Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (366 page)

   
Immunophenotyping
may be technically difficult. Both conditions have CD4
⁺
, CD3
⁺
, CD45RO
⁺
CLA
⁺
phenotype. In MF, the cells are positive for CD4, CD2, CD3, CD5, and CLA, but, in most cases, MF cells are negative for CD8. In addition to CD4, SS cells express CD27, CCR7,
L
-selectin, and CCR4. Alterations in the expression of T-cell antigens are commonly seen, with loss of expression of CD7 and CD26 being the most common, but not distinctive for malignant T cells. Immunophenotyping helps to distinguish CTCL from reactive or inflammatory lymphoid infiltrates in the skin, which usually express all mature T-cell antigens. An epidermal/dermal discordance for CD2, CD3, CD5, and CD7 suggests the diagnosis of CTCL. In SS, the neoplastic lymphocytes are markedly expanded in the peripheral blood with a CD4/CD8 ratio of >10.

   
Molecular genetic studies
: T-cell receptor gene rearrangement may help establish the diagnosis of MF when the skin biopsy and immunophenotyping results are ambiguous. Gene expression profiles and microRNA profiling suggest that MF and SS may be separate entities with differing pathogenesis.

   
Cytogenetics
: In many patients, the tumor cells have complex karyotypes.

Suggested Reading

Van Doorn R, van Kester MS, Dijkman R, et al. Oncogenomic analysis of mycoides fungoides reveals major differences with Sezary syndrome.
Blood.
2009;113:127–136.

DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL)

   Definition

DLBCL is characterized by clinical, morphologic, cytogenetic, and molecular heterogeneity and can be divided in many subgroups that are biologically distinct, with different responses to therapy. One of the most consistent predictors of outcome is the Rituxan-International Prognostic Index.

   Who Should Be Suspected?

Patients in their 60s who present with rapidly enlarging lymphadenopathy and/or with tumors at extranodal sites, the most common being the GI tract. The bone marrow may also be involved, and in many of these cases, lymphoma cells may be detected in the peripheral blood.

   Laboratory Findings

   
Diagnosis is best established by biopsy of an enlarged lymph node or another affected organ. The morphologic pattern and immunophenotype establish the diagnosis and its variants.

   
Immunophenotype
: In most cases, the tumor cells are positive for the B-cell markers CD19, CD20, CD22, CD79a, and CD45. Monoclonal cell surface membrane IgM is usually positive. Occasionally, DLBCL cells may be CD5 or CD10 positive. It has recently been reported that expression of CD30 by the lymphoma cells is associated with better outcome in patients treated with R-CHOP chemoimmunetherapy.

   
Cytogenetics
: There are no karyotypic abnormalities specific for DLBCL. Up to 30% of cases show rearrangement of 3q27, involving the BCL6 gene; 30% carry a t(14;18)(q32;q21) causing a
BCL2-IGH
rearrangement, more typically found in follicular lymphomas, and 10–20% carry a
C-MYC
rearrangement (see below).

   
Genetics
: Increasingly, genomic studies offer better differentiation and prognostication. Gene expression profiling—not universally available for clinical use—has identified three distinct molecular subgroups: germinal center B-cell like, activated B-cell like, and primary mediastinal B-cell lymphoma. They have different survival patterns and respond differently to therapy. C-MYC expression or amplification is associated with resistance to therapy and a poor prognosis, especially if associated with BCL2 and BCL6 translocations or overexpressions.