Amphicrine differentiation in bronchioloalveolar cell carcinoma.

We report for the first time a classical bronchioloalveolar cell carcinoma with both exocrine and endocrine differentiation (amphicrine) in the same cell. At electron microscopy the tumor cells showed a mixed type II alveolar cell/Clara cell and mucous differentiation. In addition, there were many dense-core neurosecretory granules at the base of the majority of the cells. Immunocytochemically the tumor showed positivity for surfactant and a panel of neuroendocrine antibodies, including NSE, PGP9.5, synaptophysin, and chromogranin A. The presence of neuroendocrine differentiation was not hinted at by routine histology and did not indicate a more aggressive behavior in this case since the patient is well 3 years after the resection.

Distribution of the cytoskeletal protein beta-tubulin in normal lung, cryptogenic fibrosing alveolitis and lung tumours.

Tubulin is the major protein of microtubules. The immunocytochemical distribution of tubulin within the human respiratory tract has not been investigated in detail and no analysis of diseased lung or lung tumours has been undertaken. We therefore studied the distribution of beta-tubulin in formalin-fixed normal lung (n = 6), cryptogenic fibrosing alveolitis (n = 10) and lung tumours (n = 66), using a monoclonal antibody to beta-tubulin. In normal lung positive immunostaining was observed in all ciliated epithelium from the trachea down to bronchiolar level; blood vessel endothelium, vascular smooth muscle and nerve bundles were also strongly positive; pneumocytes, cartilage and airway smooth muscle gave weak staining. A similar distribution of beta-tubulin was seen in cryptogenic fibrosing alveolitis, but with strong tubulin immunostaining of fibroblasts in the interstitium and of the cytoplasm of ciliated respiratory epithelial cells. In lung tumours, six of 17 (35%) adenocarcinomas, one of two adenosquamous and one of 17 (5%) squamous cell carcinomas gave strong immunostaining. All six large cell carcinomas gave strong immunostaining for tubulin. In neuroendocrine tumours, two of seven (28%) carcinoids, two of seven (28%) atypical carcinoids and seven of 10 (70%) small cell carcinomas were strongly positive for tubulin. beta-Tubulin is widely distributed in the normal and diseased respiratory tract and is found in many lung tumours, particularly in large cell and small cell carcinomas which are highly aggressive in behaviour.

Pleural mesothelioma of connective tissue type, localized fibrous tumour of the pleura, and reactive submesothelial hyperplasia. An immunohistochemical comparison.

Ten diffuse pleural mesotheliomas of connective tissue type have been compared with 14 examples of pleural granulation tissue and 7 localized fibrous tumours of the pleura, using immunohistochemistry to identify cytokeratins of low and high molecular weight and vimentin. Low molecular weight cytokeratin and vimentin were both detected in 8 of the 10 mesotheliomas and in 12 of the 14 reactive lesions. High molecular weight cytokeratin was rarely detected in either lesion. The seven localized fibrous tumours of the pleura were all positive for vimentin and negative for both cytokeratins. These findings support an origin of connective tissue type mesotheliomas from multipotential submesothelial spindle cells and of localized fibrous tumours of the pleura from either conventional fibroblasts or resting submesothelial spindle cells. Antibodies to cytokeratin help distinguish these two neoplasms but provide no assistance in the more difficult diagnostic problem of distinguishing mesotheliomas of connective tissue type from pleural reactions characterized by abundant granulation tissue.

Giant cell carcinoma of the lung--immunohistochemical and ultrastructural evidence of dedifferentiation.

Ten examples of giant cell carcinoma of the lung were examined by immunohistochemistry for expression of keratin and vimentin intermediate filaments and for epithelial membrane antigen (EMA). Six cases were also examined electron microscopically. Keratin expression and, to a lesser extent, EMA immunoreactivity were reduced in comparison with better differentiated forms of lung carcinoma. Vimentin expression was increased, often taking the form of strong paranuclear staining. This may correspond to dense paranuclear aggregates of intermediate filaments seen ultrastructurally. Desmosomes were absent or sparse in most tumours. We propose that giant cell carcinoma arises by a process of dedifferentiation. The resulting loss of epithelial features gives rise to neoplastic cells which have features in common with some forms of sarcoma.