Dermatology Online Journal

A case of CD4+/CD56+ hematodermic neoplasm (plasmacytoid dendritic cell neoplasm)
Ozlem Su MD¹, Nahide Onsun MD¹, Cuyan Demirkesen MD², Yildiz Aydin MD³, Serpil Pirmit MD¹, Muge Gereli MD¹, Yasemin Kural MD¹
Dermatology Online Journal 16 (4): 8

1. Department of Dermatology, Vakif Gureba Teaching and Research Hospital, Istanbul, Turkey
2. Department of Pathology, Istanbul University Cerrahpasa Medical Faculty, Istanbul, Turkey
3. Department of Haematology, Istanbul University Cerrahpasa Medical Faculty, Istanbul, Turkey

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Abstract

CD4+/CD56+ hematodermic neoplasm (blastic plasmacytoid dendritic cell neoplasm) involving the skin is relatively rare and has been of significant interest in the recent literature. We report here a 64-year-old male who presented with multiple purple-red nodules and plaques on his face, back, and chest. Histological examination of skin biopsies showed an intense hematolymphoid infiltration in the dermis and in the subcutaneous tissue. Stains were positive for CD4 (weak), CD56, and terminal deoxynucleotidyl transferase (TdT). These cells were negative for CD2, CD3, CD5, CD10, CD20, CD30, CD68, and T cell intracellular antigen (TIA). In situ hybridization (ISH) for Epstein-Barr virus was negative and the diagnosis was blastic NK cell lymphoma. The patient was treated with a hyper-CVAD regimen (cyclophosphamide, vincristine, doxorubicine, dexamethasone, methotrexate, and cytarabine).This treatment regimen achieved partial remission but the patient died eight months after the diagnosis. The patient presented with exclusively cutaneous involvement at the beginning but progressed rapidly and died shortly after despite aggressive chemotherapy. Due to its rarity, we present here a case of CD4+/CD56+ hematodermic neoplasm.

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Clinical synopsis

Figure 1
Figures 1a and 1b. Multiple, purple-red nodules and plaques on the face and trunk

A 64-year-old man developed pruritic lesions on his back with a gradual increase in numbers and size over a five-month period. Dermatological examination revealed multiple, purple-red nodules and plaques mainly on the face, back, and chest (Figures 1a and 1b). Upon physical examination, there was no lymphadenopaty or hepatosplenomegaly. The patient had a history of cerebrovascular hemorrhage and para-umbilical hernia. He was otherwise healthy with only hypercholesterolemia. His systemic medications were fluvastatin and cetirizine. The results of routine laboratory tests including blood count, liver function, renal function and lactate dehydrogenase were within normal ranges. The peripheral blood picture did not show any atypical lymphocytes. Human T-cell lymphotropic virus-1 (HTLV-1) serology was negative.

Figure 2	Figure 3
Figure 2a. Diffuse monomorphic infiltration in the dermis, extending to the subcutaneous fat tissue (H&E, x40) Figure 2b. Medium-sized blastic cells with irregular nuclei, fine chromatin, one or several small nucleoli and scant cytoplasm (H&E, x200) Figure 3a. The neoplastic cells show immunreactivity for CD56 (x200) Figure 3b. The neoplastic cells show widespread immunreactivity for CD4 (x40)

Histological examination of nodules (from back and leg) demonstrated an intense hematolymphoid infiltration in the dermis and in the subcutaneous tissue (Figures 2a and 2b). The phenotype of the cells was CD3-, CD8-, CD7-, CD5-, CD45RO-, CD20-, CD30-, granzyme B(-), perforin(-), CD79α myeloperoxidase (-),CD4+, CD56+ (Figures 3a and 3b), and terminal deoxynucleotidyl transferase+ (TdT+). A diagnosis of precursor CD56 hemato-lymphoid neoplasia was made. The bone marrow biopsy (Fig 2c), chest X-ray, computed tomography of mediastinum, and ultrasonography of abdomen showed no evidence of extracutaneous involvement. Flow cytometric analysis showed the presence of CD4+ 53 percent (range 27-57) and CD8+ 24 percent (range 14-34). Biopsy specimens were sent to the Pathology Department of Leids University for detailed analysis. Histopathological examination at Leids University revealed a diffuse atypical infiltration that consisted of polymorphic, intermediate-size cells, which sometimes had a small nucleolus. Stains were positive for CD4 (weak), CD56 and TdT. These cells were negative for CD2, CD3, CD5, CD10, CD20, CD30, CD68 and T cell intracellular antigen (TIA) -1. In situ hybridisation (ISH) for Epstein-Barr virus was negative and the diagnosis was blastic NK cell lymphoma. The patient was treated with a hyper-CVAD regimen (300 mg/m² of cyclophosphamide, 2 mg of vincristine, 2.5 mg/m² of doxorubicine, 40 mg of dexamethasone) fortified with 1000 mg/m² of methotrexate and 1000 mg/m² of cytarabine in the hematology department. This treatment regimen achieved partial remission but the patient died eight months after the diagnosis because of systemic involvement.

Discussion

Cutaneous T-cell lymphomas are a heterogeneous group of lymphoproliferative disorders caused by clonally derived skin-homing T cells. Most cutaneous T-cell lymphomas have the phenotype of T helper memory lymphocytes (CD3+, CD4+ and CD 45RO+). A CD4+/CD56+ hematodermic neoplasm (plasmacytoid dendritic cell neoplasm), formerly designated primary cutaneous natural killer (NK)/T cell lymphoma, is an aggressive and rare hematologic neoplasm recently recognized by the WHO-EORTC classification consensus for cutaneous lymphomas [1]. The neoplasm tends to affect elderly patients [2]. Skin is typically involved at presentation, but widespread dissemination to bone marrow is rapid [3]. The lesions are composed of cells with a lymphoblast-like morphology and an NK-cell phenotype, exhibiting a CD4+, CD56+ positive immunophenotype. Recently, the plasmacytoid dendritic cell origin of this neoplasm has been demonstrated [2, 4].

The first case of plasmacytoid dendritic cell neoplasm was reported by Adachi et al. in 1994; since then, more than 100 cases have been described [5]. It was included in the 2001 WHO classification as blastic NK cell lymphoma [6]. In the WHO-EORTC classification, the disease was named CD4+/CD56+ hematodermic neoplasm [1].

CD4+/CD56+ hematodermic neoplasm is a rare disease without any known racial or ethnic predilection. Most of the patients are elderly with a mean age at diagnosis of 61-67 years, but the disease can occur at any age, including during childhood and infancy [7]. Because of the blastic appearance and CD56 expression, a NK precursor origin was suggested initially but more recent studies pointed out the derivation from plasmacytoid dendritic cells. A relationship with plasmacytoid dendritic cells was first suggested by Lucio et al. [8] and then confirmed by several authors [9, 10]. The terms blastic plasmacytoid dendritic cell neoplasm was introduced in 2008 by the updated WHO classification [11]. In general, these neoplasms have a poor prognosis. Hematologists have suggested that CD4+/CD56+ HN neoplasm should be considered as a leukemia originating from bone marrow, involving skin secondarily [12, 13]. There are rare cases that do not show cutaneous involvement but primary cutaneous origin cannot be excluded because of those rare occurrences. The blastic plasmacytoid dendritic cell neoplasm presents with cutaneous involvement primarily; subsequently invasion of bone marrow and peripheral blood can be detected. A blastic appearance, CD4/CD56 expression, and expression of markers of plasmacytoid dendritic cells, such as CD123, along withthe absence of lymphoid, NK, and myeloid lineage-associated antigens, are characteristic immunophenotypical features of this neoplasm [4]. Prognosis of this neoplasm is very poor. The median survival is 14 months irrespective of the treatment given. There are no standardized treatments. Conventional chemotherapy regimens used for the treatment of aggressive lymphomas or acute myeloid leukemia are ineffective [14].

Our patient showed characteristic clinical, histopathological, and immunophenotypical features of CD4+/CD56+ HN. Unfortunately we could not determine CD123 expression because of unavailability of this test. Although there was no evidence indicating systemic involvement at the beginning, an aggressive course and bone marrow involvement occurred later. The patient was treated with a hyper-CVAD regimen in the hematology department. After the second cycle, almost all of the cutaneous lesions disappeared, leaving post-inflammatory pigmentation. In similar to our case, Shiman et al. [15] gave two cycles of hyper-CVAD fortified with methotrexate and cytarabine to their patient and achieved complete cutaneous remission. In the beginning, response to chemotherapy is good; unfortunately relapses and drug resistance frequently occur [16]. Our patient relapsed quickly and died eight months after the diagnosis. An autopsy was not performed.

In conclusion, CD4+/CD56+ hematodermic neoplasm (blastic plasmacytoid dendritic cell neoplasm) is a distinct and rare entity with an aggressive clinical course and poor outcome.

ACKNOWLEDGEMENT: The authors would like to thank the Pathology Department of Leids University

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