)
)
)
FINAL DIAGNOSIS
Amyloid myopathy and cardiac amyloidosis due to primary AL amyloidosis
Our initial diagnosis was myofibrillar myopathy (MFM), but after the negative genetic testing we broadened our differential diagnosis to include hypogammaglobulinemia and hypertrophic cardiomyopathy. Our final diagnosis was amyloid myopathy and cardiac amyloidosis due to primary AL amyloidosis. Serum and urine electrophoresis showed a band in the beta-gamma region. Immunofixation showed monoclonal gammopathy to be of the Bence Jones lambda type. The concentration of the Bence Jones proteins was 1.25 g/day. Through further analyses of the muscle sample, we found Congo red-positive interstitial tissues. Immunohistochemistry for lambda-type light chain was positive on the interstitium (Figure 1C), which appeared apple-green under the polarized light microscope (Figure 2A). Electron microscopy revealed fine fibrillar structures in the perimysium (Figure 2B). This finding was further confirmed by subcutaneous abdominal fat and rectum biopsy. Furthermore, cardiac muscle biopsy confirmed the diagnosis of cardiac amyloidosis. Bone marrow biopsy showed no evidence of myeloma. A final diagnosis of amyloid myopathy and cardiac amyloidosis due to primary AL amyloidosis was made.
DISCUSSION
Amyloid myopathy is an underdiagnosed disease entity due to the rarity of the disease and its non-specific diagnostic features (1). Among 1,596 patients with primary systemic amyloidosis, only 12 patients were complicated with amyloid myopathy (2). In addition, 16 cases were diagnosed with amyloid myopathy from 3,937 muscle biopsy specimens at the Cleveland Clinic, (5). Among the 79 reported patients of amyloid myopathy (1), clinical features include proximal weakness (89%), macroglossia/muscle pseudohypertrophy (34%), dysphagia (22%), cardiac amyloidosis (15%), and diarrhea (11%). Of the 79 patients, 23 patients were treated with various therapies, including plasmapheresis, corticosteroids, cyclophosphamide, and melphalan. Among them, 8 patients responded well and, in some successful cases, even resolution of congestive heart failure was accomplished. Considering the possible responsiveness to therapies, it is important to establish a timely diagnosis. Regarding therapies, the peripheral blood stem cell transplantation was delayed in our patient due to the complication of cardiac amyloidosis. Although the patient began treatment with melphalan plus dexamethasone, he died at age 70 (five years after the onset) due to congestive heart failure secondary to cardiac amyloidosis.
Radiologically, establishing a diagnosis of amyloid myopathy is difficult without disease-specific findings. In the present patient, amyloidoma-like localized lesions were observed bilaterally in the adductor magnus muscles. Furthermore, there was reticulation of the subcutaneous fat, which was previously indicated as being a notable radiological feature for distinguishing amyloid myopathy from other neuromuscular disorders (4). Localized amyloidosis presenting as a tumorous lesion or amyloidoma was described as a key radiological feature in the case of a patient with amyloid myopathy (3).
Pathologically, amyloidosis is often initially misdiagnosed. Among the 79 patients of amyloid myopathy, the initial diagnosis was incorrect in 19 cases (24%) since the presence of amyloid was missed/unrecognized upon initial biopsy (1). In some cases, necrotic and regenerating fibers (22%) and inflammatory cells (6%) misled the diagnosis, resulting in the initial incorrect diagnosis of other neuromuscular disorders, including inflammatory myopathy. In our case, in addition to the endomysial and perivascular amyloid depositions, the pathological finding of myofibers with CBs/SBs was the conspicuous feature. To date, the pathological findings of amyloid myopathy other than amyloid depositions have not been fully reported partly due to its rarity. Accordingly, there are no reports that describe CBs/SBs in amyloid myopathy. Although it is a possibility that a pathophysiology other than amyloidosis is complicated/underlying in our case, we have to emphasize that the CBs/SBs finding could be one of the pathological presentations of amyloid myopathy.
In conclusion, this case highlights that amyloid myopathy could exhibit a pathological feature mimicking myofibrillar myopathy.
REFERENCES
ACKNOWLEDGMENTS
We thank Kaoru Tatezawa, Kazu Iwasawa, and Yoriko Kojima in NCNP for their technical assistance.
Contributed by Tomoya Kawazoe, MD, PhD, Akinori Uruha, MD, PhD, Madoka Mori-Yoshimura, MD, PhD, Yuko Saito, MD, PhD, Shu-ichi Ikeda, MD, PhD, Mike Saji, MD, Akira Tanimura, MD, PhD, Tomofumi Amano, MD, PhD, Tomoko Okamoto, MD, PhD, Yasushi Oya, MD, Miho Murata, MD, PhD, Ichizo Nishino, MD, PhD, Yuji Takahashi, MD, PhD
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