Sarcoidosis is a systemic granulomatous disease with systemic vascular involvement, that is, granulomatous angiitis and microangiopathy. To determine if there is vascular involvement in cutaneous sarcoidosis, we examined 42 skin specimens taken from 32 patients with cutaneous lesions of sarcoidosis. Cutaneous sarcoidosis was prevalent in older females with high serum angiotensin-converting enzyme (ACE) levels. Most skin lesions appeared during the following-up of sarcoidosis. Granulomatous angiitis was present in 12 specimens of sarcoid skin lesions (30.8%). Eight of the 12 specimens showed venous involvement in the dermis. There was no correlation between the incidence of granulomatous angiitis and the gross pattern of cutaneous sarcoidosis. Immunohistochemically, thrombomodulin was negative in the vascular endothelium close to the granuloma or a periphlebitis lesion. Electron microscopy revealed endothelial swelling, luminal narrowing, and basal lamina layering of the basement membrane in the capillaries and venules in the dermis. These findings demonstrated that granulomatous angiitis and microangiopathy coexist in cutaneous sarcoidosis.

To evaluate the occurrence of granulomatous angiitis and microangiopathy in the lung with sarcoidosis, transbronchial lung biopsy specimens were examined from 174 cases with sarcoidosis. Granulomatous angiitis was seen in 72 cases, which corresponded to 53% of the cases with granulomata. Granulomatous angiitis showed venous involvement (65%), both venous and arterial involvement (24%) or arterial involvement only (11%). There was no significant difference in occurrence of granulomatous angiitis between upper and lower lobes. The cases with granulomatous angiitis in the lung had a higher frequency of ophthalmic symptoms and elevated serum angiotensin converting enzyme level. Basal lamina layering in the microvasculature was more often observed in the bronchial mucosa than in the alveolar walls and is not exclusively related to granulomata. Endothelial proliferation and basal lamina alterations in granulomatous angiitis may be closely associated with granulomas. The present study revealed coexistence of granulomatous angiitis and microangiopathy in the lung with sarcoidosis and suggests that both may participate in the development of pulmonary sarcoidosis.

Seventy-two cases of idiopathic pulmonary fibrosis (IPF) were examined from 2856 consecutive autopsy cases at the Japanese Red Cross Medical Center in Tokyo from 1973-1996. Primary lung cancer had arisen in 31 of 72 cases of IPF (43%), significantly higher than the incidence in cases without IPF (8.1%) and in the cases with non-IPF chronic lung diseases (11.9%). Hyperplastic epithelial foci in the honeycomb lesions of IPF cases were significantly more prominent in the lower than in the upper lobe, in cases with or without lung cancer, and they were more prominent in the lower lobe of IPF with than in those without cancer. The length of hyperplastic epithelial foci in the lower lobe of IPF cases was longer than that in interstitial pneumonia-associated with collagen vascular diseases. There was a higher PCNA labeling index of hyperplastic epithelial foci in IPF cases than in cases of interstitial pneumonia-associated with collagen vascular diseases. The PCNA labeling index was almost the same between smokers and nonsmokers with IPF. Overexpression of p53 was observed in hyperplastic epithelial foci in honeycomb lesion of IPF. DNA ploidy analysis of hyperplastic epithelial foci in the paraffin sections of 12 IPF cases revealed aneuploidy patterns in eight cases. These results strongly suggest that accelerated cell proliferation occurs in the honeycomb lesion of IPF, and that regenerative epithelia becomes susceptible to carcinogenic agents in addition to the smoking effect.

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Objective To elucidate the cut off levels of serum KL-6 indicating patients with interstitial pneumonitis (IP) and patients with active IP associated with connective tissue diseases (CTDs). Methods CTD patients whose serum KL-6 level was measured were included. IP was diagnosed on the basis of medical records including XP/CT findings, and active IP was assumed in case that intervention for IP was newly added. The cut off levels were determined by receiver operating characteristic (ROC) curve analysis. Results Among 240 (174 females) patients, 67 (42) had IP and 15 (9) had active IP. The ages of patients with and without IP, and with active IP and with inactive IP were 70.3±9.5 and 62.8±15.3, and 72.8±8.1 and 69.6±9.8, respectively. IP was significantly more prevalent in males and the elderly. The KL-6 levels were 990±90 and 301±12 U/mL in patients with and without IP, and 1,905±236 and 726±54 U/mL in those with active IP and with inactive IP, respectively. ROC curve analysis showed a cut off level of 509 U/mL for indicating IP, and that of 1,051-1,060 U/mL for indicating active IP. Conclusion A serum KL-6 level of higher than 500 U/mL is a marker of the presence of IP, and a level of higher than 1,000 U/mL is a marker of the presence of active IP associated with CTDs.