Page 1727 - Williams Hematology ( PDFDrive )

1702 Part XI: Malignant Lymphoid Diseases Chapter 104: Mature T-Cell and Natural Killer Cell Lymphomas 1703

the lymphoma occasionally presents primarily in these sites without an Even though the IPI has been found to be effective in risk strat-
apparent nasal primary. These “nonnasal” ENKTLs were thought to be ification of ENKTL, Lee and colleagues have developed an NK/T-cell
more aggressive. Modern imaging technology, such as PET/CT, shows lymphoma-specific prognostic index that also predicts prognosis (see
183
that most, if not all, nonnasal lymphomas are associated with occult Table 104–3). 2,3,186 This model includes B-symptoms, elevated LDH,
nasal primaries, and imply that they are disseminated nasal lympho- stage, and presence of regional lymph nodes. Those with no risk fac-
mas. 184,185 With improved treatment strategies, primary sites of presen- tors, one risk factor, two risk factors, and three or more risk factors
186
tation are no longer an independent prognostic indicator. Rarely, the had a 5-year OS of 81 percent, 64 percent, 34 percent, and 4 percent,
lymphoma can evolve into NK-cell leukemia, which is characterized by respectively. 198
widespread systemic dissemination and involvement of the marrow and
blood.
SUBCUTANEOUS PANNICULITIS-LIKE T-CELL
LYMPHOMA
LABORATORY FINDINGS
Histopathology Definition
Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is a primary
The histopathology shows angiocentric plesiomorphic small- or cutaneous T-cell lymphoma presenting with painful subcutaneous
medium-size atypical lymphoid cells with vascular invasion and ische- nodules. 199-202 The lesions consist of atypical lymphoid cells, and reactive
mic tissue necrosis. Marrow hemophagocytosis may be present. As NK histiocytes with admixed adipose tissue often associated with coagu-
and T cells share a common ontogeny, the malignant cells express CD2 lation necrosis. Histologically, the cells express an α/β phenotype. The
and CD7 but are negative for surface CD3. They also express CD16, γ/δ phenotype of this disease is now classified as cutaneous γ/δ T-cell
CD56, cytoplasmic CD3ε, and CD57, and often demonstrate clonal lymphoma. 1,202
rearrangements in the TCR genes. 1,175,182 Neoplastic cells are invariably
infected by EBV which is detected most reliably by in situ hybridization Epidemiology
for EBV-encoded RNA (EBER), a diagnostic requisite. Rare cases may As discussed in a worldwide retrospective analysis, SPTL is a rare disor-
177
not express CD56. 1 der accounting for 0.9 percent all T-cell lymphomas. 7,203 SPTL is primar-
ily a disorder of adults with an average age at diagnosis in the mid to late
Laboratory Assessments 30s, although cases have also been reported in children. SPTL has a
204
EBV DNA polymerase chain reaction (PCR) measured in plasma has female predominance with a male to female ratio of 0.5. 204
been found to correlate with tumor burden and serial EBV PCR moni-
toring is useful for assessing responses and disease recurrence. 187,188 Clinical Features
Patients present with subcutaneous nodules that typically begin in the
TREATMENT AND PROGNOSIS extremities and may spontaneously regress for a number of years, but
205
Outcomes of localized NK/T-cell lymphoma are best with combined eventually progress. They may ulcerate, and patients may have systemic
chemotherapy and radiation therapy. In studies of radiation therapy symptoms.
alone, 75 to 100 percent of patients respond; however, systemic relapse
rates are as high as 25 to 40 percent. 189,190 Previously, patients were Laboratory Features
treated with CHOP-based therapy in combination with radiation with a The lesions consist of atypical lymphoid cells, and reactive histiocytes
CR rate of 59 percent and 3-year disease-free survival of 25 percent. 191–193 with admixed adipose tissue often associated with coagulation necrosis.
l-Asparaginase has a major single-agent activity in NK/T-cell lympho- In most cases, the tumor is composed of mature CD8+ αβ cytotoxic T
mas, and is incorporated into most modern regimens for this disease. cells that express TIA-1, granzymes, and perforin genes. 202,204,205
194
l-Asparaginase combined with gemcitabine, oxaliplatin, and radiation
therapy exhibits an ORR of 96 percent and a local and systemic relapse Treatment and Prognosis
195
rate of 10 to 15 percent in a phase I study. Vincristine and predniso- Responses to combination chemotherapy have been reported but are
lone in combination with l-asparaginase produce an ORR of 89 per- usually of short duration. 204–207 Responses to glucocorticoids, interferon-α,
cent when combined with radiation therapy. SMILE (dexamethasone, zidovudine, and cyclosporine also have been reported. 206,208,209 Therapy
methotrexate, ifosfamide, l-asparaginase, and etoposide) in combina- for this disease remains controversial. Although standard chemother-
tion with radiation therapy demonstrates an 82 percent response rate apy may be effective, CRs are rare. Single patient cases of successful
186
with a CR rate of 78 percent. l-Asparaginase has also been studied allogeneic stem cell transplantation have been reported, but the rarity
in combination with methotrexate and dexamethasone with an ORR of of this disease hampers further investigation of this modality. 210,211 The
78 percent. In patients with localized ENKTL, it is standard to consol- use of denileukin diftitox in two patients has been reported with evi-
197
idate asparaginase-based chemotherapy with radiation therapy. In the dence of activity, and bexarotene restored a clinical response in one of
212
setting of patients with advanced stage or relapsed/refractory disease, the patients after disease progression. Single-agent bexarotene has
182
combination chemotherapy remains the standard treatment. Stud- also been shown to have significant clinical activity with an ORR of
ies of SMILE demonstrate an ORR of 25 to 80 percent in disseminated 82 percent. 213
disease. 186,196 NK-cell leukemia is characterized by widespread systemic
dissemination and involvement of the marrow and blood and is associ-
ated with an extremely poor survival measured only in weeks. REFERENCES
EBV DNA PCR measured in the plasma has been found to cor- 1. Swerdlow SH, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, eds: WHO
relate with tumor burden and serial EBV PCR monitoring is useful Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th ed. International
for assessing responses and disease recurrence. 187,188 In view of the Agency for Research on Cancer (IARC), Lyon, France, 2008.
improved efficacy of l-asparaginase–based regimens, the role of ASCT 2. Savage KJ, Chhanabhai M, Gascoyne RD, et al: Characterization of peripheral T-cell
lymphomas in a single North American institution by the WHO classification. Ann
remains unclear. Oncol 15:1467–1475, 2004.

Kaushansky_chapter 104_p1693-1706.indd 1702 9/21/15 12:48 PM