Dedifferentiated Adenoid Cystic Carcinoma: A Clinicopathologic Study of 6 Cases

Abstract

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.

Sinonasal Tract and Nasopharyngeal Adenoid Cystic Carcinoma: A Clinicopathologic and Immunophenotypic Study of 86 Cases

“…Using a cutoff of 5 % or higher, there was no statistically significant difference in outcome for those with a high proliferation index versus those with a low proliferation index: mean 8.2 versus 10.5 years, respectively; and 64.3 versus 53.6 % dead of disease, respectively. This is different from others who have reported a statistically significant difference [76,77,105]. However, an increased ki-67 index is noted in pleomorphic adenoma that undergo malignant transformation to ACC ex-pleomorphic adenoma [105,145,146].…”

“…It is important to note that recurrences often developed soon after resection, but late recurrences can be seen up to 14.8 years after initial presentation. When distant metastases are present, lung, liver, and bone are the most common sites, followed by brain, kidney, skin and soft tissues [10,57,65,76,99,121,153].…”

Adenoid cystic carcinoma intermingled with ductal carcinoma of the breast: a case report and review of the literature

“…The de-differentiation of ACC to more aggressive types in salivary gland tumors was first reported by Cheuk et al [7] in 1999. Nagao et al [8] and Ide et al [9] also reported similar cases for ACC located outside the breast.…”

“…The existence of a de-differentiated component of higher malignancy grade worsens the prognosis [7,8]. However, the exact magnitude of this is difficult to estimate because of the limited number of cases described in the literature and the wide diversity of the de-differentiation patterns.…”

Adenoid Cystic Carcinoma: Clinical and Molecular Features

“…That this grading scheme does indeed reflect a form of tumor progression is supported by cases where ACC tumors have displayed increasing solid growth and histologic atypia during the course of tumor recurrence, with increasingly aggressive clinical behavior [17]. ACC may also rarely undergo dedifferentiation, with a high grade anaplastic carcinoma component arising in a conventional ACC [18][19][20]. High-grade transformation is characterized by irregular, jagged infiltrating islands of tumor cells or large confluent areas of solid growth, and the background stroma displays a fibrocellular desmoplasic change, which is typically not seen in conventional ACC.…”