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Table of Contents    
Year : 2016  |  Volume : 64  |  Issue : 5  |  Page : 1052-1055

Amyloid myopathy: An underdiagnosed entity

1 Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Neurology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Date of Web Publication12-Sep-2016

Correspondence Address:
Rakesh Vasishta
Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.190278

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How to cite this article:
Gaspar B, Singh R, Mehta S, Goyal MK, Modi M, Lal V, Radotra B, Vasishta R. Amyloid myopathy: An underdiagnosed entity. Neurol India 2016;64:1052-5

How to cite this URL:
Gaspar B, Singh R, Mehta S, Goyal MK, Modi M, Lal V, Radotra B, Vasishta R. Amyloid myopathy: An underdiagnosed entity. Neurol India [serial online] 2016 [cited 2020 Sep 25];64:1052-5. Available from:


Immunoglobulin light chain amyloidosis is a rare systemic disease that results from the secretion of a monoclonal light chain of lambda or kappa type by clonal plasma cells in the bone marrow.[1],[2] Amyloid myopathy is an unusual manifestation of amyloid light (AL) chain disease and is often misdiagnosed because of its atypical clinical manifestations.[3] Herein, we report an uncommon case of amyloid myopathy, where the preliminary work-up for systemic amyloidosis was non-contributory and a definitive diagnosis was made on muscle biopsy.

A 57-year-old gentleman presented with a 6-month history of stiffness and vague tightness in the leg muscles after walking for a distance of 500 m. He was forced to take rest for at least 10–15 min before walking again. The symptoms were progressive, and at the time of admission, he was not able to walk for even 50 m. He had a similar feeling of stiffness in the upper limb, jaw, and neck muscles. He also had hoarseness of voice, numbness and tingling in both the forefeet and lateral three fingers, and a significant loss of weight. There was no positive history pertaining to cranial nerve involvement, thinning of limbs, fasciculations, or bowel and bladder disturbances. Family, drug, and past history were non-contributory. Examination of the nervous system revealed a hypophonic speech and diminished deep tendon reflexes. Muscle bulk, tone, and power were within normal limits. There was no myotonia or paramyotonia. Pain, temperature, and touch sensations were reduced by 20% on the plantar surface of both forefeet. The autonomic system examination was normal. On dynamic testing, he developed stiffness within 15s of sustained arm abduction without any decrement in power. Similarly, he complained of stiffness of the respective muscles after walking for a distance of 25 m, chewing, and voluntary repetitive blinking. Other general (including peripheral pulses), physical, and systemic examinations were unremarkable. The possibilities considered were: Metabolic myopathy (glycogen storage disease, hyperparathyroidism, or hypothyroidism), mitochondrial myopathy, and immune-mediated disorder affecting both the muscles and nerves (autoimmune/paraneoplastic channelopathy). Laboratory investigations including a complete hemogram, renal and liver function tests, serum electrolytes, calcium, phosphorus, thyroid functions; anti-nuclear antibody (ANA) test for human immunodeficiency virus as well as levels of vitamin D3, intact parathyroid hormone, creatine kinase, and acetylcholine receptor antibodies were within normal limits. Serum and urine protein electrophoresis for the M-band were also negative. Serum lactate dehydrogenase and uric acid levels were raised. Contrast-enhanced computed tomography (CECT) of the chest and abdomen and whole body positron emission - computed tomography (PET-CT) did not reveal any abnormality. Forearm ischemic lactate test was normal. Nerve conduction studies revealed sensorimotor axonal polyneuropathy. Pulmonary function tests were normal. Repetitive nerve stimulation (RNS), electromyography, abdominal fat pad aspirate, and skin biopsy were normal. Alternative causes of claudication were also considered and ruled out by angiography, and magnetic resonance imaging (MRI) of the lumbar spine ruled out lumbar canal stenosis.

He underwent a biopsy from the left deltoid muscle. Preliminary hematoxylin and eosin (H&E) staining did not reveal any specific abnormality in the muscle fibers. However, Stoke's Congo red and thioflavin T stains complemented by electron microscopy confirmed the material to be amyloid in the blood vessels, sarcolemma, endomysium, perimysium, and the capsule of muscle spindles. The frozen sections were also subjected to immunofluorescence studies that revealed lambda light chain restriction [Figure 1] and [Figure 2]. Hence, a final diagnosis of amyloid myopathy with lambda light chain restriction was made and further work-up for myeloma was advised. Subsequently, serum light chain assay showed kappa (12.9 mg/l) and lambda (2190 mg/l) chains with a kappa: lambda ratio of 0.01. Bone marrow examination revealed 5% plasma cells with amyloid deposits. His 24-h urinary protein was normal (20 mg), two-dimensional echocardiography was normal, troponin I was 0.01 ng/ml (normal range: 0–0.02 ng/ml) and serum N-terminal pro-B-type natriuretic peptide (NT Pro-BNP level) was 45.3 pg/ml (normal range: 0–100 pg/ml). Once the diagnosis of amyloid myopathy was made, the patient was offered hematopoietic stem cell transplantation, which he refused to be undertaken due to financial constraints. Hence, he was given one cycle of oral melphalan (22 mg) and prednisolone (100 mg) for 4 days in addition to thalidomide (100 mg). He tolerated the drugs well and was discharged to be followed-up for the next cycle of chemotherapy. At a follow up of 9 months, there was a mild improvement in his symptoms with an increase in walking distance by 100 m.
Figure 1: (a and b) Hematoxylin and eosin stain demonstrates deposition of amorphous acellular eosinophilic material in the interstitium, blood vessels, and muscle spindles (black arrows). (c and d) Congo red-stained section visualized under polarized light confirms the apple-green birefringent deposits to be amyloid (black arrows)

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Figure 2: (a) Congo red-stain visualized under Texas Red filter demonstrates amyloid deposits in the vessel walls and sarcolemma (white arrows). (b) Thioflavin T- stain visualized under fluorescein isothiocyanate (FITC) filter (excitation spectra 470 ± 20 nm and emission spectra >515 nm, white arrow). (c) FITC labelled lambda light chain immunofluorescence staining shows 3+ intensity in the interstitium, blood vessel wall, perimysium, and sarcolemmal membranes (white arrows). (d) Electron microscopic image (×500 nm) exhibits sarcolemmal non-branching 9–20 nm crisscrossing fibrils typical of amyloid deposits (white arrow)

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Amyloid myopathy is a very rare disease with less than 90 cases reported in the literature. The clinical manifestations are varied and most often are non-specific. The age range is wide (3rd to 10th decade).[3] Young patients tend to present with unusual manifestations such as fatigability and proximal muscle weakness.[4] These non-specific symptoms often result in a diagnostic delay, which ranges from 2 weeks to as long as 26 years (mean: 21.7 months).[3] The diagnosis in our case was delayed by 6 months, which was less than that reported in the literature but was still significant considering the grave implications associated with a delay in the treatment of systemic amyloidosis. The chief and, in fact, the only presenting complaint in our patient was the feeling of muscle stiffness after minimal exertion. This is likely related to the vascular deposition of amyloid with luminal compromise and decreased blood supply to the muscles, with resultant symptoms akin to vascular claudication. The only another positive finding on examination apart from prominent exertional stiffness was hoarseness of voice. There was no evidence of any weakness on examination, which is reported in 89.9% of cases in the literature.[3] In fact, the two features exhibited by our patient, namely muscle stiffness suggestive of claudication as well as dysphonia, are seen only in 4.2 and 7% of patients, respectively.[3] Patients with primary systemic amyloidosis often present with renal and cardiac manifestations. On the contrary, there was no evidence of cardiac, renal, or pulmonary involvement in our patient despite his undergoing a detailed evaluation, making his case more unique. In a reported case series of 12 patients with amyloid myopathy, 11 had evidence of cardiac dysfunction on echocardiography (concentric or restrictive cardiomyopathy) and 5 had evidence of renal dysfunction.[4] In another review of 79 patients, 3 patients presented with respiratory failure as an initial manifestation of amyloid myopathy, stressing on the need to perform a detailed pulmonary evaluation in all the patients.[4]

A characteristic clinical feature which can point to a diagnosis of amyloid myopathy (though absent in our patient) is macroglossia. Electromyographic findings in amyloid myopathy are similar to that of other chronic and inflammatory myopathies.[5] The initial work-up for amyloidosis (serum and urine protein electrophoresis, abdominal fat pad aspirate, and skin biopsy) can be misleading because approximately 15–20% of patients with myeloma have only free monoclonal light chain secretion, which may not be detected as a distinct monoclonal band on electrophoresis.[6] The sensitivity of abdominal fat pad and skin biopsy for the detection of amyloid deposits in systemic amyloidosis ranges from 54–93% and 50%, respectively.[7],[8] Abdominal fat pad and skin biopsy were negative in our patient. This stresses on the need for a muscle biopsy to establish the diagnosis in a patient with compatible clinical syndrome and light chain abnormality.[9] However, the frequency of detecting amyloid deposits in biopsy samples varies in different studies. This difference is probably because amyloid deposits are often overlooked.[10],[11] While routine serum and urine electrophoresis fail to detect monoclonal proteins in approximately half of the patients, immunoelectrophoresis can detect monoclonal proteins in 80–90% of patients. With the currently available diagnostic techniques, estimation of free light chain assay, monoclonal proteins may be of diagnostic significance in almost all the patients.

Once the diagnosis of amyloid myopathy has been established, the next step is to trace the source of amyloid and assess for the extent of the disease. The most important investigation is the bone marrow examination. The plasma cell burden in the bone marrow is usually small (median: 5–7%). Overall, only less than 10% of the AL amyloidosis patients have multiple myeloma.[12] Not only plasma cell dyscrasias but secretory B cell lymphoproliferative disorders such as Waldenstrom's macroglobulinemia, chronic lymphocytic leukemia, and certain non-Hodgkin's lymphomas can also result in AL amyloidosis.[13] Hence, when the bone marrow examination turns out to be negative, additional investigations such as CECT and PET-CT of the neck, chest, and abdomen are needed to look for enlarged lymph nodes and/or organomegaly. If found, appropriate sites could be sampled and further subjected to either histopathological examination (biopsy) or flow cytometry (fine-needle aspiration cytology). To determine the extent of the AL amyloidosis, investigations pertaining to end-organ damage such as the heart (B-type natriuretic peptide (BNP), cardiac troponin, echocardiogram, etc.), kidneys (24-h urine protein, creatinine, etc.), and liver (serum alkaline phosphatase and imaging) need to be performed.[14]

The treatment of amyloid myopathy includes hematopoietic stem cell transplantation or trials of systemic chemotherapy depending upon the performance status.[10] Till date, there is no consensus regarding the treatment and prognosis of amyloid myopathy. However, it appears that patients who have amyloid deposits that result in a major end-organ damage follow a downhill course as compared to patients whose deposits are not distributed in the major end organs.

We conclude that amyloid myopathy should always be kept in the differential diagnosis of chronic myopathy. If not diagnosed at an early stage, it can be fatal. Early diagnosis and intervention could possibly change the eventual outcome in these patients. Larger studies are needed to draw meaningful conclusions.

Financial support and sponsorship

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Conflicts of interest

All of the authors declare that they have no conflicts of interest or disclosures to report.

  References Top

Zhou P, Comenzo RL, Olshen AB, Bonvini E, Koenig S, Maslak PG, et al. CD32B is highly expressed on clonal plasma cells from patients with systemic light-chain amyloidosis and provides a target for monoclonal antibody-based therapy. Blood 2008;111:3403-6.  Back to cited text no. 1
Pinney JH, Smith CJ, Taube JB, Lachmann HJ, Venner CP, Gibbs SD, et al. Systemic amyloidosis in England: An epidemiological study. Br J Haematol 2013;161:525-32.  Back to cited text no. 2
Chapin JE, Kornfeld M, Harris A. Amyloid myopathy: Characteristic features of a still underdiagnosed disease. Muscle Nerve 2005;31:266-72.  Back to cited text no. 3
Simmons Z, Specht CS. The neuromuscular manifestations of amyloidosis. J Clin Neuromuscul Dis 2010;11:145-57.  Back to cited text no. 4
Rubin DI, Hermann RC. Electrophysiologic findings in amyloid myopathy. Muscle Nerve 1999;22:355-9.  Back to cited text no. 5
Bhole MV, Sadler R, Ramasamy K. Serum-free light-chain assay: Clinical utility and limitations. Ann Clin Biochem 2014;51:528-42.  Back to cited text no. 6
van Gameren II. The role of abdominal fat tissue FNA for early detection and typing of systemic amyloidosis. Cancer Cytopathol 2015;123:139-40.  Back to cited text no. 7
Kyle RA, Greipp PR. Amyloidosis (AL). Clinical and laboratory features in 229 cases. Mayo Clin Proc 1983;58:665-83.  Back to cited text no. 8
Gertz MA. Immunoglobulin light chain amyloidosis: 2014 update on diagnosis, prognosis, and treatment. Am J Hematol 2014;89:1132-40.  Back to cited text no. 9
Hull KM, Griffith L, Kuncl RW, Wigley FM. A deceptive case of amyloid myopathy: Clinical and magnetic resonance imaging features. Arthritis Rheum 2001;44:1954-8.  Back to cited text no. 10
Jowitt SN, Yin JA, Schady W, Burton I, Snowden N. Polymyositis in association with multiple myeloma. Br J Hosp Med 1991;45:234-5.  Back to cited text no. 11
Kourelis TV, Kumar SK, Gertz MA, Lacy MQ, Buadi FK, Hayman SR, et al. Coexistent multiple myeloma or increased bone marrow plasma cells define equally high-risk populations in patients with immunoglobulin light chain amyloidosis. J Clin Oncol 2013;31:4319-24.  Back to cited text no. 12
Merlini G, Stone MJ. Dangerous small B-cell clones. Blood 2006;108:2520-30.  Back to cited text no. 13
Muchtar E, Buadi FK, Dispenzieri A, Gertz MA. Immunoglobulin light-chain amyloidosis: From basics to new developments in diagnosis, prognosis and therapy. Acta Haematol 2016;135:172-90.  Back to cited text no. 14


  [Figure 1], [Figure 2]


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