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Year : 2015  |  Volume : 58  |  Issue : 3  |  Page : 377-380
Blastic plasmacytoid dendritic cell neoplasm presenting as leukemia without cutaneous involvement in a 25 years male patient: Unusual presentation of a rare entity

1 Department of Pathology, HIMS, Lucknow, Uttar Pradesh, India
2 Department of Pathology, RGCIRC, New Delhi, India
3 Department of Hematology, SGPGI, Lucknow, Uttar Pradesh, India

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Date of Web Publication14-Aug-2015


Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive neoplasm classified under "acute myeloid leukemia (AML) and related precursor neoplasm" by current WHO classification. Elderly male are commonly affected with cutaneous lesion being the hallmark of disease presentation. The disease progresses rapidly and sooner or later involves bone marrow and peripheral blood. Cases presenting primarily as leukemia without cutaneous involvement is a rarity with about 29 cases reported in literature till date. Characteristic immunophenotype of CD4 + /CD56 +/− cells expressing antigens associated with plasmacytoid dendritic cells like CD123, TCL1, BDCA2/CD303, cutaneous lymphocyte-associated and interferon dependent molecule MxA, in absence of any other lineage specific marker confirms the diagnosis. The disease has a poor survival and no standardized therapeutic strategy in the current scenario. A case of 25-year-male presenting with leukemic BPDCN without cutaneous involvement is presented here, who was treated with AML like protocol followed by hematopoietic stem cell transplantation, but succumbed to the disease within 8 months of diagnosis. The present case is being first to be reported from India.

Keywords: Blastic plasmacytoid dendritic cell neoplasm, flow cytometry, plasmacytoid dendritic cell leukemia

How to cite this article:
Qayoom S, Durga G, George S, Rahman K. Blastic plasmacytoid dendritic cell neoplasm presenting as leukemia without cutaneous involvement in a 25 years male patient: Unusual presentation of a rare entity. Indian J Pathol Microbiol 2015;58:377-80

How to cite this URL:
Qayoom S, Durga G, George S, Rahman K. Blastic plasmacytoid dendritic cell neoplasm presenting as leukemia without cutaneous involvement in a 25 years male patient: Unusual presentation of a rare entity. Indian J Pathol Microbiol [serial online] 2015 [cited 2022 Jan 22];58:377-80. Available from: https://www.ijpmonline.org/text.asp?2015/58/3/377/162912

   Introduction Top

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, clinically aggressive neoplasm derived from precursors of plasmacytoid dendritic cells (also known as professional type 1 interferon producing cells or plasmacytoid monocytes. [1] In the current WHO classification, it has been categorized under "acute myeloid leukemia (AML) and related precursor neoplasm." It occurs usually in elderly population with a median age of 61-67 yrs at diagnosis and a male preponderance with an M:E ratio of 3:1. But it can affect any age including the children. [2] The clinical hallmark is presence of cutaneous lesion at time of presentation that is seen in almost all cases. Some cases without skin manifestation at the time of diagnosis have been reported. [3] In flow cytometry, these cells are characterized by low side scatter, CD45 dim, CD4 + , CD56 + / profile accompanied by expression of one or more markers of plasmacytoid dendritic cells, in absence of any lineage specific marker. Due to the rarity of this entity there is no standardized therapeutic approach, with some cases been treated like AML while other like acute lymphoblastic leukemia/lymphoma (ALL) protocol. [4] Despite an initial response to therapy, the disease invariably relapses with a median overall survival of 12-14 months. [5] We report here such an uncommon case of BPDCN in a young patient with primary leukemic involvement without cutaneous manifestation along with a brief literature review.

   Case Report Top

A 25-year-male presented with 10 days history of fever, anorexia, and occasional epistaxis. Examination revealed pallor, some purpuric spots, hepatomegaly of 2 cm and just palpable spleen. No lymph node or cutaneous lesion was identified. Complete blood count showed hemoglobin of 86 g/L, white blood cell of 18.5 × 10 9 /L and platelets of 32 × 10 9 /L. Peripheral blood examination showed normocytic normochromic anemia, thrombocytopenia and presence of 65% blasts. These blasts were medium sized, with a high N:C ratio, scant cytoplasm, fine chromatin with the occasional presence of nucleoli [Figure 1]. Immunophenotypic analysis by flow cytometry using a four-color panel showed presence of 68% blasts in dim CD45 and low side scatter region. These were positive for CD4, CD56, CD123 and HLADR; while negative for CD19, CD10, CD20, CD3, CD5, CD8, CD7, CD11c, CD13, CD33, CD64, Cyt CD3, myeloperoxidase (MPO), Cyt CD79a [Figure 2]. Bone marrow examination showed proliferation of similar type of blasts with suppression of normal hematopoiesis. Conventional karyotype showed 46,XY genotype. Based on the above findings, a diagnosis of leukemic BPDCN (plasmacytoid dentritc cell leukemia [PDCL]), was put forth.
Figure 1: Microphotograph: Smears show blasts, having a high N:C ratio, scant bluish gray cytoplasm without any granules. These blasts are negative for myeloperoxidase (MPO) (Leishman oil immersion, MPO stain)

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Figure 2: Flow cytometric immunophenotyping showed approximately 68% cells in dim CD45 low side scatter region. These cells are positive for CD56, CD4, CD123, and HLADR, while being negative for CD34, CD19, Cyt CD79a, myeloperoxidase, CD5. These were also negative for CD3, CD8, CD7, CD11c, CD13, CD33, CD20, CD10, CD33, CD117, cyt CD3, CD41a (not shown in figure). Features suggest a diagnosis of blastic plasmacytoid dendritic cell neoplasm

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The plan of management was to induce the patient with standard "3 + 7" AML oriented therapy followed by hematopoietic stem cell transplantation (HSCT) in the very first complete remission. Postinduction marrow was in the morphological remission and showed trilineage hematopoiesis. Due to unavailability of donor at that time, first consolidation chemotherapy was administered. It was followed by a related haplo-transplant as full match was not available. Posttransplant period was complicated by febrile neutropenia and hepatosplenic candidiasis. After the initial features of graft uptake, the patient presented on Day +38 of transplant with generalized weakness and evaluation showed pancytopenia. Bone marrow aspiration and biopsy was hypo cellular. Chimerism showed graft rejection. Two weeks later the patient showed disease relapse and finally succumbed to illness in another 1½ months.

   Discussion Top

Blastic plasmacytoid dendritic cell neoplasm was reported for 1 st time in 1994 and was described as a CD4-positive cutaneous lymphoma with high expression of CD56. [6] Earlier it was known with different names like blastic natural killer leukemia/lymphoma, agranular CD4 + CD56 + hematodermic neoplasm, and agranular CD4 positive natural killer cell leukemia. The current WHO classification has categorized it in the "AML and related precursor neoplasm" group. The proposed cell of origin has been found to be precursors of plasmacytoid dendritic cells.

This is a rare entity with an overall incidence of 0.44% of all hematological neoplasm. [7] Most of the patients are elderly and show a male preponderance with a male:female ratio of 3:1. They usually present with asymptomatic skin nodules and plaques and invariably progress to acute leukemia. [8] After an extensive literature search, we could find 29 such cases in English literature. A brief overview is presented in [Table 1]. [4] The present case is an addition to this small group and first case report from India. The patient had two unique features, first being a young patient and second having no cutaneous lesion at presentation or during the course of the disease.
Table 1: Blastic plasmacytoid dendritic cell neoplasm with the primary leukemic presentation without cutaneous involvement

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Morphologically, the leukemic cells are medium sized and have immature blastic appearance or can be pleomorphic. [1],[8] These usually have a high N:C ratio with irregular nuclei, fine chromatin having one to several small nucleoli, scant cytoplasm that is gray blue and agranular. These may show cytoplasmic microvaoules localized along the cell membrane and pseudopodia. Immunophenotypically, these cells are positive for CD4, CD56 CD43, CD45RA along with antigens of plasmacytoid dendritic cells, such as CD123, TCL1, BDCA2/CD303, cutaneous lymphocyte-associated and interferon dependent molecule MxA. Expression of other lymphoid and myeloid associated antigens like CD7, CD2, TdT, CD68, CD33, CD36 and CD38 has also been seen. [1] The established PDCL immunophenotypic profile is based on CD4 and CD56 expression by CD45dim malignant cells that do not express myeloid, lymphoid B, T or NK lineage markers.However, due to the immunophenotypic heterogeneity and absence of CD56 in many reported cases, Garnache-Ottou et al. [9] performed a study aimed to validate PDCL-specific markers for diagnosis by flow-cytometry or quantitative reverse transcription polymerase chain reaction on bone marrow samples. They found BDCA2/CD303 to be the most specific marker for PDCL. Among the molecular markers, they found that high levels of LILRA4 and TCL1A transcripts distinguished PDCL from all other acute leukemia. They proposed a scoring system based on four parameters:

  1. A profile of CD4 + CD56 + /–, CD11c–, MPO–, cCD79a–, cCD3–, and expression of
  2. CD123,
  3. BDCA2/CD303 and
  4. BDCA4. Each of these parameters was given a score of 1 except CD303 expression that was given a score of 2 owing to its better specificity.

A score more than 2 was found to be definitive for the diagnosis of PDCL. However, Tsagarakis et al., [10] in a study of 22 cases of BPDCN concluded that a diagnosis of BPDCN can be safely made on flow cytometry with an aim of achieving CD4, CD56, HLADR and CD123 Hi expression on CD45 dim low side scatter population. In the present case, expression of BDCA2/CD303 and BDCA4 could not be evaluated due to unavailability of this antibody. But in view of strong triple positive profile of CD4/CD56/CD123 along with HLADR expression and absence of any lineage specific marker, this case was best regarded as PDCL.

A multidisciplinary approach involving hematology, pathology and stem cell transplant team is critical in managing PDCL owing to its rarity, unique presentation, and aggressive behavior.

Currently, there are no established consensus guidelines for the optimal therapeutic strategy. Both AML as well as ALL like treatment protocols have been used. Some studies have justified AML-like treatment while others have shown better outcomes with ALL like therapy. [4],[10] A majority of patients initially respond favorably; however, this response is short-lived and relapses occur within 9-11 months, on average, with median length of survival being 38 months for patients <40 years and only 10 months for those >40 years in age. [5 In a multicenter trial by Pagano et al., [4] patients treated with ALL like therapy showed a better rate of complete remission, but the relapse rate was also subsequently higher in these patients. Median overall survival was 7.1 months (range, 0.2-19.5) in patients treated with an AML-type regimen and 12.3 months (range, 1-32.9) in those treated with an ALL/lymphoma-type regimen. Based on their observation of higher incidence of relapse and knowing the myeloid lineage derivation of blastic dendritic cells, they suggested that the addition of myeloid based strategies could be useful especially in patient who were to undergo HSCT. Central nervous system (CNS) involvement is seen in a fair number of cases and warrant for preventive intrathecal therapy in the management, as CNS may act as a sanctuary site in these cases. [4] Role of HSCT in the management of these patients is justified by compelling evidences from some studies. Pagano et al. [4] showed an overall survival of 22.7 (range, 12-32.9) months in allogeneic HSCT recipients which was significantly higher with respect to nontransplanted patients (median 7.1 months; range, 0.2-21.3). Our patient was treated with AML like protocol followed by HSCT. But, after an initial response patient showed a loss of chimerism, disease relapse and subsequently succumbed to the disease, suggesting an overall poor prognosis.

   Conclusion Top

Primary leukemic involvement of BPDCN (PDCL) without cutaneous involvement is a rare occurrence. The clinical course is aggressive with poor outcome. A deligent immunophenotypic analysis with an extensive panel of antibodies is required to characterize this disease. High-dose chemotherapy with HSCT in first complete remission should be considered for a better survival of these patients.

   References Top

Facchetti F, Jones D, Petrella T. Blastic plasmacytoid dendritic cell neoplasm. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H et al., editors. WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues. Lyon: IARC Press; 2008. p. 145-7.  Back to cited text no. 1
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. 2
Paluri R, Nabell L, Borak S, Peker D. Unique presentation of blastic plasmacytoid dendritic cell neoplasm: A single-center experience and literature review. Hematol Oncol 2014.  Back to cited text no. 3
Pagano L, Valentini CG, Pulson A, Fisogni S, Carluccio P, Manelli F et al. Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation: An Italian multicenter study. Hematologica 2013;98:239-46.  Back to cited text no. 4
Petrella T, Bagot M, Willemze R, Beylot-Barry M, Vergier B, Delaunay M, et al. Blastic NK-cell lymphomas (agranular CD4+CD56+ hematodermic neoplasms): A review. Am J Clin Pathol 2005;123:662-75.  Back to cited text no. 5
Adachi M, Maeda K, Takekawa M, Hinoda Y, Imai K, Sugiyama S, et al. High expression of CD56 (N-CAM) in a patient with cutaneous CD4-positive lymphoma. Am J Hematol 1994;47:278-82.  Back to cited text no. 6
Bueno C, Almeida J, Lucio P, Marco J, Garcia R, de Pablos JM, et al. Incidence and characteristics of CD4(+)/HLADR hi dendritic cell malignancies. Haematologica 2004;89:58-69.  Back to cited text no. 7
Fachetti F. Blastic plasmacytoid dendritic cell neoplasm. In: Jaffe E, Harris NL, Vardiman JW, Campo E, Arber DA, editors. Hematopathology. Philadelphia, PA, USA: Saunders; 2011. p. 788-98.  Back to cited text no. 8
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. 9
Tsagarakis NJ, Kentrou NA, Papadimitriou KA, Pagoni M, Kokkini G, Papadaki H, et al. Acute lymphoplasmacytoid dendritic cell (DC2) leukemia: Results from the Hellenic Dendritic Cell Leukemia Study Group. Leuk Res 2010;34:438-46.  Back to cited text no. 10

Correspondence Address:
Dr. Khaliqur Rahman
Department of Hematology, SGPGI, Raebareli Road, Lucknow - 226 014, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.162912

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  [Figure 1], [Figure 2]

  [Table 1]

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