Multifocal tumorigenesis in the upper female genital tract--implications for staging and management

A review of 128 cases of "primary" ovarian müllerian carcinoma treated at the King George V Memorial Hospital was undertaken to determine the relative frequency with which such tumors were associated with evidence of multifocal primary neoplasia. Of the 128 cases studied, 115 were invasive carcinomas and 13 were noninvasive or borderline ovarian tumors ("tumors of low malignant potential"). Eight of 10 borderline serous ovarian tumors (80%) and 37 of 75 invasive serous carcinomas (49%) exhibited evidence of independent primary neoplasia at more than one anatomical site in the biopsy material available for review. Many of these cases represented bilateral primary ovarian tumors, but autochthonous extraovarian neoplasia was also commonly encountered. A single borderline endometrioid ovarian tumor and six of 15 endometrioid carcinomas (40%) were associated with biopsy-proven multifocal primary tumorigenesis. These were predominantly neoplasms in one or both ovaries plus adenocarcinoma in the uterine corpus. Other histological types of malignant common epithelial tumors of the ovaries did not demonstrate any such tendency, highlighting major differences in pathogenesis between members of this loosely associated group of ovarian cancers. Our study suggests that gynecological endometrioid and serous malignancies are commonly multifocal and we feel this has significant implications for the way these neoplasms are staged and therefore treated.     

林奇综合征患者子宫内膜癌及卵巢癌的筛查与预防

患有林奇综合征(Lynch syndrome,LS)的妇女终生患子宫内膜癌和卵巢癌风险大幅增加.而子宫内膜癌或卵巢癌可以是LS患者的首发恶性肿瘤,也可以是第二原发恶性肿瘤.LS相关子宫内膜癌主要类型是子宫内膜样腺癌.近年来,有关LS相关子宫内膜癌及卵巢癌的筛查研究较少,主要是通过门诊子宫内膜活检、微卫星高不稳定性(mi...     

Alpha-fetoprotein-producing serous carcinoma of the uterus metastasizing to the ovaries, mimicking primary ovarian yolk sac tumor: a case report and review of the literature.

In the uterus, most alpha-fetoprotein (AFP) producing neoplasms belong to the categories of malignant mixed muellerian tumor, hepatoid carcinoma, and yolk sac tumor. We describe the case of a 44-year-old woman who presented with vaginal bleeding, pelvic mass, and preoperative elevated AFP serum level, clinically suggestive of a primary ovarian yolk sac tumor. However, histological examination revealed a uterine AFP-producing papillary serous carcinoma, which has metastasized to the ovaries. Upon review of the literature on primary endometrial neoplasms with AFP production, 2 categories with possibly different histogenesis and biological behavior become evident: the primary yolk sac tumor of the uterus in young patients (range, 24-49 years; mean, 34 years) and the common high grade endometrial carcinoma with yolk sac dedifferentiation or aberrant AFP production in elderly patients (range, 55-69 years; mean, 63.7 years). In addition to being only the second case of uterine AFP-producing papillary serous carcinoma, this case is unusual for its clinical and radiological presentation as well as the relatively young age of the patient.     

Clinicopathologic analysis of the prognostic factors in women with coexistence of endometrioid adenocarcinoma in the endometrium and ovary

AIM: To compare the survival and prognostic factors of patients with dual primary ovarian and endometrial cancers (primary group), and endometrial cancers metastatic to the ovaries (metastatic group). METHODS: Thirty-six patients with gross tumors confined to the pelvis and of endometrioid adenocarcinoma subtype in both the endometrium and ovary were selected from our file of 546 Japanese women with endometrial carcinoma. The patients were divided into two groups. Eleven were classified into the primary group. Twenty-five were classified into the metastatic group. Both univariate and multivariate regression analyses were carried out. RESULTS: The mean age of the primary group was significantly younger than that of the metastatic group (45.2 years vs 51.2 years; P < 0.01). The cumulative 10-year survival of the primary group was significantly better than that of the metastatic group (90.9%vs 46.6%; P < 0.05). Univariate analyses showed that older age (P < 0.05) and the presence of lymphovascular space invasion (LVSI; P < 0.004) of the tumor of the uterus were significantly associated with a poor prognosis in the metastatic group. Multivariate analysis including the above variables showed no independent prognostic factor (older age, P < 0.60 and LVSI, P < 0.06). CONCLUSION: When encountering women with coexisting endometrioid carcinoma in the endometrium and ovary with gross tumor limited to the pelvis, more attention should be paid to LVSI of the tumor of the uterus as a poor prognostic indicator.     

Endometrial adenocarcinoma: genetic analysis suggesting heritable site-specific uterine cancer.

Genetic factors are clearly integral to the etiology of neoplasia. A cancer family syndrome (Lynch syndrome II) consisting of uterine, colon, and ovarian cancer is recognized, but the heritability of isolated endometrial adenocarcinoma has not otherwise been thoroughly investigated. We have performed pedigree studies in index cases with endometrial adenocarcinoma, using spouses as controls. Preliminary results from 64 probands showed four families in which endometrial adenocarcinoma was diagnosed in at least one first-degree relative of the proband (mother, daughter, sister); none showed relatives with colon or ovarian cancer. In none of the 34 control pedigrees did either a mother or sister have endometrial adenocarcinoma. In four other families, multiple first- and second-degree relatives of probands had adenocarcinoma of the uterus, colon, or ovary, presumably representing a cancer family syndrome (Lynch syndrome II). Conclusion: Our preliminary data not only show familial and probably heritable tendencies for endometrial adenocarcinoma, but further suggest that there are at least two distinct forms: (1) the previously described Lynch syndrome II (cancer family syndrome), and (2) a heretofore unemphasized entity characterized by a tendency to endometrial adenocarcinoma alone.     

Myoma uterus as a marker of oncogynecological pathology in pre- and post-menopause

Development and (or) growth of myoma uteri in pre- and post-menopause is accompanied by hyperestrogenia which is shown by histological investigation of the endometrium and the ovaries. A comparative clinical and morphological study of 853 patients with myoma uteri, 996 patients with glandular, atypical hyperplasia and endometrial carcinoma was carried out. Benign tumors of the ovaries were revealed in 9.5% of patients with myoma, 12.7% of patients with atypical endometrial hyperplasia and 19.8% of patients with endometrial cancer. A significant increase of the occurrence of endometrial cancer in postmenopausal patients with myoma, in comparison with patients in the reproductive period was determined, 13.4% and 1.1% respectively, P = 0.01. In postmenopause "growth" of the tumor was more often and significantly simulated by malignant disease of the uterus and adnexa. In postmenopausal patients with myoma and uterine bleeding, endometrial carcinoma was 5.5 times more often revealed in comparison with the analogous group of patients in the reproductive period. The "relative risk" of the development of endometrial cancer, sarcoma uteri and ovarian tumors was calculated. The "relative risk" was shown to increase in the postmenopausal period. In the processes of observation of patients with myoma in postmenopause, cytological investigation of endometrial aspirates, ultrasound and mammographic screening should be carried out.     

Angiogenesis in malignancies of the female genital tract

OBJECTIVE: The purpose of this work was to review current knowledge pertaining to angiogenesis in malignancies of the female genital tract. METHODS: We identified studies published in the English language regarding angiogenesis in gynecologic malignancies. The studies were obtained from a MEDLINE search from 1966 through June 1998; additional sources were identified through cross-referencing. RESULTS: A growing body of evidence confirms the ability of vulvar and cervical squamous cell carcinomas and endometrial and ovarian adenocarcinoma to induce angiogenesis. In vulvar intraepithelial neoplasia a correlation between vascular endothelial growth factor (VEGF) expression, microvessel density (MVD), and progression of dysplasia has been demonstrated. In invasive vulvar carcinoma, high VEGF expression and MVD portend poor prognosis. Currently a debate exists regarding the ability of cervical squamous intraepithelial neoplasia to induce angiogenesis. Most studies, however, indicate angiogenesis to be of prognostic value in patients with invasive squamous cell carcinoma. The ability of complex endometrial hyperplasia to induce angiogenesis has been demonstrated. A direct correlation between angiogenesis, higher grade and depth of invasion in Stage I adenocarcinoma, and prognostic value in Stage I and II and recurrent disease has been noted. In ovarian epithelial adenocarcinoma, higher microvessel counts in the primary ovarian tumor or omental metastases may serve as a prognostic indicator for survival. CONCLUSIONS: Similar to other malignant diseases, angiogenesis appears to play an important role in disease progression and survival in patients with gynecologic malignancies. Preliminary data indicate angiogenesis may serve as a prognostic indicator in vulvar and cervical squamous cell carcinomas and endometrial and ovarian adenocarcinomas. These findings may lead to future application of therapeutic trials with antiangiogenic factors.     

Transvaginal color Doppler imaging for hemodynamic assessment of reproductive tract tumors.

Transvaginal color Doppler flow imaging was carried out on 68 Japanese women (normal, 10; uterine myoma, 21; cervical carcinoma, 7; endometrial carcinoma, 10; benign ovarian tumor, 12; ovarian carcinoma, 8). Blood flow velocity waveforms were evaluated by calculation of the resistance index (RI). In 6 patients with cervical carcinoma neovascularization was evident within the cervix. In all patients with endometrial carcinoma such signs were present adjacent to and/or within the endometrium. These findings were absent in normal women and in those with myomata. There was a significant difference between the RI (0.510 +/- 0.097) in patients with cervical carcinoma and in normal women (0.881 +/- 0.048) in the ascending branch. In endometrial carcinoma the RI (0.535 +/- 0.158) was significantly lower in the arcuate artery compared to the normal uterus (0.768 +/- 0.075) and patients with uterine myoma (0.679 +/- 0.131), respectively. There was no area of neovascularization in the normal ovaries. Neovascularization was confirmed in four patients with a benign ovarian tumor and in all patients with an ovarian carcinoma. A significantly lower RI was obtained in cases of ovarian carcinoma (0.503 +/- 0.122) than in patients with benign ovarian tumors (0.888 +/- 0.216). Transvaginal color Doppler imaging and pulsed Doppler analysis may be useful diagnostic tools to differentiate benign and malignant tumors.     

The analysis of the coexistence of endometrial carcinoma and uterine myoma

OBJECTIVE: An epidemiologic study of coexistence uterus myoma with endometrial cancer patients is presented. Coexistence of endometrial carcinoma with uterus myoma was evaluated and controlled for age, residence, civil status, education, parity, menarche age, last menstruation age, length of reproductive period, blood group, hypertension, diabetes, body mass index, sterility, histological subtype, grading, staging. DESIGN: From 1984-1998 136 endometrial carcinomas have been evaluated in the Department of Gynecology & Obstetrics in Hospital of S?upsk retrospectively. MATERIAL AND METHODS: Uterus myoma was coexistence with endometrial cancer in 22 cases (16.2%). Of 136 endometrial carcinomas 16 (11.6%) were multiple malignant neoplasms. Of these neoplasms 9 (6.6%) occur together with breast cancer, 3 (2.2%) with ovarian carcinoma, 1 (0.7%) with stomach carcinoma, 1 (0.7%) with rectum carcinoma, 1 (0.7%) with carcinoma in focus of endometriosis and 1 (0.7%) coexists with double neoplasms (bowel and endometriosis carcinoma) During the 14-year period of study 15 patients (11.0%) out of 136 patients diagnosed as having endometrial cancer had double and 1 (0.6%) had triple primary malignant neoplasms. There was not significant difference in age rate (p = 0.16), residence rate (p = 0.72), civil status rate (p = 0.37), education rate (p = 0.53), parity rate (p = 0.49), menarche age rate (p = 0.33), last menstruation age rate (p = 0.12), length of reproductive period rate (p = 0.66), blood group rate (p = 0.19), hypertension rate (p = 0.38), diabetes rate (p = 0.96), overweight status rate (p = 0.76), sterility rate (p = 0.35), histological subtype rate (p = 0.25), grading rate (p = 0.29), staging rate (p = 0.54), second primary malignant neoplasma (p = 0.77) between both patients group (with and without uterus myoma). CONCLUSION: Patients with endometrial cancer should be carefully and regularly followed up by monitoring et every anatomic site, especially the breast, stomach, and colon, in order that the development of a second primary carcinoma can be detected as early as possible, and not be overlooked in examinations. There is not additional risk factors for endometrial carcinoma between patients with and without coexistence uterus myoma. In the observation of patients with myoma in postmenopause, cytological investigation of endometrial aspirates, ultrasound and mammographic screening should be carried out.     

Clinico-pathological profile of endometrial carcinoma in young women (under 40 years of age)

Twenty primary endometrial carcinomas in 40 year-old or younger women were collected from a series of 845 carcinomas and newly re-evaluated. The typical histological profile was well-differentiated adenocarcinoma (30%) or adenoacanthoma (35%); however, a case of adenosquamous carcinoma and an exceptional malignant mixed mesodermal tumor were also observed. No tendency for myometrial infiltration (M0) was displayed by 11 (55%) of the cases, while 6 were M1 and 3 were M2 infiltrating neoplasias. Adenomatous hyperplasia was associated with cancer in 53% of the 15 assessable cases. Histopathological diagnostic problems were elicited in 5 cases only. Typical Stein-Leventhal syndrome occurred in 7 patients (35%), while polycystic ovaries were observed in 15 cases (75%). Usually, the patients were obese (40%) and nulligravida (65%). All but one case were stage I disease. Prognosis seems to be excellent following surgery.     

Benign, borderline, and malignant endometrioid neoplasia arising in endometriosis in association with tamoxifen therapy.

Tamoxifen therapy may result in a variety of endometrial proliferative lesions, including adenocarcinoma, and as recently suggested, proliferative changes within endometriosis. This report describes an endometrioid adenocarcinoma arising in ovarian endometriosis in a patient taking tamoxifen. There were also foci of benign and borderline endometrioid adenofibroma in the same ovary and a synchronous endometrioid endometrial adenocarcinoma in the uterus. The spectrum of benign, borderline, and malignant endometrioid neoplasia arising within endometriosis suggests that tamoxifen, as a result of its estrogenic effects, may cause proliferative and, in rare instances, malignant changes in endometriosis.     

Medroxyprogesterone acetate therapy for patients with adenocarcinoma of the endometrium who wish to preserve the uterus-usefulness and limitations

BACKGROUND: To determine the effectiveness of medroxyprogesterone acetate therapy for women with endometrial adenocarcinoma who wish to preserve their uterus. STUDY DESIGN: Fifteen patients with endometrial carcinoma (12 with grade 1 endometrioid adenocarcinoma. 2 with grade 2 adenocarcinoma and 1 with adenoacanthoma) were treated with high-dose medroxyprogesterone acetate alone as primary therapy and their clinical responses evaluated. RESULTS: Seven of the 12 cases (58%) with grade I adenocarcinoma and one of the two (50%) with grade 2 carcinoma responded initially to medroxyprogesterone acetate. The median length of treatment required for regression was 29 weeks. Three patients who initially responded relapsed. Thirteen patients are alive without evidence of disease as of December 1999 (10 to 146 months, median; 4 years and 11 months) and one is continuing medroxyprogesterone acetate therapy as a final follow-up. One patient was lost to follow-up. Two patients have conceived having three healthy infants. CONCLUSION: Treatment of endometrial carcinoma with high-dose medroxyprogesterone acetate could be an alternative to hysterectomy, although the successful rate is limited.     

Secondary tumors of the intestines in females: a retrospective clinicopathologic study of seven cases

OBJECTIVE: To investigate the primary site and the pathological features of secondary intestinal tumors in females, with emphasis on their differential diagnosis from primary neoplasms of the intestines. METHODS: Seven cases of secondary intestinal tumors in females were retrieved from the archival files of our laboratory. The relative clinical data were also reviewed. Inmmunohistochemistry was performed in cases with diagnostic difficulties. RESULTS: The primary site of the tumor was defined as follows: the ovary (ovarian adenocarcinoma) in five cases (71.4%), the skin (cutaneous malignant melanoma) in one case (14.28%) and the uterine corpus (mixed mullerian tumor) in one case (14.28%). In two cases the primary site was not determined initially, but the investigation showed that the primary tumor was ovarian in origin. In five cases the existence of a primary tumor was already known. Immunohistochemistry was applied in three cases for confirmation of the suspected primary tumor by histological examination. CONCLUSION: Histological diagnosis of secondary intestinal tumors may be extremely difficult, especially when the primary site is not previously known, and because of the tendency of certain secondary tumors to mimic, both grossly and microscopically, the primary ones. Immunohistochemistry is extremely helpful in resolving these diagnostic difficulties.     

Incidence of ovarian metastasis in patients with cancer of the uterine cervix

During the period from 1970 to 1985, 706 patients with cervical cancer of stage 0 and Ia were treated by a simple hysterectomy without oophorectomy. In 326 patients with invasive carcinoma in stage Ib to stage III, who were treated by a radical hysterectomy from 1977 to 1985, histological examinations were performed to detect ovarian metastasis. A total of 674 autopsy specimens were obtained from the Annual of the Pathological Autopsy Cases in Japan. (Japanese Pathological Society, 1965 to 1978). Follow-up observations on stage 0 and stage Ia revealed no recurrence in the ovaries. In invasive cases of epidermoid carcinoma (stage Ib to stage III), no ovarian metastases were detected, despite discovery of metastases to the pelvic lymph node in 21.6% of the cases. Conversely, in the cases of cervical adenocarcinoma (pure adenocarcinoma and mixed carcinoma), 6 of 48 cases (12.5%) showed ovarian metastases. Ovarian metastases were found in 22 of 77 (28.6%) autopsy cases of adenocarcinoma, but in only 104 of 597 (17.4%) cases of epidermoid carcinoma. This finding is statistically significant (P less than 0.02). Both corpus invasion and metastasis to the ovaries were found in 20 of 54 cases (37.0%). This rate was significantly higher than the rate of ovarian metastasis in cases without corpus invasion (P less than 0.001).     

Synchronous ovarian and endometrial carcinoma: a strong link to endometriosis?

PURPOSE: To further study the clinicopathological features of synchronous ovarian and endometrial carcinomas. METHODS: We retrospectively studied all cases of synchronous ovarian and endometrial carcinomas diagnosed in our laboratory over the last 15-year period. The pathological findings were correlated with the clinical records of the patients. RESULTS: Seven cases of synchronous primary ovarian and endometrial carcinomas were retrieved. The most common presenting symptom was abnormal vaginal bleeding (5 cases, 71.4%). Five patients (71.4%) were postmenopausal and two (28.6%) were nulliparous. All seven patients had Stage I ovarian and endometrial carcinomas of endometrioid histology. Moreover, in all seven ovarian carcinomas endometriosis foci were observed, while atypical endometriosis was found in four of them. With the exception of one patient, who received adjuvant postoperative radiation, all remaining patients were treated with surgery alone. All patients were alive and free of disease at completion of the study. CONCLUSION: The correct classification of synchronous primary ovarian and endometrial carcinomas is often problematic because of the frequent confusion with their metastatic counterparts. Although the exact etiology remains unclear, endometriosis seems to be a major risk factor for their development.     

Ovarian metastasis in women with clinical stage I endometrial carcinoma

BACKGROUND: The incidence of ovarian metastasis in women with clinical stage I endometrial carcinoma is generally reported to be 5%, leading to the practice of removing the ovaries at surgery even in young patients. METHODS: A retrospective study of 84 patients with clinical stage I endometrial cancer was carried out. Patients were excluded if the pathologic study revealed any evidence of extrauterine, apart from adnexal, spread or if the peritoneal cytology was positive. Patients with serous papillary or clear cell tumor histology were also excluded. RESULTS: Sixty-seven patients fulfilled the inclusion criteria. Only three (4%) patients were found to be in surgical stage IIIA, all three had grade 3 tumors. Of these patients, two had uterine serosal involvement and one had a microscopic tumor implant in a fallopian tube; none had ovarian metastasis. CONCLUSIONS: The risk of ovarian metastasis in women with well to moderately differentiated endometrial cancer, myometrial invasion limited to less than one half of the myometrium, negative peritoneal cytology and no evidence of metastatic lymph node spread is negligible. Young patients with a preoperative histological diagnosis of well to moderately differentiated endometrial carcinoma may be surgically staged, leaving the final decision regarding removal of the ovaries pending a thorough pathological review of the surgical specimens.     

Clinical and pathologic correlation of endometrial cavity fluid detected by ultrasound in the postmenopausal patient

A registry of ultrasound procedures spanning nearly 5 years was searched retrospectively to discover cases of endometrial cavity fluid collections in postmenopausal women. Twenty cases were identified; all medical records were available for review. One patient was lost to follow-up. Seventeen patients had surgical procedures: 11 had only a D&C, and six had a primary evaluation of laparotomy with removal of the uterus and adnexa. Five women had cancer (two ovarian, one tubal, one endometrial, and one cervical); eight women had benign gynecologic conditions, including uterine fibroids (five), ovarian serous cystadenoma (two), and cervical dysplasia (one). There were two cases of apparent subclinical pyometra. Five women had endometrial pathology consistent with prescribed hormone therapy for breast cancer (four) or endometrial hyperplasia (one).     

Sarcomas metastatic to the ovary: a report of 21 cases

Twenty-one cases in which sarcomas metastasized to the ovaries are reported. The patients ranged from 18 to 79 (average 42) years of age; only five of them were over 50 years old. Eleven tumors were primary in the uterus and 10 outside the genital tract. Three uterine tumors were leiomyosarcomas, and eight, endometrial stromal sarcomas. The extragenital primary tumors were leiomyosarcoma of the stomach (1) and small intestine (2), retrovesical leiomyosarcoma (1), fibrosarcoma of the anterior abdominal wall (1), sarcoma of the mesentery of smooth muscle or neural type (1), hemangiosarcoma probably primary in the heart (1), osteosarcoma of the maxilla (1), chondrosarcoma of the rib (1), and Ewing's sarcoma of the pubic bone (1). The ovarian tumors, most of which were large, were discovered at the same time as the primary tumors in 11 cases; in seven cases, the ovarian tumor was discovered 7 months to 9 years after diagnosis of the primary tumor. In three cases, the ovarian tumors were discovered 4, 7, and 10 months before detection of the primary neoplasm. Two of these tumors were endometrial stromal sarcomas, and one, an epithelioid leiomyosarcoma of the stomach. Eleven ovarian metastases were bilateral. On microscopic examination, the greatest difficulty in pathologic interpretation was posed by the metastatic endometrial stromal sarcomas because of their simulation of sex cord-stromal tumors. Features helpful in their distinction from these tumors included the frequent presence of extra-ovarian disease, bilaterality, and a characteristic content of small arteries resembling the spiral arteries of the late secretory endometrium. The other tumor that caused major diagnostic difficulty was the metastatic epithelioid leiomyosarcoma from the stomach, which had a pattern that initially suggested the solid-tubular pattern of a Sertoli cell tumor.     

Endometrial carcinoma and diabetes revisited

OBJECTIVE: To investigate whether endometrial adenocarcinomas are intrinsically different in diabetic as compared to non-diabetic patients. METHODS: A series of 208 patients with histologically confirmed endometrial adenocarcinomas were divided into groups of diabetic (n = 63) and non-diabetic (n = 145) patients. The two groups were compared in terms of tumor morphology, FIGO stage, clinical risk factors and 12-year survival. RESULTS: A history of a second neoplasia was significantly more frequent in diabetic than in non-diabetic patients (p = 0.001), but other endometrial cancer associated characteristics, such as tumor morphology, FIGO stage, obesity, hypertension, nulliparity, estrogen use and menopausal status did not differ between the groups. More importantly, the two groups had a similar 12-year survival rate (p = 0.8742). CONCLUSIONS: A second neoplasia occurred significantly more frequently in diabetic than in non-diabetic patients with endometrial carcinoma, but long-term survival and other clinical and histological features were the same in the two groups. These results indicate that endometrial adenocarcinoma is not intrinsically different in diabetic patients.     

Clinical evaluation of follow-up methods and results of atypical glandular cells of undetermined significance (AGUS) detected on cervicovaginal Pap smears.

OBJECTIVES: The aim of this study was to evaluate the efficacy of the follow-up methods and results of atypical glandular cells of undetermined significance (AGUS) detected on cervicovaginal Pap smears. METHODS: From May 1991 to December 1996, we have performed 407, 451 cervicovaginal Pap smears, of which 326 patients were identified as AGUS. Of the 326 patients, 268 patients were followed by repeat Pap smears, colposcopy, cone biopsy, or endometrial curettage. RESULTS: The incidence of AGUS on Pap smears is approximately 0.08%. The mean age of the patients was 43 years (range 22-79 years). The most common complaint was abnormal vaginal bleeding. The gross findings of the cervix were normal to mild erosion. The following past histories of patients could affect the AGUS results on Pap smear: 30 had cone biopsy, 21 had Pap smears on pregnancy and within 8 weeks after delivery or evacuation, 3 were on hormonal replacement therapy, 2 had intrauterine devices for contraception, and 5 were undergoing follow-up after treatment of cervical cancer. The benign lesions detected during follow-up periods were 6 microglandular hyperplasia of the cervix, 5 atypical squamous metaplasia of the cervix, 2 cervical endometriosis, 2 tubal metaplasia, 10 cervical myoma, 11 cervical polyps, 9 endometrial polyps, 3 uterine myoma, 1 pelvic endometriosis, 1 ovarian endometriosis, and 4 uterine adenomyosis. The premalignant or malignant lesions of the cervix were 4 low-grade squamous intraepithelial lesions, 24 high-grade squamous intraepithelial lesions, 8 glandular atypia/dysplasia, 5 adenocarcinoma in situ, 3 microinvasive adenocarcinoma, and 4 invasive adenocarcinoma. The neoplastic lesions of the uterus were 6 endometrial hyperplasia, 11 endometrial adenocarcinoma, 1 malignant mixed Müllerian tumor, and 1 metastatic endometrial adenocarcinoma. Sixty-seven (25%) of 268 patients followed up were identified as having clinically significant lesions of the cervix or uterus. The detection rates of abnormal lesions were 3.1% with repeated Pap smears (3/98), 28.4% with colposcopic-directed biopsy (31/109), 63.6% with cone biopsy (35/55), and 29.7% with endometrial curettage (19/64). CONCLUSION: AGUS on Pap smears showed various benign and malignant lesions of the cervix or uterus. The clinicians must communicate with the pathologists regarding the patient's clinical information as well as the origin of the atypical glandular cells in Pap smears. We recommend that patients with AGUS on Pap smear should undergo immediate intensive diagnostic studies, including colposcopic-directed biopsy with endocervical curettage or cone biopsy, to detect cervical lesions and endometrial curettage to detect endometrial lesions.