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The female breast produces milk from glands located in the lobule.  These lobules drain into a system of ducts which lead to larger ducts called the lactiferous sinus which ultimately drain to the nipple.   The ductal epithelial cells are responsive to hormones, the most important being estrogen and progesterone.  The pathologist is often called to the operating room to perform a frozen section upon a breast lesion.  A small portion is taken, frozen, and cut in a microtome.  These thin slices are then placed on a microscope slide, stained, and analyzed under the microscope.  Depending upon the pathologist's diagnosis, a more extensive surgery may be avoided or carried out. The pathologist is also responsible for evaluating the hormone receptor status of all breast cancers.  By using immunohistochemical studies, antibodies directed against hormone receptors to estrogen and progesterone can be utilized and the results quantified.  These results are used by the oncologists to plan future chemotherapy.

Male breast diseases are covered in another section.

Normal Anatomy and Histology
Microscopic Photo-Normal Breast
Microscopic Photo-Normal Breast

Breast Cancer General
Breast Cancer Genes (BRCA1 and BRCA2)
Breast Cancer Prognosis
Breast Cancer Treatment
Cystic Hypersecretory Hyperplasia
Ductal Carcinoma in Situ (DCIS)
Fibrocystic Changes (Disease) (Sclerosing adenoisis, radial scar)
Juvenile Papillomatosis
Lobular Carcinoma in Situ (LCIS)
Male breast diseases (Gynecomastia and cancer)
Nevoid Hyperkeratosis of the Nipple and Areola
Paget's disease of the nipple
Phyllodes tumor
Proliferative Breast Disease (Atypical Lobular and Ductal Hyperplasia)
Pseudoangiomatous Stromal Hyperplasia (PASH)


Disease Associations  
Laboratory/Radiologic/Other Diagnostic Testing  
Histopathological Features and Variants  
Special Stains/
Electron Microscopy
Differential Diagnosis  
Commonly Used Terms  
Internet Links  



Cyclosporine and the Development of Multiple Mammary Nodules

Cristina Caetano Stefenon, MD,* Roberto de Oliveira Lima, MD, and Ana Luiza Gualandi Murad, MD

The Breast J 2002;8:177 Abstract quote

We report here the case of an immunosuppressed patient who developed multiple nodules in both breasts while on cyclosporine therapy.

In this case, the benign appearance on imaging and benign clinical course made possible conservative management, thus avoiding invasive diagnostic procedures. For evaluation of these nodes, after cyclosporine was discontinued, the nodules involuted.



Benign-Appearing Mammographic Abnormalities in Women Aged 40-49

Murray H. Seltzer, MD,* and Jill R. Glassman, Ph.D.

Breast J 2002;8:162 Abstract quote

The ongoing debate was addressed concerning the appropriateness of mammographic screening for women aged 40-49 years, with particular emphasis on those patients with benign-appearing mammographic abnormalities (BMA), and whether findings differed from those of successive age decades.

A review was conducted of 2,482 patients presenting for surgical consultation with a mammographic abnormality as a chief complaint, with particular emphasis on the 1,632 patients with BMA and more specifically those aged 40-49 years. Surgical interventions and risk factors for breast cancer were evaluated. Although 16 of 393 patients with BMAs biopsied were proven to have breast cancer, only 2.7 of all patients with BMAs were found to have breast cancer as a result of biopsy or short-term follow-up. Women aged 40-49 years represented 48 of patients with BMAs, and only 1.5 of these patients had breast cancer. The finding of breast cancer in the BMA population was progressive by decade of age, as would be expected, and in a cut-point analysis of those biopsied, age 60 best divided patients into high- and low-risk groups.

Women aged 40-49 years with BMAs should not be excluded from mammographic screening, as they represented part of a continuum when successive decades were compared. Efforts should be directed at minimizing patient and physician anxieties as well as diagnostic interventions related to a BMAs.


Biopsy of amorphous breast calcifications: pathologic outcome and yield at stereotactic biopsy.

Berg WA, Arnoldus CL, Teferra E, Bhargavan M.

Department of Radiology (W.A.B., C.L.A., E.T.) and Greenebaum Cancer Center (W.A.B.), University of Maryland, 419 W Redwood St, Suite 110, Baltimore, MD 21201

Radiology 2001 Nov;221(2):495-503 Abstract quote

PURPOSE: To assess the pathologic outcome of amorphous breast calcifications and the success of stereotactic biopsy for such lesions.

MATERIALS AND METHODS: From July 1995 through February 2000, biopsy of all clustered amorphous calcifications not clearly stable for at least 5 years or in a diffuse scattered distribution was recommended. Logistic regression analysis was used to stratify the risk of malignancy by patient risk factors, calcification distribution, and stability.

RESULTS: Calcifications were retrieved from 150 biopsies; 30 (20%) proved malignant and included 27 ductal carcinomas in situ and three low-grade invasive and intraductal carcinomas (2-5 mm). Another 30 (20%) yielded high-risk lesions, including 21 atypical ductal hyperplasia, eight atypical lobular hyperplasia, and one lobular carcinoma in situ. In 150 lesions, stereotactic biopsy was performed on 113 and aborted in 10. Calcifications were retrieved from all 113 stereotactic biopsies. Of those with calcification retrieval, there were three histologic underestimates (accuracy, 97%). Stereotactic biopsy spared a surgical procedure in 57 (46%) of 123 patients. Needle localization was required for 23 (15%) of 150 patients due to poor conspicuity. Five (45%) of 11 biopsies performed in women with ipsilateral breast cancer showed malignancy (P =.025). When multiple lesions of amorphous calcifications were present in one breast, sampling of one reliably predicted the outcome of others.

CONCLUSION: We found a substantial rate of ductal carcinoma in situ and high-risk lesions associated with amorphous calcifications. Stereotactic biopsy can be successfully performed for the majority of subtle amorphous calcifications; however, only a minority were spared a surgical procedure.


The pathology of breast biopsy site marking devices.

Guarda LA, Tran TA.

From the Department of Pathology, Florida Hospital Medical Center, Orlando, FL.

Am J Surg Pathol. 2005 Jun;29(6):814-9. Abstract quote  

This report presents our experience with 54 cases of patients who had excision of breast lesions after deployment of radiographic biopsy site markers at the time of stereotactic biopsy.

These were of two types: pellets of a resorbable copolymer of polylactic acid/polyglycolic acid (31 cases) and plugs of bovine collagen (23 cases), both containing embedded metallic clips for long-term radiographic marking.

On gross examination, the pellets have a characteristic appearance similar to a soft grain of rice, whereas the collagen plugs are spongiform with variable hemorrhagic changes. Microscopically, there are distinct differences in the morphologic features of these two types of biopsy site markers and the associated tissue reactions. With the pellets, there is an initial cell-poor fibrotic reaction around empty spaces followed by a multinucleate giant cell reaction and penetration of the marker core by eosinophilic fibrinous material. The collagen plugs are recognized as eosinophilic, hyalinized, acellular material, accompanied by an inflammatory infiltrate composed predominantly of lymphocytes, plasma cells, eosinophils and, occasionally, neutrophils, which penetrate the core of the marker with time.

The degradation of the collagen plug appears to be associated with infiltration of the marker by fibrovascular tissue and deposition of native collagen; of note is the absence of a significant multinucleate giant cell reaction. These novel breast biopsy site markers do not interfere with the histologic processing of the tissue or with their histopathologic interpretation.

Reappraisal of breast hamartomas. A morphological study of 41 cases.

Charpin C, Mathoulin MP, Andrac L, Barberis J, Boulat J, Sarradour B, Bonnier P, Piana L.

Department of Pathology Hopital de la Timone, Marseille, France.

Pathol Res Pract 1994 Apr;190(4):362-71 Abstract quote

Mammary hamartomas are breast disorders currently underestimated and not well recognized. Forty-one hamartomas diagnosed among 5,834 breast biopsies, histologically examined during the last 7 years, are reported. Hamartomas accounted for 1.2% of benign lesions and 4.8% of benign breast tumors.

Clinically, hamartomas were revealed by breast palpable lump, usually painless. Typically, but inconsistently, mammography showed sharply circumscribed density, separated from adjacent normal breast by a thin radiolucent zone. Macroscopically, hamartomas were slightly larger and softer than common adenofibromas, were well limited, whitish, pinkish and fleshy, with yellow islands of fat tissue. Histologically, hamartomas exhibited pushing borders with a pseudoencapsulation, and consisted of a combination of variable amount of stromal and epithelial components. Stromal components mainly consisted in a prominent fibrohyalin feature usually associated to small islands of adipose tissue and edematous changes. Epithelial structures showed variable features of benign breast disease.

The overall architecture was lobulated but not nodular. The histological diagnosis was mainly a diagnosis of exclusion and hamartomas diagnosis relies on clinical, radiological and pathological criteria. Hamartomas result more from breast dysgenesis than from tumorous process.



Morphological Changes in Breast Tissue with Menstrual Cycle

Rathi Ramakrishnan, M.D. (Path.), Seema A. Khan, M.D. and Sunil Badve, M.D., F.R.C.Path.

Departments of Surgery (RR, SAK) and Pathology (SB), Northwestern University Medical School, Chicago, Illinois and Department of Pathology, Indiana University School of Medicine (SB), Indianapolis, Indiana

Modern Pathology 2002;15:1348-1356 Abstract quote

Whether the breast tissue undergoes morphologic changes in relation to the menstrual cycle had been a subject of debate. Elegant studies performed in the early 1980s provided conclusive evidence of cyclical changes in the normal breast lobules. These studies were almost entirely based on autopsy material and have not been validated in the clinical setting.

In the present study, we examine breast tissues from surgical specimens from 73 premenopausal women and use morphological criteria to characterize the stage of the menstrual cycle. Patients taking oral contraceptives or hormonal therapy were excluded from this study.

The following histological parameters were used to assess the menstrual stage: number of cell layers in the acini and presence and degree of vacuolation of the myoepithelial cells, stromal edema, infiltrate, mitosis, and apoptosis. The morphological stage was then correlated with the stage of the cycle, as determined by last menstrual period and the usual menstrual cycle length and in some patients with serum estrogen and progesterone levels.

The morphologic stage was concordant with dates in 54 of the 73 patients (74%, P = .001). In 31 of these patients, serum levels of estradiol and progesterone at the time of surgery were available for correlation. Twenty-five (80%) of these were phase concordant by morphology and progesterone levels (P = .01), and 25 (80%), by dates and progesterone levels (P = .007). Women with a high morphologic score were seven times as likely to be in luteal phase as were women with a low score (odds ratio, 7.1; 95% confidence interval).

Menstrual phase can be determined by the morphology of the normal lobules present within the surgically excised breast specimens. This will permit retrospective analysis of large archival databases to analyze the effect of timing of surgery in relation to menstrual cycle phase. It will also aid the design of epidemiological studies for breast cancer risk assessment.

Practical Considerations in the Pathologic Diagnosis of Needle Core Biopsies of Breast

Syed A. Hoda, MD, and Paul Peter Rosen, MD

Am J Clin Pathol 2002;118:101-108 Abstract quote

The success of needle core biopsy procedures and the validity of pathologic diagnoses made on material from the procedures are key determinants in planning the optimal management of a wide variety of breast diseases.

The most common diagnostic problems encountered in these biopsy specimens include lobular and ductal proliferations, sclerosing and papillary lesions, cellular fibroepithelial tumors, and minimally invasive or microinvasive carcinoma.

This review provides practical guidance to help narrow the differential diagnosis of lesions on needle core biopsies and offers guidelines for the pathologic reporting of these specimens.

Pathologic Findings in Reduction Mammaplasty Specimens

Mona T. Ishag, MD, Dmitry Y. Baschinsky, MD, Irina V. Beliaeva, Theodore H. Niemann, MD, and William L. Marsh, Jr, MD
Am J Clin Pathol 2003;120:377-380 Abstract quote

Reduction mammaplasty (RM) is a common surgical procedure that yields a variable amount of tissue for pathologic examination. Occult breast carcinomas are detected rarely in these specimens.

We evaluated the pathologic findings in RM specimens performed in our institution during an 11.5-year period (July 1989 to December 2000). A total of 560 patients who had undergone RM were identified, 503 bilateral and 57 unilateral. The average number of blocks submitted per breast was 3.9 (range, 1-23). Pathologic changes were present in 338 cases (60.4%). Unsuspected carcinomas (small invasive carcinomas, 3; ductal carcinoma in situ, 1) were found in 4 cases (0.7%). Atypical ductal and/or atypical lobular hyperplasia were identified in 8 cases (1.4%).

Lesions associated with a mildly increased carcinoma risk (moderate/florid ductal hyperplasia, sclerosing adenosis, and papilloma) were identified in 52 cases (9.3%). Other findings included fibrocystic changes, fibrosis, mild ductal hyperplasia, fibroadenoma, and adenosis. Pathologic examination of RM specimens provides important clinical information and should be performed routinely.

Histological findings in breast tissue specimens from reduction mammoplasties.

Karabela-Bouropoulou V, Liapi-Avgeri G, Iliopoulou E, Agnantis NJ.

Department of Pathology, KAT Regional General Hospital, Kiphissia, Greece.

Pathol Res Pract 1994 Sep;190(8):792-8 Abstract quote

Tissue specimens from 55 consecutive reduction mammoplasty operations were studied histologically for changes considered to be associated to an increased risk in the development of invasive breast cancer. A thorough sampling of all removed tissues was performed and nearly all solid parts were processed for histological evaluation.

We found that in 47 specimens, most of which belonged to women younger than 40 years of age (39), both breasts presented either no-proliferative changes or mild hyperplastic lesions of the usual type and thus the women had no increased risk for breast cancer development.

In 7 breast specimens, all of them from women older than 30 years, the changes observed ranged from florid hyperplasia to atypical ductal or lobular hyperplasia, which are lesions considered to be associated to a relatively increased risk of invasive carcinoma.

Finally we present a case of infiltrative ductal carcinoma with extensive lesions of atypical hyperplasia and combined ductal and lobular carcinoma in situ in both breasts, which developed 3 years after reduction mammoplasty in which changes of atypical hyperplasia were found.

We suggest that reduction mammoplasty specimens should be handled with particular care and according to the women's age.



Expression of PC-cell-derived growth factor in benign and malignant human breast epithelium.

Serrero G, Ioffe OB.

Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy and Program in Oncology, Marlene and Stewart Greenebaum Cancer Center of the University of Maryland, Baltimore, Maryland, USA.
Hum Pathol. 2003 Nov;34(11):1148-54. Abstract quote  

PC-cell-derived growth factor (PCDGF, progranulin) is a novel autocrine growth factor that is overexpressed in human breast cancer cell lines. We have examined immunohistochemical PCDGF expression in 206 paraffin-embedded human breast lesions and investigated its association with clinicopathological variables. PCDGF staining was observed in breast carcinoma, whereas it was almost always negative in benign breast epithelium.

PCDGF expression was more common in invasive ductal carcinoma (80% cases positive) than in invasive lobular carcinoma (53% positive). PCDGF staining was almost never observed in lobular carcinoma in situ. Ductal carcinoma in situ expressed PCDGF in 66% of the cases, and this expression correlated strongly with nuclear grade. Similar correlation was observed between PCDGF expression and histologic grade of invasive ductal carcinoma. Average Ki-67 index of PCDGF-negative/weakly positive invasive carcinomas (30.3) was significantly lower than that of strongly PCDGF-positive tumors (48.8, P=0.01). A larger percentage of tumors that expressed PCDGF with a staining intensity of 2+ or 3+ were p53 positive (44%) than were PCDGF-negative tumors (25%), P=0.02. PCDGF expression was independent of c-erbB-2 overexpression and of ER and PR status. Our study provides the first evidence of high incidence of PCDGF expression in human breast cancer in which it correlates with clinicopathological variables such as tumor grade, proliferation index, and p53 expression.

These characteristics, as well as the virtual absence of expression in benign breast tissue, suggest an important role of PCDGF in breast cancer pathogenesis and make it a potential novel target for the treatment of breast cancer.

Surfactant Protein A Expression in Human Normal and Neoplastic Breast Epithelium

Paola Braidotti, DSc,1 Claudia Cigala, MD,1,2 Daniela Graziani, DSc,1 Barbara Del Curto, DSc,1 Enrico Dessy, MD,3 Guido Coggi, MD,1,2 Silvano Bosari, MD,1,2 and Giuseppe G. Pietra, MD4

Am J Clin Pathol 2001;116:721-728 Abstract quote

We studied the presence of surfactant protein A (Sp-A) immunoreactivity and messenger RNA in 62 normal and abnormal breast samples.

Sections were immunostained with polyclonal anti–Sp-A antibody. The association between Sp-A immunoreactivity and histologic grade of 32 invasive ductal carcinomas was assessed by 3 pathologists who scored the intensity of Sp-A immunoreactivity times the percentage of tumor immunostained; individual scores were averaged, and the final scores were correlated with tumor grade, proliferative index, and expression of estrogen and progesterone receptors. Strong Sp-A immunoreactivity was present at the luminal surface of ductal epithelial cells in normal breast samples and in benign lesions; carcinomas displayed variable immunoreactivity, inversely proportional to the degree of differentiation. Sp-A messenger RNA was detected by reverse transcriptase–polymerase chain reaction in 3 of 3 normal breast samples and 9 of 9 carcinomas.

The significance of Sp-A expression in breast epithelium requires further study; possibly it has a role in native host defense or epithelial differentiation.


BREAST TUMORS IN CHILDREN The differential diagnosis of tumors in adults usually centers around fibrocystic disease and carcinoma. Carcinoma is seen in less than 1% of all mammary carcinomas diagnosed in patients less than 25 years of age. In the adolescent and child, the spectrum of disease includes the former diseases as well as diseases primarily seen in this age group. The following chart
Fibroadenoma 166 (44)
Gynecomastia 81 (22)
Macromastia (juvenile hypertrophy) 52 (14)
Fibrocystic changes 19 (5)
Soft tissue tumors 18 (4.5)
Tubular adenoma 10 (3)
Cysts, including galactocele 8 (2)
Lactating adenoma 5 (1)
Cystosarcoma phyllodes 4 (1)
Papillary ductal hyperplasia 4 (1)
Juvenile papillomatosis 3 (1)
Abscess 1 (<1)
Fat necrosis 1 (<1)
Papillary carcinoma 1 (<1)
Nipple duct adenoma 1 (<1)
Soft tissue tumors Soft tissue tumors includes the following:
Granular cell tumors
Low-grade angiosarcoma
Myoid hamartoma
High grade stroma sarcoma
Metastastic alveolar rhabdomyosarcoma
Giant cell fibroblastoma

Semin Diagn Pathol 1999;16:235-247
Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

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Last Updated June 6, 2005

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