The in vivo function of murine granulocyte-macrophage colony-stimulating factor (GM-CSF) was investigated in mice, carrying a null allele of the GM-CSF gene, that were generated by gene targeting techniques in embryonic stem cells. Although steady-state hematopoiesis was unimpaired in homozygous mutant animals, all animals developed the progressive accumulation of surfactant lipids and proteins in the alveolar space, the defining characteristic of the idiopathic human disorder pulmonary alveolar proteinosis. Extensive lymphoid hyperplasia associated with lung airways and blood vessels was also found, yet no infectious agents could be detected. These results demonstrate that GM-CSF is not an essential growth factor for basal hematopoiesis and reveal an unexpected, critical role for GM-CSF in pulmonary homeostasis.

Three-hundred-sixty cases of solitary fibrous tumor of the pleura from the literature are analyzed, and eight new cases are described. Of patients reported on prior to 1972, 72% had symptoms due to the tumor at the time of diagnosis, but only 54% of patients reported on since then were symptomatic. This probably reflects earlier diagnosis as a result of increased use of chest radiographs in asymptomatic populations. Cough, chest pain, dyspnea, and/or pulmonary osteoarthropathy are each found in at least one-third of patients who have symptoms. Approximately 80% of solitary fibrous tumors of the pleura originate in the visceral and 20% in the parietal pleura. In the literature and in this experience these tumors are on the whole circumscribed. The range in size from 1-36 cm with a mean of 6 cm. Many are pedunculated on pleural-based pedicles that contain hypertrophic arteries and veins. Histologic examination of the tumor usually discloses cellular areas alternating with hyalinized and/or necrotic areas. Spindle-shaped cells typically have minimal nuclear pleomorphism and rare or absent mitoses. Numerous thin-walled vessels constitute an additional feature of large tumors. Electron microscopical examination reveals features of both fibroblasts and mesothelial cells. Solitary fibrous tumors behave in a benign fashion in 88% of cases after surgical resection. In 12% of the cases the tumor is responsible for the patient's death because of its extensive intrathoracic growth, by virtue of either late diagnosis or unresectable recurrence. No single histologic feature allows a definite prognosis. The best indicator of a good prognosis is the presence of a pedicle supporting the tumor. Also favorable in circumscription of the tumor without invasion of lung, mediastinum, or chest wall. Nuclear pleomorphism and a high mitotic rate are seen in larger tumors but do not necessarily indicate a poor prognosis if the tumor is circumscribed. Solitary fibrous tumors of the pleura are not associated with asbestos.

The sex cord tumor with annular tubules (SCTAT) is a distinctive ovarian neoplasm the predominant component of which has morphologic features intermediate between those of the granulosa cell tumor and those of the Sertoli cell tumor; focal differentiation into either granulosa cell or Sertoli cell tumor may occur. Of the 74 cases that form the basis of this investigation 27 were associated with the Peutz-Jeghers syndrome; these tumors were all benign and were typically multifocal, bilateral, very small or even microscopical in size and calcified. Twelve of the 27 patients had symptoms suggestive of hyperestrinism attributable to the SCT4T; menstrual irregularity had occurred in eleven cases and postmenopausal bleeding in one. Four of the 27 patients had "adenoma malignum" of the cervix and two of them died of it. The 47 tumors from patients without evidence of the Peutz-Jeghers syndrome were unilateral and usually large. Twenty-five of them were accompanied by symptoms suggestive of hyperestrinism, such as menstrual irregularity, postmenopausal bleeding or sexual precocity; seven were malignant and four of these were fatal.