1. Histochemistry of the lung in pulmonary lymphangioleiomyomatosis During the past year we have published a number of papers on various aspects of the ultrastructure and histochemistry of the lesions associated with lymphangioleiomyomatosis (LAM) a multisystem disorder that effects women almost exclusively and is characterized by: 1) proliferation of abnormal smooth muscle cells (LAM cells) in the lung and axial lymphatics of the thorax and abdomen, and 2) formation of pulmonary parenchymal cystic lesions. Two types of LAM cells are recognizable: 1) small, spindle-shaped cells that have a high rate of proliferation, a low rate of apoptosis, and 2) large, more highly differentiated epithelioid LAM cells, which are reactive for HMB-45 antibody (a biomarker for LAM), contain an abundance of receptors for estrogen and progesterone, and have low rates of proliferation. Immunostaining with HMB-45 antibody, which recognizes gp100, a melanosomal glycoprotein, is the most specific biomarker for the diagnosis of lymphangioleiomyomatosis (LAM). It became of interest to determine whether other melanosomal components are present in LAM cells, since these cells do not contain fully developed melanosomes. Tyrosinase, tyrosinase-related protein 1, gp100, MART-1 and Microphthalmia-Transcription Factor (expression of which results in activation of the transcription of melanogenic genes) were identified in LAM tissue by Immunohistochemical and immunoblotting studies. The presence of tyrosinase activity in LAM tissue was confirmed by biochemical measurements and by a newly developed modification of the DOPA-silver stain (DOPA reaction), which revealed staining in stage I and stage II melanosomes. Thus, this study demonstrates the presence of various melanogenic proteins in LAM cells, and presents evidence suggesting that impaired glycosylation and/or increased degradation can prevent completion of melanogenesis in LAM cells. 2. Significance of histologic patterns of chronic interstitial pneumonia Nonspecific interstitial pneumonia (NSIP) has been proposed as a histologic subtype of idiopathic interstitial pneumonia with lung biopsy findings that are inconsistent with those of other idiopathic interstitial pneumonias. NSIP has a broad spectrum of histologic findings and a variable prognosis. We classified lung biopsies from 101 patients with idiopathic interstitial lung disease as having histologic patterns of desquamative interstitial pneumonia (DIP), usual interstitial pneumonia (UIP), or cellular or fibrosing NSIP. Due to histologic, clinical and survival similarities, the cases of idiopathic NSIP with lung biopsies showing fibrosing as well as fibrosing and cellular patterns were combined into a single group of NSIP, fibrosing pattern. Of the 101 patients, 16 (9females, 7 males) had idiopathic DIP, 56 (17 females, 39 males) had idiopathic UIP, 22 (7 females, 15 males) had idiopathic NSIP, fibrosing pattern and 7 (2 females, 5 males) had idiopathic NSIP, cellular pattern. The patients had mean ages of 42, 51, 50, and 39 years, respectively. Patients with idiopathic NSIP, cellular pattern had a better 5 and 10-year survival than those with idiopathic NSIP, fibrosing pattern (100% vs 90% and 100% vs 35%, respectively, p=0.027). Survival of patients with idiopathic UIP was worse than that of patients with idiopathic NSIP, fibrosing pattern (p=0.014). The difference, however, was more evident at 5 years (43% vs 90%) than at 10 years (15% vs 35%). The 5- and 10-year survival of patients with idiopathic NSIP, cellular pattern and DIP was 100%, which was significantly better than that of patients with idiopathic UP (P<0.0001). Based on these data NIP should be separated into cellular and fibrosing patterns, since these histologic patterns are associated with different clinical characteristics and prognoses.
