Definition
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
Initial posting/updates : 9/1/07, 4/16/10
Supplemental studies
Microscopy
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)
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
Lists
Plasma cell neoplasms / Immunosecretory disorders (WHO 2008)
Bibliography
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.
