The Practice of Mammography E-Book

• Herausgeber: Thieme
• Kategorie: Fachliteratur
• Sprache: Englisch

Seitenzahl: 520

Veröffentlichungsjahr: 2001

Beschreibung

Even with the advent of many new radiographic techniques, mammography remains the most important and effective method of breast examination available today. This outstanding guide, using anatomy and pathology as a starting point, gives you clear and accurate instructions on all facets of performing breast mammograms, from proper positioning to analyzing the findings. In addition to mammography, this teaching guide focuses on the non-radiological aspects of breast carcinoma such as clinical diagnosis, treatment, epidemiology, and risk factors. You'll also learn about screening methods to detect and avoid potential problems. The instructive nature of this text makes it an excellent resource for students and residents. Radiologists and OB/GYN's who need a quick update or refresher will also appreciate its value. Here is the book that belongs on the shelves of every medical school library, residency program, and specialist's office!

Leseprobe

Library of Congress Cataloging-in-Publication Data

Radiologische Mammadiagnostik. English

The practice of mammography: pathology,technique, interpretation, adjunct modalities/

Daniel J. Dronkers… [et al.].

p. cm.

Includes bibliographical references and index.ISBN 3-13-124371-6 – ISBN 1-58890-004-5 (U.S.)1. Breast—Radiography. 2. Breast – Cancer – Diagnosis.I. Dronkers, Daniël J. II. Title.[DNLM: 1. Mammography – methods.2. Breast Neoplasms – radiography. WP 815 R1294 2001a]

RG493.5.R33R3413 2001

616.99’44907572 – dc21

2001041467

This book is an authorized translation of the German edition published and copyrighted 1999 by Georg Thieme Verlag, Stuttgart, Germany. Title of the German edition: Radiologische Mammadiagnostik.

© 2002 Georg Thieme VerlagRüdigerstraße 14, D-70469 Stuttgart, GermanyThieme New York, 333 Seventh Avenue,New York, N. Y. 10001, U. S. A.

Typesetting by Druckhaus Götz GmbH,D-71636 Ludwigsburg

Printed in Germany by Staudigl-Druck, Donauwörth

ISBN 3-13-124371-6 (GTV)ISBN 1-58890-004-5 (TNY)                             1 2 3 4 5

Important Note: Medicine is an ever-changing science undergoing continual development. Research and clinical experience are continually expanding our knowledge, in particular our knowledge of proper treatment and drug therapy. Insofar as this book mentions any dosage or application, readers may rest assured that the authors, editors, and publishers have made every effort to ensure that such references are in accordance with the state of knowledge at the time of production of the book.

Nevertheless this does not involve, imply, or express any guarantee or responsibility on the part of the publishers in respect of any dosage instructions and forms of application stated in the book. Every user is requested to examine carefully the manufacturers’ leaflets accompanying each drug and to check, if necessary in consultation with a physician or specialist, whether the dosage schedules mentioned therein or the contraindications stated by the manufacturers differ from the statements made in the present book. Such examination is particularly important with drugs that are either rarely used or have been newly released on the market. Every dosage schedule or every form of application used is entirely at the user's own risk and responsibility. The authors and publishers request every user to report to the publishers any discrepancies or inaccuracies noticed.

Some of the product names, patents, and registered designs referred to in this book are in fact registered trademarks or proprietary names even though specific reference to this fact is not always made in the text. Therefore, the appearance of a name without designation as proprietary is not to be construed as a representation by the publisher that it is in the public domain.

This book, including all parts thereof, is legally protected by copyright. Any use, exploitation, or commercialization outside the narrow limits set by copyright legislation, without the publisher's consent, is illegal and liable to prosecution. This applies in particular to photostat reproduction, copying, mimeographing or duplication of any kind, translating, preparation of microfilms, and electronic data processing and storage.

Preface

When Thomas Scherb, MD, from Thieme Publishers approached us for a German textbook on mammography, we readily accepted this opportunity.

We deemed it prudent not to rely exclusively on the knowledge and experience from Nijmegen, The Netherlands, but to use a broader basis by including experts from other mammographic centers in the Netherlands and Germany. We wanted to create a short new textbook on clinical mammography.

Based on the anatomy and pathology of the breast, the radiological findings are presented plainly and clearly, with emphasis on instruction as found in a teaching book rather than on completeness as expected from a reference text. We have tried to accommmodate the underlying physics and the importance of positioning in mammography.

Mammography is one of the best-perfected conventional radiographic methods. Even after the advent of newer techniques, such as sonography (ultrasound) and MRI (magnetic resonance imaging), mammography remains the most important radiological examination of the breast. Radiological imaging of the breast is primarily directed at discovering breast carcinoma, which forms the core of this book. Nonimaging aspects of breast carcinoma, such as clinical diagnosis, treatment, epidemiology, and risk factors, are also discussed. Certain details are covered in more than one chapter, which should make it easier to study each chapter separately.

Mammographic screening is discussed in addition to diagnostic mammography. After the screening trials in Nijmegen and Utrecht in 1975, national screening began in the Netherlands in 1988. The LRCB (National Expert and Training Center for Breast Cancer Screening) was established in Nijmegen for this purpose. Besides their commitment to scientific research, LRCB experts conduct technical quality control of all 60 screening centers in the Netherlands, as well as postgraduate training of all radiologists, pathologists, and radiologic technologists involved in national breast cancer screening. The experience of the LRCB is incorporated into this book.

We would like to thank all contributors for their cooperation, especially Horst Aichinger, Ph D, who coordinated Chapter 5. We are grateful for the support of the Stichting Vroege Opsporing Kanker Oost-Nederland (SVOKON). K. Siekman and W. Veldkamp, both from LRCB in Nijmegen, provided the digitization of the mammographic images. Cooperation with the publisher and its co-workers on this edition was as good as it was for the German edition; special thanks go to Clifford Bergman, MD, Ms. Annie Hollins, and Gert A. Krüger for their support. F. Hartmann provided the instructive illustrations and graphics. When the publisher decided on an English edition of this book, we updated the text. Ms. Annelies Schef and Johan Schouten supported us in the translation of some of the chapters. Peter Winter, MD, was responsible for the final English version.

The German edition was dedicated to Professor W. H. A. M. Penn, former head of the Department of Radiology of the University Hospital St. Radboud, Nijmegen, the Netherlands, and a great advocate of screening for breast carcinoma in the Netherlands, and to the late professor W. Höffken, Cologne, Germany, one of the pioneers of mammography. We dedicate this English edition to our wives.

Nijmegen, Fall 2001                                                     The Editors

Contributors

Aichinger, H., PhDFormerly: Siemens AGMedical technology, basic researchErlangen, Germany

Beex, L. V. A. M., MDUMC St. RadboudDept. OncologyNijmegen, Netherlands

Boetes, Carla, MDUMC St. RadboudDept. RadiologyNijmegen, Netherlands

Bun, Petra A. M., MDUMC LeidenDept. RadiologyLeiden, Netherlands

Dronkers, D. J., MDRadiologistVelp, Netherlands

Hendriks, J. H. C. L., MDUMC St. RadboudDept. Radiology and LRCBNijmegen, Netherlands

Heywang-Köbrunner, Sylvia H., MDProfessor of RadiologyMartin-Luther-UniversitätKlinik für Radiologische DiagnostikHalle, Germany

Holland, R., MDProfessor of PathologyUMC St. RadboudLRCBNijmegen, Netherlands

Hoogenhout, J., MDUMC St. RadboudDept. RadiotherapyNijmegen, Netherlands

Hoogenraad, W. J., MDUMC St. RadboudDept. RadiotherapyNijmegen, Netherlands

Karssemeijer, N., PhDUMC St. RadboudDept. RadiologyNijmegen, Netherlands

McGauran, Natalie, MDOtto-von-Guericke-UniversitätInstitut für SozialmedizinMagdeburg, Germany

Muller, J. W. Th., MDDiakonessen ZiekenhuisDept. RadiologyUtrecht, Netherlands

Rijken, Henny,Chief technologistUMC St. RadboudLRCB Nijmegen, Netherlands

Robra, B.-P., MDProfessor of EpidemiologyOtto-von-Guericke-UniversitätInstitut für SozialmedizinMagdeburg, Germany

Rosenbusch, G., MDProfessor Emeritus of RadiologyNijmegen, Netherlands

Säbel, M., PhDProfessor of Medical PhysicsUniversitäts-FrauenklinikMedizinische PhysikErlangen, Germany

Stargardt, A., PhDKlinikum derRWTH Klinik für Radiologische DiagnostikAachen, Germany

Thijssen, M. A. O., PhDUMC St. RadboudDept. Radiology and LRCBNijmegen, Netherlands

Verbeek, A. L. M., MDProfessor of EpidemiologyUMC St. RadboudDept. EpidemiologyNijmegen, Netherlands

von Volkmann, T., PhDKodak AGGB MedizinStuttgart, Germany

Wobbes, Th., MDProfessor of SurgeryUMC St. RadboudDept. SurgeryNijmegen, Netherlands

Zonderland, Harmine M., MDUMC LeidenDept. RadiologyLeiden, Netherlands

Contents

1 Clinical Characteristics of Breast Cancer

Th. Wobbes

Physiological Lumps and Tenderness

Mastalgia

Nodularity

Dominant Lumps

Breast Cancer

Nipple Discharge

Fibroadenoma

Cysts

Inflammation and Infections

Skin and Nipple Changes

2 Anatomy

J. H. C. L. Hendriks, D. J. Dronkers, and G. Rosenbusch

Mammary Gland

Fasciae and Connective Tissue

Parenchymal Pattern and Skin Pattern

Arteries, Veins, Lymphatics

Physiological Changes of the Breast

Embryology and Anomalies

3 Benign and Malignant Disorders of the Breast

R. Holland, G. Rosenbusch, J. H. C. L. Hendriks, and D. J. Dronkers

Benign Disorders

Fibrocystic Disease

Cysts

Epitheliosis

Adenosis

Radial Scar

Benign Tumors

Fibroadenoma

Phyllodes Tumor

Intraductal Papilloma

Juvenile Multiple Intraductal Papilloma

Lipoma

Fibroadenolipoma

Rare Benign Tumors

Inflammation and Abscesses

Duct Ectasia

Mondor Disease

Hematoma

Fat necrosis

Carcinoma in Situ and Invasive Carcinoma

Carcinoma in Situ

Ductal Carcinoma in Situ (DCIS)

Lobular Carcinoma in Situ (LCIS)

Invasive Breast Cancer

Invasive Ductal Carcinoma (IDC)

Invasive Lobular Carcinoma (ILC)

Invasive Tubular Carcinoma

Invasive Medullary Carcinoma

Invasive Mucinous (Colloid, Gallertous) Carcinoma

Rarely Occurring Carcinomas

Papillary Carcinoma, Intraductal

Intracystic Carcinoma

Paget Disease of the Nipple

Inflammatory Carcinoma of the Breast

Unilateral Multifocality and Multicentricity

Bilateral Occurrence

Metastases in the Breast

Locally and Regionally Recurrent Carcinomas

Pregnancy and Breast Cancer

Growth Rate of Breast Carcinoma

Missed, Mammographically Occult and Interval Cancer

Missed Carcinoma

Mammographically Occult Carcinoma

Interval Cancers

4 Epidemiology and Treatment of Breast Cancer

Epidemiology and Risk Factors

B.-P. Robra, A. L. M. Verbeek, and Natalie McGauran

Epidemiology

Risk Factors

Other Possibly Causal Factors

Prevention

Treatment

J. Hoogenhout, Th. Wobbes, W. J. Hoogenraad, andL. V. A. M. Beex

Curative Therapy

Palliative Therapy

Ductal Carcinoma in Situ

Lobular Carcinoma in situ

Breast Cancer in Older Women

Interdisciplinary Cooperation in Diagnostic Procedures and Treatment

D. J. Dronkers

Team of Experts (“Breast Team”)

Sequence of Work-up

Cooperation during Surgery

Feedback of Histopathological Findings to the Radiologist

Quality Assurance and Control

Patient Self-help Groups

5 Physical and Technical Aspects of Mammography

Introduction

M. A. O. Thijssen

The Imaging Chain

Definitions

Image Quality

Medical Quality Criteria of X-ray Mammography

M. Säbel

Resulting Demands on Radiological Imaging Systems

H. Aichinger

Sharpness

Contrast

Noise

Image Quality Figure

Dose

The Effect of the Radiographic Imaging System on Dose, Contrast, Resolution, and Noise

H. Aichinger

Contrast

Dose

Compression

Antiscatter Grid

Sharpness

The Effect of the Image Receptor on Dose, Contrast, Resolution, and Noise

T. von Volkmann

Composition of Mammography Films

Structure of Intensifying Screens

Characteristic Curve

Speed of the Film–Screen System

Density of the Mammogram

Radiographic Contrast

Image Blur

Noise

Summary

The Importance of Constancy and Reproducibility of the Entire Imaging System

H. Aichinger

Automatic Exposure Control

The Role of the Viewbox and Viewing Conditions

T. von Volkmann, M. A. O. Thijssen, and A. Stargardt

European Quality Assurance Guidelines for Mammography Screening

Luminance of the Viewbox

Illuminance of Ambient Light

Masking

A New Digital Film-Reading Modality

D. J. Dronkers and G. Rosenbusch

Possible Digital Image Receptors

H. Aichinger

Digital Detectors (Full-field Mammography)

Image Processing

Computer-aided Reading of Mammograms

N. Karssemeijer

Radiation Exposure

M. Säbel

Quality Assurance

H. Aichinger, M. Säbel, and M. A. O. Thijssen

Quality Control Regarding ACR and EPMS

6 Positioning in Mammography

Henny Rijken

Technical Aspects

Equipment

Ergonomics

Film processing

Tasks of the Radiologic Technologist (Radiographer) within the Breast Imaging Team

Technical Quality Control

Social Skills

Introduction to the Examination

Positioning

Compression

Placement of Automatic Exposure Control (AEC) Detector

Anatomical Basis for Mammographic Projections

Positioning

Standard Projections

Craniocaudal (CC) View

Mediolateral Oblique (MLO) View

Most Important Additional Projections

Lateral Projections (Mediolateral, Lateromedial)

Spot and Magnification Views

Extended CC View (“Cleopatra View”)

Less Frequently Used Additional Projections

Axillary View

Tangential View

Caudocranial View

Views with Recumbent Patients

Mammographic Positioning in Males

Mammography in Women with Breast Implants

General Quality Criteria for Mammograms

Final Remarks

7 Supplemental and Advanced Examinations

Magnification Mammography

J. H. C. L. Hendriks and G. Rosenbusch

Percutaneous Diagnostic Procedures, Preoperative Localization, and Specimen Radiography

D. J. Dronkers

Percutaneous Diagnostic Procedures

Diagnostic Puncture of Cysts

Fine-Needle Aspiration (FNA) for Cytology

Histological Core-Needle Biopsy

Image Guidance Modalities in Nonpalpable Lesions

Sonographic Guidance

Stereotactic Mammographic Guidance

Radiology Support for Surgical Excisional Biopsy

Preoperative Localization (Marking)

Specimen Radiography

GalactographyJ. H. C. L. Hendriks and G. Rosenbusch

PneumocystographyJ. H. C. L. Hendriks and G. Rosenbusch

Computed TomographyJ. H. C. L. Hendriks and G. Rosenbusch

Sonography of the BreastHarmine M. Zonderland

Technical Considerations and Imaging Technique

Technical Considerations

Imaging Technique

Interpretation of Sonographic Images

Normal Anatomy

Lesion Characteristics

Cystic Lesions

Solid Lesions, Benign and Malignant Characteristics

Doppler Sonography

Indications for Sonography

Differentiation between Cystic and Solid Lesions

Indeterminate Mammographic Results

Palpable Lesion Not Visible with Mammography

Nonpalpable Lesion Visible with Mammography

Evaluation of Benign Lesions

Young Patients and Pregnancy

Puerperal and Nonpuerperal Mastitis

The Contribution of Sonography

Summary

Magnetic Resonance ImagingSylvia H. Heywang-Köbrunner and Carla Boetes

Obsolete MethodsJ. H. C. L. Hendriks

Transillumination

Thermography

8 Mammographic Findings and Their Interpretation

Strategy for Viewing the Mammogram

Petra A. M. Bun

Circumscribed Lesions

J. W. Th. Muller

Nodular Lesions

Nodular Lesions with Well-defined Margins

Nodular Lesions with Ill-defined Margin

Stellate Lesions

Mammographically Occult Cancers

Calcifications

Petra A. M. Bun

Analysis of Calcifications

Benign Macrocalcifications

Benign Microcalcifications

Malignant Microcalcifications

Architectural Distortion and Asymmetry

D. J. Dronkers

Changes of the Skin

D. J. Dronkers

Lymph Nodes

D. J. Dronkers

Axillary Lymph Nodes

Intramammary Lymph Nodes

Mammographic Findings after Surgery and Radiation Therapy

Harmine M. Zonderland

Excisional Biopsy and Breast-conservation Therapy

Skin Thickening and Edema

Scar

Hematoma and Seroma

Fat Necrosis and Fibrosis

Radiotherapy

Locoregional Recurrence

Breast Reduction

Breast Augmentation

9 Breast Cancer Screening

D. J. Dronkers, J. H. C. L. Hendriks, B.-P. Robra, and A. L. M. Verbeek

Results of Breast Cancer Screening Programs

European Guidelines

Theoretical Basis for Screening Programs

Operational Models of Mammography Screening

Practical Advice on the Execution of a Screening Program

Interpretation, Double Reading

Radiation Risk

Analysis of Cost–Benefit and Cost-Effectiveness

Interval Cancers

Conclusion

10 Diagnosis of Breast Diseases in Males

Benign and Malignant Changes of the Male Breast

Th. Wobbes and L. V. A. M. Beex

Gynecomastia

Breast Cancer

Mammography of the Male Breast

D. J. Dronkers

11 Retrospective View of Diagnostic Radiology of the Breast

J. H. C. L. Hendriks and G. Rosenbusch

Index

Abbreviations

CC

Craniocaudal

CIS

Carcinoma in situ

DCIS

Ductal carcinoma in situ

FNA

Fine-needle aspiration for cytology

IDC

Invasive ductal carcinoma

ILC

Invasive lobular carcinoma

LCIS

Lobular carcinoma in situ

MLO

Mediolateral oblique

TDLU

Terminal ductal lobular unit

1 Clinical Characteristics of Breast Cancer

Th. Wobbes

To a woman, any change in the breast is cause for concern. The fear of breast cancer makes most breast complaints a great emotional burden on the patient. The omnipresent possibility of breast cancer means that any breast complaint, even if it is only pain or swelling, should be taken seriously. The adage that any lump in the breast is malignant until proven otherwise still holds true today. Modern diagnostic modalities almost always enable the distinction between a benign or a malignant lump, though only histological biopsy can provide the final diagnosis.

To avoid missing a malignancy, it is necessary to know the limitations of the various diagnostic methods.

The typical complaints encountered in daily practice and their underlying clinical findings are summarized in Table 1.1.

Table 1.

1

Typical complaints and specific pathological condition

• Physiologic lumps and tenderness

– Mastalgia (mastodynia)

• Nodularity

• Dominant lumps

– Breast cancer

– Fibroadenoma

– Cysts

• Nipple discharge

• Inflammation and infections

– Lactation

– (Peri-) Subareolar

– Mondor disease

• Skin and nipple changes

– Eczema

– Retraction

– Edema

Physiological Lumps and Tenderness

Mastalgia

During a woman's menstrual years, the breasts are continuously under the influence of cyclic hormonal stimulation. Almost half of all women experience some pain during the luteal phase of their cycle, often associated with some swelling.

The normal nodularity is often rather pronounced, particularly in the upper outer quadrants. This is a physiological condition with no increased incidence of breast cancer. Up to half of women older than 30 years complain of some breast pain (mastalgia) in the period preceding menstruation. This pain is not necessarily accompanied by the nodularity mentioned earlier, and may be diffuse throughout the breasts as well as local in the outer halves. Sometimes the pain is unilateral. Mastalgia is probably caused by parenchymal swelling during the luteal phase of the cycle because of increased water retention (Milligan et al., 1975). This cyclic painful swelling is commonly regarded as physiological, but is reported as something abnormal or pathological in 5% of women. Besides cyclic mastalgia, noncyclic breast pain can be experienced, particularly by women after age 40, and is described as a continuously burning or shooting sensation.

Nodularity

Swelling that may fluctuate with the menstrual cycle is physiological, but some women have a definite nodularity that is always present. The irregular lumps are mostly in the upper outer quadrants and are frequently painful. It is difficult to distinguish a normal finding from a pathological condition. Some consider such a nodularity pathological if it lasts for more than a week (Love et al., 1987). The clinician has to be concerned not to overlook an early carcinoma, although nodularity as such has no direct relationship with the development of a carcinoma. It is difficult to detect a malignancy in these breasts with either palpation or mammography. A discrete palpable lump that does not change during the menstrual cycle should be biopsied and examined histo-logically.

Dominant Lumps

Dominant lumps always need close attention. It is important to realize that breast cancer may present at any age. Fibroadenomas are found particularly in young women (age 20–30 years), and cysts are mostly found in older women (age 35–50 years). In pubertal girls, a giant fibroadenoma is sometimes diagnosed as a palpable firm lump in a unilaterally enlarged breast.

Breast Cancer

Breast cancer presents mostly as a painless lump and is difficult to separate from surrounding tissue. Almost 70% of carcinomas are located centrally or in the upper outer quadrants. Most women have no visible signs of the tumor. Cutaneous changes may occur if the tumor is located just beneath the skin, and nipple retraction is seen if the tumor is located in the nipple area. In addition, skin changes, nipple retraction, and edema (peau d'orange) with or without erythema or red to blue discoloration may be present as signs of cutaneous infiltration. Sometimes even ulceration can be seen. In some patients, breast cancer presents as diffuse induration of the gland, together with some shrinking of the breast. A special manifestation of breast cancer is the inflammatory carcinoma, a locally advanced stage with erythema of the skin, edema, and induration, but without a palpable dominant lump. The erythema is caused by tumorous infiltration of the skin.

If breast cancer is suspected, the regional lymph nodes should be palpated (axilla, supraclavicular and infraclavicular region).

Paget disease of the nipple is an eczematoid change of the nipple, sometimes preceded by itching and/or a pain sensation. This is at least the manifestation of a ductal in situ carcinoma (microcalcifications), and sometimes that of an invasive carcinoma.

Fibroadenoma

The fibroadenoma is a painless, circumscribed, mobile lump, usually measuring not more than 1–3 cm, although a giant fibroadenoma that exceeds 5 cm can occur in young girls. Histologically, the lump consists of both epithelial and stromal tissue. In case of a lump larger than most fibroadenomas found in women who are about 30 years of age, a phyllodes tumor should be considered. This tumor usually is benign but may display malignant behavior.

Cysts

Cysts are found primarily in perimenopausal women. It is frequently difficult to differentiate a cyst from a carcinoma despite its smooth surface. Fluctuation may be felt with superficial cysts. Often, additional cysts can be found in the same breast as a manifestation of cystic disease. Cysts are generally asymptomatic, but rapidly expanding cysts may be painful. A definitive diagnosis can be made by aspirating the contents.

Nipple Discharge

Several types of nipple discharge are encountered in clinical practice. A mostly bilateral milky discharge (galactorrhea) is physiological. A clear, but usually dis-colored (green, black, brown), discharge indicates ectasia of the major subareolar ducts; it also has no pathological significance. A bloody or serosanguinolent discharge may indicate intraductal pathological changes:

• Duct ectasia

• Benign intraductal epithelial proliferations

• Breast cancer.

It is important to search for a palpable lump as indication for an underlying malignant tumor. Mammography may disclose clinically occult pathology by displaying micro-calcifications. A carcinoma is found in not more than 5% of patients with bloody nipple discharge.

Inflammation and Infections

Breast infections are common, especially during lactation. Almost 10% of nursing women encounter a more or less severe infection of the breast, mostly occurring within six weeks after delivery. The infections present with pain, fever, and malaise. While the early phase of the infection might not have visible signs, full-blown mastitis presents with redness and swelling. Fluctuation may be elicited in superficially located abscesses. Antibiotic treatment of mastitis over a longer period of time may mask the abscess, which is then detectable only by sonography.

Out of the lactation period, periareolar or subareolar infections occur and are mostly seen in women between ages 30 and 35 years. The infection is located behind or just around the areola and causes erythema. It is attributed to an obstructed lactiferous duct, and in the early phase there is usually no sign of microorganisms. The infection frequently recurs even with adequate treatment. Smoking seems to be a predisposition. Mastitis is occasionally seen in women with cystic disease and presents clinically as an abscess.

Mondor disease is an inflammation of a superficial vein (thrombophlebitis) and is mostly located in the upper outer quadrant. It occurs primarily in older women. Redness and a cordlike painful infiltration develop along the involved vein. Thrombophlebitis may also be present in other parts of the body.

A special type of inflammation is the inflammatory carcinoma of the breast. This is an aggressive breast cancer that infiltrates the overlying skin. The breast may show redness and feel warmer than the contralateral breast. The skin shows edematous thickening, characteristically presenting as peau d〈orange. In contrast to a true mastitis, this neoplastic manifestation is not associated with fever.

Skin and Nipple Changes

Changes of the skin and/or the nipple may reflect an infection but can indicate an underlying carcinoma.

• Eczema. Eczema of the nipple is called Paget disease. It is usually a manifestation of an underlying malignancy, but a real eczema can occur, mostly arising in the areola. The underlying carcinoma is generally a ductal carcinoma in situ, but invasive breast cancers also may induce this finding.

• Retraction. Retraction of the nipple and/or the skin or asymmetry of the breasts are suspicious for underlying breast cancer. If the tumor infiltrates the underlying muscle, the retraction characteristically appears more pronounced, with muscle contraction or elevation of the ipsilateral arm.

• Edema. Edema of the skin (peau d'orange) is almost always a sign of breast cancer. It frequently is associated with redness.

References

Hughes, L. E., R. E. Mansel, D. J. T. Webster: Benign Disorders and Diseases of the Breast. Baillière Tindall, London 1989

Love, S. M., S. J. Schnitt, J. J. Connolly, R. L. Shirley: Benign breast disorders. In Harris, J. R., et al.: Breast Diseases, Lippincott, Philadelphia 1987 (pp. 15–53)

Milligan, D., J. O. Drife, R. V. Short: Changes in breast volume during normal menstrual cycle and after oral contraceptives. Brit. med. J. 4 (1975) 494–496

2 Anatomy

J. H. C. L. Hendriks, D. J. Dronkers and G. Rosenbusch

The glandular tissue of the breast changes not only during pregnancy and in the lactation period but also, to a lesser degree, during the menstrual cycle. Furthermore, breast tissue undergoes changes over the woman's life. Normal breast anatomy, therefore, exhibits great variation, which is also reflected on mammograms.

The mammary structures are completely developed only after the first full-term pregnancy. In most women, fatty infiltration appears after the first lactation period. The breast arises on the curved thoracic wall and is movable against the major pectoral muscle. The highest mobility is inferior and lateral. This is an essential consideration when positioning the breast for mammography (see p. 101).

Fig. 2.1a, b Glandular and connective tissue with fasciae of the breast

a Schematic drawing

b Galactography with filling of two segments of the lactiferous ductal system

Mammary Gland (Fig. 2.1)

The breast consists of 15–20 lobes or segments, each with one lactiferous duct. Two or three lactiferous ducts unite to form a total of five to eight lactiferous sinuses, which exit at the nipple. On mammograms the lactiferous ducts appear as linear or slightly nodular densities, radiating from the nipple into the breast. The ducts have a diameter of 1–2 mm. Ampullae or lactiferous sinus are local dilatations up to 4 mm of these ducts, just behind the mamilla. The lactiferous ducts are formed by uniting lactiferous ductules. The active secretory glandular tissue is located in the periphery of the breast.

The TDLU (terminal ductal lobular unit) (Fig. 2.2) is the basic histological unit. It consists of the extra- and intralobular terminal ducts and the blind ending acinar ductules. A lobule consists of 25–35 acini. Fibrofatty tissue surrounds the ductular and lobular structures, forming the major component of breast tissue. Cuboid epithelial cells line the ducts. Myoepitheliocytes form a discontinuous layer between lining cuboid cells and basement membrane. The myoepitheliocytes transport the milk through the ducts. The basement membrane separates the epithelial cells from the connective tissue. Evaluation of the basement membrane is important because its interruption by malignant cells means that the carcinoma is invasive. Toward the nipple, the cuboid cells of the ducts change to squamous cells. The lobules measure 0.5 to 1(or 2) mm and are visible on mammo-grams as small nodules as long as they are separated from each other in the encompassing adipose tissue. Superimposition makes them appear confluent, resulting in densities of various sizes and forms. Several hundred lobules form a lobe at the time of sexual maturity.

Fig. 2.2a–cAnatomy of the lobe

a Schematic drawing

b Several TDLUs. Three-dimensional specimen

c A single TDLU (HE)

Fasciae and Connective Tissue

The glandular body is enveloped by the deep and superficial layers of the superficial fascia. A thin layer of loose adipose and connective tissue behind the deep layer provide a connection with the fascia of the pectoral muscle. The connective tissue of the breast consists of interlobular and intralobular components. Cooper ligaments are delicate septa of the superficial layer of the superficial fascia and run through the breast to act as suspensory ligaments for the breast tissue. Along the superficial layer, the Cooper ligaments follow a scalloped course and are anchored in the subcutaneous fatty fibrous tissue and the skin.

Under normal conditions the Cooper ligaments are not thickened and exhibit a regular pattern. The connective tissue determines form and consistency of the breast.

The intralobular connective tissue surrounds the TDLU. It is the active component of the connective tissue. Under hormonal influence of the menstrual cycle it shows edematous changes. It is the zone of ductal growth by cellular proliferation, the site of inflammatory reaction, and the origin of mesenchymal tumors such as fibroadenoma and sarcoma.

The lobules also enlarge in adenosis, sclerosing adenosis, and fibrocystic changes. The single lobules are mammographically visible only along the border of involuted glandular tissue. In the center they look bigger or even may form a homogeneous density due to super-imposition.

The TDLU is the region where most of the benign and malignant tumors originate, apparently related to the functional and morphological changes the cells are subjected to during the menstrual cycle and pregnancy.

Normally the glandular tissue is relatively symmetrical in both breasts, but asymmetry does occur, sometimes requiring further examination. With increasing age the glandular parenchyma is replaced by adipose tissue.

Parenchymal Pattern and Skin Pattern

On the basis of the relative amount of epithelial and connective tissue, J. N.Wolfe (1976) divided the parenchyma on mammograms into four groups (Tab. 2.1), with the groups P2 and DY presumably having a 3–4 times greater cancer risk. The breast density is expressed in percentages on the CC-projection. The parenchymal pattern is almost always symmetrical.

A parenchymal pattern with a higher risk for carcinoma is found more often in nulliparous than in multi-parous women. With increasing number of full-term pregnancies the pattern changes to one with a lower cancer risk.

The skin (epidermis and corium syn. dermis) is 0.5–2 mm thick, and increases inferiorly and at the transition to the axillary fold to 2–4 mm. In the less dense parts of the breast the skin can produce a reticular structure on the mammogram. This is not caused by skin pores but probably by dermal papillae and epidermal ridges (Fig. 2.3). The dermal papillae consist of relatively radiolucent, vascularized connective tissue and the epidermal ridges of less radiolucent, squamous cells around the papillae. The papillae correspond to the central radiolucencies on the mammogram, and the epidermal ridges to the more reticular radiodensities. As the result of the projection geometry, the reticular structure usually originates from the skin nearest to the film.

Table 2.

1

Parenchymal breast pattern classification according to Wolfe (from Byrne and colleagues).

Pattern

Mammographic features

N1

Normal aspect of the breasts, predominantly composed of fat with little, if any, dense areas. Low breast cancer risk. Dense area: 1–25% of the total breast area.

P1

Mainly composed of fatty tissue with dense areas of ductal prominence represented by nodular or linear densities, predominantly in the anterior part of the breast. Dense area: 25–49% of the total breast area.

P2

Dense areas of ductal prominence. P1 and P2 reflect hyperplasia of connective tissue around the ducts. Dense area: 50–74% of the total breast area.

DY

More or less general increase of parenchymal density, with homogeneous sheet–like areas of density, without recognizable ducts. Epithelial changes varying from hyperplasia to atypia. Dense area: > 75% of the total area.

Fig. 2.3a–cReticular structure on mammogram

a Papillae of the corium, which are anchored in grooves of the epidermis, causing the reticular structure on mammograms. Schematic drawing

b Oblique view of the left breast

c Detail of (b) with the reticular structure

Arteries, Veins, Lymphatics

The arterial supply of the breast is derived from branches of the subclavian artery (internal mammary artery), axillary artery (lateral thoracic artery and intercostal arteries. Smaller branches often run along the major lactiferous ducts and form a capillary network around the lobules. Larger arteries can be seen on mammograms as linear densities that do not converge toward the nipple. Calcified vascular walls occur exclusively in arteries. Veins cross the breast as bands of 2–4 mm thickness.

Veins have a larger diameter in the upper outer quadrant than in the other quadrants. The superficial veins run in the subcutaneous fat and the deep veins are more deeply situated. The veins carry the blood mainly to the axillary vein (Fig. 2.4).

The more cellular and vascularized stroma contains lymph vessels (Fig. 2.5), which are not visible on mammograms. Their drainage occurs deeply in the glandular tissue into regional lymph nodes, at least in 75% into the axillary lymph nodes and in the rest into parasternal lymph nodes (intrathoracic). An additional superficial lymphatic system with subareolar plexus is part of the subcutaneous plexus of the thoracic wall. The deep and superficial systems are connected. Intramammary lymph nodes can be found in 25% of anatomic breast specimens, but only 5% are seen on mammograms, more often in the upper outer quadrant than in the other quadrants. Multiple occurrence is possible. By definition, intramammary lymph nodes have to be surrounded by fibroglandular tissue to differentiate them from axillary lymph nodes. On mammograms, intramammary lymph nodes display the typical appearance of lymph nodes: they are less than 0.5 to 1 (or 1.5) cm in diameter and, depending on the projection, they are oval or round. A small recess corresponds to the hilum. In the absence of the recess, fibroma, cyst, hemangioma, and carcinoma have to be considered. A central radiolucency within a lymph node (“fatty degeneration”) is a sign of benignity. The fatty content can enlarge the lymph node and its length can exceed 1.5 cm.

Fig. 2.4Veins of the breast

1 Anonymous vein

2 Axillary vein

3 Thoracoepigastric vein

4 Internal mammary vein

5 Intercostal veins with perforating veins

Fig. 2.5Regional lymph nodes and lymphatic drainage of the breast (according to Bässler)

1 Deep cervical nodes

2 Infraclavicular nodes

3 Nodes along the axillary vein

4 Axillary nodes

5 Nodes to the abdominal wall

6 Parasternal nodes (intrathoracic location)

Intramammary lymph nodes can be metastatically involved. Metastases to the intramammary lymph nodes do not necessarily imply involvement of the axillary lymph nodes.

Physiological Changes of the Breast

• One to two years before menarche, enlargement of the breasts begins by an increase in connective tissue. With menarche, the gland buds branch and a greater number of TDLUs are formed. The TDLUs enlarge by proliferation of the epithelial cells that line the ducts of TDLUs.

• In young women before the first pregnancy, the lobules are not fully developed and fatty infiltration is low. The breasts consist mainly of connective tissue, and mammography shows homogenously dense breasts.

• At menopause, the glandular tissue involutes. The intralobular and interlobular connective tissue also becomes atrophic. At first the lower inner quadrant involutes, then the upper inner quadrant and finally the lower outer and upper outer quadrants. This occurs relatively symmetrically. In the sixth decade, the atrophy progresses and fat tissue becomes dominant. As the lactiferous ducts do not involute, they become more visible in the more adipose breasts. During hormone replacement therapy, the involution of the glandular tissue reverses to some extent in about 20% of women, indicating a reactivation of the mammary tissue.

• During the first half of pregnancy, the synergic effect of several hormones (estrogen, progesterone, prolactin) leads to growth and further branching of the TDLUs, with proliferation of the acini. The acini cells are cuboid and become columnar during lactation. They produce milk, which is secreted in the ductules. After lactation the epithelial cells resume their cuboid shape. In the growth period, i.e., the first half of the pregnancy, the enlargement of the breast reflects hypertrophy of the glandular cells and distension of the ductules caused by increased secretion. The breasts are very dense on mammograms, with the structures blurred and difficult to evaluate.

• During the menstrual cycle the breast also undergoes changes: early in the cycle the epithelial cells of the acini are reduced and form a more or less solid cord. Later in the cycle the cells of the acini become cuboid, a lumen appears and the connective tissue is more strongly vascularized. In the premenstrual phase, the breast may be tender. Proper compression might fail and the mammographic examination is best deferred until mid-cycle.

Embryology and Anomalies

In the second fetal month, an ectodermal ridge, the milk line, develops ventrolaterally at both sides of the fetus, running from the axilla to the groin. Buds branch out from the milk line. One bud on each side, usually the fourth bud, develops to form the breast and the milk line disappears, but supernumerary buds can remain and later appear as supernumerary nipples (hyperthelia) or breasts (hypermastia, polymastia). Typically, the super-numerary nipples are arranged along the original milk line (Fig. 2.6).

Accessory breast tissue. In about 2–3% of women, accessory mammary tissue occurs inferiorly or superiorly in the axilla as the axillary tail (or axillary process, tail of Spence). This accessory tissue has a duct, which drains into the ductal system of the major gland. Affected women notice an atypical intumescence during pregnancy as evidence of an axillary process. Accessory breast tissue rarely occurs below the breast. Caution: Accessory breast tissue should not be mistaken for a tumor, but may well harbor a cancer.

Accessory breast tissue seems to involute later than the breast itself and might then simulate a tumorlike process on the mammogram.

Besides the mentioned excess formations, defective breast development may occur.

Defective developmental anomalies

• Amastia (absence of the breast)

• Athelia (absence of the nipple, in the presence of mammary tissue)

• Micromastia (hypoplasia; bilateral symmetrical hypoplasia is found in gonadal dysgenesis with Turner syndrome)

• Anisomastia (unequally sized breasts by uni-lateral hypoplasia or macromastia)

Fig. 2.6Schematic drawing of the embryonal milk line, where accessory mammary tissue can occur

Fig. 2.7a, b Schematic drawing of the axillary process (tail of Spence)

Fig. 2.8Ectopic glandular tissue cranially in the left breast

References

Bässler, R.: Mamma. In Remmele, W.: Pathologie Band 3. Springer, Berlin 1984

Barth, V.: Die Feinstruktur der Brustdrüse im Röntgenbild. Thieme, Stuttgart 1979

Byrne, C., Schairer, C., Wolfe, J., Parekh, N., Salane, M., Brinton, L.A., Hoover, R.N., Haile, R.: Mammographic features and breast cancer risk: effects with time, age and menopause status. Journal of the National Cancer Institute 87 (1995) 1622–1629.

Cyrlak, D., C. H. Wong: Mammographic changes in post-menopausal women undergoing hormonal replacement therapy. Amer. J. Roentgenol. 161 (1993) 1177–1183

Egan, R. L.: Breast embryology, anatomy and physiology. In Eagan, R. L.: Breast Imaging: Diagnosis and Morphology of Breast Diseases. Saunders, Philadelphia 1988

Gils, van C. H., J. D. M. Otten, A. L. M. Verbeek, J. H. C. L. Hendriks: Short communication: breast parenchymal patterns and their changes with age. Brit. J. Radiol. 68 (1995) 1133–1135

Meyer, J. E., F. A. Ferraro, T. H. Frenna, P. J. DiPoro, C. M. Denison: Mammographic appearance of normal intramammary lymph nodes in an atypical location. Amer. J. Radiol. 161 (1993) 779–780

Osborne, M.: Breast development and anatomy. In Harris, J. R., et al.: Diseases of the Breast. Lippincott, Philadelphia, 1996 (pp. 1–14)

Page, D. L., T. J. Anderson: Diagnostic Histopathology of the Breast. Churchill Livingstone, Edinburgh 1987

Wellings, S. R., H. M. Jensen, R. G. Marcum: A hypothesis of the origin of human breast cancer from the terminal ductal lobular unit. Pathol. Res. Pract. 166 (1975) 515–535

Wolfe, J. N.: A study of breast parenchyma by mammography in the normal woman and those with benign and malignant disease of the breast. Radiology 89 (1967) 201–205

Wolfe, J. N.: Breast patterns as an index of risk for developing breast cancer. Amer. J. Radiol. 126 (1976) 1130–1139

Wolfe, J. N., A. F. Saftlas, M. Salane: Mammographic parenchymal patterns and quantitative evaluation of mammographic densities: a case-control study. Amer. J. Radiol. 148 (1987) 1087–1092

3 Benign and Malignant Disorders of the Breast

R. Holland, G. Rosenbusch, J. H. C. L. Hendriks, andD. J. Dronkers

Benign Disorders

The breast can develop a variety of benign disorders. Some are easily recognizable as benign by mammography, whereas others may resemble breast cancer. The most important benign disorders will be described.

Fibrocystic Disease

Fibrocystic disease (synonyms: mastopathy, fibroadenosis, mastopathia cystica fibrosa, dysplasia) includes various changes of the breast that differ only slightly from the normal aging process and are often characterized by hyperplasia of the parenchymal tissue.

Fibrocystic Changes of the Breast

• Cysts

• Epitheliosis

• Adenosis

• Radial scar.

Cysts

Cysts are classified by their size as microcsysts or macro-cysts. Microcysts have a diameter of 3–5 mm. Secretion accumulates due to inadequate resorption by the epithelium or obliteration of the terminal duct by fibrosis or epithelial hyperplasia, leading to increased pressure in the TDLU (Fig. 3.1). With increasing size, adjacent acini become involved, and larger cysts may develop. The cysts are lined with flattened epithelium, often showing apocrine metaplasia.

Macrocysts

These cysts may reach 6–10 cm in diameter and are unilocular or multilocular. They are filled with cloudy or milky fluid that may contain calcium particles, which appear mammographically round (Fig. 3.2) or amorphous granular. With time, the color of the fluid of the cyst may change from bright yellow or bright green to black due to denaturation of the protein in the fluid. The cyst's contents then become hygroscopic, causing the cyst to be under tension. If the cyst ruptures, the denatured protein in the escaped fluid may induce a sterile inflammatory reaction of the stroma.

Fig. 3.1a–c Development of cysts

a TDLU. Initial dilation of lobule due to hypersecretion. 3-D preparation

b Multiple microcysts and a duct with fibrocystic changes. 3-D preparation

c Multiple cysts and fibrocystic changes. 3-D preparation

Fig. 3.2a, b Calcifications in cysts

a Microcysts with one solitary laminated calcification.

b Cysts with multiple crystalline calcifications

Larger cysts under high tension (tension cysts) are palpable and may become painful due to further fluid accumulation during the premenstrual phase. This occurs in about 7% of women diagnosed with cysts. Cysts may spontaneously decrease in size or even disappear, mainly around the menopause. Mammographically, the solitary larger cysts are round or oval, depending on their tension, and are well demarcated. A thin radiolu-cent zone (the so-called halo) is often visible around the cysts, representing compressed fat tissue or the Mach effect. Calcifications may appear in the walls of larger cysts.

Sonography usually provides quick and reliable information as to whether a mammographically detected mass is a cyst or a solid lesion: a cyst should be well-defined, lack internal echoes, and demonstrate dorsal acoustic enhancement due to increased transmission.

Microcysts

Mammographically, multiple small cysts (microcysts) produce a nodular image. It is only possible to differentiate these cysts from adenosis when they contain so-called “milk of calcium,” which consists of numerous small calcium particles. On the CC view, the milk of calcium appears as round calcific densities (Fig. 3.3a). On the MLO view, it presents as upward concave, crescentic calcific densities due to sedimentation along the bottom of the cyst (described by Lányi as “teacup phenomenon”) (Figs. 3.3b, 8.15).

Fig. 3.3a, b Diffusely distributed calcifications in micro-cysts (“milk of calcium”)

a CC view with punctate calcifications

b ML view with sedimentary microcalcifications, resulting in levels (so-called “teacup phenomenon”)

Fig. 3.4a–g Schematic representation of the types of adenosis (according to Lányi)

a Normal lobule

b Simple adenosis

c Blunt duct adenosis

d Small or microcystic adenosis

e Advanced small or microcystic adenosis

f Tension cyst

g Sclerosing adenosis

Epitheliosis

Epitheliosis (synonyms: ductal epithelial hyperplasia, papillomatosis) is an abnormal proliferation of epithelial and also myoepithelial cells within the ducts of the TDLU. The proliferating epithelial cells fill the lumen partly or entirely. The morphological features of some of these intraductal epithelial proliferations might be close to but not fully identical with those of a DCIS (so-called atypical ductal hyperplasia [ADH]). These lesions must be differentiated from DCIS. Epitheliosis, ADH, simple adenosis and blunt duct adenosis do not induce any mammographic signs.

Adenosis

Adenosis (Fig. 3.4) refers to an increase in the number of the acini within the lobules, which is sometimes associated with hyperplasia of the epithelial and myoepithelial cells. The hyperplasia develops in a relatively orderly way, or may be dominated by one of the components.

Types of adenosis

• Simple adenosis

• Blunt duct adenosis

• Microglandular (microcystic or small cystic adenosis)

• Sclerosing adenosis

Simple Adenosis

In simple adenosis, the size and number of lobules are increased and the normal structure becomes accentuated. The lobules are about 1 mm in diameter.

Blunt Duct Adenosis

In blunt duct adenosis, proliferations in small ducts lead to dilation with hyperplasia of myoepithelial cells. Epitheliosis may exist at the same time and calcium may precipitate. The lobules measure about 1–2 mm.

Microglandular (microcystic or small cystic) Adenosis

In microglandular adenosis, the glandular parenchyma proliferates within the fibrous and adipose tissue, leading to cystic dilation of the terminal ductules (acini). Mammographically, 3–5 mm nodular densities are visible. A differentiation from microcysts can be made by sonography or identified mammographically by calcium content.

Sclerosing Adenosis

Sclerosing adenosis represents sclerosis around the ductules of the hyperplastic lobule and resultant luminal narrowing. This distorts the architecture on the microscopic level. Lumps are rarely palpable. Mammographically, this disorder shows an irregular density, a stellate lesion or a well-defined density, sometimes with typical small round calcifications.

Radial Scar

The radial scar (synonyms: radial sclerosing lesion, complex sclerosing lesion, non-encapsulated sclerosing lesion, benign sclerosing ductal proliferation) consists of a fibrotic core with radiating extensions. Different benign proliferations may be encountered within a radial scar.

Benign proliferations

• Sclerosing adenosis

• Cyst

• Obliterated ducts due to epitheliosis

• Ductal ectasia

Histologically, it may be difficult to differentiate the center of a radial scar from an invasive tubular carcinoma. For this reason, frozen sections should not be obtained from a mammographically suspected radial scar. The mammogram (Fig. 3.5) shows a stellate density without a distinct center, often containing radiolucent areas caused by adipose deposition or small cysts. Microcalcifications are rare. The differential diagnosis from invasive tubular carcinomas is almost impossible. The lesion is not palpable (see p. 212).

Fig. 3.5a–c Radial scar

a Stellate lesion without a central dense core. Relatively thin and long spicules. Magnification view

b True size of histological specimen

c The central part of the radial scar with benign adenosis resembling a tubular carcinoma, especially in frozen sections, leading to erroneous diagnosis and possible overtreatment

Benign Tumors

Fibroadenoma

Fibroadenoma is the most common circumscribed breast lesion before menopause. It occurs in more than 25% of all women, most frequently in the third decade. Pregnancy and lactation stimulate growth, and the lesion tends to regress during menopause. The lesion is a fibroepithelial proliferation and may lead to a palpable, elastically compressible, sometimes lobulated, freely movable tumor. The fibroadenoma varies in size (mostly 1–5 cm) (Fig. 3.6), can be painful, mostly occurs uni-laterally (bilaterally in only 3–5% of cases), and is generally solitary, rarely multiple (10–17%). Fibroadenomas tend to become hyalinized and calcified, especially during menopause. Malignant change of a fibroadenoma is rather rare (1/1000 cases) and, if it occurs, it usually becomes a LCIS and very seldom a DCIS.

Mammographically, the fibroadenoma is round or oval, but can be lobulated, and is well defined. Calcifications are mostly coarse (“popcornlike”). Local blurring of the margin and spicules due to hyalinization can make the differentiation from a carcinoma difficult. The differential diagnosis includes the also well-defined mucinous and medullary carcinoma and a cyst. Sonography with core biopsy or fine-needle aspiration is needed for further evaluation.

Phyllodes Tumor

The phyllodes tumor (synonym: cystosarcoma phyllodes) differs from the fibroadenoma by a hypercellular stroma with characteristic epithelium-lined clefts. It occurs mainly in the fourth to fifth decade. These tumors are usually big, solitary and unilateral, and show rapid growth. Most phyllodes tumors are benign, but they tend to recur after incomplete resection. Metastases are found in about 3–12% of cases. Mammographically, phyllodes tumors are homogeneously dense, well defined and without calcifications. They may grow to 2–6 cm in size. Mitoses > 10/10 HPF (high power field) suggest malignancy, while mitoses < 3/10 HPF suggest a benign process.

Intraductal Papilloma

The intraductal papilloma (synonym: papillary adenoma) is a benign, often branching proliferation of the epithelium within a major mammary duct. Histologically, it has a fibrovascular center covered with a layer of epithelial cells. The papilloma may fill the duct completely and lead to retained secretion and ductal ectasia, resulting in a palpable lump. The solitary intraductal papilloma occurs most frequently toward the end of the fifth decade, is located in the subareolar region, manifests itself by serous or bloody nipple discharge, and may lead to sclerosis, calcification, and infarction. The multiple intraductal papilloma (papillomatosis) causes nipple discharge in only 20% of all cases, is located mostly peripherally and more often bilaterally, and occurs in women around the age of 40 years.

The solitary papilloma is a lesion with a low cancer risk, while papillomatosis has a higher cancer risk and may progress to a DCIS. Since an intraductal papilloma is only a few millimeters in diameter, it may at most induce a minor dilation of a retromamillary duct. When the papilloma reaches a certain size, it may appear as a longitudinal nodular density on the mammogram. Papillomas may also develop in cysts (Fig. 3.7).

Fig. 3.6a, b Giant fibroadenoma

a Well-defined homogeneous round density on the MLO view

b Excised tumor after sectioning

Fig. 3.7a, b Intracystic solid lesion

a Well-defined round density on the MLO view

b Intracystic proliferation on ultrasound. Histology: benign papilloma

Juvenile Multiple Intraductal Papilloma

The juvenile multiple intraductal papilloma (synonym: juvenile papillomatosis) occurs predominantly in young women (around the age of 20 years). It produces a palpable tumor and is unilaterally located. It is assumed to have precancerous potential.

Lipoma

Lipoma is soft at palpation and therefore difficult to define. Mammographically, it is a radiolucent round or lobulated mass. The tumor is enveloped by a pseudo-capsule and is easily recognized.

Fibroadenolipoma

Fibroadenolipoma (FAL) (synonym: hamartoma) is a mixed tumor showing features both of lipoma and fibroadenoma. Mammographically, the encapsulated radiolucent adipose tissue is traversed by densities caused by fibroglandular elements.

Rare Benign Tumors

Rare benign tumors of the breast

• (Adeno-) Myoepithelioma

• Juvenile fibroadenoma

• Lactating adenoma

These lesions appear mammographically as round opacifications and lack any characterizing features.

Inflammation and Abscesses

Inflammations. Acute mastitis mainly occurs during lactation (mastitis puerperalis) and easily is diagnosed clinically. The causative organism usually is Staphylococcus aureus haemolyticus. Acute mastitis unrelated to lactation is caused by inadequate draining resulting in retained secretion. It can even be seen in menopause (retention mastitis). Because of the increased parenchymal density, skin thickening, and enlarged axillary lymph nodes, the mammographic findings of mastitis may simulate breast cancer (mastitis carcinomatosa).

Abscesses. Abscesses appear mammographically as nodular densities with spicules or ill-defined margins. Treatment with antibiotics and puncture/drainage is effective, resulting in quick resolution.

Duct Ectasia

Chronic inflammation of the walls of the major mam-mary ducts and their adjacent tissue (periductal mastitis) (synonyms: plasma cell mastitis, mastitis obliterans) leads to dilation of the ducts through weakening of the walls, including loss of elasticity. Only one segment may be involved. Furthermore, papillomas or DCIS can cause duct ectasia. The secretion thickens, the walls become fibrotic, and the duct eventually obliterates (mastitis obliterans). Duct ectasia mainly occurs during menopause and may cause nipple retraction. Galactorrhea is observed in 20% of cases and patients may complain of retromamillary pain, but most patients are clinically asymptomatic. Any association with a breast carcinoma is incidental. Mammographically, the dilated, thickened mammary ducts appear in the retromammillar region as serpentine tubular structures, which converge toward the nipple.

Through periductal inflammatory reaction and fibrosis, duct ectasia evolves to plasma cell mastitis with histological predominance of plasma cells. Calcifications appear in the retained secretion within the dilated ducts and in their walls. The mammogram shows linear, well-defined, needlelike macrocalcifications, which may branch (Fig. 8.17). These calcifications can in the majority of cases be differentiated from the linear branching calcifications seen in DCIS. These comedo calcifications are irregular, smaller and of different densities.

Mondor Disease

Mondor disease is a local thrombophlebitis of the thoracoepigastric vein and its branches. The disease occurs between the ages of 20 and 55 years and usually affects the upper outer portion of the breast. A painful pencil-like thrombophlebitic cord is palpable immediately under the skin. A longitudinal retraction of the skin along the obliterated vein is pathognomonic. Most cases resolve spontaneously. The typical mammographic finding consists of a superficially located, often beadlike linear density. A carcinoma can be excluded by sonography (Fig. 8.43b).

Hematoma

A hematoma may develop after needle biopsy, surgical procedure, or trauma (e.g., caused by safety belts in motor vehicle accidents). It also occurs spontaneously in thrombocytopenia and during anticoagulant therapy.

The mammographic finding of a hematoma is an ill-defined diffuse density. In advanced stages a hemorrhagic cyst can evolve, which has a higher density than a simple cyst due to the hemoglobin content. Spicules or microcalcifications as seen in a carcinoma are not present. The lesion regresses spontaneously, leaving behind scarring, distortion, or calcifications.

Fat necrosis

Fat necrosis may develop after needle biopsy, surgical biopsy, or trauma (see Hematoma) and may be solitary or multiple. Local destruction of adipose cells forms viscous lipidic fluid, in which giant cells and foamy histiocytes develop. The mammographic findings depend on the morphological stage. Fibrotic reaction in a later stage produces an ill-defined opacity that may simulate a carcinoma. When a central cavity is formed and filled with oily material, an oil cyst is present. The oil cyst has a thin capsule around a radiolucent center. Curvilinear calcifications in the wall or dystrophic calcifications are not infrequently seen. A fat necrosis located relatively close to the skin may cause retraction of the overlying skin.

Carcinoma in Situ and Invasive Carcinoma

It is essential to differentiate noninvasive cancer (CIS) from invasive cancer (Fig. 3.8) because of the difference in management. If invasive cancer is present, assessing the state of the axillary nodes is usually the next diagnostic step. It is generally assumed that all invasive cancers develop from noninvasive precursors (CIS), but not every CIS may progress to an invasive carcinoma in the patient's lifetime.

Carcinoma in Situ

Carcinoma in situ (CIS) of the breast is a preinvasive carcinoma characterized by proliferation of malignant-appearing cells found in either ducts (DCIS) or lobules (LCIS), without invasion of the surrounding connective tissue at histological examination, that is, the basement membrane of the duct or lobule is not interrupted. Excluding small areas of invasion requires careful review of the slides and, even then, the risk of sampling error remains due to unrecognized sites of microinvasion. This explains the nodal metastases found in about 1% of patients with the diagnosis of a DCIS.

Ductal Carcinoma in Situ (DCIS)

In the past, DCIS (synonym: intraductal carcinoma) was an incidental diagnosis (3–5% of breast malignancies), mainly diagnosed in patients with nipple discharge or a palpable lump. Presently, screening mammography has made it a much more frequent diagnosis due to the detection of microcalcifications in clinically occult cases (15–20% of all malignancies detected by screening). Morphologically, DCIS is not a homogeneous disease but comprises a heterogeneous group of changes with differences in morphology and biological behavior (Table 3.1). The division into comedo- and non-comedo DCIS was an improvement, but is still inadequate because it reflects only the predominant growth pattern of the lesion and not its biological behavior. The term comedo is used for intraductal carcinoma with solid growth pattern and central necrosis. Pressure on the sectioned specimen can extrude necrotic tumor material like comedos on the skin. However, necrosis may also occur in other types of DCIS with various architectures.

Fig. 3.8a–e Schematic representation of ductal and lobular carcinoma (according to Bässler)

a Noninvasive ductal carcinoma

b Noninvasive ductal carcinoma with Paget disease (Paget carcinoma)

c Invasive ductal carcinoma

d Ductal carcinoma with involvement of the lobule

e Invasive lobular carcinoma

Subdivision of non-comedo CIS

• Cribriform

• Micropapillary

• Solid

• Other types

The following classification was proposed on the basis of the cytonuclear and architectural differentiation and the biological behavior (Holland et al., 1994).

Poorly differentiated DCIS (Fig. 3.9). This consists of poorly differentiated cells containing pleomorphic nuclei, which show marked variation in size and shape. The nuclei have irregular contours, coarse clumped chromatin, and prominent, sometimes multiple, nucleoli. Mitoses are often evident. The architectural differentiation (cellular polarization) is usually absent. The cellular growth pattern is generally solid, but can be pseudo-cribriform and pseudo-micropapillary. A central necrosis often appears in the intraductal tumor cords, frequently with amorphous calcifications in the necrotic material.

Table 3.

1

Features of DCIS

• DCIS is to be differentiated from infiltrating ductal carcinoma by the absence of histopathologic stromal invasion through the basement membrane.

• Incidence increases with the large-scale use of screening mammography.

• Not all lesions that are incompletely excised progress to invasive lesions.

• Lesions are almost always unicentric, arising in one area and not in two separated areas, however, the lesions can be very extensive.

• Treatment of regional lymph nodes is not necessary.

• DCIS refers to lesions with heterogeneous features:

– histological

– radiological

– biological

(From EORTC Consensus Meeting 1992)

On the mammogram, the calcifications are linear (Fig. 3.10), branching, or coarse granular. The affected ducts often dilate and show extensive periductal fibrosis and lymphocytic reaction. Poorly differentiated DCIS has no recognizable pre-existing condition. Poorly differentiated DCIS has a high malignant potential, and most cases progress to a poorly or intermediately differentiated invasive ductal carcinoma (IDC).

Well-differentiated DCIS (Fig. 3.11). Well-differentiated DCIS is composed of cells with monomorphic, evenly arranged small nuclei, which contain fine chromatin, no suspicious-appearing nucleoli, and only few mitoses. The cells have a well-defined apex and show a definite polarization, with the apex oriented toward the ductal lumen, producing a cribriform, micropapillary or rosettelike pattern. Calcifications are not associated with necrosis. If calcifications are present, they are formed by crystallization in extracellular secretory material. Mammography shows clustered microcalcifications, which are usually fine and granular and appear benign. These clusters are often multiple. The well-differentiated DCIS possibly develops from atypical hyperplasia. It is more often found together with invasive tubular, invasive lobular, and well-differentiated IDC. Not every well-differentiated DCIS will lead to an invasive cancer. Such a progression may take many years.

Fig. 3.9a–d Poorly differentiated DCIS

a Initial tumor development in duct epithelium

b Advanced tumor proliferation with obstruction of the ductal lumen

c The central part of the DCIS shows necrosis

d Poorly differentiated DCIS with continuous spread in the duct system. 3-D preparation

Intermediately differentiated DCIS. This category is composed of intermediately differentiated cells, with features intermediate between the other two groups. The nuclei of the cells are not as pleomorphic as they are in the poorly differentiated group. Shape, size, and irregular outline show moderate variation. Mitoses are rare. The architecture may be solid or nonsolid. An additional feature differentiating this group from the poorly differentiated category is the presence of polarization of cells, with orientation toward the intercellular spaces. Necrosis may or may not be present. Calcifications, when present, may be crystalline within secretions or amorphous particles within necrotic material. Mammo-graphically, these calcifications are coarse granular or fine granular, but can be linear.

DCIS is almost always unicentric and segmental in distribution. Large lesions often involve the subareolar region. Mammographically, DCIS is usually detected by the microcalcifications but in few cases also by increased density. As microcalcifications are not in all parts of the DCIS, the mammographic extent is usually smaller than the true histopathological extent. In the study of Holland et al., (1994), about 15–20% of cases were found to have a difference of more than 2 cm between mammographic and histological extent.

Lobular Carcinoma in Situ (LCIS)

Lobular carcinoma in situ is a proliferation of small cells in the acini within a lobule. The cells have small round or oval nuclei. The cells fill and distend the ductules, occluding the lumen. The delineation from a well-differentiated solid DCIS is sometimes difficult. LCIS is often an incidental histological finding diagnosed in surgical specimens since it is not recognizable clinically or mammographically. It is multicentric in about 70% of cases, and bilateral in 30%. LCIS often occurs in the premenopausal phase.

The cumulative risk of progression into an invasive carcinoma is 1% per year. Both breasts are at almost equal risk. The cancer may not only be the invasive lobular type (ILC), but can also be the invasive ductal type (IDC).

Fig. 3.10a–d Calcifications in poorly differentiated DCIS

a Coarse calcifications in the necrotic part of the DCIS, filling the entire duct (HE and von Kossa staining)

b Linear and coarse granular calcifications. Only calcifications are visible (von Kossa staining). This also shows deposits of very fine “calcium dust” in the necrotic material adjacent to the calcifications

c The same specimen as (b), with additional HE staining. The calcifications emerge from the necrotic areas of the DCIS. Their shape is irregular. The powdery calcium deposits around the calcifications are responsible for the slightly ill-defined outline of the calcifications on the mammogram

d Specimen radiograph. Multiple linear branching and coarse granular calcifications, typical of poorly differentiated DCIS

LCIS does not have any typical mammographic features. If microcalcifications have prompted the biopsy, calcifications are usually also found outside the LCIS.

Invasive Breast Cancer

Most invasive breast cancers are adenocarcinomas of the ductal or lobular type (Fig. 3.12).

Other invasive carcinomas

• Tubular carcinoma

• Medullary carcinoma

• Mucinous (colloid) carcinoma

• Papillary carcinoma

Table 3.2 shows the histopathologically distinguishable types of invasive cancer.

Invasive Ductal Carcinoma (IDC)

Three-quarters of all invasive breast cancers are an IDC. In IDC, tumor cells proliferate not only in the ducts, as in DCIS, but also in the tissue surrounding the ducts. Macroscopically, IDC is often lobulated with spicules radiating from its center, producing a stellate configuration on the mammogram. The spicules consist not only of tumor cells but also of connective tissue (Fig. 3.13