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Papilloma, Benign
Lori Strachowski, MD; Cecilia L. Mercado, MD
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KEY FACTS

  • Terminology

    • Imaging

      • Top Differential Diagnoses

        • Clinical Issues

          • Diagnostic Checklist

            TERMINOLOGY

            • Synonyms

              • Intraductal papilloma
              • Large duct papilloma = central papilloma
              • Intracystic papilloma = papilloma in cystically dilated duct
            • Definitions

              • Papilloma: Benign ductal neoplasm with proliferation of ductal epithelial and myoepithelial cells supported by frond-forming fibrovascular stalk
                • Central: Arise in main lactiferous duct, usually solitary
                • Peripheral: Beyond subareolar region, arise in TDLU, often multiple
                • Microscopic: < 2 mm, entirely contained in CNB specimen; usually incidental (not seen on imaging and not targeted lesion)
                • Sclerosing: Focally or completely involved by sclerosis; may mimic invasion
                • Atypical: Associated with atypical epithelial proliferation and low-grade nuclei meeting criteria for atypical ductal hyperplasia or extent < 3 mm of what would otherwise be low-grade DCIS
              • Papillomatosis = type of usual ductal hyperplasia (UDH) → papillary hyperplasia but lacks fibrovascular stalks; proliferative lesion with 1.5-2x risk of subsequent breast cancer, but not true papillary lesion

            IMAGING

            • General Features

              • Mammographic Findings

                • Ultrasonographic Findings

                  • Ductography

                    • MR Findings

                      • Image-Guided Biopsy

                        • Imaging Recommendations

                          DIFFERENTIAL DIAGNOSIS

                            PATHOLOGY

                            • General Features

                              • Gross Pathologic & Surgical Features

                                • Microscopic Features

                                  CLINICAL ISSUES

                                  • Presentation

                                    • Demographics

                                      • Natural History & Prognosis

                                        • Treatment

                                          DIAGNOSTIC CHECKLIST

                                          • Consider

                                            • Image Interpretation Pearls

                                              Selected References

                                              1. Boufelli G et al: Papillomas of the breast: factors associated with underestimation. Eur J Cancer Prev. 27(4):310-314, 2018
                                              2. Grimm LJ et al: Concordant, non-atypical breast papillomas do not require surgical excision: A 10-year multi-institution study and review of the literature. Clin Imaging. 51:180-185, 2018
                                              3. Lamb LR et al: Pathologic upgrade rates of high-risk breast lesions on digital two-dimensional vs tomosynthesis mammography. J Am Coll Surg. 226(5):858-867, 2018
                                              4. Mishima C et al: Mutational Analysis of AKT1 and PIK3CA in Intraductal Papillomas of the Breast with Special Reference to Cellular Components. Am J Pathol. 188(5):1106-1112, 2018
                                              5. Symbol B et al: Management of intraductal papilloma without atypia of the breast diagnosed on core biopsy: Size and sampling matter. Breast J. 24(5):738-742, 2018
                                              6. Ahn SK et al: Management of benign papilloma without atypia diagnosed at ultrasound-guided core needle biopsy: Scoring system for predicting malignancy. Eur J Surg Oncol. ePub, 2017
                                              7. Bahl M et al: JOURNAL CLUB: Diagnostic utility of MRI after negative or inconclusive mammography for the evaluation of pathologic nipple discharge. AJR Am J Roentgenol. 209(6):1404-1410, 2017
                                              8. Expert Panel on Breast Imaging:. et al: ACR Appropriateness Criteria® Evaluation of Nipple Discharge. J Am Coll Radiol. 14(5S):S138-S153, 2017
                                              9. Scarpa Carniello JV et al: Diagnostic dilemmas and pitfalls in ThinPrep® cytology of breast fine needle aspiration biopsy:: Report of Six Cases with Histological Correlates. Diagn Cytopathol. 45(7):655-661, 2017
                                              10. Yildiz S et al: Contribution of diffusion-weighted imaging to dynamic contrast-enhanced MRI in the characterization of papillary breast lesions. Breast J. ePub, 2017
                                              11. Yoon JH et al: Ultrasonographic evaluation of women with pathologic nipple discharge. Ultrasonography. 36(4):310-320, 2017
                                              12. Ni YB et al: Pathological criteria and practical issues in papillary lesions of the breast - a review. Histopathology. 68(1):22-32, 2016
                                              13. Rageth CJ et al: First International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions). Breast Cancer Res Treat. 159(2):203-13, 2016
                                              14. Yang Y et al: The significance of combined CK5/6 and p63 immunohistochemistry in predicting the risks of subsequent carcinoma development in intraductal papilloma of the breast. Pathol Int. 65(2):81-8, 2015
                                              15. C Ang D et al: Frequent phosphatidylinositol-3-kinase mutations in proliferative breast lesions. Mod Pathol. 27(5):740-50, 2014
                                              16. Choi SH et al: Clinical and imaging characteristics of papillary neoplasms of the breast associated with malignancy: a retrospective cohort study. Ultrasound Med Biol. 40(11):2599-608, 2014
                                              17. Maxwell AJ et al: Benign papilloma diagnosed on image-guided 14 G core biopsy of the breast: Effect of lesion type on likelihood of malignancy at excision. Clin Radiol. 68(4):383-7, 2013
                                              18. Nayak A et al: Benign papillomas without atypia diagnosed on core needle biopsy: experience from a single institution and proposed criteria for excision. Clin Breast Cancer. 13(6):439-49, 2013
                                              19. Sohn YM et al: Comparison of sonographically guided core needle biopsy and excision in breast papillomas: clinical and sonographic features predictive of malignancy. J Ultrasound Med. 32(2):303-11, 2013
                                              20. Swapp RE et al: Management of benign intraductal solitary papilloma diagnosed on core needle biopsy. Ann Surg Oncol. 20:1900-5, 2013
                                              21. Wen X et al: Nonmalignant breast papillary lesions at core-needle biopsy: a meta-analysis of underestimation and influencing factors. Ann Surg Oncol. 20(1):94-101, 2013
                                              22. Brennan SB et al: Papilloma diagnosed at MRI-guided vacuum-assisted breast biopsy: is surgical excision still warranted? AJR Am J Roentgenol. 199(4):W512-9, 2012
                                              23. Fu CY et al: Papillary breast lesions diagnosed by core biopsy require complete excision. Eur J Surg Oncol. 38(11):1029-35, 2012
                                              24. Holley SO et al: Pathologic outcomes of nonmalignant papillary breast lesions diagnosed at imaging-guided core needle biopsy. Radiology. 265(2):379-84, 2012
                                              25. Lee KA et al: Risk of malignancy when microscopic radial scars and microscopic papillomas are found at percutaneous biopsy. AJR Am J Roentgenol. 198(2):W141-5, 2012
                                              26. Li X et al: Microcalcification is an important factor in the management of breast intraductal papillomas diagnosed on core biopsy. Am J Clin Pathol. 138:789-95, 2012
                                              27. Zhu Y et al: Solitary intraductal papillomas of the breast: MRI features and differentiation from small invasive ductal carcinomas. AJR Am J Roentgenol. 199(4):936-42, 2012
                                              28. Chang JM et al: Clinical application of shear wave elastography (SWE) in the diagnosis of benign and malignant breast diseases. Breast Cancer Res Treat. 129(1):89-97, 2011
                                              29. Kim MJ et al: The diagnosis of non-malignant papillary lesions of the breast: comparison of ultrasound-guided automated gun biopsy and vacuum-assisted removal. Clin Radiol. 66(6):530-5, 2011
                                              30. Youk JH et al: Benign papilloma without atypia diagnosed at US-guided 14-gauge core-needle biopsy: clinical and US features predictive of upgrade to malignancy. Radiology. 258(1):81-8, 2011
                                              31. Chang JM et al: Risk of carcinoma after subsequent excision of benign papilloma initially diagnosed with an ultrasound (US)-guided 14-gauge core needle biopsy: a prospective observational study. Eur Radiol. 20(5):1093-100, 2010
                                              32. Debnath D et al: Multiple Papillomatosis of Breast and Patient's Choice of Treatment. Patholog Res Int. 2010:540590, 2010
                                              33. Jung SY et al: Risk factors for malignancy in benign papillomas of the breast on core needle biopsy. World J Surg. 34(2):261-5, 2010
                                              34. Troxell ML et al: High prevalence of PIK3CA/AKT pathway mutations in papillary neoplasms of the breast. Mod Pathol. 23(1):27-37, 2010
                                              35. Chang JM et al: Does ultrasound-guided directional vacuum-assisted removal help eliminate abnormal nipple discharge in patients with benign intraductal single mass? Korean J Radiol. 10(6):575-80, 2009
                                              36. Cheng TY et al: Risk factors associated with conversion from nonmalignant to malignant diagnosis after surgical excision of breast papillary lesions. Ann Surg Oncol. 16(12):3375-9, 2009
                                              37. Maxwell AJ: Ultrasound-guided vacuum-assisted excision of breast papillomas: review of 6-years experience. Clin Radiol. 64(8):801-6, 2009
                                              38. Rosen PP: Papilloma and Related Benign Tumors. In Rosen PP: Rosen's Breast Pathology. Philadelphia: Lippincott Williams & Wilkins. 85-136, 2009
                                              39. Muttarak M et al: Spectrum of papillary lesions of the breast: clinical, imaging, and pathologic correlation. AJR Am J Roentgenol. 191(3):700-7, 2008
                                              40. Shin HJ et al: Papillary lesions of the breast diagnosed at percutaneous sonographically guided biopsy: comparison of sonographic features and biopsy methods. AJR Am J Roentgenol. 190(3):630-6, 2008
                                              41. Skandarajah AR et al: Benign papilloma on core biopsy requires surgical excision. Ann Surg Oncol. 15(8):2272-7, 2008
                                              42. Bhattarai N et al: Intraductal papilloma: features on MR ductography using a microscopic coil. AJR Am J Roentgenol. 186(1):44-7, 2006
                                              43. Lewis JT et al: An analysis of breast cancer risk in women with single, multiple, and atypical papilloma. Am J Surg Pathol. 30(6):665-72, 2006
                                              44. Lewis JT et al: An analysis of breast cancer risk in women with single, multiple, and atypical papilloma. Am J Surg Pathol. 30:665-72, 2006
                                              45. Liberman L et al: Is surgical excision warranted after benign, concordant diagnosis of papilloma at percutaneous breast biopsy? AJR Am J Roentgenol. 186(5):1328-34, 2006
                                              46. Mercado CL et al: Papillary lesions of the breast at percutaneous core-needle biopsy. Radiology. 238(3):801-8, 2006
                                              47. Nelson RS et al: Twenty-year outcome following central duct resection for bloody nipple discharge. Ann Surg. 243(4):522-4, 2006
                                              48. Dooley WC et al: Office-based breast ductoscopy for diagnosis. Am J Surg. 188(4):415-8, 2004
                                              49. Daniel BL et al: Magnetic resonance imaging of intraductal papilloma of the breast. Magn Reson Imaging. 21(8):887-92, 2003
                                              50. Mercado CL et al: Papillary lesions of the breast: evaluation with stereotactic directional vacuum-assisted biopsy. Radiology. 221(3):650-5, 2001
                                              51. Hild F et al: Ductal orientated sonography improves the diagnosis of pathological nipple discharge of the female breast compared with galactography. Eur J Cancer Prev. 7 Suppl 1:S57-62, 1998
                                              Related Anatomy
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                                              Related Differential Diagnoses
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                                              References
                                              Tables

                                              Tables

                                              KEY FACTS

                                              • Terminology

                                                • Imaging

                                                  • Top Differential Diagnoses

                                                    • Clinical Issues

                                                      • Diagnostic Checklist

                                                        TERMINOLOGY

                                                        • Synonyms

                                                          • Intraductal papilloma
                                                          • Large duct papilloma = central papilloma
                                                          • Intracystic papilloma = papilloma in cystically dilated duct
                                                        • Definitions

                                                          • Papilloma: Benign ductal neoplasm with proliferation of ductal epithelial and myoepithelial cells supported by frond-forming fibrovascular stalk
                                                            • Central: Arise in main lactiferous duct, usually solitary
                                                            • Peripheral: Beyond subareolar region, arise in TDLU, often multiple
                                                            • Microscopic: < 2 mm, entirely contained in CNB specimen; usually incidental (not seen on imaging and not targeted lesion)
                                                            • Sclerosing: Focally or completely involved by sclerosis; may mimic invasion
                                                            • Atypical: Associated with atypical epithelial proliferation and low-grade nuclei meeting criteria for atypical ductal hyperplasia or extent < 3 mm of what would otherwise be low-grade DCIS
                                                          • Papillomatosis = type of usual ductal hyperplasia (UDH) → papillary hyperplasia but lacks fibrovascular stalks; proliferative lesion with 1.5-2x risk of subsequent breast cancer, but not true papillary lesion

                                                        IMAGING

                                                        • General Features

                                                          • Mammographic Findings

                                                            • Ultrasonographic Findings

                                                              • Ductography

                                                                • MR Findings

                                                                  • Image-Guided Biopsy

                                                                    • Imaging Recommendations

                                                                      DIFFERENTIAL DIAGNOSIS

                                                                        PATHOLOGY

                                                                        • General Features

                                                                          • Gross Pathologic & Surgical Features

                                                                            • Microscopic Features

                                                                              CLINICAL ISSUES

                                                                              • Presentation

                                                                                • Demographics

                                                                                  • Natural History & Prognosis

                                                                                    • Treatment

                                                                                      DIAGNOSTIC CHECKLIST

                                                                                      • Consider

                                                                                        • Image Interpretation Pearls

                                                                                          Selected References

                                                                                          1. Boufelli G et al: Papillomas of the breast: factors associated with underestimation. Eur J Cancer Prev. 27(4):310-314, 2018
                                                                                          2. Grimm LJ et al: Concordant, non-atypical breast papillomas do not require surgical excision: A 10-year multi-institution study and review of the literature. Clin Imaging. 51:180-185, 2018
                                                                                          3. Lamb LR et al: Pathologic upgrade rates of high-risk breast lesions on digital two-dimensional vs tomosynthesis mammography. J Am Coll Surg. 226(5):858-867, 2018
                                                                                          4. Mishima C et al: Mutational Analysis of AKT1 and PIK3CA in Intraductal Papillomas of the Breast with Special Reference to Cellular Components. Am J Pathol. 188(5):1106-1112, 2018
                                                                                          5. Symbol B et al: Management of intraductal papilloma without atypia of the breast diagnosed on core biopsy: Size and sampling matter. Breast J. 24(5):738-742, 2018
                                                                                          6. Ahn SK et al: Management of benign papilloma without atypia diagnosed at ultrasound-guided core needle biopsy: Scoring system for predicting malignancy. Eur J Surg Oncol. ePub, 2017
                                                                                          7. Bahl M et al: JOURNAL CLUB: Diagnostic utility of MRI after negative or inconclusive mammography for the evaluation of pathologic nipple discharge. AJR Am J Roentgenol. 209(6):1404-1410, 2017
                                                                                          8. Expert Panel on Breast Imaging:. et al: ACR Appropriateness Criteria® Evaluation of Nipple Discharge. J Am Coll Radiol. 14(5S):S138-S153, 2017
                                                                                          9. Scarpa Carniello JV et al: Diagnostic dilemmas and pitfalls in ThinPrep® cytology of breast fine needle aspiration biopsy:: Report of Six Cases with Histological Correlates. Diagn Cytopathol. 45(7):655-661, 2017
                                                                                          10. Yildiz S et al: Contribution of diffusion-weighted imaging to dynamic contrast-enhanced MRI in the characterization of papillary breast lesions. Breast J. ePub, 2017
                                                                                          11. Yoon JH et al: Ultrasonographic evaluation of women with pathologic nipple discharge. Ultrasonography. 36(4):310-320, 2017
                                                                                          12. Ni YB et al: Pathological criteria and practical issues in papillary lesions of the breast - a review. Histopathology. 68(1):22-32, 2016
                                                                                          13. Rageth CJ et al: First International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions). Breast Cancer Res Treat. 159(2):203-13, 2016
                                                                                          14. Yang Y et al: The significance of combined CK5/6 and p63 immunohistochemistry in predicting the risks of subsequent carcinoma development in intraductal papilloma of the breast. Pathol Int. 65(2):81-8, 2015
                                                                                          15. C Ang D et al: Frequent phosphatidylinositol-3-kinase mutations in proliferative breast lesions. Mod Pathol. 27(5):740-50, 2014
                                                                                          16. Choi SH et al: Clinical and imaging characteristics of papillary neoplasms of the breast associated with malignancy: a retrospective cohort study. Ultrasound Med Biol. 40(11):2599-608, 2014
                                                                                          17. Maxwell AJ et al: Benign papilloma diagnosed on image-guided 14 G core biopsy of the breast: Effect of lesion type on likelihood of malignancy at excision. Clin Radiol. 68(4):383-7, 2013
                                                                                          18. Nayak A et al: Benign papillomas without atypia diagnosed on core needle biopsy: experience from a single institution and proposed criteria for excision. Clin Breast Cancer. 13(6):439-49, 2013
                                                                                          19. Sohn YM et al: Comparison of sonographically guided core needle biopsy and excision in breast papillomas: clinical and sonographic features predictive of malignancy. J Ultrasound Med. 32(2):303-11, 2013
                                                                                          20. Swapp RE et al: Management of benign intraductal solitary papilloma diagnosed on core needle biopsy. Ann Surg Oncol. 20:1900-5, 2013
                                                                                          21. Wen X et al: Nonmalignant breast papillary lesions at core-needle biopsy: a meta-analysis of underestimation and influencing factors. Ann Surg Oncol. 20(1):94-101, 2013
                                                                                          22. Brennan SB et al: Papilloma diagnosed at MRI-guided vacuum-assisted breast biopsy: is surgical excision still warranted? AJR Am J Roentgenol. 199(4):W512-9, 2012
                                                                                          23. Fu CY et al: Papillary breast lesions diagnosed by core biopsy require complete excision. Eur J Surg Oncol. 38(11):1029-35, 2012
                                                                                          24. Holley SO et al: Pathologic outcomes of nonmalignant papillary breast lesions diagnosed at imaging-guided core needle biopsy. Radiology. 265(2):379-84, 2012
                                                                                          25. Lee KA et al: Risk of malignancy when microscopic radial scars and microscopic papillomas are found at percutaneous biopsy. AJR Am J Roentgenol. 198(2):W141-5, 2012
                                                                                          26. Li X et al: Microcalcification is an important factor in the management of breast intraductal papillomas diagnosed on core biopsy. Am J Clin Pathol. 138:789-95, 2012
                                                                                          27. Zhu Y et al: Solitary intraductal papillomas of the breast: MRI features and differentiation from small invasive ductal carcinomas. AJR Am J Roentgenol. 199(4):936-42, 2012
                                                                                          28. Chang JM et al: Clinical application of shear wave elastography (SWE) in the diagnosis of benign and malignant breast diseases. Breast Cancer Res Treat. 129(1):89-97, 2011
                                                                                          29. Kim MJ et al: The diagnosis of non-malignant papillary lesions of the breast: comparison of ultrasound-guided automated gun biopsy and vacuum-assisted removal. Clin Radiol. 66(6):530-5, 2011
                                                                                          30. Youk JH et al: Benign papilloma without atypia diagnosed at US-guided 14-gauge core-needle biopsy: clinical and US features predictive of upgrade to malignancy. Radiology. 258(1):81-8, 2011
                                                                                          31. Chang JM et al: Risk of carcinoma after subsequent excision of benign papilloma initially diagnosed with an ultrasound (US)-guided 14-gauge core needle biopsy: a prospective observational study. Eur Radiol. 20(5):1093-100, 2010
                                                                                          32. Debnath D et al: Multiple Papillomatosis of Breast and Patient's Choice of Treatment. Patholog Res Int. 2010:540590, 2010
                                                                                          33. Jung SY et al: Risk factors for malignancy in benign papillomas of the breast on core needle biopsy. World J Surg. 34(2):261-5, 2010
                                                                                          34. Troxell ML et al: High prevalence of PIK3CA/AKT pathway mutations in papillary neoplasms of the breast. Mod Pathol. 23(1):27-37, 2010
                                                                                          35. Chang JM et al: Does ultrasound-guided directional vacuum-assisted removal help eliminate abnormal nipple discharge in patients with benign intraductal single mass? Korean J Radiol. 10(6):575-80, 2009
                                                                                          36. Cheng TY et al: Risk factors associated with conversion from nonmalignant to malignant diagnosis after surgical excision of breast papillary lesions. Ann Surg Oncol. 16(12):3375-9, 2009
                                                                                          37. Maxwell AJ: Ultrasound-guided vacuum-assisted excision of breast papillomas: review of 6-years experience. Clin Radiol. 64(8):801-6, 2009
                                                                                          38. Rosen PP: Papilloma and Related Benign Tumors. In Rosen PP: Rosen's Breast Pathology. Philadelphia: Lippincott Williams & Wilkins. 85-136, 2009
                                                                                          39. Muttarak M et al: Spectrum of papillary lesions of the breast: clinical, imaging, and pathologic correlation. AJR Am J Roentgenol. 191(3):700-7, 2008
                                                                                          40. Shin HJ et al: Papillary lesions of the breast diagnosed at percutaneous sonographically guided biopsy: comparison of sonographic features and biopsy methods. AJR Am J Roentgenol. 190(3):630-6, 2008
                                                                                          41. Skandarajah AR et al: Benign papilloma on core biopsy requires surgical excision. Ann Surg Oncol. 15(8):2272-7, 2008
                                                                                          42. Bhattarai N et al: Intraductal papilloma: features on MR ductography using a microscopic coil. AJR Am J Roentgenol. 186(1):44-7, 2006
                                                                                          43. Lewis JT et al: An analysis of breast cancer risk in women with single, multiple, and atypical papilloma. Am J Surg Pathol. 30(6):665-72, 2006
                                                                                          44. Lewis JT et al: An analysis of breast cancer risk in women with single, multiple, and atypical papilloma. Am J Surg Pathol. 30:665-72, 2006
                                                                                          45. Liberman L et al: Is surgical excision warranted after benign, concordant diagnosis of papilloma at percutaneous breast biopsy? AJR Am J Roentgenol. 186(5):1328-34, 2006
                                                                                          46. Mercado CL et al: Papillary lesions of the breast at percutaneous core-needle biopsy. Radiology. 238(3):801-8, 2006
                                                                                          47. Nelson RS et al: Twenty-year outcome following central duct resection for bloody nipple discharge. Ann Surg. 243(4):522-4, 2006
                                                                                          48. Dooley WC et al: Office-based breast ductoscopy for diagnosis. Am J Surg. 188(4):415-8, 2004
                                                                                          49. Daniel BL et al: Magnetic resonance imaging of intraductal papilloma of the breast. Magn Reson Imaging. 21(8):887-92, 2003
                                                                                          50. Mercado CL et al: Papillary lesions of the breast: evaluation with stereotactic directional vacuum-assisted biopsy. Radiology. 221(3):650-5, 2001
                                                                                          51. Hild F et al: Ductal orientated sonography improves the diagnosis of pathological nipple discharge of the female breast compared with galactography. Eur J Cancer Prev. 7 Suppl 1:S57-62, 1998