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

All of the tumors were described as being poorly circumscribed white tan nodules. The location of tumor origin of the third case, trachea versus thyroid, was not discernible. The thyroid gland surrounds the trachea. Papillary growth is simply nipple like growth (table 1, first half).

Left Image showing trachea, larynx and thyroid glands. Right side show 2 immunohistology slides showing atypical nuclei and nuclear grooves in cancer patients of Table 1 above.

Images illustrating content in the first half of Table 1, Dettloff 2016

Atypical nuclei are classic features of MASC. Nuclear grooves are features of PTC.

The second half of Table 1 documents differences in clinical outcomes.

Second half of Table 1 documents differences in clinical outcomes of patients.

Table 1, second half, Dettloff 2016, IBT, involvement beyond thyroid; LN, lymph node metastasis; ENE, extranodal extension; NED, no evidence of disease; DOD, death of disease

This table is a bit confusing. All of the cases are listed as not having extranodal metastasis, yet patient number one died with liver metastasis.

Some nice H&E histology to compare with salivary gland secretory carcinoma

The authors presented some nice, high resolution H&E images of their three cases of thyroid secretory carcinoma.  These quality images allow for zooming in on features the authors want the reader to know about. These images can also be compared to MASC tumors on our sister site.

The first case

High resolution H&E images of three cases of thyroid secretory carcinoma.

Case 1 from Dettloff 2016

The second case

One of the interesting aspects of case 2 is the way Dettloff and coworkers described nuclei that had single nucleoli, some with features of PTC (panel B). The authors did not directly indicate if the atypical nuclei in Panel C were classically MASC/secretory carcinoma. We have enlarged regions of interest in the insets of panels B and C as indicated by the connecting lines.

High resolution H&E images of thyroid secretory carcinoma showing nuclei that has single nucleoli, some with features of PTC (panel B).

Case 2 and from Dettloff 2016

The purple hematoxylin in these H&E images stains DNA.  How this relates to nuclear clearing was not discussed.

The third case

A image of the cribriform plate is shown to illustrate cribriform morphology in panel A.

IHC images showing cribriform plate is shown to illustrate cribriform morphology in panel A.

Case 3 from Dettloff 2016. Images below illustrate the original figure legend claims.

The authors did not really discuss the origin of “Nuclear grooves” and “overlapping nuclei.”  These features are part of the histological features of PTC.

The immunohistochemistry of the three cases of thyroid secretory carcinoma

While it is hard to establish a trend with just three specimens, the immunohistochemistry results are very interesting because the ETV6 gene disruption suggests secretory carcinoma.

Table showing presence or absence of various markers in 3 patients with thyroid secretory carcinoma.

Table 2 from Dettloff 2017

TTF-1 and thyroglobulin are proteins one would expect to find in differentiated thyroid cells. They are also good ways of differentiating thyroid secretory carcinoma from PTC. Pax-8 is generally considered a thyroid specific transcription factor, though its transcripts can be found in smaller amounts in other tissues such as the kidney.  S100 and mammaglobin are well referenced markers for salivary gland secretory carcinoma that could have interesting functions in tumor biology. Gata3 is a cancer associated transcription factor that has been explored as a marker for salivary gland secretory carcinoma. The presence of the DOG1 gene coded chloride channel is interesting because this channel is seen in salivary gland acinic cell carcinoma but not in salivary gland secretory carcinoma.

Who really had the first three cases?

Dettloff and coworkers acknowledged a fine report of thyroid secretory carcinoma by Reynolds and coworkers in their discussion. Like patient #1 in this study, their patient experienced a progressive disease. This patient is described on a thyroid secretory carcinoma page on this site. Therese Bocklage, one of Samuel Reynolds’ coworkers, made this point in a 2017 letter to the editor. Her concluding remarks were profound

” it is vital that patients with MASC of the thyroid be correctly identified and followed closely over the long term. Furthermore, for patients with advanced disease, consideration should be given for novel therapies including NTRK inhibitors, as radioactive iodine does not appear to be effective treatment, at least in our patient.”

Jennifer Detloff and coworkers, in a 2017 response to the Bocklage letter to the editor, acknowledged that they might not have had the first three cases in this closely packed time line. More importantly, they acknowledged the importance of identifying these cancers

“We echo the sentiments of the authors in that these cases are important to identify since they would (as expected) not appear to respond to radioactive iodine. We would also add given the limited case number and follow-up, there is still concern that at least some of the cases reported to date may be metastases or extension from occult sites (i.e. breast or salivary gland), yet another reason to be aware of this entity.”

Important Information

Both groups express the concern that ETV6-NTRK3 driven tumors of the thyroid may be refractory to radioactive iodine, it is important to get tested. Information on getting Trk tested is available on line. This site is for physicians only. Information to help patients interact with their physicians on thyroid cancer treatment options is also available on line. This is a general site to help you interact with your physician on a multiple variety of head and neck cancers that might be driven by an “actionable target.” On this site we are ignoring other Trk family members NTRK1 and NTRK2 that might be involved in cancer driving gene rearrangement.

What is precision medicine?  What is entrectinib ?  These patient friendly sites summarize the essence of the above discussions.

References

Bocklage TJ, Reynolds S, Shaheen M, Olson G, Barry M, Wu J. (2016) Regarding Dettloff et al. Mammary analog secretory carcinoma (MASC) involving the thyroid gland: a report of the first three cases. Head Neck Pathol. [PubMed

Dettloff J, Seethala RR, Stevens TM, Brandwein-Gensler M, Centeno BA, Otto K, Bridge JA, Bishop JA, Leon ME. (2017) Regarding Bocklage et al. “Regarding Dettloff et al. Mammary Analog Secretory Carcinoma (MASC) Involving the Thyroid Gland: A Report of First 3 Cases”.  Head Neck Pathol. 2017 Jun;11(2):266-267. PubMed

Dettloff J, Seethala RR, Stevens TM, Brandwein-Gensler M, Centeno BA, Otto K, Bridge JA, Bishop JA, Leon ME. (2017) Mammary Analog Secretory Carcinoma (MASC) Involving the Thyroid Gland: A Report of the First 3 Cases.  Head Neck Pathol.11(2):124-130. PubMed

Reynolds S, Shaheen M, Olson G, Barry M, Wu J, Bocklage T. A case of primary mammary analog secretory carcinoma (MASC) of the thyroid masquerading as papillary thyroid carcinoma: potentially more than a one off. (2016) Head Neck Pathol. 10(3):405–13 PubMed

Stevens TM, Kovalovsky AO, Velosa C, Shi Q, Dai Q, Owen RP, Bell WC, Wei S, Althof PA, Sanmann JN, Sweeny L, Carroll WR, Siegal GP, Bullock MJ, Brandwein-Gensler M. (2015) Mammary analog secretory carcinoma, low-grade salivary duct carcinoma, and mimickers: a comparative study. Mod Pathol.28(8):1084-100.
PubMed