CD4⁺56⁺ leukemia from dendritic cells type DC2

Česká verzia

Authors: M. Pevná ¹; J. Kissová ²; M. Doubek ¹; Z. Adam ¹; M. Klabusay ¹
Authors place of work: Interní hematoonkologická klinika Lékařské fakulty MU a FN Brno, pracoviště Bohunice, přednosta prof. MU Dr. Jiří Mayer, CSc. ¹; Oddělení klinické hematologie FN Brno, pracoviště Bohunice, přednosta prof. MU Dr. Miroslav Penka, CSc. ²
Published in the journal: Vnitř Lék 2010; 56(Supplementum 2): 183-187
Category: Langerhans cell histiocytosis and some other Hematology rare diseases

Summary

CD4⁺CD56⁺ malignancies are rare hematological tumours with poor prognosis affecting primarily the skin; despite good initial response to chemotherapy, they result in early relapse and rapid progression and dissemination of the disease into the bone marrow, peripheral blood and lymphatic nodes. Even though the origin of tumorous cells was initially being associated with NK cells because of the CD56 expression, recent studies suggest the disease is derived from precursor plasmocytoid dendritic cells. It is the co- expression of CD4 and CD56 and an absence of line- specific markers that defines this new entity within the last WHO- EORCT classification for cutaneous lymphomas. Patients with this immunophenotype have common clinical features and morphological findings. The specific genetic anomaly is not known. Immunohistochemical and flow cytometric analyses have an exclusive place in the diagnostics. We present two cases of CD4⁺CD56⁺ malignancies with different clinical course. In an 18 years old female, the disease presented as an acute leukemia without the typical cutaneous lesions, was chemoresistant and the patient died 12 months following diagnosis for relapse of the disease after allogeneic hematopoietic stem cell transplantation. In a 64 years old male, the disease manifested as cutaneous lymphoma only. Chemotherapy resulted in an 8 months lasting first complete remission. Treatment of the first relapse with disease dissemination resulted in a short-term 2^nd complete remission. The second relapse followed and the patient died 2 years following diagnosis.

Key words:
CD4⁺CD56⁺ haematodermic neoplasm – DC2 cells – DC2 malignancy

Zdroje

1. Petrella T, Dalac S, Maynadié M et al. CD4+ CD56+ cutaneous neoplasms: a distinct hematological entity? Am J Surg Pathol 1999; 23: 137– 146.

2. Willemze R, Jaffe ES, Burg G et al. WHO- EORTC classification for cutaneous lymphomas. Blood 2005; 105: 3768– 3785.

3. Reimer P, Rüdiger T, Kraemer D et al. What is CD4+CD56+ malignancy and how should it be treated? Bone Marrow Transplant 2003; 32: 637– 646.

4. Bueno C, Almeida J, Lucio P et al. Incidence and characteristics of CD4+/ HLA DRhi dendritic cell malignancies. Haematologica 2004; 89: 58– 69.

5. Brody JP, Allen S, Schulman P et al. Acute agranular CD4– positive natural killer cell leukemia. Comprehensive clinicopathologic studies including virologic and in vitro culture with inducing agents. Cancer 1995; 75: 2474– 2483.

6. Chaperot L, Bendriss N, Manches O et al. Identification of a leukemic counterpart of the plasmacytoid dendritic cells. Blood 2001; 97: 3210– 3217.

7. DiGiuseppe JA, Louie DC, Williams JE et al. Blastic natural killer cell leukemia/ lymphoma: a clincopathologic study. Am J Surg Pathol 1997; 21: 1223– 1230.

8. Scott AA, Head DR, Kopecky KJ et al. HLA-DR– , CD33+, CD56+, CD16– myeloid/ natural killer cell acute leukemia: a previously unrecognized form of acute leukemia potentially misdiagnosed as French- American- British acute myeloid leukemia M3. Blood 1994; 84: 244– 255.

9. Van Camp B, Durie BG, Spier C et al. Plasma cells in multiple myeloma express a natural killer cell-associated antigen: CD56(NKH- 1; Leu- 19). Blood 1990; 76: 377– 382.

10. Savoia P, Fierro MT, Novelli M et al. CD56- positive cutaneous lymphoma: a poorly recognized entity in the spectrum of primary cutaneous disease. Br J Dermatol 1997; 137: 966– 971.

11. Khoury JD, Medeiros LJ, Manning JT et al. CD56+ TdT+ blastic natural killer cell tumor of the skin: a primitive systemic malignancy related to myelomonocytic leukemia. Cancer 2002; 94: 2401– 2408.

12. Herling M, Teitell MA, Shen RR et al. TCL1 expression in plasmacytoid dendritic cells (DC2s) and the related CD4+ CD56+ blastic tumors of skin. Blood 2003; 101: 5007– 5009.

13. Feuillard J, Jacob MC, Valensi F et al. Clinical and biologic features of CD4+CD56+ malignancies. Blood 2002; 99: 556– 1563.

14. Kazakov DV, Mentzel T, Burg G et al. Blastic natural killer- cell lymphoma of the skin associated with myelodysplastic syndrome or myelogenous leukaemia: a coincidence or more? Br J Dermatol 2003; 149: 869– 876.

15. Garnache- Ottou F, Chaperot L, Biichle Set al. Expression of the myeloid-associated marker CD33 is not an exclusive factor for leukemic plasmacytoid dendritic cells. Blood 2005; 105:1256– 1264.

16. Petrella T, Comeau MR, Maynadié M et al. “Agranular CD4+ CD56+ hematodermic neoplasm “ (blastic NK- Cell lymphoma) originates from a population of CD56+ precursor cells related to plasmacytoid monocytes. Am J Surg Pathol 2002; 26: 852– 862.

17. Herling M, Teitell MA, Shen RR et al. TCL1 expression in plasmacytoid dendritic cells (DC2s) and the related CD4+ CD56+ blastic tumors of skin. Blood 2003; 101: 5007– 5009.

18. Ko YH, Kim SH, Park K et al. CD4+CD56+CD68+ hematopoietic tumor of probable plasmacytoid monocyte derivation with weak expression of cytoplasmic CD3. J Korean Med Sci 2002; 17: 833– 839.

19. Trimoreau F, Donnard M, Turlure P et al. The CD4+ CD56+ CD116– CD123+ CD45RA+ CD45RO– profile is specific to DC2 malignancies. Haematologica 2003; 88: ELT10.

20. Meyer N, Petrella T, Poszepczynska- Guigné E et al. CD4+ CD56+ blastic tumor cells express CD101 molecules. J Invest Dermatol 2005; 124: 668– 669.

21. Urosevic M, Conrad C, Kamarashev J et al. CD4+ CD56+ hematodermic neoplasms bear a plasmacytoid dendritic cell phenotype. Hum Pathol 2005; 36: 1020– 1024.

22. Leroux D, Mugneret F, Callanan M et al. CD4+, CD56+ DC2 acute leukemia is characterized by recurrent clonal chromosomal changes affecting 6 major targets: a study of 21 cases by the Groupe Francais de Cytogénétique Hématologique. Blood 2002; 99: 4154– 4159.