Biopsy findings in five hundred thirty-one patients with atypical glandular cells of uncertain significance as defined by the Bethesda system.

OBJECTIVES: Histologic findings in biopsy specimens obtained from patients with atypical glandular cells of uncertain significance were studied to define the utility and limitations of this category. STUDY DESIGN: Computerized records over a 3-year period were retrospectively analyzed. The most significant histologic diagnosis from all biopsy specimens submitted was compared with the subcategory of the first Papanicolaou smear obtained showing atypical glandular cells of uncertain significance. RESULTS: Biopsy results were available for 531 of 1117 patients with atypical glandular cells of uncertain significance (48%). Biopsy-proved preinvasive (83%) or invasive (17%) lesions were present in 191 patients (36%). Eighty-nine percent of the preinvasive lesions were squamous, whereas 97% of the invasive lesions were glandular. Glandular lesions were more likely to be invasive, whereas squamous lesions were more likely to be preinvasive (p < 0.001). Twenty-eight patients had endometrial carcinoma, which represents 88% of all invasive carcinomas detected. CONCLUSIONS: Almost three fourths of patients with atypical glandular cells of uncertain significance and with lesions have squamous lesions, not glandular as suggested by the name of the category. Unlike patients with atypical squamous cells of uncertain significance, patients with atypical glandular cells of uncertain significance have a significant risk of malignant lesions, which are nearly all glandular and predominantly arise from the endometrium.

Papanicolaou smears by the Bethesda system in endometrial malignancy: utility and prognostic importance.

OBJECTIVE: To evaluate the prognostic significance of the Bethesda system's cytologic categories in patients with endometrial malignancy. METHODS: Patients with biopsy or hysterectomy-proven endometrial malignancy and a Papanicolaou smear result reported using the Bethesda system within 1 year of diagnosis were identified through retrospective review of our computerized database. RESULTS: After introduction of the Bethesda system in our laboratory on November 1, 1992, until January 1, 1997, 112 eligible patients were identified (108 with carcinomas and four with carcinosarcomas). Patients with cytologic diagnoses of malignancy (n = 17) were significantly more likely to have International Federation of Gynecology and Obstetrics (FIGO) grade 3 tumors and high-risk histology (serous, clear cell, and adenosquamous carcinoma and carcinosarcoma) than those with atypical glandular cells of uncertain significance (n = 33) or those with cytology not suspicious for malignancy (n = 63). Patients with malignant smears were also significantly more likely to have cervical extension, malignant peritoneal cytology, and FIGO stage II, III, or IV than those with atypical glandular cells of uncertain significance or those with cytology not suspicious for malignancy. CONCLUSION: Papanicolaou smears obtained within 1 year of histologic diagnosis of endometrial malignancy and interpreted using the Bethesda system were suspicious for (atypical glandular cells of uncertain significance) or diagnostic of malignancy in nearly half of all cases (29 and 15%, respectively). Patients having malignant glandular cells were more likely to have poor prognostic pathologic findings.

Incidence of atypical glandular cells of uncertain significance in cervical cytology following introduction of the Bethesda System.

OBJECTIVE: To establish the frequency of the atypical glandular cells of uncertain significance (AGCUS) category, and its subcategories, as defined by the Bethesda System (TBS). METHODS: Our computerized records of cervical/vaginal cytology specimens submitted from January 1, 1993, through December 31, 1995, were retrospectively reviewed for specimens diagnosed as AGCUS. When appropriate, our subcategory of "AGCUS favor premalignant/malignant lesion" was further qualified as "favor endocervical adenocarcinoma in situ" or "suspicious for endometrial carcinoma." The number of specimens and patients diagnosed for each subcategory were grouped by calendar year. Differences in frequency between time periods were tested for statistical significance using chi 2 analysis. RESULTS: AGCUS was diagnosed in 1181 of 177,715 submitted specimens (0.66%). The frequency of subcategories was as follows: "favor reactive" (65%), "unable to further classify" (30%), "favor premalignant/malignant" (2.9%), "suspicious for endometrial carcinoma" (1.9%), and "favor endocervical adenocarcinoma in situ" (0.4%). From 1993 to 1995 there was an increase in the rate of diagnosis of AGCUS (0.55 to 0.73%; P < 0.001) and a decrease in the percentage of specimens with AGCUS subclassified as "favor premalignant/malignant" (6.2 to 0.5%; P < 0.001). Other subcategories showed no significant change in frequency over this time period. The rate of biopsy-proven preinvasive or invasive lesions in AGCUS patients also showed no significant change from year to year over this time period. CONCLUSION: The AGCUS diagnosis can be anticipated at a low but consistent rate from a cytology laboratory using TBS. Any comparison of laboratories should take into consideration the change in reporting frequencies that occurs as part of the "learning curve" following introduction of TBS reporting. Uniform diagnostic criteria and additional reports with large numbers of cytologic specimens will be needed to establish the expected frequency of AGCUS and its subcategories.

Pelvic hematoma following angiography: another cause of elevated serum CA-125.

The presence of a pelvic mass in a patient with an elevated serum CA-125 suggests the possibility of a gynecologic malignancy. However, an increasing number of nonneoplastic causes of elevated serum CA-125 have been reported. This is the first report of a pelvic hematoma associated with elevated serum CA-125. Two weeks following cardiac catheterization at time of myocardial infarction a patient was noted to have a complex pelvic mass on ultrasound and serum CA-125 of 53 units per milliliter. Abdominal-pelvic CT-scan showed a small left pleural effusion, minimal ascites, left lower quadrant abdominal wall masses consistent with omental metastases, and a 9.4 x 10.3 x 9.0-cm complex left adnexal mass. At exploratory laparotomy a large organized hematoma in the left paravesical space was adherent to both the left external iliac artery and the left bladder wall. This mass could have been managed expectantly with percutaneous aspiration if a nonmalignant diagnosis had been more strongly considered.

Endolymphatic stromal myosis associated with tamoxifen use.

A case of low-grade endometrial stromal sarcoma (endolymphatic stromal myosis) occurring in a patient who had received tamoxifen citrate for 3 years following surgical treatment for breast cancer is presented. Endometrial adenocarcinomas have been the most frequently reported tumor associated with tamoxifen use. More recently, uterine sarcomas have also been described in association with the use of tamoxifen. This report adds only the second case of a low-grade endometrial stromal sarcoma associated with tamoxifen use. As in the first report, the tumor demonstrated a sex-cord-like pattern of differentiation, an uncommon feature of endometrial stromal sarcomas. This suggests a possible association between tamoxifen use and the subsequent development of low-grade endometrial stromal sarcoma.

Neoadjuvant chemotherapy before surgery in cervical cancer.

Eighteen phase II clinical trials have demonstrated the relative ease of administering intravenous neoadjuvant chemotherapy before radical surgery in patients with cervical cancer. Toxicity has been modest, with the exception of occasional severe bleomycin-induced pulmonary toxic effects. All regimens tested have been cisplatin based with no clearly superior combination. Overall objective response rates were 85% for patients with International Federation of Obstetrics and Gynecology stage IB or IIA disease, 88% for those with stage IIB disease, 74% for those with stage III disease, and 47% for those with stage IV disease. There was a corresponding decrease in clinical complete response rates with increasing stage from 28% for those with stage IB or IIA disease to 7% for those with stage IV disease. Operability was also stage dependent: 94% for patients with stage IB and IIA disease, 74% for patients with stage IIB disease, and 58% for patients with stage III or IV disease. All inoperable patients received primary radiation therapy. Fifty-five percent of operable patients received postoperative radiation therapy. Most phase II trials using historical controls demonstrated comparable survival. Only a few trials showed improved survival with the use of neoadjuvant chemotherapy before radical surgery. To date, there has been only one reported prospective trial of neoadjuvant chemotherapy before surgery. Patients with stage IB disease were randomly assigned to receive radical hysterectomy and pelvic lymphadenectomy with or without neoadjuvant chemotherapy. A survival advantage was present only in patients with a tumor volume of greater than 60 cm3. Randomized, prospective trials of neoadjuvant chemotherapy followed by radiation therapy have shown either no advantage or a statistically significant reduction in survival when neoadjuvant chemotherapy is administered before radiation therapy. In light of this finding and the operability of only 58% of the patients with stage III or IV disease, it would be prudent to limit neoadjuvant trials to patients with stage I or II disease with an initial tumor volume of greater than 60 cm3. Four such trials either are under way or are approved an awaiting activation.

Secretory endometrial adenocarcinoma in a patient on tamoxifen for breast cancer: a report of a case.

Well-differentiated endometrial adenocarcinoma of the secretory type (FIGO Grade 1) with minimal myometrial invasion occurred in a postmenopausal patient on tamoxifen therapy 5 years after mastectomy for breast carcinoma. We believe that this is the first report of secretory carcinoma of the endometrium associated with tamoxifen use. This unusual pattern of low-grade endometrial carcinoma adds to the spectrum of uterine neoplasia associated with tamoxifen therapy.

Neoadjuvant chemotherapy with vincristine and cisplatin followed by radical hysterectomy and pelvic lymphadenectomy for FIGO stage IB bulky cervical cancer: a Gynecologic Oncology Group pilot study.

Thirty-five patients with bulky (designated as > or = 4 cm size) International Federation of Gynaecology and Obstetrics (FIGO) Stage IB cervical cancer were treated with cisplatin, 50 mg/m2, and vincristine, 1 mg/m2, administered intravenously at 10-day intervals for a total of three courses before planned radical hysterectomy. One patient died of unrelated cause following one course of chemotherapy and was not evaluated for response. Of the 34 evaluable patients who completed chemotherapy, a complete clinical response was noted in two patients (6%) and a partial response in 26 patients (76%). Five patients (15%) had stable disease and one patient (3%) had disease progression. All chemotherapy was completed within 4 weeks (range 17-28 days). There was no grade 4 toxicity noted. Only one case each of reversible grade 3 granulocytopenia and stomatitis and two cases of reversible grade 3 peripheral neuropathy were noted. Of the 34 patients who received chemotherapy, the only patient with disease progression received standard pelvic radiation therapy in lieu of radical surgery. A second patient with stable disease had unresectable pelvic lymph node metastases and underwent confirmatory lymph node biopsy only and received standard radiation therapy postoperatively. The remaining 32 patients underwent radical hysterectomy and pelvic lymphadenectomy from 12 to 49 days following chemotherapy. Surgery was performed without significant difficulty. Eight of these patients (25%) had pelvic node metastases and received postoperative pelvic radiation therapy. Twenty-four months following initiation of treatment, 25 (74%) were alive and presumed free of disease, 4 had died of cancer (12%), 1 was alive with recurrence (3%), and 4 patients (12%) were lost to follow-up. A prospective randomized study is needed to assess the value of this approach compared with standard management.

Adverse effect of electrosurgical loop excision on assignment of FIGO stage in cervical cancer: report of two cases.

Electrosurgical loop conization of the cervix is a new procedure that is being rapidly accepted for treatment of cervical intraepithelial neoplasia (CIN). Concerns include fragmentation of the specimen that is frequently mandated by the size of the transformation zone and difficulty in using the largest electrosurgical loops. Two cases are presented that demonstrate the inability to accurately assign depth of invasion in cervical cancer when the focus of invasion is transfected. As a result, the patient and physician were forced to decide on whether a radical hysterectomy and pelvic lymphadenectomy were needed based on incomplete information. It is recommended that electrosurgical loop conization be confined to patients where invasive carcinoma is not expected. The use of this new technique for patients with suspected invasive carcinoma needs further evaluation.

Effect of radiotherapeutic technique on local control in primary vaginal carcinoma.

A retrospective analysis of 73 patients treated for primary vaginal carcinoma with radiation therapy was performed to evaluate the effect of radiotherapeutic technique on local control. Local control was achieved in five of 22 patients (23%) treated with pelvic external beam therapy alone, three of four patients (75%) treated with intracavitary cylinder or Bloedorn applicator alone, and 30 of 47 patients (64%) treated with combination of external beam and brachytherapy. Radiation therapy complications requiring hospitalization occurred in six patients (8%). A statistically significant difference in local control was achieved only when patients receiving external beam and brachytherapy were compared with patients receiving external beam therapy alone (P < 0.005). Total mid-tumor dose was defined as the sum of midplane tumor dose from external beam therapy, mid-tumor dose from interstitial radium needles, and the vaginal surface dose from intracavitary radium systems. Total mid-tumor doses ranged from 16 to 121.7 Gy. Only two of 16 patients receiving less than 55 Gy total mid-tumor dose achieved local control. As a result, dividing doses of 45, 55, 65 and 75 Gy produced a statistically significant superior local control rate in the patients receiving the higher dose (P < 0.01). None of the 16 patients receiving less than 55 Gy total mid-tumor dose had received brachytherapy. We conclude that the combination of external beam therapy and brachytherapy is essential to achieve optimal control of primary vaginal carcinoma.

A phase II trial of vincristine in advanced or recurrent endometrial carcinoma. A Gynecologic Oncology Group Study.

Thirty-three evaluable patients who had not received prior chemotherapy were entered on a study of vincristine therapy for advanced or recurrent endometrial carcinoma. Vincristine 1.4 mg/m2 was given weekly as an i.v. bolus for 4 weeks and then every other week. There was one complete response (CR) lasting 5 months. Five patients had partial responses (PR) lasting 3-18 months. The CR+PR rate was 18% (95% confidence interval for CR+PR was 7-36%). Thirteen patients (38%) had stable disease from 2-28 months, and 14 had progressive disease. The major toxicity was neurological, with 11 patients having grade 2 or 3 peripheral neuropathy. Vincristine at this dose and schedule has modest activity, but troublesome toxicity in advanced or recurrent endometrial carcinoma.

Echinomycin (NSC 526417) in recurrent and metastatic squamous cell carcinoma of the cervix. A phase II trial of the Gynecologic Oncology Group (GOG).

Nineteen evaluable patients with recurrent or metastatic squamous cell carcinoma of the uterine cervix were treated with 1,500 micrograms/m2 of echinomycin every 4 weeks. No patient had received prior chemotherapy. There was one partial response (5% response, 95% confidence interval for response of 0% to 26%). The major toxicity was nausea and vomiting which was moderate to severe in six patients. Myelosuppression was not observed. Echinomycin, in this dose and schedule displays no major activity in chemotherapy-naive patients with advanced squamous-cell carcinoma of the cervix.

Primary invasive vaginal carcinoma.

A review of primary vaginal carcinoma treated at the Medical University of South Carolina from January 1970 through December 1989 included 76 squamous carcinomas, 12 adenocarcinomas, and 3 undifferentiated carcinomas. Staging was done according to the system of the International Federal of Gynecology and Obstetrics as modified by Perez et al. Stages I, II, III, and IV included 25, 39, 15, and 12 patients, respectively. Corrected 5-year survival rates were 73% for stage I, 39% for stage II, 38% for stage III, and 25% for stage IV. Sixteen percent of patients had received prior pelvic radiation. Invasive cervical cancer preceded vaginal cancer in 21% of patients. Detection of cancer was accomplished by routine cytologic testing in 17% of patients, palpation of an asymptomatic mass in 10% of patients, or palpation of a symptomatic mass in 72% of patients. Eighty-seven percent of patients were treated with radiation therapy. Survival curves of patients grouped by stage and other potential prognostic factors were compared. Lower stage (p less than 0.01), younger age (p less than 0.02), and no symptoms at detection (p less than 0.01) were statistically significant favorable prognostic factors. Histologic type, extent of vaginal involvement, vaginal location, prior radiation therapy, prior cervical cancer, and prior hysterectomy are factors that did not significantly affect survival.

Superficially invasive carcinoma of the vagina following treatment for cervical cancer: a report of six cases.

Six patients with superficially invasive squamous carcinoma of the vagina are described. All patients meet recently proposed criteria for the diagnosis of microinvasive vaginal carcinoma. The depth of invasion measured from the surface was less than 2.5 mm. There was no lymph-vascular space involvement. The invasive foci arose within a field of carcinoma in situ. Five of these six patients had previously been treated for invasive cervical cancer with pelvic radiation from 82 to 246 months before the diagnosis of vaginal carcinoma. All but one patient had the carcinoma confined to the upper one-third of the vagina. All patients were treated with a single vaginal radium application following vaginectomy. One of these six patients expired from recurrent vaginal cancer 35 months following diagnosis. During the same 17-year period, 17 other cases of Stage I epidermoid cancer of the vagina were treated which did not meet the above criteria for microinvasion. There were no statistically significant differences between these two groups with regard to age at diagnosis, history of cervical cancer, hysterectomy, or pelvic radiation or in survival. Additional experience with early vaginal carcinoma is needed before microinvasive carcinoma of the vagina should be accepted as a distinct clinical entity.

Recent advances in endometrial cancer.

There are well-defined prognostic factors that identify patients with clinical stage I (confined to the uterus) endometrial adenocarcinoma and patients at high risk vs. low risk for recurrent disease and allow for treatment tailored to those specific prognostic indicators. This had led the International Federation of Gynecologists and Obstetricians (FIGO) in 1988 to revise the FIGO staging from a clinical to a surgical/histopathological evaluation. The use of these prognostic factors should lead to improved initial surgery and adjuvant therapy for patients considered at high risk for recurrence.

Eclampsia as a possible risk factor for persistent trophoblastic disease.

Twenty cases of hydatidiform mole complicated by eclampsia with adequate postevacuation follow-up are identified in a review of the literature since 1866. The clinical presentation of each of these patients is reviewed with particular attention to the existence of known risk factors for persistent trophoblastic disease. After excluding 3 women with coexisting fetus and 2 others who were treated initially with a total abdominal hysterectomy, it was discovered that 14 of the remaining 15 women developed persistent trophoblastic disease. This frequency of persistent trophoblastic disease is greater than can be explained based on previously described risk factors and suggests that the occurrence of eclampsia may be an independent risk factor for persistent trophoblastic disease.

Necrotizing fasciitis in a renal transplant patient.

We have described a 28-year-old diabetic woman who had necrotizing fasciitis of the perineum three years after receiving a living related renal transplant. The diagnosis of necrotizing fasciitis was made early and she was referred to a tertiary care center where she received radical perineal debridement and aggressive medical and surgical follow-up. Necrotizing fasciitis in a transplant patient is rare; review of the literature shows few cases and no survivors. Our patient has returned to a normal life despite continuation of all immunosuppressive therapy throughout the entire hospital course. In addition, she had a good cosmetic result despite the large necrotic perineal infection. Her survival can be attributed to early diagnosis and referral, immediate and extensive debridement, and aggressive protein replacement.

Association of eclampsia and hydatidiform mole: case report and review of the literature.

A patient with a hydatidiform mole complicated by eclampsia is presented. The findings from 57 other cases discovered in a review of the literature since 1866 are summarized to define the clinical characteristics of women experiencing eclampsia as a manifestation of their hydatidiform mole. Eclampsia complicating a molar pregnancy is generally preceded by typical preeclamptic symptomatology and uniformly by severely elevated blood pressure. Neurological or visual symptoms also commonly warn of impending eclampsia. Although the reported cases of eclampsia complicating molar pregnancies are rare, this risk argues for the liberal use of prophylactic antiseizure medication when caring for women with a hydatidiform mole and hypertension, neurological complaints, or other preeclamptic symptoms.

Second-look laparotomy in fallopian tube carcinoma.

From August 1974 through August 1980, eight patients with primary fallopian tube carcinoma underwent second-look laparotomies at The University of Texas M.D. Anderson Hospital and Tumor Institute. Prior to the second-look laparotomies all patients were clinically free of disease. Initial treatment consisted of surgery and chemotherapy for four of these patients, surgery and radiation therapy for two patients, and surgery, radiation therapy, and chemotherapy for two patients. The second-look laparotomies showed five patients were free of disease, one patient had microscopic residual disease, and two patients had persistent macroscopic disease. Recurrences following negative second-look laparotomies developed in two patients. One recurrence occurred at 41 months after the procedure and the other 69 months afterward. Both patients lived more than 5 years after the second-look laparotomies were performed. Three patients with negative findings at second-look procedures and the patient with microscopic residual disease remain clinically free of disease 34, 53, 74, and 50 months after the laparotomies, respectively. Following additional chemotherapy, the two patients who evidenced macroscopic disease at the second-look procedure died 16 and 32 months following the second-look laparotomies. The second-look findings can be used to predict disease behavior and may have a role in the management of patients with fallopian tube carcinoma.