Case 4 -

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) S. David Hudnall, Yale University School of Medicine, New Haven, CT

Click on slide thumbnail images for an enlarged view.

If you have any difficulties viewing these slides, email the webmaster.

Clinical History 9 year old afebrile boy presents with skin lesions of the upper extremities and face along with generalized lymphadenopathy. Pertinent Laboratory Data: CBC reveals pancytopenia. Biopsy of subcutaneous tissue from arm is obtained. Case 4 - Figure 1 Subcutaneous tissue from right arm. The monomorphic infiltrate consists of medium-sized blastic cells with round-oval nuclei and pale agranular cytoplasm. Based solely upon the morphology the differential diagnosis included lymphoblastic leukemia/lymphoma, acute monocytic leukemia, and extranodal NK/T cell lymphoma, nasal type. Case 4 - Figure 2 Bone marrow aspirate. The marrow contained a majority of large immature blastic cells with delicate folded nuclei and agranular vacuolated cytoplasm. On morphologic grounds alone this was considered to most likely represent acute monocytic leukemia. Introduction: An afebrile 9-year-old boy presented with a skin rash on the face and upper extremities in association with pancytopenia and generalized lymphadenopathy. The rash was described as maculopapular with "multiple purple patches". Past history was significant for a 1-year history of juvenile rheumatoid arthritis treated with methotrexate and the TNF inhibitor etanercept (Enbril). Biopsies of subcutaneous tissue from the right arm and bone marrow were obtained (see figures 1 and 2 below). Pathological/Microscopic Findings and any Immunohistochemical or Other Studies: The blastic cells from both locations were positive for CD45, CD4, CD56, and CD123, and negative for CD3, CD8, CD20, CD68, CD117, CD138, S-100, EBV, lysozyme, myeloperoxidase (MPO), and Tdt. Differential Diagnoses: CD45 confirmed the impression that the tumor was hematopoietic in origin. CD3 and CD20 negativity indicated that the tumor cells were not mature T or B cells, respectively. TdT negativity indicated that the tumor cells were not lymphoblasts. Negative CD138 staining confirmed that these cells were not plasma cells. The negative staining with CD68 and lysozyme indicated that the tumor cells were not monoblastic in origin. Negativity for CD117 and myeloperoxidase indicated that these cells were not likely to be myeloblasts. Negative S-100 staining indicated that the tumor cells were not Langerhans cells. Importantly, the tumor cells were positive for CD4, CD56, and CD123. This positive triad is virtually diagnostic of blastic plasmacytoid dendritic cell neoplasm. Other markers that may be quite helpful in diagnosis are TCL-1, BDCA-2 (CD303), and CD2AP. Final Diagnosis: Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Case Discussion: This rare malignant neoplasm was formerly known as "blastic NK cell lymphoma" and "CD4+/CD56+ hematodermic neoplasm". The median age at presentation is 65 years but the tumor can be seen in childhood. Skin lesions are very common at presentation (85%), with a variety of presentations including papules, nodules, and plaques. Marrow and CNS involvement are also quite common, and marrow involvement is often accompanied by pancytopenia. The prognosis in adults is very poor even with chemotherapy and stem cell transplantation. In contrast, the prognosis in children is much better following high dose AML chemotherapy (Jegalian, 2010). The most effective current treatment for BPDCN is high dose AML-type chemotherapy and stem cell transplantation. The tumor cells in BPDCN are derived from plasmacytoid dendritic cells (pDC). pDC accumulate in sites of chronic inflammation where they secrete large quantities of IFNα. Increased pDC have been described in the skin in lupus, psoriasis, lichen planus, and contact dermatitis. pDC are negative for lymphocytic, myelomonocytic, and stem cell markers. pDC do stain for CD4 and CD56, but the most specific markers for pDC (and BPLDCN) are CD123, BDCA-2, and CD2AP. The cells of BPDCN are medium- sized immature cells with morphologic features suggestive of lymphoblasts or monoblasts. In conjunction with morphology, variable positivity for blast markers CD117 and TdT can lead to a misdiagnosis of acute monocytic or lymphoblastic leukemia. Conclusion(s): Blastic plasmacytoid dendritic cell neoplasm is a recently-described malignant hematopoietic neoplasm that often presents in the skin. Whiel most cases occur in older adults, the disease is also seen in childhood (as illustrated in the present case). While the neoplasm often resembles lymphoblastic or monoblastic leukemia, judicious use of immunohistochemical markers CD4, CD56, CD123, along with TIA-1, CD2AP, and/or BDCA-2 in difficult cases should lead to definitive diagnosis. References: Cota C, Vale E, Viana I, Requena L, Ferrara G, Anemona L, Metze D, Fink- Puches R, Wiesner T, Cerroni L. Cutaneous manifestations of blastic plasmacytoid dendritic cell neoplasm-morphologic and phenotypic variability in a series of 33 patients. Am J Surg Pathol. 2010 Jan;34(1):75-87. Herling M, Jones D. CD4+/CD56+ hematodermic tumor: the features of an evolving entity and its relationship to dendritic cells. Am J Clin Pathol. 2007 May;127(5):687-700. Jegalian AG, Facchetti F, Jaffe ES. Plasmacytoid dendritic cells: physiologic roles and pathologic states. Adv Anat Pathol. 2009 Nov;16(6):392-404. Jegalian AG, Buxbaum NP, Facchetti F, Raffeld M, Pittaluga S, Wayne AS, Jaffe ES. Blastic plasmacytoid dendritic cell neoplasm in children: diagnostic features and clinical implications. Haematologica. 2010 Nov;95(11):1873-9. Niakosari F, Sur M. Agranular CD4+/CD56+ hematodermic neoplasm: a distinct entity described in the recent World Health Organization-European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas. Arch Pathol Lab Med. 2007 Jan;131(1):149-51. Shiman M, Marchione R, Ricotti C, Romanelli P, Alonso-Llamazares J.CD4+/CD56+ Hematodermic neoplasm (plasmacytoid dendritic cell tumor). Dermatol Online J. 2008 Nov 15;14(11):5.