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CASE REPORT Table of Contents  
Ahead of print publication
Diagnosis of AL amyloidosis on bone marrow aspirate smears - A Case Report


1 Department of Hematology and Clinical Pathology, Cardiology Apollo Hospital, Chennai, Tamil Nadu, India
2 Department of Clinical Haematology, Cardiology Apollo Hospital, Chennai, Tamil Nadu, India
3 Department of Internal Medicine, Cardiology Apollo Hospital, Chennai, Tamil Nadu, India

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Date of Submission21-Mar-2022
Date of Decision26-Jul-2022
Date of Acceptance29-Jul-2022
Date of Web Publication01-Sep-2022
 

  Abstract 


Introduction: An amyloidosis is a group of diseases associated with the deposition of abnormal protein fibrils in the tissues. Primary amyloidosis (AL) type is the most common form of systemic amyloidosis encountered in clinical settings resulting from the deposition of abnormal light chains associated with underlying plasma cell dyscrasia. Amyloid deposits are rarely seen in bone marrow aspirate smears. Methods: Amyloidosis occurs as a result of the deposition of autologous proteins, which, when viewed under a light microscope, appear as eosinophilic, acellular, amorphous deposits. Results: We presented a case of AL amyloidosis presenting with cardiac manifestations and detected to have amyloid deposits in bone marrow aspirates. Conclusion: To the best of our knowledge, reporting amyloid deposition in bone marrow aspirate smears is very rare and unusual, with sparse mention of its occurrence in literature. Careful examination of bone marrow aspirate for this striking finding leads us to a quicker diagnosis of amyloidosis for a prompt determination of therapeutic protocol, improving the outcomes for the patients.

Keywords: Amyloidosis, bone marrow, plasma cells


How to cite this URL:
Sundaram S, Soni M, Pandurangan P, Ali S. Diagnosis of AL amyloidosis on bone marrow aspirate smears - A Case Report. Apollo Med [Epub ahead of print] [cited 2022 Sep 27]. Available from: https://apollomedicine.org/preprintarticle.asp?id=355258





  Introduction Top


Amyloidosis occurs as a result of the deposition of autologous proteins, which, when viewed under a light microscope, appear as eosinophilic, acellular, amorphous deposits. Under polarized light after staining with Congo red, it produces a characteristic apple-green birefringence.[1] The structure of an amyloid protein is complex, composed predominantly of strands of protein arranged in an antiparallel direction and a cross β-pleated sheet with strands perpendicular to the long axis.[1] Deposition of amyloid can be local or systemic. AL or primary amyloidosis is the most common form of systemic amyloidosis; it is known to be associated with plasma cell dyscrasia. Moreover, the degree of plasma cell infiltration of the bone marrow can vary.[2] Amyloid deposition is generally well appreciated in bone marrow biopsy specimens when compared to aspirate smears, where they are either absent or present in sparse amounts, which may get missed. Here, we presented a case of AL amyloidosis presenting with cardiac manifestations and detected to have amyloid deposits in bone marrow aspirates.


  Case Report Top


Clinical history and presentation

A 63-year-old male presented to the cardiac outpatient department with complaints of Grade 3 dyspnea for 5 months with associated orthopnea and generalized weakness. He was diagnosed elsewhere with mediastinal tuberculosis and was on antituberculosis treatment for the past 3 months. He was also diagnosed with restrictive cardiomyopathy.

Investigations

His complete blood counts revealed hemoglobin of 13 g/dl, white blood count of 7600 cells/cumm, and platelets of 150,000 cells/cumm. His erythrocyte sedimentation rate was 53 mm/h. Since the patient had restrictive cardiomyopathy, cardiac magnetic resonance imaging was done, which showed features suspicious of cardiac amyloidosis. Further investigations revealed elevated serum-free kappa levels and lambda levels of 186.2 mg/dl and 34.79 mg/dl, respectively, with a kappa/lambda ratio of 5.35 [Table 1]. Serum capillary immunotyping did not reveal any presence of monoclonal gammopathy. However, urine protein electrophoresis showed the presence of kappa Bence Jones. Bone marrow aspiration and trephine biopsy were done for the patient to evaluate the presence and quantification of plasma cells. Bone marrow aspirate (BMA) revealed mild plasmacytosis (6%) with deposition of pinkish amorphous deposits in the smears suggestive of amyloid [Figure 1]a, [Figure 1]b, [Figure 1]c. Trephine biopsy also revealed plasmacytosis with pale eosinophilic deposits in the interstitium and around blood vessels which were periodic acid–Schiff positive, and Congo red stain showed apple-green birefringence under the polarizing lens [Figure 1]d. Molecular studies detected Immunoglobulin heavy chain (IGH) translocation and t (11:14) in 18% of the nuclei scored. The patient was diagnosed with cardiac amyloidosis and secondary to plasma cell dyscrasia.
Table 1: Laboratory investigations

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Figure 1: (a) Bone marrow aspirate smear showing amyloid with plasma cells, ×40, Giemsa stain. (b) Bone marrow aspirate smear showing amyloid with plasma cells, ×100 Giemsa stain. (c) Bone Marrow Aspirate Smear 40X showing amyloid with plasma cells (d) Trephine biopsy showing green birefringence, ×40, Congo red

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Management

He was treated with standard therapy for AL amyloidosis comprising cyclophosphamide, bortezomib, and dexamethasone and was subsequently discharged from the hospital.


  Discussion Top


Patients diagnosed at advanced stages of amyloidosis, especially with heart involvement, are at high risk of death in a few months.[3],[4] Such patients can also be misdiagnosed with another condition leading to further delays in initiating the correct treatment. In this case, the patient had been previously misdiagnosed as having mediastinal tuberculosis and was on antitubercular treatment for 3 months.

Early diagnosis and therapeutic interventions determine the long-term clinical outcomes. Compared to bone marrow aspirate smears, BM biopsy has been considered the standard to diagnose amyloidosis. Most of the cases reported in the literature have been diagnosed on biopsy. However, processing of BM sections takes time, while BM aspirate and imprints can be evaluated much earlier.[5] In this case, the first diagnosis of amyloidosis was made within 2 h on BM aspiration, giving a time advantage in initiating therapeutic interventions. On suspicion of amyloidosis, a biopsy should be performed along with aspiration, but careful examination of aspirate smears should be carried out to look for evidence of the presence of amyloid deposition for prompt therapeutic interventions. Identifying the deposits in the aspirate becomes highly valuable when a biopsy is not performed or when the facility of histopathological examination is not available.

In AL amyloidosis, the number of plasma cells in the marrow can be as high as in overt myeloma or <10% in which case they are classified as monoclonal gammopathy of undetermined significance or plasma cell dyscrasia.[2] In this patient, about 6% of plasma cells were detected in the aspirates. Studies have detected the association with IGH and t(11:14) translocation in 72.4% and 55%, respectively, of patients with primary amyloidosis.[1] Strikingly similar findings were also detected in our patient, where we detected IGH translocation and t(11:14) in 18% of the nuclei scored.


  Conclusion Top


To the best of our knowledge, reporting amyloid deposition in bone marrow aspirate smears is very rare and unusual, with sparse mention of its occurrence in the literature. Careful examination of bone marrow aspirate for this striking finding leads us to a quicker diagnosis of amyloidosis for a prompt determination of therapeutic protocol, improving the outcomes for the patients.

Declaration of patient consent

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

Acknowledgement

Nil.

Conflicts of interest

There are no conflicts of interest.

Author's contribution

Dr. Supraja Sundaram: Diagnosing the case, conception of the idea, drafting the article. Dr Mamta Soni: Diagnosing the case, conception of the idea, submission and final approval of the version to be published. Dr. Prabu P – Critical revision of the manuscript Dr. Soukat Ali – Critical revision of the manuscript.

Financial support and sponsorship

Nil.



 
  References Top

1.
Bahlis NJ, Lazarus HM. Multiple myeloma-associated AL amyloidosis: Is a distinctive therapeutic approach warranted? Bone Marrow Transplant 2006;38:7-15.  Back to cited text no. 1
    
2.
Ahuja A, Prabhat P, Rastogi A, Panda D, Kumar CK, Sarin SK. Extensive amyloid deposit in bone marrow aspirate. Indian J Hematol Blood Transfus 2013;29:187-8.  Back to cited text no. 2
    
3.
Li TH, Wong KF, Wong WS. Extensive amyloid deposits in bone marrow aspirate smears. Clin Case Rep 2020;8:3581-2.  Back to cited text no. 3
    
4.
Palladini G, Milani P, Merlini G. Management of AL amyloidosis in 2020. Blood 2020;136:2620-7.  Back to cited text no. 4
    
5.
Soni M, Menon M, Vasudevan S, Govindarajan V. Diagnosis of hyperoxalosis on bone marrow aspirate smears. Apollo Med 2021;18:S45-7.  Back to cited text no. 5
  [Full text]  

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Correspondence Address:
Mamta Soni,
Department of Haematology and Clinical Pathology, Apollo Hospital, Greams Road, Chennai - 600 031, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/am.am_50_22



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