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Blood, 1 March 2002, Vol. 99, No. 5, pp. 1556-1563
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Clinical and biologic features of
CD4+CD56+ malignancies
Jean Feuillard,
Marie-Christine Jacob,
Françoise Valensi,
Marc Maynadié,
Rémy Gressin,
Laurence Chaperot,
Christine Arnoulet,
Françoise Brignole-Baudouin,
Bernard Drénou,
Eliane Duchayne,
Annie Falkenrodt,
Richard Garand,
Emanuelle Homolle,
Bernard Husson,
Emilienne Kuhlein,
Geneviève Le Calvez,
Danielle Sainty,
Marie-France Sotto,
Franck Trimoreau, and
Marie-Christine Béné
From the Service d'Hématologie Biologique,
Hôpital Avicenne, Université Paris 13 Bobigny, France;
Laboratoire d'Immunologie Cellulaire, EFS Rhône-Alpes Grenoble,
La Tronche, France; Laboratoire Central d'Hématologie,
Hôpital Necker, Paris, France; Service d'Hématologie
Biologique, CHU Bocage, Dijon, France; Service d'Hématologie
Clinique, CHU Michallon, Grenoble, France; Laboratoire R et D, EFS
Rhône-Alpes Grenoble, La Tronche, France; Département de
Biologie, Unité d'Hématologie, Institut Paoli-Calmettes,
Marseille, France; Laboratoire d'Immuno-Hématologie,
Hôpital Ambroise Paré, Boulogne, France; Laboratoire
d'Hémato-Immunologie, Hôpital Pontchaillou, Rennes,
France; Laboratoire d'Hématologie et Laboratoire d'Immunologie
Cellulaire, Hôpital Purpan, Toulouse, France; Service de
Séro-Hématologie, Hôpital de Hautepierre, Strasbourg,
France; Laboratoire d'Hématologie, Institut de Biologie des
Hôpitaux, Nantes, France; Laboratoire d'Hématologie,
Hôpital Debrousse, Lyon, France; Laboratoire de Biologie
Clinique, Hôpital de Jolimont, Haine St Paul, Belgique;
Laboratoire d'Hématologie, CHU de Brest, Brest, France;
Laboratoire d'Hématologie, CHU Michallon, Grenoble, France;
Laboratoire d'Hématologie, CHU Dupuytren, Limoges, France; and
Laboratoire d'Immunologie, Faculté de Médecine and CHU de
Nancy, Vandoeuvre les Nancy, France.
CD4+CD56+ malignancies are rare hematologic
neoplasms, which were recently shown to correspond to the so-called
type 2 dendritic cell (DC2) or plasmacytoid dendritic cells. This study
presents the biologic and clinical features of a series of 23 such
cases, selected on the minimal immunophenotypic criteria defining the DC2 leukemic counterpart, that is, coexpression of CD4 and CD56 in the
absence of B, T, and myeloid lineage markers. Clinical presentation
typically corresponded to cutaneous nodules associated with
lymphadenopathy or spleen enlargement or both. Cytopenia was frequent.
Circulating malignant cells were often detected. Massive bone marrow
infiltration was seen in 20 of 23 (87%) patients. Most tumor cells
exhibited nuclei with a lacy chromatin, a blastic aspect, large
cytoplasm-containing vacuoles or microvacuoles beside the plasma
membrane, and cytoplasmic expansions resembling pseudopodia. Other
immunophenotypic characteristics included both negative (CD16, CD57,
CD116, and CD117) and positive (CD36, CD38, CD45 at low levels, CD45RA,
CD68, CD123, and HLA DR) markers. The prognosis was rapidly fatal in
the absence of chemotherapy. Complete remission was obtained in 18 of
23 (78%) patients after polychemotherapy. Most patients had a
relapse in less than 2 years, mainly in the bone marrow, skin, or
central nervous system. Considering these clinical and biologic
features, the conclusion is made that CD4+CD56+
malignancies constitute a genuine homogeneous entity. Furthermore, some
therapeutic options were clearly identified. Finally, relationships between the pure cutaneous indolent form of the disease and acute leukemia as well as with the lymphoid/myeloid origin of the
CD4+CD56+ malignant cell are discussed.
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