Sudden death due to amyloidosis of intramural coronaries in a patient with amyloidosis of hip joint - An autopsy report with a review of literature

Dhaneshwar Namdeorao Lanjewar; Pradeep Vaideeswar; Nitin Subhash Deore; Nirag Chandrakant Jhala

doi:10.4103/ijpm.ijpm_1486_20

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CASE REPORT

Year : 2021 | Volume : 64 | Issue : 4 | Page : 791-794

Sudden death due to amyloidosis of intramural coronaries in a patient with amyloidosis of hip joint - An autopsy report with a review of literature

Dhaneshwar Namdeorao Lanjewar¹, Pradeep Vaideeswar², Nitin Subhash Deore³, Nirag Chandrakant Jhala⁴
¹ Department of Pathology, Gujarat Adani Institute of Medical Sciences, Bhuj, Kachchh, Gujarat; Formerly Professor of Pathology, Grant Government Medical College, Mumbai, India
² Department of Pathology, Seth G. S. Medical College and K. E. M. Hospital, Parel, Mumbai, India
³ Formerly Professor of Pathology, Grant Government Medical College, Mumbai; Consultant Pathologists, Shivay Pathology Laboratory, Near Captain Corner, Laxmi Nagar, Chalisgaon, Dist. Jalgaon, India
⁴ Professor Pathology and Laboratory Medicine, Temple University, Lewis Katz School of Medicine, Philadelphia, USA

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Date of Submission	31-Dec-2020
Date of Decision	28-Apr-2021
Date of Acceptance	30-Apr-2021
Date of Web Publication	20-Oct-2021

Abstract

Amyloidosis is caused by an extracellular accumulation of insoluble fibrillary protein predominantly in the kidneys, spleen, and heart. The deposition of amyloid into the joints, synovia, and osseous tissues (amyloid arthropathy) is an uncommon condition with only a few case reports in the English literature. Similarly, amyloid deposition predominantly limited to the vascular wall is rarely described. In this report, we describe an additional case of amyloidosis of the hip joint along with amyloidosis of intramural coronaries leading to sudden death in a middle-aged male.

Keywords: Amyloidosis, arthropathy, heart, sudden death

How to cite this article:
Lanjewar DN, Vaideeswar P, Deore NS, Jhala NC. Sudden death due to amyloidosis of intramural coronaries in a patient with amyloidosis of hip joint - An autopsy report with a review of literature. Indian J Pathol Microbiol 2021;64:791-4

How to cite this URL:
Lanjewar DN, Vaideeswar P, Deore NS, Jhala NC. Sudden death due to amyloidosis of intramural coronaries in a patient with amyloidosis of hip joint - An autopsy report with a review of literature. Indian J Pathol Microbiol [serial online] 2021 [cited 2023 Mar 26];64:791-4. Available from: https://www.ijpmonline.org/text.asp?2021/64/4/791/328545

Introduction

The current classification of amyloidosis is based on the type of amyloid protein, and to date, around 36 proteins are known to be amyloidogenic. The common proteins are amyloid light chain (AL), amyloid-associated (AA) protein, amyloid transthyretin (ATTR), and amyloid β2-microglobulin (Aβ2m).^[1] The clinical presentation depends on the etiology of the amyloidogenic process and the site of predominant deposition. In the heart, predominant interstitial amyloid deposition results in restrictive cardiomyopathy—a condition investigated and treated by the cardiologist.^[2],[3] Patients with amyloid accumulation in the articular and periarticular structures are often referred to the rheumatologist.^[4] In this report, we describe a second case of amyloidosis of the hip joint in the Indian literature in a patient with sudden cardiac death. The autopsy revealed extensive cardiovascular involvement.

Case Report

A 52-year-old male, non-hypertensive and non-diabetic, presented with pain in the left hip joint and inability to walk for the past 2 months, which was followed by high-grade fever, exertional dyspnea, and swelling of the entire left lower limb for a month. There had been no history of trauma. The general condition of the patient was fair; the pulse rate was 92/min and the blood pressure was 110/80 mmHg. The left limb was 3 cm shorter than the right with diffuse pitting edema. The left hip joint was painful with restricted movements and crepitus. There was no tenderness, warmth, redness, scar, or sinuses. The laboratory investigations were these: hemoglobin 9.1 g/dL, total leukocyte count 4500/cmm (neutrophils 84%, lymphocytes 14%, eosinophils 1%, and monocytes 1%), platelet count 180000/cumm, erythrocyte sedimentation rate 85 mm after 1 h, total protein 6.8 gm/dL, albumin 2.6 gm/dL, globulin 4.2 gm/dL, and absent rheumatoid arthritis (RA) factor/anti-CCP antibody. Abdominal ultrasonography and computed tomography showed a 10.3 cm × 7.14 cm well-defined solid/cystic mass in the retroperitoneum over the left ileo-psoas and adductor muscle, suggestive of a chronic hematoma. The magnetic resonance imaging of the left hip joint showed anterolateral subluxation of the left femoral head, diffuse thinning of the acetabulum, fracture head/neck femur, and hyper-intense proliferation of the synovium (possibly pigmented villonodular synovitis). A Doppler study showed absent blood flow in the left anterior tibial vein and recanalization in the posterior tibial vein. Intravenous antibiotics and low-molecular-weight heparin were started. A biopsy of the synovium and soft tissue of the left hip joint was performed and 2 days after the biopsy, the patient became acutely breathless and expired. A possibility of pulmonary embolism was considered and a clinical autopsy was advised.

Autopsy findings

A complete autopsy was performed. The examination of the thoracic cavity showed a moderately enlarged heart due to biventricular enlargement [Figure 1]a with no evidence of pulmonary thromboembolism. The left side of the pelvic cavity showed a dark-red friable hematoma measuring 10 cm × 7 cm × 6 cm in size. The systemic examination showed normal myocardium and heart valves [Figure 1]b and [Figure 1]c. The walls of the coronary arteries were slightly thickened, but the lumens were patent. Both lungs showed focally thickened pleura and the cut surfaces did not show any evidence of tuberculosis. Other organs appeared normal. The histology of the heart showed thickening and luminal narrowing of the radicles of the epicardial vessels [Figure 2]a and most of the intramyocardial coronary arteries [Figure 2]b and [Figure 2]c due to deposition of acellular amorphous eosinophilic material, which were Congophilic [Figure 2]d. Similar depositions were focally seen to surround individual myofibers [Figure 3]a with fine scarring in both ventricles; areas of replacement fibrosis were not seen. Deposits were also present in the mitral [Figure 3]b and aortic valves. Small deposits were seen in the aortic adventitia; the pulmonary trunk was normal on histology. The alveolar septa and intra-pulmonary arteries were also involved [Figure 4]a and [Figure 4]b, exhibiting Congo red positivity. Immunohistochemistry (IHC) for kappa/lambda light chains and β2m was negative; IHC for ATTR and AA could not be done due to the non-availability of the antibodies. Electron microscopy showed randomly arranged non-branching fibrils measuring about 12–15 nm in diameter, indicating amyloid fibrils [Figure 4]c. The histology of the liver, spleen, adrenals, kidneys, pancreas, and gastrointestinal tract showed dominant vascular involvement by amyloidosis. The histology of the pelvic mass showed features of organized hematoma. The examination of the bone marrow could not be done as the tissue was not preserved during autopsy. The microscopic section of the periarticular soft tissue was reviewed. It showed interstitial [Figure 4]d and predominantly vascular amyloid deposits having the characteristic apple-green birefringence under polarized light [Figure 4]e, confirming amyloidosis of the hip joint.

Figure 1: (a) Cardiomegaly due to moderate biventricular enlargement; (b) Normal appearance of the right-sided inflow tract; (c) Normal appearance of the left-sided inflow and outflow tracts (AA: ascending aorta, AV: aortic valve, LA: left atrium, LV: left ventricle, MV: mitral valve, PT: pulmonary trunk, RA: right atrium, RAA: right atrial appendage, RV: right ventricle, TV: tricuspid valve)

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Figure 2: Acellular homogeneous eosinophilic material is seen in the walls of (a) the epicardial vasculature (H and E X250); (b) intramural coronary arteries in the right ventricle (H and E X250); (c) intramural coronary artery in the sub-endocardial region of the left ventricle (H and E X250); (d) the material displays strong Congophilia with pale orange staining (Congo red X250)

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Figure 3: (a) Prominent peri-cellular deposition of amyloid-producing cardiomyocyte vacuolation (H and E X250); (b) Amyloid deposit within the mitral valve (H and E X250)

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Figure 4: Amyloidosis of the lung showing deposition in the (a) alveolar septa and (b) muscular pulmonary artery (H and E X250); (c) Amyloid fibrils on electron microscopy (original magnification X60000); (d) Amyloid deposition in the periarticular adipose tissue; (e) Characteristic apple-green birefringence on polarizing microscopy (Congo red X250)

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Discussion

The first report of amyloidosis of the joint cartilage was described in 1959 in a patient with primary amyloidosis.^[5] Such amyloid arthropathy is seen in approximately 5% of systemic amyloidosis.^[6] When amyloid is deposited in the periarticular regions and the synovia, it is associated with pain and swelling, which leads to misdiagnosis of the more common joint maladies like RA or osteoarthritis. The Indian literature describes a report of two patients with primary amyloidosis presenting as polyarthritis.^[7] In our patient, the initial manifestations were arthritis of the left hip joint that subsequently progressed to the fracture of the head/neck of the femur. It is, therefore, necessary to consider amyloidosis in the differential diagnosis of patients presenting with swelling and tenderness in the joints with negative serological tests.

Cardiac amyloidosis typically presents as restrictive cardiomyopathy secondary to interstitial amyloid deposition. Although congestive heart failure is the most common complication, presentation with symptoms of myocardial ischemia due to narrowing of an intramural coronary artery by amyloid deposition can rarely occur. In one case series, 3% of the patients with angina and normal angiogram, had small vessel amyloid disease.^[8] Occasional reports of sudden death due to unsuspected amyloidosis predominantly involving the arterial walls of multiple organs, including the heart, are described in the literature.^[9] In the present case, the extensive vascular involvement was not suspected clinically and was diagnosed only after autopsy. In Indian literature, there is only one report of amyloidosis of intramural coronaries.^[10] This patient, with ischemic symptoms and elevated cardiac troponin level, was diagnosed with cardiac amyloidosis by radionucleotide uptake scan using 99 mTc and histopathologic confirmation by abdominal fat biopsy. The proteinaceous deposit was composed of kappa light chains. Amyloidosis can be associated with abnormal bleeding tendency due to acquired hemostatic abnormalities such as coagulation factor deficiencies, hyper-fibrinolysis, and platelet dysfunction.^[11] In the present case, vascular amyloidosis in the pelvic vessels also manifested as bleeding within the pelvic cavity seen as a large organizing hematoma.

Conclusions

In most of the medical institutes in India, the histopathological evaluation of synovial tissue is not carried out on a regular basis. The present case emphasizes the value of routine histopathological evaluation of the capsule and the synovium in patients with degenerative and inflammatory arthritis. The lesson from this case is that the site of amyloid deposition can differ between patients, and therefore, clinical presentation can vary. While cardiac involvement in amyloidosis is not uncommon, isolated intramural vessel involvement is rarely seen, which can result in sudden cardiac death. The vascular amyloidosis identified in this case reiterates the value of clinical autopsy not only in identifying the amyloid protein but also in describing the unusual pattern of vascular amyloidosis, which can manifest as infarction of vital organs. Further investigation is needed to develop a reliable protocol for early detection of vascular-limited amyloid deposition.

Acknowledgments

Dr. Arun Chitale, MD, Former Head, Department of Pathology, Jaslok Hospital and Medical Research Institute, Mumbai, India. MD, Professor, Pathology and Laboratory Medicine, Director, Anatomic Pathology/Cytology, Temple University, Lewis Katz School of Medicine, Philadelphia, USA.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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