Expanding the spectrum of monoclonal light chain deposition disease in muscle

Abstract

Introduction: The diagnosis of amyloid myopathy is delayed when monoclonal gammopathies are not detected on initial testing and muscle biopsies are nondiagnostic, and the EMG and symptoms can mimic an inflammatory myopathy.

Methods: Case report of a patient presenting with severe progressive muscle weakness of unclear etiology despite an extensive workup including two nondiagnostic muscle biopsies.

Results: Directed by MRI, a third biopsy revealed amyloid angiopathy and noncongophilic kappa light chain deposition in scattered subsarcolemmal rings and perimysial regions. A serum free light chain (FLC) assay revealed a kappa monoclonal gammopathy, which was not detected by multiple immunofixations.

Conclusions: The spectrum of immunoglobulin deposition in muscle is similar to other organs. It comprises a continuum that includes parenchymal amyloid deposition, amyloid angiopathy, and noncongophilic Light Chain Deposition Disease (LCDD). We recommend including the FLC assay in the routine investigation for monoclonal gammopathies. This case also highlights the value of MRI-guided muscle biopsy.

FIGURE 1

Thigh MRI scans: (A) T2-weighted axial and (C) coronal images show diffuse hyperintensity within several muscles, with sparing of others, such as the rectus femorii (arrows). (B) T1-weighted axial images show negligible streaky fatty replacement within some muscles. Note that the subcutaneous tissues appear normal, without the pronounced T2-hyperintensity described in published cases of amyloid myopathy. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

FIGURE 2

Muscle biopsy pathology. Panels A–D show frozen sections of the same fibers, stained with: (A) hematoxylin and eosin (H&E), (B) NADH, (C) PAS, and (D) ATPase at pH9.4. Note that the entire fibers are dark on NADH, while the rings stain positively for PAS and exclude the ATPase stain. E,F: Higher magnification pictures of two abnormal fibers on paraffin sections, illustrating three apparent zones: (1) An outer pale ring with perpendicularly oriented sarcomeres (seen best in panel F), and enlarged nuclei with prominent nucleoli tending to cluster at the inner edge of the ring, (2) a thinner circumferentially oriented band, and (3) relatively normal appearing sarcoplasm in the middle of the fiber (cracking is artifactual). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

FIGURE 3

Congo Red (CR) staining to visualize amyloid. Panels A–C show apple green birefringence in the walls of a blood vessel in the top half of the frame as a polarizing filter is rotated. Note that the abnormal ringed fiber in the lower half of the frame (arrow) is completely devoid of CR staining. (D,E)Mid-polarized images of the other intramuscular vessel with congophilia, characteristic of the ubiquitous amyloid angiopathy seen throughout the specimens from this MRI-guided biopsy. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

FIGURE 4

Immunohistochemistry (IHC) for kappa light chains. (A) Prominent kappa light chain staining of blood vessels corresponding to congophilic amyloid. (B) Perimysial staining around a normal-appearing fiber (black arrow), and staining within the abnormal ring encircling an abnormal fiber (red arrow). (C,D) Magnified images of hematoxylin and eosin (H&E) and kappa light chain IHC staining of the abnormal fiber in panel B. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]