The cellular composition of adenoid cystic carcinoma. An immunohistochemical study

Abstract

To investigate the cellular differentiation of adenoid cystic carcinomas (ACC), a comparative immuno-histochemical study of 12 normal salivary glands and eight specimens of ACC was performed. Antibod-ies were used against S l O O protein (S), keratins (K) of various molecular weights, vimentin (V), muscle-specific actin (A,), epithelial-membrane antigen, human milk fat globules, and collagen type IV. A panel of four of these antibodies (SKVA) was identified as the most helpful in characterizing cells in normal salivary glands and ACC. The immunophenotypes depended on the histologic patterns of ACC. Cells in morphologically recognizable duct structures in the cribriform and trabecular areas expressed a phenotype similar to that of the intercalated duct. Cell layers around pseudocysts and occasional cellular islands had an immunophenotype suggesting myoepithelial-cell differentiation. The most clear cut epithelial/myoepithelia.l bilaminar differentiation was present in areas with a trabecular pattern, in which the layers facing the stroma and the central ductal elements had SKVA phenotypes of myoepithe-lial and ductal differentiation, respectively. In areas with a reticular pattern, most of the cells showed ductal differentiation. Many of the cells in the cribriform and basaloid regions were immunophenotypi-cally undifferentiated. These results indicate that ACC consists of undifferentiated cells and of cells that are differentiating toward ducts, predominantly intercalated ducts, and toward myoepithelium. These findings support previous observations by electron microscope. Cancer 60:1589-1598, 1987. DENOID CYSTIC CARCINOMA (ACC) is a distinct A type of relatively low-grade adenocarcinoma most commonly involving minor salivary glands and, less frequently, other sites such as the parotid glands, breasts, skin, uterine cervix, esophagus, lungs, and prostate.' U1-trastructural studies of ACC of the salivary gland'-4 and have indicated that ACC is composed of undif-ferentiated cells and of cells with myoepithelial and ductal differentiation. Immunohistochemical investigations of ACC have been rather limited, and only SlOO protein was employed as a marker for myoepithelial-cell differentiation in most previous The results of these studies are somewhat contradictory, since some investigators reported no, or virtually no, myoepithelial I whereas otheirs'0.'2 demonstrated that From the Sylvia

Adenoid cystic carcinoma: A review of recent advances, molecular targets, and clinical trials

“…Nonetheless, after resection of the primary tumor, local and distant recurrences are quite common. This high recurrence rate likely reflects the known tendency for perineural invasion with occult extension beyond surgical margins and a tendency for hematogenous dissemination at early stages of tumor development 6, 8. The most common sites for metastatic disease are the lungs followed by bone and liver.…”

“…The original histopathologic term for ACC of the salivary gland was “cylindroma” based on the histologic appearance of cylinders of epithelial/secretory cells and a hyaline stroma 8, 9. The tumor cells have angulated hyperchromatic nuclei and minimal cytoplasm, which is usually clear or eosinophilic.…”

“…The tubular pattern has a similar cytologic appearance but with the tumor cells arranged in nests surrounded by variable amounts of eosinophilic, often hyalinized stroma. The solid histologic subtype shows aggregates of basaloid cells without tubule nor pseudocystic formations 8, 13…”

“…By immunohistochemistry, the myoepithelial tumor cells that surround the pseudocysts stain positively for smooth muscle actin, S100, vimentin, and smooth muscle myosin heavy chain 8. Also, ACC cells are strongly positive for the receptor tyrosine kinase c‐KIT (CD117) and MYB (Figure 1B) regardless of grade 8, 14, 15. Biomarkers, such as c‐KIT, vascular endothelial growth factor receptor (VEGFR)−3, Ki‐67, and p53, have been linked to biologic aggressiveness and poor prognosis 8.…”

“…Also, ACC cells are strongly positive for the receptor tyrosine kinase c‐KIT (CD117) and MYB (Figure 1B) regardless of grade 8, 14, 15. Biomarkers, such as c‐KIT, vascular endothelial growth factor receptor (VEGFR)−3, Ki‐67, and p53, have been linked to biologic aggressiveness and poor prognosis 8. Other genes, such as Beclin‐1 ,16 may interact with p53 and Bcl‐2 and may have a role in the pathogenesis as well.…”