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Aims: Early invasive lobular breast carcinoma (ILC) is associated with few symptoms and signs. The individual sensitivity of clinical examination, mammography, ultrasonography, cytology and core biopsy have each been reported to be of limited value. The aim of this study was to evaluate the accuracy of triple assessment in the pre-operative detection of patients identified to have ILC from their surgical pathology. Methods: Pure ILC was defined as tumours containing at least 90% lobular features. The triple assessment of 273 patients diagnosed primarily at our institution were reviewed. Results: 87.5% of women were symptomatic and 12.5% were screen detected. The mean patient age was 59 (range 30–81) years and the median tumour size was 26 (range 5–110) mm. The main mammographic abnormalities were a spiculated lesion (33.3%), an ill-defined mass (33.3%) or architectural distortion (23.5%). The sensitivities for detecting ILC of each modality were: clinical examination (76.6%), mammography (79.8%), ultrasound examination (93.9%), fine-needle aspiration cytology (FNAC) (60.5%) and core biopsy (90.8%). Combining the three modalities of clinical examination, imaging and cyto/pathology increased the pre-operative detection rate of ILC. Conclusion: Triple assessment is useful in the diagnosis of ILC. As the features of ILC may be subtle, a high index of suspicion is required to facilitate early diagnosis.

The lymph node diagnostic clinic was set up at the Royal Marsden Hospital to provide a direct access service for general practitioners. In the first year 82 patients were seen. The malignancy pick-up rate was 19.5% which compares very favourably to rates in breast and colorectal clinics. Patient and general practitioner satisfaction with the service was high. Keywords: rapid diagnosis; lymphadenopathy

Squamous cell carcinoma of the breast: clinico-pathologic implications and outcome. Aims: Pure squamous cell carcinoma (SCC) of the breast is a rare tumour and little is known about long-term outcome. We report our experience of a consecutive series of patients. Methods: All patients with SCC treated at our institution between 1970 and 2001 were included. The pathological features, outcome and prognosis were studied. Results: Eleven patients were identified. The median age was 55 (38-90) years and median follow-up was 62 (3-332) months. Four tumours were T1, three were T2 and three were T3 (one tumour size was unknown). There were seven poorly differentiated and three moderately differentiated SCC. Tumour grade could not be assessed in one patient. Primary treatment was mastectomy in six patients, wide local excision in four patients and radiotherapy in one patient. There was lymph node (LN) involvement in two patients. Oestrogen receptor status was assessed in seven patients and only one tumour was positive. Adjuvant chemotherapy was given to three patients and five patients received adjuvant radiotherapy. Two patients developed local recurrence at 5 and 12 months and three patients developed distant metastasis at 2, 36 and 306 months. Three patients were treated with chemotherapy at recurrence. Three patients have died of the disease, two are alive with disease and six remain well. The 2-and 5-year overall survival was 80% (SE = 13%) and 67% (SE = 16%) respectively. Large tumour size and positive LN status were prognostic indicators of poor outcome. Conclusion: SCC of the breast adopts an aggressive course with outcome comparable to poorly differentiated breast adenocarcinoma. (C) 2003 Elsevier Science Ltd. All rights reserved.

Cellular characteristics of nipple aspiration fluid during the menstrual cycle in healthy premenopausal women Fifteen healthy premenopausal female volunteers underwent weekly nipple aspiration of ductal fluid from both breasts during two menstrual cycles to investigate the variability of the cellular profile of the ductal fluid. Ductal fluid was successfully obtained using breast massage and nipple-areolar suction from 247/280 (89%) breasts. 83% of samples available for cytological analysis were cellular and 30% of cellular aspirates contained ductal epithelial cells identified using standard morphological criteria. No significant variation in cell number or cell type was identified during the menstrual cycle. All samples tested had an 'H' score of zero for oestrogen receptor. Seven out of 14 women expressed the proliferation marker Mcm-2 in the cells of at least one of the specimens, with no evidence of a menstrual cycle influence on expression. In conclusion, the cellular profile of breast ductal fluid did not vary consistently during the menstrual cycle, permitting future breast cancer screening studies incorporating serial nipple aspirations to be performed independent of the phase of the cycle.

OBJECTIVE--To assess the individual and combined diagnostic accuracy of clinical examination, mammography, and fine needle aspiration biopsy in young women with breast cancer. DESIGN--Analysis based on case notes of patients presenting with breast cancer during 1971-89. SETTING--A combined breast clinic. PATIENTS--Consecutive series of 81 women aged less than 36 with histologically proved breast cancer presenting with a discrete mass over 19 years. MAIN OUTCOME MEASURES--Results of clinical examination, xeromammography or conventional mammography, fine needle aspiration biopsy, and examination of tissue removed by surgery. RESULTS--The clinical diagnosis was correct in 47 women and radiography in 35. Fine needle aspiration biopsy was correct in 47 of the 63 women in whom it was successfully performed. Fine needle aspiration was significantly more accurate than mammography (78% v 45%, p less than 0.01). Ten (16%) patients had negative results on clinical examination, mammography, and fine needle aspiration. CONCLUSION--Mammography alone seems inadequately sensitive to detect breast cancer in young patients. When all investigations give negative results excision biopsy is the only way of obtaining a definitive diagnosis.

Our aim was to determine whether biological molecular markers can predict response to neoadjuvant chemoendocrine therapy in patients with early breast cancer. Ninety patients (median age 56 years; range, 28-69 years) with primary operable breast carcinoma were studied. They were treated with four 3-weekly cycles of chemotherapy with mitozantrone, methotrexate (+/- mitomycin C), and tamoxifen prior to surgery. Fine-needle aspiration was used to obtain samples from patients prior to therapy, and the following parameters were assessed: estrogen receptor (ER), progesterone receptor (PgR), p53, Ki67, Bcl-2, and c-erbB-2 measured by immunocytochemistry, and ploidy and S-phase fraction (SPF) by flow cytometry. The tumors of 78% of the subjects responded (complete response, 9%; partial response, 69%) and 22% did not (no change, 20%; progressive disease, 2%). Response rates according to disease stage and patient age were as follows: T1, 74%; T2, 79%; T3/T4, 78%; age/=50 years, 76%;50, 79% (P = not significant). Response rates for other parameters were as follows: ER-positive, 82%, and -negative, 70%; PgR-positive, 86%, and -negative, 71%; p53-positive, 74%, and -negative, 81%; Bcl-2-positive, 85%, and -negative 61%; c-erbB-2-positive, 57%, and -negative, 93%; Ki67 high, 77%, and low, 81%; SPF high, 77%, and low, 77%; aneuploid, 71%; and diploid, 85%. Only the difference for c-erbB-2 was statistically significant (P = 0.007). A trend for higher response rates to neoadjuvant chemoendocrine therapy for tumors that were positive for ER, PgR, and Bcl-2 was observed but did not reach statistical significance. Tumors negative for c-erbB-2 had a higher response rate, which was statistically significant. In contrast, Ki67, ploidy, SPF, and p53 failed to predict for response.

The objective of this study was to look at the effect of tamoxifen on the endometrium by comparing gynaecological cervical and endometrial cytology in breast cancer patients on tamoxifen for 3 years compared with controls. In addition, pelvic ultrasonography was employed to detect ovarian abnormalities and to measure endometrial thickness. Patients followed-up after primary surgical therapy for breast cancer were invited for gynaecological assessment consisting of clinical examination pelvic ultrasonography and a cervical smear and endometrial sampling. The patients taking tamoxifen (n = 49) has been on adjuvant hormone therapy for a minimum of 3 years. Control patients (n = 45) were also being followed-up for breast cancer. On examination the tamoxifen patients had very similar clinical findings to the control patients with regard to the cervix (normal in 84% of tamoxifen takers compared to 87% of controls). The uterus was clinically enlarged in eight patients on tamoxifen and in none of the control patients (P = 0.006) and only one ovarian cyst was clinically detectable in a patient taking tamoxifen. Pelvic ultrasonography between the two groups of patients was not statistically different (chi 2 test) and ovarian cysts were noted in nine patients from each group (tamoxifen patients 18% vs control patients 20%, n.s.). There was a highly significant difference in endometrial thickness in premenopausal patients (9.2 mm) compared with postmenopausal patients (6.4 mm, P = 0.001). There was also a suggestion that endometrial thickness was greater in tamoxifen treated patients (P = 0.08). In general, a greater proportion of patients taking tamoxifen had cervical and endometrial cells exhibiting hyperplastic nuclei, and in endocervical smears, this difference achieved statistical significance (Mann-Whitney test, P = 0.046). These findings show that a significantly increased proportion of patients taking tamoxifen had endocervical nuclear hyperplasia, and a trend towards increased endometrial thickness. These findings confirm that tamoxifen has mild oestrogenic activity. However, the lack of any difference in the incidence of dysplasia suggests that the carcinogenic potential of tamoxifen on the uterus is very low and the beneficial effects of tamoxifen as an adjuvant therapy for breast cancer outweighs its theoretical risks.

Fifty-one patients with pure squamous cell carcinoma of the bladder were treated between 1958 and 1978. The overall 5-year survival rate was 16%. Ninety-two per cent of cancer deaths were caused by failure to control local disease; treatment by radiotherapy and elective cystectomy resulted in no long-term survivors. It is concluded that earlier diagnosis would reduce the number of cases presenting with advanced local disease and that future research should be directed towards adjuvant studies with chemotherapeutic agents known to have activity against bladder cancer.

Swabs of acetone-soluble cellulose acetate were used to obtain fragments of tissue in cases of urethral carcinoma. The histological appearances of tissue obtained in this way were comparable with those following biopsy and orthodox histology. The method is relatively automatic and appears to be valuable in the diagnosis of carcinoma of the urethra.

Summary 36 patients with flat carcinoma in situ of the bladder have been reviewed. Those with widespread disease usually presented with dysuria or obstructive outflow tract symptoms and radical surgery appeared to give better results than radiotherapy. However, when the lesion was confined to small areas of the bladder mucosa, haematuria or pain were the main presenting symptoms and a conservative approach seemed justified. It is suggested that the term flat carcinoma in situ be used for this lesion whose behaviour differs significantly from that of the commoner papillary or invasive tumours. The pathological appearances are to be reported elsewhere in full.

Summary 3 additional cases of “nephrogenic adenoma” of the bladder are added to the 20 previously reported cases. Light and electron microscopic studies of the first 2 cases support the hypothesis of urothelial metaplasia. The name “adenomatous metaplasia” should replace “nephrogenic adenoma”. Malignant change occurred in the third case, suggesting that this ought to be regarded as a potentially dangerous form of metaplasia. In the absence of malignant change, ileocaecocystoplasty with subtotal cystectomy afforded symptomatic cure in 2 cases: radical cystectomy was performed in the third because of malignant adenocarcinoma.

A technique is described for obtaining samples of bladder epithelium using soluble swabs. Changes indicating neoplasia were seen in a large proportion of patients with bladder carcinoma. These changes were absent in the non-neoplastic control cases. The method provided tissue similar to that obtained by biopsy and surgical removal. The cellular appearances resembled those seen in neoplastic cells exfoliated into urine.