Blood Res 2014; 49(3): 198-200  https://doi.org/10.5045/br.2014.49.3.198
Leukemic manifestation of blastic plasmacytoid dendritic cell neoplasm: laboratory approaches in 2 cases
Sang Hyuk Park1,2, Hyun-Sook Chi3*, Young-Uk Cho3, Seongsoo Jang3, and Chan-Jeoung Park3

1Department of Laboratory Medicine, Pusan National University School of Medicine, Busan, Korea.

2Biomedical Research Institute, Pusan National University Hospital, Busan, Korea.

3Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.

Correspondence to: Correspondence to: Hyun-Sook Chi. Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, 88 Olympic-ro, 43-gil, Songpa-gu, Seoul 138-736, Korea. hschi@amc.seoul.kr
Received: April 15, 2014; Revised: May 25, 2014; Accepted: August 25, 2014; Published online: September 25, 2014.
© The Korean Journal of Hematology. All rights reserved.

cc This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
CASES

TO THE EDITOR: The blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare subtype of the myeloid neoplasm, with an incidence of 0.44% among all hematologic malignancies and characterized by clonal plasmacytoid dendritic cell presence [1, 2]. Patients with BPDCN typically display skin lesions and aggressive clinical features with rapid systemic dissemination, exhibiting bone marrow (BM) involvement in 60-90% of cases [3, 4]. However, leukemic presentation of BPDCN is rare, with a reported incidence of less than 1% among those with acute leukemia [5]. Moreover, BPDCN with leptomeningeal involvement has been reported to be more infrequent compared with lymph node or liver/spleen involvement, as only 4 of 43 BPDCN patients experienced cerebrospinal fluid (CSF) involvement in a large-scale multicenter study [1]. Herein, we report 2 patients with BPDCN who exhibited leukemic manifestation (1 with simultaneous leptomeningeal involvement) diagnosed by using immunohistochemical staining and flow cytometry analysis for CD4, CD56, and CD123.

The first case of BPDCN was observed in a 36-year-old woman who was admitted to the authors' institution for workup of a left cheek skin lesion that had developed 6 months previously. An incisional biopsy of the skin lesion demonstrated BPDCN with CD4, CD56, and CD123 positivity. Her hemogram results at admission were as follows: WBC count, 7.6×109/L; hemoglobin, 12.0 g/dL; and platelet count, 199.0×109/L. A peripheral blood smear showed no evidence of blasts, but BM aspiration revealed infiltration of neoplastic cells with oval to round nuclei, prominent nucleoli, and abundant bluish cytoplasm at a frequency of 27.8% among BM-nucleated cells (Fig. 1A). The BM clot section also showed neoplastic cell infiltration in an interstitial pattern (Fig. 1B) and positivity for CD4, CD56, and CD123 on immunohistochemical staining. Flow cytometry analysis also revealed positivity for both CD4 (22.7%) and CD56 (79.5%). Karyotype analysis results from the BM aspiration specimen demonstrated 46,XX, add(1) (p13),+del(1)(q21),del(6)(q21q23),add(8)(q24),-9,add(13)(q 34)[6]/46,XX[14], indicating a complex karyotype including monosomy 9. Based on these findings, the patient was diagnosed with a leukemic manifestation of BPDCN. She received chemotherapy based on a vincristine, prednisolone, dexamethasone, and L-asparagine (VPDL) regimen for 2 months and underwent stem cell transplantation from a sibling donor 4 months previously. She has been in complete remission with no evidence of relapse.

The second case of BPDCN was observed in a 49-year-old man who was admitted to the authors' institution because of a right inguinal lymph node mass that developed 3 years previously. The lymph node mass was reported as BPDCN with CD4, CD56, and CD123 positivity via an excisional biopsy. The patient received chemotherapy based on a VPDL regimen and achieved complete remission for 2 years. However, he experienced his first relapse 1 year previously and received autologous stem cell transplantation (ASCT) after 6 months; 2 months after ASCT, he developed a seizure-like movement for which he was readmitted. His hemogram results at readmission were as follows: WBC count, 6.4×109/L; hemoglobin, 14.7 g/dL; and platelet count, 78.0×109/L. A peripheral blood smear showed no evidence of blasts. However, BM aspiration showed neoplastic cell infiltration, with a frequency of 20.8%. BM biopsy revealed neoplastic cells in an interstitial pattern (Fig. 2A), with weak positivity for CD4 and strong positivity for CD56 on immunohistochemical staining (Fig. 2B). Flow cytometry analysis results also demonstrated positivity for both CD4 (49.4%) and CD56 (99.0%) antigens. His karyotype was 44,XY,del(4)(p16),del(5)(q31q35),del(6)(q23q27),der(8)add (8)(p11.2)add(8)(q24),-9,der(10)t(8;10)(q22;p13),der(12;14) (q10;q10),add(19)(p13.3),der(19)t(9;19)(q13;p13.3)[18]/44, XY,t(3;15)(q21;q24),del(4),add(5)(q35),del(6),der(8)add(8)a dd(8),-9,der(10)t(8;10)der(12;14),add(19)[4]/46,XY[3], indicating a complex chromosomal rearrangement. Based on these results, he was diagnosed with a leukemic manifestation of BPDCN. Simultaneously performed cytospin analysis of the CSF showed neoplastic cells with a frequency of 92.0% (Fig. 2C) and positivity for both CD56 and CD123 on immunocytochemical staining (Fig. 2D). He was diagnosed with leptomeningeal involvement of BPDCN. He was treated with intrathecal injections of high-dose cytarabine (40 mg) and methotrexate (15 mg) for 3 months, and he has been in complete remission for 4 months without evidence of residual disease.

DISCUSSION

Because markers are useful for confirming BPDCN, a recently performed multicenter study recommends immunohistochemical staining using 6 antigens, such as CD4 (positive in 94.6% of cases), CD56 (positive in 96.5% of cases), CD123 (positive in 95.3% of cases), TCL1 (positive in 89.3% of cases), CD2AP (positive in 80.5% of cases), and BDCA2/CD303 (positive in 75.0% of cases) [1]. As a single antigen does not exhibit positivity in all cases of BPDCN, immunohistochemical staining using at least the 3 antigens mentioned previously (CD4, CD56, and CD123), all of which possess higher positivity rates compared with other antigens, should be performed to confirm BPDCN to provide maximum sensitivity. Our 2 cases demonstrated positivity for all these 3 antigens, which is adequate evidence of BPDCN involvement. Given that leptomeningeal involvement in BPDCN is a rare phenomenon, our second patient, who developed simultaneous leukemic manifestation and leptomeningeal involvement of BPDCN, is a very rare case and worth being reported.

In conclusion, we report 2 cases of BPDCN exhibiting leukemic manifestation (1 with simultaneous leptomeningeal involvement) confirmed with positive CD4, CD56, and CD123 expression on immunohistochemical staining and flow cytometry. Immunohistochemical staining for CD4, CD56, and CD123 can confirm the BPDCN diagnosis, and it should be performed in all cases suspected of having BM involvement in BPDCN.

Figures
Fig. 1.

Bone marrow (BM) aspiration and biopsy findings in the first case. BM aspiration showed the presence of neoplastic cells (27.8%) with oval to round nuclei, prominent nucleoli, and abundant amount of bluish cytoplasm (A, Wright staining, ×1,000). The BM clot section also showed interstitial infiltration of neoplastic cells (B, hematoxylin and eosin staining, ×400) positive for CD4, CD56, and CD123 on immunohistochemical staining.


Fig. 2.

Findings obtained with bone marrow biopsy and cytospin analysis of the cerebrospinal fluid in the second case. The bone marrow biopsy demonstrated an infiltration of neoplastic cells (A, hematoxylin and eosin staining, ×400) with weak positivity for CD4 and strong positivity for CD56 (B, ×400) on immunohistochemical staining. Cytospin analysis of the cerebrospinal fluid showed neoplastic cells with at frequency of 92.0% (C, Wright staining, ×400); immunocytochemical staining for both CD56 and CD123 (D, ×400) demonstrated positive neoplastic cells.


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