difference in the numberof spotting days.     

不同手术方式治疗异常子宫出血对卵巢功能的影响

目的：探讨不同手术方式治疗异常子宫出血对卵巢功能的影响。方法：选取2013年12月至2016年1月在我院接受治疗的异常子宫出血患者114例,按随机数表法将所有患者分成三组,其中A组患者38例,行子宫全切术;B组患者的38例,行子宫内膜电切术;C组患者38例,行子宫内膜去除术,观察并比较三组患者术前、术后3个月以及术后6个月的激素水平和术后排卵情况。结果：比较得知,术前、术后3个月和术后6个月,A组患者FSH、LH、E2水平差异较大,其中FSH和LH呈上升趋势,E2呈下降趋势,结果具有统计学差异,P<0.05;B组和C组患者性激素水平虽有较小波动,但组内和组间均无显著性差异,P>0.05;A组患者和B、C组患者相比,术后3、6个月各项指标均有差异,P<0.05;三组患者术后排卵功能恢复正常情况差异较大,其中C组患者总恢复率(80.95%)和B组患者总恢复率(71.05%)明显大于A组患者(40.63%),C组患者恢复情况最为显著,结果具有统计学差异,P<0.05。结论：三种手术治疗方式中,子宫全切术后6个月即开始出现卵巢早衰的征象,而子宫内膜电切术和子宫内膜去除术对卵巢功能影响较小,又因子宫内膜去除术简单高效,术后患者卵巢功能恢复较好,建议选择子宫内膜去除术。     

Contraception: Expression of progesterone receptor mRNA in the endometrium during the normal menstrual cycle and in Norplant(R) users

The expression of endometrial progesterone receptor mRNA duringthe human menstrual cycle and in Norplant users was studiedusing digoxigenin-labelled ribonucleic probes for in-situ hybridizationon 6 µm paraffin embedded endometrial sections. The stainingintensity was scored blind semi-quantitatlvely. Blood ovariansteroid concentrations were measured in Norplant users. Alldata were analysed by analysis of variance. Glandular progesteronereceptor mRNA concentrations were low during the menstrual-to-earlyproliferative stage but increased during the early-to-mid tolate-proliferative stage then declined non-significantly overthe secretory stage. No such variation was observed in stromalcells. Progesterone receptor mRNA concentrations were lowerin Norplant than controls during early-to-mid to late-proliferativestages (in glandular epithelium and stroma) and during secretorystage (in stroma only). Norplant subjects with amenorrhoea hadhigher concentrations of stromal progesterone receptor mRNAbut lower plasma oestrogen concentrations than subjects withbreakthrough bleeding. The pattern of variation in progesteronereceptor mRNA concentrations during the normal menstrual cycleresembles the published pattern for the receptor protein. Theresults demonstrate: (i) a differential sensitivity of glandularand stromal progesterone receptors to steroid regulation; (ii)in contrast to previous findings of an increase in immunoreactiveprogesterone receptor protein in Norplant endometrium, progesteronereceptor mRNA concentrations in these tissues were reduced;and (iii) there was significantly more progesterone receptormRNA in subjects with amenorrhoea than in those with breakthroughbleeding.     

Doxycycline alters the expression of inflammatory and immune-related cytokines and chemokines in human endometrial cells: implication in irregular uterine bleeding

BACKGROUND: Increased production of pro-inflammatory mediators is considered central in the manifestation of events leading to irregular uterine bleeding in progestin-only contraceptive users. Evidence suggests that in addition to its antimicrobial property, doxycycline (Dox) acts as an anti-inflammatory agent mainly through the suppression of pro-inflammatory mediators. METHODS: We tested this hypothesis in the endometrial environment using an in vitro model consisting of isolated human endometrial glandular epithelial and stromal cells and a human endometrial surface (HES) epithelial cell line cultured under defined conditions. RESULTS: We found that Dox at doses ranging from 1 to 100 microg/ml had a limited growth-inhibitory effect on these cells, whereas Dox in a dose-dependent manner inhibited the production of tumour necrosis factor-alpha (TNF-alpha). Using multiplex cytokine/chemokine protein analysis to test a broader range of Dox activity, we found that Dox at 25 microg/ml either alone or in the presence of 17beta-estradiol (E2), medroxyprogesterone acetate (MPA) and E2+MPA (10(-8) M) as well as TNF-alpha (25 ng/ml), representing the endometrial environment exposed to contraceptives as well as inflammatory conditions, respectively, altered the production of multiple cytokines and chemokines as compared with untreated controls. These actions of Dox occurred in cell-, ovarian steroid- and cytokine/chemokine-dependent manners. Although Dox reduced the regulatory action of steroids on the production of these cytokines/chemokines, it was less effective on TNF-alpha-treated cells. CONCLUSIONS: The results support the hypothesis that Dox, by modulating the endometrial expression of multiple inflammatory-related cytokines/chemokines in a cell- and cytokine/chemokine-dependent manner, may have a therapeutic potential in patients experiencing irregular uterine bleeding, in particular in progestin-dominant contraceptive users.     

Active pharmaceutical ingredients and mechanisms underlying phasic myometrial contractions stimulated with the saponin extract from Paris polyphylla Sm. var. yunnanensis used for abnormal uterine bleeding

BACKGROUND: Total steroidal saponins of Paris polyphylla Sm. var. yunnanensis (TSSP) have been widely used in China for the treatment of abnormal uterine bleeding (AUB). But until now, the main active constituents and the mechanisms underlying the pharmacological actions on uterine activity have not been described. METHODS: Total steroidal saponins were extracted with EtOH and purified by chromatography. In vitro isometric contraction studies were performed using myometrial strips from estrogen-primed or pregnant rats. Intracellular calcium was monitored under a confocal microscope using Fluo-3 AM-loaded myometrial cells. RESULTS: TSSP dose-dependently induced phasic myometrial contractions in vitro. Experiments with calcium channel blockers or kinase inhibitors demonstrated that the TSSP-stimulated myometrial contraction was mediated by an increase in [Ca(2+)](i) via influx of extracellular calcium and release of intracellular calcium. Through bioassay-guided separation, it was found that total spirostanol saponins exhibited contractile activity in myometrium and Pennogenin-3-O-alpha-L-arabinofuranosyl(1-->4)[alpha-L-rhamnopyranosyl(1-->2)]-beta-D-glucopyranoside (PARG) was identified as the active ingredient of TSSP. Furthermore, the contractile response of rat myometrium to PARG was significantly enhanced with advancing pregnancy. CONCLUSIONS: These data provide evidence that myometrial contractility stimulated by TSSP results from [Ca(2+)](i) increase and supports the possibility that some spirostanol gylcosides may represent a new type of contractile agonist for the uterus.     

Endometrial thickness measured by ultrasound scan in women with uterine outlet obstruction due to intrauterine or upper cervical adhesions

BACKGROUND: A subgroup of women with Asherman's syndrome has adhesions of limited extent completely blocking the lower uterine cavity or upper cervix, whereas the upper endometrium remains normal. Haematometra are rarely found in these women. We tested the hypothesis that women with localized adhesions occluding the uterine outlet (but not affecting the upper uterine cavity) will have much thinner endometrium than controls. METHODS: Twenty-six women with Asherman's syndrome (16 with limited outlet adhesions only) and 50 with normal menstrual cycles underwent transvaginal ultrasound scan where endometrial double thickness was measured precisely and the cycle phase assessed. The presence of any fluid in the uterine cavity was noted. RESULTS: The endometrium in women with Asherman's syndrome, in whom uterine outlet blockage was the sole abnormality (subgroup 3), was substantially thinner (mean +/- SEM: 3.9 +/- 0.4 mm) than controls (8.5 +/- 0.05; P < 0.001), and haematometra were very uncommon (1 of 16). Endometrial thickness at all stages of the ovarian/menstrual cycle in all three subgroups of Asherman's syndrome was significantly less than in normal menstruating controls. CONCLUSIONS: Non-invasive ultrasound measurements have demonstrated very thin endometrium and absence of haematometra in most women with uterine outlet occlusion by adhesions. This unusual phenomenon of failure of cyclical endometrial growth and breakdown in the sole presence of cervical occlusion by adhesions merits further study.     

Endometrial responses to hormone replacement therapy: the bleeding pattern

Little information is available concerning the response of theendometrium to exogenous sex steroid therapy, particularly inthe post-menopausal state. In this study we examined the variabilityof the bleeding pattern in 103 post-menopausal women receivingcyclical sequential combined hormone replacement therapy (HRT)over 6 months. All patients kept menstrual diary cards to recordthe onset, duration and subjective assessment of the severityof bleeding. We defined a cycle as starting from the commencementof treatment till the day of onset of bleeding. Two groups wereidentified amongst 99 women who experienced bleeding: thosewith a mean cycle length of 29 or more days (late bleeders,n = 50) and those with shorter mean cycle length (early bleeders,n = 49). The former were characterized by less variability incycle length and bleeding that was of shorter duration. Fourwomen experienced no bleeding. There were no significant differencesbetween the two groups in age, year since the menopause, weight,height, body mass index (BMI), parity, or in the previous useof HRT. The only significant difference was in their smokinghabits. This suggests a possible link of a hypo-oestrogenicstate to poor cycle control.     

Immunolocalization of endothelin and neutral endopeptidase in the endometrium of users of subdermally implanted levonorgestrel (Norplant(R))

Subdermally implanted slow-release levonorgestrel (Norplant®),a widely used effective contraceptive, has a high rate of discontinuationdue to unacceptable menstrual bleeding disturbances. Endothelin(ET), a potent vasoconstrictor,varies across the menstrual cyclein normal endometrium.It has been proposed that ET has a potentialparacrine role in the regulation of uterine blood flow.Neutralendopeptidase (NEP), a membrane-bound ectoenzyme,can inactivateET and is localized principally in endometrial stroma. We havecompared the immunolocalization of ET and NEP in endometrialbiopsies from Indonesian women using Norplant® with normalcontrols.Differences were observed in the glandular and luminalepithelium of Norplant®-treated subjects, where ET immunostainingwas low while NEP immunoreactivity was increased. The lattermay represent a local increase in enzyme activity, potentiallyexplaining the reduced ET immunoreactivity. There was no correlationof ET immunoreactivity with the duration of implant use or totalnumber of bleeding days. The marked differences in the ET immunostainingpattern in Norplant® users, with their increased risk ofabnormal uterine bleeding, suggest that ET may be importantin controlling menstrual bleeding.Whether endometrial epithelialcell ET has a role as a mitogen in endometrial repair and regeneration,or as a vasoconstrictor important in the cessation of bleedingfollowing menstruation, remains to be determined.     

The levonorgestrel-releasing intrauterine system (LNG-IUS) in HIV-infected women--effects on bleeding patterns, ovarian function and genital shedding of HIV

BACKGROUND: Safe and effective contraceptives are needed for human immunodeficiency virus (HIV)-infected women. The levonorgestrel-releasing intrauterine system (LNG-IUS) is a highly effective contraceptive with additional health benefits. The objective of this study was to evaluate the effects of the LNG-IUS among HIV-infected women. METHODS: Twelve systematically managed HIV-infected women were studied prospectively. Following a 2-month run-in period, the subjects had an LNG-IUS inserted and were followed up for 1 year. Patterns of bleeding, blood haemoglobin and CD4-lymphocyte content, plasma HIV RNA, serum levels of LNG, of estradiol (E(2)) and of ferritin and genital shedding of HIV RNA were monitored. RESULTS: Menstrual bleeding was reduced significantly during the use of the LNG-IUS; this was associated with slight increases in serum haemoglobin and ferritin levels. Serum E(2) concentrations remained in the follicular range in all subjects. Among subjects using antiretroviral medication, the proportion of cervicovaginal lavage specimens with detectable HIV RNA was 10% before and after the insertion of the LNG-IUS. CONCLUSIONS: The effects of the LNG-IUS on bleeding patterns, body iron stores and ovarian function were similar to those seen in healthy women. Genital shedding of HIV RNA was not affected by the LNG-IUS. These data encourage further studies on the effects of the LNG-IUS on reproductive health among HIV-infected women.     

Intraperitoneal levonorgestrel-releasing intrauterine device following uterine perforation: the role of progestins in adhesion formation

BACKGROUND: Intrauterine contraception is a widely used, highly effective means of birth control. Uterine perforation is a serious, albeit rare, complication of intrauterine device (IUD) use. Although uterine perforation by levonorgestrel-releasing (20 micro g/day) intrauterine system (LNG-IUS) has already been reported, the peritoneal adhesion potential of this IUD is unknown. METHODS: The medical files of all patients diagnosed with an intra-peritoneal IUD between the years 1990-2002 at Hadassah Medical Center were reviewed. Histopathological study of peritoneal adhesion tissue adjacent to levonorgestrel medicated IUD was conducted in one case. RESULTS: Eight cases of dislocated IUDs were found. Four cases used LNG-IUS and four other cases used copper-IUD. Laparoscopy for IUD removal disclosed mild local peritoneal adhesions between omentum and pelvic organs in all cases. No difference was noted in the appearance of the peritoneum in the presence of either a copper-IUD or LNG-IUS. Histological examination of peritoneal tissue encasing the levonorgestrel-intrauterine system revealed loose connective tissue with aggregates of submesothelial cells with a pseudo-decidual change. Immunohistochemical staining for progesterone receptor was negative. CONCLUSIONS: The peritoneal adhesions potential of LNG-IUS is low, similar to that of the copper-bearing IUD.     

Endometrial cells of the “Lower uterine segment” (LUS) in cervical smears obtained by endocervical brushings: A source of potential diagnostic pitfall

The use of endocervical brushes has led to a generous sampling of both endocervical and “lower uterine segment” (LUS) cells. to an unfamiliar eye, the large fragments of endometrial tissue from the LUS may lead to misinterpretation as endometriosis or glandular malignancy, as happened in our institution when the use of endocervical brush and recognition of LUS cells in cervical smears were limited. Eight cases, cytologically interpreted as such, were proven to be benign following cervical biopsy or endometrial curettage. the nature of LUS cells was recognized only on retrospective review of this cytologic material. However, in recent years, routine use of the endocervical brush resulted in an influx of similar cases referred by the cytotechnologists to the pathologist as glandular atypia. Thus, to get familiarized with the cytomorphology of LUS cells and its diagnostic pitfalls, a prospective study was undertaken. This entailed a review of 62,187 consecutive cervicovaginal smears (women of post-hysterectomy status were excluded) received within a 12-mo period (July 1, 1992-June 30, 1993). A total of 344 smears (0.55%) showed large tissue fragments of branching tubular endometrial glands with and without surrounding stroma. Patients ranged from 14–82 yr of age. History of cervical cone biopsy was noted in nine patients (2.6%). Repeat cervical smear or concurrent endometrial or endocervical biopsy available in 84 patients (24.4%) were negative. LUS cells may be mistaken for endometriosis, epithelial glandular atypia, as well as carcinoma of both endocervical and endometrial origin. in addition to glandular abnormality, LUS cells may also be misinterpreted as that of squamous intraepithelial lesion. the characteristic presentation of LUS cells with long tubular branching glands embedded in a loose monomorphic stromal cells containing delicate capillaries is best appreciated at low power magnification. Familiarity with the cytomorphologic features of LUS and awareness of the diagnostic pitfalls may avoid interpretative errors and unnecessary surgical procedures. © Wiley-Liss, Inc.     

Guanylyl cyclase inhibitors NS2028 and ODQ and protein kinase G (PKG) inhibitor KT5823 trigger apoptotic DNA fragmentation in immortalized uterine epithelial cells: anti-apoptotic effects of basal cGMP/PKG

The cGMP/protein kinase G (PKG) signalling pathway, at basal levels, has anti-apoptotic/pro-survival effects in certain neural cells. The present study determined apoptosis-regulating effects of basal cGMP/PKG in an immortalized uterine epithelial cell line, HRE-H9 cells, using two soluble guanylyl cyclase (sGC) inhibitors, NS2028 and ODQ, and a PKG inhibitor, KT5823. A new quantitative, ultrasensitive technique using capillary electrophoresis with laser-induced fluorescent detector (CE-LIF), recently developed in our laboratory, was used to quantify levels of apoptotic DNA fragmentation. NS2028 and ODQ increased apoptotic DNA fragmentation by 3.5- and 9-fold respectively, suggesting that lowering basal cGMP levels causes spontaneous apoptosis. 8-Br-cGMP, a cell-permeable cGMP analogue that directly activates PKG, reduced ODQ-induced apoptosis by 81%, indicating that replacement of lowered cGMP with a direct PKG activator prevents apoptosis. Western blot analysis, using PKG type I (PKG-I)-specific antibody, indicated that HRE-H9 cells express PKG-I at moderate levels. Inhibiting basal PKG activity with KT5823 increased apoptotic DNA fragmentation by 9.8-fold. Overall, the data show that inhibitors of basal sGC and PKG activities in immortalized uterine epithelial cells cause apoptosis, suggesting that normal basal levels of cGMP and PKG activity may be necessary to prevent a spontaneous development of apoptosis in these cells.     

Oestradiol enhances in vitro the histamine release induced by embryonic histamine-releasing factor (EHRF) from uterine mast cells.

The relationship between maternal hormones and factors secreted by the implanting embryo is still controversial. We have analysed the in-vitro effect of oestradiol and human embryo-derived histamine-releasing factor (EHRF) on histamine release from rat uterine mast cells. Rat uterine mast cells which were preincubated with oestradiol and then challenged with human EHRF gave histamine release values two- to threefold higher than those without preincubation. The enhancement observed was time- and temperature-dependent. A similar enhancement was obtained with human sensitized basophils but not with rat peritoneal mast cells. Oestradiol, used as a direct challenge, did not induce any histamine release from either rat uterine or peritoneal mast cells, or from human sensitized basophils. Oestradiol preincubation also enhanced the histamine release induced by anti-IgE but did not enhance the histamine release induced by substance P or compound 48/80, two secretagogues that are not mediated by IgE. Moreover, uterine fragments derived from rats at various oestrus phases, with different amounts of endogenous oestrogen, were challenged in vitro with EHRF. The release of histamine by mast cells was higher at the proestrus and preimplantation phases than at dioestrus. All these findings suggest that the interaction of oestradiol with rat uterine mast cells was capable of enhancing in vitro the histamine releasing effect of EHRF.     

Endometrial atypical (bizarre) stromal cells: a potential diagnostic pitfall in biopsy

Atypical stromal cells (ASCs) may be detected in endometrial polyps and, more rarely, in normal endometrium. Owing to their worrisome cytological features, these cells may represent a potential diagnostic pitfall and are often misinterpreted as malignant, particularly in biopsy samples. We report on ASCs in proliferative phase endometrium of a woman who underwent biopsy for vaginal bleeding. Morphological and immunohistochemical features are discussed in detail. The differential diagnosis to endometrial malignant tumors containing atypical mesenchymal cells is provided.