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Table of Contents
LETTER TO EDITOR
Year : 2020  |  Volume : 3  |  Issue : 3  |  Page : 630-634

Blastic plasmacytoid dendritic cell neoplasm of the thigh: A case report and narrative review of literature


1 Department of Hematology and Medical Oncology, Tata Memorial Centre, Homi Bhabha Cancer Hospital, Varanasi, Uttar Pradesh, India
2 Department of Haematopathology, Tata Memorial Centre, Homi Bhabha Cancer Hospital, Varanasi, Uttar Pradesh, India
3 Department of Hematology and Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India

Date of Submission16-May-2020
Date of Decision18-Jun-2020
Date of Acceptance16-Jul-2020
Date of Web Publication19-Sep-2020

Correspondence Address:
Somnath Roy
Department of Hematology and Medical Oncology, Tata Memorial Centre, Homi Bhabha Cancer Hospital, Varanasi, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/CRST.CRST_202_20

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How to cite this article:
Mandal TK, Roy S, Singh S, Lali BS, Chowdhury Z, Nayak L. Blastic plasmacytoid dendritic cell neoplasm of the thigh: A case report and narrative review of literature. Cancer Res Stat Treat 2020;3:630-4

How to cite this URL:
Mandal TK, Roy S, Singh S, Lali BS, Chowdhury Z, Nayak L. Blastic plasmacytoid dendritic cell neoplasm of the thigh: A case report and narrative review of literature. Cancer Res Stat Treat [serial online] 2020 [cited 2020 Oct 25];3:630-4. Available from: https://www.crstonline.com/text.asp?2020/3/3/630/295540




  Introduction Top


Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare clonal disease derived from the precursor of plasmacytoid dendritic cells.[1] It is characterized by the overexpression of CD123 and BCL-2 and shares several of its molecular characteristics with acute myeloid leukemia (AML) and myelodysplastic syndrome. It has a very aggressive clinical course and poor outcome, with an approximate survival of 1 year with conventional chemotherapy.[2] Currently, there is a lack of consensus guidelines for the treatment of BPDCN, but most of the cases are treated along the principles of AML or acute lymphoblastic leukemia (ALL).[3]


  Case History Top


A 58-year-old male without comorbidities presented to our hospital in December 2019 with a 3-month history of a progressively increasing ulceroproliferative lesion over the anterior portion of the left thigh without any constitutional symptoms. On physical examination, an ulcerative lesion on the skin over the left thigh that extended to the left knee was observed, along with multiple subcutaneous nodules around the lesion and left inguinal lymphadenopathy [Figure 1]. A routine blood examination at baseline revealed a hemoglobin count of 12.4 g/dL, total leukocyte count of 10.16 × 109/L, platelet count of 483 × 109/L, creatinine level of 0.97 mg/dL, urea level of 16 mg/dL, uric acid level of 4.6 mg/dL, potassium level of 4.7 mmol/L, calcium level of 9 mg/dL, and phosphate level of 3.5 mg/dL. The rest of the baseline laboratory parameters were normal.
Figure 1: Ulcerative lesion over the skin involving left thigh extending to left knee along with multiple subcutaneous nodules around the lesion

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A baseline positron emission tomography–computed tomography (PET–CT) scan showed a fluorodeoxyglucose (FDG)-avid (maximum standardized uptake value [SUVmax] of 16.82) ulcerative lesion extending from the left lower thigh to the left knee, with multiple FDG-avid subcutaneous nodules and metabolically active left external iliac nodes [Figure 2]a.
Figure 2: (a) Positron emission tomography–computed tomography on December 2019 showed fluorodeoxyglucose avid (maximum standardized uptake value 16.82) ulcerative lesion involving left lower thigh extending to left knee with fluorodeoxyglucose avid multiple subcutaneous nodules with left inguinal adenopathy with metabolically active left external iliac nodes. (b) Positron emission tomography–computed tomography on March 2020 showed near complete metabolic remission of primary site and bone marrow

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The histopathological examination of the biopsied tissue revealed that the tumor comprised sheets of monotonous medium-sized atypical lymphoid cells infiltrating the dermis with a focal single-file pattern [Figure 3]a. These cells displayed fine chromatin, irregular nuclei, small nucleoli, and scant cytoplasm [Figure 3]b and c]. On immunohistochemistry (IHC), the atypical cells were found to be diffusely positive for CD4 and focally positive for CD68, and were negative for MPO, CD20, CD3, CD8, CD30, ALK1, TdT, AE1/AE3, desmin, and HMB-45; the Ki-67 labeling index was high (80%–85%) [Figure 4]. Subsequently, a bone marrow aspiration with trephine biopsy was performed. Multiparametric flow cytometry revealed that the cells were positive for CD123, CD304, HLA-DR, CD38, CD45, CD36, and CD4 and negative for CD56, CD64, CD34, CD117, CD11b, and CD11c [Figure 5]. Thus, both flow cytometry and IHC conclusively proved the diagnosis of BPDCN.
Figure 3: Histopathology from left thigh biopsy showed (a) tumour composed of sheets of monotonous medium sized atypical lymphoid cells infiltrating the dermis with focal single file pattern (×10). (b and c) These cells displayed fine chromatin, irregular nuclei, small nucleoli and scant cytoplasm

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Figure 4: On immunohistochemistry, the atypical cells were diffusely positive for CD4 (a) and focally positive for CD68 (b) while they were negative for CD20 (c), CD3 (d), CD8 (e), CD30 (f), Alk1 (g), TdT (h), AE1/AE3 (i), desmin (j) and HMB-45 (k). Ki-67 (l) labelling index was high (80%–85%)

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Figure 5: Multiparametric flow-cytometry was positive for CD123, CD304, HLA-DR, CD38, CD45, CD36 along with positivity for CD4 and negativity for CD56, CD64, CD34, CD117, CD11b, and CD11c

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The patient was started on L-asparaginase with methotrexate and dexamethasone (Aspa-Met-Dex Regimen-French Protocol). The regimen comprised L-asparaginase at a dose of 6000 U/m2 administered intravenously on days 2, 4, 6 and 8; methotrexate at a dose of 3 g/m2 administered intravenously on day 1; and oral dexamethasone at a dose of 40 mg from day 1 to 4; as an every 21-day cycle.

After 3 months of intensive chemotherapy, a restaging PET-CT was performed in March 2020 and revealed a near-complete metabolic remission of the primary tumor [Figure 2]b. A repeat bone marrow aspiration revealed that the marrow was in remission too. The patient completed the treatment without any undue toxicity, with regular follow-up and good clinical outcome. The timeline of the case is depicted in [Figure 6].
Figure 6: Timeline of history and current information on the case (PET CT: Positron Emission Tomography and Computed Tomography Scan, IHC: immunohistochemistry: CMR: complete metabolic remission

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  Discussion and Conclusion Top


The first retrospective analysis of BPDCN was reported from the Czech Republic and comprised 14 patients diagnosed and treated between 2000 and 2017.[4] BPDCN usually affects older men in their late seventies, with an incidence of 0.45% of all hematological malignancies.[5] The skin is the most commonly affected site; around 70% of patients have skin lesions. Other patients present with a more traditional leukemic type of picture with blasts in the bone marrow, lymph nodes involvement, organomegaly, and central nervous system (CNS) involvement.[6] Skin lesions are usually erythematous and purplish papules or plaques of various sizes without any anatomic preference. In this case, the skin lesion was erythematous with a central necrotic component seen over the anterior portion of the left thigh.

Histopathologically, it is characterized by diffuse monomorphous infiltrates of medium-sized lymphoblasts or myeloblasts with a high mitotic rate.[7] Immunophenotypically, the cells express CD4, CD43, CD45RA, and CD56 along with the dendritic-cell-associated antigens such as CD123, CD304, TCL1A, and SPIB. Around 50%–80% of the cases are associated with CD68 positivity.[8] Although, in this case, cytogenetic analysis was not done, it has been reported that BPDCN is associated with a complex karyotype in 75% of the cases and MYC translocation in 40% of the cases.[9] MYC positivity has been found to be associated with a good response to ALL-based chemotherapy.

BPDCN has been found to be inherently resistant to standard chemotherapy regimens used for AML and ALL. However, the response rates and survival outcomes are better with ALL regimens, possibly because it has multiple drugs during induction and an aggressive CNS prophylaxis.[10] In general, the intensive ALL regimens such as cyclophosphamide, vincristine, adriamycin, dexamethasone (hyper-CVAD), and Berlin-Frankfurt-Munster are more effective than the standard cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP)-like regimens.

L-asparaginase in combination with high-dose methotrexate and dexamethasone, has shown good clinical activity in BPDCN.[11] As our patient was older and not fit to receive an intensive ALL regimen, we used the less intensive French protocol with an Asp-Met-Dex regimen with a good clinical outcome.

Venetoclax, the BCL-2 inhibitor, used in the first-line setting and at relapse either as monotherapy or in combination with chemotherapy for patients with BPDCN has shown safety, efficacy, and a long duration of response.[12],[13] A Phase I clinical trial with Phase II expansion is currently ongoing to establish the role of venetoclax in BPDCN.

Recently, a novel targeted therapy Tagraxofusp (CD123-directed conjugated immunotoxin) approved by the Food and Drug Administration has emerged as an alternative approach to chemotherapy. However, despite the higher complete response rate, its use is limited because of several class-related adverse effects.[14],[15] Allogenic stem cell transplant after remission induction showed prolonged survival and reduced chances of relapse. The various regimens and their outcomes are summarized in [Table 1].
Table 1: Treatment regimens used and their outcomes in patients with blastic plasmacytoid dendritric cell neoplasm

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In conclusion, we report a rare case of BPDCN of the thigh successfully treated with the Aspa-Met-Dex regimen, without any undue toxicity with good clinical outcomes. However, large scale prospective studies to establish proper consensus guidelines for the treatment of BPDCN are the need of the hour.

Declaration of patient consent

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

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Ladikou E, Ottolini B, Nawaz N, Allchin RL, Payne D, Ali H, et al. Clonal evolution in the transition from cutaneous disease to acute leukemia suggested by liquid biopsy in blastic plasmacytoid dendritic cell neoplasm. Haematologica 2018;103:e196-9.  Back to cited text no. 1
    
2.
Wang W, Khoury JD, Miranda RN, Jorgensen JL, Xu J, Loghavi S, et al. Immunophenotypic characterization of reactive and neoplastic plasmacytoid dendritic cells permits establishment of a 10-color flow cytometric panel for initial workup and residual disease evaluation of blastic plasmacytoid dendritic cell neoplasm. [published online ahead of print, 2020 Apr 2]. Haematologica. 2020; haematol.2020.247569. doi:10.3324/haematol.2020.247569.  Back to cited text no. 2
    
3.
Sullivan JM, Rizzieri DA. Treatment of blastic plasmacytoid dendritic cell neoplasm. Hematology Am Soc Hematol Educ Program 2016;2016:16-23.  Back to cited text no. 3
    
4.
Cernan M, Szotkowski T, Hisemova M, Cetkovsky P, Sramkova L, Stary J, et al. Blastic plasmacytoid dendritic cell neoplasm:First retrospective study in the Czech Republic. Neoplasma 2020;67:650-9.  Back to cited text no. 4
    
5.
Pemmaraju N, Utengen A, Gupta V, Thompson MA, Lane AA. Blastic plasmacytoid dendritic cell neoplasm (BPDCN) on social media: #BPDCN-increasing exposure over two years since inception of a disease-specific twitter community. Curr Hematol Malig Rep 2018;13:581-7.  Back to cited text no. 5
    
6.
Yu F, Sun K, Wang Z. Atypical presentation of blastic plasmacytoid dendritic cell neoplasm: A potential diagnostic pitfall in nasal cavity. Oral Surg Oral Med Oral Pathol Oral Radiol 2018;126:e212-4.  Back to cited text no. 6
    
7.
Shapiro R, Sangle N, Keeney M, Chin-Yee IH, Hsia CC, Lam S, et al. Blastic plasmacytoid dendritic cell neoplasm: A review of diagnosis, pathology, and therapy. J Cell Sci Ther 2015;8:2.  Back to cited text no. 7
    
8.
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. 8
    
9.
Sakamoto K, Katayama R, Asaka R, Sakata S, Baba S, Nakasone H, et al. Recurrent 8q24 rearrangement in blastic plasmacytoid dendritic cell neoplasm: Association with immunoblastoid cytomorphology, MYC expression, and drug response. Leukemia 2018;32:2590-603.  Back to cited text no. 9
    
10.
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. 10
    
11.
Gruson B, Vaida I, Merlusca L, Charbonnier A, Parcelier A, Damaj G, et al. L-asparaginase with methotrexate and dexamethasone is an effective treatment combination in blastic plasmacytoid dendritic cell neoplasm. Br J Haematol 2013;163:543-5.  Back to cited text no. 11
    
12.
Agha ME, Monaghan SA, Swerdlow SH. Venetoclax in a patient with a blastic plasmacytoid dendritic-cell neoplasm. N Engl J Med 2018;379:1479-81.  Back to cited text no. 12
    
13.
Beziat G, Ysebaert L, Gaudin C, Steinmeyer Z, Balardy L. Venetoclax to treat relapsed blastic plasmacytoid dendritic cell neoplasm: A case-report and review of literature. Leuk Res 2019;85:106199.  Back to cited text no. 13
    
14.
Gourd E. Promising results with tagraxofusp in BPDCN. Lancet Oncol 2019;20:e295.  Back to cited text no. 14
    
15.
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. 15
    


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