The ongoing revolution in breast imaging calls for a similar revolution in breast pathology.

COMMUNICATION BETWEEN PATHOLOGISTS AND RADIOLOGISTS SUFFERS FROM A LACK OF COMMON GROUND: the pathologists examine cells in ultrathin tissue slices having the area of a postage stamp, while the radiologists examine images of an entire organ, but without seeing the cellular details. The current practice of examining breast cancer specimens is analogous to scrutinizing individual pieces of a jigsaw puzzle, without examining all of them and never putting all the pieces into place. The routine use of large section histopathology technique could help to alleviate much of this problem, especially with nonpalpable, screen-detected breast cancers. The study of three-dimensional (3D) images of subgross, thick section pathology specimens by both radiologists and pathologists could greatly assist in the communication of findings.

Mammography and breast cancer: the new era.

OBJECTIVES: To review the evidence demonstrating that early detection of breast cancer substantially decreases death from the disease, and to demonstrate that the significant change in the outcome of breast cancer patients results from a combination of early detection and surgical removal of breast cancer, as treatment of the late stage disease provides little impact on ultimate outcome. METHOD: Review results of the randomized controlled trials of mammographic screening and the published results of service screening. RESULTS: Both randomized controlled trials and service screening, when performed properly, provide unequivocal evidence demonstrating that arresting the disease in its preclinically detectable phase has significant impact on outcome. Primary emphasis should be upon preventing breast cancer from developing to metastatic disease. CONCLUSIONS: Numerous scientific trials have repeatedly and convincingly confirmed that breast cancer is progressive rather than a systemic disease from its inception. Progression of breast cancer can be arrested through detection and treatment at an early phase. The time at which disease progression is arrested has significant impact on clinical outcome, making mammographic screening a key factor in the control of breast cancer.

The rationale and current controversies of mammographic screening for breast cancer.

The impact of mammography screening upon the chances of a woman dying from breast cancer has been studied for four decades. Until this century the results have always been presented in terms of benefit to populations, and have erroneously been assumed to be directly transferable to individual women. A multitude of factors combine to reduce the effect of screening upon a population as measurable in a randomized controlled trial. The most serious problem has been the misunderstanding that an invitation to mammography screening would be equivalent to actually getting a mammogram. Additionally, the control population also benefits from the screening program, and these benefits reduce the measurable effect of screening. Recent long-term trials, which have been able to fully document participation in mammography screening on an individual basis, have demonstrated an even more substantial reduction in breast cancer mortality attributable to mammography screening, with a much more limited impact of therapeutic advances against advanced breast cancer.

Mammographic screening: international perspective.

The twentieth century saw the introduction of mammography as a diagnostic tool and its refinement as a screening method. It appears guaranteed that women who are well informed will seek mammography screening with high expectations of technical quality and accurate interpretation. More refined knowledge of breast anatomy and pathology will assist radiologists to interpret with high specificity. We will learn how to recognized more accurately normal structures and doubtful findings. We will gain experience in interpretation through faithful review of interval cancers and subtle screen-detected cancers, and will use educational tools that have the potential to improve the efficiency of education by directing attention to specific deficiencies. Mammographic screening has been advanced through the efforts of dedicated teams of physicians, scientists, and other professionals throughout the world. The international communication of ideas and discoveries will continue to challenge the boundaries of what can be accomplished in early detection as well as noninvasive therapy, and this body of knowledge will continue to be enriched by these diverse contributions.

The demands of screening mammography on surgical inpatient services of breast cancer.

A nationwide mammographic screening of women ages 50 to 59 years commenced in Finland in January 1987. We studied the demands of screening on surgical inpatient services by comparing the treatment strategy, volume of breast biopsies, and hospital stay before and after implementation of mass screening of women age 50 to 59. Approximately 20 patients per 100,000 inhabitants were referred annually from mass screening for surgical biopsies, in half of which cancer was detected. In 1985 through 1986 (before screening) we operated on 134 patients suspected of having breast cancer. After the first (in 1990) and the second (in 1995) round of mammographic screening we operated on 161 patients in 2 years suspected of having breast cancer. Concurrently 25 of 92 cancers (27%) were found only because of the screening. Before the screening period clinical symptoms and palpable tumors were cause for referral to surgery in 84 per cent of the cases and abnormal mammography in only 16 per cent. During screening these ratios were 34 and 61 per cent, respectively. The number of T(is)-1 cancers (<2 cm) increased from 44 per cent before screening to 70 per cent during screening. In contrast the number of T2 cancers (2-4 cm) decreased from 40 to 20 per cent. The mammographic screening did not increase the hospital stay of patients. We conclude that the mammographic screening program of all women age 50 to 59 years increased the number of surgical biopsies in our hospital by only 30 per cent. Breast cancer was found at an earlier stage during screening. More than one-fourth of breast cancers are currently found through the mass screening program in Finland.

Algorithmic 3D simulation of breast calcifications for digital mammography.

We present a framework for algorithmic three-dimensional simulation of breast calcifications. The simulated calcifications can be viewed from any angle at a higher spatial resolution than currently available for digital mammography, and they can be placed onto a simulated or real mammographic background to provide example cases for computers and radiologists. In order to simulate calcification clusters, we also show how to simulate duct networks and terminal ductal lobular units. We evaluated the model with a double-blind evaluation of 60 cases with four experienced radiologists by mixing 30 cases of simulated calcification clusters on a real or simulated mammographic background with 30 cases of real breast calcification clusters digitized at a spatial resolution of 15 microm from high-resolution radiographs of 5 mm slices of breast specimens. The results indicate that the majority of the 2D projections of the 3D simulated calcifications compare favorably with the radiographic images of real breast calcifications.

The pressing need for better histologic-mammographic correlation of the many variations in normal breast anatomy.

Mammography screening calls for a reevaluation of the working relationship between physicians dealing with the diagnosis and treatment of breast diseases. In this new era, histologic-mammographic correlation needs to be extended to correctly describe the deceptive mammographic findings that correspond to variations in normal breast tissue. Progress in histologic-mammographic correlation can only be made by overcoming the limitations inherent to the traditional histologic technique by examining a histologic specimen of greater length, width, and depth. There are several distinct advantages to using the large-section histology technique in the diagnosis of breast diseases. The subgross (three-dimensional) histology technique serves to bridge the gap that separates the pathologist and radiologist, bringing them to a common ground for a better understanding of breast morphology. These improvements in communication between the members of the diagnostic team will serve to optimize the sensitivity and specificity of breast cancer diagnosis.

Osteoarthritis-like lesions in transgenic mice harboring a small deletion mutation in type II collagen gene.

OBJECTIVE: The present study was conducted on transgenic Del1 (+/-) mice harboring six copies of a transgene with small deletion mutation engineered into mouse type II collagen gene. Incorporation of transgene into mouse genome was predicted to cause reduced mechanical strength of articular cartilage with deposition of structurally inferior collagen network and consequently to predispose the animal to early-onset joint degeneration. DESIGN: Progression of degenerative chances in the knee joints of Del1 (+/-) and control mice was followed by macroscopic and histologic analyses at 3-5 month intervals between 3 and 22 months of age. Expression and distribution of type II collagen was studied with Northern hybridization, RNase protection assay and immunohistochemistry. RESULTS: Articular cartilage degeneration began with superficial fibrillation at the age of 3 months in Del1 (+/-) mice. These changes coincided with a significant reduction in the expression of both endogenous and transgene-derived type II collagen mRNA. The defects gradually progressed into erosions penetrating the articular cartilage, bony sclerosis, degeneration of menisci, mineralization of various joint structures, cyst formation and exposure of subchondral bone. Nontransgenic controls also developed osteoarthritic lesions, but these appeared significantly later and were less severe. Increased transcription of type IIA procollagen mRNA, typical for chondroprogenitor cells and cartilage repair was also observed at six months in Del1 (+/-) mice. CONCLUSION: These findings suggest that the impact of truncated type II collagen transgene, together with maturation-related reduction in type II collagen production significantly contribute to the early-onset degeneration of knee joints in Del1 (+/-) mice. These mice with osteoarthritis-like phenotype should provide a useful model for studies on the early pathogenic mechanisms involved in articular cartilage degeneration.

A multiscale algorithm for segmenting calcifications from high-resolution mammographic specimen radiographs.

We have developed a multiscale algorithm for segmenting breast calcifications from high-resolution specimen radiographs. The algorithm was evaluated using 152 mammographic regions of interest digitized at a 15-microm spatial resolution. The true-positive detection rate was approximately 97.4% with 0.67 false-positives per image, and the segmentation error of individual calcification particles was approximately 5%. The performance of the algorithm is highly satisfactory.

A novel method for prediction of long-term outcome of women with T1a, T1b, and 10-14 mm invasive breast cancers: a prospective study.

BACKGROUND: Women with small mammographically detected breast cancers generally have good long-term outcomes, but a few with T1a (1-5 mm) and T1b (6-10 mm) tumours will eventually die from breast cancer. We investigated whether women at high risk of breast-cancer death could be identified with mammographic criteria and differentiated from women with small cancers of the breast and good outcomes. METHODS: We prospectively applied mammographic classifications of tumour type to a consecutive series of 343 mammograms of invasive breast cancers of size 1-14 mm. Classifications were: stellate (spiculated) mass with no calcifications; circular or oval lesions with no calcifications; spiculated or circular lesions with non-casting-type calcifications; and casting-type calcifications. FINDINGS: 20-year survival for women with 1-14 mm invasive tumours with casting-type calcifications was 55%. 14% of 138 women with 1-9 mm tumours had casting-type calcifications on mammography, which accounted for 73% of all breast-cancer deaths (p<0.001). T1a, T1b, and 10-14 mm tumours with casting-type calcifications behaved as if they were larger lesions, since the rate of death was similar to that for women with advanced high-grade tumours. Most women who died were node-negative. The long-term survival of women who had tumours of 1-9 mm with no casting-type calcifications was about 95%. INTERPRETATION: Mammographic classification seemed to reliably predict good and bad long-term outcomes for survival in tumours of 14 mm or smaller, and especially for those smaller than 10 mm. The implications for therapy are substantial.

A new era in the diagnosis of breast cancer.

The regular use of high-quality mammography on asymptomatic women enables most breast cancers to be detected in the preclinical phase. Earlier detection dramatically rearranges the spectrum of breast cancer outcomes, resulting in better control of breast cancer. The new era requires a shift in thinking and a re-evaluation of the traditional diagnostic and therapeutic approaches to breast diseases. Tumors are smaller, less often node-positive, and have a more favorable malignancy grade. The challenge for diagnosticians is to find as many breast cancers as possible in the preclinical phase. The challenge for therapists is to adapt the treatment guidelines accordingly, in order to avoid over-treatment.

Screening mammography in Finland--1.5 million examinations with 97 percent specificity. Mammography Working Group, Radiological Society of Finland.

A nationwide mammography screening program including women aged 50 59 years at the time of the first invitation and involving more than 100 radiologists was started in Finland in January, 1987. From 1987 through 1997, a total of 1690496 invitations to biennial two-view mammography screening was sent out. The compliance for screening was 88.5% with 1 495744 screening examinations performed during this 11-year period. There were 49020 recalls (3.28% of those attending) for further work-up studies and 9689 women (0.65% of those attending) were referred for surgery. The total number of screening-detected breast cancers was 5595, giving a detection rate of 3.7 cancers per 1000 screening studies. More than half (57.7%) of all surgical biopsies revealed breast cancer and 67.8% of the invasive cancers were at Stage I. The positive predictive value of referral to surgical biopsy increased from 33.2% in 1987 to 65.5% in 1997. and the ratio of malignant to benign biopsies more than tripled from the first to the fifth year of screening. The observed/expected ratio of invasive cancer detection was 2.44. Only 0.27% (1 out of every 372) of all screening mammograms were followed by a benign biopsy, and 2.90% (1 out of every 34) of all screening mammograms were followed by the women being recalled for further studies and not found to have breast cancer. This gave a specificity of recall after screening mammography greater than 97.0% and a specificity of referral to surgical biopsy greater than 99.7%. Measures of specificity improved considerably during the first three years of the screening program. The high specificity of screening mammography can be attributed to the nature of the screening process as well as to the opportunity for individual radiologists to attain a greater level of experience and competence. The decision to recall appears to have been crucial in determining the specificity.

Glomus tumor of the trachea.

We report a case of a glomus tumor in the trachea which was an incidental finding in a 66-year-old man. The histological picture and immunohistochemical profile were typical for this tumor. The glomus tumor is an exceedingly rare mass lesion in the trachea, but it is useful to keep it among differential diagnostic alternatives when a tracheal tumor is seen on radiographs or endoscopy.

Traumatic fistula between the left anterior descending coronary artery and a left ventricular pseudoaneurysm.

A 44-year-old man presented with a fistula of the left anterior descending (LAD) coronary artery to a left ventricular pseudoaneurysm 6 months after a stab injury in the left anterior chest. The color Doppler echocardiography suggested, and angiography confirmed, the diagnosis and the lesion was treated successfully. Traumatic coronary artery fistulas are rare complications, and color Doppler echocardiography proved useful for the diagnosis.

Dynamic Gd-DTPA-enhanced MR imaging of the kidney: comparison between T1- and T2-weighted sequences.

OBJECTIVE: To determine whether T1- or T2-weighted sequences are more informative and practical in dynamic Gd-DTPA-enhanced MR imaging for the evaluation of renal blood flow and function. MATERIALS AND METHODS: Dynamic Gd-DTPA-enhanced MR imaging of the kidney was performed in 7 patients by either T1-weighted TurboFLASH (TR/TE/TI/FA = 9/4/27/8) or T2-weighted FLASH (TR/TE/FA = 32/22/10) sequences for comparison of the enhancement pattern. None of the subjects had a suspicion of renal dysfunction from laboratory data, and the absence of renal artery stenosis was confirmed by conventional angiography. RESULTS: During the early phase, the marked signal increase in T1-weighted imaging in the renal cortex corresponded to a similar marked decrease in signal intensity in T2-weighted imaging. During the middle and late phases, the medulla was dramatically decreased in intensity on the T2-weighted imaging resulting in a good contrast between the cortex and medulla. CONCLUSION: Both sequences may provide almost similar information about the renal cortical blood flow. However, T2-weighted dynamic MR imaging may be more informative than T1-weighted dynamic MR imaging about the concentrating ability in the renal medulla. A high concentration of Gd-DTPA in the tubular structure was suspected to cause a dramatic decrease in intensity in the medulla in T2-weighted imaging.