Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (384 page)

   
Cytogenetics
: There are no single chromosomal abnormalities typical for ILCA. Monosomy of chromosome 18 was recently found to be the most common cytogenetic abnormality in bone marrow biopsies. Trisomy of a variety of chromosomes was also found to be common. t(11;14), del(13q14) and gain of 1q21 have also been described.

   
Mass spectrometry and gene sequencing
: Amyloid typing and genetic sequencing of amyloid fibrils are recommended because numerous different proteins can cause systemic amyloidosis. Each may require distinct therapeutic modalities.

   Prognosis

   In PA, the median survival is approximately 2 years from diagnosis, with cardiac failure being the major cause of death.

Suggested Readings

Leung N, Nasr SH, Sethi S. How I treat amyloidosis: the importance of accurate diagnosis and amyloid typing.
Blood.
2012;120:3206–3213.

Merlini G, Wechalekar AS, Palladini G. Systemic light chain amyloidosis: an update for treating physicians.
Blood.
2013;121:5124–5130.

CRYOGLOBULINEMIA

   Definition

Cryoglobulins (CG) are proteins that precipitate in the body at low temperature or on storage of serum at refrigerated temperature. They are insoluble at 4°C and may aggregate at up to 30°C. CG are either immunoglobulins or a mixture of immunoglobulins and complement components. CG can fix complement and initiate inflammatory reactions. The term cryoglobulinemia is often used to refer to a systemic inflammatory syndrome that generally involves small- to medium-sized vessels due to CG-containing immune complexes. The majority of individuals with CG are asymptomatic, except for the symptoms attributable to the underlying disease. CG can also be detected in patients with chronic infection and/or inflammation.

   Classification

   
Type I:
monoclonal immunoglobulin, especially IgG or IgM κ type.

   May cause hyperviscosity syndrome in 5–25% of cases, or thrombosis.

   Most commonly associated with plasma cell myeloma and Waldenström macroglobulinemia (lymphoplasmacytic lymphoma); other lymphoproliferative neoplasms with M components; it may be idiopathic.

   The CGs are often present in great amounts (5–10 mg/dL) with cryocrits >70%. The blood may gel when drawn.

   Severe symptoms (Raynaud syndrome, gangrene without other causes).

   Skin, kidney, and bone marrow are predominantly involved.