Earlier studies have shown frequent mutations in the BRAF and NRAS genes in cutaneous melanoma, but these alterations have not been examined in the rare category of melanoma from black Africans. Moreover, the frequency of epidermal growth factor receptor (EGFR) mutations in melanocytic tumors is not known. We therefore examined 165 benign and malignant melanocytic lesions (including 118 invasive melanomas and 18 metastases collected as consecutive cases from various time periods and from two different pathology departments; the 51 nodular melanomas were randomly selected from a larger, consecutive, population-based series of nodular melanomas) with respect to alterations in the EGFR, BRAF and NRAS genes. Mutations in EGFR (exons 18-21) were not detected. EGFR protein expression was observed in a subgroup of melanomas, but without associations with clinicopathologic phenotype or prognosis. Cytoplasmic EGFR expression was, however, significantly increased from benign nevi to melanomas. Mutations in BRAF and NRAS were detected in superficial melanoma (25 and 29%, respectively), nodular melanoma (29 and 28%, respectively) and lentigo maligna melanoma (15 and 16%, respectively). In a series of melanomas from black Africans (n=26), only two BRAF mutations (8%) were found, both being different from the common T1799A substitution. Moreover, melanomas from black Africans exhibited mutations in NRAS exon 1 only (12%), whereas NRAS exon 2 mutations were predominant in melanomas from Caucasians. Thus, the frequencies of BRAF and NRAS mutations were particularly low in melanomas from black Africans, supporting a different pathogenesis of these tumors.
The clinico-pathologic, immunohistochemical and radiological features of 12 jaw cysts with a prominent orthokeratinized epithelial lining were studied and compared with those of typical odontogenic keratocysts and dentigerous cysts. They differed significantly from odontogenic keratocysts in terms of biologic behavior and histopathologic findings. Although immunohistochemical staining of the epithelial linings for cytokeratins, EMA, CEA and involucrin has not shed any light on the histogenesis of these lesions, staining patterns for these markers were significantly different from those of odontogenic keratocysts and non-keratinized dentigerous cysts. Radiologically, nine cases appeared as dentigerous cysts; two cases, one with sebaceous differentiation, as non-dentigerous unilocular cysts, and the remaining one was exceptional as it showed multiple epidermal cysts with prominent dermal appendages histologically. It is suggested that most of the orthokeratinized jaw cysts may belong to clinico-pathological entities different from odontogenic keratocysts with the majority representing dentigerous cysts with orthokeratinization. The possibility of the existence of rare central dermoid or epidermoid cysts is also to be considered.
The quantification of argyrophilic nucleolar organizer regions (AgNOR) was performed in 34 cases of adenoid cystic carcinoma (ACC) to determine (1) whether AgNOR count correlates with its different histologic grades pertinent to prognosis, and (2) whether AgNOR counts can offer any additional prognostic advantage over histologic grading. According to Szanto et al.'s histologic grading criteria (4), 12 cases were Grade 1, 7 cases Grade 2, and 15 were Grade 3. Patients were divided into 20 favorable cases (without metastases) and 14 unfavorable cases (with metastases). Although most Grade 3 tumors had high AgNOR counts (> or = 4) and Grade 1 tumors with low (< 4) AgNOR counts outnumbered those with high AgNOR counts, considerable overlap of AgNOR values in different grades was observed. However, all unfavorable cases had high AgNOR counts regardless of their histologic grades, suggesting that the metabolic alterations associated with the malignancy level of ACC may partly be portrayed by the AgNOR count, irrespective of the histologic appearance. Cumulative survival rates of Grade 1 tumors and of tumors with low AgNOR counts were better than those of Grade 3 tumors and those with high AgNOR counts. Within the limited number of cases in this series the AgNOR count exhibits a potential for identifying some aggressive ACCs that cannot be detected by histology alone.
Thirteen examples of pleomorphic adenoma (PA) and 4 of myoepithelioma (Me, 2 plasmacytoid cell type, 2 mixed cell type) were examined with respect to their proliferative activity on the basis of proliferating cell nuclear antigen (PCNA) immunohistochemistry. In PA, PCNA labeling index (LI) in tubular/trabecular/solid areas was significantly higher than that in myxomatous or chondroid areas. Although the mean value of LI in PA and Me was not statistically different (PA; 3.02 +/- 1.03%, Me; 3.19 +/- 1.76%), the Me of mixed cell type composed of epithelial, spindle or clear neoplastic myoepithelial cells had significantly higher LI, indicating the possibility of more rapid growth than PA. The small difference in the mean value of PCNA LI between PA and the mixed cell type of Me, however, suggests that enucleation with a margin of normal uninvolved tissue remains the recommended treatment for Me, as well as for PA.
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