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We assessed the occurrence of atypical adenomatous hyperplasia (AAH) in whole lung lobes with primary cancer lesions. Following surgical resection, tissue specimens were sliced to a thickness of 4 mm (3,641 specimens from 61 cases; mean = 59.7 specimens per case). A total of 119 AAH foci were found and an association was evident in 25 (57%) of 44 adenocarcinomas, 3 (30%) of 10 squamous cell carcinomas, and 2 (29%) of 7 other lung cancers. Histologic evaluation showed that 108 AAH foci were categorized as low-grade and the other 11 as highgrade AAH. These 11 foci of high-grade AAH were present in 7 patients with adenocarcinoma, and in 1 patient there was a synchronous double primary lung adenocarcinoma. High-grade AAH was closely associated with bronchioloalveolar carcinoma (BAC) type adenocarcinoma, and low-grade AAH with nonBAC adenocarcinoma. The mean ± SD Ki-67 labeling index in high-grade AAH (3.5% ± 2.9%) was significantly higher than for the low-grade index (1.4% ± 1.6%). We propose that foci of high- but not lowgrade AAH may be potential precursor lesions of lung adenocarcinoma, especially with the BAC component. Generally, atypical adenomatous hyperplasia (AAH) has been detected by chance during histopathologic studies on surgically resected lung specimens or for autopsy. AAH is a solitary alveolar lesion with proliferation of type II alveolar pneumocyte-like and/or Clara cell–like cells with a varied cellular atypia. Miller et al 1 suggested that AAH might be an adenomatous lesion as there was an analogy to colonic tumor, and subsequent studies supported this hypothesis. 2-11 AAH

Tissue factor pathway inhibitor (TFPI) plays a key role in modulating tissue factor-dependent blood coagulation. This study was done to determine not only the inhibitory effects of recombinant human TFPI (rTFPI) on thrombus formation in rat models with disseminated intravascular coagulation (DIC), but also to identify the distribution of exogenous TFPI in vivo . Disseminated intravascular coagulation was induced by administering a priming dose of carrageenan 10 mg/kg body weight and was followed 24 hours later by a provocative dose of lipopolysaccharide (LPS) 500 mg/kg body weight. The rTFPI was administered intravenously at a dose of either 1 or 4 mg/kg body weight immediately after LPS treatment. Exogenous rTFPI at a dose of 4 mg/ kg significantly inhibited the consumption of fibrinogen, platelets and factor Vila (P < .05) and also reduced the number of fibrin thrombi formed in the liver, lungs, kidneys, and spleen (P < .05), whereas rTFPI at a dose of 1 mg/kg had no significant inhibitory effect on these DIC parameters. Recombinant human rTFPI activity was rapidly cleared from the plasma; however, a significant amount of the inhibitor was still present in tissues even 3 to 6 hours after intravenous administration. Exogenous TFPI was mainly identified in Kupffer cells, macrophages, and on the microvascular endothelial lining of different organs. In the kidney, rTFPI was identified on both the abluminal surface of the renal tubules and the luminal surface of the proximal convoluted tubules. No rTFPI, however, was detected in the hepatocytes. Tissue factor was mainly expressed by monocytes/macrophages. These findings suggest that TFPI plays an important role in modulating TF-dependent thrombogenesis. The elucidation of the rTFPI distribution and interactions in vivo might thus provide valuable insight into its inhibitory mechanisms as well as its therapeutic implications in DIC.

Lung tissues from 16 patients with pulmonary sclerosing hemangioma were studied with the use of serial sections and immunoperoxidase staining for surfactant apoprotein, secretory component (SC), and epithelial membrane antigen (EMA). The cells lining papillary projections or cystic spaces were stained with surfactant apoprotein, SC, and EMA. Characteristic round stromal cells, which were considered to be the main component of the sclerosing hemangioma, consisted of immunohistochemically heterogenous cells, that is, positive findings were attained with all three antigens, surfactant apoprotein- and EMA-positive ones, SC- and EMA-positive ones, only EMA-positive ones, and all three negative. When investigating the immunoreactivity of neoplastic type II pneumocytes in bronchioalveolar cell carcinoma and hyperplastic ones in nonneoplastic pulmonary disorders, the authors found that almost all the neoplastic type II pneumocytes had all three antigens. Many of the hyperplastic and normal type II pneumocytes, however, were stained with surfactant apoprotein and EMA but not with SC. The authors' findings add further support for the proposal that sclerosing hemangioma of the lung is epithelial in origin. In view of the various staining patterns found in the stromal cells, sclerosing hemangioma probably consists of immunohistochemically heterogenous epithelial cells. The staining pattern of the cells lining papillary projections or cystic spaces was similar to that of neoplastic type II pneumocytes rather than that of hyperplastic type II pneumocytes.

Monoclonal antibody KP16D3 was produced by immunizing mice with monkey bronchoalveolar lavage. KP16D3 revealed the immunohistochemical reactivity in the cytoplasm of some nonciliated bronchiolar epithelial cells and type II pneumocytes and thereby recognized specifically a protein with an apparent molecular weight of 60 kD with the use of Western blotting and immunoaffinity column chromatography followed by SDS-PAGE. Examination of 76 primary and 4 metastatic lung carcinomas in primary lung carcinoma KP16D3 showed immunohistochemical positivity only to mucin-nonproducing papillary adenocarcinoma (27/28) and bronchioloalveolar carcinoma (2/2), except for one case of large cell carcinoma. All other primary lung carcinomas such as squamous cell carcinoma, acinar adenocarcinoma, and small cell carcinoma had negative results. From these findings, KP16D3 seems to be an effective immunohistochemical marker of mucin-nonproducing papillary adenocarcinoma and bronchioloalveolar carcinoma of the lung and it appears to be useful to investigate both the histogenesis and functional expression of primary lung adenocarcinoma.

Three cases of infantile hemangioendothelioma were immunohistochemically studied with the use of antibodies against von Willebrand factor (vWF), Ulex europaeus I lectin (UEA I), vimentin, thrombomodulin (TM), and actin, as endothelial cell (EC) markers. Because of a broad variety of histologic features, the growth pattern of the tumor cells was subclassified into the following four subtypes: capillary, sinusoidal, cavernous, and myxomatous parts. The solitary tumor from patients 1 and 2 was composed of these four components, but the multiple tumor in the patient 3 consisted of capillary and sinusoidal parts. Immunohistochemically, vWF and vimentin were dominantly expressed in the ECs of the cavernous and myxomatous parts. UEA I had strongly positive results in all histologic types, except the myxomatous part. Expression of vWF and vimentin in neo-plastic EC suggests that functional differentiation of the tumor tissue occurs in the myxomatous and cavernous parts and may be related to the spontaneous regression of the infantile hemangioendothelioma.