Secretory Carcinoma of the Breast IHC

Some detailed secretory carcinoma of the breast images to be compared with MASC

Dali Li and coworkers (2012) of the Fudan University Shanghai Cancer Center reviewed 15 FFPE preserved secretory breast carcinomas (SBC) that were collected between 2006 and 2010. One of their goals was to use histology and immunohistochemical (IHC) markers to determine if SBC in a Chinese population had a basal cell phenotype. The basal cell phenotype was defined as

  • HER2/ER negative
  • CK5/6 and EGFR positive

A goal on this post is to compare SBC with mammalian analog of secretory carcinoma (MASC) in salivary glands.  Both are now considered secretory carcinomas.

Patient Demographics

Table showing patient demographic data.

Table 1 from Li 2012

 

Age and sex  Note that three of the 15 patients, two of them males, are under the age of 20. Also note the number of female patients under the age of 40.

Symptoms were usually simple masses. The duration was usually  not defined (ND).

Site/locations  Note that two thirds of the 15 cases were in the axillary (arm pit) or upper outer quadrants. Areola are the pigmented region of the breast surrounding the nipple itself.

Size  Most of these tumors were caught before they became very large.

Treatments were fairly conservative

  • LE, local excision
  • MRM, modified radical mastectomy
  • CT, chemotherapy
  • RT, radiotherapy
  • SLNB, sentinel lymph node biopsy
  • SM, simple mastectomy
  • WLE, wide local excision

Axillary status seems to refer to axillary lymph nodes, second in line of defense after the sentinel lymph nodes.

Follow up All of the patients appeared to do fairly well.

Similarities to MASC via H&E staining

Hematoxylin Eosin (H&E) staining is a way of viewing structures in tissue and within cells. The nucleic acids in the nuclei stain purple whereas collagen tends to stain pink.

Hematoxylin Eosin (H&E) staining showing microcystic and eosinophilic secretions.

Figure 1a from Li 2012

Microcysts with eosinophilic (pink) secretions are a hallmark of MASC as well as secretory carcinoma of the breast.

Hematoxylin Eosin (H&E) staining showing tumor nests separated by dense collagen stroma.

Figure 1b from Li 2012

Li and coworkers commented on tumors being arranged in nests with dense pink staining collagen (Figure 1b).

Hematoxylin Eosin (H&E) staining showing follicle like struuctures with eosinophilic secretions and papillary growth pattern with fibrovascular core.

Figure 1c-d from Li 2012

The follicle like structures are a hallmark of MASC and secretory carcinoma of the thyroid.

Hematoxylin Eosin (H&E) staining showing macrocystic pattern with eosinophilic secretions.

Figure 1e from Li2012

Macrocysts are also a feature of MASC. This particular image came from case 10.

Hematoxylin Eosin (H&E) staining showing single and double nucleoli in Scretory breast carcinoma (SBC).

Figure 1f from Li 2012, arrows point to nucleoli seen in MASC

IHC antibodies used

Immunohistochemical (IHC) staining was performed on all 15 cases.

Table showing immunophenotype of 15 cases of SBC.

Table 2 Li 2012

triple negative”  markers estrogen receptor (ER), progesterone receptor (PR), and HER-2 (now ErbB2). Negative staining for all three is “triple negative breast cancer.” All 15 tumors were “triple negative.”

cytokeratin 5/6 This basal cell marker was seen in 12 of the 15 tumors.

Immunohistochemical staining using basic marker cytokeratin5/6.

Figure 2a from Li 2012. Cytokeratin 5/6

epidermal growth factor receptor (EGFR) Only six of the 16 tumors were positive for this basal cell marker.  EGFR is really not a definition of MASC either.

Immunohistochemical staining using EGFR.

Figure 2b from Li 2012 EGFR

S100 The polyclonal S-100 protein antibody from Dako, advertised to be selective for the S100B isoform. All 15 tumors were positive for what may be S100B.  S100 is part of the definition of MASC.

Immunohistochemical staining using Dako antibody specific for S100B.

Figure 2c from Li 2012. The Dako antibody used is specific for S100B, an isoform that binds transcription factor p53. S100B is also seen in the nucleus in MASC.

mammaglobin All 15 tumors were positive for mammaglobin. This may not be all of that surprising. Note that mammaglobin is also a protein marker for MASC.

GCDFP-15 (gross cystic disease fluid protein-15) None of the 15 tumors were positive for marker.
Ki-67, a proliferation marker. All tumors scored 10% or less.

Is secretory carcinoma of the breast a basal carcinoma?

Li reported that 13 of the 15 of their cancers met the definition. These IHC markers did not however correlate with an aggressive histology in that most of their basal-like secretory breast carcinomas showed mild dysplasia without necrosis and active cell proliferation. Local recurrence and distal metastases were not observed in the follow up. The authors recommended avoidance of aggressive treatments that might be employed in true basal cell carcinomas.

The authors added some interesting observations on patient 9, the 39 year old female who had the mass for 126 months!   During her first pregnancy, the mass became itchy. She was able to squeeze out a milky liquid while the  epidermis remained intact. The mass (20 mm) remained “dormant” between giving birth and surgical excision. The mass neither grew further nor caused any discomfort during this time. This mass was located in the  deep dermal-subcutaneous region of the right axillary skin  and was shaped in lobules. Normal mammary lobules were observed adjacent to the tumor. This tumor might have arisen from ectopic breast tissue.

Important Information

Li and coworkers never defined “aggressive treatments” that should be avoided in secretory breast carcinoma. These authors also never established if their cases had the ETV6-NTRK3 gene fusion. Use of a panTRK antibody in a two step test might have established the over expression of the TRK kinase domain as would be expected in an ETV6-NTRK3 rearrangement. It is not the purpose of this post to decide if precision TRK treatment that inhibits the kinase activity of the TEL-TRKC fusion is non aggressive.

Finally, Ignyta has an informative video on the small molecule TRK inhibitor entrectinib.