Bronchioloalveolar Adenocarcinoma Research Articles

Bronchiolo-alveolar adenocarcinoma associated with pulmonary aspergilloma: Report of a case and review of the literature.

Aspergillosis is an uncommon complication of pulmonary carcinoma. A 60-year-old female was performed right lower lobectomy because of adenocarcinoma with pseudocavities. The diagnosis was bronchiolo-alveolar adenocarcinoma, and there was aspergilloma in one of the cysts in the tumor. Cavitation or cystic change in bronchiolo-alveolar adenocarcinoma is rare because of nondestructive growth pattern with an adequate blood supply in this histologic type. Additionally, bronchiolo-alveolar adenocarcinoma associated with pulmonary aspergilloma is rare.

Lepidic intrapulmonary growth of malignant mesothelioma presenting as recurrent hydropneumothorax

We report a case of malignant mesothelioma with unusual clinical and histological findings. The patient presented with recurrent hydropneumothorax and minimal pleural thickening on chest computed tomography (CT). Histologically, the pleura was involved by the malignant mesothelioma, albeit to a limited degree. Unexpectedly, the lung parenchyma from two different lobes showed focal nests of mesothelioma cells filling the alveolar spaces and growing on the luminal surface of the alveolar septa, closely resembling the multicentric growth pattern of bronchioloalveolar adenocarcinoma. Immunohistochemical and ultrastructural studies confirmed that the pulmonary lesions were an extension of the malignant mesothelioma. This case illustrates clinically, the importance of a high index of suspicion for malignancy in older patients with unexplained recurrent hydropneumothorax; and histologically the potential of malignant mesothelioma to invade the lung at an early stage of growth.

Comparative Pathology of Dust-Induced Pulmonary Lesions: Significance of Animal Studies to Humans

The proper interpretation of animal experiments on particulate materials is essential in order to properly identify the relative risk associated with human exposure to these materials. This article reviews the pathology of experimental dust-induced pulmonary lesions, discusses factors necessary for the proper interpretation of these results, and makes recommendations for the design and conduct of future studies. In experimental studies, animals are often exposed to high concentrations of dusts that overwhelm normal lung clearance mechanisms, resulting in the somewhat poorly defined condition of “dust overload.” The pulmonary response to this intra-alveolar dust loading is nonspecific and thus morphologically similar regardless of the dust type studied. In the rat, these lesions are characterized by alveolar macrophage accumulation, necrosis of pneumocytes, granuloma formation, fibrosis, and bronchiolarization and squamous metaplasia of alveoli. Depending on exposure concentration and duration, bronchiolo-alveolar ademonas and adenocarcinomas and cystic keratinizing squamous lesions may occur. The squamous lesions appear to represent a response unique to the rat. The significance of studies using dust concentrations that produce these nonspecific lesions is questionable since such conditions, with extreme exception, do not occur in humans. Further, fibrogenic or carcinogenic properties that may be specific to a particular dust at exposure concentrations relevant to humans may actually be masked by the nonspecific response that occurs following dust overload. Studies with dust at concentrations that produce an interstitial dust loading but that are below the threshold for intra-alveolar dust overload are more relevant for human health hazard identification. This has been best demonstrated by the results of numerous studies with asbestos in rats where fibrosis and neoplasia, morphologically similar to that seen in humans, have been produced in the absence of the nonspecific lesions seen in dust overload. The interpretation of studies where dusts are administrated by nonconventional routes should also be undertaken with caution. For example, serosa tests bypass an important mechanistic step in fiber-induced mesothelioma, namely, the ability of a dust to reach the pleura surface following inhalation. In addition, such tests may produce diagnostic dilemmas since reactive changes on serosal surfaces, which are expected following application of any foreign substance, may be difficult to differentiate from a neoplastic response. Future studies to assess the human health hazards of fibrous and nonfibrous dusts should be conducted at concentrations that allow for the characterization of responses specific to a given dust and by exposure routes most representative of that experienced by humans.

K-ras gene mutations: an unfavorable prognostic marker in stage I lung adenocarcinoma.

Activation of K-ras gene by point mutations, a common finding in lung adenocarcinomas, has been suggested to decrease patient survival. We investigated 109 lung adenocarcinomas, mostly small, peripheral, stage I tumours (81/109) for presence of K-ras gene mutations at codons 12 and 13. Mutations were detected by denaturing gradient gel electrophoresis analysis of specific sequences amplified by polymerase chain reaction from DNA extracted from archival pathological material. Thirty-three of 109 (30.3%) tumours showed mutations at codon 12 (28/33, 84.8%) or 13 (5/33, 15.2%) of the gene. Mutations and type of nucleotide substitutions were differently distributed among cytological subtypes, being more prevalent among less differentiated (G2 and G3) tumours and among bronchial than bronchiolo-alveolar type adenocarcinomas. Survival analysis showed an adverse effect of K-ras mutation on survival, restricted to stage I tumours. Median survival for 81 stage I patients was 30 months for non-mutated tumours versus 20 months for mutated tumours (p = 0.016). Multivariate analysis showed that age of patient (p = 0.001) and K-ras mutation status (p = 0.04) were the only independent factors influencing survival significantly. These data strengthen the hypothesis that K-ras gene mutations may be useful in identifying a subgroup of patients with poor outcome.

Induction of squamous cell carcinomas in the mouse lung after long-term inhalation of polycyclic aromatic hydrocarbon-rich exhausts.

A 10-month inhalation study using newborn female mice was performed to determine pulmonary tumorigenicity of polycyclic aromatic hydrocarbon (PAH)-enriched exhausts. At two exhaust doses containing 50 micrograms/m3 (group II) and 90 micrograms/m3 benzo(a)pyrene (BaP) (group III) a significant increase of lung tumors was observed and the incidence of malignant lung tumors was dose-dependent. Bronchiolo-alveolar adenomas were observed in all mice of groups II and III (40/40 each) as compared to 5/40 in the control (group I). Bronchiolo-alveolar adenocarcinomas developed in 10/40 and in 33/40 mice of groups II and III, respectively, but were absent in group I. Single or multiple squamous cell carcinomas, which showed variable degrees of differentiation were observed exclusively in 6 mice of group III. One adenosquamous carcinoma was seen in an further animal of this group.

Bronchioloalveolar adenocarcinoma with myoepithelial cells

A unique variant of papillary lung carcinoma in a 58-year-old woman with both Clara cell and myoepithelial components is reported. The tumor was characterized by the presence of glandular spaces lined by two cell layers. The superficial (luminal) layer was made up of columnar cells with ultrastructural and immunohistochemical features of Clara cells, and occasional interspersed type 2 pneumocytes. The cells of the basal layer possessed ultrastructural and immunohistochemical features of myoepithelial cells. Myoepithelial cells have not previously been reported in a bronchioloalveolar adenocarcinoma.

Ultrastructure of Neoplastic Cells in Different Histologic Subtypes of Pulmonary Adencocarcinoma

57 pulmonary adenocarcinomas were classified according to the WHO Classification of Lung Tumours. 55 cases were primary adenocarcinomas and two were metastases from the gastrointestinal tract. The acinar, papillary and bronchiolo-alveolar carcinomas were well or moderately differentiated and the solid adenocarcinomas were poorly differentiated tumours secreting mucus in intracytoplasmic vacuoles. All tumours, including the two metastases, were analyzed by transmission electron microscopy. Most of the acinar, papillary and all bronchiolo-alveolar adenocarcinomas contained a great or moderate number of secretory granules which were pale fibrillar or dense homogeneous. Among the solid adenocarcinomas there were no tumours with a great number of secretory granules. The surface fine structure of the metastatic carcinomas differed from those of the primary adenocarcinomas, having a brush-border instead of microvilli. The ultrastructure of the primary adenocarcinomas resembled the normal surface epithelial cells of bronchi and bronchioli, and two papillary adenocarcinomas contained lamellar bodies similar to granular pneumocytes. Instead of dividing into four different subtypes pulmonary adenocarcinomas can be classified according to histological grading.

Structural study of the sugar chains of alpha-amylases produced ectopically in tumors.

About thirty percent of two alpha-amylases produced from a serous papillary cystadenocarcinoma of the ovarium (case 1) and a bronchioloalveolar adenocarcinoma of the lung (case 2) was glycoproteins containing 1 mol of asparagine-linked sugar chain, respectively. The structures of the sugar moieties were found by sequential enzymatic degradation and methylation analysis to be as follows: [(Gal beta 1 leads to 4)0 or 1GlcNAc beta 1 leads to 2Man alpha 1 leads to 6(3)][GlcNAc beta 1 leads to 2Man alpha 1 leads to 3(6)]Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc and [(Gal beta 1 leads to 4)0 or 1GlcNAc beta 1 leads to 2Man alpha 1 leads to 6][NeuAc alpha 2 leads to 6Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3]Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAc. Structures of asparagine-linked sugar chains were the same in the tumors of cases 1 and 2 and were incomplete in comparison with those of the parotid amylase.