A unique case of dendritic cell neoplasm from monocyte-derived myeloid origin with distinct immunophenotype and cytomorphology

Abstract

Dear Editor, Two distinct subsets of circulating dendritic cells (DCs) have been identified: myeloid (CD11cCD123) DCs and lymphoid or plasmacytoid (CD11cCD123) DCs [1]. Here, we demonstrate an unusual dendritic cell neoplasm presenting the acute leukemic phase, and thought to originate from monocyte-derived circulating myeloid DCs (mDC). A 69-year-old woman with a history of essential thrombocythemia was evaluated for fever and respiratory failure. The patient was diagnosed 11 years earlier and was treated at varying intervals with hydroxyurea. A computed tomography scan demonstrated hepatosplenomegaly with multiple lymphadenopathy. A few days later, cytopenia had progressed: white blood cell count, 8.8×10/L; hemoglobin, 9.0 g/dL; and platelet count, 34×10/L. In a peripheral blood smear, 25 % of the lymphoid cells were medium to large and had irregular nuclear outlines, indistinct nucleoli, basophilic cytoplasm, minimal granules, and some membrane protrusions (Fig. 1a). Flow cytometry showed a CD45 population expressing CD4 and CD56. There was no B cell, T cell, or myeloid expression except for CD2 and CD11c (partial), and no expression of CD34, terminal deoxynucleotidyl transferase or killer cell immunoglobulin-like receptors on natural killer (NK) cells. The cells diffusely infiltrated the bone marrow (Fig. 1b). Immunohistochemistry was positive for CD56, but negative for CD123 and myeloperoxidase (Fig. 1c, d). Diffuse bone marrow fibrosis was evident by reticulin and Masson’s trichrome stains (Fig. 1e, f). Based on these features, the cells were considered to most likely be monocyte-derived mDCs. Infectious pathogens which have been linked to the genesis of hematologic malignancy, such as Epstein–Barr virus and human T cell lymphotropic virus type I, were excluded. The karyotype showed complex structural and numerical abnormalities, 45,XX,+1,dic(1;15)(p13;q22),-16,-19,+mar1[15]/45,sl,13,+mar2 [5]. The patient’s condition rapidly worsened during her hospital stay. Marked leukocytosis (144×10/L) with abnormal cells (72 %) was noted in peripheral blood. Despite first cycle chemotherapy, she expired due to respiratory failure combined with septic shock after only 3 weeks of hospitalization. Two DC subsets can arise from common hematopoietic stem cells in the bone marrow; however, mDCs and plasmacytoid DCs (pDCs) are phenotypically and functionally different. mDCs are monocytoid in appearance with a characteristically hyperlobulated nucleus and express myeloidassociated antigens, whereas pDCs possess a more rounded morphology with an oval nucleus and express lymphoidassociated antigens [1]. Both DC subsets are potent stimulators of allogeneic lymphocytes, but mDCs predominantly prime a T helper type I cell antimicrobial response, whereas pDCs seem to support the generation of a T helper type II cell response [2]. Furthermore, mDCs are known to have a higher capacity for antigen uptake and presenting capacity than pDCs [1]. Other immunophenotypic markers including CD2 and CD7 have been used to further classify circulating DC subsets. Strong CD2 expression has been suggested to define mDC differentiation from monocyte precursors [3] and CD7 and CD56 coexpression may be a very useful marker for discrimination monocyte-derived mDCs from NK cells [4, 5]. In summary, this case suggests that a circulating myeloid DC subset could alsomanifest as leukemiawith an aggressive clinical course. However, these cells have a distinct immunophenotype M.<A. Jang : S.<T. Lee : S.<H. Kim (*) Department of LaboratoryMedicine and Genetics, SamsungMedical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, South Korea e-mail: drsunnyhk@gmail.com