Ductal adenomas of salivary gland showing features of striated duct differentiation ('striated duct adenoma'): a report of six cases.

AIMS: To describe a salivary adenoma composed largely of unilayered ducts resembling striated ducts, and to differentiate it from similar adenomas, including canalicular and intercalated duct adenoma. METHODS AND RESULTS: Six unilayered ductal adenomas were identified in parotid (four) and palate (two). They were encapsulated, ranged from 0.5 to 3.0 cm and composed of closely apposed ducts with virtually no stroma. The ducts varied in size and showed cysts up to 0.1 cm. The cells were eosinophilic and bland. Prominent cell membranes, reminiscent of 'striations' of normal striated ducts, were seen. The typical epithelial 'beading' pattern with abundant stroma of canalicular adenoma was absent. The tumours expressed keratins (six of six) and S100 (five of six). Smooth muscle actin (SMA) revealed no myoepithelial cells. Two tumours showed focal bilayered ducts with calponin or smooth muscle myosin heavy chain, but the tumours were largely unilayered. Only isolated cells in three tumours were positive with p63; a pattern identical to striated ducts. In contrast, the normal excretory and intercalated ducts all contained diffuse bilayering with basal or myoepithelial markers. CONCLUSIONS: Striated duct adenomas are unilayered ductal tumours that recapitulate normal striated ducts.

Epithelial-myoepithelial carcinoma with high grade transformation.

Epithelial-myoepithelial carcinoma (EMC) is a rare salivary gland tumor of presumed intercalated duct origin with a low risk of metastasis and mortality. Factors shown to affect behavior include positive margins, vascular invasion, necrosis, and myoepithelial anaplasia. The latter category and dedifferentiated EMCs have been separated on the basis of presumed myoepithelial versus ductal origin, respectively. Three additional cases of typical EMC with transition to high-grade carcinoma are presented. Two of the tumors were stained with CAM5.2, 34betaE12, cytokeratin 14, p63, S100, calponin, smooth muscle actin, and muscle-specific actin. All tumors showed a gradual transition to a high-grade carcinoma from an EMC, each composed of clear cells even in the high-grade regions. One case also showed a discrete area with ductal lumina and another had plasmacytoid morphology. Squamous differentiation was seen in all cases as well. A consistent immunostaining pattern was not noted. Areas with focal lumina were diffusely positive for CAM5.2 only. Areas with clear cells showed patchy S100 positivity only, whereas cytokeratin 14 and 34betaE12-stained squamous pearls. The case with plasmacytoid morphology was diffusely positive for p63. No immunoexpression was noted with smooth muscle actin, muscle-specific actin, or calponin. It was not possible to convincingly separate the high-grade component in these cases into ductal dedifferentiated EMC versus myoepithelial. Recently, there has been a move to abandon the term "dedifferentiation" in favor of "high-grade transformation" in other salivary gland malignancies. We report these 3 such cases, review the literature and propose that these lesions be regarded as "EMC with high-grade transformation."

Sialoblastoma in adults: distinction from adenoid cystic carcinoma.

Essentially, sialoblastoma is a disease of infancy with the oldest case presenting at 4 years of age. About one third of pediatric sialoblastoma cases will have a cribriform growth pattern. No adult cases have been reported with a specific diagnosis of sialoblastoma. If even focal cribriforming were present, such cases have undoubtedly been diagnosed as adenoid cystic carcinoma. Such was the circumstance in the 3 adult tumors presented in this report. Each case, however, has the primitive histopathology with discrete nests of basaloid tumor cells, associated bilayered ductal structures and the fibromyxoid stroma characteristic for sialoblastoma with its resemblance to fetal salivary gland or salivary gland with arrested development. One key example has 28-year follow-up. Sialoblastoma, whether in a child or adult with or without a cribriform growth pattern, appears to have a more favorable prognosis than adenoid cystic carcinoma. Aspects of the histological differential diagnosis of these 2 tumors are discussed.

Clear cell carcinoma: review of its histomorphogenesis and classification as a squamous cell lesion.

In current classification schemes, clear cell carcinoma-including both the hyalinized and nonhyalinized variety--is now an accepted subtype of malignant salivary gland tumors. Despite this, the underlying cellular differentiation process leading to the typical histomorphology of this neoplasm remains unclear. This review summarizes and illustrates the histologic, ultrastructural, and immunohistochemical evidence for the underlying squamous cell nature of clear cell carcinoma. Squamous cell differentiation is not an uncommon feature of nonneoplastic and neoplastic lesions of the salivary glands. Clear cell carcinoma needs to be added to this list as a unique but specific variety of clear cell squamous carcinoma.

Intercalated duct lesions of salivary gland: a morphologic spectrum from hyperplasia to adenoma.

Intercalated duct lesions (IDLs) are rare, poorly understood and not well-studied lesions that have been associated with a small number of epithelial-myoepithelial carcinomas (EMC) and basal cell adenomas. To examine the nature of IDLs and their association with salivary gland tumors, we reviewed 34 lesions in 32 patients. The IDLs were stained with CK7, estrogen receptors (ER), progesterone receptors, lysozyme, S100, calponin, and CK14. The patients ranged in age from 19 to 80 years (mean 53.8) with a 1.7:1 female predominance. The majorities of IDLs were parotid lesions (82%), were small and nodular (average size 3.1 mm) and showed 3 architectural patterns: hyperplasia (20), adenoma (9), and hybrid forms (5). In 59% of cases, IDLs were seen in conjunction with another salivary gland tumor, most commonly basal cell adenoma (8 cases), followed by EMC (3 cases). One case showed a combination of intercalated duct hyperplasia and basal cell adenoma. The IDLs stained diffusely with CK7 (100%) and S100 (73%) and focally for ER (91%) and lysozyme (100%). Calponin and CK14 highlighted a thin myoepithelial cell layer around all ducts (100%). Normal intercalated ducts were also consistently positive for CK7 and lysozyme, and focally for ER, but were S100 negative. In summary, IDLs have a variety of patterns ranging from hyperplasia to adenoma with hybrid lesions and share morphologic and immunophenotypic features with normal intercalated ducts. There is an association with basal cell adenomas and EMC, which lends credence to their role as a putative precursor lesion.

Lymphadenoma of parotid gland: Two additional cases and a literature review.

For classification purposes, proper identification of infrequent and unique salivary gland tumors requires the gradual accumulation of a sufficient number of cases. Lymphadenoma (i.e., an adenomatous, generally parotid-based lesion with an exaggerated lymphocytic infiltrate, but a lack of sebaceous differentiation) has approximately 9 reported cases. This report adds 2 additional cases occurring as a discrete, at least partially encapsulated nodule in the parotid gland. Embedded within the extensive lymphocytic component were isolated nests of solid or glandular epithelium, with 1 case displaying a few foci of chondrocytic differentiation. Immunohistochemical investigation of the latter case revealed the presence of both luminal and myoepithelial cells.

Molecular characterization of salivary gland malignancy using the Smgb-Tag transgenic mouse model.

The molecular mechanisms underlying salivary gland tumorigenesis remain unclear. In order to identify genetic changes that occur during the development of invasive adenocarcinoma from normal salivary gland, we used the Smgb-Tag transgenic mouse model. This transgene induces the progressive development of dysplasia to invasive adenocarcinoma in the submandibular salivary gland. Gene expression patterns from 20 submandibular glands (two normal, nine dysplasia and nine adenocarcinoma samples) were assessed using a mouse 15 K cDNA array. Unsupervised hierarchical clustering was used to group gene expression based on 157 differentially expressed genes distinguishing between dysplasias and adenocarcinomas. Further analysis identified 25 significantly overexpressed and 28 underexpressed cDNA sequences in adenocarcinoma as compared to dysplasia. Differential expression of five genes (Lcn2, Ptn, Cd24a, Mapk6 and Rnps1) was validated by quantitative real-time RT-PCR in a total of 48 mouse salivary gland tissues (seven histologically normal, 13 dysplasias and 28 adenocarcinomas), including the 20 samples analyzed by cDNA arrays. Immunohistochemical analysis was used to validate the expression of Ptn and Cd24a at the protein level in a subset of 16 mouse salivary glands (four normal, five dysplasia and seven adenocarcinoma samples), as well as in 23 human submandibular gland tumors (16 pleomorphic adenomas, three adenoid cystic carcinomas, one acinic cell carcinoma, one adenocarcinoma NOS, one myoepithelial and one mucoepidermoid carcinoma). We thus demonstrated that the Smgb-Tag transgenic mouse model is a useful tool for the identification of genes that are deregulated in salivary gland adenocarcinomas. Our data suggest that Ptn and Cd24a may be genetic markers associated with salivary gland tumorigenesis and/or progression.