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Blastic plasmacytoid dendritic cell neoplasm: report of a case presenting with lung and central nervous system involvement and review of the literature.


Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematopoietic malignancy. The recognition and nomenclature of BPDCN has been dramatically evolving. BPDCN was first described by Adachi et al. in 1994 as a CD4+CD56+ cutaneous lymphoma. The World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissue in 2001 named it as blastic natural killer (NK)-cell lymphoma due to its CD56 expression. (1) Later, the European Organisation for Research and Treatment of Cancer (EORTC) classification of cutaneous lymphoma renamed it as CD4+CD56+ hematodermic neoplasm in 2005. (2) BPDCN was first suggested of dendritic cell origin by Lucio et al. in 1999. More recently, it was confirmed as a tumor of precursor plasmacytoid dendritic cells (PDCs) (Chaperot et al., 2001; Chaperot et al., 2004). PDCs produce type 1 interferon (IFN1) and play an important role in the modulation of innate and adaptive immunity. PDCs are produced in the bone marrow and account for less than 0.1% peripheral blood mononuclear cells. When immune response is activated, PDCs can be recruited into lymph nodes, tonsils, spleen, and mucosa-associated lymphoid tissue. (3) PDCs generally are not identified in skin and subcutaneous tissue, and how cutaneous involvement almost invariably occurs in BPDCN is unclear. In 2008, the latest WHO classification renamed it as BPDCN as a distinct entity under the category of myeloid neoplasm. (4) The etiology of BPDCN is not, but it has been suggested to be associated with acute myeloid/myelomonocytic leukemia (Petrella et al., 2005; Herling et al., 2007).

The literature of formerly called blastic NK-cell lymphoma published prior to 2008 may be heterogeneous because CD56 can be expressed in other hematopoietic lineages, including true NK lymphoma and acute myeloid leukemia with monocytic differentiation. In addition, markers recently developed for PDCs, including CD123 (the interleukin-3 receptor), blood dendritic cell antigen 2 (BDCA2/CD303), (5) and T-cell leukemia/lymphoma 1 (TCL1) and CD2-associated protein (CD2AP), (6) were rarely tested in the literature published prior to 2008. In this article, we report a case of BDPCN presenting with skin, lymph node, bone marrow, peripheral blood, lung, and central nervous system involvement and have reviewed the literature since the latest WHO classification of tumors of hematopoietic and lymphoid tissue in 2008 to delineate the characteristics of the disease.


Light microscopy slides were prepared from paraffin-embedded tissue sections and stained with routine hematoxylin and eosin after fixation in 10% neutral buffered formalin. Immunohistochemical analyses were performed on formalin-fixed paraffin-embedded tissue sections using the avidin-biotin-peroxidase method and antibodies to CD3, CD4, CD5, CD8, CD10, CD20, CD43, CD45, CD56, CD57, CD68, and terminal deoxynucleotidyl transferase (TDT). CD123 was performed by Mayo Clinic. Three-color flow cytometric analysis (FACScan, Becton Dickinson, Mountain View, CA) was performed on fresh cell suspension and cerebrospinal fluid (CSF) using antibodies to CD2, CD3, CD4, CD5, CD7, CD13, CD16, CD19, CD56, CD57, and TDT. In situ hybridization for Epstein-Barr virus (EBV), encoded small mRNAs (EBER) were performed. Cytogenetic studies were performed with standard protocols. Q banding was used for chromosome identification and karyotypes were defined according to the International System for Human Cytogenetic Nomenclature. Fluorescence in situ hybridization (FISH) analysis was performed using LSI TCR alpha/ delta dual color break-apart DNA probe (Vysis, Downers Grove, IL). The LSI TCR alpha/delta probe was a mixture of two probes that hybridize to the opposite sites of 14q11.2 with spectrum green on the telomeric side and spectrum orange on the centromeric side of the breakpoints. Gene rearrangement studies of the joining (J) region of the B-cell immunoglobulin heavy chain (IgH) and/or the T-cell receptor (TCR) gamma chain were analyzed utilizing polymerase chain reaction (PCR) amplification to detect the presence of monoclonal populations which were visualized as a discrete band in the range of 160 base pairs (bp) to 190bp for the TCR gamma region and 75bp to 150bp for the JH region of the IgH, respectively. Literature review was conducted by searching PubMed (U.S. National Library of Medicine) with the following keyword "blastic plasmacytoid dendritic cell neoplasm".


A 58-year-old man presented with a two-week history of generalized weakness, fatigue, and dyspnea on exertion in December 2009. On examination, the patient had a 5 cm soft, non-tender, purplish-red nodular skin lesion on the right forearm that grew larger over the past couple of weeks. There were also multiple small purplish papular lesions on the face, back, and left shoulder. Bilateral cervical multiple enlarged lymph nodes were present. Upon admission, he had anemia and thrombocytopenia with white blood cell 5,400/ul, hemoglobin 10.1 g/dl, and platelets 84,000/ul. Bone marrow core biopsy showed a markedly hypercellular marrow that was diffusely replaced by medium-sized blasts with high nuclear cytoplasmic (N:C) ratio, scant pale cytoplasm, irregular nuclear contour, and prominent nucleoli occupying more than 90% of marrow space (Figure 1A). Few mitotic figures were also noted. Bone marrow aspirate smears showed a predominance of blasts with high N:C ratio, grey-blue agranular cytoplasm with a clear intracytoplasmic vacuole, pseudopodia-shaped cytoplasmic extension, finely dispersed chromatin, and prominent nucleoli, comprising more than 90% of the cells (Figure 1B). By immunohistochemistry (IHC), the blasts were positive for CD2 (weak), CD4 (strong), CD56, CD43, CD68 (weakly positive), and CD45 (weak non-specific staining) but were negative for CD1a, CD3, CD8, CD20, CD117, TDT, myeloperoxidase, lysozyme, and TIA-1. Immunophenotypic analysis of bone marrow by flow cytometry identified 89% CD45-positive cells with expression of CD4, CD56, TDT and cytoplasmic CD3, partial expression of CD2, CD5, and CD7, but negative for surface CD3, CD13, CD16, CD19, and CD57. CT thorax showed a 4.8 x 8.5 cm consolidation within the right lower lung and multiple enlarged mediastinal lymph nodes. Transbronchial lung biopsy showed lung parenchyma involved by the same tumor cells. Fine needle aspiration of subcarinal lymph node showed infiltrate of the tumor cells. CSF showed detection of CD4+CD56+ tumor cells comprising 32% of CD45-positive cells by flow cytometry. Peripheral blood smears showed circulating blasts. Cytogenetic analysis showed normal male karyotype 46, XY. (20) FISH analysis showed no translocation affecting TCR A/D constant region. Gene rearrangement studies of TCR gamma and JH of IgH were negative. Serological studies showed that the patient was positive for EBV VCA IgG (3.30; reference range 0.00-1.09) and negative for EBV VCA IgM (0.13; reference range 0.00-1.09). The patient was diagnosed with BPDCN and treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy for six cycles, as well as intrathecal therapy. The patient achieved only partial remission and subsequently was treated with ICE (ifosfamide, carboplatin, and etoposide) chemotherapy for two cycles. While waiting for bone marrow transplantation (BMT), the patient had a relapse of the disease with newly developed multiple 1-1.5 cm slightly raised red lesions on the extremities in August 2010. Skin punch biopsy showed a superficial and deep dermal predominantly perivascular infiltrate of tumor cells with irregular nuclei, fine chromatin, and prominent nucleoli. By IHC, the tumor cells were positive for CD4 and CD56 but negative for CD3. The patient was treated with BEAM (carmustine, etoposide, cytarabine, and melphalan) chemotherapy, along with targeted radiation for the skin lesions, but showed only partial response. The patient then received matched related donor allogeneic peripheral blood stem cell transplantation (SCT) in August 2010. In January 2011, the patient had another relapse of the disease with new skin lesions. By IHC, skin punch biopsy showed the tumor cells were positive for CD4, CD43, CD56, and CD123 and negative for CD3, CD5, CD8, CD20, CD57, CD68, and TDT (Figure 2A-2D). EBER by in situ hybridization was negative. Complete blood count showed pancytopenia. The patient was given high-dose cytosine arabinoside (ara-C) chemotherapy and attained clinical remission. Unfortunately the disease relapsed again in April 2011 with multiple new skin lesions and 80% blasts in the peripheral blood. Due to resistant/refractory to treatment, comfort and supportive measures were given to the patient. The patient died of the disease 17 months after diagnosis.


Clinical Features

Since BPDCN was classified as a distinct entity by WHO in 2008, more than 200 cases that meet the new diagnostic criteria have been reported in the literature. (4) BPDCN is a rare hematopoietic malignancy without known predisposing factors. It has a male-to-female ratio of 2.6-2.7:1. (3,7,8) Most patients are elderly with a median age of 62-67 years at the time of diagnosis. (3,7-9) Pediatric cases as young as 4 years of age (10) and a unique congenital case of a 3-day-old baby (Yang et al., 2012), although much less common, have been reported. The diagnosis is generally based on skin biopsy. BPDCN usually presents with solitary, multiple, or generalized skin or subcutaneous lesions in the presence or absence of systemic involvement such as peripheral blood, bone marrow, and lymph nodes. (4) The skin lesions can be macules, papules, plaques, or nodules and range in size from 0.5 to 12 cm with a median size of 3 cm at diagnosis. (8,10) Ulceration is not a feature, although Jegalian et al. reported a 12-year-old female patient presenting with a 12 cm ulcerated cutaneous lesion died from infectious complication six months after diagnosis. (10) In the largest case series since 2008 by Dalle et al., all 47 patients had cutaneous involvement (100%) at diagnosis, with 40% as solitary lesion, 38% as multiple lesions affecting one or two areas, and 21% as disseminated skin disease. (7) Systemic involvement at diagnosis usually occurs in bone marrow (48%-68%), peripheral blood (33%-73%), and lymph nodes (24%-41%). (7-9) Initial presentation at uncommon sites including maxilla, breast, kidney, liver, spleen, and lung has been reported in very rare cases. (10,11) To the best of our knowledge, our patient is the first case presenting with CNS involvement since the latest WHO classification in 2008. By literature studies, no cases with CNS involvement at diagnosis were reported, although relapse in the CNS was documented in few cases. (12,13) Nearly half of BPDCN patients (35%-48%) presented with only cutaneous disease at diagnosis. (7-9) Nonetheless, systemic involvement eventually develops with progression of the disease. Leukemic disease without cutaneous involvement at presentation, albeit rare, has been reported. (8,12,14) Although response occurs after treatment, relapse invariably occurs, and fatal outcome occurs rapidly. Complete remission (CR) after initial treatment was seen in 47%-68% patients with a mean relapse-free period of 12.6 months (range 2-42 months). (7-9) BPDCN has an aggressive course and a poor prognosis with a mean survival of 16.7 months. (7) In an Austrian study of 33 patients, there was no difference in survival between patients with cutaneous disease only and patients with both cutaneous and extracutaneous diseases. (15) Initial staging results did not affect survival. (7,15) Therefore, even though BPDCN presents with only cutaneous diseases in almost half of the cases, it has been suggested these patients should also be treated with initial aggressive therapy.


Due to its rarity and dramatically evolving recognition, no standard treatment is available, and patients usually receive multiple regimens. First-line treatments are variable, including palliative care, monochemotherapy, nonHodgkin's lymphoma (NHL)-type, acute myeloid leukemia (AML)-type and acute lymphoblastic lymphoma (ALL)-type, radiation therapy, and BMT/SCT. Previous studies on formerly called blastic NK-cell lymphoma/agranular CD4+CD56+ hematodermic neoplasm demonstrated that CHOP/CHOP-like regimen was inadequate; AML-type regimen was associated with a poor prognosis; and hyperCVAD regimen was associated with a favorable prognosis. (16) Dalle et al. showed that, when used as first-line therapy, CHOP/CHOP-like regimens and radiation therapy had a mean relapse free survival of five and five and a half months respectively compared to 25.3 months with BMT. (7) In a recent retrospective study of 39 BPDCN patients (Roos-Weil et al., 2013), allogeneic SCT in first remission was associated with favorable survival, while age, donor type, stem cell source, and chronic graft versus host disease (GVHD) had no significant impact on outcomes. In a case series of six BPDCN patients (Dietrich et al., 2010), two patients without allogeneic SCT died rapidly of the disease at six and 13 months after first-line treatment; two patients with allogeneic SCT in active disease achieved CR but relapsed at six and 18 months after transplantation; and two patients with allogeneic SCT in remission remained disease free at 57 and 16 months after SCT. The authors suggested that allogeneic SCT in first CR should be considered in patients up to 70 years of age. Dalle et al. showed that survival of patients with BMT was significantly higher (31.3 months vs. 12.8 months) than those without BMT. (7) Ham et al. (2012) reported a 26-year-old patient who was treated with AMLtype chemotherapy followed by allogeneic SCT in first CR-achieved long-term disease free survival at 30 months after diagnosis. Jegalian et al. indicated that BPDCN was less aggressive in pediatric patients than in adult patients. Of the total 25 pediatric patients, all three patients who received AML-type therapy were dead at the time of clinical follow-up. In contrast, among 14 patients who received ALL-type therapy, only one patient who presented with a 12 cm ulcerated cutaneous lesion died of therapy related infectious complications. The authors suggested that, for pediatric patients, high-risk ALL-type chemotherapy should be used as first-line treatment, and SCT may be reserved for those with relapse of disease or on their second remission. (10) Interestingly, Dohm et al. (2011) reported a patient after allogeneic SCT developed fulminant leukemic progression during extracorporeal photopheresis for GVHD. Whether extracorporeal photopheresis stimulates malignant transformation of PDCs remains to be determined, but careful clinical selection of GVHD treatment might be warranted.


Histopathologically, BPDCN in the skin is characterized by a diffuse infiltrate of medium-sized blasts with high N:C ratio, scant cytoplasm, finely dispersed chromatin, and prominent nucleoli in the dermis underlying a Grenz zone without epidermotropism present. Cota et al. showed that the typical blasts were seen in 44% of skin biopsy specimens of BPDCN, with the majority (56%) of cases presenting as a rather pleomorphic infiltrate with admixed blastoid cells in the background. (15) On bone marrow aspirate smears, the blasts have scant agranular cytoplasm with eccentrically located nucleus and perinuclear hof. (4) On cytology preparation, the blasts have round to oval nuclei, finely dispersed chromatin, prominent nucleoli, scant pale-blue agranular cytoplasm, occasional cytoplasmic microvacuoles, and pseudopodia-shape cytoplasmic extension. (8,13)


The immunophenotypic profiles of BPDCN are summarized in Table 1. BPDCN characteristically expresses CD4, CD56, CD43, CD45, and PDC-associated antigens such as CD123, TCL-1, BDCA2 (CD303) without expression of T-cell, B-cell, and NK-cell or myelomonocytic lineage specific markers, although expression of CD2 and CD7 is not an uncommon finding. (4) CD4-negative cases (9,14,15) and CD56-negative (8-10,15) cases have rarely been reported in case reports. Despite CD123 and TCL1 being generally positive in BPDCN, CD123-negative and TCL1-negative cases were reported. (8,14,15,17) BPDCN also expressed BDCA2, CD2AP, BCL11A (B-cell lymphoma/leukemia 11A), and CLA (cutaneous lymphocyte antigen). (9,10,14,15) TDT-positive and HLA-DR-positive cases were not uncommon. (9-12,15) TDT was expressed in 14%-64% of cases. (9,10,15) Interestingly, our case showed that TdT was expressed in bone marrow by flow cytometry but not expressed in skin by IHC. Khoury et al. demonstrated that the level of TdT expression by IHC was higher in lymph node than in skin. (18) These findings may suggest different patterns of TdT expression in various involved tissues and potential association with various stages of the disease. CD2 was aberrantly expressed in 33%-52% of cases. (8,9,15) CD5 expression was extremely rare and reported in a single case on bone marrow specimen. (19) We speculate that the partial expression of CD5 in our case is either an aberrant expression or may represent neoplastic PDCs undergoing cell fate conversion to lymphoid phenotype. CD7 was expressed in a few cases, occasionally in the form of subset or focal positivity. (10,11) BPDCN was generally negative for CD3, CD20, CD34, CD117, myeloperoxidase, and EBV. (8-10,14,15) Rare cases were reported to express cytoplasmic CD3. (11,18,20) CD34 and CD117 were expressed in rare cases (Adams et al., 2009; Chen et al., 2011). CD33 is generally negative, (9) but rare CD33-positive cases were reported. (8,13) CD68 was expressed in quite a few cases, and in some cases, in the form of cytoplasmic dots. (8-10) In three case series, CD68 positivity was 53%-86%. (8,9,15) Focal positivity of S100 was reported in three-fourths of pediatric cases (75%) and may represent a favorable prognostic factor, (10) whereas S100 was expressed in 17%-25% of adult patients. (3,8) Hashikawa et al. showed 8 out of 15 (53%) skin biopsy specimen-expressed CXCL12, which was associated with high leukemic change and poor prognosis. (8) EBV antigens/EBV-encoded nuclear RNA (EBER) and T-cell/B-cell gene rearrangement were consistently negative. (8-10)

The Specificity of PDC-Associated Antigens

The diagnosis of BPDCN is largely based on the PDC-associated antigens such as CD123, TCL1, BDCA2, and CLA, but most of these markers have been shown to be expressed by other lesions as well. The specificity of PDC-associated antigens is summarized in Table 2. (6,14,15,17,21-23) Benet et al. showed that CD123 and CD303 (BDCA2) were expressed in 11 out of 123 (9%) and 4 out of 124 (3%) myeloid leukemia cutis (LC) cases, respectively. (21) Vitte et al. reported that, in 42 chronic myelomonocytic leukemia (CMML) patients with skin involvement, 45%-50% of the skin lesions expressed CD123, CD303 (BDCA2), and TCL1, indicating the association of BPDCN with myelodysplastic/myeloproliferative neoplasms such as CMML. (23) Cronin et al. revealed that CD123 was expressed in 4 out of 23 (17%) of myeloid leukemia cutis (LC) and 10 out of 12 (83%) of BPDCN cases, while TCL1 was expressed in 2 out of 23 (9%) of LC and 9 out of 11 (82%) of BPDCN cases. (17) In a study by Petrella et al. of 29 formerly called agranular CD4+CD56+ hematodermic neoplasms (HN) cases and 18 myelomonocytic leukemia cutis (LC) cases, TCL1 was expressed in 26 out of 29 (90%) of HN and 3 out of 18 (17%) LC cases, while CLA was expressed in 26 out of 29 (90%) of HN and 14 out of 18 (78%) of LC cases. (22) CLA as a skin lymphocyte homing molecule is rather nonspecific for BPDCN, and has been reported to be universally expressed in myeloid LC and cutaneous T-cell lymphoma (Campbell et al., 2010; Sachdev et al., 2012). Marafioti et al. showed that CD2AP was expressed in 35 out of 37 (95%) of formerly called CD4+CD56+ HN and 1/24 (4%) of LC cases, but not expressed in 24 CML, CMML, B-ALL, and T-ALL cases. In contrast, BCL11A was expressed in 39 out of 39 (100%) HN, 6 out of 24 (25%) LC, 1 out of 7 (14%) CML, 3 out of 5 (60%) CMML, 7 out of 7 (100%) B-ALL, and 4 out of 5 (80%) T-ALL cases. (6) Therefore, it has been suggested that immunophenotypic analysis using a panel of antibodies including CD4, CD56, and at least 2 PDC-associated antigens (such as CD123, TCL1, BDCA2, CD2AP, and BCL11A), as well as specific markers to rule out other lineages, should be performed to confirm the diagnosis.


Genetic studies are limited for BPDCN, and no defining recurrent genetic abnormalities have been identified. BPDCN was shown to be associated with normal karyotype (8,10,11,17) and variable genomic changes by conventional cytogenetic analysis, comparative genomic hybridization (CGH) and PCR. (9,12,24,25) The most frequent genomic alterations in BPDCN are summarized in Table 3. (9,12,24,25) Lucioni et al. showed deletion of 9p21.3 containing CDKN2A (encoding p16-INK4a) and CDKN2B was found in 14 out of 21 (66.6%) patients and represented a worse prognosis factor (median overall survival of 11 months for homozygous loss versus 26 months for hemizygous loss). (9) Interestingly, Petrella et al. (2012) reported an 82-year-old male patient had normal karyotype on bone marrow specimen by conventional cytogenetic analysis; losses of chromosome 6, 12 (CDKN1B and ETV6), and 13 on skin biopsy specimen and additional losses of chromosome 2 and 5 on bone marrow specimen by CGH; loss of 2p, 5q, 12p (ETV6), and 13q but not 17 (TP53) on bone marrow specimen; and loss of ETV6 on snap-frozen skin sections by FISH analysis, suggesting that the difference in CGH results between skin and bone marrow specimens may reflect genomic alterations associating with progression of the disease. Other sporadic genomic aberrations include loss of 1p31.3-33 (containing CDKN2C/p18) and gain of 16p/q, loss of 6q and 7p, t(1;6), t(9;22), t(11;19)(q23;p13.3), trisomy 7, gain of 9p24 and loss of 11q22, and loss of Y. Jardin et al. showed that TET2 (ten eleven translocation 2) and TP53 mutation were seen in 54% and 38% of BPDCN patients by using PCR. (12) Additionally, Wiesner et al. demonstrated that expression of cell cycle inhibitor p27 KIP1 (encoded by CDKN1B) and p16 INK4a (encoded by CDKN2A) was downregulated in tumor cells. (25) These findings suggest that loss of tumor suppressor genes such as CDKN1B, CDKN2A, ARF, CDKN2B, RB1, and TP53, and resultant functional loss of cell cycle checkpoint controlling proteins, may lead to dysregulation of G1/S transition of the cell cycle and tumorigenesis.

To the best of our knowledge, this is the first case of BPDCN with central nervous system involvement as initial presentation since the latest WHO classification in 2008. Dermatologists and dermatopathologists should be aware of this rare disease for which nearly half of the patients present with only cutaneous lesions at diagnosis. The diagnosis of BPDCN is generally based on the skin biopsy and immunophenotypic analysis. High-dose chemotherapy followed by allogeneic SCT in first remission has been suggested to provide durable remission and favorable survival.


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(7.) Dalle S, Beylot-Barry M, Bagot M, et al. Blastic plasmacytoid dendritic cell neoplasm: is transplantation the treatment of choice? Br J Dermatol. 2010;162:74-79.

(8.) Hashikawa K, Niino D, Yasumoto S, et al. Clinicopathological features and prognostic significance of CXCL12 in blastic plasmacytoid dendritic cell neoplasm. J Am Acad Dermatol. 2012;66:278-291.

(9.) Lucioni M, Novara F, Fiandrino G, et al. Twenty-one cases of blastic plasmacytoid dendritic cell neoplasm: focus on biallelic locus 9p21.3 deletion. Blood. 2011;118:4591-4594.

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(11.) Borchiellini D, Ghibaudo N, Mounier N, et al. Blastic plasmacytoid dendritic cell neoplasm: a report of four cases and review of the literature. J Eur Acad Dermatol Venereol. 2012.

(12.) Jardin F, Ruminy P, Parmentier F, et al. TET2 and TP53 mutations are frequently observed in blastic plasmacytoid dendritic cell neoplasm. Br J Haematol. 2011;153:413-416.

(13.) Zheng G, Schmieg J, Guan H, Ali SZ. Blastic plasmacytoid dendritic cell neoplasm: cytopathologic findings. Acta cytologica. 2012;56:204-208.

(14.) Facchetti F, Pileri SA, Agostinelli C, et al. Cytoplasmic nucleophosmin is not detected in blastic plasmacytoid dendritic cell neoplasm. Haematologica. 2009;94:285-288.

(15.) Cota C, Vale E, Viana I, 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.

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(19.) Chang HJ, Lee MD, Yi HG, et al. A case of blastic plasmacytoid dendritic cell neoplasm initially mimicking cutaneous lupus erythematosus. Cancer Res Treat. 2010;42:239-243.

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(21.) Benet C, Gomez A, Aguilar C, et al. Histologic and immunohistologic characterization of skin localization of myeloid disorders: a study of 173 cases. Am J Clin Pathol. 2011;135:278-290.

(22.) Petrella T, Meijer CJ, Dalac S, et al. TCL1 and CLA expression in agranular CD4/CD56 hematodermic neoplasms (blastic NK-cell lymphomas) and leukemia cutis. Am J Clin Pathol. 2004;122:307-313.

(23.) Vitte F, Fabiani B, Benet C, et al. Specific skin lesions in chronic myelomonocytic leukemia: a spectrum of myelomonocytic and dendritic cell proliferations: a study of 42 cases. Am J Surg Pathol. 2012;36:1302-1316.

(24.) Jardin F, Callanan M, Penther D, et al. Recurrent genomic aberrations combined with deletions of various tumour suppressor genes may deregulate the G1/S transition in CD4+CD56+ haematodermic neoplasms and contribute to the aggressiveness of the disease. Leukemia. 2009;23:698-707.

(25.) Wiesner T, Obenauf AC, Cota C, Fried I, Speicher MR, Cerroni L. Alterations of the cell-cycle inhibitors p270KIP1) and p16(INK4a) are frequent in blastic plasmacytoid dendritic cell neoplasms. J Invest Dermatol. 2010;130:1152-1157.

Zhuang Feng, MD, PhD; Jun Zhou, MD; Gail Bentley, MD

Dr. Feng is with the Department of Pathology and Laboratory Medicine at Tulane University School of Medicine in New Orleans. Drs. Zhou and Bentley are with the Department of Pathology at the Detroit Medical Center and Wayne State University School of Medicine.

Table 1: Summary of the immunophenotypic profiles of BPDCN

Antibody                        Expression

CD2                             variable, + in 33%-51%
CD3                             -; rare cases cytoplasmic CD3+
CD4                             + (80%-100%)
CD5                             -; one case +
CD7                             -; a few cases + (subset or focal)
CD33                            -; rare cases +
CD43                            + (96%)
CD45RA                          + (dim)
CD56                            + (75%-100%)
CD68                            variable, + in 52%-85%, cytoplasmic
                                dots in some cases
CD34                            -; rare cases +
CD117                           -; rare cases +
TdT                             variable, + in 14%-63%
CD123                           + (75%-100%)
TCL1                            + (82%-100%)
BDCA2/CD303                     + (50%-100%)
CD2AP                           + (45%-95%)
BCL11A                          + (83%-100%)
CLA                             + (90%-100%)
CD19, CD20, CD22, CD79a, PAX5   --
EBER                            --
MPO, Lysozyme                   --
S100                            variable, + in 75% children, + in
                                16%-25% adults

Antibody                        Reference

CD2                             8,9,15
CD3                             11,18,20
CD4                             4,6,14,15,17,21-23
CD5                             19
CD7                             10,11
CD33                            8,13
CD43                            4,6,14,15,17,21-23
CD45RA                          4,6,14,15,17,21-23
CD56                            6,14,15,17,21-23
CD68                            8-10,15

CD34                            4
CD117                           4
TdT                             9-12, 15
CD123                           6,14,15,17,21-23
TCL1                            6,14,15,17,21-23
BDCA2/CD303                     6,14,15,17,21-23
CD2AP                           6,14,15,17,21-23
BCL11A                          6,14,15,17,21-23
CLA                             6,14,15,17,21-23
CD19, CD20, CD22, CD79a, PAX5   4,7-10
EBER                            4,7-10
MPO, Lysozyme                   4,6,14,15,17,21-23
S100                            3,8,10

Table 1: Summary of the immunophenotypic profiles of BPDCN, or
blastic plasmacytoid dendritic cell neoplasm. BPDCN; BDCA2/
CD303, blood dendritic cell antigen 2; TCL1, T-cell
leukemia/lymphoma 1; CD2AP CD2-associated protein; CLA,
cutaneous lymphocyte antigen; BCL11A, B-cell lymphoma/leukemia
11A; MPO, myeloperoxidase; TdT, terminal deoxynucleotidyl
transferase; EBER, EBV-encoded nuclear RNA.

Table 2: Summary of the specificity of
immunohistochemical profiles of BPDCN vs.
myeloid leukemia cutis

              BPDCN %   Myeloid leukemia
                        cutis %

CD123         75-100    9-17
TCL1          82-100    9-17
BDCA2/CD303   50-100    3
CD2AP         45-95     4
BCL11A        83-100    25
CLA           90-100    78
CD4           80-100    9-61
CD56          75-100    52
MPO           0         30-67

Table 2: Summary of the specificity of
immunohistochemical profiles of BPDCN versus
myeloid leukemia cutis. (6-14,15,17-21-23)

Table 3: Summary of the most frequent genomic
alterations in BPDCN

Change   Chromosome   Cytoband

Loss     13           q12.11-q34
Loss     12           p13.2
Loss     9            p21.3
Loss     9            q34
Loss     5            q23.1-a35.2
Loss     15           q11.2-a26.3
Loss     3            p22.2-p21.1
Loss     19           p13.4-p13.2
Loss     17           p13.3-p11.2
Loss     7            p22.3-p22.1
Loss     6            q23.3-q27

Change   % of patients   Candidate genes

Loss     50-78           RB1
Loss     50-67           CDKN1B, ETV6
Loss     50-66           CDKN2A, CDKN2B, MTAP
Loss     50-55           NOTCH, TRAF2, CARD9
Loss     21-44           SMAD5, MSH3, MCC, APC
Loss     33-36           CYP1A1
Loss     29              PTPN23
Loss     22-29           CDKN2D, PRKCSH
Loss     22              TP53
Loss     21              MAD1L1
Loss     11-21           PARK2

Table 3: Summary of the most frequent genomic
alterations in BPDCN. Adapted from ref. 25. BPDCN,
blastic plasmacytoid dendritic cell neoplasm;
CDKN, cyclin-dependent kinase inhibitor; MTAP,
methylthioadenosine phosphorylase; TRAF2, tumor
necrosis factor receptor-associated factor 2;
CARD9, caspase recruitment domain; RB1, retinoblastoma
tumor suppressor gene; CYP1A1, cytochrome P450
family 1 subfamily a polypeptide 1; PRKCSH,
protein kinase C substrate 80K-H; PTPN23,
protein-tyrosine-phosphatase-n23; MCC, mutated
in colorectal cancer; APC, adenomatous polyposis
coli tumor suppressor gene; PARK2, Parkinson
protein 2; MAD1L1, mitotic arrest deficient-like
1; TP53, tumor protein 53. (9,12,24,25)
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Author:Feng, Zhuang; Zhou, Jun; Bentley, Gail
Publication:The Journal of the Louisiana State Medical Society
Article Type:Case study
Date:Jan 1, 2014
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