Pathological study of endometrial carcinogenesis in androgen-sterilized-rats

As reported previously, squamous metaplasias, endometrial hyperplasias and cancers of the uterus occurred more frequently in androgen-sterilized-rats (ASR) than in normal rats (NR). This time we pathologically examined the endometrium of ASP in detail and obtained the following results: 1) In NR, aged from 70 to 750 days, no abnormal findings were found. In 61 ASR, aged more than 500 days, were found 8 simple endometrial hyperplasias, 2 atypical endometrial hyperplasias, 15 simple squamous metaplasias, 1 atypical squamous metaplasia, 2 adenocarcinomas, 1 adenosquamous carcinoma and 1 squamous carcinoma. 2) In ASR, proliferative and metaplastic changes coexisted in the endometrium. Two adenocarcinomas were accompanied by metaplasias and atypical hyperplasias, and one squamous carcinoma was accompanied by simple hyperplasias. 3) The endometrial carcinogenesis of ASR was thought to be as follows. In ASR, the endometrial epithelium loses its secretory function, becoming low columnar epithelium. A part of the non-secretory endometrium gains proliferative activity and progresses to metaplastic epithelium or to glandular hyperplasia. The former may develop to atypical metaplasia and squamous carcinoma, the latter to atypical hyperplasia and adenocarcinoma.     

Case of atypical polypoid adenomyoma that possibly underwent a serial progression from endometrial hyperplasia to carcinoma

Atypical polypoid adenomyoma is a rare uterine tumor composed of atypical endometrial glands, which often exhibit squamous metaplasia, and a cellular smooth muscle stroma. Although atypical polypoid adenomyoma is categorized as a benign lesion, it is reportedly associated with endometrial cancer, and it shows persistence and recurrence even after conservative medical treatment. We present a rare case of atypical polypoid adenomyoma that possibly underwent a serial pathological change from endometrial hyperplasia to carcinoma in a 40-year-old woman with no history of pregnancy. She was diagnosed with atypical polypoid adenomyoma during polypectomy surgery. After resecting the atypical polypoid adenomyoma, endometrial hyperplasia complex was detected. This condition eventually progressed from atypical hyperplasia complex to endometrial adenocarcinoma, and total abdominal hysterectomy was performed. A patient with atypical polypoid adenomyoma who wishes to preserve her fertility should be carefully monitored for endometrial carcinoma. If endometrial hyperplasia is detected in such a patient, a meticulous follow-up examination by performing endometrial biopsy is mandatory.     

Endometrial metaplasia associated with endometrial carcinoma.

OBJECTIVE: To clarify the relationship of metaplasia to endometrial carcinoma. METHODS: Between 1984-1990, 73 cases of stage I-II endometrial carcinoma treated initially by hysterectomy were reviewed histologically. The metaplasias were classified as squamous, syncytial papillary, ciliated-cell, eosinophilic, mucinous, clear-cell, or hobnail. We assessed the histologic type and grade of the carcinoma, depth of myometrial invasion, presence or absence of lymph-vascular space invasion, and presence or absence of lymph node metastases. RESULTS: Forty of 73 patients (55%) had one or more areas of metaplasia in the endometrium adjacent to the carcinoma. Ciliated-cell metaplasia (28 of 73; 38%) was the most common type encountered. Women with both endometrial carcinoma and metaplasia were significantly younger than those with carcinoma without metaplasia (P < .05). Compared with carcinomas without metaplasia, those with metaplasia were well differentiated (P < .01) and lacked myometrial invasion (P < .01) and pelvic lymph node metastases (P < .05). The presence of metaplasia was also significantly correlated with the presence of endometrial hyperplasia (P < .01). CONCLUSION: In endometrial carcinomas, the presence of endometrial metaplasia suggests a favorable prognosis.     

Primary in situ squamous cell carcinoma of the endometrium,with extensive squamous metaplasia and dysplasia

BACKGROUND: Primary squamous cell carcinoma of the endometrium is exceedingly rare. It has been described in association with pyometra but its etiology is still unclear. CASE: The authors report the case of a 75-year-old woman who presented with pelvic pain and pyometra. No gross tumor was identified in the uterus; however, extensive epidermalization of the endometrial mucosa was noted. Microscopic findings were consistent with a primary in situ squamous carcinoma of the endometrium associated with extensive squamous metaplasia and areas of dysplasia. HPV antigen and DNA detection were negative in both the endometrial lesions and the cervix. CONCLUSIONS: These results support the sequence of change with squamous metaplasia, progressing through dysplasia to carcinoma as a possible pathogenetic process. HPV's role, however, remains uncertain.     

Endometrial metaplasia associated with endometrial adenocarcinoma

Endometrial metaplasia is a complex group of epithelial proliferations. The relationship of metaplasia, other than squamous metaplasia, to endometrial adenocarcinoma has not been clearly established. Between 1969 and 1979, 183 patients diagnosed as having Stage I endometrial adenocarcinoma (according to International Federation of Gynecology and Obstetrics) were treated at the University of Virginia Medical Center. Sixty of the patients were treated with hysterectomy without preoperative irradiation. A histopathologic review was performed without knowledge of the clinical outcome and subsequent clinicopathologic correlations were analyzed. On review, 32/60 had carcinoma without metaplasia and 15/60 had both carcinoma and metaplasia. Thirteen of the 60 patients were judged not to have cancer: 12 had both hyperplasia and metaplasia and one had hyperplasia without metaplasia. None of the 12 patients reclassified as having metaplasia had a recurrence or died of endometrial carcinoma. Patients with both metaplasia and carcinoma were significantly younger than patients with only carcinoma and the associated carcinomas were more frequently well differentiated.     

Persistence of endometrial activity after radiation therapy for cervical carcinoma

Radiation therapy is a proved treatment for cervical carcinoma; however, it destroys ovarian function and has been thought to ablate the endometrium. Estrogen replacement therapy is often prescribed for patients with cervical carcinoma after radiation therapy. A review of records of six teaching hospitals revealed 16 patients who had endometrial sampling for uterine bleeding after standard radiation therapy for cervical carcinoma. Fifteen patients underwent dilatation and curettage, and one patient underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy when a dilatation and curettage was unsuccessful. Six patients had fibrosis and inflammation of the endometrial cavity, seven had proliferative endometrium, one had cystic hyperplasia, one had atypical adenomatous hyperplasia, and one had adenocarcinoma. Although the number of patients who have an active endometrium after radiation therapy for cervical carcinoma is not known, this report demonstrates that proliferative endometrium may persist, and these patients may develop endometrial hyperplasia or adenocarcinoma. Studies have indicated that patients with normal endometrial glands have an increased risk of developing endometrial adenocarcinoma if they are treated with unopposed estrogen. Patients who have had radiation therapy for cervical carcinoma should be treated with estrogen and a progestational agent to avoid endometrial stimulation from unopposed estrogen therapy.     

Extensive squamous metaplasia (morulosis) of the endometrium as a clinical and pathological problem: a case report and literature study

Abstract

The article presents a case of a 28-year-old woman with so-called morulosis – a form of squamous metaplasia of the endometrium, which may mimic malignancy. The term ‘morulosis’ indicates extensive squamous mulberry-like metaplasia, which in a large part or nearly entirely affects endometrium, whereas in turn, benign squamous metaplasia or single morules, refers to a limited, usually small regional pathology of endometrium. Because the endometrial glands and stroma gradually undergo the process of squamous metaplasia, in a scanty biopsy material the picture may lead to overdiagnosis. In the epithelioid regions small inactive glands with an immunofenotype different from the remaining endometrium might be observed. So far 21 cases have been reported in English literature. The patients (age 19–45) had presented with abnormal bleeding, infertility or after hormonal therapy. The mechanism of the extensive squamous metaplasia of endometrium is still not clear. The prevailing view holds that morulosis appears to be a result of hormonal imbalance. To shed light on possible pathogenic background of morulosis, we present a case of particularly severe extensive squamous metaplasia of the endometrium (morulosis).     

Transitional cell carcinoma of the endometrium: a case report and review of the literature.

We report a case of primary transitional cell carcinoma of the endometrium and review the literature which reveals only 12 cases described to date. The patient presented with postmenopausal bleeding, and there were no distinctive clinical features. An endometrial sample taken at hysteroscopy was reported as a poorly differentiated, papillary, nonserous carcinoma with probable squamous metaplasia. The tumor removed at hysterectomy and bilateral salpingo-oophorectomy was almost all transitional cell with small areas of endometrioid, glandular differentiation. Immunohistochemistry demonstrated a similar immunoprofile to endometrioid carcinoma of the endometrium and different from reported cases of transitional cell carcinoma of the ovary and of the urinary tract.     

Atypical endometrial hyperplasia in an 18-year-old woman

The natural history and the factors that lead to the acquisition of atypia in endometrial hyperplasias in young aged women, especially under the age of 20, have not been fully elucidated. In such cases, although there exists a considerable risk of progression to carcinoma, a conservative antiestrogenic treatment is primarily indicated, in attempt to preserve the reproductive ability of the young woman. We report of a 18-year-old girl with atypical hyperplasia of the endometrium, a diagnosis confirmed by reviewing of the histologic material by specialized gynecopathologists. The patient has been treated with gonadotropin releasing hormone agonist (leuprolide acetate) and tibolone for 1 year, which led to endometrial atrophy and amenorrhea, without hypoestrogenic side effects. Six months after cessation of the therapy the endometrial hyperplasia relapsed (this time without atypia), but in about 2 years of follow-up and after short courses of treatment with clomiphene citrate and progestins the biopsy of the endometrium revealed a functional endometrium and the patient presents with an almost regular menstrual cycle.     

Treatment of atypical endometrial hyperplasia with an insulin-sensitizing agent.

Endometrial cancer and hyperplasia have long been associated with diabetes. Hyperinsulinemia may have a direct mitogenic effect on the endometrium and may inhibit the effect of progestogen therapy. This case report describes the treatment of a patient with atypical endometrial hyperplasia with an insulin-sensitizing agent. A 37-year-old patient presented after failed treatment of endometrial hyperplasia with progestogen therapy. One month after initiating metformin therapy the patient's endometrial biopsy demonstrated proliferative endometrium. This patient's atypical endometrial hyperplasia regressed after the initiation of treatment with an insulin-sensitizing agent. This relatively new class of drugs may provide an adjunct to the therapy of endometrial hyperplasia.     

Treatment of atypical endometrial hyperplasia with an insulin-sensitizing agent

Endometrial cancer and hyperplasia have long been associated with diabetes. Hyperinsulinemia may have a direct mitogenic effect on the endometrium and may inhibit the effect of progestogen therapy. This case report describes the treatment of a patient with atypical endometrial hyperplasia with an insulin-sensitizing agent. A 37-year-old patient presented after failed treatment of endometrial hyperplasia with progestogen therapy. One month after initiating metformin therapy the patient's endometrial biopsy demonstrated proliferative endometrium. This patient's atypical endometrial hyperplasia regressed after the initiation of treatment with an insulin-sensitizing agent. This relatively new class of drugs may provide an adjunct to the therapy of endometrial hyperplasia.     

The significance of intrauterine lesions detected by ultrasound in asymptomatic postmenopausal patients

A retrospective study on 82 women with an incidental sonographic finding suspected to be intrauterine polyps was undertaken to assess the histopathologic characteristics of such polyps utilising operative hysteroscopy. Endometrial polyps were found in 68 patients, submucousal myomas in 7, atrophic endometrium in 6 and thickened proliferative endometrium was found in 1 patient. Simple hyperplasia was found in one polyp but neither endometrial carcinoma nor complex hyperplasia was found. The total complication rate was 3.6%. It appears that the risk of endometrial carcinoma in postmenopausal women with asymptomatic endometrial polyps is low, although a larger series is required to confirm this finding.     

高脂饮食诱导胰岛素抵抗对于大鼠子宫内膜的影响

目的:建立胰岛素抵抗大鼠模型,比较胰岛素抵抗及雌激素水平增高对子宫内膜增殖的影响。方法:给予性成熟的Sprague Dawley大鼠高脂饮食以建立胰岛素抵抗大鼠模型,40周后对大鼠行去势手术后,灌胃给予大鼠17β-雌二醇4周。无胰岛素抵抗大鼠为对照组。通过测定葡萄糖耐量、胰岛素耐量、胰岛素抵抗指数、血脂等确定胰岛素抵抗。通过阴道脱落细胞巴氏染色判断雌激素的作用,HE染色检测实验组与对照组大鼠子宫内膜增殖的情况。结果:高脂饮食大鼠的葡萄糖耐量、胰岛素耐量试验曲线下面积及胰岛素抵抗指数均增加。给予雌激素后,阴道脱落细胞巴氏染色可见成熟阴道上皮细胞,HE染色可见子宫内膜厚度明显增加;与无胰岛素抵抗的大鼠相比,有胰岛素抵抗的大鼠子宫内膜出现鳞状细胞化生比例大,子宫间质中嗜酸性粒细胞增多。结论:胰岛素抵抗大鼠发生子宫内膜增殖时更易发生子宫内膜鳞状细胞化生,这一现象可能与体内高胰岛素水平有关。     

Verrucous carcinoma of the endometrium: case history, pathologic findings, brief review of literature and discussion

BACKGROUND: Verrucous carcinoma is a rare condition. A defined disease of the oral cavity, larynx, esophagus, skin, vulva, vagina and cervix. But a verrucous carcinoma arising from the endometrium without evidence of cervical malignancy or endometrial adenocarcinoma is extremely rare. CASE: A 67-year-old G2P2 menopausal patient that was referred for consultation 1 year after presenting with vaginal bleeding to her gynecologist who subsequently underwent several endometrial biopsies where the pathological findings were repetitively similar: papillary squamous proliferation, cytologically bland with low mitotic activity but extensive proliferation. A hysterectomy with bilateral salpingo-oophorectomy was performed. The final histologic examination revealed a squamous cell carcinoma of endometrium, verrucous and well differentiated, and there was no cervical invasion identified. CONCLUSION: This is a rare form of endometrial cancer with apparent favorable prognosis that must be considered when squamous cells are identified on endometrial samplings.     

Adenocarcinoma of the endometrium: Analysis of 256 cases with carcinoma limited to the uterine corpus: Pathology review and analysis of prognostic variables

Histologic specimens of all patients undergoing hysterectomy for clinical Stage I adenocarcinoma of the endometrium at Stanford University Hospital between 1959 and 1975 were reexamined. From this group 256 acceptable cases of adenocarcinoma confined to the uterine corpus (Pathologic Stage I) were identified. In patients treated with initial surgery, relapse rate was highly correlated with depth of myometrial invasion (P = 0.0001) and also with the histologic grade of the uterine adenocarcinoma (P = 0.008). Twenty-six patients (10%) had lesions with papillary architecture and anaplastic cytology similar to papillary serous carcinoma of the ovary. These women with uterine papillary serous carcinoma (UPSC) had a 50% relapse rate and accounted for one-half the treatment failures ( ) in the entire study group. Six of the seven upper abdominal relapses in this study were in patients with UPSC, suggesting that this histologic variant may behave more like ovarian serous carcinoma than the usual endometrial adenocarcinoma. Twenty-one patients (9%) had endometrial carcinomas with extensive mucinous differentiation (mucinous carcinoma), while 38% of all the cases of endometrial carcinoma showed at least some focal mucin production. Twenty percent showed focal squamous differentiation. Neither mucinous nor squamous differentiation, as we have applied these designations, were significantly correlated with relapse rate. Among the patients undergoing hysterectomy for clinical Stage I adenocarcinoma, 99 patients were found on review to have lesions which fell short of our current criteria for diagnosis of carcinoma in the uterine corpus and were reinterpreted as metaplasia and/or hyperplasia. None of these patients subsequently developed clinical relapse. The results of this study suggest a need for modification in the FIGO grading system for endometrial cancer and also support a definition of well-differentiated endometrial carcinoma more restrictive than that commonly employed.     

Endometrial foam cells. Non-estrogenic and estrogenic

Four patients with endometrial foam cells are described. In one the endometrium was obtained after parturition. It showed decidua and endometritis, whereas in the second patient, who had received birth control medication in the past, the endometrium was proliferative. In both cases there was a considerable amount of endometrial hemorrhage. The foam cells in these two patients had little granularity, and their cytoplasm contained hemosiderin. The other two patients received exogenous estrogen and presented with endometrial hyperplasia and adenocarcinoma. In these latter cases the foam cells were more granular, and contained no hemosiderin. Our findings confirm the presence of two types of histologically similar endometrial foam cell: a histiocytic, "non-estrogenic" reactive type capable of phagocytosis, and a stromal, "estrogenic" non-phagocytic type which is associated with hyperplasia or carcinoma and which may also be related to estrogen administration. Staining for hemosiderin may be particularly helpful in differentiating between the two types of foam cell. Such a differentiation is of practical importance because of the biologic significance attached to the "estrogenic" foam-cells which are usually indicative of endometrial hyperplasia or carcinoma.     

Endometrial carcinoma associated with pregnancy: A report of three cases and review of the literature.

Endometrial carcinoma associated with pregnancy is uncommon. In case 1, a 40-year-old gravida 2, para 2, was diagnosed with focal well-differentiated papillary adenocarcinoma 4 months postpartum. In case 2, a 35-year-old gravida 1, para 0, was diagnosed with a well-differentiated papillary adenocarcinoma of the endometrium after a D&C for an incomplete abortion at 7 weeks gestation. In case 3, a 32-year-old gravida 2, para 1, was diagnosed with a moderately differentiated adenocarcinoma with squamous metaplasia 4 months postpartum. All are without evidence of disease more than 2 years after therapy. A literature review shows 24 previous cases of pregnancy associated with endometrial cancer. These cases demonstrate the importance of endometrial sampling for abnormal postpartum bleeding despite the protective effects of pregnancy.     

1189例取环诊刮子宫内膜临床病理分析

本文回顾性总结分析了１１８９例取环诊刮子宫内膜病理情况，１１４０例因症取环，占９５．８８％，表现为不规则流血者６２８例，占５２．８２％，其次为经期延长和月经过多，病理改变以炎症出血为首位，共６５０例，占５４．６７％，其中伴鳞状上皮化生１５例，个别病例观察到内膜表面有炎性糜烂及溃疡形成，内膜发育异常２９７例，占２４．９８％，表现为子宫内膜增生过长９５例，分泌反应不同步２７例，不规则脱落及持续分泌２３     

p16、Cyclin D1在增生性子宫内膜及子宫内膜癌中的表达

目的 :探讨 p16和 Cyclin D1在内膜癌发生、发展中的作用。方法 :采用免疫组化 S—P法对 12例正常子宫内膜、2 2例增生性子宫内膜及 4 1例子宫内膜癌中 p16和 Cyclin D1表达进行了研究。结果 :在单纯加复合增生、不典型增生及子宫内膜癌中 ,p16表达呈下降趋势 ,内膜癌与正常内膜及增生性内膜有显著性差异 (P<0 .0 1,P <0 .0 5 ) ;而Cyclin D1表达呈上升趋势 ,增生性子宫内膜、子宫内膜癌与正常内膜有显著性差异 (P<0 .0 5 ,P<0 .0 1)。不典型增生与单纯加复合增生 Cyclin D1过表达有显著性差异 (P<0 .0 1)。子宫内膜癌中 ,p16表达随细胞分化程度下降而降低 ,而Cyclin D1则随分化程度下降而上升 ,二者呈负相关。结论 :p16、Cyclin D1异常参与子宫内膜癌的发生 ;p16低表达、Cyclin D1过表达与内膜癌的恶性生物学行为有关 ;Cyclin D1核过表达可能是一个早期分子事件     

Failure of megestrol acetate to reverse tamoxifen induced endometrial neoplasia: two case reports

Abstract. Rose PG, Brandewie EV, Abdul-Karim FW. Failure of megestrol acetate to reverse tamoxifen induced endometrial neoplasia: two case reports.
Tamoxifen's agonist effect on the endometrium has been associated with an increased incidence of endometrial carcinoma. It has been suggested that this agonist effect may be averted by the concomitant use of a progestational agent. We report two patients with breast cancer receiving tamoxifen who developed endometrial carcinoma and atypical endometrial hyperplasia, respectively. In one patient, this occurred despite the use of concomitant megestrol acetate. In the other patient, tamoxifen-associated endometrial hyperplasia persisted and progressed despite cessation of tamoxifen and initiation of megestrol acetate therapy. These cases may have implications for strategies to avert tamoxifen induced endometrial neoplasia.