Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (375 page)

   
Serum calcium
may be elevated due to bony involvement or overproduction of calcitriol.

   
Immunophenotype
: The neoplastic cells in
cHL
express CD30, and CD15, but
lack
pan-B antigens (CD19, CD20, CD79a), pan-T antigens (CD3, CD7), and CD45. The expression of epithelial membrane antigen (EMA) is mostly negative. Ninety-five percent of cases are weakly positive for PAX-5/ BSAP. The HRS cells of cHL also express MUM1. By contrast, in NLPHL, the neoplastic cells stain positively for CD20, CD79a, CD45, OCT-2, BOB.1, and EMA. They lack CD15 and CD30.

   
Cytogenetics
: Cytogenetic abnormalities are found in the majority of cases of cHL; however, there are no typical cytogenetic abnormalities, and cytogenetic analysis is not considered to be clinically important.

   
Molecular genetic studies
have not reached the clinical practice yet. Genomic analysis detects EBV positivity in 40% of LRHL, 70% of MCHL, and nearly 100% of LDHL, but not in NSHL or NLPHL. Activation of NF-κB pathway is a central event in HL pathogenesis.

Suggested Readings

Aster JC. Epidemiology, pathologic features, and diagnosis of classical Hodgkin lymphoma. In: Basow DS (ed).
UpToDate,
Waltham, MA: UpToDate Inc.; 2013.

Greaves P, Gribben JG. Laser-capturing the essence of Hodgkin lymphoma.
Blood.
2012;120:4451–4452.

   
MONOCLONAL GAMMOPATHIES
^§§

This section describes disorders of plasma cells and of plasma proteins. These neoplasms result from the expansion of a clone of Ig-secreting, terminally differentiated B lymphocytes. These neoplasms are known as monoclonal gammopathies because they express monoclonal products of homogenous immunoglobulins (or fragments) produced by the neoplastic abnormal B cells. The monoclonal proteins may be present in serum, urine, and CSF. The section will follow the fourth edition of the
WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues
. It includes plasma cell myeloma, plasmacytoma, the benign precursor monoclonal gammopathy of undetermined significance (MGUS), and the syndromes defined by the consequence of tissue immunoglobulin deposition, primary amyloidosis (AL), and light and heavy chain deposition disease. Lymphoplasmacytic lymphoma and the heavy chain diseases are described separately.

Suggested Reading

Swerdlow SH, Campo E, Harris NL, et al.
WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues
, 4th ed. Lyon, France: International Agency for Research on Cancer; 2008:200–213.

PLASMA CELL MYELOMA (PCM)

   Definition

Plasma cell myeloma (multiple myeloma, MM) is a B-cell neoplasm consisting of neoplastic proliferation of plasma cells primarily occurring in the bone marrow. The current WHO classification stratifies this disorder into two distinct categories based on specific criteria: (1) symptomatic plasma cell myeloma and (2) asymptomatic (smoldering) myeloma (see below).

Clinically, plasma cell myeloma is manifested by osteolytic lesions, renal failure, hypercalcemia, anemia, hyperviscosity, and serum/urine M (monoclonal) protein.

   Who Should Be Suspected?

Patients in their 60s and 70s who present with anemia, bone pain, unexplained fractures, frequent infections, bleeding, symptoms of hypercalcemia (excessive thirst and urination, constipation, nausea, loss of appetite and mental confusion), and neurologic symptoms arising from compression fractures of vertebrae. There is a wide clinical spectrum ranging from an asymptomatic state to aggressive forms and disorders due to deposition of immunoglobulin chains in tissues.

   Diagnosis and Laboratory Findings

The diagnosis is based on established criteria (WHO) for plasma cell myeloma:

   Symptomatic plasma cell myeloma

   M protein in serum or urine: >30 g/L IgG, or >20 g/L IgA, or >1 g/24 hour urine light chain; some patients with symptomatic myeloma may have lower levels.