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1368 Part VII Hematologic Malignancies

Molecular and immunologic studies suggest a mature clonal helper include multiagent chemotherapy and antibody or recombinant
T-cell process. However, reports have suggested a massive reactive toxins directed against the IL-2 receptor. Patients with acute ATL
T-cell infiltrate driven by a small number of clonal B cells. have poor survival rates, with a median duration of 4–6 months.
EBV DNA sequences are frequently present, and their role in the Patients with disease that is not “acute” are considered to have
pathogenesis of this disorder remains poorly defined. Although the “smoldering” disease and have lesions that may wax and wane in size
clinical course is variable, the prognosis for patients with diffuse and shape despite treatment.
pulmonary involvement or evolution to high-grade lymphoma is
poor, with a median survival of less than 2 years. Treatment depends
on histologic findings and extent and location of disease, and may Prognosis
include corticosteroids, radiotherapy, and chemotherapy. IFN has
shown significant activity against this disease. Related conditions The goals of treatment in MF are the relief of symptoms with
include the recently reported EBV-induced mucocutaneous ulcer improved quality of life, generally through prevention or delay in
seen in immunosuppressed patients and B-cell lymphomas of older development of advanced skin disease and improvement in cosmetics.
adults. Despite some uncontrolled clinical trial results that have been
reported to suggest “cures” in this disease, the general perception
remains that this disease is not curable with standard therapies avail-
Adult T-Cell Leukemia able today. The disease behaves similarly to other low-grade lympho-
mas, with periods of remission gradually becoming shorter with
ATL is in most instances a rapidly progressive T-cell neoplasm subsequent therapeutic interventions. Unlike B-cell low-grade lym-
expressing a helper phenotype that is described earlier in this chapter. phomas, however, advanced-stage MF is associated with a relatively
It is endemic in southern Japan and the Caribbean islands, and is short median life expectancy. Patients with significant nodal involve-
associated with the retrovirus HTLV-1. However, most HTLV-l– ment (LN3 or LN4) or extensive skin involvement (T4) have median
infected patients remain asymptomatic, and only 2%–4% develop life expectancies of 30–55 months (Table 85.5). A driving force in
ATL. The clinical presentation is polymorphous and can resemble the development of treatments for this disease is the goal of altering
MF or SS. Cutaneous lesions are variable, ranging from a rash simu- the natural history for this group of poor-prognosis patients. No
lating a viral exanthem, to annular lesions resembling erythema clinical trial has determined that aggressive early therapy is better than
multiforme, to large tumors and plaques similar to MF (Fig. 85.21). sequential palliative approaches or investigational approaches, and
Advanced stages of the disease, which affects a younger population new treatments continue to be developed and tested for these patients.
than seen with MF, are characterized by visceral involvement, immu- In 1979 the staging committee at an international workshop on
nodeficiency, elevated LDH level, and hypercalcemia. Malignant MF proposed a staging system based on the international tumor-
lymphocytes often have convoluted or multilobed nuclei and can be node-metastasis (TNM) system (see Table 85.5). This classification
detected in the peripheral blood in 75% of patients. The neoplastic was based on the evaluation of 347 patients and a multivariate analysis
T cells express high levels of the IL-2 receptor (CD25). For purposes of potential prognostic factors. This group identified several indepen-
of treatment and prognosis, it is wise to view ATL as a spectrum with dent prognostic factors: extent of skin disease at diagnosis (T), type
two subgroups—acute and all others—with treatment, although of lymph node (N) involvement, presence or absence of peripheral
inadequate, reserved for those with acute ATL. Therapeutic options blood (PB) involvement, and presence or absence of visceral (M)
involvement. In 2007 this staging system was revised by the Inter-
national Society for Cutaneous Lymphomas (ISCL) and the EORTC
to incorporate advances related to tumor cell biology and diagnostic
techniques, including status of blood involvement, and to improve
inter-investigator communication and development of standardized
clinical trials (see Table 85.5). Investigators at the National Cancer
Institute retrospectively analyzed 152 patients who underwent
uniform pathologic staging. They were able to identify three distinct
prognostic groups. Good-risk patients had plaque-only skin disease
without lymph node, blood, or visceral involvement, and a median
survival of more than 12 years. Less than 10% of patients with stage
1A (limited patch) and less than 30% with stage 1B (extensive patch
or plaque) progress to more advanced disease. Intermediate-risk
patients had skin tumors, erythroderma, or plaque disease with
lymph node or blood involvement (but no visceral disease) and a
median survival of 5 years. Poor-risk patients had visceral disease or
complete effacement of lymph nodes by lymphoma, and a median
survival of 2.5 years.
In addition to the classic TNM staging, implementation of
techniques such as flow cytometry, cytogenetic analysis, and determi-
nation of nuclear contour indices may also improve diagnostic and
prognostic specificity. Flow cytometry and cytogenetic analysis are
complementary techniques. Flow cytometry allows the detection of
cell populations with a normal (diploid) number of chromosomes
versus abnormal (aneuploid) numbers, and cytogenetic analysis pre-
cisely identifies the individual chromosomal structure and number.
Bunn et al demonstrated that in MF/SS the presence of aneuploidy
during the clinical course was associated with more aggressive disease.
Hyperdiploid cell clones were demonstrated in patients with large-cell
histology, aggressive disease, and shortened survival time. Specific
chromosomal deletions also influenced prognosis.
The nuclear contour index has been used by several groups in an
Fig. 85.21 SKIN LESIONS IN ADULT T-CELL LYMPHOMA/ effort to separate “benign” cutaneous lymphocytic disorders, such as
LEUKEMIA. LyP and pityriasis lichenoides, from MF/SS. Electron microscopy