Dedifferentiated adenoid cystic carcinoma: a clinicopathologic study of 6 cases

Dedifferentiated adenoid cystic carcinomas are a recently defined, rare variant of adenoid cystic carcinomas characterized histologically by two components: conventional low-grade adenoid cystic carcinoma and high-grade "dedifferentiated" carcinoma. We examined six cases and analyzed their clinicopathologic profiles, including immunohistochemical features and p53 gene alterations. The 6 patients (3 men and 3 women) had a mean age of 46.8 years (range, 34-70 y). The mean size of the tumors was 3.5 cm (range, 1.7-6 cm). The submandibular gland, maxillary sinus, and nasal cavity were involved in 2 cases each. Postoperatively, 5 patients had local recurrence and 5 developed metastatic disease. Five patients died of disease at a mean of 33.7 months after diagnosis (range, 6-69 mo), and one other was alive with disease at 60 months. Histologically, the conventional low-grade adenoid cystic carcinoma component of the tumors consisted of a mixture of cribriform and tubular patterns with scant solid areas. The high-grade dedifferentiated carcinoma component was either a poorly differentiated adenocarcinoma (4 cases) or undifferentiated carcinoma (2 cases). Three tumors were studied immunohistochemically. Myoepithelial markers were expressed in low-grade adenoid cystic carcinoma but not in the dedifferentiated component. In 2 cases, diffusely positive p53 immunoreactivity together with HER-2/neu overexpression was restricted to the dedifferentiated component. Loss of pRb expression was demonstrated only in the dedifferentiated component of the 1 other case. The Ki-67-labeling index was higher in the dedifferentiated component than in the low-grade adenoid cystic carcinoma component. Furthermore, molecular analysis of 2 cases demonstrated the loss of heterozygosity at p53 microsatellite loci, accompanied by p53 gene point mutation, only in the dedifferentiated carcinoma component of 1 case, which was positive for p53 immunostaining. These results indicate that dedifferentiated adenoid cystic carcinoma is a highly aggressive tumor. Because of frequent recurrence and metastasis, the clinical course is short, similar to that of adenoid cystic carcinomas with a predominant solid growth pattern. Limited evidence suggests that p53 abnormalities in combination with HER-2/neu overexpression or loss of pRb expression may have a role in dedifferentiation of adenoid cystic carcinoma.