Secretory Carcioma

This slide shows Polygonal cells with eosinophilic cytoplasm, arranged in variably microcystic, solid, and tubular patterns. The individual cells have fairly uniform nuclei with punctate nucleoli. Mitotic figures are rare. There is no necrosis. There is prominent secretory material that is PAS positive. Immunostains for ER, PR and HER2 are negative. FISH analysis reveals a t(12;15) translocation resulting in the ETV6-NTRK3 gene fusion.

Secretory carcinoma

This tumor slide is composed of solid nests of cells with high nucleus cytoplasm ratio and abundant mitotic activity. These cells are associated with prominent intracellular and extracellular eosinophilic secretions. The cells have vesicular chromatin and prominent nucleoli. The tumor demonstrates an ETV6 rearrangement by fluorescence in situ hybridization.

Secretory carcinoma

This tumor slide is composed of solid nests of cells with high nucleus cytoplasm ratio and abundant mitotic activity. These cells are associated with prominent intracellular and extracellular eosinophilic secretions. The cells have vesicular chromatin and prominent nucleoli. The tumor demonstrates an ETV6 rearrangement by fluorescence in situ hybridization.

Chromosomal changes traveling with ETV6-NTRK3 in secretory carcinoma of the salivary glands

Gregor Krings led a multi-center group from the University of California, San Francisco, to compare histology and genetics of nine secretory carcinomas of the breast with six MASC salivary gland tumors. This post looks at salivary gland secretory carcinoma chromosome changes in the Krings study that were not observed in breast secretory carcinomas.

Diagram showing genomic alterations in various patients with their sex and age.

A summary of genomic alterations traveling with the ETV6-NTRK3 gene fusion.

Chromosomal changes traveling withETV6-NTRK in secretory carcinoma of the breast

Gregor Krings led a multi-center group from the University of California, San Francisco, to compare histology and genetics of nine secretory carcinomas of the breast with six MASC salivary gland tumors. This post looks at breast secretory carcinoma chromosome changes that travel with the ETV6-NTRK3 gene fusion. While the TEL-TRKC fusion protein may be many vocal passengers, it seems to be only one actionable target.

Diagram showing genomic alterations in various patients with their sex and age.

A gain in the long arm or the entire chromosome 8 is seen in cases 1 and 3. A loss of the interstitial part of 15q or the entire chromosome is seen in cases 2 and 3

Secretory carcinoma of the lips, a subset of salivary gland secretory carcinoma

The following images in this post come from case reports of minor salivary gland secretory carcinomas occurring in the lip. The conclusion is that it shares attributes with secretory carcinoma of major salivary glands. The caveat is that the glands of the lip just look different from the major salivary glands.

Picture showing lip labial glands with an inset of tissue histology.

The lip contains labial glands

The first three cases of thyroid secretory carcinoma, formerly MASC

Marino Leon of the  Head and Neck Oncology Program at the  H. Lee Moffitt Cancer Center and Research Institute in Tampa led a multi center team to describe the “first three” cases of thyroid secretory carcinoma. Jennifer Dettloff was first author on this 2017 report. The “first three cases” of thyroid secretory carcinoma are actually one previously reported case plus two more.

In the previous report Stevens and coworkers (2015) reported

  • 10 cases of secretory carcinoma of the salivary glands
  • two from the lips
  • one from the hard palate,  and
  • one from the thyroid gland.  The thyroid secretory carcinoma came from a 55 year old female.
Table showing clinical and pathological findings of 3 patients.

Table 1, first half, Dettloff 2016.  RUL, right upper thyroid lobe; hpf, high power field

A thyroid cancer with PTC and MASC components

Colombians Paula Rodrıguez-Urrego MD and Snjezana Dogan MD collaborated with Oscar Lin, MD of the  Memorial Sloan Kettering Cancer Center Department of Pathology. They presented a  report of a 47 year old man who presented for what appeared to papillary thyroid carcinoma and was treated accordingly. In this post secretory carcinoma of the thyroid will be referred to as “MASC” simply to stay consistent with with the publication.

Why testing even old tumor blocks matters

Over a decade later, a tumor “came back” a second time. Closer examination of the old FFPE preserved tumor revealed a growth that had both PTC and MASC components. The recurrence resembled MASC. Cytological and histological differentiation of  MASC from other thyroid neoplasms is necessary to lead the oncologist to the optimal treatment. Thyroid MASCs are unlikely to respond to radioactive iodine and may not be associated with serum thyroglobulin levels. Patients diagnosed with MASC may be eligible for targeted treatment with Trk inhibitors in an open clinical trial.

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.

Secretory Carcinoma of the Breast, a review

Secretory Carcinoma of the breast, a review after nine years

In 2011 Pooja Vasudev and Kazuya Onuma of McMaster University published a nice review of secretory breast cancer. The following post follows the review and adds some additional images from a case study of Arce and coworkers  (2005)  to make it easier to understand. Unlike the six year old female in which secretory carcinoma of the breast was discovered, this cancer was found in a 52 year old male. 

Molecular comparison of breast and salivary gland secretory carcinomas

Comparing Secretory Carcinoma of the breast with MASC

Gregor Krings led a multi-center group from the University of California, San Francisco, to compare histology and genetics of nine secretory carcinomas of the breast with six MASC salivary gland tumors. For this post secretory carcinoma of the salivary glands will be referred to as MASC, mammary analog of secretory carcinoma of the breast.   Secretory carcinoma of the breast will simply be referred to as SC.

The genetic profile of the tumors in one  image

Diagram showing genomic alterations in various patients with their sex and age.

Figure 1, adapted from Figure 3 of Krings 2017