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CASE REPORT
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Blastic plasmacytoid dendritic cell neoplasm: A clinicopathological diagnostic dilemma report of three cases with review of literature


1 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
2 Department of Laboratory Oncology, All India Institute of Medical Sciences, New Delhi, India
3 Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India

Date of Submission14-Apr-2020
Date of Decision01-Jun-2020
Date of Acceptance20-Oct-2020
Date of Web Publication20-Aug-2021

Correspondence Address:
Saumyaranjan Mallick,
Department of Pathology, All India Institute of Medical Sciences, New Delhi - 110 029
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_420_20

 > Abstract 


Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a highly aggressive hematologic neoplasm and classified under acute myeloid leukemia. Here, we describe the clinicopathological features of three cases of BPDCN: two with classical and one uncommon immunophenotype. A-35-year-old female (case 1) presented with complaint of nasal mass and generalized lymphadenopathy. Biopsy from axillary lymph node showed infiltration by cells with scant cytoplasm which were immunopositive for LCA, CD4, CD43, and ALK1. Flowcytometry showed positivity for CD45, CD4, CD33, and CD123 while negative for rest all markers. The other two cases have classical immunophenotype. In clinical practice, nasal mass with lymphadenopathy suggests natural killer T-cell/peripheral T-cell lymphoma. Again immunohistochemical positivity for CD4, CD43, and ALK while negativity for CD3 suggests anaplastic large cell lymphoma. In this case, morphology and extensive bone marrow involvement raise the suspicion. Fowcytometry positivity for HLADR, CD123, and CD33 helps in making diagnosis.

Keywords: Acute leukaemia, blastic plasmacytoid dendritic cell neoplasm, CD56



How to cite this URL:
Purkait S, Gupta S, Bakhshi S, Mallick S. Blastic plasmacytoid dendritic cell neoplasm: A clinicopathological diagnostic dilemma report of three cases with review of literature. J Can Res Ther [Epub ahead of print] [cited 2021 Nov 28]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=324166




 > Introduction Top


Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and highly aggressive hematologic neoplasm accounting for <1% of all hematologic malignancies.[1] Initially, it thought to be of natural killer (NK)-cell lineage, hence, named as blastic NK cell lymphoma or CD4+/CD56+ hematodermic neoplasm. However, in 2008, it was classified under acute myeloid leukemia (AML) and related precursor neoplasms. With understanding of the disease biology, BPCDN now is a separate entity under AML in the current 2016 classification.[1],[2],[3] According to the Surveillance, Epidemiology, and End Results database, the incidence BPCDN is 0.04 cases per 100,000 population with a bimodal distribution.[4] According to Japanese study, BPCDN constitutes 1.9% of all skin malignancies.[5] It predominantly affects the elderly individuals, and skin involvement is the most prominent clinical feature which includes isolated, confined, or generalized plaques or nodules.[1],[2],[6] Which is often followed by rapid progression to systemic involvement and death within 1 year.[7] Approximately 10%–20% of BPDCN cases are accompanied by, or can progress to, AML. The treatment options are controversial, and the outcome is dismal with a median survival of only 12–16 months.[8] Accurate diagnoses of BPDCN can be difficult to achieve due to its clinical and biological heterogeneity, as well as its overlapping features with other hematologic malignancies. Here, we describe three cases of BPDCN in the younger adult age group with relatively uncommon clinical presentation.


 > Case Report Top


A 35-year-old female (case 1) presented with a 3-month history of a persistent nasal blockage. Positron emission tomography (PET) scan revealed nasal mass, cervical, abdominal, axillary, and mediastinal lymphadenopathy. There is mild hepatomegaly. The complete blood count showed pancytopenia; Hb = 9 g/dl, TLC = 3300/mm3, and platelet = 70,000/mm3. Axillary lymph node and bone-marrow biopsy was done. Case 2 – A 19-year-old male presented with complaint of elbow swelling for 6 months. Initially, it was 3 cm × 4 cm, mobile lump over the left upper forearm. He underwent a resection at a local clinic, without any histopathological examination. However, the mass started reappearing again. There was no history of fever, night sweats, or weight loss. The mass now was 5 cm × 4 cm [Figure 1]a. There was no peripheral lymphadenopathy or hepatosplenomegaly. The complete blood count was normal. A PET scan showed metabolically active disease involving anteromedial aspect of left elbow only. Case 3: A 21-year-old girl presented with swelling in the upper arm, and she was diagnosed outside as acute leukemia and received chemotherapy. The swelling disappears after three cycles. Again the swelling, reappears now with size of 4 cm × 5 cm [Figure 1]b.
Figure 1: Photograph shows a globular mass in medial aspect of forearm (a: Case 2, b: Case3)

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Pathological finding

Biopsy from axillary lymph node (case 1) showed effacement architecture large atypical cells. The individual cell had large vesicular nucleus, scant cytoplasm, and occasional cell have prominent nucleoli. The tumor cells were immunopositive for LCA, CD4, CD43, and ALK, while negative for CD56, CD3, CD20, CD79a, CD138, Tdt, MPO, CD30, EMA, Perforin, granzyme, and EBV-LMP. Bone marrow (BM) showed near total replacement by immature cell. Biopsy from subcutaneous mass (case 2 and case 3) over elbow showed diffuse infiltration by small cells having high nucleo-cytoplasmic ratio with small nuclei and scant cytoplasm. The tumor cells were immunopositive for LCA, CD4, CD43, CD56, Tdt (focal), and CD68 (focal dot like), while negative for CD3, CD20, CD79a, CD138, MPO, CD30, CD34, and EMA. The peripheral smear and BM aspirate and biopsy were normal. Both cases 2 and 3 had similar morphology and immunophenotype. Flowcytometry analysis of fine-needle aspirate from the mass showed approximately 65% blast-like cells which were CD45, CD4, CD56, CD123, CD43, HLA DR, and CD5 while negative for CD3, CD5, CD7, CD8, MPO, 11c, CD79a, and CD34 while the first case shows negative for CD56 and positive for CD33 [ [Figure 2]: Case 1-a-h, Case 2: i-u].
Figure 2: (a) Microphotograph shows diffuse infiltration by small cells having high nucleo-cytoplasmic ratio with small nucleoli, scant cytoplasm, and indistinct nuclei. Microphotograph of immunohistochemistry showing immunopositive for (b) CD4 (X200), (c) CD43, (d) Alk1 (X200) and negative for (e) CD56 (X200). Flowcytometry analysis shows positive for (f) CD123 and H. CD33while negative for (g) CD56 and CD34. (Case 2) (h) Microphotograph shows diffuse infiltration by small cells having high nucleo-cytoplasmic ratio with small nuclei and scant cytoplasm (H and E ×200). (i)Biopsy from skin nodule shows intermediate size cell with scant cytoplasm. (J)Fine-needle aspiration cytology shows cells with moderate cytoplasm and fine granular chromatin and indistinct nuclei (MGG ×1000). Microphotograph of immunohistochemistry showing immunopositive for (k) LCA (n) CD4 (×200), (o) CD43 (×200), (p) LCD56 (×200), while negative for (l) CD3 (×200), (m) TDT and (q) MPO (×200). Flowcytometry analysis shows positive for ®CD4, CD43, (s) CD4 and CD56, (t) CD123 and HLADR while negative for (u) CD3and MPO

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Treatment

The two patients with classical morphology (case 2 and 3) was given a prephase of dexamethasone 8 mg BD and cyclophosphamide 500 mg intravenous D1 and D2. The tumor resolved completely in a weeks' time. He was then started on acute lymphoid leukemia (ALL) high-risk protocol. He was given induction with vincristine (1.4 mg/m2) D1, 8, 15, 22, daunorubicin (30 mg/m2) D1, 8, 15, 22, and prednisolone (60 mg/m2) d1-28. The first patient with atypical feature started prephase but succumbed after 10 days of starting treatment.


 > Discussion Top


BPDCN is an uncommon hematolymphoid neoplasm, with varied clinical and immunophenotypic features. BPDCN can occur in all age groups (range, 8–103 years); however, it predominantly occurs in the elderly affects older males, with a median age of 67 years and rare in pediatric age group.[8] Approximately 85% of BPDCN cases show cutaneous involvement at presentation, ranging from a single nodule to widespread cutaneous involvement. In a large series by Julia et al., (2014) most patients (73%) presented with nodular lesions only, whereas other patients had bruise-like patches or mixed lesions. The index case had nasal mass with generalized lymphadenopathy. Generalized lesion was present in 14% of cases.[8] Martín-Martín et al. in their study found peripheral blood and BM involvement in 61% and 93% of cases, respectively.[6]

A significant amount of heterogeneity has also been described in the morphology and immunophenotypic profile of BPCDN. In a large series, Cota et al. described 55% of cases to have pleomorphic morphology.[9] Recent studies have highlighted the existence of a broad range of atypical phenotypic profiles in a substantial proportion of cases including absence of CD56 and CD4 which is further worsen by the fact that cells from BPDCN do express markers which have been classically related to other cell lineages such as CD33, TdT, CD79a, CD2, andCD7.[10],[11],[12],[13] Sukswai et al. in his paper suggested that double immunohistochemistry for TCF4/CD123 is most sensitive to diagnose BPCDN.[14] BPCDN usually arises de novo only occasional reports of secondary BPCDN in case of chronic myeloid neoplasm and essential thrombocytosis is reported.[15] The molecular abnormality includes both genetic (TP53 and FLT3) and epigenetic (TET2, IDH2, ASXL1, MLL, and EYA2) pathways.[16]

In the present series, the first case had a unusual site of involvement and showed morphological feature of a large cell non-Hodgkin lymphoma. Further, one of our case was immune negative for CD56 while positive for Alk. Although CLTC-ALK fusion has already been described in congenital BPDCN, to the best of our knowledge, the present report for the first time highlighted immunohistochemical expression Alk.[17] On the contrary, the rest two cases had more typical clinical presentation, histomorhological features as well as immunophenotypic profile. Hence, a comprehensive multidisciplinary approach involving hematological and pathological investigation with an extensive immunohistochemical/immunophenotyping panel is mandatory for a definitive diagnosis.

Systemic therapy with standard AML-type (cytarabine in combination with idarubicin, mitoxantrone, or daunorubicin), ALL type (Spanish PETHEMA LAL-AR/2003 protocol and hyper-CVAD), or lymphoma type (i.e., CHOP) protocols with or without BM transplantation has been used as treatment option in different studies according to local criteria at the referring centers. Martín-Martín et al. found that patients treated with ALL type protocols and allogeneic stem cell transplantation had a significantly better outcome as compared to the other patients, particularly than those who received lymphoma type regimens.[6] Recently, CD123 inhibitor Tagraxofusp used for the treatment of BPCDN.[18] The 5 year overall survival (OS) is 91.5% among younger age group (<20 years) with median time to death of 18month in comparison OS of 26.9% among older age group (>60 years) with median time to death 4 months.[4]

In addition, Martín-Martín et al. also demonstrated that the presence of lymphadenopathies, hepatomegaly, skin lesions, increased serum LDH (≥450U/l), and β2-microglobulin (≥3 mg/l) and Taylor et al. suggested that abnormal karyotype, Tdt negativity, and age >60 years were all associated with a poorer outcome.[19] In our patients, the first had all the high-risk features and died after 10 days of starting therapy. The second patient had only localized disease the patient in complete remission after 9 months of follow-up. The third patient had relapse after 3 months.

Statement

Consent ware taken for publication.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that names and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Acknowledgment

We like to thank Dr Rajeev Kumar and Dr Anita Chopra for reporting of one of the case.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
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. 1
    
2.
Facchetti F, Jones M, Petrella T. Blastic plasmacytoid dendritic cell neoplasm. In: WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues. 4th ed. Lyon, France: International Agency for Research on Cancer (IARC); 2008.p. 145-7.  Back to cited text no. 2
    
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Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016;127:2391-405.  Back to cited text no. 3
    
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Guru Murthy GS, Pemmaraju N, Atallah E. Epidemiology and survival of blastic plasmacytoid dendritic cell neoplasm. Leuk Res 2018;73:21-3.  Back to cited text no. 4
    
5.
Fujii K, Hamada T, Shimauchi T, Asai J, Fujisawa Y, Ihn H, et al. Cutaneous lymphoma in Japan, 2012-2017: A nationwide study. J Dermatol Sci 2020;97:187-93.  Back to cited text no. 5
    
6.
Martín-Martín L, López A, Vidriales B, Caballero MD, Rodrigues AS, Ferreira SI, et al. Classification and clinical behavior of blastic plasmacytoid dendritic cell neoplasms according to their maturation-associated immunophenotypic profile. Oncotarget 2015;6:19204-16.  Back to cited text no. 6
    
7.
Nguyen CM, Stuart L, Skupsky H, Lee YS, Tsuchiya A, Cassarino DS. Blastic plasmacytoid dendritic cell neoplasm in the pediatric population: A case series and review of the literature. Am J Dermatopathol 2015;37:924-8.  Back to cited text no. 7
    
8.
Julia F, Dalle S, Duru G, Balme B, Vergier B, Ortonne N, et al. Blastic plasmacytoid dendritic cell neoplasms: Clinico-immunohistochemical correlations in a series of 91 patients. Am J Surg Pathol 2014;38:673-80.  Back to cited text no. 8
    
9.
Cota C, Vale E, Viana I, Requena L, Ferrara G, Anemona L, et al. Cutaneous manifestations of blastic plasmacytoid dendritic cell neoplasm-morphologic and phenotypic variability in a series of 33 patients. Am J Surg Pathol 2010;34:75-87.  Back to cited text no. 9
    
10.
Kawai K. CD56-negative blastic natural killer-cell lymphoma (agranular CD4(+)/CD56(+) haematodermic neoplasm)? Br J Dermatol 2005;152:369-70.  Back to cited text no. 10
    
11.
Montes-Moreno S, Ramos-Medina R, Martínez-López A, Barrionuevo Cornejo C, Parra Cubillos A, Quintana-Truyenque S, et al. SPIB, a novel immunohistochemical marker for human blastic plasmacytoid dendritic cell neoplasms: Characterization of its expression in major hematolymphoid neoplasms. Blood 2013;121:643-7.  Back to cited text no. 11
    
12.
Garnache-Ottou F, Chaperot L, Biichle S, Ferrand C, Remy-Martin, JP, 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. 12
    
13.
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. 13
    
14.
Sukswai N, Aung PP, Yin CC, Li S, Wang W, Wang SA, et al. Dual expression of TCF4 and CD123 is highly sensitive and specific for blastic plasmacytoid dendritic cell neoplasm. Am J Surg Pathol 2019;43:1429-37.  Back to cited text no. 14
    
15.
Khan AM, Munir A, Raval M, Mehdi S. Blastic plasmacytoid dendritic cell neoplasm in the background of myeloproliferative disorder and chronic lymphocytic leukaemia. BMJ Case Rep 2019;12:e230332.  Back to cited text no. 15
    
16.
Sapienza MR, Abate F, Melle F, Orecchioni S, Fuligni F, Etebari M, et al. Blastic plasmacytoid dendritic cell neoplasm: Genomics mark epigenetic dysregulation as a primary therapeutic target. Haematologica 2019;104:729-37.  Back to cited text no. 16
    
17.
Tokuda K, Eguchi-Ishimae M, Yagi C, Kawabe M, Moritani K, Niiya T, et al. CLTC-ALK fusion as a primary event in congenital blastic plasmacytoid dendritic cell neoplasm. Genes Chromosomes Cancer 2014;53:78-89.  Back to cited text no. 17
    
18.
Pemmaraju N, Lane AA, Sweet KL, Stein AS, Vasu S, Blum W, et al. Tagraxofusp in blastic plasmacytoid dendritic-cell neoplasm. N Engl J Med 2019;380:1628-37.  Back to cited text no. 18
    
19.
Taylor J, Haddadin M, Upadhyay VA, Grussie E, Mehta-Shah N, Brunner AM, et al. Multicenter analysis of outcomes in blastic plasmacytoid dendritic cell neoplasm offers a pretargeted therapy benchmark. Blood 2019;134:678-87.  Back to cited text no. 19
    


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