Adenoid cystic carcinoma (ACC) is a malignant tumour that most commonly arises in the salivary glands, but can also occur in other sites such as the lacrimal glands, trachea, and breast. The key histopathologic features associated with adenoid cystic carcinoma include:

1. Cribriform Pattern:
   • This is the most characteristic pattern of ACC, featuring multiple small, round to oval spaces (pseudocysts) within nests of tumor cells, resembling a “Swiss cheese” appearance.
2. Tubular Pattern:
   • ACC may also exhibit a tubular pattern, where the tumor cells form small, round to oval true gland-like structures.
3. Solid Pattern:
   • This pattern involves solid sheets or nests of tumor cells with minimal to no luminal spaces. The solid variant is often associated with a poorer prognosis.
4. Perineural Invasion:
   • A common and significant feature, ACC often shows a propensity for perineural invasion, which is the infiltration of tumor cells along nerve sheaths. This contributes to the tumor’s tendency for local recurrence and spread along nerve pathways.
5. Basaloid Cells:
   • The tumor cells are typically basaloid, with scant cytoplasm and hyperchromatic, angular nuclei. These cells often form the outer layer of the pseudocysts or tubules.
6. Hyalinized Stroma:
   • The tumor frequently has a stromal component that is hyalinized, creating a dense, eosinophilic background. This stroma may surround the pseudocystic spaces and tubules.
7. Myxoid Stroma:
   • In some cases, ACC may have areas of myxoid (mucoid) stroma, providing a more gelatinous appearance.
8. Mucin Production:
   • Although not a dominant feature, mucin production can be observed within the pseudocysts. The mucin is usually alcian blue positive and PAS (Periodic acid–Schiff) positive.

Immunohistochemistry (IHC) in Adenoid Cystic Carcinoma (ACC)

Immunohistochemistry can aid in the diagnosis and characterization of adenoid cystic carcinoma. Commonly used IHC markers include:

1. CD117 (c-Kit):
   • CD117 is often strongly expressed in ACC and can help differentiate it from other salivary gland tumors.
2. p63:
   • This marker is usually positive in the myoepithelial cells of ACC, helping to confirm the biphasic nature of the tumor.
3. S-100:
   • S-100 protein is often positive in ACC, though it is not specific and can be seen in various other tumors.
4. Vimentin:
   • Vimentin is generally positive and indicates the mesenchymal component of the tumor.
5. Cytokeratins (CK7, CK5/6):
   • Cytokeratins can help highlight the epithelial component of ACC. CK7 and CK5/6 are often positive in these tumors.
6. SOX10:
   • SOX10 is another marker that is frequently positive in ACC, supporting the diagnosis.

Prognosis and Molecular Features

1. Prognosis:
   • ACC is known for its indolent but relentless course. It is characterized by a high rate of local recurrence and a propensity for perineural invasion, leading to a challenging clinical course.
   • The prognosis of ACC is often poor in the long term due to the tumor’s tendency to recur and metastasize, particularly to the lungs.
   • Factors influencing prognosis include the tumor’s size, location, histologic pattern (solid variant being the most aggressive), perineural invasion, and completeness of surgical resection.
2. Molecular Features:
   • MYB-NFIB Fusion: A characteristic genetic alteration in ACC is the t(6;9)(q22-23;p23-24) translocation, resulting in the MYB-NFIB fusion gene. This fusion is detected in a significant proportion of ACC cases and is considered a driver mutation.
   • MYBL1-NFIB Fusion: An alternative fusion involving MYBL1 and NFIB has also been identified in some cases.
   • TP53 Mutations: TP53 mutations are relatively rare but may be associated with more aggressive disease.

Grading

ACC is traditionally graded based on the histologic pattern:

1. Grade I (Low Grade):
   • Predominantly cribriform and tubular patterns with minimal solid components.
2. Grade II (Intermediate Grade):
   • A mixture of cribriform, tubular, and solid patterns, with less than 30% solid components.
3. Grade III (High Grade):
   • Dominantly solid pattern (>30% solid areas), which is associated with a worse prognosis due to higher aggressiveness and likelihood of metastasis.

Summary

Adenoid cystic carcinoma (ACC) is characterized by specific histopathologic features and IHC profiles that aid in its diagnosis. The presence of MYB-NFIB fusion genes is a notable molecular characteristic. Prognosis is generally poor due to the tumor’s behaviour, and grading is based on histologic patterns, with higher grades associated with more aggressive disease.