Monoclonal Light Chain and Heavy Chain Deposition Diseases

Definition

• Plasma cell neoplasm that secretes immunoglobulin that deposits in tissues and causes tissue damage but does not form an amyloid-type beta-pleated sheet structure

Alternate/Historical Names

• Randall disease

Diagnostic Criteria

• Non-fibrillary, amorphous eosinophilic material
• Congo Red stain negative
• Serum M component present in 85%
• Monoclonal light or heavy chain deposits that cause organ dysfunction
• 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)

Dita Gratzinger MD PhD

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

Initial posting/updates : 9/1/07, 4/18/10

Supplemental studies

Microscopy

• Congo Red negative
• Electron microscopy shows granular, non-fibrillar deposits
• Immnohistochemistry, in situ hybridization or flow cytometry of bone marrow often demonstrates clonal plasma cells
  • Not demonstrable at site of tissue deposition
• Immunostaining of renal biopsy may demonstrate kappa light chains

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

Clinical

• Usually associated with MGUS or overt plasma cell myeloma
• 85% have monoclonal serum immunoglobulin (M component)
  • Usually kappa
• Symptomatic deposition frequently occurs in
  • Kidneys
  • Liver
  • Heart
  • Joints
• Poor prognosis

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)

• Monoclonal gammopathy of undetermined significance (MGUS)
• Plasma cell myeloma
  • Variants:
    • Non-secretory
    • Smoldering
    • Plasma cell leukemia
• Plasmacytoma
  • Solitary plasmacytoma of bone
  • Extraosseus (extramedullary) plasmacytoma
• Monoclonal immunoglobulin deposition diseases
  • Primary amyloidosis
  • Systemic light chain and heavy chain deposition diseases
• Osteosclerotic myeloma (POEMS syndrome)
• Heavy chain diseases (variants of lymphoma rather than plasma cell neoplasms)
  • Gamma heavy chain disease (see lymphoplasmacytic lymphoma)
  • Mu heavy chain disease (see chronic lymphocytic leukemia)
  • Alpha heavy chain disease / immunoproliferative small intestinal disease (variant of extranodal marginal zone lymphoma)

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.