Radiology/Pathology Correlation

Unknown 7

The patient is a 63-year-old woman with no previous medical history, who presents with worsening dyspnea on exertion and shortness of breath.

Radiology

Figure 1: Chest Radiograph

Comment on the features of the frontal chest radiograph with respect to opacities, lung volumes, effusions, and lymphadenopathy.

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Figure 2: HRCT

Look at the HRCT images in figures 2 and 3.

Describe the predominant locations of the nodules. Answer

 

 

Figure 3: HRCT

What is the differential diagnosis? Answer


Pathology

A transbronchial biopsy from this patient shows deposits of extracellular pink material in nodules surrounded by fibrosis. A multinucleated giant cell lies next to one nodule. The pink fibrous material at the lower left represents deposits on collagenous tissue.

nodule1nodule2giantcellfibrous

 

Figure 4. Biopsy

Find two nodular deposits. Click on the structure in the image to get verification.

Find the multinucleated giant cell.

Outline the pink deposits on collagenous tissue at the lower left.

What is the likely nature of these deposits? What special stain would help with the diagnosis? Answer

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The deposits stained red with the PAS stain. Note that the walls of 2 blood vessels are replaced by the red-staining deposit and also that deposits surround individual smooth muscle fibers in a clump of muscle, now atrophic. The epithelial basement membrane toward the top is stained, but that toward the bottom is not. Note the normal PAS-positive goblet cells in the epithelium.

vessel1vessel2musclemembrane

Figure 5. PAS Stain

Find 2 vessels with deposit in the walls.

Find a clump of atrophic smooth muscle fibers with deposit around individual fibers.

Find the PAS-positive portion of the epithelial basement membrane.

What other tests would help to define the deposit? Answer

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Discussion:

Light chain deposition disease (LCDD) and amyloidosis of light chain origin (AL amyloidosis) are both caused by deposits of immunoglobulin light chains in tissues and organs. (Remember that amyloidosis is caused by several different proteins that can form extracellular deposits of fibrillar material, only one of which is AL amyloid.) Although LCDD and AL amyloidosis both have deposits that are homogeneous, pink, and extracellular by H&E staining, the deposits of LCDD lack the reaction with Congo red and a fibrillar ultrastructure. Instead, the deposits of LCDD are PAS positive and have a granular ultrastructure. Whereas the light chains of AL are usually lambda type, those of LCDD are usually kappa type [1]. Occasional cases have nonamyloid deposits of immunoglobulin heavy chains alone or a combination of heavy and light chains, and rare cases of combined LCDD and amyloid have been reported [2]. Serum amyloid P component (SAP), present in all amyloids, is absent from LCDD, meaning that radioactive SAP cannot be used to identify the location or regression of deposits. Environmental factors as well as somatic mutations of the light chains may determine the fibrillar or granular nature of the deposits [3].

Both LCDD and AL amyloidosis are associated with multiple myeloma, and infrequently with B-cell lymphoproliferative disorders, monoclonal gammopathies of unknown significance, or even lack of a detectable paraprotein [1]. Whereas renal disease is the usual manifestation of LCDD, heart and liver are also frequently involved. The lung is rarely involved, but lung disease may be the presenting feature of a plasma cell dyscrasia [4], as in our patient.

Several radiographic patterns of amyloid deposition in the thorax have been described, based on anatomic location: tracheobronchial, nodular/multinodular parenchymal, and diffuse nodular interstitial parenchymal (some authors use the term alveolar septal for this type, but histologically, alveolar septal refers to deposits confined to the alveolar walls) [5-7]. Tracheobronchial LCDD has not been described, but the other two patterns have similar appearances in both LCDD and AL amyloidosis. In nodular parenchymal lesions, HRCT sometimes shows calcification that suggests benign disease. In diffuse nodular interstitial parenchymal disease, recognition on HRCT of the perilymphatic distribution of deposits in bronchovascular bundles, interlobular septa and pleura is important for developing the differential diagnosis [5-7].

Histologically, the deposits may be located in basement membranes of airways and alveolar walls, in vascular and airway smooth muscle, and diffusely throughout the interstitial tissues of the lung. They may form discrete nodules. The variation in intensity of pink staining can erroneously suggest a fibrosing disease although some degree of reactive fibrosis may be present (see figure 4). Multinucleated giant cells are often associated with the deposits as in amyloidosis, and the deposits may calcify or ossify [4].

Primary AL amyloidosis may regress after therapy with high dose melphalan and autologous stem cell transplant that cures the underlying plasma cell dyscrasia [8]. Although there are yet no reports of LCDD responding to this therapy, chemotherapy alone has produced remission of deposits in cardiac and renal disease [9,10].

Comments on the Radiographic Features of LCDD

Comments on the Pathologic Features of LCDD

Diagnosis: Light-chain deposition disease (LCDD), diffuse nodular interstitial parenchymal type. The patient was subsequently given the diagnosis of multiple myeloma, kappa type. She was treated with high-dose melphalan and autologous stem cell transplant. HRCT of the lung shows some regression of the densities 2 1/2 years later.

References

1. Buxbaum J, Gallo G. Nonamyloidotic monoclonal immunoglobulin deposition disease. Light-chain, heavy-chain, and light- and heavy-chain deposition diseases. Hematol Oncol Clin North Am 1999;13:1235-1248 Abstract

2. Stokes M, Jagirdar J, Burchstin O, Kornacki S, Kumar A, Gallo G. Nodular pulmonary immunoglobulin light chain deposits with coexistent amyloid and nonamyloid features in an HIV-infected patient. Mod Pathol 1997; 10:1059-1065. Abstract

3. Davis D, Gallo G, Vogen S, Dul J, Sciarretta K, Kumar A, Raffen R, Stevens F, Argon Y. Both the environment and somatic mutations govern the aggregation pathway of pathogenic immunoglobulin light chain. J Mol Biol 2001;313:1021-1034 Abstract

4. Kijner C, Yousem S. Systemic light chain deposition disease presenting as multiple pulmonary nodules. A case report and review of the literature. Am J Surg Pathol 1988;12:405-413. Abstract

5. Webb W, Müller N, Naidich D. High-resolution CT of the lung. Lippincott-Raven: Philadelphia. 2000.

6. Pickford H, Swensen S, Utz J. Thoracic cross-sectional imaging of amyloidosis. AJR 1997; 168:351-355. Abstract

7. Kim H, Im J, Song K, Lee K, Kim S, Kim J, Lee J, Lim T. Localized amyloidosis of the respiratory system: CT features. J Comput Assist Tomogr 1999; 23:627-631. Abstract

8. Sanchorawala V, Wright D, Seldin D, Dember L, Finn K, Falk R, Berk J, Quillen K, Skinner M. An overview of the use of high-dose melphalan with autologous stem cell transplantation for the treatment of AL amyloidosis. Bone Marrow Transplant 2001; 28:637-642 Abstract

9. Pozzi C, Locatelli F. Kidney and liver involvement in monoclonal light chain disorders. Semin Nephrol 2002; 22:319-330. Abstract

10. Nakamura M, Satoh M, Kowada S, Satoh H, Tashiro A, Sato F, Masuda T, Hiramori K. Reversible restrictive cardiomyopathy due to light-chain deposition disease. Mayo Clin Proc 2002; 77:193-196. Abstract

TOP----Rad/Path Home Page

Last modified 10/8/02

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

The chest radiograph shows diffuse increased interstitial opacities, roughly linear in appearance, but vaguely nodular also. Lung volumes are not diminished. No effusion or lymphadenopathy is present.

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HRCT images show numerous small nodules diffusely throughout the upper, mid, and lower lungs. The nodules are well-defined and are seen primarily along the costal and fissural pleural surfaces and bronchovascular bundles, as well as along irregularly thickened interlobular septa.

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Differential diagnosis: The distribution of the nodules is best characterized as perilymphatic. The differential diagnosis of perilymphatic nodules on HRCT includes sarcoidosis, primary lymphangitic spread of carcinoma, amyloidosis, silicosis, and lymphocytic interstitial pneumonitis and related lymphoproliferative diseases of the mucosa-associated lymphoid tissues of the lung.

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Nodular deposit

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Multinucleated giant cell

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Deposits on collagenous tissue

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These deposits were initially thought to be amyloid. The cellular fibrosis and giant cell should not be interpreted as a granulomatous reaction in which some of the collagen has become hyalinized (homogeneous and pink). A giant cell reaction often occurs in the presence of amyloid. A Congo red stain was done. It showed no orange staining and no green birefringence with polarized light. What other histochemical stain might help with the diagnosis? Answer

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Vessel with deposit in the wall

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Clump of atrophic smooth muscle with deposits

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PAS-positive basement membrane

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