How predominant cell and stroma types harmonize to predict head and neck adenoid cystic carcinoma outcomes?

Abstract

Adenoid cystic carcinoma (ACC) is an uncommon tumor that usually appears in the major salivary glands of the head and neck region, including the minor glands in the oral cavity, sinonasal tract, and other sites. ACC of the head and neck may have a low-grade histological appearance. This malignant tumor has unusual clinical characteristics such as occasional regional lymph node metastases and a prolonged yet continuously advancing clinical course. Additionally, it is an invasive tumor with perineural invasion, difficult-to-clear margins, metastasis, and localized recurrence. The cribriform and tubular proliferation of basaloid cells, which mostly display a myoepithelial cellular phenotype, are ACC's distinct histologic characteristics. The degree of genetic alterations and aneuploidy observed in tumor genomes are linked to the severity of histologic grade, which correlates with clinical prognosis. The three predominant cell types (PCTs) i.e., conventional ACC (C-ACC), myoepithelial-predominant ACC (M-ACC), and epithelial-predominant ACC (E-ACC)-and their respective applications will be reviewed. The function of extracellular matrix (ECM) components such as laminin, type IV collagen, fibronectin, and tenascin are also emphasized. An attempt has been made to explore the recent molecular diversity, regulatory pathways prevalent in PCT, ECM with its genetic changes, and translational utility with targeted therapies for ACC.

Keywords: Adenoid cystic carcinoma; Extracellular matrix; Laminin; Myoepithelial.

Fig. 1

Figure (A) 10X depicting predominance of myoepithelial cells residing between luminal epithelial cells and the stromal compartment. Inset (40X) showing angulated, deeply basophilic, eccentrically placed nuclei of myoepithelial cell (B) under 4X depicts cribriform structures of low cuboidal epithelial cells with eosinophilic coagulum in center (C) 40X depicts epithelial low cuboidal, hypechromatic, polyhedral epithelial cells with eosinophilic coagulum in center. (D) Multiple areas of small tubular structures lined by angulated hyperchromatic myoepithelial cells with extracellular matrix (E) Showing predominance of epithelial cells with reduction or absence of myoepithelial cells with a transition of solid compartment to hyalinized stroma is seen. (F) Depicts abundantly hyalinized extracellular matrices with few solid tubular structures.

Fig. 2

Flowchart outlining the predominant cell type of ACC along with its associated immunohistochemical features, molecular signaling pathways, and targeted therapeutic interventions.

Fig. 3

Flowchart outlining immunohistochemical features, molecular signaling pathways, and targeted therapeutic interventions of extracellular matrix comprising laminin, type IV collagen, fibronectin, and tenascin.