Yasuo Matsui

CLINICOPATHOLOGICAL STUDY ON FATAL MYOCARDIAL SARCOIDOSIS

Presented here was an outline of fatal myocardial sarcoidosis in Japan based on 42 autopsy cases. The incidence, clinical features, pathological findings (particularly the distribution of sarcoid lesions in various organs, and gross as well as histological patterns have been reviewed. The ratio of fatal myocardial sarcoidosis to the total number of sarcoidosis deaths is higher than that of other countries and it appears characteristic of Japanese sarcoidosis that the disease occurs here predominantly after the fourth decade in females. Only 12% of myocardial sarcoidosis cases are diagnosed exactly. Conduction disturbances and dysrhythmias due to myocardial damage are its most common manifestations. The modes of presentation or cardiac death are sudden death, 16 cases (41%); congestive heart failure, 9 cases (23.1%); Adams-Stokes syndrome, except sudden death, 7 cases (17.9%); death due to dysrhythmia, 6 cases (15.4%); and 2 pacemaker deaths among the application of pacemakers, 7 cases. As for the ECG findings, A-V block and bundle-branch block was observed in most cases and ectopic beats were also frequently observed. The difficulty in exact diagnosis of myocardial sarcoidosis appears to be due to the frequency of lack of manifestation of systemic sarcoidosis as well as insidious cardiac involvement. The gross findings on myocardial lesions showed 3 patterns and each of the localized patterns corresponded to the histological extension. The conglomerate-band-like pattern corresponded to expansive invasion, the dendrite pattern to interstitial extension. The histological findings on the myocardial lesions were classified into four types: 1) exudative type, 2) granuloma type, 3) combined type of granuloma and fibrosis, 4) fibrotic type. Two extreme cases showed the exudative and fibrotic type, respectively, and were discussed.

Pathological studies on sarcoidosis autopsy. I. Epidemiological features of 320 cases in Japan

Three hundred and twenty autopsy cases of sarcoidosis during a 32 year period were collected from the Annuals of the Pathological Autopsy Cases in Japan, published yearly since 1958, and from a literature survey. A statistical analysis of these reviewed autopsy cases was carried out on the epidemiological features of the disease and on the causes of death.

Pulmonary vascular involvement in sarcoidosis : a report of 40 autopsy cases

We examined pulmonary vascular involvement in 40 autopsy cases of sarcoidosis. In these cases granulomatous involvement was observed at all levels from large elastic pulmonary arteries to venules, and venous involvement was more prominent than arterial involvement. The extent of granulomatous vascular involvement was related to that of parenchymal granuloma. No significant difference was found between upper and lower lobes in the incidence of granulomatous vascular involvement. The distribution of granulomata in the blood vessels was segmental and adventitial, and medial involvement was prominent in the larger vessels. Healed lesions of granulomatous vascular involvement also were observed at various levels in blood vessels. Prominent granulomatous involvement was found in the lymphatic capillaries and collecting lymphatic vessels in lungs with sarcoidosis. Serial sections of the lungs demonstrated interstitial granuloma directly connecting the lymphatic capillaries around small blood vessels. Granulomatous involvement in vasa vasorum and lymphatic capillaries is likely to be an important factor in the pathogenesis of granulomatous vascular involvement in lungs with sarcoidosis. The present study suggests that granulomatous vascular involvement and its sequelae may contribute to the development of pulmonary sarcoidosis.

Pathological studies on sarcoidosis autopsy. II. Early change, mode of progression and death pattern.

Three hundred and twenty autopsy cases of sarcoidosis in Japan were analyzed to determine the pathological changes in the early stage, the mode of progression in each organ and the changes in the final stage of the disease.

Pulmonary vascular involvement in sarcoidosis: granulomatous angiitis and microangiopathy in transbronchial lung biopsies.

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.

VASCULAR INVOLVEMENT IN CUTANEOUS SARCOIDOSIS

Sarcoldorls is a systemlc granulomatous disease with systemic vascular Involvement, that Is, granulomatous anglitis and mieroanglapathy. To detarmlne if there is vascular Invoivement In cutaneous sarcoidosls, we examined 42 skin specimens taken from 32 patients with cutaneous lesions of narcoidosls. Cutaneous sarcoidosis was prevalent In older females with high serum anglotensin‐converting enzyme (ACE) levels. Most skin lesions appeered during the following up of narcoldosis. Granulomatous anglitls was present in 12 specimens of sarcold skin lesions (30.8%). Eight of the 12 specimens showed venous Involvement In the dermis. There was no correlation between the Incldence of granulomatous anglitis and the gross pattern of cutaneous sarcoldosls. Immunohistochemically, thrombomodulln was negative in the vascular endothelium close to the granuloma or a peri‐phlebltis lesion. Electron mlcroscopy revealed endothelial swelling, Iumlnal narrowing, and basal Iamina Iayering of the basement membrane in the capillaries and venules in the dermis. These findings demonstreted that granulomatous anglitis and mictoanglopathy coexist in cutaneous sarcoldosis.

Detection of antibodies to Borrelia species among patients with confirmed sarcoidosis in a region where Lyme disease is nonendemic

Abstract• Background: Lyme disease is a multisystemic disorder caused by the spirochete Borrelia burgdorferi, while sarcoidosis is a multisystemic granulomatous disease of unknown etiology. The purpose of this study was to evaluate the relationship between Lyme disease and sarcoidosis. • Methods: We examined the seroprevalence of antibody to Borellia species in patients with sarcoidosis. We performed the enzyme-linked immunosorbent assay, using three Japanese Borrelia species in addition to B. burgdorferi, and dotblot analysis using purified Borrelia-specific proteins in 38 patients with histopathologically confirmed sarcoidosis and 80 healthy controls. • Results: Two patients (5.3%) were positive for antibodies to Borrelia species according to one or both assays, and one (1.2%) healthy control was positive. In both patients it was suspected that Borrelia infection had developed prior to the development of sarcoidosis. • Conclusion: Borrelia species were thought not to be responsible for the development of sarcoidosis in a nonendemic region in Japan.Since clinical manifestations of Lyme disease share certain similarities with those seen in sarcoidosis, ophthalmologists should be aware of the need to differentiate between the two diseases and the need for prompt treatment in each case.

AN AUTOPSY CASE OF SARCOIDOSIS FOLLOWED UP FOR 27 YEARS, WITH SPECIAL REFERENCE TO PULMONARY FIBROSIS

An autopsy case of sarcoidosis followed up for 27 years in a 48‐year‐old woman with pulmonary fibrosis is presented. Chest roentgenography demonstrated an interstitial pneumonia‐like pattern with gradual contraction of the upper lobes. Focal and extending fibrosis and hyalinizatlon were observed in various organs including the lung, lymph nodes, heart and liver. Most of the fibrosis was thought to be derived from solitary or confluent granuloma, showing hyalinized nodular, stellate or band‐like fibrosis. There was also another type of fibrosis, not derived from granuloma, manifested as fibrosing alveolitis in the lung, and diffuse fibrosis extending throughout the other organs. In the lymph nodes, chromogenic bodies (Hamazaki‐Wesenberg bodies) were seen. The process of fibrosis and the significance of chromogenic bodies in cases of chronic sarcoidosis are discussed. ACTA PATHOL JPN 38: 909 ∼ 920, 1988.