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Immunoreactivity for fascin, an actin-bundling protein related to cell motility, has been reported in breast, ovary, pancreas, skin, and non-small cell carcinomas, and associated with more advanced disease stage and poorer prognosis. Data on pulmonary neuroendocrine (NE) tumors, however, are lacking. We evaluated the expression of fascin by immunohistochemistry—using two different monoclonal antibodies—in surgical specimens of pulmonary NE tumors of all the diverse histological types from 128 consecutive patients recruited between 1987 and 2001, and investigated its relationship with the presence of lymph node metastases. Overall, fascin immunoreactivity was detected in 5% of 38 typical carcinoids (TC), 35% of 23 atypical carcinoids (AC), 83% of 40 large-cell neuroendocrine carcinomas (LCNEC), and 100% of 27 small-cell lung carcinomas (SCLC) (P<0.001), Normal NE cells or hyperplastic NE tumorlets were consistently unreactive. No statistically significant differences in fascin immunoreactivity were found between the two antibodies. In TC and AC but not high-grade NE tumors, fascin immunoreactivity closely correlated with the occurrence of lymph node metastases, the pN class and the number of involved lymph nodes (P<0.001). It was also significantly associated with an increased proliferative activity (Ki-67 labeling index >5%) (P=0.020), and with either down-regulation or altered subcellular compartmentalization of E-cadherin (P<0.001) and CD99 (P=0.030), two cell adhesion complexes in pulmonary NE tumors. At multivariate analysis, only fascin emerged as an independent predictor of lymph node metastases in this tumor group (HR 30.28; 95% confidence intervals: 1.59–574.49; P=0.023). This study indicates that fascin immunoreactivity may identify subsets of pulmonary carcinoid patients with different metastatic potential to regional lymph nodes. Targeting the fascin pathway could be a novel therapeutic strategy of pulmonary carcinoids. [Copyright &y& Elsevier]

Most granular cell tumours (GCTs) are benign proliferations of purported Schwannian derivation, showing immunoreactivity for Schwann cell-related antigens. Due to incomplete agreement on the precise nature of GCTs (reactive vs neoplastic), we performed an immunohistochemical study with the alkaline phosphatase/anti-alkaline phosphatase (APAAP) technique on 30 GCTs. The aim was to evaluate their growth patterns and the possible relationships of granular cells with other nerve sheath-related cell types (i.e., Schwann and perineurial cells, and dendritic cells displaying CD34/vimentin immunoreactivity). An expansive growth pattern was detected in five cases, a pseudoinfiltrative growth pattern in nine cases and a mixture of the above in the remaining 16 cases. Besides immunoreactivity for S-100 protein, neuron-specific enolase, vimentin, CD57, CD68, MAC 387, alpha-1-antitrypsin and alpha-1-antichymotrypsin in granular cells, we documented intimate architectural relationships between granular cells, Schwann and perineurial cells, and a third type of CD34/vimentin-positive nerve sheath-related cell in most GCTs. These results suggest that GCTs are heterogeneous lesions. Some of them show a pseudoinfiltrative growth pattern and retain close relationships with the normal components of the nerve sheath. In other lesions, granular cells grow in an expansive fashion and constitute the predominant cell component of the tumour. These architectural and immunophenotypic differences may reflect a different nature of GCTs: they may initially represent reactive or hamartomatous lesions that subsequently acquire truly neoplastic potential. [ABSTRACT FROM AUTHOR]