Solon R. Cole

Respiratory failure due to pulmonary leukostasis following chemotherapy of acute nonlymphocytic leukemia

Four patients with acute nonlymphocytic leukemia and leukocyte counts of more than 200,000/mm3 developed respiratory distress due to pulmonary leukostasis within 10–48 hours after initiation of chemotherapy. Clinically, the patients manifested fever, dyspnea, tachypnea, diffuse pulmonary rales, pleural effusions, and severe hypoxemia. Chest roentgenograms displayed diffuse pulmonary infiltrates, vascular engorgement, cardiomegaly, and pleural effusions. Three patients died from progressive respiratory failure despite ventilatory support. Pulmonary histology revealed thrombi composed of leukemic blast cells which obstructed and distended the lumens of pulmonary arterioles, capillaries, and venules. Electron microscopy studies of lung tissue showed pulmonary alveolar endothelium and basement membrane damage and interstitial edema. The pathophysiologic basis of pulmonary leukostasis and potential treatment modalities are discussed.

Pulmonary disease with chlorambucil therapy.

A 73‐year‐old female developed pulmonary disease during treatment with chlorambucil for polycythemia vera. Cough and dyspnea were prominent symptoms. A chest roentgenogram revealed interstitial fibrosis. The diffusing capacity was markedly reduced. Pathologic findings included alveolar lining cell dysplasia, interstitial round cell infiltrates and interstitial fibrosis. Resolution of the pulmonary symptoms and partial clearing of the fibrosis on chest roentgenogram followed discontinuation of the chlorambucil and institution of steroid treatment. Chlorambucil may cause pulmonary fibrosis similar to busulfan and cyclophosphamide and this may be a potential complication of all alkylating agents.

Interstitial Pulmonary Emphysema in Children and Adults: Roentgenographic Features

Chest films of 12 patients ranging in age from 3 to 55 years with autopsy-verified interstitial pulmonary emphysema (IPE) were reviewed. All had received positive pressure breathing. Opacification of the lungs due to edema, hemorrhage, or pneumonia often made IPE visualization possible. Diagnostic radiographic features include direct visualization of interstitial air, and the appearance of subpleural air cysts formed by continued dissection of interstitial air into the subpleural connective tissues. Recognition of IPE is of importance because it may directly impair pulmonary ventilation and perfusion and may be followed by development of pneumomediastinum, pneumothorax, and secondary infection.

Angioimmunoblastic lymphadenopathy: pleural-pulmonary disease.

A 48‐year‐old female with angioimmunoblastic lymphadenopathy is described. Her disease was complicated by pleuritic chest pain, an exudative pleural effusion and pulmonary infiltrates attributable to underlying pleural‐pul‐monary angioimmunoblastic lymphadenopathy.

Alu profiling of primary and metastatic nonsmall cell lung cancer

The metastatic potential of nonsmall cell carcinoma of lung (NSCLC), is currently recognized post factum, when lymph nodes or distant organs are already involved. Our ability to determine which tumors have acquired metastatic potential could help direct therapy to be more aggressive or less aggressive based upon this information. Evaluation of microsatellite instability via detection of LOH at specific loci may be useful in identifying specific markers and/or genes associated with this process. We examined Alu insertional elements as a potential marker of genetic changes associated with the metastatic potential of NSCLC. We analyzed archived, paraffin embedded tissue from 20 proven cases of NSCLC. DNA was extracted from 10 micron paraffin sections and amplified using an Alu PCR protocol. This technique does not examine specific loci but rather results in a banding profile of cellular genomic DNA. Informative allelic banding patterns, noted as differences between primary and metastatic lesions from the same patient, were observed in five of six cases (83%) with intrapulmonary metastases and in only nine of 14 (64%) cases with extrapulmonary metastases. Multiple genomic changes were detected in metastatic tumor cells as compared to normal lung tissue or primary lung tumor tissue. It appears that Alu profiling may be useful in the detection of metastatic vs primary lesions, and this technique may offer a method for identifying novel genes responsible for tumor progression and metastases.