Adnexal masses in pregnancy.

With the widespread use of routine abdominal ultrasound examination during pregnancy, adnexal masses are observed with increasing frequency. Most patients are clinically asymptomatic at the time of presentation, and most of the adnexal masses detected during early pregnancy disappear during the first 16 weeks of pregnancy. Ovarian tumors are estimated to occur in about 1 in 1,000 pregnancies and of these 3% are malignant. Here we present an overview about frequency, diagnostic procedures and pathological characteristics of these ovarian tumors. Moreover, current modalities for treatment during pregnancy are summarized. Surgical treatment of the adnexal masses has to be performed with adequate staging and debulking equal to the treatment of non-pregnant women. However, whereas during organogenesis abortion has to be considered prior to chemotherapy, later in pregnancy surgical debulking as complete as possible, followed by taxol-platinum chemotherapy is indicated. If the fetus is not viable at the time of primary surgery, neoadjuvant chemotherapy and complementation of surgery after delivery of the baby should be performed. It should be stressed that chemotherapy for ovarian cancer applied during pregnancy appears to be safe. However, no studies have evaluated the long-term consequences for children exposed to intra-uterine chemotherapy. Aspiration of cysts should be avoided, as the correlation between the histological evaluation of an ovarian malignancy and the cytological evaluation of aspirates is poor. Moreover, spillage of malignant cysts is hazardous for the patient.

Age-specific differences in treatment and survival of patients with cervical cancer in the southeast of The Netherlands, 1986-1996.

Age at diagnosis has been proven to be an important determinant of the choice of initial treatment for several sites of cancer. Elderly patients are more likely to receive no treatment or less intensive treatment modalities. This study analysed the influence of age on treatment choice and survival in patients diagnosed with cervical cancer. This population-based study used data on 1176 new cases of invasive cervical cancer diagnosed in the period of 1986-1996 from three regional cancer registries in the Netherlands. All available information on treatment and survival (on 1 January 1998) was recorded. Relative survival rates were calculated according to the Hakulinen method. Relative risks (RR) for excess mortality due to the diagnosis of cervical cancer were calculated with a regression model for relative survival rates. Only 5% of the patients aged 70 years and older (n=224) were diagnosed with stage IA disease, compared with 11 and 30% of the patients aged 50-69 years and 49 years and younger, respectively. Almost 50% of the 70+ patients with stage IB-IIA were treated with radiotherapy as a single treatment modality, whereas 64% of the patients aged < or =49 years were treated with surgery alone. In all age groups, treatment for advanced stage disease (stage > or =IIB) was radiotherapy alone. No treatment was given to 10% of the patients aged 70 years and older, 5% of those aged 50-69 years and 1% of those aged 49 years and younger. Five-year relative survival was 69% (95% Confidence Interval (CI): 66-72%) and differed significantly (P=0.001) with age (70+ years: 49%; 50-69 years 58%; < or =49 years: 81%). Multivariate analyses on a subset of patients showed that age was not an independent prognostic factor, whereas stage and treatment modality were very important prognostic factors. Although elderly cancer patients were sometimes treated differently from younger patients, this was in accordance with the guidelines. Relative survival rates differed significantly by age. The multivariate analyses on the subset of patients also revealed that excess mortality increased with age. However, when adjustment was made for stage and treatment, this difference disappeared. The influence of treatment on survival is likely to be due to the selection of patients based on other characteristics, such as tumour volume, comorbidity and performance status.

Chemotherapy resistant ovarian cancer in carriers of an hMSH2 mutation?

Hereditary Non-Polyposis Colorectal Cancer (HNPCC, Lynch syndrome) is an autosomal dominant condition of cancer susceptibility with high penetrance, characterised by early onset of colon tumours as well as a variety of extracolonic tumours including ovarian cancer and, in particular, cancer of the endometrium. Germline mutations in one of five DNA-mismatch repair (MMR) genes (hMLH1, hMSH2, hMSH6, PMS1, PMS2) are known to cause HNPCC. To date, mutations in two of these genes (hMSH2 and hMLH1) are found in the majority of mutation positive families. Recent literature suggests that especially hMSH2 mutations are associated with extracolonic tumours. We describe two women from an HNPCC family carrying an hMSH2 mutation (deletion of exon 6 of this gene) who developed ovarian cancer. In these patients (full cousins) the ovarian cancers were noted for their aggressive development and rapid recurrence after surgical debulking and during regular multichemotherapy including Cisplatin. This report strengthens recent in vitro studies suggesting an involvement of MMR-gene mutations in ovarian cancer cell biology with decreased susceptibility to Cisplatin therapy. The possible implications for the therapy of ovarian cancer, the screening and genetic counselling of family members are discussed.

Clinical value of DNA image cytometry in effusions with atypia.

Malignant cells in serosal effusions provide essential information about the extent of malignant disease. The main aim of this study was to examine the additional diagnostic value of DNA image cytometry for cases with uncertainty in the cytological diagnosis. In addition, the feasibility of automated nuclei detection was investigated. Out of 457 cases, 33 samples in 32 patients were diagnosed with "atypia" (probably benign) and 21 as "suspicious for malignancy." DNA image cytometry was performed on these 54 cases and on an additional group of 14 cytologically malignant cases. The results show that automatic classification is useful for separation of control cells, i.e., lymphocytes and neutrophilic granulocytes from other mononuclear cells. In 21 cases an insufficient number of control cells were measured. Seventy-two percent of the cytologic malignant cases were aneuploid. In contrast, in none of the cases with "atypia" and in only 2 of the cases "suspicious for malignancy" was aneuploidy present (2 of the remaining 32, 6%). From the cases with follow-up, a malignancy in the pleural fluid was present in 2 out of 17 cases with "atypia" and in 5 out of 10 with a "suspicious for malignancy" cytologic diagnosis, respectively. In conclusion, the additional diagnostic value of DNA image cytometry in cases with a cytological diagnosis of "atypia" or "suspicious for malignancy" is limited. Diagn. Cytopathol. 1999;21:112-116.

Laparoscopic ovarian transposition.

Preservation of ovarian function is both safe and feasible in many young women with pelvic malignancies. Techniques utilized to transpose the ovaries to date have uniformly required a laparotomy either at the time of surgical treatment or as a separate operation in patients about to undergo pelvic radiotherapy. We report our preliminary results in 3 patients who underwent laparoscopic ovarian transposition and pelvic lymphadenectomy as part of an experimental protocol using intracavitary radiation alone in patients with small node negative stage 1B cervical carcinoma desiring preservation of fertility. Dose calculations were performed to estimate the amount of radiation each transposed ovary received from the intracavitary radiation, as well as the dosage that would have been received had external pelvic (4500 cGy) with or without para-aortic nodal irradiation (4500 cGy) been required. The mean estimated distance each ovary was transposed was 14.4 cm for the right ovary and 14.3 cm for the left ovary. Operative times ranged from 2.75-4.0 hours, and the blood loss 100-300 mls. Post-operative hospital stays ranged from 1-2 days, and no complications were encountered. Two of the 3 patients are menstruating regularly 25-32 months after completion of treatment with serum FSH in the normal premenopausal range. Based on the above distances, the mean dose of radiation each transposed ovary received was estimated to be 126 cGy, whereas the range in dosage of radiation each ovary would have received had external pelvic +/- para-aortic nodal irradiation been required was 135-190 cGy, and 230-310 cGy respectively. One patient has become menopausal after her transposed ovaries slipped back into the pelvis. Laparoscopic ovarian transpositions can be performed. This procedure is technically easy to perform for those surgeons skilled in laparoscopic surgery and its preliminary morbidity appears to be low. More experience, longer followup, and refinement in the methods of ovarian transfixation are required.

Tumor angiogenesis: an independent prognostic parameter in cervical cancer.

OBJECTIVE: The purpose of this study was to investigate whether the intensity of tumor angiogenesis, expressed as microvessel density, is a parameter predicting the probability of lymph node metastasis and survival in patients with cervical cancer stages IB and IIA. STUDY DESIGN: In a retrospective study of 114 patients with cervical cancer stages IB and IIA, microvessel density, lymph node status, and several other prognostic parameters were correlated with disease-free survival by a multivariate analysis according to Cox proportional-hazards model. RESULTS: There was a significant difference in mean microvessel density between tumors with and without pelvic lymph node metastasis (p = 0.002). Both microvessel density (vessels per square millimeter of stroma). (p = 0.05) and pelvic lymph node metastasis (p = 0.007) correlated significantly and independently with disease-free survival. CONCLUSION: This study demonstrates that microvessel density is an independent prognostic parameter for disease-free survival in patients with cervical cancer stages Ib and IIa.

p53 tumor suppressor gene protein expression in cervical cancer: relationship to prognosis.

OBJECTIVE: Mutation of the p53 gene can be found in several human tumors. We tested the hypothesis whether overexpression of p53 protein is a parameter of more aggressive disease in patients with cervical cancer. STUDY DESIGN: In this study, we describe the effects of p53 overexpression in 156 patients with cervical cancer (Figo stage IB-IV) by assessing expression patterns of the p53 gene product using a monoclonal anti-p53 antibody (DO7). RESULTS: Overexpression of p53 tumor suppressor gene protein was observed in 30.2% of the tumors, low expression in 30.7% and 39.1% of the tumors showed no p53 immunoreactivity. With increase in stage, p53 overexpression raised from 20.1% in stage IB to 60% in stage IV. A significant correlation between p53 overexpression and disease-free survival of patients was observed, however, after stratification for stage, this effect disappeared. CONCLUSIONS: The p53 mutation expressed as p53 tumor suppressor gene protein overexpression is a late event in cervical cancer genesis and does not appear to be of prognostic significance in cervical cancer.

Basement membranes in cervical cancer: relationship to pelvic lymph node metastasis and prognosis.

In this retrospective study, the pattern of basement membrane expressed by type IV collagen immunostaining was evaluated in 156 patients with cervical cancer FIGO stage IB-IV. Staining patterns were assessed semiquantitatively and divided into three patterns, according to intensity and continuity of staining: thick basement membranes with minimal discontinuity (pattern I), thin basement membranes with moderate discontinuity (pattern II), and fragmentary or absent basement membranes (pattern III). Correlations between basement membrane pattern, FIGO stage, and pelvic lymph node status were tested using chi 2 statistics. Kaplan-Meier estimates of disease-free survival were calculated for groups of patients with basement membrane pattern I, II, or III and compared using the log-rank test. A fragmented or absent basement membrane, pattern III, was more frequently observed in advanced cervical cancer stage IIB/IV (P = 0.02). In patients with early cervical cancer stage Ib/IIA this pattern was associated with the presence of pelvic lymph node metastasis (P < 0.0001) and significantly associated with a decreased survival rate (P = 0.05). In advanced-stage disease no prognostic value was observed. These data indicate that in patients with early-stage cervical cancer the basement membrane pattern, expressed as the type IV collagen staining pattern, may be a useful marker in predicting lymph node metastasis and survival.

Composition of cervical smears in patients with and without a cervical ectropion.

AIMS: To test the hypothesis that absence of squamous cells in cervical smears obtained by an endocervical sampling technique is more prominent in patients with a cervical ectropion. METHODS: Prospective study exploring the relation between the composition of cervical smears obtained using an endocervical cotton swab in patients with (n = 188) and without (n = 341) a cervical ectropion. Subjects were 529 consecutive patients from whom a cervical smear was prepared at a university gynaecological clinic. RESULTS: In 7% of the endocervical samples no squamous cells were found. There was no correlation, however, between the presence or the size of an ectropion and the absence of squamous cells in those samples. CONCLUSIONS: It was confirmed that endocervical sampling alone is insufficient to obtain good quality cervical smears. The presence of an ectropion proved to be an unreliable predictor of the absence of squamous cells.

Five different histological subtypes of germ cell malignancies in an XY female.

A case of a 19-year-old female with 46 XY gonadal dysgenesis and five different histological subtypes of germ cell malignancies is described. Both adnexa were removed, preserving the uterus. Pathology revealed gonadoblastoma with dysgerminoma differentiation present in both gonads and in the left gonad mature teratoma, embryonal carcinoma, and endodermal sinus tumor were identified as well. She received no adjuvant treatment and has remained well 30 months after diagnosis.

Early stage cervical cancer: aborted versus completed radical hysterectomy.

In a retrospective study, the treatment results of patients with stage IB and IIA cervical cancer were evaluated. In 26 patients radical hysterectomy was discontinued after intra-operative finding of positive lymph nodes. These patients received radiotherapy. In 57 patients lymph nodes were negative, and radical hysterectomy was completed. Of these, 13 patients received adjuvant radiotherapy because of positive surgical margins or parametrial involvement, and 44 patients received no adjuvant therapy. Five-year survival was 61% in patients with positive pelvic lymph nodes and 88% in patients with negative pelvic lymph nodes, comparable with the results mentioned in the literature. The complication rate did not differ from similar other reports. This management shows treatment results comparable with other reports with minimal morbidity.

Assessment of the risk on endometrial cancer in hyperplasia, by means of morphological and morphometrical features.

The value of two "cancer risk" assessment rules (one consisting of qualitative microscopical features and one consisting of morphometric characteristics) has been evaluated in 39 patients with hyperplasia of the endometrium. Of these, in seven (7139 = 18%) cancer was detected in the follow-up and 32 remained stable or became less abnormal. The results of the qualitative analysis were well in agreement with those published earlier. In none of the eight patients with simple hyperplasia cancer was detected, in contrast to five of the 11 patients (45%) with cytologic atypia and glandular complexity. Twenty patients showed cytologic atypicality in the absence of glandular complexity, or no atypicality but glandular complexity; in two (10%) of these patients cancer was detected later in the follow-up. The morphometric rule (consisting of volume percentage of stroma, log-normally transformed standard deviation of the shortest nuclear axis and outer surface density of the glands) results in a multivariate score. Nineteen patients had a score value above 0.6 and in none of them cancer was found. In contrast, in seven of the 20 patients (35%) with a score value below 0.6, cancer was detected. Regarding the question which of the techniques is more powerful, the specificity is better with the qualitative evaluations; the sensitivity is higher with the morphometric rule. An advantage of the morphometric rule is that only two groups (very low/very high risk) are discerned.

Prognostic value of quantitative pathologic features and DNA content in individual patients with stage I endometrial adenocarcinoma.

The prognostic value of clinical features, qualitative and quantitative pathologic characteristics and steroid receptor incidence was evaluated in 50 patients with Stage I endometrial adenocarcinoma. It turned out that many of these features were prognostically important. Estrogen receptor content was not significantly associated with prognosis in our material, but patients with progesterone receptor positive lesions had a better survival than those in which the tumors were progesterone receptor negative. Multivariate analysis also clarified that only three features in combination had independent significance: mean shortest nuclear axis, DNA index, and depth of myometrial invasion (in sequence of decreasing importance). The prognostic rule consisting of these features overshadowed the value of all other features investigated. The overriding prognostic value of this highly reproducible rule was clear from the complete separation of 27 survivors and six nonsurvivors in the learning set of 33 patients. In an independent test set, all three nonsurvivors and 13 of the 14 survivors were correctly classified, thus confirming the accuracy and reliability of the developed rule to predict the outcome of future patients with Stage I endometrial adenocarcinoma.