A case of ROS1-rearranged lung adenocarcinoma with osteoblastic bone metastasis.

A 53-year-old woman was referred to our hospital for detailed examination of abnormal chest shadows recognized on CT imaging. Transbronchial lung biopsy of a right S6 nodular shadow led to a diagnosis of lung adenocarcinoma. FDG-PET-CT showed FDG accumulation in the Th11 and L2 vertebral bodies and osteoblastic bone lesions. Since osteoblastic bone metastasis in lung cancer is extremely rare, CT-guided bone biopsy was performed. The tumor was diagnosed as ROS1-rearranged lung adenocarcinoma, for which crizotinib was administered, which led to improvement of both the primary and metastatic lesions. We report here a rare case of ROS1-rearranged lung adenocarcinoma with osteoblastic bone metastasis of lung cancer.

Altered lung surfactant system in a Rab38-deficient rat model of Hermansky-Pudlak syndrome.

Several Long-Evans rat substrains carrying the phenotype of oculocutaneous albinism and bleeding diathesis are a rat model of Hermansky-Pudlak syndrome (HPS). The mutation responsible for the phenotype (Ruby) was identified as a point mutation in the initiation codon of Rab38 small GTPase that regulates intracellular vesicle transport. As patients with HPS often develop life-limiting interstitial pneumonia accompanied by abnormal morphology of alveolar type II cells, we investigated lung surfactant system in Long-Evans Cinnamon rats, one strain of the Ruby rats. The lungs showed conspicuous morphology of type II cells containing markedly enlarged lamellar bodies. Surfactant phosphatidylcholine and surfactant protein B were increased in lung tissues and lamellar bodies but not in alveolar lumen. Expression levels of mRNA for surfactant proteins A, B, C, and D were not altered. Isolated type II cells showed aberrant secretory pattern of newly synthesized [(3)H]phosphatidylcholine, i.e., decreased basal secretion and remarkably amplified agonist-induced secretion. [(3)H]phosphatidylcholine synthesis and uptake by type II cells were not altered. Thus Rab38-deficient type II cells appear to carry abnormality in lung surfactant secretion but not in synthesis or uptake. These results suggest that aberrant lung surfactant secretion may be involved in the pathogenesis of interstitial pneumonia in HPS.

A mutation in Rab38 small GTPase causes abnormal lung surfactant homeostasis and aberrant alveolar structure in mice.

The chocolate mutation, which is associated with oculocutaneous albinism in mice, has been attributed to a G146T transversion in the conserved GTP/GDP-interacting domain of Rab38, a small GTPase that regulates intracellular vesicular trafficking. Rab38 displays a unique tissue-specific expression pattern with highest levels present in the lung. The purpose of this study was to characterize the effects of Rab38-G146T on lung phenotype and to investigate the molecular basis of the mutant gene product (Rab38(cht) protein). Chocolate lungs exhibited a uniform enlargement of the distal airspaces with mild alveolar destruction as well as a slight increase in lung compliance. Alveolar type II cells were engorged with lamellar bodies of increased size and number. Hydrophobic surfactant constituents (ie, phosphatidylcholine and surfactant protein B) were increased in lung tissues but decreased in alveolar spaces, consistent with a malfunction in lamellar body secretion and the subsequent cellular accumulation of these organelles. In contrast to wild-type Rab38, native Rab38(cht) proteins were found to be hydrophilic and not bound to intracellular membranes. Unexpectedly, recombinant Rab38(cht) proteins retained GTP-binding activity but failed to undergo prenyl modification that is required for membrane-binding activity. These results suggest that the genetic abnormality of Rab38 affects multiple lysosome-related organelles, resulting in lung disease in addition to oculocutaneous albinism.

[Case of broncholithiasis lithoptysis occurring spontaneously after repeated pneumonia].

An abnormal chest shadow was pointed out in a 56-year-old woman in a health check in 2001. She had pulmonary tuberculosis at age 11. Because of repeated fever for the previous 2 years, she visited our hospital in 2003 and right upper lobe pneumonia was detected with a calcified nodule that completely obstructed the right upper lobe bronchus on CT. After admission, she spontaneously expectorated a stone. The composition of the stone was 57% calcium phosphate and 43% calcium carbonate. Radiological findings and the composition of the stone suggested that this broncholith was calcified bronchial mucus rather than a calcified lymph node that might have perforated into the airway. Bronchiectasis of the right B3 broncus was observed on CT scan after lithoptysis. Although the bronchiectasis was unchanged 2 years later, she had no symptoms, such as fever or cough.