Malignant Melanoma With Osteoclast-Like Differentiation.

Osteoclast-like giant cells are frequently encountered in nonskeletal malignancies; however, the evidence to date suggests that they represent a tissue response to the lesion rather than neoplastic differentiation. We describe a case of metastatic melanoma demonstrating osteoclast-like differentiation in the lung. The lung nodule was diagnosed as a metastatic melanoma by histological features and confirmed by immunohistochemistry. Resection specimen showed numerous multinucleated giant cells exhibiting osteoclast-like morphology dispersed throughout the lesion. Both the neoplastic melanocytes and giant cells were reactive for HMB-45, Melan-A, and S100. In addition, the multinucleated neoplastic giant cells were also reactive for the monocyte/macrophage lineage markers CD68 and CD163, and alkaline phosphatase, an enzyme present in normal osteoclasts. The neoplastic melanocytes and the multinucleated neoplastic giant cells were also reactive for microphthalmia-associated transcription factor, a protein required for the development of both melanocytes and osteoclasts. Collectively, a co-expression of monocyte/macrophage markers along with melanocytic markers and alkaline phosphatase in the multinucleated neoplastic giant cells in metastatic melanoma suggest that malignant melanocytes are capable of differentiating into osteoclast-like cells and consequently aid invasion into various structures and eliciting the aggressive behavior.

Nuclear morphometry in flat epithelial atypia of the breast as a predictor of malignancy: a digital image-based histopathologic analysis.

OBJECTIVE: To identify morphometric features unique to flat epithelial atypia associated with cancer using digital image analysis. STUDY DESIGN: Cases with diagnosis of flat epithelial atypia were retrieved and divided into 2 groups: flat epithelial atypia associated with invasive or in situ carcinoma (n = 31) and those without malignancy (n = 27). Slides were digitally scanned. Nuclear features were analyzed on representative images at 20x magnification using digital morphometric software. RESULTS: Parameters related to nuclear shape and size (diameter, perimeter) were similar in both groups. However, cases with malignancy had significantly higher densitometric green (p = 0.02), red (p = 0.03), and grey (p = 0.02) scale levels as compared to cases without cancer. A mean grey densitometric level > 119.45 had 71% sensitivity and 70.4% specificity in detecting cases with concomitant carcinoma. CONCLUSION: Morphometry of features related to nuclear staining appears to be useful in predicting risk of concurrent malignancy in patients with flat epithelial atypia, when added to a comprehensive histopathologic evaluation.