A 55 year old male, presents with difficulties and pain during chewing and swallowing. Oral examination show mass in posterior part and base of tongue

Adenoid cystic carcinoma (ACC) of base of tongue

Histopathology:

• Tumor shows predominant cribriform pattern, in a lobular/nested fashion, with extensive infiltration into the muscle tissue
• Tumor composed of predominantly myoepithelial cells, which are dark angulated hyperchromatic, basaloid look with scanty cytoplasm, lined the cylindromatous microcystic spaces. These are not the true glands.
• Few small ducts and few tubules are lined by cuboidal epithelium with eosinophilic cytoplasm, surrounded by dark angulated basaloid looking myoepithelial cells, resembles like “Swiss cheese”.
• Pseudocysts contain pale eosinophilic, thin mucoid material, but hyalinised basement membrane material is not seen.
• Frequent mitoses and necrosis are not seen. Perineural invasion is not appreciated.

Practical Points of Pathoclinics:

1. ACC is a malignant epithelial tumor with myoepithelial and ductal differentiation. Common age group is 5-7th decade with presenting compliant of pain and slow growing mass.
2. In minor salivary gland palate is the most common site followed by Tongue and lip
3. In tongue, most common site of ACC is base of tongue and commonest pattern is cribriform.
4. Grossly, ACC is poorly circumscribed and infiltrative, firm white-grayish mass
5. Perineural invasion is commonly seen in ACC but not the specific features, as other tumors like mucoepidermoid carcinoma, polymorphous low grade adenocarcinoma, salivary duct carcinoma, acinic cell carcinoma can show perineural invasion.
6. ACC can infiltrates into adjacent fat, skeletal muscle and soft tissue.
7. Most common pattern of ACC is cribriform pattern, with hyalinized basement membrane material. Other next common is tubular pattern, comprising of elongated glands, lined by ductal and myoepithelial cells. Solid pattern shows diffuse sheets of dark hyperchromatic cells, with more atypia, mitotic activity and necrosis. Predominance of solid pattern are associated with poor prognosis. Solid ACC commonly has alteration of p53 and high possibility of tumor recurrence and metastasis.
8. Classic morphology doesn’t require immunohistochemistry, however in difficult cases actin, calponin, p63, p40, and S 100 for myoepithelial cells and c-kit and EMA for epithelial cells can be used.
9. Most cases harbour t(6;9) which create MYB-NFIB fusion. MYB may help to confirm the diagnosis. Some cases show EWSR1-ATF1 gene fusions.
10. Recently described entity comes in the differential is HPV-related carcinoma with adenoid cystic-like features, commonly involving sino-nasal tract and palate. It has area of cribriform architecture, dual population of cells, and immunohistochemical expression of myoepithelial markers. But it shows mostly solid growth pattern and squamous dysplasia. and evidence of high risk HPV type and strong and diffuse positivity for P16. Take note that, p16 overexpression is commonly observed in adenoid cystic carcinoma of the head and neck.
11. Other close differentials in present case are polymorphous low-grade adenocarcinoma and epithelial-myoepithelial carcinoma. Polymorphous low-grade adenocarcinoma has only one cell type, forming a variety of pattern like papillary, cribriform, tubular and single cell columns. Angulated cells favours ACC over PLGA, later contain uniformly bland oval to polygonal cells, without angulated cells. Epithelial-myoepithelial carcinoma has two cell types – inner cuboidal and outer myoepithelial, but later show clear cell changes with abundant clear cytoplasm, some with spindled and plasmacytoid morphology, but not with scanty cytoplasm and angulated appearance like ACC.
12. Surgical management is tailored based on the anatomic site of involvement. Radical excision is done where possible, otherwise safe margins and negative neural invasion are good prognostic factor.
13. Large size, solid pattern, perineural invasion, high Ki-67 index, lymph node and distant metastasis, high MYB expression are indicator of poor prognosis.
14. ACC is commonly recur and may develop metastases, especially lymph node, lung and bone. 5-yr survival rate is good but long term survival is poor, due to slow but relentless progression.

Reference:

Luna-Ortiz, K., Carmona-Luna, T., Cano-Valdez, A.M. et al. Adenoid cystic carcinoma of the tongue – clinicopathological study and survival analysis. Head Neck Oncol 1, 15 (2009). https://doi.org/10.1186/1758-3284-1-15

Boland, J., McPhail, E., García, J. et al. Detection of human papilloma virus and p16 expression in high-grade adenoid cystic carcinoma of the head and neck. Mod Pathol 25, 529–536 (2012). https://doi.org/10.1038/modpathol.2011.186