Baylor University Medical Center Proceedings October 2017 - 451

dendritic cells (2-4). This entity has been known under various names including agranular CD4+ natural killer (NK) cell
leukemia, blastic NK-cell lymphoma, blastic NK leukemia,
and agranular CD4+, CD56+ hematodermic neoplasm. In the
2016 revision to the World Health Organization classiﬁcation
of myeloid neoplasms and acute leukemia, this entity is classiﬁed
under the acute myeloid leukemias (5). This is a clinically aggressive tumor derived from precursors of plasmacytoid dendritic
cells, also known as professional type I interferon-producing
cells or plasmacytoid monocytes (3).
The clinical features of BPDCN consist of two main patterns
(6). One is characterized by an indolent onset (70%-90% of
cases) dominated by skin lesions followed by tumor dissemination. The other (10%-30% of cases) has features of acute leukemia and systemic involvement from the beginning. BPDCN is
characterized by a diﬀuse monomorphic blastic inﬁltrate of cells
that can resemble lymphoblasts or myeloblasts. The diagnosis
is based on immunophenotyping and relies on expression of
CD4 and CD56 along with antigens more speciﬁc for plasma
dendritic cells, including CD123, TCL1, CD303, CD2AP,
BCL11a, and SPIB. Currently there is no consensus as to the
minimal phenotype necessary to establish the diagnosis, but it
is proposed that a conﬁdent diagnosis may be established when
four of the ﬁve principal markers (CD4, CD56, CD123, TCL1,
and CD303) are expressed (7, 8).
T-cell and B-cell receptor genes are usually germline with
clonal bystander T cells responsible for the rare cases of reported
T-cell receptor gene rearrangements. There are no speciﬁc karyotypic abnormalities, but complex aberrations may be present with
six major recurrent targets, namely 5q (72%), 12p (64%), 13q
(64%), 6q (50%), 15q (43%), and loss of chromosome 9 (28%)
(9). Next-generation sequencing shows that TET2 is the most
common mutated gene (8). Gene expression proﬁling studies
have shown a signature distinct from myeloid and lymphoid acute
leukemia (10). The presence of TET in the patient's original diagnosis along with the presence of TET2 in BPDCN raises the
possibility that this current lesion may have arisen from his prior
underlying myelodysplastic lesion. BPDCN appears to be commonly associated with myelodysplastic features (8).
Despite the deceptively indolent clinical presentation with
initial response in most cases to a variety of intensive chemotherapy regimens, the course is most always invariably aggressive, with median survival times from 10 to 16.4 months (7,
11). Occasional reports have noted longer survival/remission
times following allogeneic hematopoietic stem cell transplantation (12, 13).
1.
2.

Lindsey K, Burch M, Krause JR. A case of erythropoietic protoporphyria.
Proc (Bayl Univ Med Cent) 2016;29(3):311-312.
Chaperot L, Bendriss N, Manches O, Gressin R, Maynadie M, Trimoreau
F, Orfeuvre H, Corront B, Feuillard J, Sotto JJ, Bensa JC, Briere F, Plumas
J, Jacob MC. Identiﬁcation of a leukemic counterpart of the plasmacytoid
dendritic cells. Blood 2001;97(10):3210-3217.

October 2017

10.

11.

12.

13.

Petrella T, Comeau MR, Maynadié M, Couillault G, De Muret A,
Maliszewski CR, Dalac S, Durlach A, Galibert L. Agranular CD4+,
CD56+ hematodermic neoplasm (blastic NK-cell lymphoma) originates
from a population of CD56+ precursor cells related to plasmacytoid monocytes. Am J Surg Pathol 2002;26(7):852-862.
Maraﬁoti T, Paterson JC, Ballabio E, Reichard KK, Tedoldi S, Hollowood
K, Dictor M, Hansmann ML, Pileri SA, Dyer MJ, Sozzani S, Dikic I,
Shaw AS, Petrella T, Stein H, Isaacson PG, Facchetti F, Mason DY. Novel
markers of normal and neoplastic human plasmacytoid dendritic cells.
Blood 2008;111(7):3778-3792.
Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau, MM,
Bloomﬁeld CD, Cazzola M, Vardiman JW. The 2016 revision to the
World Health Organization classiﬁcation of myeloid neoplasms and acute
leukemia. Blood 2016;127(20):2391-2405.
Feuillard J, Jacob MC, Valensi F, Maynadie M, Gressin R, Chaperot L,
Arnoulet C, Brignole-Baudouin F, Drenou B, Duchayne E, Falkenrodt
A, Garand R, Homolle E, Husson B, Kuhlein E, Le Calves G, Sainty D,
Sotto MF, Timoreau F, Bene MC. Clinical and biologic features of CD4+,
CD56+ malignancies. Blood 2002;99(5):1556-1563.
Julia F, Dalle S, Duru G, Balme B, Vergier B, Ortonne N, VignonPennamen MD, Costes-Martineau V, Lamant L, Dalac S, Dellattre C,
Dechelotte P, Courville P, Carlotti A, De Muret A, Fraitag S, Levy A,
Mitchell A, Petrella T. Blastic plasmacytoid dendritic cell neoplasms:
clinico-immunohistochemical correlations in a series of 91 patients. Am
J Surg Pathol 2014;38(5):673-680.
Alayed K, Patel KP, Konoplev S, Singh RR, Routbort MJ, Reddy N,
Pemmaraju N, Zhang L, Shaikj AA, Aladily TN, Jain N, Luthra R,
Medeiros LJ, Khoury JD. TET 2 mutations, myelodysplastic features and
a distinct immunoproﬁle characterize blastic plasmacytoid dendritic cell
neoplasm in the bone marrow. Am J Hematol 2013;88(12):1055-1061.
Leroux D, Mugneret F, Callanan M, Radford-Weiss I, Dastugue N,
Feuillard J, Le Mee F, Plessis G. Talmant P, Gachard N, Uettwiller F,
Pages MP, Mozzoconacci MJ, Eclache V, Sibille C, Avet-Loiseau H, LafagePochitaloﬀ M. CD4+, CD56+ DC2 acute leukemia is characterized by
recurrent clonal chromosomal changes aﬀecting 6 major targets: a study
of 21 cases by the Groupe Français de Cytogénétique Hématologique.
Blood 2002;99(11):4154-4159.
Sapienza MR, Fuligni F, Agostinelli C, Tripodo C, Righi S, Laginestra MA,
Pileri A Jr, Mancini M, Rossi M, Ricci F, Gazzola A, Melle F, Mannu C,
Ulbar F, Arpinati M, Paulli M, Maeda T, Gibellini D, Pagano L, Pimpinelli
N, Santucci M, Cerroni L, Croce CM, Facchetti F, Piccaluga PP, Pileri
SA; AIRC 5xMille Consortium Genetics-Driven Targeted Management of
Lymphoid Malignancies and the Italian Registry on Blastic Plasmacytoid
Dendritic Cell Neoplasm. Molecular proﬁling of blastic plasmacytoid
dendritic cell neoplasm reveals a unique pattern and suggests selective sensitivity to NF-kB pathway inhibition. Leukemia 2014;28(8):1606-1616.
Piccaluga PP, Paolini S, Sapienza MR, Pileri SA. Blastic plasmacytoid
dendritic cell neoplasm: is it time to redeﬁne the standard of care. Expert
Rev Hematol 2012;5(4):353-355.
Roos-Weil D, Dietrich S, Boumendi A, Polge E, Bron D, Carreras E,
Iriondo A, Arcese W, Beelen DW, Cornelissen JJ, Kroger NS, Milone
G, Rossi G, Jardin F, Peters C, Rocha V, Sureda A, Mohty M, Dreger P;
European Group for Blood and Marrow Transplantation Lymphoma,
Pediatric Diseases, and Acute Leukemia Working Parties. Stem cell transplantation can provide durable disease control in blastic plasmacytoid
dendritic cell neoplasm: a retrospective study from the European Group
for Blood and Marrow Transplantation. Blood 2013;121(3):440-446.
Unteregger M, Valentin A, Zinke-Cerwenka W, Troppan K, Deutsch A,
Cerroni L, Linkesch W, Neumeister P. Unrelated SCT induces long-term
remission in patients with blastic plasmacytoid dendritic cell neoplasm.
Bone Marrow Transplant 2013;48(6):799-802.

Blastic plasmacytoid dendritic cell neoplasm following acquired erythropoietic protoporphyria

451

Table of Contents for the Digital Edition of Baylor University Medical Center Proceedings October 2017