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Salivary glands

Primary salivary gland neoplasms

Malignant

Adenoid cystic carcinoma

Author: Bin Xu, M.D., Ph.D.

Editorial Board Member: Molly Housley Smith, D.M.D.

Editor-in-Chief: Debra L. Zynger, M.D.

Last author update: 30 July 2021

Last staff update: 8 December 2022

Copyright: 2012-2024, PathologyOutlines.com, Inc.

PubMed Search: Adenoid cystic carcinoma

Table of Contents

Cite this page: Xu B. Adenoid cystic carcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/salivaryglandsadenoidcystic.html. Accessed December 25th, 2024.

Definition / general

A carcinoma of primary salivary gland or minor salivary gland of upper aerodigestive tract characterized by its biphasic ductal and myoepithelial differentiation, tubular / cribriform / solid architecture (Head Neck 2017;39:456)
May occur in major and minor salivary glands
- Among major salivary glands, the most commonly affected site is the parotid gland
- Minor salivary glands that may be affected include those of oral cavity, sinonasal tract, nasopharynx, oropharynx and trachea

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

M=F (Head Neck 2017;39:456)
Mean age 57 (Head Neck 2017;39:456)

Diagrams / tables

Images hosted on other servers:

Histologic impact on survival

Clinical features

Characterized by a propensity of perineural invasion, high frequency of local and distant recurrence and poor long term prognosis (Eur J Cancer 2015;51:2768, Head Neck 2017;39:456, Braz J Otorhinolaryngol 2015;81:329, Head Neck 2014;36:998)
5 year overall survival 55 - 89%
15 year or 20 year survival is dismal, in the range of 20 - 40%
Rates of local recurrence and distant metastasis are 16 - 67% and 8 - 46%
Lung is most common site of distant metastasis (Head Neck 2017;39:456)

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:

MRI parotid mass

Lung metastases

Prognostic factors

Independent prognostic predictors include AJCC TNM staging, margin status, high mitotic index (defined as ≥ 5 per 10 high power fields) and solid architecture (Am J Surg Pathol 2017;41:1422)

Presence and percentage of solid architecture reflects clinical outcome and should be reported in the pathology report

Some studies showed that the presence but not the percentage of solid growth is an independent predictor for adverse outcome (Am J Surg Pathol 2017;41:1422, Oral Surg Oral Med Oral Pathol Ora Radio 2013;115:368, Head Neck 2017;39:456)
Other studies show that tumors with higher percentage of solid pattern, defined as 30% or more, are associated with increased risk of recurrence and decreased survival (Cancer 1984;54:1062, Cancer 1978;42:265)
Based on the above data, 2 grading systems have been proposed (table)
Current WHO classification does not endorse any specific grading system (IARC: WHO Classification of Head and Neck Tumours, 4th Edition, 2017)
Other poor prognostic factors include female sex, older age, sinonasal location, lymphovascular invasion, high grade transformation and intraneural invasion


Perzin 1978 and Szanto 1984	Van Weert 2015, Zhang 2013 and Xu 2018
Grade 1 (low grade): no solid component	Grade 1: no solid component
Grade 2 (intermediate grade): 1 - 29% solid component	Grade 2 (high grade): with solid component
Grade 3 (high grade): ≥ 30% solid component

Perzin 1978 (Cancer 1978;42:265) and Szanto 1984 (Cancer 1984;54:1062)
Van Weert 2015 (Head Neck 2017;39:456), Zhang 2013 (Oral Surg Oral Med Oral Pathol Ora Radio 2013;115:368) and Xu 2018 (Am J Surg Pathol 2017;41:1422)

Case reports

27 year old woman with parotid adenoid cystic carcinoma and high grade transformation (Diagn Pathol 2013;8:113)
36 year old man with tracheal tumor: an autopsy case (Head Neck Pathol 2019;13:243)
39 year old woman with lacrimal gland tumor (Head Neck Pathol 2013;7:85)
70 year old woman with soft palate adenoid cystic carcinoma extending to bilateral orbits through perineural spread along cranial nerves (Digit J Ophthalmol 2018;24:1)
70 year old man with laryngeal tumor (Oncol Lett 2018;16:2783)

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:

Vocal cord mass

Gross description

Infiltrative ill defined firm mass

Gross images

Contributed by Bin Xu, M.D., Ph.D. and Kelly Magliocca, D.D.S., M.P.H.

Parotid mass

Cut section turbinate to palate

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:
- Focal squamous metaplasia / differentiation, especially in cases with high grade transformation (Am J Surg Pathol 2007;31:1683, Am J Surg Pathol 2017;41:1422)
- Areas in which myoepithelial cells show clear cell changes, resembling epithelial myoepithelial carcinoma (Am J Surg Pathol 2018;42:319)

Microscopic (histologic) images

Contributed by Bin Xu, M.D., Ph.D. and Kelly Magliocca, D.D.S., M.P.H.

Tubular pattern

Cribriform pattern

Solid pattern

High grade transformation

Perineural invasion

Squamous metaplasia

Clear myoepithelial cells

p40

SMA

CAM5.2

MYB

H&E of turbinate to palate

Cytology description

Matrix containing and basaloid
Diff-Quik stained smears: metachromatic matrix spheres with sharply defined border (hyaline globules) surrounded by basaloid tumor cells
Uniform basaloid cells with scant cytoplasm, oval to angulated hyperchromatic nuclei and indistinct nucleoli
Various architecture patterns, including microcystic, tubular and syncytial clusters
Characteristic extracellular hyaline globules or cylinders of acellular metachromatic stroma with sharp borders best seen on Romanowsky type stain
Marked cytologic atypia and necrosis in cases with high grade transformation

Cytology images

Contributed by Bin Xu, M.D., Ph.D. and Jen-Fan Hang, M.D.

Smear, Diff-Quik

Smear, Papanicolaou

Basaloid cells

Microcystic pattern

Branching pattern

Positive stains

Ductal component is typically positive for CK7 and CAM 5.2
Myoepithelial component is positive for myoepithelial markers, e.g. SMA, S100, calponin, p40, p63, GFAP and cytokeratins
Other positive stains: c-KIT (CD117)
MYB overexpression is a sensitive but nonspecific immunomarker for adenoid cystic carcinoma (Am J Surg Pathol 2017;41:1422)

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
- Typically p63 positive / p40 negative, whereas adenoid cystic carcinoma is typically positive for both p63 and p40 (Am J Surg Pathol 2014;38:257)
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 style question #1

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

Board review style answer #1

C. Solid pattern is associated with adverse clinical outcome

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Reference: Adenoid cystic carcinoma

Board review style question #2

t(6,9) MYB-NFIB fusion
t(11,19) MAML2-CRTC1 fusion
t(12,15) ETV6-NTRK3 fusion
t(12,22) ATF1-EWSR1 fusion

Board review style answer #2

A. t(6,9) MYB-NFIB fusion

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Reference: Adenoid cystic carcinoma

Board review style question #3

Which histological diagnosis is most likely to correspond to this cytologic aspirate?

Acinic cell carcinoma
Adenoid cystic carcinoma
Mucoepidermoid carcinoma
Secretory carcinoma

Board review style answer #3

B. Adenoid cystic carcinoma

Basaloid tumor cells with prominent hyaline globules arranging in cribriform pattern are characteristic for an adenoid cystic carcinoma.

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Reference: Adenoid cystic carcinoma

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