Axillary Node Metastases with occult Primary Breast Cancer

Incidence and Differential Diagnosis

• Occult primary breast cancer was first recognized by William Halsted:
  • Who described three patients presenting with axillary tumors that were eventually found to represent breast cancer.
• In modern series:
  • Occult breast cancer accounts for 0.1% to 0.8%  of all newly diagnosed breast cancers:
    • The incidence has not decreased with improvements in breast imaging.
• Differential diagnosis:
  • In general:
    • Palpable axillary nodes are more often related to benign rather than malignant disorders:
      • However, when cancer is identified:
        • The most common tumor causing axillary lymphadenopathy is:
          • Breast cancer.
    • In several series:
      • The incidence of breast cancer in mixed populations of men and women with metastatic axillary adenopathy:
        • Is 50% or higher:
          • The vast majority are women:
            • Although occult primary breast cancer has been reported in men:
              • It is very rare.
  • Other neoplasms that may present with axillary nodal involvement are:
    • Lymphomas
    • Melanomas
    • Sarcomas
    • Thyroid cancers
    • Skin cancers
    • Lung cancers
    • Less often:
      • Uterine, ovarian, sweat gland, or gastric cancers.
  • In approximately 30% of cases:
    • The primary site is never identified.

• Initial Diagnostic Workup:
  • Biopsy:
    • The first step in the diagnostic workup of a patient with unexplained axillary adenopathy is:
      • A biopsy:
        • Besides standard light microscopic examination of hematoxylin and eosin-stained sections:
          • Other techniques such as;
            • Immunohistochemistry and sometimes electron microscopy.
              • Can help to narrow the differential diagnosis.
    • Immunohistochemistry:
      • The pathologic examination of a biopsy specimen for an isolated axillary lymph node metastatic adenocarcinoma or poorly differentiated carcinoma in a woman should include immunohistochemical staining for the following markers:
        • Carcinoembryonic antigen (CEA)
        • Cytokeratins 7 and 20
        • Estrogen receptor (ER) and progesterone receptor (PR)
        • Gross cystic disease fluid protein-15:
          • GCDFP:
            • Is identified by staining with the monoclonal antibody BRST2.
        • Mammaglobin
        • Thyroid transcription factor (TTF-1)
        • CA125
        • Men:
          • Should have routine staining for prostate cancer markers as well.
      • While none of these markers is sufficiently sensitive or specific to be used alone, certain patterns of expression favor the diagnosis of an occult breast cancer:
        • Positive staining for:
          • CEA, CK7, ER/PR, mammaglobin, CA125, and BRST2.
        • Negative staining for:
          • CK20 and TTF-1.
      • CEA is a sensitive marker for:
        • Adenocarcinomas of the breast, lung, and gastrointestinal tract:
          • But does not help to distinguish among these sites of origin.
      • On the other hand, differential expression of cytokeratins (CKs) can assist in this differentiation:
        • CK20 is a low molecular weight cytokeratin:
          • That is normally expressed in the gastrointestinal epithelium, urothelium, and in Merkel cells.
        • CK7 is expressed by tumors of the:
          • Lung, ovary, endometrium, and breast:
            • Not in the lower gastrointestinal tract.
              • The pattern of CK20 and CK7 may be particularly helpful in suggesting a primary site:
                • The presence of CK7 and absence of CK20:
                  • Favors a diagnosis of breast cancer.
      • TTF-1:
        • Is rarely positive in breast cancers:
          • While it is positive in 70% to 80%  of nonsquamous cancers arising in the lung.
      • CA-125:
        • Is commonly positive in ovarian carcinomas
          • But is positive in about 10% of breast cancers.
      • ER/PR:
        • Its presence in an axillary node, particularly in conjunction with other compatible IHC findings:
          • Lends support to a diagnosis of an occult breast primary.
        • Although positive staining for ER and/or PR supports a possible diagnosis of breast cancer:
          • These markers are nonspecific and they may also be expressed in:
            • Ovarian, uterine, lung, stomach, thyroid, and hepatobiliary cancers:
              • However:
                • ER/PR staining of an axillary node is compelling evidence of a primary breast cancer.
      • Other breast cancer-specific IHC stains are:;
        • BRST2 (for GCDFP) and mammaglobin:
          • BRST2 is positive in 65% to 80% of cases:
            • Is relatively specific for breast cancer:
              • Rarely, it is positive in:;
                • Skin adnexal tumors, endometrial cancers, and salivary gland tumors.
          • While mammaglobin is more sensitive, it is less specific for breast cancer:
            • Gynecologic, lung, urothelial, thyroid, colon and hepatobiliary tumors may stain positive:
              • Both stains are thus typically used together.
      • HER2 immunostaining:
        • Is not generally useful for the differential diagnosis of a carcinoma arising in the axillary nodes as it lacks specificity:
          • Furthermore, only 18% to 20%  of breast cancers overexpress this protein:
            • However, assay for HER2 overexpression by IHC or fluorescent in situ hybridization (FISH) is a routine component of the evaluation of all breast cancers:
              • As it permits the identification of those women who are most likely to respond to treatments targeting HER2 (eg, the therapeutic monoclonal antibody trastuzumab). 

Rodrigo Arrangoiz MS, MD, FACS cirujano oncology y miembro de Sociedad Quirúrgica S.C en el America British Cowdray Medical Center en la ciudad de Mexico:

• Es experto en el manejo del cáncer de mama.

Training:

• General surgery:

• Michigan State University:

• 2004 al 2010

• Surgical Oncology / Head and Neck Surgery / Endocrine Surgery:

• Fox Chase Cancer Center (Filadelfia):

• 2010 al 2012

• Masters in Science (Clinical research for health professionals):

• Drexel University (Filadelfia):

• 2010 al 2012

• Surgical Oncology / Head and Neck Surgery / Endocrine Surgery:

• IFHNOS / Memorial Sloan Kettering Cancer Center:

• 2014 al 2016

#Arrangoiz

#Surgeon

#Cirujano

#SurgicalOncologist

#CirujanoOncologo

#BreastSurgeon

#CirujanodeMama

#CancerSurgeon

#CirujanodeCancer