The respiratory tract in amyloidosis and the plasma cell dyscrasias

The Respiratory Tract in Amyloidosis the Plasma Cell Dyscrasias By

Barry

Ii.

Gross,

Benjamin

Felson,

and

Frederick

A.

and

Birnberg

AMYLOIDOSIS From the Division of Chest Radiology, University of Michigan Hospital, Ann Arbor; the University of Cincinnati College of Medicine: and the Department of Radiology, Kaiser Hospital, Sacramento. Calif Barry H. Gross: Associate Professor of Radiology, Director, Division of Chest Radiology University of Michigan Hospital, Ann Arbor, Benjamin Felson: Professor Emeritus of Radiology, University of Cincinnati College of Medicine; Frederick A. Birnberg: formerly Assistant Professor of Radiology, University of Michigan; present address: Department of Radiology, Kaiser Hospital. Sacramento, Calif: Address reprint requests to Barry H. Gross. MD. Department of Radiology, Box 13, University of Michigan Medical Center, Ann Arbor, MI 48109-0010. 0 1986 by Grune & Stratton, Inc. 0037-198X/86/2102-0004$05.00/0

T

HE RESPIRATORY SYSTEM is involved in approximately half of the patients with amyloidosis, but radiographically demonstrable involvement is considerably less common.‘-3 The disease may be confined to the respiratory tract or represent a manifestation of systemic amyloidosis. The localized form is the more common.4 Respiratory amyloidosis occurs in three characteristic forms: tracheobronchial, nodular, and diffuse parenchymal.5 Tracheobronchial

Amyloidosis

The tracheobronchial form is probably the most common and is often symptomatic.6m8

Fig 1. Tracheobronchial gram shows lobulated nodules the right side of the trachea ICourtesy of St Louis Veterans

Seminars

m Roentgenology,

amyloidosis. protruding and right Adminstration

Vol XXI,

The bronchointo the lumen main bronchus. Hospital.)

No 2 (April),

1986:

of

pp 1 13-

127

113

114

Fig shows

GROSS,

2. Tracheobronchial lobulated masses

(M)

amyloidosis. narrowing

the

FELSON,

AND

AP tomogram airway.

Fig 3. Tracheobronchial amyloidosis. Oblique bronchogram reveals diffuse tracheal narrowing abruptly (arrowheads) and extending downward carina. (Courtesy of St Elizabeth Hospital, St NJ.)

Fig 4. Amyloidoma of the left (arrow), with obstruction and lobar Dr HR. Senturia, St Louis.)

upper collapse.

BIRNBERG

lobe bronchus (Courtesy

of

view of beginning to the Elizabeth,

Hemoptysis is the most frequent complaint; stridor, cough, dyspnea, hoarseness, and wheezing are other important symptoms.’ Radiographically, amyloid lesions of the upper respiratory tract, trachea, and large bronchi may be demonstrated on plain films, tomography, or bronchography. They generally appear as multiple nodules protruding from the wall of the trachea (Figs 1 and 2). Occasionally, the disease may present with diffuse rigid narrowing of a long segment of the trachea (Fig 3). An amyloid mass may cause bronchial obstruction with collapse, airtrapping, or pneumonia (Fig 4). A rare condition, tracheobronchopathia osteoplastica, may be related to amyloidosis.’ It is

RESPIRATORY

TRACT

IN AMYLOIDOSIS

Fig 5. Tracheobronchopathia CT of same patient. The trachea

osteoplastica. is deformed

115

(A) Tomogram. Partly by the calcified nodules.

characterized by nodular or diffuse ossification of the tracheobronchial mucosa. Radiographically, there are small irregular calcific densities in the wall of the trachea and proximal bronchi (Figs 5 and 6). Pathologically, amyloid deposits have been occasionally demonstrated in the lesions, suggesting that tracheobronchopathia

calcified

nodular

lesions

protrude

osteoplastica may represent tory amyloidosis.239 Nodular

into

the trachea.

end-stage

(B)

respira-

Amyloidosis

From the literature, it is uncertain whether the nodular or diffuse parenchymal form of the disease is more frequent.3.5-7 Our own experience

116

GROSS,

FELSON,

AND

BIRNBERG

Fig 6. Tracheobronchopathia osteoplastica. (A and B) AP and lateral tomograms show diffuse calcification or ossification of the larger bronchi. (Courtesy of Dr Kenneth Kattan, Cincinnati.)

clearly favors the former, but it should be noted that a normal chest film is frequently found in the presence of histologically diffuse pulmonary amyloidosis. Nodular amyloidosis generally occurs in patients over age 60; there is no sex predilection.” It seldom causes symptoms until the involvement becomes extensive, in which case cough and dyspnea may occur. It is seldom as-

sociated with involvement of other organs. Bence-Jones or M proteins are rarely found. The prognosis is good, and patients seldom die of the disease. Amyloid nodules may be solitary or, much more commonly, multiple. The solitary nodule is often located peripherally in the lung (Fig 7), for unexplained reasons. When multiple, the nodules are not uniform in size, number, or shape in the

RESPIRATORY

TRACT

IN AMYLOIDOSIS

117

amyloidosis, metastases must, of course, receive prime consideration. The peculiar shapes and indolent nature of these noduIes militate against metastasis or lymphoma. Other multinodular entities in the lung, such as granulomatous diseases, benign metastasizing leiomyomatosis, rheumatoid lung, sarcoidosis, and mucoid impaction, must also be considered.16 The sharp lobulated contour of the nodules, the multiple shapes, the presence of calcium, and slow growth have enabled us to suggest the diagnosis of amyloidosis on a number of occasions. Dizuuse Parenchymal

Fig 7. (Courtesy

Solitary smyloidoma (A) of right upper of Dr E. Nicholas Sargent, Los Angeles.)

lobe.

individual patient (Figs 8 and 9). They may vary from less than 0.5 cm to as large as 15 cm in diameter.‘,3X” The nodules are often sharply defined, sometimes remarkably so. Although many are round, a number are of oval or other shapes, and some are distinctly lobulated in contour.‘* In about half the autopsied cases, some of the nodules are calcified or ossified (Fig 10).6S8S13.‘4 This is often apparent on the radiograph, particularly with tomography or CT. The calcification may be central or distributed throughout the nodule as an irregular or cloud-like shadow (Fig 1 l), resembling that seen in hamartochondroma. Indeed, the mucopolysaccharides in amyloid resemble those in cartilage.’ Rarely, cavitation is present, the walls of which may be thin and smooth (Fig 12).” The nodules usually grow slowly, over a period of years rather than months. We have seen a patient with no change at all in three years, and another with minimal growth over a time span of ten years. The nodules do not regress. The nodular and diffuse forms of amyloidosis seldom if ever coexist. In the differential diagnosis of this form of

Amyloidosis

The diffuse parenchymal form of amyloidosis also usually presents after age 60. It may be asymptomatic, often encountered as an incidental finding at autopsy.” However, when radiographic changes are evident, cough, dyspnea, and other pulmonary symptoms are commonly present. If a patient with multiple myeloma develops respiratory insufficiency, diffuse pulmonary amyloidosis should be suspected. even in the absence of radiographic findings. Bence-Jones or M proteins may be present in diffuse pulmonary amyloidosis, nearly always when it is associatedwith multiple myeloma. The alveolar-arterial oxygen tension gradient may be abnormal, and there may be severe impairment of pulmonary function.13 Cor pulmonale may supervene.‘* Histologically, the appearance is totally different from the nodular form. The involvement is almost exclusively interstitial, with each alveolar septum infiltrated with amyloid. particularly around the capillaries. This is associated with a prominent inflammatory infiltrate.” The process often spreadsdiffusely throughout the lungs, but it may be regional in distribution. Honeycombing occasionally occurs late in the course of the disease,as a result of the interstitial process.’ The radiographic findings of diffuse pulmonary amyloidosis are variab1e.‘-‘~5~“-‘3~‘s In many cases, the chest film is entirely normal. The earliest abnormality is usually a diffuse pattern of small irregular shadows, sometimesconfined to the lung bases but more often widespread throughout the lungs (Fig 13). Kerley B lines may be associated.The small irregular shadows

the

Fig 8. sharp

Multiple definition

parenchymal nodules of most of the nodules.

in amyloidosis. (Courtesy

(Al Right lung. (8) Left of Dr Arch W. Templeton,

lung. Note the variety Kansas City, Kan.)

of sizes

and

shapes

and

Fig 9. Innumerable amyloid nodules of various sizes and shapes. Some are partly calcified. Lateral view of chest. (Courtesy of Frederick J. Sante, Dallas.)

RESPIRATORY

TRACT

IN AMYLOIDOSIS

ed and ossified Fig 10. Calcifi film amyloid nodules. (P L) The chest coalescent and shows a combined of irregular caloverlapping pattern Radiograph of cific nodules. (B) lung in the autopsy specimen oi f sliced discrete same patient show! E mostly that summation lesions, indicating of the pattern in accounts for much Hospital, (A). (Courtesy of Roper Charleston. SC.)

GROSS,

Fig 11. show which

may occasionally become confluent, creating a flocculent appearance (Figs 13 and 14). Sometimes honeycombing is evident (Fig 15).* Large nodules seldom if ever coexist. The rare miliary pattern will be illustrated later (Fig 19). The radiographic appearance of diffuse pulmonary amyloidosis is not at all specific, and many conditions may simulate it. Among them are idiopathic interstitial fibrosis, pneumoconio-

Fig 12. AP tomogram of the right lower demonstrating several amyloid lung nodules, of which is cavitated (Cl. (Courtesy of Robert Heitzman. Syracuse. NY.1

lobe, one Dr E.

Multiple prominent

FELSON,

AND

emyloid nodules, calcification.

BIRNBERG

most

of

sis (especially asbestosis), rheumatoid lung, histiocytosis X, and scleroderma.16 The diagnosis of diffuse pulmonary asbestosis can only be made by lung biopsy, but in the presence of systemic amyloidosis or multiple myeloma, a presumptive diagnosis of pulmonary amyloidosis can be made on the basis of symptomatic, physiologic, or radiographic evidence of diffuse pulmonary involvement consistent with the disease.

RESPIRATORY

TRACT

121

IN AMYLOIDOSIS

Fig 13. Diiuse parenchymal amyloidosis with extensive small irregular opacities, confluent in the upper lobes. Despite widespread disease, the patient was asymptomatic. (Courtesy of Dr E. Nicholas Sargent, Los Angeles.)

Cardiac impairment may result from amyloidosis alone or from pulmonary disease.” The former results in diffuse cardiac dilatation; the latter, of course, causes predominantly rightsided enlargement. Diffuse pulmonary amyloidosis is, as a rule, very slowly progressive. Spontaneous improvement has been reported in one case, but this was

Fig 14.

Diffuse

parenchymal

amyloidosis

not well documented.‘7 The prognosis is poor and the patients usually die of respiratory insuth ciency or of heart disease.“’

Other Manifestations

of Thoracic ,dm~~loidosis

Pathologically, amyloidosis affects thoracic lymph nodes in almost 20% of the cases’; radiographically, lymph node enlargement is less fre-

with

coalescent

small

irregular

opacities.

GROSS,

Diffuse parenchymal Fig 15. combing. Close-up view of right Sjiigren (sic4 syndrome.

The hilar and mediastinal nodes are quent. 14~18-20 usually enlarged bilaterally (Fig 16), but sometimes only one group of nodes is affected. Lymph node calcification is uncommon; it may be diffuse or of the eggshell type (Figs 17 through 20) .l’ Other intrathoracic manifestations are rare. Pleural effusion in the absence of congestive heart failure has been recorded.’ We have seen

Fig 16. Lymphadenopathy in amyloidosis. and right paratracheal node enlargement. Patrick Perkins. Oakland, Calif.)

Bilateral (Courtesy

hilar of Or

FELSON,

amyloidosis lung. The

AND

BIRNBERG

with honeypatient also had

one patient with a localized amyloidoma in the pleura (Fig 21), and another in whom the thoracic wall was involved with numerous calcified amyloid masses (Fig 22). The diagnosis of amyloidosis, once suggested, is generally readily established by laboratory or pathologic methods. However, the condition is seldom considered, and thus often missed. Since the chest radiograph often provides the most

Fig 17. radiograph tion (Cl.

Calcified nodes demonstrates

in amyloidosis. diffuse lymph

Lateral chest node calcifica-

Fig 18. .adiogl raph

Fig 19. Calcified parenchymal and nodal amyloidosis. There is bilateral paratracheel node calcification of the eggshell type (arrowheads). Diffuse parenchymal involvement has resulted in calcified miliary nodules as well. (Courtesy of Dr E.V. Bouffard Ill, Olney, Ill.1

Same reveals

patient as many diffusely

in

Fig 17. AP nodes. calcified

abdominal

124

GROSS,

FELSON,

Fig 20. Eggshell calcific nodes (arrow). (Courtesy Henschke, Boston.)

important clue, the radiologist can play an important role in the diagnostic process merely by mentioning that the possibility of amyloidosis exists. The indolent odd-shaped, often partly calcified nodules, the widespread or diffuse pat-

21. Focal pleural of this illustration

amyloid mass not recalled.)

(M)

on

CT

scan.

BIRNBERG

:ation in left of Dr Claudia

Inilar H.

terns, or the adenopathy, sometimes calcific, should bring amyloidosis to mind. The diagnosis may also be facilitated by percutaneous aspiration of an amyloid lung nodule or by transbronchial biopsy.** PLASMA

Fig (Source

AND

CELL DYSCRASIAS

Radiographic abnormalities of the respiratory tract in patients with one of the plasma cell dyscrasias frequently are caused by the associated amyloidosis rather than the underlying dyscrasia itself. This is particularly true in patients with multiple myeloma, in 10% of whom amyloidosis develops. Amyloidosis may also be present in Waldenstrom’s macroglobulinemia, in heavy chain diseaseof Franklin, and in Sjiigren syndrome (Fig 15).23m27 Waldenstrom’s macroglobulinemia may also affect the respiratory tract in the absence of amyloidosis. We have seenthree such cases(Figs 23 through 25).26 Excluding congestive heart failure and secondary infection, the incidence of thoracic involvement in this diseaseis about 25%, according to Winterbauer et al.*’ Intrathoracic lesions were found in 15 of the 20 cases they collected; six had pleural effusion, six had diffuse

was

the

Amyloidosis Fig 22. the cause of the

of thoracic cardiac failure.

Fig 23. WaldenstrLim’s lung bases. No evidence

Fig 24. D. Hunter,

WaldenstrGm’s Denver.1

soft

macroglobulinemia of amyloidosis

macroglobulinemia

tissues.

was

Note

of the found

without

the

widespread

calcifications.

lung, confirmed histologically. at biopsy or autospy. The

amyloidosis.

The

similarity

Noncalcified

diffuse

cardiac

amyloidosis

The small irregular lesions are confined patient developed leukemia terminally.

to Fig 23 is striking.

ICourtesy

of Dr Robert

to

GROSS,

126

Fig fested

small irregular opacities, six had solitary or multiple lung nodules, and three had hilar lymph node enlargement. The pleural effusion was usually unilateral and the pulmonary lesions were often asymmetrical. Most of the patients with Waldenstrom’s disease are over age 60. To our knowledge, thoracic radiographic manifestations have not been reported in the other plasma cell dyscrasias. We have encountered one patient with biopsy-proved heavy chain disease

Fig 26. Heavy chain disease of Franklin. Bilateral pleural effusions, confluent basilar parenchymal disease, and hilar and mediastinal lymph node enlargement are present. Lung and lymph node biopsies revealed plasma cell infiltration consistent with heavy chain disease, with no evidence of amyloidosis.

25. Waldenstrijm’s as diffuse small irregular

FELSON,

AND

macroglobulinemia opacities.

BIRNBERG

mani-

in whom the lungs, pleura, and lymph nodes were involved (Fig 26). Broader experience with these rare conditions is required before their radiographic aspects can be elucidated. ACKNOWLEDGMENT We wish to express our gratitude to those who supplied cases for this presentation. We regret that in several instances we do not recall the physician who supplied the material.

RESPIRATORY

TRACT

IN AMYLOIDOSIS

127

REFERENCES 1. Wilson SR, Sanders DE, Delarue NC: Intrathoracic manifestations of amyloid disease. Radiology 1976;120:283289 2. Felson B: Chest Roentgenology. Philadelphia: Saunders, 1973, pp 320, 341,486 3. Fraser RG, Pare JAP: Diagnosis of Diseases of the Chest. Philadelphia: Saunders, 1978, pp 1110-I 116 4. Schtiller H, Bolin H, Linder E, et al: Tumor-forming amyloidosis of the lower respiratory system. Dis Chest 1962:42:58-67 5. Prowse CB: Amyloidosis of the lower respiratory tract. Thorax I958;13:308-320 6. Rubinow A, Celli BR. Cohen AS, et al: Localized amyloidosis of the lower respiratory tract. Am Rev Resp Dis 1978~1 18:603-61 I 7. Cohen AS: Amyloidosis. N Engl J Med 1967;277:522530,574-583,628638 8. Weiss L: Isolated multiple nodular pulmonary amyloidosis. Am .I Clin Pafhol 1960;33:318-329 9. Alroy GG, Lichtig C, Kaftori JK: Tracheobronchopathia osteoplastica: End stage of primary lung amyloidosis? Chest 1972;6 11465-468 10. Lee S-C, Johnson HA: Multiple nodular pulmonary amyloidosis. A case report and comparison with diffuse alveolar septal pulmonary amyloidosis. Thorax 1975;30:178185 I 1. Wang CC, Robbins manifestations. Radiology 12. Himmelfarb logic spectrum 1977;72:327-332 Crit

of

LL: Amyloid disease: 1956;66:489-501

Its roentgen

E, Wells S, Rabinowitz JG: The radiocardiopulmonary amyloidosis. Chest

13. Pear BL: Radiographic studies Rev Radio1 Sci 1972;3:425-452

of amyloidosis.

CRC

14. Desai RA, Mahajan VK, Benjamin S, et al: Pulmonary amyloidoma and hilar adenopathy. Chest 1979;76: 170173

15. Gordonson JS, Sargent EN, Jacobson G, et al: Roentgenographic manifestations of pulmonary amyloidosis J Gun Assoc Radio1 1972;23:269-272 16. Reeder MM, Felson B: Gamuts in Radiology: Comprehensive Lists of Roentgen Differential Diagnosis. Cincinnati: Audiovisual Radiology of Cincinnati, 1975, F-1 2 to F-14 17. Hof DC, Rasp FL: Spontaneous regression of diffuse tracheobronchial amyloidosis. Chest 1979;76:237~ 339 18. Schmidt HW, McDonald JR, Clagett OT: Amyloid tumors of the lower part of the respiratory tract and mediastinum. Ann Oral 1953;62:880-893 19. Brown J: Case of the season. Srmin Roenrgenol I977;12:93-94 20. Osnoss KL, Harrell DD: Isolated mediastinal mass in primary amyloidosis. Chest 1980;78:786--788 21. Gross BH: Radiographic manifestations of lymph node involvement in amyloidosis. Radiofogy I98 1; 138: 1 1 14 22. Bierny J: Multinodular primary amyloidosis of the lung: Diagnosis by needle biopsy. AJR 1978; 13 1: 1082 - IO83 23. Renner RR, Smith JR: Plasma cell dyscrasias (except myeloma). Semin Roentgen01 1974;9:209-2 18 24. Glenner GG, lgnaczak TF, Page DL: The inherited systemic amyloidoses and localized amyloid deposits. In: Stanbury JB. Wyngaarden JB, Fredrickson DS (eds): The Metabolic Basis of Inherited Disease. New York: McGrawHill, 1978, pp 1308-I 339 25. Glenner GG: Medical Progress: Amyloid deposits and amyloidosis---the fl fibrilloses. N Engl J Me-d !980;302: 1283-I 292, 1333-I 343 26. Kobayashi H, Ii K, Hizawa K. et al: Two cases of pulmonary Waldenstrom’s macroglobulinemia. C’hesr 19X5: 88:297-299 27. Winterbauer RH, Riggins RCK, Griesman FA. et al: Pleuropulmonary manifestations of Waldenstriim’s macroglobulinemia. Chest 1974;66:368-375