The significance of new densities and microcalcification in the second round of breast screening.

AIM: To assess the nature of new densities and microcalcifications in the second round of breast screening. MATERIALS AND METHODS: A total of 34 634 women were screened at our unit in the second round of the United Kingdom National Health Service Breast Screening Programme. Of those attending for the second time, 302 were recalled for further work-up of 311 new lesions. The lesions were divided into masses, microcalcifications, asymmetric densities and architectural distortions. Masses were classified according to margin and density, and microcalcifications according to morphology and distribution. RESULTS: Among women attending for the second time, the cancer detection rate was 0.45% (89 cancers). One hundred and eighty-eight new masses were identified: 53 well-defined (two malignant), 67 partially defined (six malignant), 54 ill-defined (18 malignant), and 14 spiculate (14 malignant). Well-defined masses were usually cysts, especially in women on hormone replacement therapy. Of 97 new microcalcifications, 71 were pleomorphic (28 malignant), 12 linear (one malignant), and 14 punctate (none malignant). Twenty-five new asymmetric densities were identified (five malignant). One of two architectural distortions was malignant. Malignancy was found in 21% of new masses, 30% of new microcalcification and 20% of asymmetric densities. CONCLUSION: Carcinoma was found in 24% of all new mammographic abnormalities appearing in a 3-year screening period. Spiculate and ill-defined masses, clustered pleomorphic microcalcification, and new asymmetric densities should be regarded with particular suspicion. The use of fine needle aspiration cytology in combination with imaging assessment may help to reduce the number of benign excisional biopsies for new mammographic lesions.

An audit of patient acceptance of one-stop diagnosis for symptomatic breast disease.

AIMS: The impetus for optimizing outpatient provision of breast-care services has come both from the patient and management in order to reduce anxiety and make full use of scarce resources. The one-stop diagnostic clinic for the investigation of symptomatic breast lesions is a relatively recent concept with well-known service benefits. However, acceptance to the patient has not been previously investigated. RESULTS: The results of this prospective audit demonstrate a high level of patient satisfaction with the multi-disciplinary, one-stop breast clinic.

The role of cytology in the diagnosis of periocular basal cell carcinomas.

The accurate diagnosis of eyelid tumors such as basal cell carcinoma (BCC) requires histological confirmation, usually obtained by biopsy. Cytology provides a rapid alternative that can yield a diagnosis during the initial outpatient appointment. The accuracy of this technique has been reported to be very good but its sensitivity in the diagnosis of periocular lesions is unknown. In order to assess the accuracy of cytology in eyelid lesions suspected clinically to be BCCs, the cytological and histopathological diagnoses were compared retrospectively in 20 lesions from 17 consecutive patients who underwent cytology followed by excision biopsy. The sensitivity of cytology for the diagnosis of BCC was 92% compared with 88% for the diagnosis of malignant tumor. The predictive accuracy was 75% for either diagnosis. This was compared with a second group of 26 clinical BCCs from 22 consecutive patients who had incisional biopsy and histological examination followed by excision with histological confirmation, in which case the sensitivity was 100% and accuracy 96%. It was concluded that cytology was sufficiently accurate to plan excision and reconstructive surgery, when a confirmatory tissue diagnosis can be made, but not sufficiently sensitive for conservative regimens such as radiotherapy because of the small risk of false negative diagnoses.

Clinical audit of a specialist symptomatic breast clinic.

The efficient delivery of health care requires vigilant quality assurance. We describe the audit of our symptomatic breast clinic, which includes the option of a one-stop diagnostic service. A total of 134 new and 386 follow-up patients attended over four consecutive clinics. The majority of new referrals (68%) were seen by a consultant surgeon. Urgent referrals were seen significantly sooner than routine referrals (P < 0.001, chi 2-test), and the mean wait from designated appointment to seeing the surgeon was 37.6 (range-68 to 171) min. One-stop investigations were offered to 50 patients; of these, 36 women (72%) had a total wait of less than 2 h. For those not investigated at the same clinic, the mean time until investigations was 6.1 (range 0-36) days and mean recall was 2.7 (range 1-8) weeks. Patients undergoing definitive surgery for cancer (n = 5) were operated on average 14.2 (range 7-27) days after the decision was made in outpatients, while the mean waiting time for non-cancer operations was 49.7 (range 15-98) days. Objective audit on outpatient services is possible and can lead to improvement of services.

One-stop diagnosis for symptomatic breast disease.

A consultant-led one-stop diagnostic service has been available at a busy symptomatic breast clinic each week at St Bartholomew's Hospital for 18 months. Women can be investigated appropriately using mammography, ultrasonography and cytology with immediate reporting. The aim is to achieve a diagnosis and management plan for each patient at the initial outpatient visit. A prospective audit of four consecutive clinics was undertaken to assess the impact of this service on clinical practice. Fifty patients out of 134 new and 386 follow-up clinic attenders had one-stop investigations. As a result of immediate reporting, 48 (96%) patients had a management decision made at the first outpatient visit, 9 (18%) were offered surgery, and 18 (36%) were discharged with a benign diagnosis and no dominant mass. Four symptomatic cancers were detected and evaluated on a one-stop basis, constituting 8% of the workload of this clinic. The mean wait from designated appointment until surgical consultation was 37.7 min (range -68-171 min) and that for investigation until subsequent clinical review was 56.9 min (range -4-191 min). Thirty-six (72%) one-stop patients had a total wait of less than 2 h and 95% were seen in under 3 h. It is felt that the one-stop clinic allows optimum patient management, minimises anxiety associated with symptomatic breast disease, and maximises utilisation of hospital outpatient resources.

Impression cytology of conjunctival melanosis and melanoma.

Impression cytology using cellulose acetate paper has been used in various ocular surface disorders as a simple non-invasive diagnostic test. To assess its value in differentiating melanocytic tumours, 24 patients with a range of pigmented lesions of the conjunctiva were examined using this technique. Cytological and histological diagnoses were compared in 23 cases. In 73% of cases impression cytology predicted the histological diagnosis by detection of superficial atypical melanocytes and their proportion relative to benign epithelial cells. This pilot study shows impression cytology to be a useful diagnostic aid in the differentiation of pigmented tumours of the bulbar conjunctiva.

An audit of surgical treatment of ovarian cancer in a metropolitan health region. Association of Obstetricians and Gynaecologists of the North East Thames Region.

The varied application of surgery to the initial treatment of 908 cases of primary ovarian cancer is analysed. In patients with advanced disease (FIGO Stages IIb, III and IV) 256 (46%) of 555 women achieved minimal residual disease status by primary surgery and this proportion fell to 24% when only stages III and IV were considered; of these cases 7% underwent adjunctive intestinal resection or urinary tract surgery. Although not in a clinical trial situation the women achieving minimal residual disease status before chemotherapy survived better in the short term, although long-term survival remained disappointing. In early disease 3% of young women have been subjected to hysterectomy and removal of both ovaries. By contrast, in 16% of women over the age of 40 years with early ovarian cancer bilateral oophorectomy was not carried out.

Oncogene expression in ovarian cancer: a pilot study of c-myc oncoprotein in serous papillary ovarian cancer.

The nuclear-associated protein product of the c-myc gene, p62c-myc, was assayed simultaneously with total DNA using flow cytometry in nuclei extracted from archival biopsies of serous papillary carcinoma of the ovary. The oncoprotein was probed with a synthetic peptide-induced mouse monoclonal antibody which was subsequently labeled with a fluorescent rabbit anti-mouse immunoglobulin and DNA was assayed using the nucleic acid fluorochrome propidium iodide. Serous papillary ovarian carcinoma expressed significantly higher p62c-myc levels compared with normal ovary (P less than 0.00003 Mann-Whitney U test). Biopsies classified as "borderline" low-potential malignancy exhibited levels between normal ovary and carcinoma. The difference between normal and "borderline" was significant at P less than 0.003, but no difference between "borderline" and frankly invasive biopsies was observed, P = 0.149. There was no difference among the histological grades of carcinomas. All normal ovaries had diploid DNA content as did 5/6 cases of "borderline" malignancy. The majority of cases of carcinoma, 28/36, were aneuploid. There was a statistically significant difference in the distribution of aneuploidy, P less than 0.005, between invasive carcinomas and those classified as "borderline" low-potential malignancy.

The value of fine needle aspiration cytology in the management of metastatic germ cell tumours.

Review of 19 patients with advanced metastatic malignant teratomas has revealed five serious complications possibly related to the surgical biopsy procedure, three of which led to the patient's death. Preliminary results from a small series of patients diagnosed by fine needle aspiration (FNA) cytology suggest that this procedure is a reliable alternative method for diagnosing these patients. In addition, when used after chemotherapy this procedure may save patients with residual malignancy from having to undergo post-treatment surgical staging. However, the absence of malignant cells in the aspirate cannot exclude malignancy because of the focal distribution of residual tumour in these masses.

Malignant change in benign cystic teratoma of the ovary.

In a clinico-pathological study of malignant disease of the ovary in the former North East Metropolitan Region, malignant transformation of benign cystic teratoma has emerged as the commonest malignancy of "germ cell" origin. The clinical and pathological details of 12 patients are reported.

Active specific immunotherapy for ovarian cancer.

Ten patients with advanced or recurrent ovarian cancer were treated with a combination of chemotherapy and active specific immunotherapy after tumour stasis had been induced. They were inoculated with irradiated allogeneic cryopreserved tumour cells and B.C.G. once monthly in addition to receiving conventional chemotherapy. The overall duration of "remission", median survival, and projected 24-month actuarial survival in the patients receiving immunotherapy were apparently better than in a retrospectively matched control group treated by chemotherapy alone.

Tumour associated immunity and immunocompetence in ovarian cancer.

Cell-free extracts of autologous ovarian cancer cells evoked a delayed hypersensitivity response (DHR) in skin in four out of six patients in remission from disease and none of seven patients in relapse. These initial results appear to be consistent with in vitro blastogenic assay using the same autologous extracts. To assess whether diminished tumour-associated immunity was due to impaired cell-mediated immunocompetence, blastogenic responses to purified protein derivative of tuberculin (PPD), a secondary recall antigen, and phytohaemagglutinin (PHA) were assessed. Impaired responses to PHA were seen in the relapse group of patients, but responses to PPD did not appear to be impaired in this group.

Tumour-associated immune responses and isolated carcinoembryonic antigen and alpha feto-protein levels related to survival in ovarian cancer patients.

The presence of a tumour-associated immune response in 37 patients with ovarian cancer as assessed by blastogenesis (lymphocyte transformation) evoked by ovarian cancer cell extracts, has been correlated with survival following the test. The difference in these responses is unlikely to be accounted for on the basis of general impairment of cell-mediated immuno-competence. Serum carcinoembryonic antigen (CEA) was also determined in 27 ovarian cancer patients to assess its prognostic significance. Raised CEA levels and absence of blastogenic response to tumour cell extract during relapse are associated with a worse prognosis but neither of these parameters are significant in remission. Possible applications of these findings to the clinical management of ovarian cancer patients are discussed. Serum alpha feto-protein levels measured by radioimmunoassay were not found to be raised in any of the 32 ovarian cancer patients in whom it was measured.

Tumour antigenicity in ovarian cancer.

The blastogenic response to a crude cell extract of ovarian cancer cells has been studied in 48 patients with ovarian cancer (9, autologous, 39 allogeneic), in 26 female controls matched for age and in 18 female patients with other types of cancer in remission from disease. The responses in ovarian cancer patients in remission and relapse were considered separately. The blastogenic responses to cell extracts of foetal ovary, foetal lung, foetal liver and normal adult ovary were also assessed in a proportion of all 3 groups. The blastogenic responses to ovarian cancer and foetal ovary cell extracts were found to be significantly greater in the ovarian cancer patients in remission than in the controls, but the responses to ovarian cancer extract were not greater in the relapse group or in patients with other cancers. As a blastogenic response to normal ovarian extract was also present in some of these patients, the data so far do not support the hypothesis of a tumour specific antigen. This tumour associated response may be occurring to determinants in foetal or adult ovarian tissue to which the patient becomes sensitized in malignant disease. The response is complex and the nature of the antigen requires further analysis.

Endometrioid tumours of the ovary.

From 291 cases of malignanat disease of the ovary in the North East Metropolitan Region of London, 250 have been classified as of epithelial origin. Of these, 44 have been designated as endometrioid carcinoma. The recognition and features of endometrioid ovarian carcinoma are discussed.