Stanford School of Medicine

Surgical Pathology Criteria

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Primary Amyloidosis


  • Plasma cell neoplasm (rarely lymphoid neoplasm) that secretes abnormal immunoglobulin that deposits in tissues and forms a beta-pleated sheet

Alternate/Historical Names

  • Immunoglobulin light chain (AL) amyloidosis
  • Myeloma associated amyloidosis

Diagnostic Criteria

  • Symptomatic amyloid deposition in organs
    • Extracellular amorphous, hyalinized, eosinophilic material
    • Often interstitial or in blood vessel walls
  • Confirmed as amyloid by Congo Red stain
    • Alternate method: electron microscopy
  • Deposits should be present prior to development of symptomatic plasma cell burden
  • Diagnostic biopsies usually abdominal fat-pad, bone marrow, or rectum
    • These are used because of accessibility, rather than predisposition to disease
    • Reported sensitivity of abdominal fat pad aspiration highly variable

Dita Gratzinger MD PhD

Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Initial posting/updates : 9/1/07, 4/16/10

Supplemental studies


  • Congo Red positive with apple-green birefringence
    • Fluorescence microscopy of Congo red stain using rhodamine filter may improve sensitivity
  • Electron microscopy shows non-branching fibrils witih twisted beta-pleated sheet conformation
  • Immnohistochemistry, in situ hybridization or flow cytometry may prove clonality of associated plasma cell population
  • Immunostaining for kappa versus lambda light chain restriction in amyloid deposits often has high background in paraffin embedded tissue

Useful Laboratory Tests

  • Serum or urine protein electrophoresis, immunofixation, light chain quantification
  • Quantitation and typing of monoclonal immunoglobulin / light chain
  • Serum free light chain analysis may be required to demonstrate clonal light chains
  • These studies may be used to
    • Establish presence of a monoclonal plasma cell population
    • Quantitation helps subtype the plasma cell dyscrasia (i.e. >3g/dL serum monoclonal protein is a major criterion for myeloma)
    • Track disease burden over time


Differential Diagnosis

Amyloidoses and Deposition Diseases

Primary (AL) Secondary (AA) Familial (AF) Hemodialysis Associated (β2) Light/Heavy Chain Deposition Disease
M component in 80% (usually lambda) No M component No M component No M component M component often present (usually kappa)
Clonal plasma cells No clonal population No clonal population No clonal population Clonal plasma cells may be demonstrable in marrow
Clonal light chain in deposits may be demonstrable No clonal light chain deposits No clonal light chain deposits No clonal light chain deposits Clonal light/heavy chain deposits may be demonstrable
Congo Red positive Congo Red positive Congo Red positive Congo Red negative Congo Red negative
Heavy chain deposition disease is very rare, so the following must be ruled out
  • Lymphoplasmacytic lymphoma with IgG deposition
  • SLL/CLL witih IgM deposition
  • Extranodal marginal zone lymphoma with IgA deposition (IPSID)
  • Clinical

    • 20% have myeloma
    • 80% have monoclonal serum immunoglobulin (M component)
      • Usually lambda
    • End organ effects due to deposition include
      • Nephrotic syndrome
      • Cardiomyopathy
      • Malabsorption
      • Polyneuropathy
      • Macroglossia
    • Median survival 2 years

    Grading / Staging / Report

    • Grading is not applicable
    • Staging is applicable only if myeloma is present

    The pathology report should contain the following information:

    • Results of supplementary studies if performed



    Plasma cell neoplasms / Immunosecretory disorders (WHO 2008)


    • Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW . WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, International Agency for Research on Cancer, Lyon, 2008
    • Warnke RA, Weiss LM, Chan JKC, Cleary ML, Dorfman RF . Tumors of the Lymph Nodes and Spleen, Atlas of Tumor Pathology, AFIP Third Series, Fascicle 14, 1995
    • Ansari-Lari MA, Ali SZ Fine-needle aspiration of abdominal fat pad for amyloid detection: a clinically useful test? Diagn Cytopathol. 2004 Mar;30(3):178-81.
    • Giorgadze TA, Shiina N, Baloch ZW, Tomaszewski JE, Gupta PK. Improved detection of amyloid in fat pad aspiration: an evaluation of Congo red stain by fluorescent microscopy.  Diagn Cytopathol. 2004 Nov;31(5):300-6.
    • Halloush RA, Lavrovskaya E, Mody DR, Lager D, Truong L. Diagnosis and typing of systemic amyloidosis: The role of abdominal fat pad fine needle aspiration biopsy. Cytojournal. 2010 Jan 15;6:24.
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