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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.

Significant intra-and interobserver variability exists in diagnosing and grading oral epithelial dysplasia. Mutations in the tumor-suppressor gene p16 are common in oral cavity dysplastic lesions, but whether immunohistochemical detection of the gene product p16INK4a (p16) can be used as a reliable biomarker for dysplasia is unclear. In total, 119 biopsy specimens representing various oral cavity sites and degrees of dysplasia were retrieved from the pathology files of Emory University Hospital. Formalin-fixed, paraffinembedded sections were stained with hematoxylin and eosin (H&E) and with a monoclonal antibody to p16 (LabVision Corporation, Clone JC2). A blinded review of the H&E slides and the pattern and degree of p16 expression was independently performed by two pathologists. A consensus was obtained when diagnoses differed. Morphologic diagnoses were then compared to p16 immunohistochemical expression. Overall, 61/119 (51%) cases showed no p16 immunoreactivity, including 12/33 (36%) cases of no dysplasia, 11/28 (39%) cases of mild dysplasia, and 38/58 (66%) cases of moderate/severe dysplasia. The remaining cases showed p16 expression limited to the basal and suprabasal nuclei and generally confined to the lower one-third of the epithelium. A logistic regression model showed a trend toward absent p16 expression with increasing severity of dysplasia (P ¼ 0.006). Decreased expression of p16 in dysplastic lesions, as found in this study, may reflect the biologic events involving loss of p16 gene function in the pathogenesis of oral cancer. Our findings suggest that p16 immunohistochemistry is not helpful in differentiating dysplastic from nondysplastic mucosa in oral cavity biopsies, and thus is not a reliable biomarker for use in routine clinical practice.

Traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) is an ulcerative lesion of the oral mucosa with unknown pathogenesis. A few recent case reports have demonstrated molecular evidence of T-cell clonality in TUGSE and CD30 immunoreactivity in the large atypical mononuclear cells, raising the possibility that a TUGSE subset may represent the oral counterpart of primary cutaneous CD30+ T-cell lymphoproliferative disorders. We examined the immunoreactivity for CD30 and T-cell receptor (TCR) gamma gene rearrangement in 37 TUGSE cases. Clonal TCR gene rearrangements were demonstrated in 7 (24%) of 29 cases with amplifiable DNA, and the morphologic features and CD30 immunoreactivity of these cases did not differ from those with polyclonal TCR gene rearrangements. Clinical follow-up was available for 5 of 7 TUGSE cases with clonal TCR gene rearrangement for an average period of 1.75 years after the initial biopsy or excision, and there was no evidence of local recurrence or development of systemic T-cell lymphoproliferative disorder. Without morphologic and/or clinical evidence of lymphoma, T-cell clonality and/or CD30 positivity in these lesions is not indicative of malignancy and should be interpreted with caution.

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