Visual inspection of the uterine cervix after the application of acetic acid in the detection of cervical carcinoma and its precursors

BACKGROUND: Organized cervical cytology screening programs are not feasible in many developing countries where cervical carcinoma is an important cause of mortality among adult women. This study compared visual inspection of the cervix after application of 3-4% acetic acid (VIA, or cervicoscopy) with cytology as methods for the detection of cervical carcinoma and its precursors. METHODS: Three thousand women were examined by both VIA and cytology. Those positive on one or both of the screening tests (n = 423) or those who had clinically suspicious lesions even if the tests were negative (n = 215) were invited for colposcopy. Directed biopsies were obtained from 277 of 573 women at colposcopy. Those with moderate dysplasia or worse lesions diagnosed by histology were considered true-positives. Those with no lesions or with reactive or reparative changes at colposcopy and those for whom histology revealed no pathology, reactive or reparative changes, atypia, or mild dysplasia were considered false-positives. The detection rate of true-positive cases and the approximate specificity of the two tests were compared. RESULTS: VIA was positive in 298 women (9.8%), and cytology was positive (for atypia or worse lesions) in 307 women (10.2%). Of the 51 true-positive cases (20 cases of moderate dysplasia, 7 of severe dysplasia, 12 of carcinoma in situ, and 12 of invasive carcinoma), VIA detected 46 (90.1%) and cytology 44 (86.2%), yielding a sensitivity ratio of 1.05. VIA detected five lesions missed by cytology, and cytology detected three missed by VIA; both missed two lesions. The approximate specificities were 92.2% for VIA and 91.3% for cytology. The positive predictive value of VIA was 17.0%, and that of cytology was 17.2%. CONCLUSIONS: These results indicate that VIA and cytology had very similar performance in detecting moderate dysplasia or more severe lesions in this study. VIA merits further evaluation as a primary screening test in low-resource settings.     

Breast cancer screening: first round in the population-based program in Valencia, Spain. Collaborative Group of Readers of the Breast Cancer Screening Program of the Valencia Community

PURPOSE: To analyze the results of round 1 of the population-based Valencia Breast Cancer Screening Program. MATERIALS AND METHODS: In this program, 78,224 (72.98%) of the 107,178 women invited (aged 45-65 years) underwent screening. Complementary views were obtained in 5,771 women (7.38%). Among the total population studied, 3,502 (4.48%) underwent short-term mammographic follow-up studies; 3,898 (4.98%) underwent additional studies and treatment at hospitals. Five hundred eighty-seven women (0.75%) underwent biopsy. RESULTS: Cancer was detected in 334 patients (4.27 cancers per 1,000 women [3.24 per 1,000 women aged 45-49 years, 6.30 per 1,000 women aged 60-65 years]; six patients with lobular carcinoma in situ excluded). The estimated sensitivity was 89%; specificity, 99%. The positive predictive value of mammography was 8.56%; of mammography with additional examinations, 26.82%; and of biopsy, 56.89%. Forty-one patients (12.28%) had ductal carcinoma in situ; 284 (85.03%) had infiltrating carcinoma. In 73 (25.70%) of the 284 patients, infiltrating carcinomas were smaller than 1 cm. Two hundred twenty-five patients (76.27%) had no lymph node involvement. One hundred seventy-nine (61.09%) had stage 0 or 1 cancer. CONCLUSION: Results are consistent with other published results; differences are due to methods and patient population characteristics.     

Tailored written invitations for second round breast cancer screening: a randomised controlled trial

OBJECTIVES: Firstly, to determine if attendance for second round mammography screening in those sent a tailored letter (that is, making reference to their screening history) is increased compared with those sent a standard letter; secondly, to investigate the acceptability of tailored letters. SETTING: North West Glasgow Breast Screening Centre. METHODS: A randomised controlled trial. RESULTS: Overall attendance was unrelated to whether the women were sent a tailored or standard letter; 60% of those sent the standard letter attended (922/1531) compared with 62% of those sent the tailored letter (956/1552) (chi 2 = 0.61, P = 0.4) (difference 2%; 95% confidence interval -2% to 5%). There were no significant differences in percentage attendance within each of the study subgroups: women who attended previously and received an all clear result, women who attended previously and received a false positive result, women who were invited previously and failed to attend, and women who were previously too young to be invited for screening. However, there was a statistically significant difference in percentage attendance between these four groups, independent of letter type (chi 2 = 510, P < 0.00001). Although women found the letters acceptable and understandable, they did not seem to pay close attention to the content. CONCLUSIONS: Tailoring invitation letters does not have a significant effect on uptake rates for breast screening and does not justify the additional workload required.     

CD1d-mediated recognition of an alpha-galactosylceramide by natural killer T cells is highly conserved through mammalian evolution

BACKGROUND: Although increasing rates of breast carcinoma incidence have been observed in Asian countries, appropriate strategies for detecting early stage breast carcinoma in such communities have been difficult to formulate, particularly because no large population screening trial specifically involving Asian women has been reported. The objective of this study was to evaluate the effectiveness and quality of mammography as a screening technique for Singaporean women, who are predominantly Chinese. METHODS: In this prospective study, 166,600 women in Singapore ages 50-64 years were randomized to either 2-view mammography without physical examination (67,656) or observation (97,294, controls) over 2 years. RESULTS: Of these women, 28,231 (41.7%) responded and were screened; they were more likely to be married, have more formal education, be working, be Chinese, and be in a higher socioeconomic group (P < 0.001 for all variables). To assess for response bias that could affect outcome, results were also evaluated for nonrespondents (n = 39,425). The incidence rate of cancers among nonrespondents (1 per 1000 woman-years) was less than the 1.3 in women not invited to have screening (P = 0.03, relative risk [RR], 1.3; 95% confidence interval [CI], 1.0-1.7). However, cancers arising from nonrespondents did not differ significantly in stage distribution when compared with cancers within the control group. For every 1000 women screened, 4.8 cancers were detected. The prevalence ratio (the number of cancers detected per 1000 women at first screening divided by the corresponding incidence rate in controls per year) was 3.6 for screened women and 2.4 for women invited to have screening. The majority of cancers detected through screening were early stage, with 64% as either ductal carcinoma in situ (26%) or Stage I disease (38%) and was significantly more than the corresponding 26% in women not invited to have screening (P < 0.001). When only invasive cancers were considered, screened women still had more early cancers, with 65% having no lymph node involvement, compared with 47% in the group not invited to have screening (P = 0.001; RR, 1.4; 95% CI, 1.2-1.7). Women who were screened had half the risk of having Stage II or later cancers (P < 0.0001; RR, 0.5; 95% CI, 0.4-0.7) when compared with women not invited to have screening. This higher detection rate of early cancers through screening was accomplished with acceptable recall rates of 8% for further mammographic films or physical examination and a biopsy rate of 1.0% (10 per 1000 women screened). The interval cancer rate was 2.1 per 10,000 women screened in the first year of follow-up. CONCLUSIONS: These positive results of intermediate measures suggest that, in Asian communities, screening mammography could be an important modality for detecting early stage breast carcinoma. However, the low compliance rates suggest that health education efforts must focus on issues related to acceptability if such programs are to succeed.     

Breast cancer in patients treated for Hodgkin's disease: clinical and pathological analysis of 76 cases in 63 patients

In a retrospective multicentric analysis, 63 women treated between 1941 to 1988 for Hodgkin's disease (HD) subsequently developed 76 breast cancers (BC). The median age at diagnosis of HD was 26 years (range 7-67), and 22 women (35%) were 20 years old or less. Exclusive radiotherapy (RT) was used in 36 women (57%) and combined modalities with chemotherapy (CT) in 25 (39%). Breast cancer occurred after a median interval of 16 years (range 2-40) and the median age at diagnosis of the first BC was 42 years (range 25-73). TNM classification (UICC, 1978) showed 10 T0 (non-palpable lesions) (13%), 20 T1 (26%), 22 T2 (29%), 8 T3 (11%), 7 T4 (9%) and 9 Tx (12%), giving altogether a total of 76 tumours, including, respectively, 5 and 8 bilateral synchronous and metachronous lesions. Among the 68 tumours initially discovered, 53 ductal infiltrating, one lobular infiltrating and two medullary carcinomas were found. Moreover, two fibrosarcomas and 10 ductal carcinoma in situ (DCIS) were also found. Among 50 axillary dissections for invasive carcinomas, histological involvement was found in 31 cases (62%). 45 tumours were treated by mastectomy, without (n = 35) or with (n = 10) RT. 27 tumours had lumpectomy, without (n = 7) or with RT (n = 20). 2 others received RT only, and one only CT. 7 patients (11%) developed isolated local recurrence. 20 patients (32%) developed metastases and all died; 38 are in complete remission, whereas 5 died of intercurrent disease. The 5-year disease-specific survival rate by the Kaplan-Meier method was 61%. The 5-year disease-specific survival rate for pN0, pN1-3 and pN > or = 3 groups were 91%, 66% and 0%, respectively (P < 0.0001) and 100%, 88%, 64% and 23% for the T0, T1, T2 and T3T4 groups, respectively. These secondary BCs seem to be of two types: a large number of aggressive tumours with a very unfavourable prognosis (especially in the case of pN > 3 and/or T3T4); and many tumours with a 'slow development' such as DCIS and microinvasive lesions, especially in patients treated exclusively by RT. Moreover, a very unusual rate of bilateral tumours (21%) was observed. These secondary BC could be 'in field', in 'border of field' or 'out of field'. However, a complete analysis of doses delivered by supradiaphragmatic irradiation was often very difficult, due to large variations in several parameters. We conclude that young women and girls treated for HD should be carefully monitored by clinical examination, mammography and ultrasonography.     

Results in irradiation of the in situ carcinomas of the vocal cords

From 1952 through 1973, 79 patients with the diagnosis of in situ carcinoma and seven with the diagnosis of leukoplakia and/or atypical hyperplasia were treated with irradiation. The staging system was the same as for the invasive squamous carcinomas. The irradiation techniques were also identical to those used for invasive squamous cell carcinomas. The failure rate for the T1 lesions was 11% and 26% for the T2 lesions--in the same range as the failure rates observed for the invasive squamous carcinomas. Only two of the 12 failures were on the initially involved cord. These two facts suggest that most of the failures were not recurrences but were new disease developing on the dysplastic epithelium. There was a delay in the appearance of failure for the in situ carcinomas as compared with that for the invasive squamous cell carcinomas of the supraglottic larynx. Seventy-six percent of the patients have a normal voice.     

What attendance rate can be achieved for Pap smear screening? A case-control study of the characteristics of non-attenders and results of reminder efforts

OBJECTIVE: To understand participation failures in a national Pap smear screening programme by studying characteristics of non-attenders and results of further reminder efforts. DESIGN: A case-control and an intervention study. SETTING: The community health centre in the town of Hafnarfj?rdur, Iceland. SUBJECTS: The target population comprised 2510 women aged 35-69, who were invited regularly every second year for cervical cancer screening. MAIN RESULTS: 2241 (89.3%) had attended screening during the preceding five years, 102 (4.1%) had never attended, and 167 (6.7%) had attended previously but not during the preceding five years. Women with a mental disorder and those who had never married were more likely not to attend. The most usual explanations given by non-attenders were that they did not like to participate, or they felt they did not need to, some of them because their uterus had been removed. Of the non-attenders 29 (10.8%) came for a Pap smear after repeated reminding efforts. CONCLUSIONS: Total participation rate in cervical cancer screening programmes in Iceland is high. When efforts are taken to lower the non-attendance rate it has to be kept in mind that many women are unwilling or unable to participate in such preventive measures.     

Radiosurgical correlations of 61 breast microcalcification foci

OBJECTIVE. Diagnostic value of breast clustered microcalcifications discovered by mammography. DESIGN. A retrospective study. SETTING. Oncology Center of Rennes. SUBJECTS. 58 women (study group) with breast clustered microcalcifications without palpable tumour were operated. SURGERY. Prior to surgical removal of microcalcification, needle localization was performed. Histological results. We observed, 36 benign lesions (59%), 25 carcinomas (45%), 10 of them in situ and 15 infiltrative. RESULTS. Different radiological parameters were studied in relation to histological results, the vermicular morphology of microcalcification, an increased number, their triangular aspect, provide clue to the presence of breast carcinoma. The cluster of stippled calcification is not, in our series suggestive of a carcinoma, but also requires histopathological study, owig to the fact that in such cases, we have as many carcinomas as benign lesions. FINDING. Careful analysis of microcalcifications, within the clinical context, ensures a safe attitude, and enables one to operate only carcinomas.     

Screening women aged less than 50 years with a family history of breast cancer

Family history is an important breast cancer risk factor and is a common reason for referral to specialist breast clinics for consideration of breast screening. The aims of this study were to determine cancer detection rates and prognostic features of breast cancers identified in women aged less than 50 years at increased risk of breast cancer who attend a Family History Breast Screening Clinic (FHC). Between January 1988 and December 1995, 1371 asymptomatic women aged less than 50 years underwent annual clinical breast examination and biennial mammography due to a family history of breast cancer. A total of 29 cancers (23 invasive and 6 in situ) were detected or presented as interval cancer during a mean follow-up of 22 months (range 0-96 months). This gave a relative risk for invasive breast cancer in this high-risk group of 5 when compared with an age-matched female population in the U.K. The cancer screening detection rates were similar to those of women aged 50 years or over undergoing population screening in the NHS Breast Screening Programme (NHSBSP)--FHC prevalent screen 8 per 1000 screening visits versus NHSBSP 6.5 per 1000, FHC incident screen 3.3 per 1000 screening visits versus NHSBSP 3.8 per 1000. A higher proportion of in situ cancers were detected in the FHC screened group compared with cancers identified in symptomatic patients from an age-matched risk group (21% versus 4%). No differences were demonstrated for invasive tumour size, grade or lymph node stage between symptomatic and screened women. The early results of this study suggests that young women at risk of breast cancer due to a family history may benefit from regular breast screening due to the early detection of in situ lesions.     

Desmoplastic response in biopsy specimens of early colorectal carcinoma is predictive of deep submucosal invasion

PURPOSE: The aim of this study was to evaluate the role of histopathology of biopsy specimens in predicting depth of infiltration in early colorectal carcinomas before treatment. METHODS: Early colorectal carcinomas that had been resected surgically or endoscopically between 1984 and 1995 were analyzed. Histopathologic findings, including differentiation of adenocarcinoma and a desmoplastic response were investigated. RESULTS: One hundred nine early colorectal carcinomas consisted of 73 lesions of carcinoma in situ, 13 submucosal carcinomas with minimum invasion, 8 lesions with moderate invasion, and 15 lesions with deep invasion. Of 73 carcinoma in situ lesions, 72 (approximately 99 percent) showed well-differentiated adenocarcinomas and no desmoplastic response. Twelve (92 percent) of 13 submucosal carcinomas with minimum invasion also revealed well-differentiated adenocarcinoma without a desmoplastic response. Sixty-three percent (5/8) of lesions with moderate invasion revealed well-differentiated adenocarcinoma. None of the lesions had a desmoplastic response. Among lesions with deep invasion, 73 percent (11/15) demonstrated moderately differentiated adenocarcinoma, and 11 lesions had a prominent desmoplastic response (73 percent; P < 0.01). CONCLUSIONS: These results suggest that if histopathologic findings of biopsy specimens taken from them before treatment demonstrated adenocarcinoma associated with a desmoplastic response, the lesions had at least deep invasion carcinomas. These lesions should be resected surgically. Submucosal carcinomas with minimum invasion, which have no desmoplastic response, could be treated endoscopically.     

Clonal karyotypic abnormalities of the hereditary multiple exostoses chromosomal loci 8q24.1 (EXT1) and 11p11-12 (EXT2) in patients with sporadic and hereditary osteochondromas

BACKGROUND: Osteochondroma most frequently arises sporadically and as a solitary lesion, but also may arise as multiple lesions characterizing the autosomal dominant disorder hereditary multiple exostoses (HME) and the contiguous gene syndromes Langer-Giedion and DEFECT-11 syndromes. HME is genetically heterogeneous with association of three loci including 8q24.1 (EXT1), 11p11-12 (EXT2), and 19p (EXT3). Constitutional chromosomal microdeletions of 8q24.1 and 11p11-12 are features of the Langer-Giedion and DEFECT-11 syndromes, respectively. Cytogenetic studies of osteochondroma are rare. METHODS: Cytogenetic analysis was performed on 34 osteochondroma specimens from 22 patients with sporadic lesions and 4 patients with HME utilizing standard methodologies. Fluorescence in situ hybridization with chromosome specific probes was performed on three cases to define structural rearrangements further. RESULTS: Clonal abnormalities were detected in ten cases. Notably, deletion of 11p11-13 was observed in one case (a sporadic tumor) and loss or rearrangement of 8q22-24.1 in eight cases (seven sporadic and one hereditary tumor). CONCLUSIONS: These findings: 1) confirm previous observations of 8q24.1 karyotypic anomalies in sporadic osteochondroma, 2) reveal the presence of somatic chromosomal anomalies in hereditary osteochondromata, 3) suggest that similar to hereditary lesions, sporadic osteochondromas also are genetically heterogeneic (involvement of both 8q24.1 and 11p11-12), and 4) support the hypothesis that loss or mutation of EXT1 and EXT2, two putative tumor suppressor genes, may be important in the pathogenesis of sporadic as well as hereditary osteochondromata.     

The Advanced Breast Biopsy Instrumentation (ABBI), a system for stereotactic excision of mammographically suspect nonpalpable findings in the breast

Advanced Breast Biopsy Instrumentation (ABBI) allows radiologically guided stereotactic excision of non-palpable radiodense lesions with high accuracy. Tissue cylinders of 5, 10, 15 or 20 mm diameter and of variable lengths can be removed very accurately under local anaesthesia and on an outpatient basis. Thirty-six patients with suspicious clusters of microcalcifications (n = 29) and with round lesions (n = 7) of the breast were qualified for ABBI. We were able to perform the excisional biopsy in a total of 34 patients. The breast of one woman was too small to safely fit into the system and in another woman the lesion could not be visualized by the system. In 2/34 cases (6%), the excision was imprecise due to slight dislocation of the breast parenchyma by the advancing cylinder knife. In one case (3%), ABBI missed the target within a dense mastopathic breast. In all cases the excisions were well tolerated. No wound complications occurred and the cosmetic result was excellent. Histology revealed 28 benign (82%) and 6 malignant (18%) lesions. Among the 27 small microcalcifications there were 3 invasive carcinomas, 3 ductal carcinomas in situ (DCIS), 1 lobular hyperplasia, 14 mastopathies, 1 fibroadenoma, 1 duct papilloma and 4 calcifications in scars. Four of the 7 round-shaped lesions were found to be fibroadenomas, 1 lobular hyperplasia, and 2 mastopathies. With the ABBI system, non-palpable breast lesions can be precisely localized and excised.     

Effect of ethanol on myocardial infarct size in a canine model of coronary artery occlusion-reperfusion

INTRODUCTION: We investigated the effectiveness of Levovist (SHU508A, Schering AG, Berlin, Germany) in the characterization of breast lesions. MATERIAL AND METHODS: June, 1996, to May, 1997, we studied 29 solid lesions in 29 patients (aged 17 to 83 years); our patients were 28 women and 1 man. The 29 solid lesions were 20 carcinomas (15 infiltrating ductal carcinomas, 4 ductal carcinomas in situ, 1 lobular carcinoma in situ), 6 fibroadenomas, 1 suspected postoperative recurrence and 2 apparently benign lesions. We used parameters suitable for the study of slow flows. A single bolus of contrast agent (300 mg/mL) was administered at 1-2 mL/s. Before Levovist injection, we studied the lesion signal intensity and the number of vascular poles. After contrast administration we re-evaluated both these parameters and studied the changes or presence of vessels undetected on the previous images. We also investigated the beginning and duration of enhancement and the presence of vessels inside and outside the lesions. RESULTS: We observed no signal enhancement in 17% of cases, mild enhancement in 7% and strong enhancement in 76% of cases. We found 3 more vascular poles (17%) in 5 lesions and 4 more poles in 3 lesions (10%). Increased vascularization was seen inside the lesion in 17% of cases, inside and outside it in 41% and only outside in 35% of cases. Carcinomas showed a rapid and long-lasting enhancement, while fibroadenomas showed a later and weaker enhancement. CONCLUSIONS: Levovist can be useful in the differential diagnosis of benign from malignant lesions, of recurrences from postoperative fibrosis, as well as in the staging and follow-up of the patients treated with neoadjuvant chemotherapy.     

Campaign for cervical cancer screening with vaginal smears in women aged 50-69 years in Isère (France). Results of the first round (January 1991-June 1993)

The department of Isère, which is involved since 1990 in a breast cancer screening campaign concerning women aged 50 to 69, has managed to associate a cervical and colorectal cancers screening program. The target sample size is 98,000 individuals. Women are asked to refer their general practitioner or gynaecologist for cervicovaginal smears. Each woman is invited at a screening interval of 30 months. The results of the first invitation (November 1990-December 1992) are reported. Thus 29,570 women did referred, so that the screening uptake is 30% and 20,083 women (68%) had Pap smears inside the screening program. 1.1% of the smears were unsatisfactory and 1.2% of the tests showed abnormalities. Ninety-six percent of the women who had been referred for further examinations have been followed up. Thirty-eight women (representing 17% of smears with abnormalities) had surgery (conisation, hysterectomy, Wertheim). Among them, 5 cases of invasive cervical carcinoma and 25 in situ carcinoma were detected. The detected cancer prevalence per 1,000 women screened is 1.5/1000. An organised screening program for cervical cancer in association with breast cancer screening, seems to be an effective way of increasing smears realisation in women aged 50 to 69, and of involving general practitioners in cervical cancer screening.     

Limitations of imaging choroidal tumors in vivo by optical coherence tomography

AIM: To study the immunohistochemical expression of the Thomsen-Friedenreich antigen (T) and its precursor, Tn, in the skin in various cancers. METHODS: T and Tn antigens were studied with monoclonal antibodies in 91 primary premalignant and malignant lesions, 13 cases of Paget's disease, and 26 carcinomas metastatic to the skin. The material had been collected over a 10 year period, formalin fixed, and paraffin embedded. Diagnoses had been made after examination of standard histological sections, supplemented when needed by appropriate immunohistochemical staining. RESULTS: 21% and 29% of the primary cutaneous premalignant and malignant epithelial tumours expressed the Tn and T antigens, respectively. By contrast, 81% of metastatic carcinomas to the skin were Tn positive, while only 23% of them expressed the T antigen. All cases of Paget's disease were Tn positive but only 15% of them expressed the T antigen. The 21 nonepithelial tumours (including melanomas) were as a rule unreactive. CONCLUSIONS: The accumulation of the precursor (Tn) antigen in tumours metastasising to the skin highlights the incomplete glycosylation of carbohydrate antigens occurring in these tumours. The predominant Tn versus T antigen expression appears to be a useful immunohistochemical feature which may aid in the differentiation of primary cutaneous carcinomas from metastatic tumours.     

Early detection of breast cancer in Navarra. Diagnostic approach in women sent to a referral hospital

BACKGROUND: Breast cancer screening programs represent an important increase in the number of patients to be evaluated and a higher proportion of subclinical lesions detected in reference hospitals. The authors' experience related to an early detection program initiated in Navarra, Spain (PDPCM) is herein presented. METHODS: The diagnoses made in 319 women referred from the PDPCM to the authors' hospital for mammographic suspicion of malignancy were reviewed. Directed surgical biopsy was carried out in 89 women (27.9%) without previous cytologic study. Fine needle aspiration punction and cytology (FNAP-cytology) were performed as the first diagnostic test in 216 lesions (67.7%) 53 of which were palpable and 163 nonpalpable. Aggressive techniques were not indicated in 14 cases (4.4%). RESULTS: A total of 136 carcinomas (42.6%) were diagnosed and benign lesions were find at biopsy in 112 (35.1%) women. The fifty-seven lesions (17.9%) which did not show malignancy on FNAP-cytology were not biopsied given the insufficient degree of suspicion. Only one false negative has appeared in this group from 27 to 48 months after the first consultation. The global diagnostic reliability was of 99.68%. CONCLUSIONS: Directed surgical biopsy is the most reliable technique for the diagnosis of nonpalpable breast lesions in early stages and is always necessary when there is medium or high radiologic suspicion of malignancy. Fine needle aspiration puncture is a very useful technique to confirm malignancy and to avoid unnecessary biopsies in low suspicion lesions.     

Genetic alterations at 5p15: a potential marker for progression of precancerous lesions of the uterine cervix

BACKGROUND: Development of uterine cervical cancer is preceded by preneoplastic proliferative changes in the cervical epithelium called "intra-epithelial neoplasia" or "dysplasia." The genetic basis of the origin and progression of such preneoplastic lesions is not known. By analysis of carcinomas for loss of constitutional heterozygosity (LOH), we have previously shown a high frequency of allelic loss in the short arm of chromosome 5 (5p), suggesting loss of a candidate tumor suppressor gene located in 5p and associated with the development of this tumor. PURPOSE: To further understand the role of genetic alterations that affect 5p in cervical carcinogenesis, we evaluated the status of microsatellite polymorphisms at five loci mapped to 5p14-ter in precancerous and cancerous lesions. METHODS: Biopsy specimens from two groups of patients were analyzed for genetic alterations affecting 5p. One group comprised 14 cases of precancerous lesions (i.e., dysplasias) and five cases of carcinoma in situ (CIS); the second group comprised 46 previously untreated patients with invasive carcinoma. Tumor and normal DNAs were analyzed by polymerase chain reaction for genetic losses and instability at five polymorphic microsatellite loci (D5S392, D5S406, D5S208, D5S117, and D5S432) mapped to 5p. RESULTS: LOH was observed in 25 (55.6%) of 45 informative invasive carcinomas, one (20%) of five cases of CIS, and three (21%) of 14 precancerous lesions. Among the loci tested, D5S406 (5p15.1-15.2) exhibited LOH in 12 (48%) of 25 invasive carcinomas, one (33%) of three cases of CIS, and three (60%) of five precancerous lesions, suggesting this to be the site in 5p of the novel candidate tumor suppressor gene. In addition, replication error-type alterations were noted in the 5p14-ter region in six (13%) of 46 invasive carcinomas, two (40%) of five cases of CIS, and three (21%) of 14 precancerous lesions. Instability affected D5S406 in eight (66.7%) of 12 instances that showed microsatellite instability. CONCLUSION: These observations suggest that allelic loss and microsatellite instability in the region of D5S406 may play a role early in the development of cervical carcinoma and identify the site of a candidate tumor suppressor gene. These genetic markers (allelic loss and microsatellite instability) may also define CIS and precancerous lesions at high risk for progression to invasive cancer. IMPLICATIONS: The future molecular cloning of the candidate tumor suppressor gene at 5p15.1-15.2 may provide new insights into the genetic mechanisms of cervical carcinogenesis. Analysis and clinical follow-up of a large cohort of prospectively ascertained cases of precancerous lesions would help to validate the usefulness of these markers.     

Ultrasonography of cystic thyroid nodules: sonographic-pathologic correlation

Retrospectively the ultrasonographic findings of 153 surgically resected cystic thyroid nodules were reviewed. The pathologic findings in this series revealed that 86% were degenerating benign adenomas or adenomatous goiters, and 14% were malignant tumors. The sonographic appearance of these lesions was classified into 7 groups as follows: type I: entirely cystic (less than 1cm), type II: cystic(more than 1cm) [II(a)], and with small polyp or dome-like elevation on the cyst wall [II(b)], type III: larger cyst with projection (more than 1cm) into the lumen, type IV: cyst with a peripherally localized solid component, type V: irregularly mixed cystic and solid components, type VI: a solid mass with multiple crescentic cysts [VI(a)], or round cysts [VI(b)], type VII: a solid mass with only one or two cysts. Pathologic correlation revealed that malignancy in this series ranged from 80% in type III and V to only 4% in type II, where most of the lesions in this group were composed of granulation tissue in degenerating adenomatous polyps and cyst walls. Lesions in type IV showed malignancy rate of 40%. Type III showed characteristic sonographic findings seen in cystic papillary carcinomas (CPCs), with multiple punctate echogenic foci in large pedunculated projections. The typical psammomatous calcifications specific in this group were confirmed in 6 of the 8 type III CPCs. The multiple crescentic cysts in type VI(a) lesions were characteristic sonographic signs seen in adenomatous goiters, representing the pathologic finding of cysts forming around each of multiple adenomatous nodules in this group. Type VII represented non specific appearing lesions, included adenomas, adenomatous goiters, CPCs and follicular carcinomas.(ABSTRACT TRUNCATED AT 250 WORDS)     

Screening for breast cancer in Ghent, Belgium: first results of a programme involving the existing health services

In 1992, a population-based breast cancer screening programme was initiated in the municipality of Ghent: all women aged 40-69 years were personally invited to attend a local radiology unit for a mammogram, after being examined by a general practitioner or gynaecologist of their choice. The results of history taking, clinical breast examination, first and second reading, further investigation and primary treatment were registered. In total, 24.3% of the eligible population was screened in the period 1992-1994. The recall and biopsy rates were 2.9% and 1.4%, respectively. The cancer detection rate was 8.1 per 1000 women screened. Of all cancers detected, 88.0% (66/75) were invasive. Of these, 35.9% (23/64) measured 10 mm or less in diameter. The benign to malignant biopsy ratio was 0.7. Apart from the low participation, these results suggest that the programme is effective, compared with reference standards and the results of other studies.     

Papillary squamotransitional cell carcinoma of the cervix: a report of 32 cases

Papillary carcinomas of the uterine cervix with transitional or squamous differentiation are rare tumors that often resemble transitional cell carcinomas of the urinary tract. We reviewed 32 such cases of papillary cervical carcinoma and divided them into three groups: 1) predominantly (> 90%) squamous (nine cases), 2) mixed squamous and transitional (16 cases), and 3) predominantly transitional (seven cases). Overall, the patients ranged in age from 22 to 93 years (mean 50), and the most common clinical presentation was abnormal bleeding (15 patients) and an abnormal Papanicolaou smear (nine patients). The tumors ranged in size from 0.7 to 6.0 cm (mean 3.0). All cases demonstrated a papillary architecture with fibrovascular cores lined by a multilayered, atypical epithelium resembling a high-grade squamous intraepithelial lesion of the cervix. Underlying superficial to deep stromal invasion was seen in 18 of 20 cases (90%); in the remaining 12 cases, the specimen was too superficial to assess invasion. Eighteen (86%) of the 21 cases examined immunohistochemically demonstrated immunoreactivity for cytokeratin 7, whereas only two of the 21 (9.5%) showed positivity for cytokeratin 20. Of the 12 women for whom follow-up information was available, three were treated by simple hysterectomy, two underwent radical hysterectomy, one was treated with radiation alone, and one with combination chemotherapy and radiotherapy. Three patients died of disease (two in the squamous group and one transitional) within an average of 13 months after diagnosis. Local recurrence developed in two women, and one of these, a vaginal recurrence, occurred 12 years after the original diagnosis. Based on the above findings, we believe that these tumors are a clinicopathologically distinct, homogeneous group that display a morphologic spectrum. Nevertheless, because some tumors may show a purely squamous or purely transitional appearance, we propose retaining the above three separate designations for these tumors with the understanding that there is often a substantial degree of subjectivity in deciding whether a tumor is squamous or transitional. The most distinctive, objective, and easily recognizable feature of these tumors is their surface papillary architecture rather than their superficial resemblance to transitional cell carcinomas of the urinary tract, and we emphasize the need to distinguish these potentially aggressive malignant tumors from the far more common and benign papillary lesions of the cervix.