C-kit Expression Distinguishes Salivary Gland Adenoid Cystic Carcinoma from Polymorphous Low-Grade Adenocarcinoma

Abstract

Adenoid cystic carcinoma (ACC) is characterized by persistent, relentless growth and a high rate of eventual metastasis. In contrast, polymorphous low-grade adenocarcinoma (PLGA) has a much lower risk of recurrence and rarely metastasizes. The histologic patterns of these two neoplasms can be similar. Expression of c-kit, a transmembrane receptor tyrosine kinase, has recently been reported to be expressed in ACC but not PLGA. Expression of galectin-3, a nonintegrin ␤-galactosidase-binding lectin, has been reported to be significant in PLGA and decreased in ACC.Formalin-fixed paraffinembedded tissue from 9 ACC and 14 PLGA were immunostained for c-kit and galectin-3. Cases were scored as 1؉ (5-25% positive), 2؉ (26 -50% positive), or 3؉ (>50% positive). C-kit was expressed by 100% of ACC (3؉: 7 cases; 2؉: 1 case; 1؉: 1 case) and by 57% of PLGA (2؉: 2 cases; 1؉: 6 cases). In all but one ACC, c-kit expression was confined to the inner cell layer. C-kit expression was also noted in the intercalated duct epithelium of the salivary glands and the acinar cells of the lacrimal gland. Galectin-3 was expressed in 8 of 9 cases of ACC and 14 of 14 cases of PLGA.The results of this, the first study to compare c-kit and galectin-3 expression in ACC and PLGA, suggest that c-kit expression characterizes ACC, but not PLGA. Galectin-3 immunohistochemistry does not have a role in the differentiation of ACC and PLGA. C-kit immunostaining may be a valuable adjunctive tool for this differential diagnosis, particularly in the setting of a limited biopsy. Our finding of different patterns of c-kit expression in tubular and solid variants of ACC supports the concept of solid variant ACC as a highgrade tumor, with progression toward an entirely "inner cell" phenotype.

Polymorphous Low Grade Adenocarcinoma has a Consistent p63+/p40− Immunophenotype that Helps Distinguish it from Adenoid Cystic Carcinoma and Cellular Pleomorphic Adenoma

“…One useful point of differentiation reported by Skalova et al [36] and Vargas et al [37] is the fact that adenoid cystic carcinomas have a significantly higher Ki-67 index than PLGAs, although other investigators have found exceptions to this trend [38]. In another promising finding, Penner et al [15] and Epivatianos et al [20] noted diffuse c-kit positivity in adenoid cystic carcinomas and negativity in PLGAs, but other groups found no difference in c-kit expression between these tumors [14]. Likewise, Gnepp et al [9] and Curran et al [12,19] have noted glial fibrillary acidic protein to cross react with mesenchymal stroma in pleomorphic adenomas and not PLGAs, while other reports have described positivity in both neoplasms [8].…”

“…However, while many immunohistochemical stains (e.g., c-kit, Ki-67, glial fibrillary acidic protein, CD43, S100, bcl-2, etc.) have been used to aid in this differential diagnosis, none of them distinguishes these tumors in a consistently reliable manner [9][10][11][12][13][14][15][16][17][18][19][20].…”

KIT is highly expressed in adenoid cystic carcinoma of the breast, a basal-like carcinoma associated with a favorable outcome

“…Nonsentinel axillary lymph node dissection was performed in Adenoid cystic carcinoma of the breast S Azoulay et al eight cases. The median number of lymph nodes examined was 12 (range: [7][8][9][10][11][12][13][14][15][16][17][18][19]. No lymph node metastases were seen in either of these cases.…”

“…Moreover, recent studies have revealed that KIT (CD117), a transmembrane tyrosine kinase receptor encoded by the protooncogene c-KIT, is expressed in 90% of adenoid cystic carcinomas of the salivary gland but not in normal salivary gland tissue or other head and neck neoplasms. [14][15][16] This prompted us to determine whether a similar pattern of KIT reactivity could be found in adenoid cystic carcinoma of the breast.…”

Hierarchical cluster analysis of myoepithelial/basal cell markers in adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma

“…Ancillary methods, for example, immunohistochemistry with smooth muscle/myoepithelial markers, basal/stem cell markers, proliferation markers, and c-kit have been employed to help distinguish them with variable results. [2][3][4] Recently, several new myoepithelial and basal cell markers have become available, but their utility in distinguishing adenoid cystic carcinoma from polymorphous low-grade adenocarcinoma is unknown. We studied the immunohistochemical-staining pattern of two relatively new markers, metallothionein and maspin in adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma, and compared the results with some well-known myoepithelial cell markers.…”