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Purpose: An overlapping area of gain at 3q26 has been reported in lung squamous cell carcinoma (SCC), but whether this also occurs in preneoplastic/preinvasive squamous cell proliferations and early-stage invasive carcinomas of the lung is still unknown., Experimental Design: We evaluated the prevalence and the clinicopathologic implications of 3q26 amplification and polysomy of chromosome 3 in 31 preneoplastic/preinvasive squamous cell lesions of the bronchial mucosa and in 139 early-stage invasive pulmonary SCC, both of limited growth within the bronchial wall [early hilar SCC (EHSCC)] and involving the pulmonary parenchyma [parenchyma-infiltrating SCC (PISCC)]. Moreover, mRNA expression of two candidate genes (h-TERC and SKI-like), both mapping to the minimal common amplification region, was also studied by quantitative real-time reverse transcription-PCR., Results: 3q26 amplification and polysomy of chromosome 3 were confined to malignant samples, with 37% of invasive SCC, and 27% of severe dysplasias/in situ carcinomas showing these chromosomal abnormalities. Amplification (with minimal common amplification region at 3q26.2), polysomy 3, concurrent amplification and polysomy 3, or other changes (monosomy) were found in 25 SCC and 1 dysplasia, 24 and 2, 2 and 0, and 1 and 0, respectively. Amplification was significantly associated with EHSCC, polysomy 3 with PISCC. 3q26 amplification correlated with increased tumor diameter and a history of smoking, whereas polysomy 3 correlated with tumor diameter, pT class, and p53, p21, and fascin immunoreactivity. No relationship of either 3q26 gain or polysomy was found with patients' survival. Overexpression of h-TERC or SKI-like mRNA was found in 3q26-amplified or polysomic SCC, with higher levels of h-TERC in the former and of SKI-like in the latter., Conclusions: 3q26 amplification and chromosome 3 polysomy may be related to the development of invasive SCC, with differential distribution in tumor subsets, despite substantial histologic uniformity. Both h-TERC and SKI-like may be involved in tumor progression.

Nuclear translocation of beta-catenin has been correlated with epidermal growth factor receptor (EGFR) overexpression/activation in non-small cell lung cancer. Less is known on beta-catenin transactivation in high-grade pulmonary neuroendocrine tumors and on the status of beta-catenin activating EGFR and human epidermal growth factor receptor 2 (HER-2) or beta-catenin target genes cyclin D1 and matrix metalloproteinase-7 (MMP-7). beta-catenin immunoreactivity was evaluated in 51 large-cell neuroendocrine carcinomas (LCNEC) and 45 small-cell lung carcinomas (SCLC). Nineteen cases were assessed for beta-catenin gene exon 3 mutations, expression of MMP-7, and expression/gene amplification of EGFR, HER-2, and cyclin D1. beta-catenin was expressed in all 96 high-grade neuroendocrine tumors, the vast majority (94%) showing >50% immunopositive cells. A disarrayed immunoreactivity, however, was commonly encountered consisting in variably altered membrane-associated patterns of staining along with progressive accumulation of cytoplasmic immunoreactivity. In LCNEC, but not in SCLC, the disarrayed patterns correlated with EGFR and HER-2 protein expression. beta-catenin nuclear accumulation was found in nine tumors, including seven LCNEC and two SCLC, and was always associated with disarrayed immunoreactivity and increased MMP-7, but not cyclin D1 expression. These cases, however, did not show beta-catenin gene mutations or EGFR and HER-2 gene amplification or expression. No association was found between nuclear beta-catenin and any clinicopathological variable including patients' survival. The subcellular compartmentalization of beta-catenin is profoundly altered in high-grade pulmonary neuroendocrine tumors. A minor subset of these tumors shows beta-catenin nuclear accumulation in association with increased expression of MMP-7, but not of cyclin D1, independent of EGFR and HER-2 gene amplification or expression.

HER-2/neu oncogene activation by either gene amplification and/or protein overexpression has been documented in several human malignancies. Irrespective of protein overexpression, HER-2/neu gene amplification is rare in lung cancer and studies on its prevalence and clinicopathological implications in early stage non-small cell lung cancer (NCSLC) and neuroendocrine tumours (NET) of the lung are lacking. We evaluated HER-2/neu abnormalities in 345 Stage I NSCLC and 207 Stage I-III NET of the lung of all the diverse histological types, by using immunohistochemistry and fluorescent in situ hybridization in selected cases. Overall, HER-2/neu immunoreactivity was detected in 23% of 345 NSCLC and in 7% of 207 NET. Gene amplification was seen in only 7 (7.4%) of the immunoreactive tumours, with high-level amplification (HER-2/neu gene to chromosome 17 ratio > 4.0) in 3 adenocarcinomas, 1 squamous-cell carcinoma and 1 large-cell neuroendocrine carcinoma (LCNEC), and low-level amplification (HER-2/neu gene to chromosome 17 ratio from 2.0 to 4.0) in 1 squamous-cell carcinoma and 1 LCNEC. None of tested carcinoids and SCLC showed gene amplification. All but 1 gene amplified case exhibited 2+ or 3+ membrane labeling. No relationship was found between gene amplification or protein overexpression and patients' survival or other clinicopathological variables. HER-2/neu gene amplification and protein overexpression are not closely correlated in lung carcinomas and do not bear any prognostic implication. Among neuroendocrine tumours, LCNEC show a slightly higher prevalence of either HER-2/neu gene amplification or protein overexpression.

Meningiomas are common, usually benign slow-growing neoplasms of the central nervous system thought to arise from meningocytes capping arachnoid villi. Primary ectopic meningiomas are exceedingly rare extracranial and extraspinal tumors of controversial origin; they are usually limited to the head and neck region or to the paravertebral soft tissues. Only one mediastinal ectopic meningioma and few pulmonary ectopic meningiomas have been described in the literature until now. Because of their rarity and their intriguing pathogenesis, we report here a second case of primary mediastinal meningioma and an additional case of primary pulmonary meningioma. Their possible origin and differential diagnosis are discussed.

Aim of this work was to investigate the ability of the antibodies against Surfactant proteins (SP) and Thyroid transcription factor 1 (TTF-1) to distinguish primary neoplasms of the lung from metastatic carcinomas to the lung and pleural mesotheliomas. We evaluated the immunohistochemical expression of the antibodies anti SP-A, SP-B, pro SP-C, SP-D, and TTF-1 in a series of 56 primary lung carcinomas, 9 metastatic carcinomas to the lung, 5 pleural mesotheliomas and 8 non-pulmonary carcinomas. Among primary lung neoplasms, only adenocarcinomas immunostained for all SP (specificity = 1; total sensitivity = 0.52). TTF-1 had an excellent specificity (= 1), but a weak sensitivity (= 0.34) in recognizing primary lung carcinomas. TTF-1 was present in lung adenocarcinomas which were negative for SPs; however it failed to distinguish the subtypes. Pleural mesotheliomas, pulmonary metastases and non-pulmonary carcinomas were not immunoreactive for SP-A, SP-B, SP-D, and TTF-1. Pro SP-C was positive also in the adenocarcinomas of the large bowel and in their pulmonary and nodal metastases. These results demonstrate that the combined use of antibodies anti SP-A, SP-B and TTF-1 is the best association in distinguishing primary lung carcinomas from metastatic carcinomas to the lung and pleural mesotheliomas.

Peripheral papillary adenomas of the lung are uncommon neoplasms (only ten cases have been described so far in the English literature) composed predominantly of type-II pneumocytes and generally considered benign. We describe here two additional cases of this lung tumor. In both cases histological examination revealed an encapsulated papillary neoplasm with invasion of the capsule and, in one case, invasion of the adjacent alveoli and visceral pleura too. The proliferative index (Ki67) was less than 2% and the epithelial cells were positive for cytokeratins, surfactant apoproteins (SP), and nuclear thyroid transcription factor-1 (TTF- 1). Ultrastructurally, the epithelial cells showed the characteristic surface microvilli and cytoplasmic lamellar inclusions of type-II cells. Review of the literature has revealed two other cases of peripheral papillary adenoma of type-II pneumocytes with infiltrative features. Thus, we propose replacing the term peripheral papillary adenoma with peripheral papillary tumor of undetermined malignant potential.