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

From the Department of Oral & Maxillofacial Surgery, University Hospitals Bristol

Nishma Hindocha

M.H. Wilson

M. Pring C.W. Hughes

S.J. Thomas

Nishma Hindocha and coworkers reported two cases of secretory carcinoma of the upper lip.  Histology was only presented from one case. The second case  was claimed to resemble the first.  Both cases required multiple excisions to fully remove evidence of the tumor.

Hindocha Case 1

  •  27-year-old woman female
  • 1.5 cm lump on right upper lip, noted one year prior
  • ultrasound guided a fine needle aspirate
  • cytology suggested acinic cell carcinoma
  • the lesion was excised and subjected to immunohistochemistry for markers S100, mammaglobin, and DOG1
Lip lesion immunohistochemistry for markers S100 with a magnified view on right side.

S100 staining from Hindocha 2017, Figure 3.  The right hand panel a magnified view of  the white box in the panel on the left.

Compare this 40x staining with S100 staining presented in the History of MASC on a sister site. In the major salivary glands the localization appears to be more nuclear. It should be noted that S100 is a large family of related calcium binding proteins.

Lip lesion immunohistochemistry for mammaglobin with a magnified view on right side.

Mammaglobin expression in secretory carcinoma of the lip from Figure 2 Hindocha 2017 The right panel is a magnified view of the white box in the left panel.

Mammaglobin is a member of the secretoglobin family. Presence of S100 and mammaglobin suggested salivary gland secretory carcinoma, formerly MASC.  Absence of DOG1 cast doubt on the original suspicion of acinic cell carcinoma. ETV6 break apart FISH confirmed rearrangement of the ETV6 as would be expected in secretory carcinoma.

Histopathological analysis revealed that the margins of the specimen were invaded  despite the impression of macroscopic clearance at operation.

Residual tumor Histopathological analysis showing that the margins of the specimen were invaded despite the impression of macroscopic clearance at operation.

Left from Hindocha 2017, the patient had growth at what were thought to be the margins upon macroscopic excisions. Right some examples of lip histology

A 1 cm wedge excision of the scar was performed. The patient required an additional  resection after microscopic identification of residual dispersed islands of tumor in the margins. Nine months later there was no sign of local or regional recurrence.

Hindocha Case 2

  • 51-year-old male
  • former smoker, no other relevant medical history
  • three year history of an asymptomatic, firm, mobile lump in his upper right labial mucosa
  • Immunohistochemistry and histology consistent with  secretory carcinoma.
  • ETV6 break apart FISH positive
  • Staging scans showed no abnormality.

This patient also had a 1 cm margin surgical excision of the scar. Like the first patient, histology showed residual tumor. The patient opted for close monitoring instead of further excision. After six months, there were no signs of recurrence.

From the School of Dentistry, Oregon Health Science University

F. James Kratochvil III, DDS

Jeffery C. B. Stewart, DDS, MS

Stephen R. Moore, PhD

These authors presented histology of two cases of secretory carcinoma of the lip and one case of acinic cell carcinoma of the lip.  The contrast of these two cancers in minor salivary glands is interesting.  It may be helpful to review some of the genomic alterations in acinic cell carcinoma.

Kratochvil Case 1

  • 48-year-old female
  • 1-cm, slow growing, painless, submucosal mass
  • right side of the upper lip
  • original diagnosis  was “pleomorphic adenoma vs. other”

Kratochvil Case 2

  •  52-year-old male
  • 0.7 x 0.3 cm, non tender, submucosal mass, right side of the lower labial mucosa
  • original diagnosis was “minor salivary gland tumor”
  • a nodule of brown soft tissue that exuded a translucent gel from the center when bisected

Kratochvil Case 3

  •  44-year-old male
  • 0.3-cm-diameter, very slow growing, present since teenager
  • non tender, submucosal, right side of the upper lip
  • previously diagnosed as acinic cell carcinoma

ETV6 break apart FISH uses hybridization probes labeled with red and green fluorescent molecules.  An intact ETV6 gene will appear yellow because “red + green = yellow” in optics.

Pictures showing FISH where ETV6 break apart. Yellow indicates one copy of an intact ETV6. The red and green dots indicate a disrupted ETV6 gene. In case 3, the acinic cell carcinoma, mostly two yellow dots are seen.

Kratochvil 2012 ETV6 break apart FISH

In cases 1 and 2 we see a mostly yellow dot, a green dot, and a red dot.  Yellow  indicates one copy of an intact ETV6.  The red and green dots indicate a disrupted ETV6 gene. In case 3, the acinic cell carcinoma, we see two mostly yellow dots.

Histology as revealed by H&E staining

The differences in macro and microscopic morphology in these two cases of lip secretory carcinoma are noticeably different, particularly when contrasted in an acinic cell cacinoma.

3 cases showing differences in macro and microscopic morphology of lip secretory carcinoma.

Kratochvil 2012, 2x

Recall that it was case 2 that oozed a translucent gel. This seems to be visible at 2x as well as at 10x

Case 2 histology slide showing oozed translucent gel at 10x as compared to case 1 and 2.

Kratochvil 2012, 10x

Note that the colloid seen in Case 2 is also seen in major salivary gland and thyroid gland secretory carcinoma.  Another feature of secretory carcinoma of the major salivary glands is atypical nuclei with prominent, single nucleoli.

Histology slides of all 3 cases showing atypical nuclei with 40x magnified bottom panels.

Top panels:  Kratochvil 2012, 40x,  Bottom Panels, magnified regions from the top panels showing atypical nuclei

These nuclei are seen in secretory carcinoma Case 1 and acinic cell carcinoma Case 3.

Immunohistochemistry Comparison, Kratochvil 2012

IHC is the process of selectively viewing proteins in tissue sections. Kratochvil and coworkers used a Ventana polyclonal antibody rather than the Dako polyclonal antibody that is selective for the S100B isoform. In the history of salivary gland MASC nuclear localization of S100 has been reported often. The authors reported the interstitial cells, and not the tumor cells, staining positive for S100 in acinic cell carcinoma Case 3. There is some slight hint of nuclear S100 staining in Hindosa 2017 Case 1.

Immunohisto stains of 3 cases using a Ventana polyclonal antibody that is selective for the S100B isoform. In the history of salivary gland MASC nuclear localization of S100 has been reported often. The authors reported the interstitial cells, and not the tumor cells, staining positive for S100 in acinic cell carcinoma Case 3. There is some slight hint of nuclear S100 staining in Hindosa 2017 Case 1.

Kratochvil 2012, S100 protein

Vimentin is an intermediate filament that may also participate in Akt1 signaling.

Immunohisto stain in 3 cases with vimentin antibody with bottom showing highly magnified view.

Kratochvil 2012, intermediate filament protein vimentin

Like S100, only interstitial cells in case 3 were considered to stain positive for vimentin whereas the secretory carcinomas were intensely positive. The  bottom panels were digitally manipulated to see fine details.

Immunohisto stain in 3 cases with mammaglobin antibody with bottom showing highly magnified view.

Kratochvil 2012, mammaglobin, secreted protein and breast cancer marker

In Case1, there is some evidence of mammaglobin secretion in a vaguely colloid like material. See the enlargement of the white boxed region. Note, that it was Case 2 that oozed a translucent material when cut.

Secretory carcinoma of the lip shares some common features with secretory carcinoma of the major salivary glands.  There is an open clinical trial testing a TRK treatment. Either group mentioned consideration of traditional chemotherapies, radiation, or precision medicine for these tumors. An entrectinib video illustrates how a precision small molecule acts on TRK fusions.

References

Hindocha N, Wilson MH, Pring M, Hughes CW, Thomas SJ. (2017) Mammary analogue secretory carcinoma of the salivary glands: a diagnostic dilemma. Br J Oral Maxillofac Surg.55(3):290-292. PubMed

Kratochvil FJ 3rd, Stewart JC, Moore SR. (2012) Mammary analog secretory carcinoma of salivary glands: a report of 2 cases in the lips. Oral Surg Oral Med Oral Pathol Oral Radiol. 114(5):630-5. PubMed

Laco J, Švajdler M Jr, Andrejs J, Hrubala D, Hácová M, Vaněček T, Skálová A, Ryška A. (2013) Mammary analog secretory carcinoma of salivary glands: a report of 2 cases with expression of basal/myoepithelial markers (calponin, CD10 and p63 protein). Pathol Res Pract. 2209(3):167-7  PubMed