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Medullary Carcinoma
Jessica W. T. Leung, MD; Wei Tse Yang, MBBS
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KEY FACTS

  • Terminology

    • Imaging

      • Top Differential Diagnoses

        • Pathology

          • Clinical Issues

            TERMINOLOGY

            • Abbreviations

              • Medullary carcinoma (MC)
            • Definitions

              • Medullary carcinoma (MC): Rare special type of invasive ductal carcinoma (IDC)
              • Medullary refers to marrow of bones → soft mass
                • Lack of desmoplastic stroma and soft consistency differentiates medullary from other carcinomas
              • Circumscribed carcinoma with poorly differentiated cells, little stroma, and lymphoid infiltration
              • 5 key features must be present in ≥ 90% of tumor
                • Predominant syncytial growth (> 75%): Neoplastic cells arranged in broad anastomosing sheets
                • Sharply circumscribed pushing borders: Edge of tumor pushes rather than infiltrating
                  • Carcinoma cells should not invade as single cells or small nests
                • Marked lymphoplasmacytic reaction: Must involve periphery and diffusely involve tumor itself
                • High nuclear grade with frequent mitoses
                • Absence of glandular or fatty tissue within tumor
                  • DCIS scant or absent
              • Atypical MC = IDC NST with medullary features, at least 1 key feature lacking
                • Distinguish from MC
              • WHO classification of breast tumors (2013): Carcinoma with medullary features (CMF) to include both MC and atypical MC
                • Adequate treatment indicated for either; aggressive triple-negative features often present

            IMAGING

            • General Features

              • Mammographic Findings

                • Ultrasonographic Findings

                  • MR Findings

                    • Image-Guided Biopsy

                      • Imaging Recommendations

                        DIFFERENTIAL DIAGNOSIS

                          PATHOLOGY

                          • General Features

                            • Staging, Grading, & Classification

                              • Gross Pathologic & Surgical Features

                                • Microscopic Features

                                  CLINICAL ISSUES

                                  • Presentation

                                    • Demographics

                                      • Natural History & Prognosis

                                        • Treatment

                                          DIAGNOSTIC CHECKLIST

                                          • Consider

                                            • Image Interpretation Pearls

                                              Selected References

                                              1. Rechsteiner M et al: Somatic BRCA1 mutations in clinically sporadic breast cancer with medullary histological features. J Cancer Res Clin Oncol. 144(5):865-74, 2018
                                              2. Romero P et al: Medullary breast carcinoma, a triple-negative breast cancer associated with BCLG overexpression. Am J Pathol. 188(10):2378-91, 2018
                                              3. Zangouri V MD et al: Medullary breast carcinoma and invasive ductal carcinoma: a review study. Iran J Med Sci. 43(4):365-71, 2018
                                              4. Kouhen F et al: Prognosis of medullary carcinoma of the breast: 10 years' experience in a single institution. Breast J. 23(1):112-4, 2017
                                              5. Mateo AM et al: Chemotherapy significantly improves survival for patients with T1c-T2N0M0 medullary breast cancer: 3739 cases from the National Cancer Data Base. Ann Surg Oncol. 24(4):1050-6, 2017
                                              6. Stelmach A et al: Typical medullary breast carcinoma: clinical outcomes and treatment results. Breast J. 23(6):770-1, 2017
                                              7. Mateo AM et al: Atypical medullary carcinoma of the breast has similar prognostic factors and survival to typical medullary breast carcinoma: 3,976 cases from the National Cancer Data Base. J Surg Oncol. 114(5):533-6, 2016
                                              8. Wang XX et al: Difference in characteristics and outcomes between medullary breast carcinoma and invasive ductal carcinoma: a population based study from SEER 18 database. Oncotarget. 7(16):22665-73, 2016
                                              9. Chu Z et al: Clinicopathologic characteristics of typical medullary breast carcinoma: a retrospective study of 117 cases. PLoS One. 9(11):e111493, 2014
                                              10. Dieci MV et al: Rare breast cancer subtypes: histological, molecular, and clinical peculiarities. Oncologist. 19(8):805-13, 2014
                                              11. Larribe M et al: Breast cancers with round lumps: correlations between imaging and anatomopathology. Diagn Interv Imaging. 95(1):37-46, 2014
                                              12. Cao AY et al: Clinicopathologic characteristics at diagnosis and the survival of patients with medullary breast carcinoma in China: a comparison with infiltrating ductal carcinoma-not otherwise specified. World J Surg Oncol. 11:91, 2013
                                              13. Park I et al: Comparison of the characteristics of medullary breast carcinoma and invasive ductal carcinoma. J Breast Cancer. 16(4):417-25, 2013
                                              14. Sinn HP et al: A Brief Overview of the WHO Classification of Breast Tumors, 4th Edition, Focusing on Issues and Updates from the 3rd Edition. Breast Care (Basel). 8(2):149-54, 2013
                                              15. Huober J et al: Prognosis of medullary breast cancer: analysis of 13 International Breast Cancer Study Group (IBCSG) trials. Ann Oncol. 23(11):2843-51, 2012
                                              16. Jeong SJ et al: Medullary carcinoma of the breast: MRI findings. AJR Am J Roentgenol. 198(5):W482-7, 2012
                                              17. Karan B et al: Unusual malignant breast lesions: imaging-pathological correlations. Diagn Interv Radiol. 18(3):270-6, 2012
                                              18. Work ME et al: Risk factors for uncommon histologic subtypes of breast cancer using centralized pathology review in the Breast Cancer Family Registry. Breast Cancer Res Treat. 134(3):1209-20, 2012
                                              19. Linda A et al: Unusual malignant tumors of the breast: MRI features and pathologic correlation. Eur J Radiol. 75(2):178-84, 2010
                                              20. Yoo JL et al: Can MR Imaging contribute in characterizing well-circumscribed breast carcinomas? Radiographics. 30(6):1689-702, 2010
                                              21. Tominaga J et al: MR imaging of medullary carcinoma of the breast. Eur J Radiol. 70(3):525-9, 2009
                                              22. Vu-Nishino H et al: Clinicopathologic features and long-term outcome of patients with medullary breast carcinoma managed with breast-conserving therapy (BCT). Int J Radiat Oncol Biol Phys. 62(4):1040-7, 2005
                                              23. Eichhorn JH: Medullary carcinoma, provocative now as then. Semin Diagn Pathol. 21(1):65-73, 2004
                                              24. Gombos EC et al: Infiltrating carcinoma with medullary features in the male breast: imaging and pathologic findings. Breast J. 10(6):548-9, 2004
                                              25. Iau PT et al: Are medullary breast cancers an indication for BRCA1 mutation screening? A mutation analysis of 42 cases of medullary breast cancer. Breast Cancer Res Treat. 85(1):81-8, 2004
                                              26. Osin P et al: Distinct genetic and epigenetic changes in medullary breast cancer. Int J Surg Pathol. 11(3):153-8, 2003
                                              27. Yilmaz E et al: Comparison of mammographic and sonographic findings in typical and atypical medullary carcinomas of the breast. Clin Radiol. 57(7):640-5, 2002
                                              28. Cheung YC et al: Sonographic and pathologic findings in typical and atypical medullary carcinomas of the breast. J Clin Ultrasound. 28(7):325-31, 2000
                                              29. Jensen ML et al: Prognostic comparison of three classifications for medullary carcinomas of the breast. Histopathology. 30(6):523-32, 1997
                                              30. Liberman L et al: Overdiagnosis of medullary carcinoma: a mammographic-pathologic correlative study. Radiology. 201(2):443-6, 1996
                                              31. Cook DL et al: Comparison of DNA content, S-phase fraction, and survival between medullary and ductal carcinoma of the breast. Am J Clin Pathol. 104(1):17-22, 1995
                                              32. Moore OS Jr et al: The relatively favorable prognosis of medullary carcinoma of the breast. Cancer. 2(4):635-42, 1949
                                              33. Foote Jr FW et al: A histologic classification of carcinoma of the breast. Surgery. 19:74-99, 1946
                                              Related Anatomy
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                                              Related Differential Diagnoses
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                                              References
                                              Tables

                                              Tables

                                              KEY FACTS

                                              • Terminology

                                                • Imaging

                                                  • Top Differential Diagnoses

                                                    • Pathology

                                                      • Clinical Issues

                                                        TERMINOLOGY

                                                        • Abbreviations

                                                          • Medullary carcinoma (MC)
                                                        • Definitions

                                                          • Medullary carcinoma (MC): Rare special type of invasive ductal carcinoma (IDC)
                                                          • Medullary refers to marrow of bones → soft mass
                                                            • Lack of desmoplastic stroma and soft consistency differentiates medullary from other carcinomas
                                                          • Circumscribed carcinoma with poorly differentiated cells, little stroma, and lymphoid infiltration
                                                          • 5 key features must be present in ≥ 90% of tumor
                                                            • Predominant syncytial growth (> 75%): Neoplastic cells arranged in broad anastomosing sheets
                                                            • Sharply circumscribed pushing borders: Edge of tumor pushes rather than infiltrating
                                                              • Carcinoma cells should not invade as single cells or small nests
                                                            • Marked lymphoplasmacytic reaction: Must involve periphery and diffusely involve tumor itself
                                                            • High nuclear grade with frequent mitoses
                                                            • Absence of glandular or fatty tissue within tumor
                                                              • DCIS scant or absent
                                                          • Atypical MC = IDC NST with medullary features, at least 1 key feature lacking
                                                            • Distinguish from MC
                                                          • WHO classification of breast tumors (2013): Carcinoma with medullary features (CMF) to include both MC and atypical MC
                                                            • Adequate treatment indicated for either; aggressive triple-negative features often present

                                                        IMAGING

                                                        • General Features

                                                          • Mammographic Findings

                                                            • Ultrasonographic Findings

                                                              • MR Findings

                                                                • Image-Guided Biopsy

                                                                  • Imaging Recommendations

                                                                    DIFFERENTIAL DIAGNOSIS

                                                                      PATHOLOGY

                                                                      • General Features

                                                                        • Staging, Grading, & Classification

                                                                          • Gross Pathologic & Surgical Features

                                                                            • Microscopic Features

                                                                              CLINICAL ISSUES

                                                                              • Presentation

                                                                                • Demographics

                                                                                  • Natural History & Prognosis

                                                                                    • Treatment

                                                                                      DIAGNOSTIC CHECKLIST

                                                                                      • Consider

                                                                                        • Image Interpretation Pearls

                                                                                          Selected References

                                                                                          1. Rechsteiner M et al: Somatic BRCA1 mutations in clinically sporadic breast cancer with medullary histological features. J Cancer Res Clin Oncol. 144(5):865-74, 2018
                                                                                          2. Romero P et al: Medullary breast carcinoma, a triple-negative breast cancer associated with BCLG overexpression. Am J Pathol. 188(10):2378-91, 2018
                                                                                          3. Zangouri V MD et al: Medullary breast carcinoma and invasive ductal carcinoma: a review study. Iran J Med Sci. 43(4):365-71, 2018
                                                                                          4. Kouhen F et al: Prognosis of medullary carcinoma of the breast: 10 years' experience in a single institution. Breast J. 23(1):112-4, 2017
                                                                                          5. Mateo AM et al: Chemotherapy significantly improves survival for patients with T1c-T2N0M0 medullary breast cancer: 3739 cases from the National Cancer Data Base. Ann Surg Oncol. 24(4):1050-6, 2017
                                                                                          6. Stelmach A et al: Typical medullary breast carcinoma: clinical outcomes and treatment results. Breast J. 23(6):770-1, 2017
                                                                                          7. Mateo AM et al: Atypical medullary carcinoma of the breast has similar prognostic factors and survival to typical medullary breast carcinoma: 3,976 cases from the National Cancer Data Base. J Surg Oncol. 114(5):533-6, 2016
                                                                                          8. Wang XX et al: Difference in characteristics and outcomes between medullary breast carcinoma and invasive ductal carcinoma: a population based study from SEER 18 database. Oncotarget. 7(16):22665-73, 2016
                                                                                          9. Chu Z et al: Clinicopathologic characteristics of typical medullary breast carcinoma: a retrospective study of 117 cases. PLoS One. 9(11):e111493, 2014
                                                                                          10. Dieci MV et al: Rare breast cancer subtypes: histological, molecular, and clinical peculiarities. Oncologist. 19(8):805-13, 2014
                                                                                          11. Larribe M et al: Breast cancers with round lumps: correlations between imaging and anatomopathology. Diagn Interv Imaging. 95(1):37-46, 2014
                                                                                          12. Cao AY et al: Clinicopathologic characteristics at diagnosis and the survival of patients with medullary breast carcinoma in China: a comparison with infiltrating ductal carcinoma-not otherwise specified. World J Surg Oncol. 11:91, 2013
                                                                                          13. Park I et al: Comparison of the characteristics of medullary breast carcinoma and invasive ductal carcinoma. J Breast Cancer. 16(4):417-25, 2013
                                                                                          14. Sinn HP et al: A Brief Overview of the WHO Classification of Breast Tumors, 4th Edition, Focusing on Issues and Updates from the 3rd Edition. Breast Care (Basel). 8(2):149-54, 2013
                                                                                          15. Huober J et al: Prognosis of medullary breast cancer: analysis of 13 International Breast Cancer Study Group (IBCSG) trials. Ann Oncol. 23(11):2843-51, 2012
                                                                                          16. Jeong SJ et al: Medullary carcinoma of the breast: MRI findings. AJR Am J Roentgenol. 198(5):W482-7, 2012
                                                                                          17. Karan B et al: Unusual malignant breast lesions: imaging-pathological correlations. Diagn Interv Radiol. 18(3):270-6, 2012
                                                                                          18. Work ME et al: Risk factors for uncommon histologic subtypes of breast cancer using centralized pathology review in the Breast Cancer Family Registry. Breast Cancer Res Treat. 134(3):1209-20, 2012
                                                                                          19. Linda A et al: Unusual malignant tumors of the breast: MRI features and pathologic correlation. Eur J Radiol. 75(2):178-84, 2010
                                                                                          20. Yoo JL et al: Can MR Imaging contribute in characterizing well-circumscribed breast carcinomas? Radiographics. 30(6):1689-702, 2010
                                                                                          21. Tominaga J et al: MR imaging of medullary carcinoma of the breast. Eur J Radiol. 70(3):525-9, 2009
                                                                                          22. Vu-Nishino H et al: Clinicopathologic features and long-term outcome of patients with medullary breast carcinoma managed with breast-conserving therapy (BCT). Int J Radiat Oncol Biol Phys. 62(4):1040-7, 2005
                                                                                          23. Eichhorn JH: Medullary carcinoma, provocative now as then. Semin Diagn Pathol. 21(1):65-73, 2004
                                                                                          24. Gombos EC et al: Infiltrating carcinoma with medullary features in the male breast: imaging and pathologic findings. Breast J. 10(6):548-9, 2004
                                                                                          25. Iau PT et al: Are medullary breast cancers an indication for BRCA1 mutation screening? A mutation analysis of 42 cases of medullary breast cancer. Breast Cancer Res Treat. 85(1):81-8, 2004
                                                                                          26. Osin P et al: Distinct genetic and epigenetic changes in medullary breast cancer. Int J Surg Pathol. 11(3):153-8, 2003
                                                                                          27. Yilmaz E et al: Comparison of mammographic and sonographic findings in typical and atypical medullary carcinomas of the breast. Clin Radiol. 57(7):640-5, 2002
                                                                                          28. Cheung YC et al: Sonographic and pathologic findings in typical and atypical medullary carcinomas of the breast. J Clin Ultrasound. 28(7):325-31, 2000
                                                                                          29. Jensen ML et al: Prognostic comparison of three classifications for medullary carcinomas of the breast. Histopathology. 30(6):523-32, 1997
                                                                                          30. Liberman L et al: Overdiagnosis of medullary carcinoma: a mammographic-pathologic correlative study. Radiology. 201(2):443-6, 1996
                                                                                          31. Cook DL et al: Comparison of DNA content, S-phase fraction, and survival between medullary and ductal carcinoma of the breast. Am J Clin Pathol. 104(1):17-22, 1995
                                                                                          32. Moore OS Jr et al: The relatively favorable prognosis of medullary carcinoma of the breast. Cancer. 2(4):635-42, 1949
                                                                                          33. Foote Jr FW et al: A histologic classification of carcinoma of the breast. Surgery. 19:74-99, 1946