Extranodal NK/T-Cell Lymphoma, Nasal Type (ENKL)

Epidemiology

  • Sex: M>F
  • Median Age of Onset: 50’s
  • Race: occur mostly in non-Caucasians
  • Presentation: 70-80% of cases present with limited stage (stage I or II) disease

Physiology

  • Probable Derivation from Stage 4 NK Cells in Secondary Lymphoid Tissue
    • This is distinct from Aggressive NK Cell Leukemia (ANKL) (see NK Cell Leukemia), which is believed to be derived from stage 5 NK cells in peripheral blood
    • These two diseases share poor responsiveness to chemotherapy and a poor prognosis
  • Expression of the MDR1 Gene Product, P-Glycoprotein, on Tumor Cell Surface: P-glycoprotein actively exports many anti-tumor drugs out of the tumor cell (vincristine and doxorubicin are exported, but methotrexate and L-asparaginase are not)
    • Confers resistance to typical antracycline-containing lymphoma regimens

Diagnosis

  • CD16 Expression: approximately 20%

Clinical Sites of Involvement

  • Nasal Area: nasal origin ENKL accounts for 82% of all cases (however, nasal origin represents only 66% of stage IV cases)
  • Mouth/Upper Airway
    • Epipharynx
    • Palate
  • Skin: occasional origin
  • Soft Tissue
  • GI Tract
  • Hepatic: occasional origin
  • Splenic: occasional origin
  • Testes
  • Bone Marrow

Treatment

  • Poor Chemoresponsivness: 18% complete response rate
  • Localized ENKL
    • Concurrent Chemoradiotherapy
  • Advanced ENKL
    • Less Than or Equal to 65 y/o with Sufficient Organ Function: SMILE (Steroids + Methorexate + Ifosfamide + L-Asparaginase + Etoposide)
    • Over 65 y/o or Mild Organ Damage: Dose-Reduced SMILE Regimen (66-75% Dose)
    • Severe Organ Dysfunction: L-Asparaginase + Dexamethasone, Then SMILE
  • Relapsed/Refractory ENKL:
    • Less Than or Equal to 65 y/o with Sufficient Organ Function: SMILE
    • Over 65 y/o or Mild Organ Damage: Dose-Reduced SMILE Regimen (66-75% Dose)

Prognosis

  • Median Survival: 4 months

References

  • Treatment of Advanced Extranodal NK/T-Cell Lymphoma, Nasal Type and Aggressive NK Cell Leukemia. Int J Hematol 2010; 92: 697-701 [MEDLINE]