Author: Rodrigo Arrangoiz MS, MD, FACS, FSSO

Pseudoangiomatous Stromal Hyperplasia (PASH)

• Introduction:
  • Pseudoangiomatous stromal hyperplasia (PASH) of breast:
    • Is a benign proliferative breast disease
    • It was first described by Vuitch, Erlandson, and Rosen:
      • In 1986
    • This lesion is characterized by:
      • A dense, collagenous proliferation of mammary stroma:
        • Forming inter-anastomosing capillary-like spaces
    • The age of presentation of PASH is usually:
      • 12 to 70 years:
        • With most cases appearing in women:
          • In their late 30s to 40s
    • Both males and females are affected:
      • In men, PASH may occur with gynecomastia
    • It is seen in all racial and ethnic groups
    • PASH is usually discovered incidentally:
      • During screening mammography:
        • It may resemble a fibroadenoma on imaging
    • It usually appears as:
      • An oval, hypoechoic, or mixed echogenic mass without posterior shadowing
• PASH may also occur as a:
  • Firm, painless, often rubbery and mobile mass in the breast:
    • Small tumors may be asymptomatic
  • Usually only one breast is affected:
    • Though it may be bilateral
  • May present as multifocal nodules in 60% of cases
• When PASH occurs as a mass:
  • It is usually a firm and painless mass
• It may occur occasionally in a pregnant woman:
  • In which case it can enlarge rapidly
• Observation of asymptomatic PASH is appropriate:
  • Excision is not required
• If PASH occurs as a mass and is symptomatic:
  • A simple excision may be performed:
    • However, not all PASH lesions need to be excised
• With an asymptomatic and incidentally identified lesion diagnosed pathologically as PASH:
  • Routine follow-up is the appropriate treatment
• On gross examination:
  • PASH is usually a well-circumscribed fibrous mass
  • Cysts may occasionally be found within the lesion
• Microscopically:
  • PASH consists of a network of slit-like spaces lined by myofibroblasts that resemble ectatic vessels, with intervening stromal collagen fibers
  • The term “pseudoangiomatous” is used to describe this lesion:
    • As it has been confused and occasionally misdiagnosed as low-grade angiosarcoma
    • Though a new finding on mammogram or examination would be evaluated to rule out breast cancer:
      • There is no increased risk of breast cancer associated with the diagnosis of PASH
  • PASH may be mistaken for mammary angiosarcoma:
    • But is not associated with an increased risk of developing:
      • Angiosarcoma
      • Invasive ductal carcinoma, or 
      • Other breast malignancies
• There is no indication for genetic counseling or testing:
  • Based on a diagnosis of PASH
• Excisional biopsy is not required:
  • With concordant and benign findings on mammography and core biopsy
• It is thought that hormonal factors play an important role in PASH:
  • According to Anderson et al:
    • This lesion represents an important hyper-response to progesterone and estrogen
• PASH is a common histological finding in breast biopsy specimens and can also be found in a normal breast that is in association with proliferative or non-proliferative fibrocystic changes:
  • But it is rarely a symptomatic lesion
• PASH can be found in:
  • Teenage girls as well as in postmenopausal women with or without hormonal therapy replacement
• It is important to recognize this entity because it can be easily confused with:
  • Other benign tumors, such as:
    • Fibroadenoma
    • Phyllode tumor 
    • With malignant tumors, such as:
      • Angiosarcoma
  • Unfortunately, imaging features of PASH are non-specific:
    • On mammography:
      • The most common appearance described is:
        • A well-defined, uncalcified mass, with regular borders
      • Spiculated borders, suspicious borders, and architectural distortion can also be seen:
        • But are uncommon
    • On ultrasound:
      • PASH tends to be:
        • An oval, round hypoechoic mass or 
        • Can presents as a heterogeneous mass with cystic areas 
    • According to Cohen et al:
      • When a focal lesion with well-defined borders, containing no calcifications on mammography or a well-defined hypoechoic mass on ultrasound is seen:
        • PASH can be considered and included in the differential diagnosis
  • Clinically and on imaging, the differential diagnosis include:
    • Fibroadenoma:
      • Especially in young patient
    • Phyllode tumor:
      • In older women
  • Histologically:
    • PASH can be very similar to low-grade angiosarcoma
    • Definitive diagnosis is based on histology:
      • But unlike low-grade angiosarcoma:
        • PASH lacks of invasive features and contains no necrosis, mitoses, and no destruction of mammary epithelial structures
  • Management of PASH depends on presentation:
    • When PASH is incidentally discovered or when it is asymptomatic:
      • It can be followed up yearly by ultrasound or mammography for a period of 36 months
    • Surgical procedures are indicated for:
      • Symptomatic lesion with mechanical complaints, pain or apprehension for an alternative malignant lesion 

Image: Mammography performed with craniocaudal (A) and mediolateral oblique (B) incidences of the left breast shows a huge well-defined mass located between the inner and the outer inferior quadrants, with no suspicious features

Image: Ultrasound of the left breast centered on the palpable lump showing an oval, heterogeneous lesions with smooth borders.

• References:
  • Celliers L, Wong DD, Bourke A. Pseudoangiomatous stromal hyperplasia: a study of the mammographic and sonographic features. Clin Radiol. 2010;65(2):145-149.
  • Guray M, Sahin AA. Benign breast diseases: classification, diagnosis, and management. Oncologist. 2006;11(5):435-439.
  • Hargaden GC, Yeh ED, Georgian-Smith D, Moore RH, Rafferty EA, et al. Analysis of the mammographic and sonographic features of pseudoangiomatous stromal hyperplasia. AJR Am J Roentgenol. 2008;191(2):359-363.
  • Salvador R, Lirola JL, Domínguez R, López M, Risueño N. Pseudo-angiomatous stromal hyperplasia presenting as a breast mass: imaging findings in three patients. Breast. 2004;13(5):431-435.
  • Vuitch MF, Rosen PP, Erlandson RA. Pseudoangiomatous hyperplasia of mammary stroma. Hum Pathol. 1986;17(2):185-191.
  • Gresik CM, Godellas C, Aranha GV, Rajan P, Shoup M. Pseudoangiomatous stromal hyperplasia of the breast: a contemporary approach to its clinical and radiologic features and ideal management. Surgery. 2010;148:752-757.
  • Virk RK, Khan A. Pseudoangiomatous stromal hyperplasia: an overview. Arch Pathol Lab Med. 2010;134:1070-1074.
  • Neal L, Sandhu NP, Hieken TJ, Glazebrook KN, Mac Bride MB, Dilaveri CA, et al. Diagnosis and management of benign, atypical, and indeterminate breast lesions detected on core needle biopsy. Mayo Clin Proc. 2014; 89:536-547.
  • Degnim AC , Frost MH, Radisky DC, Anderson SS, Vierkant RA, Boughey JC, et al. Pseudoangiomatous stromal hyperplasia and breast cancer risk. Ann Surg Oncol. 2010;17(12):3269-3277.

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• Sentinel lymph node biopsy:
  • Is the standard of care for the majority of invasive breast cancers:
    • That are clinically node-negative regardless of patient age
• Locally advanced cancers (T3-T4):
  • Are still considered contraindications to sentinel lymph node biopsy, thus inflammatory cancer (T4d):
    • Makes her only axillary staging option:
      • An axillary lymph node dissection
    • Sentinel node biopsy is prohibited by virtue of the inflammatory diagnosis:
      • As the diagnosis suggests the dermal lymphatics are compromised with tumor
• While some studies have shown a higher false negative rate in patients undergoing sentinel lymph node biopsy after neo-adjuvant chemotherapy:
  • This does not appear to affect axillary recurrence or survival:
    • Leading to current consensus guidelines that it is safe in this population
• Several studies have shown that sentinel lymph node biopsy is safe in:
  • Multifocal and multicentric disease.
• There is no accurate axillary imaging that currently can replace sentinel lymph node biopsy in breast cancer

• References
• Lyman GH, Temin S, Edge SB, Newman LA, Turner RR, Weaver DL, et al. Sentinel lymph node biopsy for patients with early-stage breast cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2014;32(13):1365-1383.
• NCCN Breast Cancer Guidelines 2018. National Comprehensive Cancer Network website. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed October 17, 2019.
• Krag DN, Anderson SJ, Julian TB, Brown AM, Harlow SP, Costantino JP, et al. Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial. Lancet Oncol. 2010;11(10):927-933.
• Mamounas EP, Brown A, Anderson S, Smith R, Julian T, Miller B, Bear HD, et al. Sentinel node biopsy after neoadjuvant chemotherapy in breast cancer: results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol 2005;23(12):2694-2702.
• Geng C, Chen X, Pan X, Li J. The feasibility and accuracy of sentinel lymph node biopsy in initially clinically node-negative breast cancer after neoadjuvant chemotherapy: a systematic review and meta-analysis. PLoS One. 2016;11(9):e0162605.
• Knauer M, Konstantiniuk P, Haid A, Wenzl E, Riegler-Keil M, Pöstlberger S, et al. Multicentric breast cancer: a new indication for sentinel node biopsy–a multi-institutional validation study. J Clin Oncol.2006;24(21):3374-3380.

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• Breast MRI:
  • Can be a very useful tool in both the diagnosis and staging of breast cancer
• Based on the Surveillance, Epidemiology, and End Results (SEER) Program database and Medicare data pre-operative breast MRI use:
  • Has increased from:
    • 5.9% to 22.4% for ductal carcinoma in situ (DCIS)
    • 7.0% to 24.3% for invasive cancer
• In cases such as invasive lobular disease:
  • Pre-operative MRI has been shown to decrease the rate of re-excision:
    • However, data on the benefit of routine pre-operative breast MRI are mixed:
      • With some studies showing an increase in mastectomy rate:
        • While other studies have not shown an increase in mastectomy rate
      • Contralateral mastectomy has also been shown to be higher in those with pre-operative MRI
• When all tumor types were considered:
  • There was consistently no difference in the rate of re-excision in those undergoing pre-operative MRI vs. no MRI
• A recent meta-analysis showed that pre-operative MRI:
  • Was associated with increased odds of receiving ipsilateral mastectomy and contralateral prophylactic mastectomy with no difference in rates of re-excision, re-operation, or positive margins:
    • Therefore, use of MRI should be an individualized decision, and routine use in all patients is not appropriate

• References
• Henderson LM, Weiss J, Hubbard RA, O’Donoghue C, DeMartini WB, Buist DS, Kerlikowske K, Goodrich M, Virnig B, Tosteson AN, Lehman CD, Onega T. Factors Associated with Preoperative Magnetic Resonance Imaging Use among Medicare Beneficiaries with Nonmetastatic Breast Cancer. Breast J. 2016 Jan-Feb;22(1):24-34. doi: 10.1111/tbj.12522. Epub 2015 Oct 28.
• Mann RM, Loo CE, Wobbes T, Bult P, Barentsz JO, Gilhuijs KG, Boetes C. The impact of preoperative breast MRI on the re-excision rate in invasive lobular carcinoma of the breast. Breast Cancer Res Treat. 2010 Jan;119(2):415-22. doi: 10.1007/s10549-009-0616-6.
• Houssami N, Turner RM, Morrow M. Meta-analysis of pre-operative magnetic resonance imaging (MRI) and surgical treatment for breast cancer. Breast Cancer Res Treat. 2017;165(2):273-283.
• Fancellu A, Soro D, Castiglia P, Marras V, Melis M, Cottu P, et al. Usefulness of magnetic resonance in patients with invasive cancer eligible for breast conservation: a comparative study. Clin Breast Cancer. 2014;14(2):114-121.
• Fancellu A, Turner RM, Dixon JM, Pinna A, Cottu P, Houssami N. Meta-analysis of the effect of preoperative breast MRI on the surgical management of ductal carcinoma in situ. Br J Surg. 2015;102(8):883-893.
• Parsyan A, Moldoveanu D, Balram B, Wong S, Zhang DD, Svadzian A, et al. Influence of preoperative magnetic resonance imaging on the surgical management of breast cancer patients. Am J Surg. 2016;211(6):1089-1094.

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• Fibroadenomas of the breast are benign tumors:
  • Composed of stromal and epithelial elements:
  • That are commonly seen in young women 
  • Multiple or complex fibroadenomas:
    • May indicate a slightly increased risk for breast cancer: 
    • The relative risk of breast cancer in patients with such fibroadenomas: 
      • Is approximately twice that of patients of similar age without fibroadenomas 
  • A patient’s age determines the preferred imaging method:
    • In general, ultrasonography (US) is preferred:
    • If a palpable mass is found
    • If a patient is younger than 30 years
    • If the patient is pregnant 
    • Mammography and US are both useful if the patient has: 
    • A palpable mass
    • Is older than 30 years
    • Is not pregnant
    • In patients younger than 30 years: 
    • The most appropriate modality is ultrasound:
      • Because the patient is spared radiation exposure and because the likelihood for fibroadenoma is high
    • Mammography is not indicated as the primary imaging study in women younger than 30 years:
    • Unless high-risk factors are present
    • Computed tomography (CT) scanning: 
    • Is not initially indicated for assessing a palpable lump in a woman in women younger than 30 years:
      • Because of radiation exposure 
      • The inability of CT to demonstrate micro-calcifications
      • The lack of specificity in the findings
    • Magnetic resonance imaging (MRI):
    • Is not initially indicated for assessing a palpable lump in women younger than 30 year:
      • Mainly because of its high cost and the high likelihood of false-positive findings
    • Positron emission tomography:
    • Is expensive and is not universally available
    • On mammograms:
    • Fibroadenomas typically appear as:
      • Circumscribed oval or round masses:
        • Which occasionally have coarse calcifications
    • On ultrasonograms:
    • Fibroadenomas appear as:
      • Circumscribed, homogeneous, oval, hypoechoic masses: 
        • That may have gentle lobulations
        • A smooth, thin, echogenic capsule
        • Variable acoustic enhancement; and homogeneity 
    • On MRI:
    • Fibroadenomas typically appear as smooth masses with high signal intensity on T2-weighted images and enhancement with the administration of gadolinium-based contrast agent
    • Fibroadenoma:
    • Is a common benign breast lesion:
      • Results from the excess proliferation of connective tissue
    • Fibroadenomas characteristically contain both:
      • Stromal and epithelial cells 
    • Epidemiology: 
    • They usually occur in women:
      • Between the ages of 10 and 40 years
      • It is the most common breast mass:
        • In the adolescent and young adult population :
        • Their peak incidence is between:
        • 25 and 40 years
    • The incidence decreases after 40 years 
    • Clinical presentation:
    • The typical presentation is in a woman of reproductive age:
      • With a mobile palpable breast lump:
    • Due to their hormonal sensitivity:
      • Fibroadenomas commonly enlarge during pregnancy and involute at menopause:
        • Hence, they rarely present after the age of 40 years
    • The lesions are well defined and well-circumscribed clinically and the overlying skin is normal
    • The lesions are not fixed to the surrounding parenchyma and slip around under the palpating fingers:
      • Hence the colloquial term a breast “mouse”
    • Pathology:
    • A fibroadenoma is a type of adenomatous breast lesion:
      • It contains epithelium:
        • Has minimal malignant potential
    • Multiple fibroadenomas occur in:
      • 10% to 15% of patients: 
        • Patients with multiple fibroadenomas:
        • Tend to have a strong family history of these tumors
      • They are assumed to be:
        • Aberrations of normal breast development (ANDI) or the product of hyperplastic processes:
        • Rather than true neoplasms
    • Fibroadenomas can be stimulated by estrogen and progesterone:
      • Some fibroadenomas also have receptors and respond to:
        • Growth hormone and epidermal growth factor
    • When found in an adolescent girl:
      • The term juvenile fibroadenoma is more appropriate 
    • Location:
    • Although they can be located anywhere in the breast:
      • There may be a predilection for the upper outer quadrant 
    • Associations:
    • Cyclosporin use o Cowden syndrome
    • Radiographic features:
    • Mammography:
      • Fibroadenomas have a spectrum of features:
        • Well-circumscribed discrete oval mass hypodense or isodense to the breast glandular tissue
        • Mass with macro-lobulation or partially obscured margin 
        • Involuting fibroadenomas in older, typically postmenopausal patients may contain:
        • Calcification:
          • Often producing the classic, coarse popcorn calcification appearance
          • In some cases the whole lesion is calcified 
          • Calcification may also present as crushed stone-like micro-calcification:
            • Which makes differentiation from malignancy difficult 
    • Breast ultrasound: 
      • Typically seen as a well-circumscribed, round to ovoid, or macro-lobulated mass with generally uniform hypoechogenicity 
      • Intralesional sonographically detectable calcification: 
        • May be seen in approximately 10% of cases
      • Sometimes a thin echogenic rim (pseudo capsule) may be seen sonographically 
    • Breast MRI:
      • T1: typically hypo intense or isointense compared with adjacent breast tissue 
      • T2: can be hypo- or hyper intense
      • T1 C+ (Gd): can be variable but a majority will show slow initial contrast enhancement followed by a persistent delayed phase (type I enhancement curve)
        • Non-enhancing internal septations may be seen 
    • Diagnosis:
    • These lesions are easily biopsied under ultrasound guidance
    • When a lesion has the typical features of a fibroadenoma on ultrasound and there are no clinical red flags:
      • They can be safely followed clinically 
    • When lesions enlarge or have atypical imaging findings:
      • Ultrasound-guided core biopsy is a minimally invasive outpatient procedure that will give a diagnosis with virtually no complications 
      • There may be a maximum diameter above which a biopsy should be done if no previous imaging is available: 
        • The reason for intervention based on size is that a phyllodes tumor may be indistinguishable from a fibroadenoma on ultrasound:
        • A maximum diameter of 2.5 cm may be a useful benchmark for biopsy if you have no previous imaging 
      • Interval enlargement:
        • Is an indication for biopsy 
  • Symptomatic, progressively enlarging masses or atypical presentations:
    • May warrant surgical excision
  • If a needle biopsy shows that a mass less than 2 centimeters in size is a fibroadenoma, with no other concerning features:
    • It does not have to be surgically removed
  • The patient’s core biopsy pathology demonstrating a fibroadenoma is consistent with the typical imaging findings of a smooth, round, hypoechoic mass:
    • As the biopsy is concordant, no further intervention is needed:
    • Follow-up for reassurance is acceptable
  • Treatment and prognosis:
    • They are benign lesions with minimal or no malignant potential 
    • The risk of malignant transformation is extremely low: 
    • Has been reported to range around 0.0125% to 0.3%
    • Indications for biopsy include: 
    • Enlarging lesion 
    • Atypical findings on ultrasound 
    • A lesion above 2.5 cm and there are no previous studies for comparison
    • Patient peace of mind:
      • Some patients are simply not happy with a palpable mass in the breast without a histological diagnosis:
        • This is a valid and reasonable indication for biopsy

• References
  • Tan BY, Tan PH A Diagnostic Approach to Fibroepithelial Breast Lesions. Surg Pathol Clin. 2018 Mar;11(1):17-42.
  • American Society of Breast Surgeons – benign breast disease. January 8, 2018. Choosing Wisely website. http://www.choosingwisely.org/clinician-lists/asbrs-benign-breast-disease-biopsy-proven-fibroadenomas-smaller-than-2-cm/. Accessed October 17, 2019.

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• Fibromatosis (also called desmoid fibromatosis):
  • Is characterized by a proliferation of histologically bland spindle cells arranged in long fascicles, with infiltrative architecture:
    • Similar to fibromatosis in other sites
  • Fibromatosis is a rare tumor with:
    • Locally aggressive behavior
    • High incidence of local recurrence
  • Various causes have been accused of being its etiology including:
    • Genetic factors
    • Endocrine factors
    • Surgical trauma
  • For treatment of fibromatosis:
    • Wide local excision with adequate safety margins is considered the standard of care
• The breast is an unusual site for occurrence of desmoid type fibromatosis with few cases reported in literature:
  • It represents 0.2% of all breast tumors
  • 4% of all extra-abdominal desmoid tumors
  • Bilaterality has been reported in:
    • 4% of cases
  • Most of these cases were reported in:
    • Young fertile females:
      • With rare cases reported in males
  • The reported risk factors include:
    • Surgical trauma
    • Silicone implants
    • Association with Gardener’s syndrome
  • Clinically, it is presented as a firm mass with skin dimpling and nipple retraction in superficial and retro-areolar tumors
    • Neither nipple discharge nor axillary lymphadenopathy commonly occur with fibromatosis 
  • Mammography:
    • Presents irregular walled and highly dense lesion with no calcifications mimicking sometimes breast carcinoma
  • Microscopic examination of desmoid tumor usually reveals:
    • The characteristic irregular bundles of spindle cells with regular nuclei surrounded by abundant collagen 
    • Giant cells, macrophages and lymphocytes:
      • Are noticed mostly peripherally 
  • Although fibromatosis does not have metastatic potential:
    • It can be locally aggressive
  • Metaplastic carcinoma (‘fibromatosis like,’ low-grade spindle cell):
    • Should be ruled out with keratin or other epithelial stains in every case
  • The differential diagnosis also includes:
    • Nodular fasciitis
    • Myofibroblastoma
    • Fascicular pseudoangiomatos stromal hyperplasia (PASH)
    • Stromal overgrowth of phyllodes tumors
    • Other spindle cell sarcomas
  • Fibromatosis may be very difficult to distinguish from scar / granulation tissue pathologically:
    • Especially in patients with prior resection and concern for recurrence
  • Beta-catenin nuclear staining:
    • Is characteristic of fibromatosis:
      • But is positive in only up to 70% of cases and may be difficult to demonstrate

• References
• Lee A, Gobbi H. Desmoid type fibromatosis In: Lakhani SR, Ellis IO, Schnit SJ, Tan PH, van de Vijver MJ et al. eds. WHO Classification of Tumours of the Breast. Lyon: IARC Press, 2012:131-2.
• Schnitt SJ, Collins L. Biopsy Interpretation of the Breast. 3^rd edition. Philadelphia, PA: Wolters Kluwer, 2018: 412-416.
• Kuba MG, Lester SC, Giess CS, Bertagnolli MM3, Wieczorek TJ4, Brock JE. Fibromatosis of the breast: diagnostic accuracy of core needle biopsy. Am J Clin Pathol. 2017;148(3):243-250.
• Kim T, Jung EA, Song JY, Roh JH, Choi JS, Kwon JE. Prevalence of the CTNNB1 mutation genotype in surgically resected fibromatosis of the breast. Histopathology. 2012;60(2):347-356.

• According to the World Health Organization definition:
  • Complex fibroadenoma is a fibroadenoma containing:
    • Cysts greater than 3 mm in size
    • Sclerosing adenosis
    • Epithelial calcifications
    • Papillary apocrine hyperplasia
• While this is a benign diagnosis:
  • Some authors have reported a slightly increased risk of subsequent breast cancer development:
    • On par with other proliferative lesions of the breast:
      • About 2 to 3-fold
        • Thus, the terminology “complex fibroadenoma” is not always employed
• The term “complex” does not imply any relation to radial scar or epithelial atypia in the setting of a fibroadenoma

• References
  • Tan PH, Tse G, Lee A, et al. Fibroepithelial tumours. In: Lakhani SR, Ellis IO, Schnit SJ Tan PH, van de Vijver MJ. eds. WHO Classification of Tumours of the Breast. Lyon: IARC Press, 2012:142-143.
  • Dupont WD, Page DL, Parl FF, Vnencak-Jones CL, Plummer WD Jr, Rados MS, et al. Long-term risk of breast cancer in women with fibroadenoma. N Engl J Med. 1994;331(1):10-15.
  • Nassar A, Visscher DW, Degnim AC, Frank RD, Vierkant RA, Frost M, et al. Complex fibroadenoma and breast cancer risk: a Mayo Clinic Benign Breast Disease Cohort Study. Breast Cancer Res Treat.2015;153(2):397-405.
  • Krings G, Bean GR, Chen YY. Fibroepithelial lesions; The WHO spectrum. Semin Diagn Pathol. 2017;34(5):438-452.

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• Atypical lobular hyperplasia (ALH):
  • Is generally an incidental finding on core needle biopsy:
    • Without specific defining characteristics on:
      • Mammography, ultrasound, or MRI
• A palpable breast mass which yields ALH at core needle biopsy is discordant:
  •  This should prompt further diagnostic work-up with a second biopsy:
    • Either core or excisional
• ALH should only be considered for observation:
  • When there is radiologic, pathologic, and clinical concordance:
    • As the risk of upstaging to carcinoma in this scenario is:
      • Less than 5%
• ALH alone:
  • Confers a 4 to 5-fold increased risk of future breast cancer in either breast
  • The probability of upgrade to invasive carcinoma with a diagnosis of atypical lobular hyperplasia (ALH) on core needle biopsy:
    • Is reported as less than 3%
• Excision to achieve negative margins in ALH:
  • Is generally not required
• Having a family history:
  • Does not appear to increase the risk associated with atypical hyperplasia
• Relevant indications for genetic testing include:
  • A personal history of breast cancer ≤ age 45
  • Triple negative breast cancer ≤ age 60
  • A first-degree relative with breast cancer ≤ age 50
  • Two or more first- or second-degree relatives with breast cancer at any age
  • Patient or relative with bilateral breast cancer
  • Male breast cancer in a relative at any age
• Risk-reducing mastectomy:
  • Can be considered in patients with very high lifetime breast cancer risk:
    • Usually reserved for women with high-penetrance gene mutations:
      • Such as BRCA 1 or BRCA 2
• References
  • Morrow M, Schnitt SJ, Norton L. Current management of lesions associated with an increased risk of breast cancer. Nat Rev Clin Oncol. 2015;12(4):227-238.
  • Murray MP, Luedtke C, Liberman L, Nehhozina T, Akram M, Brogi E. Classic lobular carcinoma in situ and atypical lobular hyperplasia at percutaneous breast core biopsy: outcomes of prospective excision. Cancer. 2013;119(5):1073-1079.
  • Middleton LP, Sneige N, Coyne R, Shen Y, Dong W, Dempsey P. Most lobular carcinoma in situ and atypical lobular hyperplasia diagnosed on core needle biopsy can be managed clinically with radiologic follow-up in a multidisciplinary setting. Cancer Med. 2014;3(3):492-499.
  • Hartmann LC, Sellers TA, Frost MH, Lingle WL, Degnim AC, Ghosh K, et al. Benign breast disease and the risk of breast cancer. N Engl J Med. 2005;353(3):229-237.
  • Degnim AC, Visscher DW, Berman HK, Frost MH, Sellers TA, Vierkant RA, et al. Stratification of breast cancer risk in women with atypia: a Mayo cohort study. J Clin Oncol. 2007;25(19):2671-2677.
  • Smart CE, Furnival CM, Lakhani SR. Chapter 17. High-Risk Lesions: ALH/LCIS/ADH. In: Kuerer HM ed. Kuerer’s Breast Surgical Oncology. New York, NY: McGraw-Hill, 2010.
  • The American Society of Breast Surgeons (2016). Consensus Guideline on Concordance Assessment of Image-Guided Breast Biopsies and Management of Borderline or High-Risk Lesions https://www.breastsurgeons.org/docs/statements/Consensus-Guideline-on-Concordance-Assessment-of-Image-Guided-Breast-Biopsies.pdf. Accessed February 23, 2020.

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• Flat epithelial atypia:
  • Confers a relative risk of developing breast cancer of:
    • Approximately 1.5
  • Excisional biopsy may be indicated if:
    • Calcifications are incompletely removed or 
    • If there is question of sampling error:
      • But excision to negative margins is not required
  • The probability of finding a concurrent invasive carcinoma is:
    • Approximately 1% to 5% when flat epithelial atypia is found on core needle biopsy:
      • Given the small (less than two-fold) associated increase in breast cancer risk:
        • Chemoprevention is not indicated nor is routine annual screening breast MRI

• References:
  • Sudarshan M, Meguerditchian AN, Mesurolle B, Meterissian S. Flat epithelial atypia of the breast: characteristics and behaviors. Am J Surg. 2011;201(2)245-250.
  • Piubello Q, Parisi A, Eccher A, Barbezeni G, Franchini Z, Iannucci A. Flat epithelial atypia on core needle biopsy: which is the right management? Am J Surg Pathol. 2009;33(7):1078-1084.
  • Martel M, Barron-Rodriguez P, Tolgay Ocal I, Dotto J, Tavassoli FA. Flat DIN 1 (flat epithelial atypia) on core needle biopsy: 63 cases identified retrospectively among 1,751 core biopsies performed over an 8-year period (1992-1999). Virchow’s Arch. 2007;451(5):883-891.
  • Lamb LR, Bahl M, Gadd MA, Lehman CD. Flat epithelial atypia: upgrade rates and risk-stratification approach to support informed decision making. J Am Coll Surg. 2017;225(6):696-701.

• Fat necrosis of the breast:
  • Is a benign condition that most commonly occurs as the result of breast trauma or surgical intervention
• Fat necrosis can be confused with a:
  • Malignancy on physical examination and may mimic malignancy on radiologic studies
• It is sometimes necessary to biopsy these lesions to confirm the diagnosis:
  • Although experienced radiologists can usually determine that a lesion represents fat necrosis based on mammographic and ultrasound findings such as:
    • Oil cysts (collections of liquefied fat)
• Once the diagnosis is established:
  • Excision is not necessary and there is no increased risk of subsequent breast cancer
• References
  • Guaray M, Sahin AA. Benign breast diseases: classification, diagnosis and management. Oncologist. 2006;11(5):435-449.
  • Agel NM, Howard A, Collier DS. Fat necrosis of the breast: a cytological and clinical study. Breast. 2001;10(4):342-345

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• Periductal mastitis:
  • Is an inflammatory condition of the subareolar ducts:
    • That often presents with periareolar inflammation
• Secondary infection of inflamed ducts can occur:
  • Leading to duct damage and subsequent rupture with abscess formation:
    • These abscesses often drain spontaneously at the edge of the areola
  • Recurrent abscesses and a draining fistula can occur.
• Most patients with periductal mastitis are smokers:
  • It has been postulated that smoking is associated with damage of the subareolar ducts:
    • With tissue necrosis and subsequent infection
  • Therefore, smoking cessation is helpful for reducing the risk of repeat infections
• The management of subareolar abscess consists of:
  • Antibiotic therapy and abscess drainage
  • In refractory cases;
    • Excision of the fistula track is necessary
• References
  • Schafer P, Furrer C, Mermillod B. An association of cigarette smoking with recurrent subareolar breast abscess. Int J Epidemiol 1988;17(4):810-813.
  • Bundred NJ, Dover MS, Coley S, Morrison JM. Breast abscesses and cigarette smoking. Br J Surg. 1992;79(1):58-59.

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