.

1. Adenoid cystic carcinoma

2. Definition
Adenoid cystic carcinoma is a slow growing and relentless salivary
gland malignancy composed of epithelial and myoepithelial neoplastic
cells that form various patterns, including tubular, cribriform , and solid
forms.

3. Epidemiology
• the female-to-male ratio is about (1.5:1)
• there is no ethnic predilection
• wide patient age range, but are most common in the sixth to eighth
decades of life.
• ACC accounts for < 1 % of all head and neck cancers and < 10% of all
salivary gland neoplasms.

4. Localization
• Occurs most frequently in the major salivary glands, but more than
one third of cases occur in minor glands in the oral cavity, (rarely)
other sites.
• metastases occur in 40-60 % of patients.

5. Clinical features
Patients usually present with:
swelling or masses, and may have numbness, paraesthesia, or pain.
Involvement of motor nerves can cause facial or tongue weakness.
• Most adenoid cystic carcinomas are widely infiltrative at diagnosis,
invade bone early, and characteristically show perineural infiltration.

6. Histopathology
A system of three histological patterns has been shown to be of prognostic value; this
is based on the relative proportions of tubular, cribriform and solid patterns.
• the cribriform pattern: The most recognizable architectural form,
characterized by nests of tumour cells interrupted by sharply punched-out
spaces filled with basophilic matrix.
• The tubular pattern: is composed of bilayered tubules with lumina. The
tumour cells show scant cytoplasm and typically have small angulated and
hyperchromatic nuclei.
• The solid growth pattern: is characterized by sheets of tumour cells
without lumen formation and may consist of epithelial or myoepithelial
elements.

9. Grading:
• Depends on a simple analysis of the morphological pattern of the
tumour:
1. tubular (low grade)
2. cribriform (intermediate grade)
3. solid (high grade)
Some high-grade tumours also show “dedifferentiation”.

11. Immunohistochemical
• Adenoid cystic carcinoma expresses both ductal and
myoepithelial/basal cell markers, such as CK7, CAM 5.2, calponin,
SMA, SMMHC, p63, CD117, SOX10, and S100.
• MYB and MYB-NFIB.
• c-KIT expression
• Ki-67 and p53 labelling

16. Genetic profile
The adenoid cystic carcinoma-specific t(6;9) chromosomal
translocation, resulting in a MYB- NFIB gene fusion.
The key genomic alterations are at (6;9) chromosomal translocation or
more rarely a t(8;9) translocation, resulting in fusions involving the
MYB or MYBL1 oncogenes and the transcription factor gene NFIB.

17. In addition, over 80% of adenoid
cystic carcinomas show a
translocation involving the MYB
oncogene and the transcription
factor gene NFIB.
The translocation can be detected
by FISH and an antibody to the
MYB-NFIB fusion protein has also
been developed

18. Perineural invasion
• and is a feature of most adenoid cystic carcinomas However, two
studies have found it to be an independent factor in prognosis, and it
is a means by which the tumour can grow along a plane of low tissue
resistance.
• Even anatomical barriers can be breached since all are pierced by
neurovascular bundles. It is particularly important when it occurs
outside the main tumour mass, or causes clinical manifestations.
• Clinical evidence of nerve invasion is a poor prognostic indicator. Such
evidence may become manifest as paralysis, paraesthesia, deafness,
diplopia, pain or tic.

19. (Barrett & Speight, 2009)
Perineural invasion in adenoid cystic carcinoma of the salivary glands: A valid
prognostic indicator?
• The answer to the question posed at the beginning of this article,
‘‘does histological evidence of PNI affect the patient’s prognosis?”
• “Certainly ‘‘yes”. There is no consensus that PNI correlates with site,
histological grade or other clinicopathological variables. However, the
majority of studies show PNI to be an adverse factor for one or more
outcome indicators.”

20. Prognosis and predictive factors
• The 10-year survival rate is 50-70% and the local recurrence rate is
highly variable. Lymph node involvement is uncommon, but is more
frequent in solid varian.
• Distant metastasis is reported in > 50% of cases, most commonly to
the lungs, followed by bone, liver, and brain.

21. Factors that influence survival include tumour stage, node status,
patient age, tumour site, large nerve perineural invasion, and surgical
margins.
Generally, tumours with tubular and cribriform growth patterns have a
less aggressive clinical course than do tumours with a solid component
constituting more than one third of the tumour.

22. References
1. Barrett, A. W., & Speight, P. M. (2009). Perineural invasion in adenoid cystic carcinoma of the salivary
glands : A valid prognostic indicator ? Oral Oncology, 45(11), 936–940.
https://doi.org/10.1016/j.oraloncology.2009.07.001
2. Khurram, S. A., Barrett, A. W., & Speight, P. M. (2017). Diagnostic difficulties in lesions of the minor
salivary glands. Diagnostic Histopathology, 23(6), 250–259.
https://doi.org/10.1016/j.mpdhp.2017.04.008
3. Simpson, R. H. W., Skálová, A., Di Palma, S., & Leivo, I. (2014). Recent advances in the diagnostic
pathology of salivary carcinomas. Virchows Archiv, 465(4), 371–384. https://doi.org/10.1007/s00428-014-
1639-x
4. Speight, P. M., & Barrett, A. W. (2009). Leading article Prognostic factors in malignant tumours of the
salivary glands, 47, 587–593. https://doi.org/10.1016/j.bjoms.2009.03.017
5. Zhu, S., Schuerch, C., & Hunt, J. (2005). Review and Updates of Immunohistochemistry in Selected
Salivary Gland and Head and Neck Tumors. https://doi.org/10.5858/arpa.2014-0167-RA
6. WHO Classification of Head and Neck Tumours, 4ed, (2017)
7. Van Weert, S., Van Der Waal, I., Witte, B. I., René Leemans, C., & Bloemena, E. (2015). Histopathological
grading of adenoid cystic carcinoma of the head and neck: Analysis of currently used grading systems and
proposal for a simplified grading scheme. Oral Oncology, 51(1), 71–76.
https://doi.org/10.1016/j.oraloncology.2014.10.007