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Left Axilla Adenocarcinoma of Unknown Origin

Educational Objective
Based on this clinical scenario and the accompanying image, understand how to arrive at a correct diagnosis.
1 Credit CME

A 76-year-old woman presented with a palpable left axillary mass. When she was 36 years old, she underwent a hysterectomy due to abnormal uterine bleeding and was taking estradiol to control postmenopausal vasomotor symptoms for the past 20 years. Bilateral diagnostic mammography revealed a high-density irregular mass in the left axilla with no nodules, architectural distortions, or microcalcifications in the breasts. Ultrasonography of the left breast showed a 4.6-cm lobulated mixed cystic and solid left axillary mass. Contrast-enhanced magnetic resonance imaging showed an enhancing 5.2-cm left axillary mass with no breast lesions (Figure 1A). The biopsy examination indicated high-grade adenocarcinoma with papillary features (estrogen receptor– and progesterone receptor–positive, ERBB2 [formerly HER2]–negative, and a high Ki67 index). Positron emission tomography/computed tomography revealed only high uptake in the left axilla region. The patient was treated at an outside hospital with neoadjuvant dose-dense doxorubicin and cyclophosphamide, followed by weekly paclitaxel for 10 weeks. She then transferred her care to our center for surgical management. We requested the pathology slides for review at our laboratory and additional immunostaining was performed, which revealed high-grade adenocarcinoma with tumor cells positive for PAX8 (Figure 1B), p53, and WT1 and negative for GATA3.

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B. High-grade serous carcinoma of gynecological origin

This patient underwent left axillary excisional lymph node biopsy, peritoneal washings, laparoscopic bilateral salpingo-oophorectomy, omental biopsy, and bilateral ureterolysis. Laparoscopy revealed that both ovaries were affixed to the pelvic peritoneum with adhesions, requiring bilateral ureterolysis. The uterus, cervix, and proximal fallopian tubes were surgically absent. On gross examination the distal fallopian tubes appeared unremarkable, and the left ovary appeared nodular. Given the clinical scenario, the fimbrial ends of the fallopian tubes were entirely excised and submitted for microscopic examination along with both ovaries. Microscopic examination revealed a residual 2.1-mm focus of high-grade serous carcinoma (Figure 2) involving the fimbrial end of the left fallopian tube. No omental involvement was seen. The immunostaining pattern was similar to that seen in the axillary metastasis prior to therapy. No residual carcinoma was identified in the left axillary lymph node. The patient’s cancer antigen 125 level was 13 U/mL before the surgery. Disease was staged as FIGO (International Federation of Gynecology and Obstetrics) stage IVB, and the patient received additional platinum-based adjuvant chemotherapy. Test results were negative for germline pathogenic sequence variants, including BRCA1 and BRCA2.

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Article Information

Corresponding Author: Juan A. Santamaria-Barria, MD, University of Nebraska Medical Center, 986880 Nebraska Medical Center, Omaha, NE 68198 (juan.santamaria@unmc.edu).

Published Online: March 16, 2023. doi:10.1001/jamaoncol.2022.7858

Conflict of Interest Disclosures: Dr Santamaria-Barria reported nonfinancial support from an Axogen Inc educational travel stipend outside the submitted work. No other disclosures were reported.

Additional Contributions: We thank the patient for granting permission to publish this information.

Deng  K , Yang  C , Tan  Q ,  et al.  Sites of distant metastases and overall survival in ovarian cancer: a study of 1481 patients.   Gynecol Oncol. 2018;150(3):460-465. doi:10.1016/j.ygyno.2018.06.022 PubMedGoogle ScholarCrossref
Sibio  S , Sammartino  P , Accarpio  F ,  et al.  Axillary lymph node metastasis as first presentation of peritoneal carcinomatosis from serous papillary ovarian cancer: case report and review of the literature.   Eur J Gynaecol Oncol. 2014;35(2):170-173.doi:10.12892/ejgo24962014PubMedGoogle Scholar
Mirzaei  M , Eshraghi  A , Ghoddoosi  M ,  et al.  Axillary lymph-node metastases as the primary presentation of high-grade serous ovarian carcinoma: a case report.   Clin Case Rep. 2022;10(4):e05724. doi:10.1002/ccr3.5724 PubMedGoogle ScholarCrossref
Ilhan  B , Kılıç  B , Karanlik  H .  Ovarian cancer presenting as an axillary mass: case series and literature review.   Curr Res Transl Med. 2016;64(3):161-163. doi:10.1016/j.retram.2016.04.002 PubMedGoogle ScholarCrossref
Pentheroudakis  G , Lazaridis  G , Pavlidis  N .  Axillary nodal metastases from carcinoma of unknown primary (CUPAx): a systematic review of published evidence.   Breast Cancer Res Treat. 2010;119(1):1-11. doi:10.1007/s10549-009-0554-3 PubMedGoogle ScholarCrossref
Greco  FA , Lennington  WJ , Spigel  DR , Hainsworth  JD .  Molecular profiling diagnosis in unknown primary cancer: accuracy and ability to complement standard pathology.   J Natl Cancer Inst. 2013;105(11):782-790. doi:10.1093/jnci/djt099 PubMedGoogle ScholarCrossref
Greco  FA , Lennington  WJ , Spigel  DR , Hainsworth  JD .  Poorly differentiated neoplasms of unknown primary site: diagnostic usefulness of a molecular cancer classifier assay.   Mol Diagn Ther. 2015;19(2):91-97. doi:10.1007/s40291-015-0133-8 PubMedGoogle ScholarCrossref
Oien  KA , Dennis  JL .  Diagnostic work-up of carcinoma of unknown primary: from immunohistochemistry to molecular profiling.   Ann Oncol. 2012;23(suppl 10):x271-x277. doi:10.1093/annonc/mds357 PubMedGoogle ScholarCrossref
Schwartz  PE , LiVolsi  VA , Hildreth  N , MacLusky  NJ , Naftolin  FN , Eisenfeld  AJ .  Estrogen receptors in ovarian epithelial carcinoma.   Obstet Gynecol. 1982;59(2):229-238.PubMedGoogle Scholar
Sieh  W , Köbel  M , Longacre  TA ,  et al.  Hormone-receptor expression and ovarian cancer survival: an Ovarian Tumor Tissue Analysis consortium study.   Lancet Oncol. 2013;14(9):853-862. doi:10.1016/S1470-2045(13)70253-5 PubMedGoogle ScholarCrossref
AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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