blastic plasmacytoid dendritic cell neoplasm ( bpdcn ) is a rare hematologic malignancy that typically involves the skin , lymph nodes , the peripheral blood and the bone marrow .
this tumor expresses cd4 and cd56 with no obvious evidence of b- or t - cell differentiation . since adachi et al .
( 1 ) first described cd4+/cd56 + hematodermic neoplasm in 1994 , several individual cases or small groups of cases of this disease have been reported .
relapse frequently occurs within 6 months or less from the initiation of chemotherapy and most patients experience rapid progression that is refractory to conventional chemotherapy .
we report here on a case of advanced bpdcn that was initially misdiagnosed as cutaneous lupus erythematosus .
a 67-year - old man with a past history of gout had complaints of non - itching painless skin lesion on the back and it was spreading to the whole trunk , face , arms and thighs for the previous 3 months .
this lesion initially presented as a dusky erythematosus patch with indurations on the dorsal area , and it eventually grew and spread .
skin examination showed multiple hyperemic nodules and plaques on the face and trunk ( fig .
a biopsy specimen taken from the facial skin lesion revealed atrophy of the epidermis , a flattened stratum malpighii , small numbers of necrotic keratinocytes and eosinophilic swelling of the dermal collagen fibers , as well as a perivascular and interstitial lymphohistiocytic infiltration in the entire dermis ( fig .
2 ) . on the basis of positive imunophenotyping for cd3 and cd20 , the negative imunophenotyping for cd56 and the presence of a mixed reactive lymphocytic infiltration of t and b - cells , a diagnosis of lupus erythematosus was made .
the hemoglobin value was 12.2 g / dl , the platelet count was 83,000/l and the white blood cell count was 22,900/l with 3% atypical lymphocytes and 7% blasts .
the serum levels of lactate dehydrogenase , uric acid and creatinine were increased ( 1,580 iu / l , 10.5 mg / dl and 1.56 mg / dl , respectively ) .
marrow aspiration disclosed that blasts comprised 89% of the mononuclear cells and the blasts were of variable size with agranular cytoplasm , and they were positive for cd2 , cd3 , cd4 , cd5 , cd7 , cd45 , cd56 , and hla - dr , and they were negative for myeloperoxidase , terminal deoxynucleotidyl transferase , cd3 , cd8 , cd10 , cd13 , cd14 , cd19 , cd20 , cd33 , cd34 , and cd61 .
cytogenetic analysis revealed a karyotype of 46 , xy , add(9)(p24 ) , del(11)(q22 ) . repeated biopsy from the left cheek revealed a diffuse lymphoid infiltrate of cells with medium sized nuclei , and the cells were positive for cd4 , cd43 , cd56 and cd99 ( fig .
immunostaining for cd3 , cd6 , cd8 , cd20 , cd30 , t - cell intracellular antigen-1 , myeloperoxidase , and terminal deoxynucleotidyl transferase was either weak or negative ( fig .
epstein - barr virus ( ebv ) was not detected by rna in situ hybridization , nor were ebv antibodies detected .
a study of t cell receptor gene rearrangement was not performed because the patient did not give informed consent .
computed tomography of the chest and abdomen showed multiple lymphadenopathies in both axillae , the lower neck , the right lower paratracheal area , the lower anterior mediatsinum , the left gastric area , the pericholedocal site and the celiac axis area .
the patient received six courses of multidrug chemotherapy consisting of ifosphamide , methotrexed , etoposide , prednisolone and l - asparaginase , and the patient achieved a partial remission .
bpdcn is a rare hematopoietic malignancy , and there has been few data about its incidences .
spanish study ( 2 ) reporting the overall incidence of bpdcn among all acute myeloid leukaemia and non - hodgkin 's lymphoma was 0.76% and 0.27% , respectively and japanese study ( 3 ) reporting a 6.33% incidence of this malignancy among natural killer ( nk ) cell - lineage neoplasm .
in korea , a total of 17 cases of bpdcn have been reported as single cases or as clusters of cases . among these cases , 4 cases ( 4 ) were reported in 2005 and 10 new cases ( 5 ) were reported in 2007 , and all of these patients died except for three patients who had disease confined to skin . since this disease entity was first described ( 1 ) in 1994 , the nomenclature has changed several times according to the expanded knowledge of this malignancy .
the naming of blastic nk cell lymphoma / leukemia was based on the distinct cytology and nk cell origin suggested by the cd56 expression . however , the cd4 positivity and the lack of expressing other nk - lineage markers in most cases cast doubt on its derivation from nk precursors , and hence the french study group on cutaneous lymphoma ( 6 ) called it agranular cd4+/cd56 + hematodermic neoplasm . the world health organization - european organization for research and treatment of cancer ( who - eortc ) consensus classification agreed ( 7 ) because of the disease 's uncertain lineage . on further study ,
chaperot et al . ( 8) proposed that the plasmacytoid dendritic cell ( pdc ) might be the normal counterpart of this disease in 2001 . on the studies using functional , immunohistochemical and molecular tools ,
the expressions of the interleukin 3 receptor -subunit and blood dendritic cell antigen-2 were compatible with a plasmacytoid dendritic cell origin , and the authors of those studies named the disease bpdcn ( 9 ) .
the name bpdcn was enlisted in the 2008 who classification of tumors of the hematopoietic and lymphoid tissues .
although the origin of this malady has been defined , the oncogenesis at the molecular level has yet to be clarified .
histopathologically , bpdcn is characterized by a dense monomorphous infiltration of medium - sized blastoid cells that are positive for cd4 , cd56 , cd123 and tcl-1 .
( 10 ) evaluated 33 patients with a proven diagnosis of bpdcn and they found that the cutaneous lesions of bpdcn were quite variable .
most of their cases ( 80% ) presented with nodular / diffuse infiltrates in the entire dermis , fewer cases ( 20% ) presented with relatively small , perivascular or interstitial aggregates of cells , and some cases resembled the picture of a cutaneous inflammatory disorder .
the tumor cells in the latter cases were found with reactive lymphocytes , and this made the diagnosis of bpdcn difficult and dicey . in our case , the skin lesion at first biopsy was suggestive of reactive change rather than malignancy .
the second biopsy revealed an extensive diffuse lymphocytic infiltration that was positive for cd4 , cd43 , cd56 and cd99 , which is quite a different finding from the first one and it definitely favored the diagnosis of bpdcn .
this is certainly a lesson that both clinicians and pathologists should be aware of the atypical presentations of bpdcn from the onset .
the histopathologic findings of discoid lupus erythematosus are typified by an interface dermatitis involving the hair follicles and epidermis , and this is accompanied by a moderate to heavy superficial , deep perivascular and periappendageal lymphocytic infiltration .
plasmatoid dendritic cells are known to play an important role ( 11,12 ) in the pathogenesis of lupus erythematosus and these cells produce type i interferon .
( 13 ) showed that a cutaneous plasmatoid dendritic cell infiltration is a hallmark of lupus erythematosus .
although it is thought that bpdcn originates from pdcs , there has been no report of bpdcn in the setting of lupus .
bpdcn mainly occurs in older patients , although it can occur at any age , including the pediatric period .
it affects males more frequently than females ( 12 ) at a proportion of roughly 3:1 .
it frequently involves multiple sites with a predilection for skin , and this is followed by bone marrow , peripheral blood and lymph nodes .
the skin lesions tend to be localized at the onset and then they become multiple or more generalized during the course of disease , and overt leukemia is the usual finding in advanced cases or there is relapse after therapy .
frequent chromosomal aberrations in various sites have been reported for this disease , including chromosomal losses on 5q , 6q , 12p , 13q and chromosomes 9 and 15 , as well as deletion of regions on 4q34 , 9p13-p11 , pq12-q34 and 13q12-q31 .
our case demonstrated an abnormal karyotype of 46 , xy , add(9)(p24 ) , del ( 11)(q22 ) .
the comparative genomic hybridization performed in the 4 cases reported in korea ( 5 ) showed amplification of 11q12.31 in all 4 cases and 12q13.11 in three .
the clinical course of bpdcn is aggressive and generally dire at best , with the median survival time being 12 - 24 months .
although there is no consensus on the optimal treatment for this neoplasm , a systemic treatment should be started at the outset regardless of whether the disease is localized or disseminated .
the clinical course in most cases has been characterized by an initial response to chemotherapy followed by relapse and subsequent death .
as the outcomes of many therapeutic attempts have been reported to be quite variable , there is no standard treatment for bpdcn .
usually the duration of a response to topical steroid , single agent chemotherapy , radiotherapy and polychemotherapy like chop ( cyclophosphamide , doxorubicin , vincristine , prednisone ) or hypercvad ( cyclophosphamide , vincristine , doxorubicin , dexamethasone alternating with high dose methotrexate and high dose cytarabine ) has been reported to be brief .
pralatrexate was anecdotally reported to be active as a salvage treatment ( 14 ) although its impact on the clinical course looked negligible . in the face of the extremely poor outcome of conventional chemotherapy and radiation therapy , dalle et al .
( 15 ) asserted that only stem cell transplantation can significantly prolong survival regardless of the initial extent of disease .
although our patient has shown a partial response to six cycle of chemotherapy , his ultimate prognosis looks grim .
our case taught us a lesson that bpdcn should be considered in the differential diagnosis of skin rashes that are refractory to treatment .
although we could not identify pdcs in skin on the first biopsy in our case , their accumulation has been described in several inflammatory cutaneous conditions ( 12 ) such as systemic lupus erythematosus , psoriasis , lichen planus and contact dermatitis .
given its easy accessibility and relative safety , we advocate that repeated skin biopsy should be performed in every case of unusual skin lesion .
 blastic plasmacytoid dendritic cell neoplasm ( bpdcn ) is a rare disease . 
 the prognosis is poor in most cases with rapid progression despite administering chemotherapy . 
 a 67-year - old man complained of skin rashes on his back and this spread to the trunk , face , arms and thighs , and he was initially diagnosed with cutaneous lupus erythematosus according to the skin biopsy . the skin rashes then became aggravated on a trial of low dose methylprednisolone for 3 months . repeated 
 skin biopsy revealed a diffuse infiltration of lymphoid cells with medium sized nuclei , positive for cd4 and cd56 , negative for epstein - barr virus ( ebv ) , indicating a diagnosis of bpdcn . 
 further workups confirmed stage iva bpdcn involving the skin , multiple lymph nodes , the peripheral blood and the bone marrow . he was treated with six cycles of combination chemotherapy consisting of ifosphamide , methotrexate , etoposide , prednisolone and l - asparaginase , and he achieved a partial response . 
 herein we report on a rare case of bpdcn that was initially misinterpreted as cutaneous lupus erythematosus . 
Introduction
Case Report
Discussion