Clinicopathologic Characteristics and Outcome of CD4+/CD56+ Blastic Plasmacytoid Dendritic Cell Neoplasm: A Single Institutional Experience.

CD4+/CD56+ Blastic Plasmacytoid Dendritic Cell Neoplasm (BPCDC, also called hematodermic or blastic NK neoplasm) is a rare aggressive hematolymphoid malignancy with initial skin presentation and concurrent/subsequent marrow and systemic dissemination. BPCDC could pose a diagnostic challenge since it is a rare entity with varied clinical presentation, sharing overlap clinicopathologic features with other hematopoietic neoplasms such as acute leukemia of myelomonocytic differentiation given the high similarity of their ontogeny. Prognosis of this entity is poor and in contrast to AML there is no standard therapy established.

Eleven cases with a diagnosis of CD4+/CD56+ BPCD (WHO 2008 criteria) were retrieved from Moffitt Cancer Center's electronic clinical and pathology databases. Clinical notes and pathology material including skin biopsies, bone marrow aspirates and biopsies were reviewed. Immunophenotypic analyses were performed on fresh samples using flow cytometry and on paraffin-embedded samples using immunohistochemistry (IHC). Molecular analyses of TCR-alpha and TCR-gamma gene rearrangement by PCR and cytogenetic analysis were performed on available fresh skin punch biopsy and bone marrow aspirate samples to exclude T/NK cell lymphoma. In situ hybridization for detection of EBV-encoded RNA (EBER) was performed. Clinical presentation, treatment regimens, response to therapy and clinical course were analyzed.

All eleven patients were males, with age ranging from 17 to 85 years (median 68). Ten patients initially presented with cutaneous nodules (10/11) and one patient with a tonsillar mass (1/11), with or without marrow/lymph node involvement. Histopathologically, all skin biopsies demonstrated dense dermal infiltrates of primitive blasts without epidermotropism. Blasts expressed CD4 and CD56 (11/11), and HLA-DR (6/6), lacking expression of CD3, CD5, CD8. Blasts typically lacked CD11c, CD13, CD33, and CD57 (9/11). Molecular analysis showed germline configuration of TCR_b and TCR_g. In situ hybridization for EBV (EBER) was negative (3/3). One case showed complex cytogenetic karyotype (1/3). Two patients were diagnosed concurrently with transformed MDS/RAEB-1 and AMML/MPD followed by a CD4+/CD56+ BPCD. The majority (7/11) of patients were initially treated with antracycline-based induction chemotherapy regimen (CHOP n=4, CNOP n=1, hyperCVAD n=2). Results of induction therapy (Chemotherapy n=6, Radiation therapy n=1, Surgical excision n=1) were available for 8/11 patients. Overall response rate (ORR) was 73% (8/11). Equal number of patients (4/8) achieved the first complete remission (CR1) and partial remission (PR1) Median duration of CR1 was 5 (range 5-10) months. The second line therapy (Chemotherapy n=6, steroids n=1) was administered in 7/11 patients. Only 1 patient with limited disease to skin achieved CR2. Two younger patients (17 and 36yrs) underwent consolidation with autologous stem cell transplantation in CR1 and PR1, respectively. A patient transplanted in CR1 was alive with no evidence of disease at 11 months of follow-up. Overall median survival of entire cohort of patients was 8 (range 1-35) months.

CD4+/CD56+ BPCD exhibits overlapping clinicopathologic features with peripheral T cell lymphoma, NK cell lymphoma, and acute myelomonocytic/monocytic leukemia. Diagnosis requires accurate histopathology, immunophenotyping by flow cytometry, tissue immunohistochemistry, as well as molecular studies. Clinically, this disease has an aggressive course in a majority of patients with a relatively short survival. Initial responses to induction antracycline-based chemotherapy regimens are of a very short duration. Patients with disease limited to skin and younger patients who can undergo consolidation with hematopoietic stem cell transplantation might have more favorable outcome.

No relevant conflicts of interest to declare.