Adenoid Cystic Carcinoma



Adenoid Cystic Carcinoma







Key Points



  • Adenoid cystic carcinoma (ACC) is an epithelial tumor that occurs primarily in the major salivary and lacrimal glands, and the skin can be involved secondarily through direct or perineural invasion or as a site of distant metastasis


  • Primary cutaneous adenoid cystic carcinoma (PCACC) is a rare form mostly seen on the scalp and chest


  • Eyelid PCACC has a propensity for middle-aged to elderly males and occurs equally in the upper and lower eyelids


  • PCACC can arise from accessory glands in the conjunctiva and cutaneous accessory lacrimal glands of Krauss and Wolfring


  • It has a predilection for older individuals, is slow growing, usually over months to years, and is locally aggressive with a tendency for perineural invasion


  • Perineural invasion is found in more than 60% of cases


  • The recommended treatment for PCACC is wide local excision with tumor-free margins established on permanent histologic sections


  • Local recurrence is seen in up to 59%, and metastases in 17% of cases


Adenoid cystic carcinoma (ACC) is an epithelial tumor that occurs primarily in the major salivary and lacrimal glands. It is also seen rarely in other sites including the esophagus, bronchus, lungs, breast, vulva, cervix, and prostate.1,2,3,4,5,6 The skin can be involved secondarily through direct or perineural invasion or as a site of distant metastasis.7 A rare form of primary cutaneous adenoid cystic carcinoma (PCACC) was first described in 1975 by Boggio,8,9 and since then just over 100 cases have been reported in the literature,10,11,12 where it most often arises on the scalp in 40% and the chest in 18% of cases.13 To date only about 12 cases involving the eyelid have been reported.14,15,16 Eyelid PCACC has a propensity for middle-aged to elderly males and occurs equally in the upper and lower eyelids. An epidemiologic study using the Surveillance, Epidemiology, and End Results (SEER) program found 152 cases of PCACC diagnosed in the United States between 1976 and 2005, with an annual incidence of 0.23 cases per 1,000,000 population.17


Etiology and Pathogenesis

PCACC can arise from accessory glands in the conjunctiva and cutaneous accessory lacrimal glands of Krauss and Wolfring.11 It is usually considered to originate from eccrine glands, but this tumor can occur in the ear canal, where there are no eccrine glands.18 Some pathologic data indicate a more likely apocrine origin.19

Stenman et al described a t(6;9)(q22-23;p23-24) MYB–NFIB translocation in salivary gland and breast ACCs.20,21,22 Additional studies showed that this chromosomal aberration in ACCs arises from other gland-bearing tissues, including the skin.23 This translocation results in a fusion of the two transcription factor genes MYB and NFIB with activation of MYB. The MYB gene is amplified in carcinomas of the esophagus, colon, and breast, and North et al described the MYB-NFIB fusion product in 9 of 10 PCACC tumors.23


Clinical Presentation

PCACC preferentially affects older individuals with a median age of 60 years and a range from teens to old age. It is slow growing, usually over months to years, and is locally aggressive with a tendency for perineural invasion. They present as asymptomatic, flesh-colored, nontender, firm, indurated, and well-circumscribed nodules, often associated with madarosis (Figure 126.1). They may be associated with eyelid edema, ectropion, or ptosis. Eyelid cases involve males more frequently than females, with an equal distribution between upper and lower eyelids, and range in diameter from 3 to 25 mm. The mean duration between the onset of disease and the final diagnosis is about 10 years.12 Most reported cases were initially misdiagnosed as a chalazion, and the diagnosis of PCACC was established only on histopathology.1,24,25

PCACC is known to be locally aggressive and prone to metastasis. However, sentinel lymph node involvement may or may not be found on initial examination.1,2 Perineural invasion (PNI) has been reported in more than 60% of cases, and recurrence after excision due to PNI has been observed in up to 59% of cases.1,12,26


Differential Diagnosis

Primary cutaneous adenoid cystic carcinoma of the eyelid most commonly mimics a chalazion. It may also simulate other benign lesions including syringoma, cylindroma,
apocrine cystadenoma, clear cell hidradenoma, and spiradenoma. It is also sometimes confused with other malignant tumors such as sebaceous carcinoma, adenoid basal cell carcinoma, other sweat gland tumors such as adenocarcinoma of Moll glands, polymorphous sweat gland carcinoma, and apocrine cribriform carcinoma.16,27,28,29,30