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Year : 2015  |  Volume : 58  |  Issue : 1  |  Page : 72-76
Blastic plasmacytoid dendritic cell neoplasm: Report of two pediatric cases

Hematopathology Laboratory, Cytogenetics Department, Tata Memorial Hospital, Mumbai, India

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Date of Web Publication11-Feb-2015


Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare subtype of acute leukemia that typically follows a highly aggressive clinical course in adults, whereas experience in children with this disease is very limited. We report cases of two children in whom bone marrow showed infiltration by large atypical monocytoid 'blast-like' cells which on immunophenotyping expressed CD4, CD56, HLA-DR and CD33 while were negative for CD34 other T-cell, B-cell and myeloid markers. The differential diagnoses considered were AML, T/NK-cell leukemia and acute undifferentiated leukemia. Additional markers CD303/BDCA-2 and CD123 which are recently validated plasmacytoid dendritic cell markers were done which helped us clinch the diagnosis of this rare neoplasm. An accurate diagnosis of BPDCN is essential in order to provide prompt treatment. Due to its rarity and only recent recognition as a distinct clinicopathological entity, no standardized therapeutic approach has been established for BPDCN.

Keywords: Blastic plasmacytoid dendritic cell neoplasm, CD123, CD303/BDCA-2, pediatric

How to cite this article:
Dharmani PA, Mittal NM, Subramanian P G, Galani K, Badrinath Y, Amare P, Gujral S. Blastic plasmacytoid dendritic cell neoplasm: Report of two pediatric cases. Indian J Pathol Microbiol 2015;58:72-6

How to cite this URL:
Dharmani PA, Mittal NM, Subramanian P G, Galani K, Badrinath Y, Amare P, Gujral S. Blastic plasmacytoid dendritic cell neoplasm: Report of two pediatric cases. Indian J Pathol Microbiol [serial online] 2015 [cited 2021 Oct 19];58:72-6. Available from: https://www.ijpmonline.org/text.asp?2015/58/1/72/151193

   Introduction Top

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy characterized by the clonal proliferation of immature precursors of plasmacytoid dendritic cells (pDCs). [1] The term "BPDCN" was introduced in 2008 by the updated World Health Organization (WHO) classification. The few available data reported indicating that its overall incidence is extremely low, accounting for 0.44% of all hematologic malignancies. Moreover, the leukemic form of the disease is rare, representing <1% of cases of acute leukemia. [2] Most patients are elderly with median age at diagnosis of 61-67 years. [1] Pediatric experience with BPDCN is further limited, with only a few case reports described in the literature. We discuss the clinicopathological features of BPDCN in pediatric patients and emphasize the importance of accurate flow cytometric immunophenotypic analyses (IPA).

   Case Reports Top

Case 1

A 12-year-old girl presented with 2 months history of swelling over right arm of measuring 3 cm × 2 cm, it was firm and nontender, slightly mobile but fixed to the overlying skin. Magnetic resonance imaging of the swelling was suggestive of soft-tissue sarcoma. Needle biopsy was reported outside as non-Hodgkin lymphoma - T lymphoblastic type (detailed immunophenotype was not available). Routine investigations at our center showed hemoglobin (Hb) of 113 g/L, total white blood cell count (WBC) of 21.4 × 10 9 /L and platelet count of 311 × 10 9 /L with occasional blast-like-cell in peripheral smear (PS). Bone marrow (BM) aspirate revealed 80% large atypical monocytoid blast-like cells [Figure 1]. Cytochemical myeloperoxidase (MPO) and nonspecific esterase (NSE) stains were negative. Sample was processed for flow cytometric IPA by lyse-stain-wash method. Tumor cells were dim positive for CD45 (blast region) along with CD33, HLA-DR, CD4, CD56, while were negative for specific markers for myeloid including monocytic (CD13, CD117, antiMPO, CD14), T-cells (CD7, CD3, CD2, CytoCD3), B-cells (CD19, CD20, Cyto79a) and CD34. On reviewing literature, for tumors with CD4 and CD56 co-positivity, additional markers were done. CD303 (BD, clone AC144), which is a specific marker for BPDCN was positive (strong-positive) in these malignant cells along with CD123 (BD, clone 7G3) and CD43 [Figure 2]. Together these findings fulfilled the requirements for the diagnosis of BPDCN. Computed tomography (CT)-scan showed enlarged mediastinal, abdominal lymph nodes with bilateral pleural effusion and hepatosplenomegaly. Lactate dehydrogenase levels were marginally increased to 209 IU/L (48-115 IU/L). Pleural fluid cytology showed involvement by the tumor cells. Fluorescent in-situ hybridization (FISH) studies showed duplication of 13q14 locus and deletion of 13q34, monosomy 9. Conventional cytogenetics was not done. Patient was started on BFM-90 protocol. Postinduction BM was in remission. Fifteen months later, patient presented to the emergency department with fever and neurological symptoms. Investigations showed BM and central nervous system relapse of BPDCN and she succumbed to the disease.
Figure 1: Bone marrow aspirate showed 80% large-sized monocytoid blast-like cells and suppression of normal hematopoiesis (Wright's stain, × 100)

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Figure 2

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Case 2

A 17-year-old girl presented with a preauricular swelling of 3 cm × 2 cm in size. It was firm and nontender. Her hemogram showed Hb - 98 g/L, WBC count - 3.2 × 109/L and platelet count - 267 × 109/L. PS did not show any atypical cells. Biopsy of the swelling was reported as high-grade hematolymphoid malignancy. CT-scan showed enlarged axillary nodes, nodular lesions in breasts and abdominal wall nodules. BM showed infiltration by 72% atypical large-sized monocytoid cells, which were negative for cytochemical MPO [Figure 3] and [Figure 4]. On IPA, gated tumor cells expressed only CD4, CD56, HLA-DR while were negative for other T-cell, B-cell and myeloid markers and CD34. However, CD303, CD123 and CD43 were positive in tumor cells thus confirming a diagnosis of BPDCN. FISH studies showed no aberrations of chromosome 5, 7, 8 and no IgH translocation. Conventional cytogenetics was not done. Patient was started on BFM-90 protocol. Postinduction BM was in remission. Five months later, while on therapy, patient had a BM relapse and succumbed to the disease.
Figure 3: Bone marrow aspirate showed atypical large-sized monocytoid cells and suppression of normal hematopoiesis (Wright's stain, ×100)

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Figure 4: Cytochemical stain for myeloperoxidase (MPO) was negative in these atypical monocytoid cells. Myelocyte is an internal positive control (MPO stain, ×100)

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   Discussion Top

Blastic plasmacytoid dendritic cell neoplasm is recently classified among "acute myeloid leukemia (AML) and related precursor neoplasms" in the 2008 WHO classification. [1]

Blastic plasmacytoid dendritic cell neoplasm was earlier called as blastic NK-cell lymphoma, agranular CD4 NK-cell leukemia, agranular CD4, and 56 positive hematodermic neoplasm. [1],[3] It involves the skin followed by BM and lymph nodes. [1]

The ontogeny of these disorders was not clearly identified. However, recent studies showed that these leukemic cells are derived from precursors of pDCs. [1],[2] CD4+CD56+ leukemia could be considered as the malignant counterpart of normal pDCs. [3],[4]

Blastic plasmacytoid dendritic cell neoplasm has a reported elderly male/female ratio of 3.3:1. [1] Its occurrence in pediatric age group is much rarer. [5] Cutaneous and BM involvement is common at diagnosis with reported frequency of 76-80% and 80%, respectively. [3] The skin lesions are usually asymptomatic, in the form of nodules, plaques or bruises. [5]

Morphologically, our cases showed large-sized monocytoid blast-like-cells as reported in literature. [6] Based on morphologic features and cutaneous involvement, the usual differential diagnoses include leukemia cutis (acute lymphoblastic leukemia [ALL], AML or undifferentiated leukemia), cutaneous T-cell lymphoma, and extranodal NK/T-cell lymphoma, nasal-type etc. To differentiate between these entities, an extensive panel of markers is required. [7] On immunophenotyping in our cases, tumor cells expressed dim positivity for CD45 and low SSC (i.e., blast, hematogones, basophils, hypogranular myeloid precursors are usually seen in this region). Tumor cells were positive for CD4, CD56, HLA-DR and CD33. Differential diagnosis considered are AML with monocytic differentiation, AML with minimal differentiation, acute undifferentiated leukemia, NK-cell lymphoma/leukemia. NK-cell lymphoma/leukemia may be considered in cases that express CD56 along with T-associated markers such as CytoCD3 (epsilon-chain) CD7, CD2, CD4 and CD8 dual negative, provided that it lacks B-cell and myeloid markers. AML with minimal differentiation will usually show a fraction of blasts to be positive for cytoplasmic-MPO. Blasts in AML with monocytic differentiation are NSE positive and express at least two monocytic markers like CD64 and CD14. [1] Thus, these differential diagnosis were ruled out. However, to confirm a diagnosis of BPDCN, newer and specific markers such as CD303, T-cell leukemia 1 (TCL1), CD304 and CLA are now available. Of these, CD303 is a novel type-II C-type lectin is the most specific marker for pDCs. [8] Additional panel in both cases showed strong co-expression of CD303 and CD123. Garnache-Ottou et al. studied expression of markers like CD123 and CD303 expression by flow cytometry in 16 cases of typical BPDCN, 4 of atypical BPDCN and 79 of other acute leukemia. They found CD303 expression in 12/16 (75%) cases of typical BPDCN, 2/4 (50%) cases of atypical BPDCN; it was negative in all other leukemia, thus concluding that CD303 expression by leukemic cells favor a diagnosis of BPDCN. Garnache-Ottou et al. proposed an algorithm for the diagnosis of BPDCN. The authors propose that when leukemic cells exhibit the CD4+, CD56+/ - , CD11c - , MPO - , cCD3 - , cCD79a - immunoprofile along with CD123+ expression, then BDCA2/CD303 and/or BDCA4 positivity confirms the diagnosis of BPDCN. [5] Thus, CD303 and CD123 strong-positivity in our cases confirmed the diagnosis of BPDCN. Garnache-Ottou et al. also observed expression of CD33 (myeloid marker) in cases of BPDCN like in one of our cases. [9] These markers can be done on immunohistochemistry as well. [3],[10]

Blastic plasmacytoid dendritic cell neoplasm may be suspected from a set of converging features from the clinical presentation and histological findings, but overlaps with other hematologic neoplasms are considerable, and the final diagnosis relies on a compatible immunophenotype. The triple positive CD4+CD56+CD123+ phenotype associated with negativity for lineage-specific markers is a minimum requirement for defining BPDCN. In addition, the highly specific marker BDCA2/CD303, as well as other pDC-associated antigens (e.g., TCL1 and CD2AP), might be of great support for establishing the diagnosis.

Cytogenetic studies have shown that two-thirds of patients with BPDCN have an abnormal karyotype. [1] Although specific aberrations are lacking but complex aberrations are common. [1],[7],[10] Six major recurrent chromosomal abnormalities are recognized including 5q21 or 5q34, 12p13, 13q13-21, 6q23-qter, 15q and loss of chromosome 4, 9 and 13. [1],[10] FISH studies performed on one of our patients showed duplication of 13q14 locus, deletion of 13q34 and monosomy 9 as mentioned in the literature. [10]

Due to its rarity and only recent recognition as a distinct clinicopathological entity, no standardized therapeutic approach has been established for BPDCN. Reimer et al. published the one of the most comprehensive study on the treatment of BPDCN. They studied 91 previously published cases. The authors concluded that, with a median survival of 13 months and generally poor prognosis, high dose chemotherapy/radiotherapy followed by allogenic stem cell transplantation (SCT) in first remission offered the highest curative potential. [11] In the most recent multicentric study, Pagano et al. showed superiority of ALL/lymphoma-type therapy with regards to complete remission rate and better survival. [2] Jegalian et al. showed that children treated with high-risk ALL-type therapy had favorable outcomes, irrespective of SCT. [3] In contrast to the literature, both our patients received high-risk ALL-like-therapy but had a poor outcome and died within few months of starting therapy. SCT could not be performed in our patients due to financial constraints.

   Conclusion Top

Blastic plasmacytoid dendritic cell neoplasm is rare and may be misdiagnosed as AML, T/NK cell leukemia or else as undifferentiated leukemia, due to lack of awareness of this entity and/or unavailability of specific markers. The expression of CD4, CD56, and CD123 along with a specific marker like CD303 in the absence of T-cell, B-cell, or myeloid markers defines BPDCN. It is important to recognize this entity, due to differing the prognosis as compared to other blastic neoplasms. Despite an excellent initial response to cytostatic therapy, overall prognosis remains poor.

   References Top

Faccheti F, Jones DM, Petrella T. Blastic plasmacytoid dendritic cell neoplasm. In:, editors. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC Press; 2008. p. 145-7.  Back to cited text no. 1
Pagano L, Valentini CG, Pulsoni A, Fisogni S, Carluccio P, Mannelli F, et al. Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation: An Italian multicenter study. Haematologica 2013;98:239-46.  Back to cited text no. 2
Jegalian AG, Buxbaum NP, Facchetti F, Raffeld M, Pittaluga S, Wayne AS, et al. Blastic plasmacytoid dendritic cell neoplasm in children: Diagnostic features and clinical implications. Haematologica 2010;95:1873-9.  Back to cited text no. 3
Garnache-Ottou F, Feuillard J, Ferrand C, Biichle S, Trimoreau F, Seilles E, et al. Extended diagnostic criteria for plasmacytoid dendritic cell leukaemia. Br J Haematol 2009;145:624-36.  Back to cited text no. 4
Garnache-Ottou F, Feuillard J, Saas P. Plasmacytoid dendritic cell leukaemia/lymphoma: Towards a well defined entity? Br J Haematol 2007;136:539-48.  Back to cited text no. 5
Bueno C, Almeida J, Lucio P, Marco J, Garcia R, de Pablos JM, et al. Incidence and characteristics of CD4(+)/HLA DRhi dendritic cell malignancies. Haematologica 2004;89:58-69.  Back to cited text no. 6
Rossi JG, Felice MS, Bernasconi AR, Ribas AE, Gallego MS, Somardzic AE, et al. Acute leukemia of dendritic cell lineage in childhood: Incidence, biological characteristics and outcome. Leuk Lymphoma 2006;47:715-25.  Back to cited text no. 7
Pilichowska ME, Fleming MD, Pinkus JL, Pinkus GS. CD4+/CD56+ hematodermic neoplasm ("blastic natural killer cell lymphoma"): Neoplastic cells express the immature dendritic cell marker BDCA-2 and produce interferon. Am J Clin Pathol 2007;128:445-53.  Back to cited text no. 8
Garnache-Ottou F, Chaperot L, Biichle S, Ferrand C, Remy-Martin JP, Deconinck E, et al. Expression of the myeloid-associated marker CD33 is not an exclusive factor for leukemic plasmacytoid dendritic cells. Blood 2005;105:1256-64.  Back to cited text no. 9
Lucioni M, Novara F, Fiandrino G, Riboni R, Fanoni D, Arra M, et al. Twenty-one cases of blastic plasmacytoid dendritic cell neoplasm: Focus on biallelic locus 9p21.3 deletion. Blood 2011;118:4591-4.  Back to cited text no. 10
Reimer P, Rüdiger T, Kraemer D, Kunzmann V, Weissinger F, Zettl A, et al. What is CD4+CD56+ malignancy and how should it be treated? Bone Marrow Transplant 2003;32:637-46.  Back to cited text no. 11

Correspondence Address:
Dr. Preeti Ashok Dharmani
4b/9, Juhu Sangeeta Apartments, Juhu Road, Juhu, Mumbai - 400 049, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.151193

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

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