Low-grade endometrial stromal sarcoma presenting as multiple pulmonary nodules: A potential pitfall in fine needle aspiration and core biopsy specimens - A Cytological - Pathological Correlation

Low-grade endometrial stromal sarcoma (LGESS) is the second most common malignant mesenchymal tumor of the uterus. The most common location is the uterine corpus, but it can also primarily arise in a variety of extrauterine locations such as pelvis, ovary, abdominal cavity, vagina, and vulva. We are reporting a case of a 47-year-old female with no significant medical history who presented with multiple pulmonary nodules. Fine needle aspiration (FNA) specimen revealed spindle cell neoplasm consistent with the diagnosis of LGESS. The differential diagnosis included neuroendocrine tumor, synovial sarcoma, solitary fibrous tumor, smooth muscle tumors, and peripheral nerve sheath tumors. The clinical, cytological, and histopathologic details of this case, as well as a discussion of the potential pitfalls and differential diagnosis of spindle cell lesions of the lung are described.     

Endometrial stromal neoplasms of the uterus. A clinicopathologic study.

A clinicopathologic study of uterine endometrial stromal tumors (EST) has been performed with special emphasis on histologic and immunohistochemical differential criteria and prognostic factors. The material comprised three stromal nodules (SN), twelve low grade stromal sarcomas (LGESS) and five high grade stromal sarcomas (HGESS). Previously unreported endolymphatic growth was found within one SN. EST showed an association of mitotic index (IM) with atypia, degree of stromal differentiation, additional non-stromal differentiation and venous invasion. IM was the best criterion in the differential diagnosis of LGESS and HGESS and the most significant histologic prognosticator. The present study shows that a histologic grade of stromal sarcoma was a more significant prognostic factor than pTNM stage. The results suggested that clinicopathologic classification of EST could be supplemented by including the following subgroups: a) SN--without intravascular growth, and potentially malignant SN--with endolymphatic growth within the tumor; b) LGESS with IM < 2 and no atypia, and LGESS with 2 > IM < 10 and mild atypia; c) HGESS with 10 > IM < 20 and moderate atypia, and HGESS with IM > 20 and marked atypia. Contrary to common view these observations indicate that the distinction of some SN and LGESS from stromal hyperplasia is possible in an endometrial curretage material.     

子宫内膜间质肉瘤55例临床病理特点和预后分析

目的 了解子宫内膜间质肉瘤(ESS)的病理形态特征并分析影响预后的相关指标.方法 收集该院55例ESS患者的临床和病理资料,所有病例重新阅片,参照文献分类为低级别子宫内膜间质肉瘤(LGESS)、不伴核多形的未分化子宫内膜肉瘤(UES-U)、伴有核多形的未分化子宫内膜肉瘤(UES-P);同时观察肿瘤细胞的形态特点,包括纤维样、肌样、黏液样、上皮样分化,并计数核分裂象等.对所有病例进行临床资料的收集并随访.结果 LGESS、UES-U、UES-P型病例分别为39、9、7例.病理形态上,ESS有多种形态分化并存的特点,LGESS、UES-U及UES-P型病例中分别有12.8%(5/39)、5/9及5/7伴有两种以上混合的形态学分化;同一病例的不同区域核分裂象计数和组织学类型亦存在较大差异.临床上肿瘤复发比例分别为51.6%(16/31)、5/6、2/3;LGESS无死亡病例,UES-U和UES-P中各有2例死亡,且UES-U的死亡病例均有局灶UES-P区域.按核分裂象最高计数进行预后分析,≥10/10 HPF的病例复发率显著高于＜10/10 HPF的复发率(P=0.009),在LGESS病例中亦存在这种统计学差异,所有死亡病例的核分裂象最高计数均＞30/10 HPF.结论 ESS常见不同程度分化重叠及多向分化的特点,尤以UES-U和UES-P中更为常见,因此应充分取材以寻找诊断线索.肿瘤中伴有UES-P图像,同时伴核分裂象计数高度活跃可能会增加死亡风险.在LGESS病例中,核分裂象最高计数≥10/10 HPF的肿瘤复发率显著增高,在诊断时应引起重视.

Abstract：

Objective To investigate the clinicopathologic features and the prognostic factors of endometrial stromal sarcoma (ESS). Methods 55 cases of endometrial stromal sarcoma were reviewed and categorized into 3 pathologic types based on the related literatures, i.e. , low grade endometrial stromal sarcoma (LGESS), undifferentiated endometrial sarcoma with nuclear uniformity (UES-U) and undifferentiated endometrial sarcoma with nuclear pleomorphism (UES-P). Meanwhile, the pathologic features were reviewed, including fibroid, myoid, mucoid, and epithelioid differentiation and mitotic index.Clinical and follow-up data were collected. Results In endometrial stromal sarcoma, two or three pathologic types co-existed in one case, including 12. 8% (5/39) of LGESS, 5/9 of UES-U, and 5/7 of UES-P.Mitotic index varied in different regions of one tumor from rare to high. Multi-differentiation was also commonly seen in ESS. The numbers of cases in LGESS, UES-U and UES-P were 39, 9 and 7, with recurrence rate of 51.6% ( 16/31 ), 5/6 and 2/3, respectively. There was no death case in LGESS, and 2 cases were died in UES-U and UES-P, respectively. In the 2 death cases of UES-U, both had focus of UES-P. There was a significant difference in the recurrence rate between cases with different mitotic index ( ≥ 10/10 HPF and ＜ 10/10 HPF, P = 0. 009), especially in LGESS group. All death cases had high mitotic index ( ＞ 30/10 HPF). Conclusions It is a common phenomenon in ESS that two or three pathologic types may exist in one case, especially in UES-U and UES-P. And multi-differentiation is also commonly seen in ESS. So adequate pathologic sampling is important for pathologists to make a correct diagnosis of ESS in daily work. The recurrence rates are significantly higher in cases with high mitotic index,especially in LGESS. In addition, the presence of UES-P and high mitotic index may increase the risk of death in the patients.     

子宫内膜间质肉瘤9例临床病理分析

目的 探讨子宫内膜间质肉瘤(endometrial stromal sarcoma,ESS)的临床病理特征、诊断、鉴别诊断及预后.方法 对9例ESS患者进行临床、病理资料分析、免疫组化检测及随访.结果 患者年龄39～64岁,中位46.3岁.临床主要表现为阴道流血及子宫增大/占位.肿瘤直径2.3～11 cm,平均4.6 cm.光镜下8例呈低度恶性子宫内膜间质肉瘤(low grade endometrial stromal sarcoma,LGESS),均由类似增殖期子宫内膜间质肿瘤细胞构成,细胞密集,异型性不明显,呈不规则舌状或岛状浸润肌层,并伴较多薄壁螺旋小血管;1例为高度恶性子宫内膜间质肉瘤/未分化子宫内膜肉瘤(high grade endometrial stromal sarcoma/undifferentiated endometrial sarcoma,HGESS/UES),肿瘤细胞直接替代子宫肌层,具有明显的细胞异型性,无LGESS常见的螺旋小血管.免疫组化检测显示肿瘤细胞CD10、vimentin均阳性,PR、ER大部分阳性,SMA和desmin及h-Caldesmon为极少数局灶阳性,S-100、CD34均阴性.术后随访7例(平均53个月),只有1例HGESS/UES死亡.结论 ESS是女性生殖道很少见的一种恶性肿瘤,恶性度相差很大.确诊主要依靠其临床病理特点,并辅以免疫组化标记综合分析.诊断时要与子宫内膜间质结节、平滑肌肿瘤、低分化癌等鉴别.     

Retroperitoneal lymphangioleiomyoma with lymph node involvement: A pathologic-radiologic correlation of a rare form of myomelanocytic tumor

Lymphangioleiomyomatosis (LAM) is a rare and slowly progressive disorder that usually arises in the lung, affects exclusively women in their childbearing years, and typically presents with progressive dyspnea on exertion and pneumothorax. Infrequently, extra-pulmonary LAM can occur in the retroperitoneum, uterine wall, mediastinum and intraperitoneal lymph nodes. Histologically, LAM is characterized by a proliferation of perivascular epithelioid cells (PEC) that express markers for both melanocytes and smooth muscle cells.We report a case of a peripancreatic retroperitoneal mass that was incidentally discovered on magnetic resonance image (MRI) scan of a 38-year-old female. The morphologic findings and the immunohistochemical staining were consistent with a lymphangioleiomyoma. The radiologic and pathologic correlation along with differential diagnosis of this rare entity is discussed.     

Pleomorphic high grade endometrial stromal sarcoma with YWHAE gene amplification may be a novel variant with poor prognosis

Endometrial stromal neoplasms are classified by the World Health Organization (WHO) into endometrial stromal nodule (ESN), low grade (LGESS), high grade (HGESS), and undifferentiated uterine sarcoma (UUS). HGESS is subclassified based on molecular findings, YWHAE or BCOR. The HGESS with YWHAE::NUTM2A/B (alias YWHAE::FAM22A/B) fusion usually have relatively monomorphic (as with most fusion-associated malignancies) rounded to epithelioid cells with eosinophilic cytoplasm, vesicular nuclei, nucleoli, and mitotic figures >10/10 HPF. We present a 66-year-old woman with post-menopausal bleeding found to have a heterogeneous solid-cystic uterine mass on CT who underwent total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and pelvic lymph node dissection. A 15.0×9.0 cm variegated uterine mass with hemorrhage and necrosis was identified. Histologically, the tumor was hypercellular with haphazard fascicles, microcysts, and tongue-like destructive myometrial invasion. Tumor cells exhibited marked pleomorphism and high mitotic activity with atypical mitotic figures. There was extensive cyclin-D1 and subset CD10 immunopositivity. FISH showed YWHAE amplification but without rearrangement. Interestingly, we found only two other reported cases of pleomorphic HGESS with YWHAE gene amplification upon review of 259 cases from cBioPortal database, one of which was reported as carcinosarcoma with heterologous elements. Of note, all three YWHAE amplified cases were diagnosed at high-stage and succumbed to disease within six months. Our case appears to be the third case of YWHAE-amplified pleomorphic HGESS, possibly a new variant of uterine sarcoma with aggressive biologic behavior that needs further evaluation.     

Uterine adenosarcoma detected by conventional papanicolaou smear: A case report with emphasis on integrating the immunocytochemical staining

Adenosarcoma is a rare uterine malignant tumor composed of benign to atypical epithelial element and a usually low-grade sarcomatous component. Although it is well known histologically, its cytological features are rarely described in the literature. We report a case of uterine adenosarcoma being the first one that was accurately diagnosed before operation by the conventional Papanicolaou (Pap) smear with emphasis on the contribution of the integrated immunocytochemical staining. A 46-year-old woman with abnormal vaginal bleeding and a protruding mass from her cervical os. Her Pap smear revealed: (a) presence of endometrial necrotic debris in the background, which indicated the presence of an endometrial lesion, (b) presence of both abnormal endometrial glandular cells (compact and tight clusters with slight hyperchromasia, increased nucleus/cytoplasm (N/C) ratio, apparent nucleoli and moderate vimentin stain) and abnormal stromal cells (loose aggregates of spindle to polygonal cells with hyperchromasia, increased N/C ratio and very strong vimentin staining). The characteristic degenerative necrotic debris indicating endometrial lesion plus the application of immunocytochemistry, which can increase the detection rate of endometrial lesion by the Pap smears. Awareness of the cytological findings of adenosarcoma can aid to make a correct preoperative diagnosis of this rare disease.     

CD10 is a sensitive and diagnostically useful immunohistochemical marker of normal endometrial stroma and of endometrial stromal neoplasms

AIMS: The CD10 antigen is expressed in acute lymphoblastic leukaemia and follicle centre cell lymphoma. A recent study investigating the expression of CD10 in a wide range of non-haematopoietic neoplasms found positive staining in a small number of endometrial stromal sarcomas as well as in normal endometrial stroma. The present study aimed to ascertain whether CD10 positivity is indeed found in normal endometrial stroma and endometrial stromal neoplasms. Staining of a range of tumours which can be confused morphologically with endometrial stromal neoplasms was also undertaken to ascertain whether antibodies against CD10 are of value in a diagnostic sense. METHODS AND RESULTS: Neoplasms included in the study were endometrial stromal nodule (n=1), low-grade endometrial stromal sarcoma (ESS) (n=13), high-grade ESS (n=6), mixed endometrial stromal-smooth muscle tumour (n=1), uterine cellular leiomyoma (n=10), uterine leiomyosarcoma (n=5), adult granulosa cell tumour (AGCT) (n=10), undifferentiated endometrial carcinoma (n=6), uterine carcinosarcoma with an endometrial stromal component (n=1) and type II uterine mesenchymal tumour with sex cord-like elements (n=1). Cases of proliferative (n=5), secretory (n=5) and atrophic (n=3) endometrium were also stained. There was positive staining of stroma but not of glands in all cases of non-tumorous endometrium. There was positive staining of the endometrial stromal nodule and of all low-grade ESS. Staining in these varied but was often diffuse and of moderate to strong intensity. There was positive staining of four of six high-grade ESS, but this was usually focal. There was also positive staining of the endometrial stromal component in the mixed endometrial stromal-smooth muscle tumour and in the uterine carcinosarcoma. Most cellular leiomyomas were completely negative although three exhibited weak positivity. There was some positivity, usually focal or weak, of three of five leiomyosarcomas. Most AGCT and undifferentiated carcinomas were completely negative although one case of each exhibited focal staining. There was focal staining of the type II uterine mesenchymal tumour with sex cord-like elements. CONCLUSION: CD10 is a reliable and sensitive immunohistochemical marker of normal endometrial stroma. Positivity, which is often strong and/or diffuse is found in endometrial stromal nodules and low-grade ESS. Positive staining with CD10, when strong and diffuse, may be useful in distinguishing these tumours from histological mimics, especially cellular leiomyoma and AGCT which are generally negative. In this situation, CD10 should be used as part of a panel which might include desmin and alpha-inhibin depending on the differential diagnosis considered. Positive staining with CD10 in a high-grade uterine sarcoma which is negative with muscle markers might indicate endometrial stromal differentiation and identify a group of neoplasms which it is correct to diagnose as high-grade ESS rather than undifferentiated uterine sarcoma.     

Dynamic monitoring of menopause hormone therapy and defining the cut-off value of endometrial thickness during uterine bleeding

The aim of this study was to evaluate the effects of low-dose tibolone therapy on ovarian area, uterine volume and endometrial thickness, and define the cut-off value of endometrial thickness for curettage during uterine bleeding. We followed 619 postmenopausal women, aged 40-60 years, for two years. There were 301 subjects in the low-dose tibolone treatment group and 318 subjects in the control group. The ovarian area, uterine volume and endometrial thickness in all participants were measured by transvaginal ultrasound prior to, one and two years post enrollment, respectively. Endometrial specimens were collected from all subjects with abnormal uterine bleeding during the follow-up period. We found that the uterine volume in the treatment group was greater than that in the control group, and the difference was significant (P<0.05), but there were no significant differences in ovarian area and endometrial thickness between the two groups (P>0.05). When the cut-off value for endometrial thickness was 7.35 mm, the sensitivity and specificity were 100% and 79.07%, respectively, and 85.71% and 93.02% when 7.55 mm was set as the cut-off during tibolone therapy. The results indicate that low-dose tibolone therapy may postpone uterine atrophy and the cut-off value of endometrial thickness may be appropriately adjusted for curettage.     

Abnormal uterine bleeding: the importance of uterine cavity visualization

Abnormal uterine bleeding is a common gynaecological problem.It is usually due to local pathology such as uterine myoma,endometrial polyp, or to anovulatory bleeding. Occasionally,it is a manifestation of a systemic disease. In this issue ofHuman Reproduction Update, Livingstone and Fraser discuss themechanism of abnormal uterine bleeding. They correctly statethat there are many causes of abnormal uterine bleeding andthat its mechanism is complex. Abbott and Garry discuss the treatment of abnormal uterine bleeding.They imply that the success rate of medical treatment is inferiorto that of surgical treatment. One of the accepted surgicaltreatments is endometrial ablation. If the first generationendometrial ablation is done under hysteroscopic control, someof the second generation techniques including the balloon technique,microwave endometrial ablation and others are performed blindly.These are acceptable techniques, providing a hysteroscopic evaluationof the uterine cavity is incorporated. Anecdotally, myself andothers have encountered a suspicious lesion just prior to anendometrial ablation that turned out to be endometrial cancer.This underscores the importance of visualization of the endometrialcavity prior to endometrial ablation. Without hysteroscopy,it is also difficult to ascertain the completeness of the ablation.Hysteroscopy is a powerful and yet simple technique to perform.I recommend hysteroscopy examination before and after non-hysteroscopicendometrial ablation. Missed intact endometrium after ablationcan then be removed. This is in disagreement with some thatpromote ‘office endometrial ablation’ without anyvisualization of the uterine cavity. Performing the procedureblindly is equivalent to returning to the old era of missingendometrial lesions with blind curettage. Approximately 10–15% of women require another surgeryfollowing endometrial ablation. Women with uterine myoma oradenomyosis tend to be in the ablation-failure group. Here,either uterine artery embolization or hysterectomy can be offered.Because the underlying pathology is above the cervix, a laparoscopicsupracervical hysterectomy is a viable option. I hope that the papers contained in this issue will provokemore research on the subject and will assist readers in themanagement of women with abnormal uterine bleeding.     

Minimal uterine serous carcinoma: a clinicopathological study of 40 cases.

The term 'minimal uterine serous carcinoma' has been proposed to include serous carcinomas with invasion limited to the endometrium (superficial serous carcinoma), and those without stromal invasion (intraepithelial serous carcinoma or endometrial intraepithelial carcinoma). Both lesions display similar cytological and immunohistochemical profiles of a typical invasive serous carcinoma with a high nuclear grade and an overexpression of mutant p53 protein. We studied the clinicopathologic features of 40 cases of minimal uterine serous carcinoma. All patients were postmenopausal and underwent hysterectomy and surgical staging procedures. There were nine cases of intraepithelial serous carcinoma and 31 cases of superficial serous carcinoma. Five intraepithelial serous carcinomas and 16 superficial serous carcinomas exclusively involved an endometrial polyp. A total of 18 minimal uterine serous carcinomas also involved, in addition to a polyp, the endometrium proper in the form of intraepithelial serous carcinoma (13 cases) and superficial serous carcinoma (five cases). Overall, minimal uterine serous carcinomas were found to involve an endometrial polyp in 88% of the cases (35/40) and were confined to the polyp in 53% (21/40). Extrauterine tumors were present in 45% of the cases (18/40). In all, 22 patients with tumor limited to their uteri demonstrated an overall survival of 94% (2-73 months of follow-up). Eight of 18 patients with extrauterine tumors died of their malignancy (1.5-62 months of follow-up). In conclusion, a significant majority of minimal uterine serous carcinomas involve an endometrial polyp. Complete surgical staging is important to predict the prognosis. When the lesion is confined to an endometrial polyp and/or the endometrium proper, the clinical outcome is excellent.     

Endometrial and subendometrial blood flow measured by three-dimensional power Doppler ultrasound in patients with small intramural uterine fibroids during IVF treatment

BACKGROUND: The impact of intramural fibroids on the success of IVF treatment is controversial and the mechanisms leading to poor treatment outcomes remain unknown. We compared endometrial and subendometrial blood flow between women with and without intramural fibroids during IVF treatment. METHODS: Three-dimensional (3D) ultrasound examination with power Doppler was performed on the day of oocyte retrieval in 50 patients with intramural fibroids not distorting the uterine cavity and in 50 matched controls to measure endometrial thickness, uterine pulsatility index (PI)/resistance index (RI), endometrial volume and vascularization index (VI)/flow index (FI)/vascularization flow index (VFI) of endometrial and subendometrial regions. Smokers, patients with serum estradiol concentrations > or =20,000 pmol/l on the day of HCG and previous history of myomectomy were excluded. RESULTS: Endometrial thickness and pattern, averaged uterine PI and RI and endometrial and subendometrial VI/FI/VFI were similar between the fibroid group and the control group. There was no correlation between the total volume of fibroids and endometrial and subendometrial 3D power Doppler flow indices in the fibroid group. CONCLUSION: Endometrial and subendometrial 3D power Doppler flow indices were similar in patients with and without small intramural fibroids.     

Contribution of bone marrow-derived stem cells to endometrium and endometriosis

Bone marrow-derived cells (BMDCs) can differentiate into nonhematopoietic cells, suggesting that BMDCs may contribute to the maintenance of multiple tissues. Donor-derived bone marrow cells have been identified in human uterine endometrium. Here, two murine models were used to investigate the contribution of nonendometrial stem cells to endometrium. We investigate whether BMDCs can localize to uterine endometrium and to endometriosis. After bone marrow transplantation, male donor-derived bone marrow cells were found in the uterine endometrium of female mice. Although uncommon (<0.01%), these cells can differentiate into epithelial cells. After generation of experimental endometriosis by ectopic endometrial implantation in the peritoneal cavity, bone marrow from LacZ transgenic mice was used for transplantation. LacZ expressing cells were found in the wild-type ectopic endometrium implanted in the peritoneal cavity of hysterectomized LacZ transgenic mice. The repopulation of endometrium with bone marrow-derived stem cells may be important to normal endometrial physiology and also may help to explain the cellular basis for the high long-term failure of conservative alternatives to hysterectomy. The examination of a sexually dimorphic organ such as the uterus demonstrates the ability of male bone marrow, which cannot harbor circulating endometrial cells, to generate endometrium de novo and proves their mesenchymal stem cell origin. Finding Y chromosome bearing endometrial cells demonstrates the potential to recapitulate embryonic developmental pathways that were never activated in males; BMDCs may have vast regenerative capacity. Additionally, the ability of stem cells to engraft endometriosis has implications for the origin and progression of this disease. Ectopic differentiation of stem cells may be a novel mechanism of disease. Disclosure of potential conflicts of interest is found at the end of this article.     

Vaginal sildenafil (Viagra): a preliminary report of a novel method to improve uterine artery blood flow and endometrial development in patients undergoing IVF

Endometrial growth is thought to depend on uterine artery blood flow and the importance of endometrial development on in-vitro fertilization (IVF) outcome has been previously reported. Nitric oxide (NO) relaxes vascular smooth muscle through a cGMP-mediated pathway and NO synthase isoforms have been identified in the uterus. Sildenafil citrate (Viagra), a type 5-specific phosphodiesterase inhibitor, augments the vasodilatory effects of NO by preventing the degradation of cGMP. In this preliminary report we describe the use of vaginal sildenafil to improve uterine artery blood flow and sonographic endometrial appearance in four patients with prior failed assisted reproductive cycles due to poor endometrial response. The uterine artery pulsatility index (PI) was measured in a mock cycle after pituitary down-regulation with Lupron. The PI was decreased after 7 days of sildenafil (indicating increased blood flow) and returned to baseline following treatment with placebo. The combination of sildenafil and oestradiol valerate improved blood flow and endometrial thickness in all patients. These findings were reproduced in an ensuing gonadotrophin-stimulated cycle. Three of the four patients conceived. Although greater numbers of patients and randomized evaluation are needed to validate this treatment, vaginal sildenafil may be effective for improving uterine artery blood flow and endometrial development in IVF patients with prior poor endometrial response.     

Endometrial glandular dysplasia: a newly defined precursor lesion of uterine papillary serous carcinoma. Part I: morphologic features

Dysplastic epithelium frequently bridges the changes between normal epithelium and noninvasive carcinoma. However, such a dysplastic lesion has not been previously described in the development of uterine papillary serous carcinoma (UPSC) or between resting endometrium and serous endometrial intraepithelial carcinoma (EIC), which is composed of indisputably malignant noninvasive cancer cells. In this study, we hypothesize that there is a lesion bridging benign endometrium and serous EIC. Based on current understanding of carcinogenesis in general, the lesion should exhibit dysplastic features that are more atypical than "resting endometrium" but fall short of serous EIC. If the putative dysplastic endometrial lesion exists, it should be highly associated with UPSC rather than uterine endometrioid carcinoma (UEC). We examined the morphologic appearance of the endometrium from 32 uteri with UPSC, 16 with serous EIC, and 60 with UEC. The endometrial dysplastic lesions were identified and their pathologic features were characterized. Immunohistochemical staining with p53 and MIB-1 were performed in all sections containing endometrial dysplastic lesions, serous EICs, and benign areas. In addition, 25 postmenopausal endometrial biopsies including 6 benign resting endometria, 8 dysplastic lesions, and 11 serous EICs were also compared for the level of p53 overexpression and cellular proliferative activity. We found that endometrial dysplastic lesions do exist in the endometrial specimens we speculated and examined. We designate it as endometrial glandular dysplasia (EmGD). EmGD was present in 17 (53%) uteri with UPSC compared with 1 (1.7%) uterus removed for UEC (p = 0.001). EmGD was identified in 12 (75%) of 16 serous EIC uteri. Areas of both EmGD and serous EIC were found in 15 (47%) of the 32 UPSC uteri. Transitions from either EmGD to serous EIC or serous EIC to UPSC were present in 8 (25%) of the UPSC cases. No transitions from EmGD to UPSC were identified in any hysterectomy specimen. EmGD was frequently found in endometrial polyps. There was no statistically significant difference between EmGD in a polyp (48%) and EmGD in nonpolypoid endometrium (52%). The majority of EmGDs were multifocal and involved superficial endometrial glands. However, single glandular involvement and endometrial surface epithelial involvement were also seen. Immunohistochemically, EmGD lesions mostly showed intermediate scores/indices of p53 and MIB-1 in comparison with serous EIC and resting endometrium. EmGD is a morphologically distinct entity, which is commonly and specifically associated with uterine tumors with serous differentiation. EmGD may represent the earliest identifiable morphologic change in the development of UPSC. Characteristics of p53 and MIB-1 immunostains of EmGD may be of diagnostic usage in surgical pathology practice. Recognition of EmGD may provide an opportunity to improve the management of UPSC.     

Metastatic breast lobular carcinoma involving tamoxifen-associated endometrial polyps: report of two cases and review of tamoxifen-associated polypoid uterine lesions.

Two cases of lobular breast carcinoma metastatic to an endometrial polyp are described. Both patients had been treated with tamoxifen and presented with abnormal uterine bleeding. Histology of endometrial biopsy in both cases showed typical tamoxifen-associated endometrial polyps with focal subtle stromal infiltration by metastatic lobular breast carcinoma. This was confirmed by positive immunohistochemical staining with cytokeratin epithelial markers. Metastatic breast carcinoma may rarely involve tamoxifen-associated endometrial polyps. Because primary endometrial carcinomas may also arise within tamoxifen polyps, these should be extensively sampled. We briefly review polypoid uterine lesions that may occur secondary to tamoxifen therapy.     

The role of endometrial and subendometrial vascularity measured by three-dimensional power Doppler ultrasound in the prediction of pregnancy during frozen-thawed embryo transfer cycles

BACKGROUND: A good blood supply to the endometrium is usually considered as an essential requirement for implantation. OBJECTIVE: The aim of this study was to evaluate the role of endometrial and subendometrial vascularity in the prediction of pregnancy during frozen-thawed embryo transfer (FET) cycles. METHODS: Women undergoing FET in natural or clomiphene-induced cycles after the first stimulated IVF treatment were recruited. A three-dimensional (3D) ultrasound examination with power Doppler was performed 1 day after the LH surge to determine endometrial thickness, endometrial pattern, pulsatility index (PI) and resistance index (RI) of uterine vessels, endometrial volume, vascularization index, flow index and vascularization flow index of endometrial and subendometrial regions. RESULTS: Women in the pregnant group were significantly younger and used less gonadotrophins in their stimulated cycle. Endometrial thickness, endometrial volume, endometrial pattern, uterine PI, uterine RI, endometrial and subendometrial 3D power Doppler flow indices were similar between the nonpregnant and the pregnant groups. The age of women was the only predictive factor for pregnancy. Receiver operating characteristic curve analysis revealed that the area under the curve was around 0.5 for all ultrasound parameters for endometrial receptivity. CONCLUSION: Vascularity of endometrial and subendometrial layers measured by 3D power Doppler ultrasound is not a good predictor of pregnancy in FET cycles if measured at one time point only.     

Endometrial stromal polyps in rodents: biology, etiology, and relevance to disease in women

Endometrial stromal polyps (ESP) are a common spontaneous reproductive tract lesion in the female rat. However, there is limited information concerning the etiology, biology, and significance of these polyps as an end point in toxicology and carcinogenicity studies. This paper reviews relevant literature to address these aspects of ESP with respect to potential relevance to human uterine tumors. Endometrial stromal polyps in rodents appear as age-related lesions. There are only a few chemicals tested for carcinogenicity in rat and mouse cancer bioassays associated with increased incidence of ESP with no common characteristics or mechanism of action. Uterine endometrial polyps that occur in women and the uterine stromal polyps that occur in rodents have distinct characteristics, although both types of uterine lesions are common, benign, and noncancerous. Human endometrial polyps develop from both endometrial and stromal components, whereas rodent polyps develop from the stromal component of the uterus. Endometrial polyps in women are hormone sensitive, but there is no scientific or experimental evidence to date that suggests that uterine stromal polyps in rodents are hormone sensitive. Therefore, based on differences in their etiology and biology, endometrial stromal polyps observed in rodent toxicity and carcinogenicity studies appear to have limited relevance to human endometrial polyps occurring in women.     

Endometrial carcinoma recurring as carcinosarcoma: report of two cases

Endometrial carcinosarcoma is a rare, aggressive disease, accounting for approximately 3% of all uterine neoplasms. The emergence of sarcomatous elements is considered the evolution of subclones arising from high grade endometrial carcinomas. Here, we report two cases of primary endometrial carcinomas recurring as carcinosarcoma. Case 1. a 58-year-old postmenopausal woman diagnosed to have a poorly differentiated endometrial endometrioid adenocarcinoma (FIGO stage IB) developed an intra-abdominal recurrence of disease after 17 months from diagnosis. Histopathological analysis documented a biphasic neoplasia consisting of an epithelial (grade 3 endometrial endometrioid adenocarcinoma) and a sarcomatous component. Salvage chemotherapy with cisplatin, ifosfamide, epirubicin, and then with taxotere was attempted. The patient died after 2 months. Case 2. A 56-year-old woman with a diagnosis of grade 3 endometrial adenosquamous carcinoma of the endometrium (FIGO stage IIIA) experienced pelvic recurrence after five months from completion of chemotherapy. Definitive histology was malignant mixed mesodermal tumor with focal areas of chondrosarcomatous elements. The patient was triaged to exclusive concomitant chemoradiotherapy and salvage chemotherapy. The patient died after 3 months. We describe two cases of high grade endometrial carcinomas recurring as carcinosarcoma, thus providing evidence that the metaplastic sarcomatous evolution is a very rare event which can occur in patients with anaplastic endometrial cancer.