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Disease Evolution:
CD4/CD8 ratio in the skin:
| • | as the CTCL progresses, the proportion of CD4+ cells climbs to over 90% (nonneoplastic cells, including reactive CD8+ cells, disappear from the skin) |
peripheral blood:
| • | similar to the skin, the peripheral blood shows a gradual replacement of normal lymphocytes by CTCL cells (à CTCL-induced immunodeficiency) |
| • | this can be demonstrated with beta-chain variable region antibodies: |
| • | T-cells that have rearranged their alpha and beta T-cell receptor genes express a single variable region beta chain |
| • | normally none of the variable region antibodies reacts within more that 5% of circulating peripheral blood lymphocytes |
| • | a clonal expansion in the peripheral blood can easily be detected if an existing variable region antibody reacts with that clone (at the moment, antisera are only available to less than 25% of the variable regions, limiting the diagnostic utility of this technique) |
T-cell gene rearrangement:
Southern blotting:
| • | can detect clone if it is present in as little as 1% to 5% of lymphocytes under study |
| • | patches of CTCL are too sparsely infiltrated by malignant cells for a negative result to be considered significant |
PCR:
| • | can detect clonal T-cell gene rearrangements even in patch stage CTCL |
| • | can perform on paraffin embedded tissue |
Staging:
| • | CBC with differential and flow cytometry for CD3, CD4, CD8, CD45RO,CLA |
| • | look for lymphocytosis, elevated CD4/CD8, elevated levels of cutaneous T-cells (i.e. CLA +) |
| • | CD4/CD8 ratios – can detect disease in the peripheral blood (value >4 considered pathologic) |
| • | any abnormalities follow up with gene rearrangement studies |
| • | (peripheral blood involvement may not be apparent on a CBC, because malignant lymphocytes tend to appear morphologically normal, and because they tend to replace normal lymphocytes, resulting in a total lymphocyte count that is not elevated) |
| • | biopsy enlarge lymph nodes |
| • | CXR, CT abdomen and pelvis |
| • | CA screening: stool guiac, mammograms |
prognosis – poorer with erythrodermic (T4) than with tumors (T3)
| • | failing T-cell immunity occurs with progression of the disease, therefore increasing incidence of infection and of second malignancy |
| • | the major parameters that effect outcome: |
| • | tumor burden (patch vs. plaque vs. tumor; and surface area) |
| • | immunocompetence (within the same clinical stage, patients with more CD8 lymphocytes survive longer) |
| • | at this point, the clinical parameters of tumor burden and the laboratory parameters of immunocompetence are the mainstays of determining prognosis patterns of clonal lymphocytic infiltrates |
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