A c t a Path. Jap. 22(4): 833--841, 1972

PULMONARY LESIONS IN SYSTEMIC NECROTIZING ANGIITIS

Teruo WATANABE, Hideki KISHIKAWA and Kenzo TANAKA

Depscrtment of Pathology, Faculty of Medicine, Kyuahu University, Fukuoka

Pulmonary lesions in systemic necrotizing angiitis are not fully understood. An attempt was made to analyze the anatomical features of the pulmonary lesions in some of the disorders included in this category, especially in periarteritis nodosa, allergic granulomatous angiitis and Wegener’s granulomatosis.

We refered to the reports by ZEEK (1952) ALARCON-SEGOVIA and BROWN (1964), PARONETTO (1969) and others for the classification of our autopsy materials which included 26 cases of periarteritis nodosa, 3 cases of allergic granulomatous angiitis and 8 cases of Wegener’s granulomatosis.

Periarteritis nodosa: It has been said that the lesions in periarteritis nodosa are uncommon in pulmonary vessels (ZEEK, 1952). ROSE and SPENCER (1957) class& ed periarteritis nodosa into 2 groups based on the presence or absence of lung involvement and claimed that both showed peculiar clinico-pathologic character- istics. However, there seems to be no doubt that many kinds of necrotizing angiitides are included in their material. The same comment should be made on SWEENEY and BAGGENSTOSS’ report (1949).

In our 26 cases, the organs most frequently involved were the gastro-intestinal tract (88%), pancreas (84%), liver (83%), heart (77%), kidney (73%), periadrenal tissue (73%), and mesentery (73%). Among the reproductive organs, the most frequently involved was the testis (92%).

The lung was involved in 12 cases (46%); the pulmonary artery in 6 cases (19%) and the bronchial artery in 8 cases (31%). Pulmonary arteritides were com- monin the medium- and small-sized muscular artery (Fig. 1). When there was extensive necrosis of the arterial wall, the lesions were found as nodular consolida- tion, where the surrounding pulmonary parenchyma showed a variety of severe alveolitis - cellular thickening of alveolar walls with exudation of some leuko- cytes, fibrin, and accumulation of macrophages (Fig. 2). Infarction was rather a rare occurrence in the lung.

Typical hdings of periarteritis nodosa was, however, infrequent in pulmonary vessels, for many of the lesions showed rather mild arteritides of chronic inflamma-

The spleen was involved in 45%.

834 SYSTEM0 NEOROTIZING ANQDTIS

tion chiefly affecting the medial and adventitial layers. Around these lesions, one could iind frequently an alveolar inflammation with occasional formation of Masson bodies. Necrotizing alveolitis apart from the diseased muscular artery was noted in 2 cases.

In one case with lung involvement, diffuse perivascular fibrosis in the sub- pleural area was an outstanding feature, which might be called “postungiitic pulmonary Jibrosis”. Vascular walls were heavily replaced by the fibrous tissue, which narrowed and occluded their lumina, and the disruption of elastic fibers was prominent. Neighboring alveoli were obliterated by proliferation of the connective tissue and were fused to each other, the original structure remaining only along the edge of the lesions (Fig. 3).

The problem pertaining to the relationship of hypertension to periarteritis nodosa has not been settled. Among our cases, there was a case with pulmonary periarteritis which appeared to be probably related to the pre-existing pulmonary hypertension due to mitral stenosis. In this case, numerous nodular lesions were disseminated along the pulmonary arteries, in which a marked proliferation of granulation tissue was observed not only in the arterial walls but also extending outward through the adventitia (Fig. 4). Microscopic arteritides were found in other organs such as in the heart, liver, adrenals and testis, but the lung was un- doubtedly the most severely affected.

Although the pulmonary arteries have been mentioned as being free from lesions, our observations suggested that they could be affected not so rarely in periarteritis nodosa of the classical variety, for many of the cases with lung involvement belonged to the macroscopic periarteritis nodosa frequently presenting various ages of lesions simultaneously in each individual. Brief analysis of the cases is summarized in Tables 1 and 2.

A l k ~ g k granu1oma;tOus angiitis: CHURG and STRAUSS (1951) reported a clinical syndrome of asthma, fever and eosinophilia, which pathologically showed inflam- matory lesions and granulomatous foci in many organs. The vascular lesions are said to be similar to periarteritis nodosa, but small arteries and veins are more frequently involved. These lesions are usually widespread, and have a predilection in the pulmonary vessels and splenic foEcular arterioles. The inflammation is made up mainly of eosinophils, but the outstanding feature is the formation of granulomatous foci both within vessel walls and in connective tissue throughout the body. Eosinophilic infiltrate resembling that of Loffler’s syndrome is another frequently associated finding.

In our materials three cases were classified into allergic granulomatous angiitis. Pulmonary lesions in this disorder seemed to be summarized in the description of the following case.

T. WATANABE, E. KISBIIUWA AND K. TANAKA 835

Table 1. Some Characteristics of Periarteritis Nodosa with (Macroscopic P N ) or without (Microscopic PN) Arterial

Involvement of Macroscopic Sizes

No. of wses Histological stage :

Acute inflammation Granulomatous Chronic scar-forming

Glomerulonephritis Arteritis

Onion-skin lesion Follicular arteriolitis Trabecular arteritis

Pulmonary arteritis Necrotizing alveolitis Bronchial arteritis

Kidney :

Spleen* :

Lung :

Macroscopic PN

13

1 6 7

4 12

4 1 4

4 2 4

Microscopic PN

13

6 5 3

8 7

4 2 1

1 0 4

* Histology of the spleen was examined in 11 cases of macroscopic, and 9 cases of microscopic PN, respectively.

Table 2. Distribution of Rend, Splenic and Pulmonary Lesiona in Periarteritis Nodosa Divided into Three Stuges According to

Histological Changes in Arteries

I Histological Stages

Acute 1 aammatory I Granulomatous Chronic scar-forming

No. of cases Kidney :

Glomerulonephritis Arteritis

Onion-skin lesion Follicular arteriolitis Trabecular a h i t i s

Pulmonary arteritis Necrotizing alveolitis Bronchial a rb i t i s

Spleen* :

Lung :

1 1 1

0 0 2

10

4 7

1 1 1

1 0 4

10

3 9

6 1 3

4 2 2

* Histology of the spleen wm examined in 6 cmes of acute inflammatory, 0 cases of granulomatous, and 9 cases of chronic scar-forming stages, respectively.

A 46-year-old housewife was admitted to the Nagoya Red Cross Hospital in April, 1966, because of attacks of asthma which had been occurring for 5 years. There was an allergic tendency in her family and one of her brothers had died of

836 SYSTEMIO NEOROTIZINQ ANGIITIS

Fig. 1 A muscular branch of pulmonry artery showing chronic round cell infiltration H. and

Fig. 2 A variety of alveolar Mammation around the necrotic adrial lesion in a case

containing some eosinophilic leukocytes. E. x 210.

of periadritis nodosa. H. and E. x 68.

From a case of periarteritis nodosa.

bronchial asthma. After admission, petechiae developed over the extremities, and genital bleeding associated with transient loss of her consciousness occurred. Examination of the peripheral blood revealed an eosinophilia of 41% in 28,200 of the total white cell count. Cortisone and ACTH treatment appeared to be suc- cessful. In June, chest roentgenogram revealed abnormal shadows on the left side, which spread bilaterally in July. Following the reduction of steroid, generalized edema and severe dyspnea developed. A marked eosinophilia of 7 1% in 66,400 of the total white cell count was observed. The patient’s condition deteriolated rapidly and she died on August 13, 1966.

Autopsy disclosed necrotizing angiitis in many organs including the lung, heart, kidney, spleen, pancreas, liver, gall bladder, gastro-intestinal tract, mesen- tery, urinary bladder, ovaries and periadrenal tissue. The main blood vessels involved were small arteries, arterioles and those usually taken to be capillaries. Necrosis of vascular walls accompanied with a cellular exudate consisting largely of eosinophilic leukocytes was an outstanding feature in many organs, and granulomatous arteriolitis with giant cells was occasionally another feature of the lesions, especially in the spleen, lung, kidney and gall bladder. A variety of

T. WATANABE, E. KISHLKAWA AND K. TANAKA 837

Fig. 3 “Postangiitic pulmonary fibrosis” from a case of periarteritis nodosa. Elastica

Fig. 4 Changes of periarteritis nodosa in muscular branches of pulmonary artery from a van Gieson. x 20.

case of long-standing chronic mitral stenosis. H. and E. x 35.

interstitial inflammation in which eosinophilic leukocytes were the principal cel- lular element was observed in the lung, kidney, heart and gall bladder.

The lung was voluminous, firm and rubbery in consistency. Approximately 200 ml of serous fluid was present in each pleural cavity. The alveolar walls were diffusely thickened by a cellular exudate consisting mainly of eosinophilic leukocy- tes, and alveoli contained frequently serum, red cells and fibrin. Another occa- sional finding was an accumulation of both eosinophilic leukocytes and desquamated epithelial cells in alveolar lumina. Masson bodies were frequently found (Fig. 6) . There was a prominent perivascular inflammatory process in which eosinophilic leukocytes were the principal cellular element. Occasionally, actual necrosis or granulomatous inflammation was observed in the arteries (Fig. 6). Small granulo- mata with some giant cells were scattered, but most of them were confirmed with elastica staining to be located in the small muscular arteries. The bronchi were filled with mucus and desquamated epithelial cells, and the walls were heavily infiltrated with eosinophilic leukocytes. Thickening and hyalinization of the basement membrane were prominent.

Wegener’s granulomatosis : The condition was originally described by KLINGER

838 SYSTENIO NECROTIZINU ANUIITIS

Fig, Ei Eosinophilic infiltrate largely con6ned to the interstitial tissues of the lung in a cam of allergic granulomatous angiitis. Formation of Masson bodies in the lower left corner. H. and E. x 90.

Fig, 6 Necrotizing arteritis of the lung in a case of allergic granulomatous angiitis. Adjacent pulmonary tissue is infiltrated with abundant eosinophilic leukocytes. H. and E. x 90.

(1931), but WEGENER (1936, 1939) reported further cases and first characterized this disorder clinico-pathologically. The pathology of this disorder has been reviewed by GODMAN and CHURG (1954), and WALTON (1958). NOMURA and IKEDA (1969) carried out a survey of Japanese cases.

We have studied 8 cases of Wegener’s granulomatosis characterized by destructive necrotizing granulomatous inflammation of the respiratory tract, generalized angiitis and peculiar glomerular lesions, with frequent dissemination of granulomata in various organs.

Lesions of the respiratory tract were the most characteristic in this disorder. Spread of the inflammatory process led to extensive ulceration and cartilaginous or osseous destruction in the nose, paranasal sinuses and oral cavity, where it behaved not infrequently like neoplasms. In our cases, lesions of the upper respiratory tract were present in all cases. In 7 of these, antemortem or postmortem specimens of nasal or paranasal tissue were obtained for histological examination, all of which showed severe granulomatous inflammation of the mucosa and submucosa. Involvement of small vessels, both arteries and veins, by the inflammatory process

T. WATANABE, H. KISHIRAWB. AND K. TANAEA 839

Fig. 7

Fig. 8

Granulomatous pulmonary lesion with giant cell reaction in a case of Wegener’s

Granulomatous mteritis in a case of Wegener’s granulomatosis. The arterial wall x

granulomatosis. H. and E. x 65.

is replaced by edematous granulation tissue containing giant cells. H. and E. 200.

was observed in 5 cases, including 2 cases of fairly mild endoarteritis alone. Nodular areas of consolidation,

grayish-white in color, measuring up to 8 cm in diameter, occasionally showing central cavitation, were present in the lung parenchyma. Intrapulmonary bron- chial ulceration was common. Granulomatous lesions were chiefly composed of lymphocytes, plasma cells, neutrophilic leukocytes, fibroblasts and epithelioid cells, in which giant cells of both Langhans and foreign body types were mixed in varying proportions. Eosinophilic leukocytes were usually scanty. Granulomata of this disorder showed little tendency of the zonal arrangement typically observed in those of tuberculosis ((Fig. 7).

In addition t o the destructive and granulomatous pulmonary lesions, charac- teristic changes were found in the blood-vessels. The vascular lesions were necrotiz- ing or granulomatous, sometimes with many giant cells (Fig. S), and most of them seemed to be contined to the segment adjacent to the granulomatous inflammation. In the affected part of the lung, these necrotizing or granulomatous panangiitis were found in 5 of 7 cases, and the vascular lesions were of only the type of endoarteritis in the other 2 cases. At the border of the granulomatous masses, no

The lungs were abnormal in all but one case.

840 SYSTIEMIa NEOROTIZINQ ANOIITIS

cases except one exhibited sevire panangiitis and there were no conspicuous arteritides in the unaffected part of the lungs apart from the granulomata.

On the other hand, vascular lesions were minimal in the blood-vessels next to the small granulomata or discrete foci of fresh granulomatous lesions where exudative reaction was prominent, and obvious arteritis was uncommon. Many of these foci were found in peribronchial and peripheral areas of the respiratory tract as an initial stage of the mature granulomata.

The pulmonary parenchyma around the granulomata showed a variety of pneumonia with exudation of leukocytes, fibrin, and collection of macrophages, not infrequently progressing into alveolar fibrosis.

In addition to the changes in the respiratory tract, widespread granulomata and vascular lesions were present in other organs. The granulomata were most frequently perivascular and occasionally observed with close relation to the vascu- lar lesions. On the other hand, the vascular lesions were frequently isolated and independent upon the presence of the granulomata in many organs.

From these observations, it seems reasonable to consider that Wegener’s granulomatosis begins as a progressive granulomatous inflammation of unknown etiology at one or more levels in the respiratory tract. Involvement of the blood- vessels and progression in the widespread lesions occur most probably depending upon the development of a stage of generalized hypersensitivity.

Summry : Pathology of the lung in periarteritis nodosa, allergic granulomatous angiitis and Wegener’s granulomatosis was described. Although the etiology of these three disorders are yet unknown, the patho-morphology and distribution of their lesions seem to have distinctive characteristics, and findings in the lung are considered to be quite useful for conclusive diagnosis and classification of these disorders.

Aclcnuwkdgemmt: This study wae made possible by the generosity of the departments of patho- logy of the medical schools and hospitals in Japm in permitting free access to clinical and histologiocll materials from their caw.

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