Salivary glands
Primary salivary gland neoplasms - malignant
Adenoid cystic carcinoma

Editor-in-Chief: Debra Zynger, M.D.
Bin Xu, M.D., Ph.D.

Topic Completed: 3 September 2019

Revised: 12 November 2019

Copyright: 2012-2019, PathologyOutlines.com, Inc.

PubMed Search: Adenoid cystic carcinoma[TI] salivary glands[TI]

Bin Xu, M.D., Ph.D.
Page views in 2018: 29,256
Page views in 2019 to date: 32,797
Cite this page: Xu B. Adenoid cystic carcinoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/salivaryglandsadenoidcystic.html. Accessed November 19th, 2019.
Definition / general
  • A primary salivary gland or minor salivary gland of upper aerodigestive tract carcinoma characterized by its biphasic ductal and myoepithelial differentiation, tubular / cribriform / solid architecture (Head Neck 2017;39:456)
  • More common (60% of all tumors) in minor salivary gland, especially those in oral cavity but may also occur in sinonasal tract, nasopharynx, oropharynx and trachea
  • Among major salivary glands, the most common affected site is the parotid gland
Essential features
  • Grows in tubular, cribriform, and/or solid patterns: solid pattern is associated with adverse outcome
  • 60% - 90% carry MYB-NFIB or MYBL1-NFIB fusion
  • Biphasic tumor showing ductal and myoepithelial differentiation
  • Frequent perineural invasion
Epidemiology
Diagrams / tables

Images hosted on other servers:
Missing Image

Histologic impact on survival

Clinical features
Diagnosis
  • Diagnosis is based on tissue examination findings of typical histologic features or the presence of fusion involving MYB, MYBL1 or NFIB genes
Radiology images

Images hosted on other servers:
Missing Image

MRI parotid mass

Missing Image

Lung metastases

Prognostic factors
Case reports
Treatment
  • Complete surgical resection with appropriate margins is the mainstream treatment
  • Most patients receive adjuvant radiation therapy given the high rate of local recurrence and dismal long term survival
  • Chemotherapy for patients with distant metastasis
  • Multiple clinical trials are ongoing investigating the effects of tyrosine kinase inhibitors, e.g. axitinib (Ann Oncol 2016;27:1902) and dovitinib (Clin Cancer Res 2017;23:4138)
Clinical images

Images hosted on other servers:
Missing Image

Vocal cord mass

Gross description
  • Infiltrative ill defined firm mass
Gross images

Contributed by Bin Xu, M.D., Ph.D.
Missing Image

Parotid mass

Frozen section description
  • Biphasic pattern of epithelial and myoepithelial cells and the typical tubular / cribriform / solid architecture are useful diagnostic cues
Microscopic (histologic) description
  • Biphasic salivary gland tumor, composed of ductal and myoepithelial cells
  • Myoepithelial cells have dark angulated nuclei and scanty cytoplasm, giving a basaloid appearance
  • Tubular, cribriform and solid architecture
  • Tubular pattern contains simple tubules composed of inner ductal and outer myoepithelial cells
  • Cribriform pattern is composed of predominantly myoepithelial cells with myxoid or hyalinized globules
  • Scattered ductal elements may be seen within the cribriform area
  • Solid pattern is solid nests composed of sheets of basaloid cells
  • Perineural invasion is frequent
  • High grade transformation can be seen in a small number of cases, defined as comedo type tumor necrosis, frequent mitoses (often > 10 per 10 high power fields) and marked nuclear atypia; high grade transformation is associated with high risk of lymph node metastasis, distant metastasis and disease related death (Am J Surg Pathol 2007;31:1683)
  • Other rare features that may present occasionally include:
Microscopic (histologic) images

Contributed by Bin Xu, M.D., Ph.D.
Missing Image

Tubular pattern

Missing Image

Cribriform pattern

Missing Image

Solid pattern

Missing Image

High grade transformation

Missing Image Missing Image

Perineural invasion


Missing Image

Squamous metaplasia

Missing Image

Clear myoepithelial cells

Missing Image

p40

Missing Image

SMA

Missing Image

CAM5.2

Missing Image

MYB

Cytology description
  • Matrix containing and basaloid
  • Diff-Quik stained smears: metachromatic matrix spheres with sharply defined border (hyaline globules) surrounded by basaloid tumor cells
  • Cytologic features: uniform basaloid cells with scant cytoplasm and dark angulated nuclei
Cytology images

Contributed by Bin Xu, M.D., Ph.D.
Missing Image Missing Image

Smear, Diff-Quik

Missing Image Missing Image

Smear, Papanicolaou

Positive stains
Molecular / cytogenetics description
  • Absence of high risk HPV bby DNA or RNA in situ hybridization
  • 60 - 90% have characteristic and diagnostic fusion involving MYB, MYBL1 or NFIB gene, the most common being t(6,9) MYB-NFIB fusion (Nat Genet 2013;45:791, Proc Natl Acad Sci U S A 2009;106:18740, Cancer Discov 2016;6:176)
  • Additional mutations involving FGF-IGF-PI3K pathway (in 30%) and chromatin state regulators (e.g. SMARCA2, CREBBP and KDM6A) are reported (Nat Genet 2013;45:791)
  • Although commonly overexpresses c-KIT by immunohistochemistry, it is not associated with c-KIT mutation
Sample pathology report
  • Left parotid, parotidectomy:
    • Adenoid cystic carcinoma, solid, cribriform and tubular pattern (see synoptic report)
    • Comment: Solid component accounts for 20% of total tumor volume.
Differential diagnosis
  • Epithelial myoepithelial carcinoma:
    • Also biphasic with ductal and myoepithelial differentiation
    • Typically contains compact branching tubules (adenoid cystic carcinoma contains simple tubules)
    • Generally lacks cribriform growth pattern: if present, cribriform pattern is often very focal
    • Papillocystic architecture may be seen (typically absent in adenoid cystic carcinoma)
    • Contains clear myoepithelial cells (adenoid cystic carcinoma contains myoepithelial cells with dark angulated nuclei and scanty cytoplasm)
    • Characterized by HRAS mutation; lacks fusions involving MYB, NFIB or MYBL1
  • Basal cell adenocarcinoma
    • Also biphasic and basaloid
    • Trabecular, tubular and solid growth and usually lacks cribriform growth (adenoid cystic carcinoma lacks trabecular growth)
    • Prominent peripheral palisading and may contain areas with squamoid eddies
    • Characterized by mutation of Wnt / beta catenin pathway leading to abnormal nuclear accumulation of beta catenin by immunohistochemistry; lacks fusions involving MYB, NFIB or MYBL1
  • Polymorphous adenocarcinoma
    • Also may show tubular, cribriform and solid growth
    • May have other growth patterns, e.g. single files, trabecular or papillary architecture
    • Shows cytologic monotony with only one type of tumor cells
      • Nuclei contain open chromatin resemble nuclei of papillary thyroid carcinoma
  • HPV related multiphenotypic sinonasal carcinoma
    • Also can affect sinonasal tract and show similar morphology and expression
    • May have surface dysplasia
    • Positive for high risk HPV; negative for MYB-NFIB fusion
  • Squamous cell carcinoma
    • Basaloid squamous cell carcinoma and HPV+ oropharyngeal squamous cell carcinoma may contain adenoid cystic carcinoma-like areas
    • Typically shows more pleomorphism, is negative for MYB-NFIB fusion, is diffusely positive for squamous markers (p40, p63 and CK5/6), is negative for myoepithelial markers (S100, calponin and SMA) and may be HPV+
Board review question #1

    A parotid tumor is resected and the H&E is shown. Which of the following statements is true?

  1. It has an excellent prognosis with 5% risk of recurrence following complete resection of the primary tumor
  2. It is characterized by point mutation involving MYB gene
  3. Solid pattern is associated with adverse clinical outcome
  4. The most common site of this tumor is the parotid gland, followed by submandibular gland
Board review answer #1
C. Solid pattern is associated with adverse clinical outcome

Comment Here

Reference: Adenoid cystic carcinoma
Board review question #2
    What is the most common molecular alteration in adenoid cystic carcinoma?

  1. t(6,9) MYB-NFIB fusion
  2. t(11,19) MAML2-CRTC1 fusion
  3. t(12,15) ETV6-NTRK3 fusion
  4. t(12,22) ATF1-EWSR1 fusion
Board review answer #2
A. t(6,9) MYB-NFIB fusion

Comment Here

Reference: Adenoid cystic carcinoma
Back to top