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Metastatic Node, Unknown Primary
Haydee Ojeda-Fournier, MD; Wei Tse Yang, MBBS
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KEY FACTS

  • Terminology

    • Imaging

      • Top Differential Diagnoses

        • Pathology

          • Clinical Issues

            TERMINOLOGY

            • Abbreviations

              • Axillary lymph node (AXLN)
              • Carcinoma of unknown primary (CUP)
              • Inframammary fold (IMF)
            • Definitions

              • Axillary or intramammary nodal metastatic adenocarcinoma consistent with breast origin, otherwise without clinically or mammographically evident breast cancer
                • Uncommon presentation, diagnostic & therapeutic challenge

            IMAGING

            • General Features

              • Mammographic Findings

                • Ultrasonographic Findings

                  • MR Findings

                    • Nuclear Medicine Findings

                      • Imaging Recommendations

                        DIFFERENTIAL DIAGNOSIS

                          PATHOLOGY

                          • General Features

                            • Microscopic Features

                              CLINICAL ISSUES

                              • Presentation

                                • Demographics

                                  • Natural History & Prognosis

                                    • Treatment

                                      DIAGNOSTIC CHECKLIST

                                      • Consider

                                        Selected References

                                        1. Bochtler T et al: Diagnosis and management of metastatic neoplasms with unknown primary. Semin Diagn Pathol. 35(3):199-206, 2018
                                        2. Ouldamer L et al: Axillary lymph node metastases from unknown primary: a French multicentre study. Eur J Obstet Gynecol Reprod Biol. 223:103-7, 2018
                                        3. Terada M et al: Occult breast cancer may originate from ectopic breast tissue present in axillary lymph nodes. Breast Cancer Res Treat. 172(1):1-7, 2018
                                        4. McCartan DP et al: Oncologic outcomes after treatment for MRI occult breast cancer (pT0N+). Ann Surg Oncol. 24(11):3141-7, 2017
                                        5. Kandalaft PL et al: Comparative sensitivities and specificities of antibodies to breast markers GCDFP-15, mammaglobin A, and different clones of antibodies to GATA-3: a study of 338 tumors using whole sections. Appl Immunohistochem Mol Morphol. 24(9):609-14, 2016
                                        6. Miettinen M et al: GATA3: a multispecific but potentially useful marker in surgical pathology: a systematic analysis of 2500 epithelial and nonepithelial tumors. Am J Surg Pathol. 38(1):13-22, 2014
                                        7. Sohn G et al: Treatment and survival of patients with occult breast cancer with axillary lymph node metastasis: a nationwide retrospective study. J Surg Oncol. 110(3):270-4, 2014
                                        8. Hemminki K et al: Site-specific survival rates for cancer of unknown primary according to location of metastases. Int J Cancer. 133(1):182-9, 2013
                                        9. de Bresser J et al: Breast MRI in clinically and mammographically occult breast cancer presenting with an axillary metastasis: a systematic review. Eur J Surg Oncol. 36(2):114-9, 2010
                                        10. Kinoshita S et al: Metachronous secondary primary occult breast cancer initially presenting with metastases to the contralateral axillary lymph nodes: report of a case. Breast Cancer. 17(1):71-4, 2010
                                        11. Pentheroudakis G et al: Axillary nodal metastases from carcinoma of unknown primary (CUPAx): a systematic review of published evidence. Breast Cancer Res Treat. 119(1):1-11, 2010
                                        12. Schwab FD et al: Suspicious axillary lymph nodes in patients with unremarkable imaging of the breast. Eur J Obstet Gynecol Reprod Biol. 150(1):88-91, 2010
                                        13. Wang X et al: Clinical benefits of mastectomy on treatment of occult breast carcinoma presenting axillary metastases. Breast J. 16(1):32-7, 2010
                                        14. Lanitis S et al: Axillary metastatic disease as presentation of occult or contralateral breast cancer. Breast. 18(4):225-7, 2009
                                        15. Bhargava R et al: Mammaglobin vs GCDFP-15: an immunohistologic validation survey for sensitivity and specificity. Am J Clin Pathol. 127(1):103-13, 2007
                                        16. Capobianco G et al: Lymph node axillary metastasis from occult contralateral infiltrating lobular carcinoma arising in accessory breast: MRI diagnosis. Breast J. 13(3):305-7, 2007
                                        17. Ko EY et al: Breast MRI for evaluating patients with metastatic axillary lymph node and initially negative mammography and sonography. Korean J Radiol. 8(5):382-9, 2007
                                        18. Yamaguchi H et al: Occult breast cancer presenting as axillary metastases. Breast. 15(2):259-62, 2006
                                        19. Buchanan CL et al: Utility of breast magnetic resonance imaging in patients with occult primary breast cancer. Ann Surg Oncol. 12(12):1045-53, 2005
                                        20. Khandelwal AK et al: Therapeutic options for occult breast cancer: a survey of the American Society of Breast Surgeons and review of the literature. Am J Surg. 190(4):609-13, 2005
                                        21. McMahon K et al: Breast magnetic resonance imaging: an essential role in malignant axillary lymphadenopathy of unknown origin. Australas Radiol. 49(5):382-9, 2005
                                        22. Fourquet A et al: Occult primary cancer with axillary metastases. In Harris JR et al. Diseases of the Breast. 2nd ed. Philadelphia: Lippincott. 703-07, 2000
                                        23. Steunebrink M et al: Bilateral axillary metastases of occult breast carcinoma: report of a case with a review of the literature. Breast. 14(2):165-8, 2005
                                        24. Yirmibeşoğlu E et al: A patient with occult breast cancer presenting with an axillary lymph node metastasis and a synchronous contralateral breast cancer. Breast. 14(2):157-62, 2005
                                        25. Blanchard DK et al: Retrospective study of women presenting with axillary metastases from occult breast carcinoma. World J Surg. 28(6):535-9, 2004
                                        26. Muttarak M et al: Role of mammography in diagnosis of axillary abnormalities in women with normal breast examination. Australas Radiol. 48(3):306-10, 2004
                                        27. Matsuoka K et al: Occult breast carcinoma presenting with axillary lymph node metastases: follow-up of eleven patients. Breast Cancer. 10(4):330-4, 2003
                                        28. Pavlidis N et al: Diagnostic and therapeutic management of cancer of an unknown primary. Eur J Cancer. 39(14):1990-2005, 2003
                                        29. Schelfout K et al: Breast MR imaging in a patient with unilateral axillary lymphadenopathy and unknown primary malignancy. Eur Radiol. 13(9):2128-32, 2003
                                        30. Medina-Franco H et al: Occult breast carcinoma presenting with axillary lymph node metastases. Rev Invest Clin. 54(3):204-8, 2002
                                        31. Vlastos G et al: Feasibility of breast preservation in the treatment of occult primary carcinoma presenting with axillary metastases. Ann Surg Oncol. 8(5):425-31, 2001
                                        32. Foroudi F et al: Occult breast carcinoma presenting as axillary metastases. Int J Radiat Oncol Biol Phys. 47(1):143-7, 2000
                                        33. Orel SG et al: Breast MR imaging in patients with axillary node metastases and unknown primary malignancy. Radiology. 212(2):543-9, 1999
                                        34. Morris EA et al: MR imaging of the breast in patients with occult primary breast carcinoma. Radiology. 205(2):437-40, 1997
                                        35. Leibman AJ et al: Mammography in women with axillary lymphadenopathy and normal breasts on physical examination: value in detecting occult breast carcinoma. AJR Am J Roentgenol. 159(3):493-5, 1992
                                        36. Rosen PP et al: Occult breast carcinoma presenting with axillary lymph node metastases: a follow-up study of 48 patients. Hum Pathol. 21(5):518-23, 1990
                                        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

                                                    • Axillary lymph node (AXLN)
                                                    • Carcinoma of unknown primary (CUP)
                                                    • Inframammary fold (IMF)
                                                  • Definitions

                                                    • Axillary or intramammary nodal metastatic adenocarcinoma consistent with breast origin, otherwise without clinically or mammographically evident breast cancer
                                                      • Uncommon presentation, diagnostic & therapeutic challenge

                                                  IMAGING

                                                  • General Features

                                                    • Mammographic Findings

                                                      • Ultrasonographic Findings

                                                        • MR Findings

                                                          • Nuclear Medicine Findings

                                                            • Imaging Recommendations

                                                              DIFFERENTIAL DIAGNOSIS

                                                                PATHOLOGY

                                                                • General Features

                                                                  • Microscopic Features

                                                                    CLINICAL ISSUES

                                                                    • Presentation

                                                                      • Demographics

                                                                        • Natural History & Prognosis

                                                                          • Treatment

                                                                            DIAGNOSTIC CHECKLIST

                                                                            • Consider

                                                                              Selected References

                                                                              1. Bochtler T et al: Diagnosis and management of metastatic neoplasms with unknown primary. Semin Diagn Pathol. 35(3):199-206, 2018
                                                                              2. Ouldamer L et al: Axillary lymph node metastases from unknown primary: a French multicentre study. Eur J Obstet Gynecol Reprod Biol. 223:103-7, 2018
                                                                              3. Terada M et al: Occult breast cancer may originate from ectopic breast tissue present in axillary lymph nodes. Breast Cancer Res Treat. 172(1):1-7, 2018
                                                                              4. McCartan DP et al: Oncologic outcomes after treatment for MRI occult breast cancer (pT0N+). Ann Surg Oncol. 24(11):3141-7, 2017
                                                                              5. Kandalaft PL et al: Comparative sensitivities and specificities of antibodies to breast markers GCDFP-15, mammaglobin A, and different clones of antibodies to GATA-3: a study of 338 tumors using whole sections. Appl Immunohistochem Mol Morphol. 24(9):609-14, 2016
                                                                              6. Miettinen M et al: GATA3: a multispecific but potentially useful marker in surgical pathology: a systematic analysis of 2500 epithelial and nonepithelial tumors. Am J Surg Pathol. 38(1):13-22, 2014
                                                                              7. Sohn G et al: Treatment and survival of patients with occult breast cancer with axillary lymph node metastasis: a nationwide retrospective study. J Surg Oncol. 110(3):270-4, 2014
                                                                              8. Hemminki K et al: Site-specific survival rates for cancer of unknown primary according to location of metastases. Int J Cancer. 133(1):182-9, 2013
                                                                              9. de Bresser J et al: Breast MRI in clinically and mammographically occult breast cancer presenting with an axillary metastasis: a systematic review. Eur J Surg Oncol. 36(2):114-9, 2010
                                                                              10. Kinoshita S et al: Metachronous secondary primary occult breast cancer initially presenting with metastases to the contralateral axillary lymph nodes: report of a case. Breast Cancer. 17(1):71-4, 2010
                                                                              11. Pentheroudakis G et al: Axillary nodal metastases from carcinoma of unknown primary (CUPAx): a systematic review of published evidence. Breast Cancer Res Treat. 119(1):1-11, 2010
                                                                              12. Schwab FD et al: Suspicious axillary lymph nodes in patients with unremarkable imaging of the breast. Eur J Obstet Gynecol Reprod Biol. 150(1):88-91, 2010
                                                                              13. Wang X et al: Clinical benefits of mastectomy on treatment of occult breast carcinoma presenting axillary metastases. Breast J. 16(1):32-7, 2010
                                                                              14. Lanitis S et al: Axillary metastatic disease as presentation of occult or contralateral breast cancer. Breast. 18(4):225-7, 2009
                                                                              15. Bhargava R et al: Mammaglobin vs GCDFP-15: an immunohistologic validation survey for sensitivity and specificity. Am J Clin Pathol. 127(1):103-13, 2007
                                                                              16. Capobianco G et al: Lymph node axillary metastasis from occult contralateral infiltrating lobular carcinoma arising in accessory breast: MRI diagnosis. Breast J. 13(3):305-7, 2007
                                                                              17. Ko EY et al: Breast MRI for evaluating patients with metastatic axillary lymph node and initially negative mammography and sonography. Korean J Radiol. 8(5):382-9, 2007
                                                                              18. Yamaguchi H et al: Occult breast cancer presenting as axillary metastases. Breast. 15(2):259-62, 2006
                                                                              19. Buchanan CL et al: Utility of breast magnetic resonance imaging in patients with occult primary breast cancer. Ann Surg Oncol. 12(12):1045-53, 2005
                                                                              20. Khandelwal AK et al: Therapeutic options for occult breast cancer: a survey of the American Society of Breast Surgeons and review of the literature. Am J Surg. 190(4):609-13, 2005
                                                                              21. McMahon K et al: Breast magnetic resonance imaging: an essential role in malignant axillary lymphadenopathy of unknown origin. Australas Radiol. 49(5):382-9, 2005
                                                                              22. Fourquet A et al: Occult primary cancer with axillary metastases. In Harris JR et al. Diseases of the Breast. 2nd ed. Philadelphia: Lippincott. 703-07, 2000
                                                                              23. Steunebrink M et al: Bilateral axillary metastases of occult breast carcinoma: report of a case with a review of the literature. Breast. 14(2):165-8, 2005
                                                                              24. Yirmibeşoğlu E et al: A patient with occult breast cancer presenting with an axillary lymph node metastasis and a synchronous contralateral breast cancer. Breast. 14(2):157-62, 2005
                                                                              25. Blanchard DK et al: Retrospective study of women presenting with axillary metastases from occult breast carcinoma. World J Surg. 28(6):535-9, 2004
                                                                              26. Muttarak M et al: Role of mammography in diagnosis of axillary abnormalities in women with normal breast examination. Australas Radiol. 48(3):306-10, 2004
                                                                              27. Matsuoka K et al: Occult breast carcinoma presenting with axillary lymph node metastases: follow-up of eleven patients. Breast Cancer. 10(4):330-4, 2003
                                                                              28. Pavlidis N et al: Diagnostic and therapeutic management of cancer of an unknown primary. Eur J Cancer. 39(14):1990-2005, 2003
                                                                              29. Schelfout K et al: Breast MR imaging in a patient with unilateral axillary lymphadenopathy and unknown primary malignancy. Eur Radiol. 13(9):2128-32, 2003
                                                                              30. Medina-Franco H et al: Occult breast carcinoma presenting with axillary lymph node metastases. Rev Invest Clin. 54(3):204-8, 2002
                                                                              31. Vlastos G et al: Feasibility of breast preservation in the treatment of occult primary carcinoma presenting with axillary metastases. Ann Surg Oncol. 8(5):425-31, 2001
                                                                              32. Foroudi F et al: Occult breast carcinoma presenting as axillary metastases. Int J Radiat Oncol Biol Phys. 47(1):143-7, 2000
                                                                              33. Orel SG et al: Breast MR imaging in patients with axillary node metastases and unknown primary malignancy. Radiology. 212(2):543-9, 1999
                                                                              34. Morris EA et al: MR imaging of the breast in patients with occult primary breast carcinoma. Radiology. 205(2):437-40, 1997
                                                                              35. Leibman AJ et al: Mammography in women with axillary lymphadenopathy and normal breasts on physical examination: value in detecting occult breast carcinoma. AJR Am J Roentgenol. 159(3):493-5, 1992
                                                                              36. Rosen PP et al: Occult breast carcinoma presenting with axillary lymph node metastases: a follow-up study of 48 patients. Hum Pathol. 21(5):518-23, 1990