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Atypical Breast Hyperplasia

Editor: Andrew L. Walls Updated: 2/6/2023 2:13:11 PM


Atypical hyperplasia of the breast refers to abnormal epithelial proliferative breast lesions that are not qualitatively or quantitatively abnormal enough to be classified as carcinoma in situ. These lesions can occur in male and female breast tissue, but they are rare, incidental findings in male gynecomastia specimens. This article will focus on atypical hyperplasia of both ductal and lobular types of the female breast. Both of these lesions are considered pre-malignant or high-risk lesions for the development of more advanced neoplasia.

Atypical ductal hyperplasia (ADH) is a relatively common lesion reported to be found in about 5% to 20% of breast biopsies. Although not carcinoma, it is classified as a high-risk precursor lesion due to its association with and potential to progress to ductal carcinoma in situ (DCIS) as well as invasive carcinoma.

Atypical lobular hyperplasia (ALH), like ADH, is another high-risk breast lesion that has been associated with a four-fold to five-fold increased lifetime risk of developing breast cancer in either the ipsilateral or contralateral breast.[1][2][3][4]


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Atypical lobular and ductal hyperplasias are considered high-risk, pre-cursor, or pre-malignant lesions associated with either progression to advanced neoplasms or a marker for developing metachronous or synchronous breast cancer. Molecular studies have demonstrated that genomic changes occur in normal breast tissue. These changes lead to an increased proliferative capacity. A genomic change from the damaging effects of carcinogens is one of the leading theories behind the development of atypical proliferative lesions and breast cancer.

One of the leading players in initiating this genomic change is estrogen. Estrogen and its metabolites have been associated with multiple DNA-damaging effects leading to defective growth control, especially luminal progenitor cells. Women are exposed to estrogen at differing levels throughout their life, especially beginning at menarche and throughout the remainder of their lives. This life-long exposure to estrogen possibly represents a continued accumulation of genomic changes and damage, which may lead to the development of atypical proliferative breast lesions.

Molecular studies have discovered shared molecular characteristics between atypical proliferative lesions such as ADH and low-grade DCIS. This leads many to believe that ADH will continue on a spectrum to develop into low-grade DCIS. ALH, on the other hand, is not necessarily considered a pre-cursor for malignancy but a high-risk indicator. When ADH or ALH is identified in a breast biopsy, the risk of developing DCIS or invasive breast cancer increases by four to five times with a 2:1 predilection for the ipsilateral breast versus contralateral. It is unclear if a precursor lesion exists for high-grade DCIS or invasive carcinoma; however, breast cancer relative risk is increased four times when atypical hyperplasia is identified on a breast biopsy. The lifetime risk of developing breast cancer in patients with ADH or ALH on biopsy is 15% to 20%.

Molecular studies have identified important agents related to un-checked proliferation, including cyclin D1 overexpression, p16 inactivation, HOXA inactivation, and activation of telomerase. These changes can lead to inhibition of cell death and the development of malignancy. The sequence and interplay of these changes are not well understood, but further studies in their relation to each other and the development of atypical proliferative lesions and breast cancer could shed light on accurate risk stratification, prognosis, and early predictors of advanced neoplasia.[1][2][3][4]


Approximately 10% of female breast biopsies will contain an atypical proliferative lesion, with most of these lesions found in women in their 40s.

Atypical hyperplasia can also be found in males undergoing reduction mammoplasty for gynecomastia, although it is exceedingly rare. The reported incidence in one cohort of over 5000 specimens is reported to be less than 1%.[5][6]


Both atypical ductal hyperplasia (ADH) and atypical lobular hyperplasia (ALH) are characterized by the criteria put forth by Page et al. 

ADH is characterized by an atypical monomorphic epithelial population of luminal origin within the breast that is between normal/usual hyperplasia and low-grade ductal carcinoma in situ (DCIS) on the spectrum of intraductal proliferative lesions. ADH will share some of the features of DCIS without meeting the full criteria for low-grade DCIS. The architectural features of low-grade DCIS include cribriform spaces with polarized lumens composed of highly monotonous cells with fine chromatin in a solid, cribriform, or micropapillary pattern.

When the above architectural and cytologic criteria are met, size can be used to distinguish ADH from low-grade DCIS, where low-grade DCIS requires the full involvement of two or more ductal units and the lesion is greater than 0.2 cm in size. Like ADH and ALH, DCIS will retain myoepithelial cells, as evidenced by positive immunohistochemical staining (e.g., with p63).

ALH is characterized by an intraductal over-proliferative epithelial population within the acini of terminal duct lobular units. These proliferations consist of small, round uniform cells that do not overlap, appear more dyshesive, and have increased nuclear to cytoplasmic ratio. Nuclear atypia should be minimal. Loss of E-cadherin staining is characteristic for ALH and is also seen in more advanced lesions such as lobular carcinoma in situ or invasive lobular carcinoma. The distinction between ALH and lobular carcinoma in situ is that with ALH, there should be less than 50% involvement of the acini in the TDLU.[6][3][7][8][9] 

History and Physical

Atypical hyperplasia lesions are usually discovered incidentally on routine screening mammograms, often during breast biopsies performed for evidence of calcifications on imaging or in conjunction with other lesions, both benign and malignant. As atypical hyperplasia is a high-risk but non-malignant lesion, it is important to discuss breast cancer risk factors, such as estrogen exposure and family history of breast cancer.

General physical exam to include focused breast exam is vital to the patient evaluation, although atypical hyperplasia itself is very unlikely to be appreciated on the physical exam due to its small size, as a solitary focus of ADH that is larger than 0.2 cm is more likely to be designated as DCIS.[10][11][12][13][14][15]


Atypical hyperplasia cannot be identified on imaging but can be found on histopathologic examination of breast biopsy or excisions performed for other mammographic findings such as calcifications or other worrisome lesions seen on imaging. Atypical hyperplasia is less likely to be the primary finding on histopathologic examination if a biopsy is performed for a large symptomatic or palpable breast mass or lesion. Women should be encouraged to undergo mammogram screening evaluation and breast exams at the currently recommended intervals according to their risk stratification.[15][16] 

Treatment / Management

Atypical hyperplasia lesions are pre-malignant. Many authorities believe the patient should undergo complete surgical excision to exclude malignancy and prevent the development of advanced neoplasia if found on a breast biopsy. Surgical excision for core biopsies that show ADH is considered standard of care. However, ALH may be an incidental finding in small biopsies, and standard surgical resection of these lesions is more controversial. In general, excision is usually recommended in high-risk patients. In carefully selected lower-risk patients such as those without a family or personal history of breast cancer, without BRCA1 or BRCA2 mutations, solitary lesions, or lower BI-RADS score, surveillance, and/or medical therapy such as estrogen receptor modulators are possible management options. Short-term follow-up with increased mammography frequency should be recommended for patients in whom surgical resection is not performed.

ADH is considered a pre-malignant, high-risk lesion, and ALH only a high-risk lesion. Either can be found in association with or at the periphery of a more advanced lesion; therefore, it is important to remember that atypical hyperplasia found on a biopsy may not accurately represent the greater lesion. Upgrade on surgical excision after atypical hyperplasia is found on biopsy varies from 10% to as high as 30%, with cases of atypical hyperplasia suspicious for DCIS having a higher rate of an upgrade after undergoing excision. Studies have failed to show reliable, independent indicators of which atypical hyperplasia lesions are associated with more aggressive entities such as high-grade DCIS or invasive cancer.

It is important to note that while surgical excision after identifying atypical hyperplasia in a core biopsy is generally considered appropriate, some disagreement persists regarding the management of high-risk lesions in certain cases. Proper management will depend on discussing all factors with the patient, and this includes a review of current treatment modalities and recommendations, patient risk factors, careful radiologic/pathologic correlation, and the overall clinical picture.[11][12][13][14][17][1][18](B2)

Differential Diagnosis

Important differential diagnostic entities to consider when viewing possible ADH or ALH include usual ductal hyperplasia, ductal carcinoma in situ, lobular carcinoma in situ, and flat epithelial atypia, with the most important distinguisher being whether a lesion is ADH or low-grade DCIS. These distinctions can be made on the histologic features as outlined above, noting that there are also difficult cases where particularly problematic borderline lesions may be diagnosed as “ADH bordering on DCIS” or “ADH suspicious for DCIS.”[11][12][13][14]


Atypical ductal hyperplasia (ADH) is a relatively common lesion reported to be found in about 5% to 20% of breast biopsies. Although not carcinoma, it is classified as a high-risk precursor lesion due to its association with and potential to progress to ductal carcinoma in situ (DCIS) as well as invasive carcinoma.

Atypical lobular hyperplasia (ALH), like ADH, is another high-risk breast lesion that has been associated with a four-fold to a five-fold increased lifetime risk of developing breast cancer in either the ipsilateral or contralateral breast.[7][3]


Complications of atypical hyperplasia of the breast are related mainly to the surgical treatment of this disease. Infection, bleeding, anesthesia complications, disfigurement, and pain are some, but not all, of the possible complications associated with treatment of this disease.

Deterrence and Patient Education

Atypical hyperplasia of the breast is a complicated disorder, with most experts agreeing that surgical excision is appropriate. Patients should be counseled, however, on an individual basis, as factors that influence the course of treatment may include the extent of disease, atypia, family history, prior history, genetics, and overall patient health status.[19]

Enhancing Healthcare Team Outcomes

Proper management of patients with this complex disease requires collaboration between radiology, surgery, pathology, and the patient and their primary care team. The current standard of care is to excise high-risk breast lesions due to high upgrade rates on the excision of these breast lesions after a biopsy.[20][17] [Level 5]



Molecular profile of atypical hyperplasia of the breast., Danforth DN,, Breast cancer research and treatment, 2017 Sep 14     [PubMed PMID: 28913734]


Genomic Changes in Normal Breast Tissue in Women at Normal Risk or at High Risk for Breast Cancer., Danforth DN Jr,, Breast cancer : basic and clinical research, 2016     [PubMed PMID: 27559297]


Combined histologic and cytologic criteria for the diagnosis of mammary atypical ductal hyperplasia., Page DL,Rogers LW,, Human pathology, 1992 Oct     [PubMed PMID: 1328030]


Linsk A,Mehta TS,Dialani V,Brook A,Chadashvili T,Houlihan MJ,Sharma R, Surgical upgrade rate of breast atypia to malignancy: An academic center's experience and validation of a predictive model. The breast journal. 2018 Mar     [PubMed PMID: 28833923]

Level 1 (high-level) evidence


Pathological findings in gynecomastia: analysis of 5113 breasts., Lapid O,Jolink F,Meijer SL,, Annals of plastic surgery, 2015 Feb     [PubMed PMID: 23788148]

Level 2 (mid-level) evidence


Isolated Atypical Lobular Hyperplasia Diagnosed on Breast Biopsy: Low Upgrade Rate on Subsequent Excision With Long-Term Follow-up., Muller KE,Roberts E,Zhao L,Jorns JM,, Archives of pathology & laboratory medicine, 2017 Nov 21     [PubMed PMID: 29160721]


Lobular neoplasia of the breast: higher risk for subsequent invasive cancer predicted by more extensive disease., Page DL,Kidd TE Jr,Dupont WD,Simpson JF,Rogers LW,, Human pathology, 1991 Dec     [PubMed PMID: 1748429]


Breast Cancer Risk and Progressive Histology in Serial Benign Biopsies., Visscher DW,Frank RD,Carter JM,Vierkant RA,Winham SJ,Heinzen EP,Broderick BT,Denison LA,Allers TM,Johnson JL,Frost MH,Hartmann LC,Degnim AC,Radisky DC,, Journal of the National Cancer Institute, 2017 Oct 1     [PubMed PMID: 28376198]


Pathology of high-risk breast lesions and ductal carcinoma in situ., Sewell CW,, Radiologic clinics of North America, 2004 Sep     [PubMed PMID: 15337418]


Atypical ductal hyperplasia: Our experience in the management and long term clinical follow-up in 71 patients., Latronico A,Nicosia L,Faggian A,Abbate F,Penco S,Bozzini A,Cannataci C,Mazzarol G,Cassano E,, Breast (Edinburgh, Scotland), 2017 Oct 11     [PubMed PMID: 29032282]


Breast cancer risk associated with atypical hyperplasia and lobular carcinoma in situ initially diagnosed on core-needle biopsy., Donaldson AR,McCarthy C,Goraya S,Pederson HJ,Sturgis CD,Grobmyer SR,Calhoun BC,, Cancer, 2017 Oct 10     [PubMed PMID: 29023647]


High-Risk Breast Lesions: A Machine Learning Model to Predict Pathologic Upgrade and Reduce Unnecessary Surgical Excision., Bahl M,Barzilay R,Yedidia AB,Locascio NJ,Yu L,Lehman CD,, Radiology, 2017 Oct 17     [PubMed PMID: 29039725]


Active surveillance of women diagnosed with atypical ductal hyperplasia on core needle biopsy may spare many women potentially unnecessary surgery, but at the risk of undertreatment for a minority: 10-year surgical outcomes of 114 consecutive cases from a single center., Farshid G,Edwards S,Kollias J,Gill PG,, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2017 Nov 3     [PubMed PMID: 29099502]

Level 3 (low-level) evidence


Factors affecting the under-diagnosis of atypical ductal hyperplasia diagnosed by core needle biopsies - A 10-year retrospective study and review of the literature., Co M,Kwong A,Shek T,, International journal of surgery (London, England), 2017 Nov 13     [PubMed PMID: 29146271]

Level 2 (mid-level) evidence


Frequency, upgrade rates, and characteristics of high-risk lesions initially identified with breast MRI., Strigel RM,Eby PR,Demartini WB,Gutierrez RL,Allison KH,Peacock S,Lehman CD,, AJR. American journal of roentgenology, 2010 Sep     [PubMed PMID: 20729462]

Level 2 (mid-level) evidence


Atypical ductal hyperplasia on vacuum-assisted breast biopsy: suspicion for ductal carcinoma in situ can stratify patients at high risk for upgrade., Allison KH,Eby PR,Kohr J,DeMartini WB,Lehman CD,, Human pathology, 2011 Jan     [PubMed PMID: 20970167]


Understanding the premalignant potential of atypical hyperplasia through its natural history: a longitudinal cohort study., Hartmann LC,Radisky DC,Frost MH,Santen RJ,Vierkant RA,Benetti LL,Tarabishy Y,Ghosh K,Visscher DW,Degnim AC,, Cancer prevention research (Philadelphia, Pa.), 2014 Feb     [PubMed PMID: 24480577]

Level 3 (low-level) evidence


Lobular neoplasia: morphology, biological potential and management in core biopsies., O'Malley FP,, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2010 May     [PubMed PMID: 20436498]


Surgical management of high-risk breast lesions., Degnim AC,King TA,, The Surgical clinics of North America, 2013 Apr     [PubMed PMID: 23464689]


Allen A,Cauthen A,Dale P,Jean-Louis C,Lord A,Smith B, Evaluating the frequency of upgrade to malignancy following surgical excision of high-risk breast lesions and ductal carcinoma in situ identified by core needle biopsy. The breast journal. 2019 Jan;     [PubMed PMID: 30461129]