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Important advances in lung cancer treatment have been made over the last decade. Several drugs designed to target molecular pathways involved in cancer-cell growth and survival have been shown to be effective in a selected fraction (20%) of non-small cell lung cancer patients. Somatic mutations in several genes (i.e.: EGFR and KRAS) can predict patient's response to targeted therapies. Those mutations are commonly detected on histopathological samples (core-needle biopsy/ surgical resection). However, when tissue biopsies are not available, molecular testing has to be performed on cytological specimens. Issues raised by molecular testing on cytological specimen are discussed in this article.

Physiological ageing of the lung is associated with dilatation of alveoli, enlargement of airspaces, decrease in exchange surface area and loss of supporting tissue for peripheral airways ("senile emphysema"), changes resulting in decreased static elastic recoil of the lung and increased residual volume and functional residual capacity. Compliance of the chest wall diminishes, thereby increasing work of breathing when compared with younger subjects. Respiratory muscle strength also decreases with ageing, and is strongly correlated with nutritional status and cardiac index. Expiratory flow rates decrease with a characteristic alteration in the flow-volume curve suggesting small airway disease. The ventilation-perfusion ratio (V'A/Q') heterogeneity increases, with low V'A/Q' zones appearing as a result of premature closing of dependent airways. Carbon monoxide transfer decreases with age, reflecting mainly a loss of surface area. In spite of these changes, the respiratory system remains capable of maintaining adequate gas exchange at rest and during exertion during the entire lifespan, with only a slight decrease in arterial oxygen tension, and no significant change in arterial carbon dioxide tension. Ageing tends to diminish the reserve of the respiratory system in cases of acute disease. Decreased sensitivity of respiratory centres to hypoxia or hypercapnia results in a diminished ventilatory response in cases of heart failure, infection or aggravated airway obstruction. Furthermore, decreased perception bronchoconstriction and diminished physical activity may result in lesser awareness of the disease and delayed diagnosis.

The myofibroblast is an ultrastructurally and metabolically distinctive connective tissue cell identified as a key participant in tissue remodeling in human granulation tissue, organ fibrosis, and the fibroblastic host response to malignant neoplasms. In this study of myofibroblasts in human lung diffuse alveolar damage (DAD), we identified 36 autopsy cases in which DAD could be histologically documented. DAD is known to progress from initial injury through an exudative, proliferative, and terminal fibrotic phase. In the exudative phase (16 cases), myofibroblasts expressing alpha-smooth muscle actin (alpha-SMA) are found in the septa and less frequently in hyaline membranes. In the proliferative phase (18 cases), many myofibroblasts in septa, hyaline membranes, and intra-alveolar fibroplasia express alpha-SMA. The alpha-SMA phenotype should be used in additional studies of myofibroblast differentiation, replication, and apoptosis. A better understanding of the biology of this cell type should offer new therapy for patients with DAD.

Epidermal growth factor (EGF) is a potent mitogen for human mesothelial cells, and autophosphorylation of the EGF receptor (EGF-R) occurs in these cell types after exposure to asbestos, a carcinogen associated with the development of mesothelioma. Here, the intensity and distribution of EGF-R protein was documented by immunocytochemistry in a human mesothelial cell line (MET5A) exposed to various concentrations of crocidolite asbestos and man-made vitreous fibers (MMVF-10). Whereas cells in contact with or phagocytizing shorter asbestos fibers ( or =60 microm) showed intense staining for EGF-R. In contrast, human A549 lung carcinoma cells showed neither elongation nor increased accumulation of EGF-R protein in response to long fibers. Patterns of aggregation and increases in EGF-R protein in mesothelial cells phagocytizing long asbestos fibers were distinct from diffuse staining of phosphotyrosine residues observed in asbestos-exposed cultures. These studies indicate that aggregation of EGF-R by long fibers may initiate cell signaling cascades important in asbestos-induced mitogenesis and carcinogenesis.

In February 1987, a 42-year-old Caucasian man was referred to our department with symptoms of left recurrent nerve palsy and a 12-month history of lymphadenopathy involving both sides of the neck, the axillae and the anterior mediastinum. Previous neck node biopsies taken in September 1986 had shown evidence of lymphoid hyperplasia consistent with reactive lymphadenitis, and follicular and parafollicular hyperplasia was diagnosed. His past medical history included two episodes of transient transverse myelitis, in 1973 and 1980. He had suffered from nasal sinus polyposis with chronic sinusitis since infancy. Further biopsies of neck nodes were taken and showed pleomorphic malignant cells infiltrating the interfollicular areas as well as several Reed-Sternberg (RS) cells. The diagnosis of Hodgkin’s disease (HD), interfollicular type, was made and confirmed by external expert review (Fig. la). The RS cells were CD30+ (Fig. lb), CD15+, leukocyte common antigen (LCA)-, CD3-. In the perifollicular zone, small T lymphocytes formed rosette-like arrangements around the RS cells. The Ann Arbor clinical stage was IIA. The only blood abnormality was a monocytosis at 1.4 × 109/L (N

One case of undifferentiated carcinoma of the gallbladder was studied using an extensive immunohistochemical panel of antibodies. The biphasic differentiation of the tumor was highlighted by different immunoreactivity to antibodies against cytokeratins, vimentin, epithelial membrane antigen, and carcinoembryonic antigen of the adenocarcinomatous and mesenchymallike components, although the latter showed a faint positivity for CAM5.2 antibody, probably indicating an epithelial origin. Furthermore, the higher levels of expression of p53 protein and the faster growth rate in the pseudosarcomatous component suggest its more malignant phenotype. The relationship with "true" carcinosarcomas of the gallbladder and the histogenetic theories concerning these tumors are also discussed.

This study is based on the bronchial tumors biopsied and later examined between 1971 and 1986 at the Institute of Pathology, Lausanne. In each case the diagnosis based on the initial biopsy material is compared with the final surgical or autopsy diagnosis (Reference: Histological typing of lung tumours, second edition, WHO, 1981, 2). The series studied is constituted by 163 cases: 144 men (88.3%) and 19 women (11.7%). In 136 cases (83.4%), the biopsy diagnoses are identical to the diagnoses based upon surgical or autopsy material; in 27 cases (16.6%) these diagnoses differ. The positive predictive value of bronchial biopsy appears to be excellent (100%) for small cell and epidermoid carcinoma (CA). It is satisfactory for adenocarcinoma (85.7%) but insufficient for large cell CA (42.3%) and the tumors grouped under "others" (50%). The diagnosis of large cell CA, in situ CA, papillary tumor, undifferentiated CA, or carcinomatous lymphangitis should be considered with caution and in some cases it is advisable to repeat the biopsy. The discrepancies between the initial and final diagnoses can, in all cases, be attributed either to the biopsy specimen being too small and therefore nonrepresentative or, less frequently, to crushing and necrosis of the tissues.

SUMMARY Practical, unbiased stereological methods are described to estimate lung volume and external surface area, and total volume and surface area of relatively large and anisotropic structures (bronchi and arteries) inside the lung. The volume of each of five lung strata was estimated first by fluid displacement and then by computed tomography (CT) using Cavalieri's method; the reliability of CT was assessed through a calibration procedure, and image thresholding criteria for an accurate volume estimation using CT were established. The parallel, perfectly registered CT section images were also used to estimate the external surface area of each stratum by the spatial grid method. Unbiased estimation of internal surface areas in lung is a long-standing problem: since the structures are large and essentially void, large sections are needed; to facilitate identification, thin sections have to be used for light microscopy, and since such structures are anisotropic, the sections should be vertical. A practical stereological design is demonstrated here on an infant lung, which fulfils all these requirements. This study illustrates the potential of using unbiased stereology to characterize infant pulmonary hypoplasia.