Adenoid Cystic Carcinoma

Adenoid cystic carcinoma (ACC) is an uncommon and unusually indolent cancer arising within glands and occurring mainly in the head and neck but also in the breast, trachea, lacrimal glands, skin and vulva.

ACC arising in the head and neck often has a relentless progress and poor prognosis but tumours arising in some sites (notably in the breast) may have a better prognosis. ACCs are often slow-growing but locally aggressive and particularly prone to recurrence.

Epidemiology

• ACC accounts for about 1% of all head and neck malignancies.^[1]
• ACC of the breast is a rare subtype of breast cancer.^[2]
• The age range is unusually wide and it can occur in children. It is most common between the ages of 40 and 70 years. It occurs more often in females in a 3:2 ratio.
• The p53 tumour suppressor gene may be inactivated in advanced disease but otherwise no particular or consistent genetic or environmental factors have been identified.^[3]
• However, a recent study identifies loss of 1p32-p36 as the most frequent genetic change which was also a marker for poor prognosis in ACC of salivary glands.^[4]

Histopathology

It has a distinct histopathological appearance. There are three main growth patterns at histology:

• Cribiform.
• Tubular.
• Solid. This follows a more aggressive course usually.

It may, however, be confused with basaloid squamous carcinoma.

ACC is associated with a recurrent chromosomal translocation, t(6; 9) (q22-23; p23-24), with the fusion transcript involving the genes MYB and NFIB.^[5]

Presentation

Presentation depends on site, but it can present as:

• A painless slow-growing mass in the face or mouth. In one study using endoscopic resection of tumours in the paranasal sinuses and anterior skull base, ACC represented 15% of the tumours found.
• More advanced tumours may invade nerves, causing paralysis and pain. ACC is of interest to neurosurgeons and neurologists because of a tendency to infiltrate neural structures and spread perineurally. Intracranial involvement can occur but is rare.
• Tumours of the lacrimal gland may affect vision and also may cause proptosis. ACC is the most common primary malignant epithelial neoplasm affecting lacrimal glands.^[6]
• In the lung, ACC may present with respiratory symptoms. ACC is the second most common primary tumour of the trachea and carries a poor prognosis (38.5% five-year survival). Relative to squamous carcinomas it is found in younger patients and is relatively resistant to treatment.^[7]
• In the larynx it may cause voice changes and presents with hoarseness and difficulty breathing.^[8]
• ACC may present as a breast tumour and can present in men.^[9] It is a rare breast carcinoma, representing less than 1% of breast carcinomas. Generally it has a favourable prognosis.^{[10, 11]}
• Unlike most carcinomas of the head and neck, ACC rarely spreads to regional lymph nodes. Distant metastases occurs in up to 40 % of patients. The lungs are the most common site, but liver, kidney, bones and brain are also affected by metastatic disease.^[12]

Differential diagnosis

• Salivary gland tumours:
  • Benign mixed salivary gland tumour.
  • Mucoepidermoid carcinoma.
  • Polymorphous low-grade adenocarcinoma (PLGA) shares features with ACC.
• Squamous cell carcinoma.

Investigations

• Tumour (new or recurrent) may be identified by CT scan or at MRI.
• There are no serological markers, although a recent report using CD43 (a sialoglycoprotein) may be useful as an adjunct to histological examination for distinguishing ACC from PLGA and monomorphic adenoma.^[13]
• Diagnosis is by biopsy or resection followed by histological assessment.
• Investigation of immunoreactivity to identify markers has not so far proved very helpful.^{[3, 14]}

Staging

Staging to plan treatment and assess prognosis should identify:

• Site. Some sites have a worse prognosis, often a function of the difficulty of complete surgical resection.
• Clearance of surgical margins.
• Histological subtype.
• Tumour, node and metastasis (TNM) stage.

Management

• Aggressive surgical resection is the mainstay of treatment.^[6]
• Postoperative radiotherapy is used to try to reduce local recurrence.^[15] Some consider this should be standard therapy for ACC of the head and neck.^[16] However, there is also a suggestion from one study that it is unnecessary where surgical margins are negative.^[17]
• Neutron beam therapy may be more effective. It should be considered as initial primary treatment for locally advanced, unresectable ACC of minor salivary glands and in patients where surgery carries unacceptable morbidity.
• Chemotherapy has not produced good results. Clinical trials of combination chemotherapy are underway for metastatic and locally recurrent disease.^[18]

Complications

A wide range of complications can occur from local spread, metastasis and treatment. These are determined by site and extent of local invasion.

Prognosis

• ACC is a slow-growing, indolent tumour but runs a relentless course. This gives good survival figures at five years but poor figures at 15 years. The five-year survival is 89%, 10-year survival is 65% and the 15-year survival is 40%.
• Poor prognostic features include neural spread and positive surgical margins. Clinical stage, primary site and histological subtype also obviously affect prognosis.^[19]
• Although salivary gland lesions have a relatively high tendency to metastasise, ACC of the breast tends to have a much better prognosis.^[20]
• Recurrence rates are mainly influenced by tumour site, but also by clinical factors (age, sex, site and stage), postoperative treatment (radiotherapy or not) and pathological variables (grade, margins of resection and perineural invasion).
• There is a suggestion that Ki-67 markers and other markers may correlate with prognosis.^{[4, 15]}