Background

This is the most common benign tumor of the female breast. It is most common during the reproductive years, favoring age below 30 yrs. It presents as a well-circumscribed nodule that is freely movable from the surrounding breast. Its size varies from a few millimeters to 10-15 cm. The tumor is hormonally responsive and may vary in size during pregnancy and the menstrual cycle.

This tumor is a true neoplasm with cytogenetic studies identifying clonal rearrangements within the stromal and not the epithelial component. It arises form the intralobular stroma.

Under the microscope, the tumor is a well circumscribed tumor with a mildly cellular stroma surrounding glandular spaces lined by a single to a few layers of benign epithelial cells. The tumor has been characterized as pericanalicular and intracanalicular types but mixed types are common. In general, the stroma shows no cytologic atypia and mitotic figures are few. If these findings are not present, consideration should be given for a phyllodes tumor.

This is a benign tumor but rarely carcinoma may develop within it. The most common type is lobular carcinoma in situ although ductal carcinoma in situ and invasive ductal carcinomas have also been reported.

OUTLINE

Epidemiology
Pathogenesis
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Differential Diagnosis
Prognosis
Treatment
Commonly Used Terms
Internet Links

EPIDEMIOLOGY	CHARACTERIZATION
Menstrual cycle patterns and the risk of breast disease. La Vecchia C, Decarli A, di Pietro S, Franceschi S, Negri E, Parazzini F.	Eur J Cancer Clin Oncol 1985 Apr;21(4):417-22 Abstract quote The relationship between menstrual cycle patterns and the risk of breast disease was evaluated using data from a hospital-based case-control study of 288 women with benign breast disease (203 chronic cystic diseases and 85 benign tumours), 317 with breast cancer and 602 age-matched controls with a spectrum of acute conditions unrelated to any of the established or potential risk factors for breast disease. A lifelong irregular menstrual pattern [defined as frequent occurrence of menstrual-like episodes of bleeding less than 21 or more than 35 days apart) was negatively associated with the risk of benign breast lesions (relative risk, RR = 0.6, with 95% confidence interval = 0.4-1.0) and of breast cancer (RR = 0.4, with 95% confidence interval = 0.3-0.8]. This inverse association could not be explained by any of the identified potential confounding factors, including the major risk factors for breast disease. The findings of this study, showing that a lifelong history of irregular (and hence more likely anovular) cycles was less frequent among women with benign and malignant breast diseases, support the hypothesis that frequent ovular cycles might be more carcinogenic than anovular ones.
Risk factors for breast fibroadenoma in young women. Sitruk-Ware R, Thalabard JC, Benotmane A, Mauvais-Jarvis P. Department of Reproductive Endocrinology, Hopital Necker, Paris, France.	Contraception 1989 Sep;40(3):251-68 Abstract quote In a case-control study, 178 women diagnosed with fibroadenoma (FA) between 1976 and 1982 were compared with 178 age-matched controls in order to assess the risk factors for FA. Women who had a previous diagnosis of breast disease were excluded. The odds ratios (OR) of FA were calculated for different risk factors of breast disease from bivariate analysis as well as multivariate regression analysis. The highest ORs were found for a previous premenstrual mastalgia before first childbirth and a familial history (FH) of breast cancer (BC). Oral contraceptive (OC) use before a first full-term pregnancy (FFTP) does not modify this risk. Also current use of standard oral contraceptives (SOC) containing 50 micrograms of ethinyl estradiol per pill appeared to be protective and the correlation with FA was negative. These findings underline: (a) the predictive value of premenstrual mastalgia for the subsequent development of breast disease; (b) only current high-dose OC use is protective.
Risk factors for fibroadenoma: a case-control study in Australia. Yu H, Rohan TE, Cook MG, Howe GR, Miller AB. Epidemiology Unit, National Cancer Institute of Canada, University of Toronto, Ontario, Canada.	Am J Epidemiol 1992 Feb 1;135(3):247-58 Abstract quote Risk factors for fibroadenoma were examined in a case-control study involving 117 fibroadenoma cases ascertained by a major private pathology laboratory in Adelaide, Australia, between January 1983 and October 1985. For each case a population control was randomly selected from the electoral roll in Adelaide and matched to the corresponding case by sex, age, and socioeconomic grading of area of residence. Another 189 women whose first biopsy for benign breast disease was examined in the same laboratory during the same time period as those of the cases, but did not show evidence of epithelial proliferation, were also included in the study as a biopsy control group. Risk of fibroadenoma was associated inversely with the Quetelet index, but there was no evidence of an association with age at menarche or menopausal status. The risk of fibroadenoma decreased with an increasing number of full-term pregnancies and was increased in association with use of oral contraceptives at an early age (under 20 years); however, these two associations were observed only when cases were compared with the population controls. Alcohol consumption and dietary fat intake were found not to be associated with altered risk of fibroadenoma, while in multivariate analyses, duration of cigarette smoking and daily vitamin C intake were both shown to have inverse associations with risk of fibroadenoma. Although fibroadenoma does share some risk factors with breast cancer, there is insufficient evidence to suggest that it represents a precursor state.

 

PATHOGENESIS	CHARACTERIZATION
EPSTEIN-BARR VIRUS
Epstein-Barr virus infection is not associated with fibroadenomas of the breast in immunosuppressed patients after organ transplantation. Lau SK, Chen YY, Berry GJ, Yousem SA, Weiss LM. Department of Pathology, City of Hope National Medical Center, Duarte, California 91010, USA.	Mod Pathol. 2003 Dec;16(12):1242-7 Abstract quote.   Epstein-Barr virus has been linked to an increasing number of nonhematolymphoid conditions. Epstein-Barr virus was recently described in association with fibroadenomas of the breast occurring in immunosuppressed patients. To further investigate the potential association of Epstein-Barr virus with fibroadenoma in the context of immune dysfunction, 11 cases of fibroadenoma of the breast in immunosuppressed organ transplant recipients were examined. Cases were evaluated for the presence of Epstein-Barr virus by polymerase chain reaction, in situ hybridization, and immunohistochemical methods. The presence of Epstein-Barr virus genomic DNA was studied by polymerase chain reaction amplification using primers flanking the BamHI-W fragment of the Epstein-Barr virus genome, as well as the Epstein-Barr virus nuclear antigen-4 and latent membrane protein-1 genes. Cases were also evaluated for the presence of defective heterogeneous Epstein-Barr virus DNA. In addition, morphologic analysis by in situ hybridization for Epstein-Barr virus-encoded RNA-1 and immunohistochemistry for latent membrane protein-1 were performed. Epstein-Barr virus DNA was detected in 4 of 11 (36%) cases with BamHI-W polymerase chain reaction. Polymerase chain reaction studies for Epstein-Barr virus nuclear antigen-4 and latent membrane protein-1 genes were positive in two and four cases, respectively. No defective Epstein-Barr virus genomes were identified in any of the cases. Quantitative polymerase chain reaction demonstrated low levels of Epstein-Barr virus in the fibroadenomas studied. Despite the detection of Epstein-Barr virus genomes in a subset of the cases examined, the constituent epithelial and stromal components of all fibroadenomas demonstrated no evidence of Epstein-Barr virus-encoded RNA-1 by in situ hybridization or latent membrane protein-1 expression by immunohistochemistry. Rare Epstein-Barr virus-encoded RNA-1-positive lymphocytes were observed in some cases, which may account for the positive polymerase chain reaction results. The findings of the present study argue against a significant relationship between Epstein-Barr virus and fibroadenomas of the breast in the setting of transplant-associated immunosuppression.
Detection of Epstein-Barr virus in rapidly growing fibroadenomas of the breast in immunosuppressed hosts. Kleer CG, Tseng MD, Gutsch DE, Rochford RA, Wu Z, Joynt LK, Helvie MA, Chang T, Van Golen KL, Merajver SD. Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.	Mod Pathol 2002 Jul;15(7):759-64 Abstract quote Fibroadenomas are the most common benign tumors of the female breast and are associated with a slight increase in the risk of subsequent breast cancer. Multiple fibroadenomas have been described in patients after renal transplantation and are thought to be secondary to drug-related growth stimulation. Epstein-Barr virus (EBV) has been detected in many neoplasms, including breast cancer. We set out to investigate whether EBV plays a role in the development of rapidly growing fibroadenomas in immunocompromised patients. We studied 19 fibroadenomas and one invasive ductal carcinoma that developed after organ transplantation or treatment for lupus erythematosus. As a control group we included 11 fibroadenomas from non-immunocompromised patients. DNA was amplified using polymerase chain reaction (PCR) of the EBV-encoded small RNA (EBER-2) DNA sequence. EBV latent membrane protein 1 (LMP-1) transcripts were amplified using reverse transcription (RT) PCR. Immunohistochemical (IHC) staining for LMP-1 protein was performed. A total of 9 out of 20 tumors (45%) were concordantly positive by PCR and IHC. IHC stained exclusively the epithelial cells. All the fibroadenomas in non-immunocompromised patients were negative for LMP-1 (Fisher's exact test P =.0006). These data suggest that EBV is associated with fibroadenomas in this immunosuppressed population and that the infection is specifically localized to epithelial cells. This is the first study suggesting a role for EBV in the pathogenesis of fibroadenomas.
ESTROGEN RECEPTOR-BETA
Estrogen receptor-beta is expressed in stromal cells of fibroadenoma and phyllodes tumors of the breast. Sapino A, Bosco M, Cassoni P, Castellano I, Arisio R, Cserni G, Tos AP, Fortunati N, Catalano MG, Bussolati G. 1Department of Biomedical Science and Human Oncology, University of Torino, Torino, Italy.	Mod Pathol. 2006 Apr;19(4):599-606. Abstract quote   An estrogen dependency has been suggested for the growth of fibroadenomas: however, thus far, none of the steroid hormone receptors acting on breast tissues has been demonstrated in the stroma of breast fibroepithelial lesions. In this study, the expression of estrogen receptor (ER)-alpha and -beta was investigated by immunohistochemistry in 33 fibroadenomas and in 30 benign, three borderline and seven malignant phyllodes tumors, all with spindle cell growth and in one distant metastasis. In addition, the presence of ER-beta mRNA and its variants was evaluated by RT-PCR in microdissected stroma. The possible correlation between hormone receptor expression and differentiation processes of stromal cells was investigated by smooth muscle actin and calponin immunostaining. ER-beta was the only hormone receptor expressed by stroma of fibroadenomas and phyllodes tumors, both at protein and mRNA level. The highest percentage of ER-beta was observed in fibroadenomas with cellular stroma and in phyllodes tumors. In both lesions, ER-beta-positive stromal cells showed expression of smooth muscle actin and/or calponin, as demonstrated by double immunostaining. In addition, the mean age at diagnosis was significantly lower in patients with ER-beta-positive vs ER-beta-negative fibroadenomas. In contrast, in phyllodes tumors, ER-beta expression was higher in older patients. In conclusion, (i) only ER-beta is detected in the stroma of fibroadenomas and phyllodes tumors; (ii) its expression correlates with the expression of smooth muscle markers and suggests a role of ER-beta in myofibroblastic differentiation of stromal cells. These two results, together with the young age of patients carrying fibroadenomas with highly ER-beta-positive stroma cells, may further indicate a hormone-receptor mechanism involved in regulating the growth of fibroadenomas. Conversely, the older age of patients with ER-beta-rich phyllodes tumors suggests that mechanisms, probably independent from estrogen stimulation, act on the growth of these tumors.

 

VARIANT	CLINICAL	HISTOPATHOLOGY
Fibroadenomatoid hyperplasia	No mass	Histologically identical changes of a fibroadenoma without mass effect
Tubular adenoma	Similar to fibroadenomas	Composed predominately of proliferating tubules with little intervening stroma
Lactating adenoma	Seen during pregnancy	Similar to tubular adenoma with lactational changes present within the tubules
Juvenile fibroadenoma	Similar to fibroadenomas, more common during adolescence May be bilateral or multiple and may recur several times	Pericanalicular growth pattern and prominent epithelial hyperplasia Mild degree of stromal overgrowth but no cellular atypia and only rare mitotic figures
Giant fibroadenoma	Large fibroadenomas usually greater than 10 cm	Term has fallen out of favor and not used

 

OTHER GROSS OR CLINICAL VARIANTS	CHARACTERIZATION
EYELID
Fibroadenoma of the Eyelid Liron Pantanowitz, M.D.; Stephen Lyle, M.D., Ph.D.; Steven R. Tahan, M.D.	Am J Dermatopathol 2002; 24(3):225-229 Abstract quote Extramammary fibroadenomas have been previously reported to mainly occur in the anogenital region, arising from mammary-like glands. The present report describes a 45-year-old woman who presented with a fibroadenoma of her eyelid that was associated with a cystadenoma. To our knowledge, this is the first case report of a fibroadenoma of the eyelid. The differential diagnosis and histogenesis of this lesion are discussed, and the literature pertaining to cutaneous fibroadenomas arising outside the breast is reviewed.

 

HISTOLOGICAL TYPES	CHARACTERIZATION
General
Histopathology of Fibroadenoma of the Breast Arno Kuijper, etal.	Am J Clin Pathol 2001;115:736-742 Abstract quote The aim of this study was to make a thorough inventory of the histologic features of epithelium and stroma within and adjacent to breast fibroadenomas in 396 cases. Breast fibroadenomas seemed to display a wide spectrum of proliferative and nonproliferative histologic changes. Hyperplasia (excluding mild hyperplasia) within the fibroadenoma was found in 32.3% of cases. Carcinoma in situ (CIS; 5 ductal, 3 lobular) was found in 8 fibroadenomas (2.0%) removed from 6 patients, the youngest of whom was 40 years of age. In 3 cases CIS was not confined to the fibroadenoma, but also involved the adjacent parenchyma. No invasive carcinoma was present within this series. Complex histologic features were seen in 40.4% of cases, mostly in relatively older patients (mean age, 35.4 years). Hyperplasia in adjacent tissue was found in 8.8% of cases, usually in older patients (mean age, 45.5 years). Known risk-elevating lesions in and around breast fibroadenomas occur frequently and mostly in patients older than 35 years. These findings may have consequences for the clinical management of a subgroup of patients with fibroadenoma.
VARIANTS
INFARCTION
Infarction of breast fibroadenoma in a postmenopausal woman. Ichihara S, Matsuyama T, Kubo K, Tamura Z, Aoyama H. Department of Pathology, Nagoya National Hospital, Japan.	Pathol Int 1994 May;44(5):398-400 Abstract quote Infarction of a breast fibroadenoma usually occurs in young females during pregnancy or lactation. This report describes a rare case of the total infarction of a fibroadenoma in a 58 year old postmenopausal woman. The chief complaint was a rapidly enlarged, slightly painful lump. Medullary carcinoma was suspected on palpation and mammography. Microscopically, the tumor was composed of a coarsely lobulated necrotic mass invaginated into an epithelial lined cyst. This was interpreted as an infarcted intracanalicular fibroadenoma, although the possibility of an infarcted phyllodes tumor cannot be entirely excluded. The significance of this rare event is the possible confusion with carcinoma. Extensive search for viable tissue is essential for the confirmation of the diagnosis.

 

DIFFERENTIAL DIAGNOSIS	KEY DIFFERENTIATING FEATURES
ADENOMYOEPI-THELIOMA
Adenomyoepithelioma: clinical, histologic, and immunohistologic evaluation of a series of related lesions. McLaren BK, Smith J, Schuyler PA, Dupont WD, Page DL. From the Departments of Biostatistics and Pathology, Vanderbilt University Medical Center, Nashville, TN.	Am J Surg Pathol. 2005 Oct;29(10):1294-9. Abstract quote   Adenomyoepithelioma, strictly defined, is a proliferation of both epithelial and myoepithelial elements. The broad range of lesions that may fall under this umbrella, however, may be quite diverse. The diagnostic confusion surrounding this entity and its prognostic implications have led to a diagnosis by default as malignant and to overtreatment of some patients. We evaluated available material from a series of 35 women whose slides were seen in consultation and who were diagnosed with adenomyoepithelioma or a closely related lesion. This comprehensive review of the varied histology of adenomyoepithelioma and similar lesions and their immunohistochemical properties will assist general pathologists in evaluating these sometimes difficult lesions. Follow-up and treatment information demonstrates their benignity. Architecture and histologic features should be combined with immunohistochemistry when determining categorization.
Adenomyoepithelioma of the breast. A review of three cases with reappraisal of the fine needle aspiration biopsy findings. Ng WK. Department of Pathology, Pamela Youde Nethersole Eastern Hospital, 3 Lok Man Road, Chai Wan, Hong Kong.	Acta Cytol. 2002 Mar-Apr;46(2):317-24. Abstract quote   OBJECTIVE: To describe the fine needle aspiration cytology findings of adenomyoepithelioma of the breast, with histologic correlation. STUDY DESIGN: The author reviewed the cytologic findings of three cases of adenomyoepithelioma of the breast in the files of Pamela Youde Nethersole Eastern Hospital in a three-year period, 1998-2000. The diagnosis was confirmed by histologic examination, immunohistochemical study and electron microscopy. RESULTS: All cases showed similar cytologic findings. The direct smears and cytospin preparations contained an obvious biphasic cell population. There were clusters and sheets of benign apocrine cells admixed with clumps of bland-looking oval to spindle cells. The apocrine cells contained larger, round nuclei; prominent solitary nucleoli; and ample eosinophilic, granular cytoplasm. In contrast, the spindle cells had oval nuclei, fine chromatin, inconspicuous nucleoli and scanty amphophilic cytoplasm. A small number of named nuclei and foamy macrophages was noted in the background. The characteristic stromal elements seen in fibroepithelial tumor of the breast were not found. The myoepithelial nature of the spindle cells was confirmed by immunohistochemical and ultrastructural studies. Subsequent simple mastectomy and wide local excision were performed on cases 1 and 2, respectively, revealing focal carcinomatous transformation in the adenomyoepitheliomas. The carcinoma cells, however, were not sampled in the initial cytologic specimens. CONCLUSION: The cytologic features of adenomyoepithelioma, though variable and subtle, are characteristic enough for diagnosis. Recognition of the peculiar combination of benign apocrine cells and clumps of nondescript spindle cells should alert the cytologist to this rare but distinct entity, which carries a propensity for malignant transformation.
PHYLLODES TUMOR
Fibroepithelial Lesions With Cellular Stroma on Breast Core Needle Biopsy Are There Predictors of Outcome on Surgical Excision? Timothy W. Jacobs, MD, etal.	Am J Clin Pathol 2005;124:342-354 Abstract quote Fibroepithelial lesions with cellular stroma (FELCS) in breast core needle biopsy (CNB) specimens may result in either fibroadenoma or phyllodes tumor at excision. We evaluated histologic features, proliferation indices (by Ki-67 and topoisomerase II a immunostaining) and p53 expression in 29 cases of FELCS in CNB specimens and correlated these with excision findings in a blinded manner. On excision, 16 patients had fibroadenomas and 12 had phyllodes tumors. All CNB specimens with mildly increased stromal cellularity were fibroadenomas on excision (n = 4), and all with markedly cellular stroma were phyllodes tumors (n = 4). Among CNB specimens with moderate cellularity (12 fibroadenomas and 8 phyllodes tumors), only stromal mitoses were discriminatory histologically. Stromal proliferation indices were significantly higher in CNB that were phyllodes tumors vs fibroadenomas. Assessment of stromal cellularity, mitoses, and proliferation indices might help determine the probability of phyllodes tumor occurring and guide management of these cases.
Distinction of phyllodes tumor from fibroadenoma: a reappraisal of an old problem. Krishnamurthy S, Ashfaq R, Shin HJ, Sneige N. Department of Pathology, University of Texas, MD Anderson Cancer Center, Houston 77030, USA.	Cancer 2000 Dec 25;90(6):342-9 Abstract quote BACKGROUND: Using fine-needle aspiration (FNA) smears, it is difficult to distinguish low grade phyllodes tumor (PT) from fibroadenoma (FA) due to overlapping cytologic features between the two lesions. The authors retrospectively studied 45 histologically proven fibroepithelial breast tumors of which 33 were FA and 12 were PT (1 malignant, 8 borderline, and 3 benign) to define cytologic features that can help in the accurate categorization of these lesions by using FNA samples. METHODS: The cytologic features analyzed included: 1) epithelial component for number (<5 or >5), architecture, apocrine metaplasia, squamous metaplasia, nuclear pleomorphism, and mitosis; 2) stromal fragments for number (<5 or >5), cellularity (on a scale of 1+ to 3+), borders, cell characteristics, nuclear pleomorphism, and mitosis; 3) individual dispersed stromal cells in the background for cellularity (on a scale of 1+ to 3+), and cellular shape (short/round/oval or long spindle) based on whether they were smaller or larger than 2 times the size of a small round lymphocyte. RESULTS: The mean age of patients with FA was 34 years and of those with PT 44 years. The average size of FA was 2.0 cm, and the average size of PT was 4.0 cm. The characteristics of the epithelial fragments of PT and FA were not significantly different. Stromal fragments were noted in 60% of FA and 83% of PT samples examined. Fifty-six percent of PT and 30% of FA exhibited hypercellular stromal fragments (3+ cellularity), and the difference was not statistically significant. Large club-shaped hypercellular stromal fragments were present only in FA (in 21% of the samples). There was no difference in the overall cellularity of the background stromal nuclei in the two types of lesions. Long spindle nuclei averaging greater than 30% of the dispersed stromal cell population in the background were found only in cases of PT (in 57% of the samples; P < 0.001). Short/round/oval nuclei characterized most FAs. Long spindle nuclei constituting 10-30% of the dispersed stromal cells, however, occurred in both PT and FA to the extent of 43% and 21%, respectively. CONCLUSIONS: Hypercellular stromal fragments occur not only in PT, but also in FA, and hence they cannot be used as the sole criterion for making a diagnosis of PT on FNA. The proportion of individual long spindle nuclei (>30%) amid the dispersed stromal cells in the background is the most reliable discriminator between the two lesions. Lesions in which long spindle nuclei constitute between 10% and 30% may represent either PT or FA, and therefore such lesions should be categorized as indeterminate on FNA.

 

PROGNOSIS AND TREATMENT	CHARACTERIZATION
PROGNOSIS
FIBROADENOMA WITH ADH
No elevation in long-term breast carcinoma risk for women with fibroadenomas that contain atypical hyperplasia. Carter BA, Page DL, Schuyler P, Parl FF, Simpson JF, Jensen RA, Dupont WD. Department of Laboratory and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.	Cancer 2001 Jul 1;92(1):30-6 Abstract quote BACKGROUND: The authors previously showed that women with a fibroadenoma have a relative risk of invasive breast carcinoma of approximately 2.0 compared with women of similar age from the general population. This relative risk approaches 1.0 when family history and proliferative changes in the adjacent parenchyma are removed and rises to > 3.0 if the fibroadenoma has complex histology. The risk for developing breast carcinoma in women with atypical lobular hyperplasia (ALH) and atypical ductal hyperplasia (ADH) or their minimal variants within a fibroadenoma is unknown. METHODS: The authors conducted a long-term, retrospective cohort study of 1834 women with adequate follow-up who presented with fibroadenoma at three local hospitals between 1950 and 1968. Histology was reviewed using established criteria, and the patients were categorized with ALH, ADH, minimal atypia, or no atypia. RESULTS: The overall prevalence of ALH or ADH within fibroadenomas was 0.81%. Minimal or true atypia within a fibroadenoma appeared to be correlated with proliferative disease in the adjacent parenchyma but could not predict for the presence there of well-established atypia. Only 7% of women with well-developed atypia developed invasive carcinoma on follow-up. Three women with minimal atypia developed invasive carcinoma. CONCLUSIONS: In this study of a large cohort of women with fibroadenoma, the authors found that atypia within a fibroadenoma cannot predict for the presence of atypia within adjacent breast parenchyma. They also found that atypia confined to a fibroadenoma does not incur a clinically meaningful risk of future breast carcinoma development greater than that of fibroadenoma alone.
INVASIVE CARCINOMA RISK
Incidence of breast cancer in women with fibroadenoma. Levi F, Randimbison L, Te VC, La Vecchia C. Registre vaudois des tumeurs, Institut universitaire de medecine sociale et preventive, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.	Int J Cancer 1994 Jun 1;57(5):681-3 Abstract quote There is a general agreement that fibroadenoma is associated with a certain increase in breast cancer risk, but the risk estimates appear heterogeneous according to various studies. To provide further quantitative and population-based estimates of breast cancer risk in women with histologically confirmed fibroadenomas, we linked data of 1,461 incident cases of fibroadenoma (median age, 37 years) to the Cancer Registry of the Swiss Canton of Vaud (about 600,000 inhabitants) over the period 1977-1991. After exclusion of 57 synchronous breast neoplasms, a total of 17 cases of breast cancer were observed vs. 10.9 expected (standardised incidence ratio, SIR, 1.6; 90% confidence interval: 1.1-2.1). The SIR was similar in the short term (3-5 years) and in the medium-long term (> 5 years) following diagnosis of fibroadenoma. The cumulative risk of invasive breast cancer was 0.7% after 5 years and 2.2% after 12 years following diagnosis of fibroadenoma. This is not negligible on account of the young age of our cohort.
Long-term risk of breast cancer in women with fibroadenoma. Dupont WD, Page DL, Parl FF, Vnencak-Jones CL, Plummer WD Jr, Rados MS, Schuyler PA. Department of Preventive Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-2637.	N Engl J Med 1994 Jul 7;331(1):10-5 Abstract quote BACKGROUND. Fibroadenomas are benign breast tumors that are commonly diagnosed in young women and are associated with a slight increase in the risk of breast cancer. These lesions vary considerably in their histologic characteristics. We assessed the correlation between the histologic features of fibroadenomas and the risk of subsequent breast cancer. METHODS. We conducted a retrospective cohort study of a consecutive series of patients with fibroadenoma diagnosed between 1950 and 1968. Follow-up data were obtained for 1835 patients (90 percent of those eligible). Fibroadenomas with cysts, sclerosing adenosis, epithelial calcifications, or papillary apocrine changes were classified as complex. The rate of subsequent breast cancer among the patients was compared with the rates in two control groups, women listed in the Connecticut Tumor Registry and women chosen from among the patients' sisters-in-law. RESULTS. The risk of invasive breast cancer was 2.17 times higher among the patients with fibroadenoma than among the controls (95 percent confidence interval, 1.5 to 3.2). The relative risk increased to 3.10 among patients with complex fibroadenomas (95 percent confidence interval, 1.9 to 5.1) and remained elevated for decades after diagnosis. Patients with benign proliferative disease in the parenchyma adjacent to the fibroadenoma had a relative risk of 3.88 (95 percent confidence interval, 2.1 to 7.3). Patients with a family history of breast cancer in whom complex fibroadenoma was diagnosed had a relative risk of 3.72, as compared with controls with a family history (95 percent confidence interval, 1.4 to 10). Two thirds of the patients had noncomplex fibroadenomas and no family history of breast cancer and did not have an increased risk. CONCLUSIONS. Fibroadenoma is a long-term risk factor for breast cancer. The risk is increased in women with complex fibroadenomas, proliferative disease, or a family history of breast cancer.
TREATMENT	Simple excision is curative if complex changes are not present

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. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

Intracanalicular-Glands are compressed into slit-like spaces by stroma.

Pericanalicular-Intact round to oval spaces surrounded by stroma.

Stromal multinucleated giant cells-Occasionally seen in the stroma. No mitotic figures are present. It is a benign change.

Basic Principles of Disease
Learn the basic disease classifications of cancers, infections, and inflammation

Commonly Used Terms
This is a glossary of terms often found in a pathology report.

Diagnostic Process
Learn how a pathologist makes a diagnosis using a microscope

Surgical Pathology Report
Examine an actual biopsy report to understand what each section means

Special Stains
Understand the tools the pathologist utilizes to aid in the diagnosis

How Accurate is My Report?
Pathologists actively oversee every area of the laboratory to ensure your report is accurate

Got Path?
Recent teaching cases and lectures presented in conferences

Pathologists Who Make A Difference
Search for a Physician Specialist
Gross Photo
Microscopic Photo

Last Updated April 14, 2006

Send mail to The Doctor's Doctor with questions or comments about this web site.
Read the Medical Disclaimer.

Copyright © The Doctor's Doctor