Mass Spectroscopy Establishes Primary (AL) Amyloidosis

Case Report: Mass Spectroscopy Establishes Primary (AL) Amyloidosis in a 61-Year-Old Patient

Introduction

Amyloidosis is a group of disorders produced by the extracellular accumulation of misfolded protein fibrils. Although histopathological staining like Congo red is still the initial diagnostic process, sophisticated molecular tests like mass spectroscopy (MS) offers accurate amyloid typing, crucial in directing therapy.

Here, a 61-year-old African-American male with multisystem involvement had a sigmoid colon biopsy. Congo red staining established amyloid deposition, and follow-up mass spectroscopy analysis revealed a peptide profile diagnostic of primary (AL) amyloidosis.

This report emphasizes the key role of mass spectroscopy in distinguishing amyloidosis subtypes and guiding proper management.

Patient Background and Clinical Presentation

The patient had:

• Subacute presentation of abdominal distension (ascites)
• Bilateral lower extremity edema
• Jugular venous distension
  Laboratory and imaging results were:
• Hypoalbuminemia (2.1 g/dL)
• Increased liver enzymes (AP 718 IU/L, AST 158 IU/L, ALT 119 IU/L)
• Nephrotic-range proteinuria
• Normal total bilirubin (0.5 mg/dL), INR (1.07), and creatinine (0.9 mg/dL)
• Ascites with SAAG >1.1 (indicating portal hypertension)
• Echocardiogram with LV hypertrophy with infiltrative features
  A sigmoid colon biopsy was positive for Congo red–positive deposits. To determine the amyloid subtype, mass spectroscopy was done.

Why Amyloid Typing is Important

Not every case of amyloidosis is created equal. Accurate typing dictates:

• Treatment strategy (chemo for AL vs tafamidis for ATTR)
• Prognosis
• Clinical monitoring plans

Primary Types of Amyloidosis

1. AL (Primary Amyloidosis)

• Due to plasma cell dyscrasia secreting monoclonal light chains.
• Progresses rapidly, typically affecting kidneys, liver, and heart.
• Needs chemotherapy or stem cell transplant.

1. ATTR (Transthyretin Amyloidosis)

• Because of misfolded transthyretin protein.
• Can be hereditary or wild-type (age-related).
• Treated with transthyretin stabilizers such as tafamidis.

1. AA Amyloidosis

• Is linked with chronic inflammatory diseases (e.g., RA, IBD).
• Less prevalent in developing nations.
  Without typing, patients can be treated with improper therapies with minimal benefit.

Role of Mass Spectroscopy in Diagnosis

Mass spectroscopy (MS) is the gold standard for amyloid typing. It functions by:

1. Purifying proteins from biopsy tissue
2. Breaking them down into peptides
3. Creating a peptide profile (fingerprint)
4. Comparing to protein databases in order to determine the exact amyloidogenic protein

Benefits of Mass Spectroscopy

• High sensitivity and specificity
• Can distinguish between AL, ATTR, and AA amyloidosis
• More accurate than immunohistochemistry, which can have cross-reactivity problems
• Offers reproducible, accurate molecular-level confirmation

Findings in This Case

Mass spectroscopy of sigmoid colon biopsy demonstrated:

• Peptide profile consistent with light-chain amyloidosis (AL)
• No transthyretin (excluding ATTR)
• No serum amyloid A protein (excluding AA amyloidosis)
  This established primary (AL) amyloidosis as the underlying diagnosis.

Correlation with Clinical Features

The patient’s presentation was strongly consistent with AL amyloidosis:

• Renal involvement → nephrotic-range proteinuria
• Hepatic involvement → elevated AP, AST, ALT
• Cardiac involvement → echocardiographic LV hypertrophy with infiltrative features
• Systemic symptoms → ascites, edema, and hypoalbuminemia
  The multisystem profile along with MS confirmation confirmed the diagnosis.

Differential Diagnoses Considered

Prior to MS confirmation, other considerations were:

• Hypertensive heart disease – less so given systemic features
• Liver cirrhosis – ruled out by biopsy and imaging results
• ATTR amyloidosis – excluded by peptide profile
• AA amyloidosis – no chronic inflammatory disorder present
  Mass spectroscopy clarified these uncertainties.

Management After Confirmation

1. Targeted Therapy for AL Amyloidosis

• Chemotherapy regimens (bortezomib, cyclophosphamide, dexamethasone)
• Autologous stem cell transplant in carefully selected patients

2. Supportive Care

• Diuretics for ascites and edema
• ACE inhibitors/ARBs cautiously for proteinuria
• Nutritional support for hypoalbuminemia

3. Multidisciplinary Involvement

• Hematology for chemotherapy protocols
• Cardiology for infiltrative cardiomyopathy
• Nephrology for renal protection and management

Prognosis and Clinical Implications

The prognosis in AL amyloidosis is based on:

• Degree of organ involvement
• Therapeutic response
• Time of diagnosis
  Patients with cardiac involvement do poorly, but prompt detection by biopsy and MS enhances treatment options.

Conclusion

This case highlights the critical role of mass spectroscopy in the diagnosis of amyloidosis. While Congo red stain detects amyloid deposition, typing through MS provides correct categorization. Through this 61-year-old patient, a peptide pattern for primary (AL) amyloidosis was confirmed, which was used to direct specific therapy.

The combination of histology, cutting-edge proteomics, and clinical data is still the bedrock of precision medicine in amyloidosis.