Cytoplasmic nucleophosmin is not detected in blastic plasmacytoid dendritic cell neoplasm

Abstract

the presence of NPM1 mutations) but nucleus-restricted in BPDC neoplasm (because of a germline NPM1 gene). Our results, have important diagnostic implications, further clarify the cell of origin of NPMc + AML, and justify the inclusion of AML with mutated NPM1 and BPDC neoplasm as separate entities in the new WHO classification. Design and Methods Pathological samplesThe aim of this study was to investigate the presence of NPM1 mutations in a wide spectrum of PDC proliferations. The following pathological samples were studied: n=13 typical BPDC neoplasms, whose phenotypic features are summarized in Table 1; reactive lymph nodes (n=16), myelodysplastic syndromes (n=14), AML (n=9) and myeloid sarcoma (n=5) harboring nodules of mature PDCs. Since no fresh material for molecular analysis was available from these cases, we used immunohistochemistry to detect aberrant cytoplasmic expression of nucleophosmin that is known to be fully predictive of NPM1 mutations. 5 Immunohistochemical studiesParaffin sections from all pathological samples were subjected to antigen retrieval and stained with antibodies directed against fixative-resistant epitopes of the protein nucleophosmin 1 and various PDC-associated markers. Nucleophosmin was detected using the monoclonal antibody (mAb) anti-NPM (clone 376) 1 ; PDCs were identified using mAbs anti-CD4 (clone OPD4; DakoCytomation), anti-CD56 (clone 1B6; NovoCastra), anti-CD123 (clone 7G3; BD Pharmingen), anti-TCL1 (clone TCL1A; Upstate), and anti-CLA (clone HECA-452; BD Pharmingen). Four cases were immunostained with an antibody directed against the new PDC marker CD2AP (kindly provided by Dr. Teresa Marafioti, University of Oxford). All samples were also investigated for expression of C23/nucleolin (mAb anti-C23, clone MS-3; Santa Cruz Biotechnology), the CD34 (mAb antibody anti-CD34, clone Qbend/10; DakoCytomation) and CD68 macrophage-restricted molecule (mAb PG-M1 generated in B. Falini's laboratory).The antibody-antigen reaction was revealed by immunoalkaline phosphatase (APAAP) or immunoperoxidase, according to standard procedures. 1 Results and DiscussionAll 13 BPDC neoplasms expressed three or more of the PDC-associated molecules CD4, CD56, CLA, CD123, TCL1 (Table 1; Figures 1 and 2), including the recently described PDC marker CD2AP 12 that was investigated in 4 cases (data not shown); all 10 samples investigated were CD34-negative (Table 1). Notably, tumor cells from all specimens showed nucleus-restricted expression of nucleophosmin (Figures 1 and 2) that was the same as C23/nucleolin and was fully predictive of NPM1 gene in a germline configuration. Interestingly, the nucleusrestricted positivity for nucleophosmin was also observed in paraffin sections from bone marrow biopsies of 14 patients with leukemias of ambiguous lineage (Online Supplementary Figure 1S) as defined by WHO, i.e. pathological conditions which share some but not all immunophenotypic features of BPDC neoplasm.11 The nucleophosmin staining pattern in BPDC neoplasm and leukemias of ambiguous lineages clear...

Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation: an Italian multicenter study

“…13,23,24 In our series cytogenetic analysis confirmed that most patients had unfavorable cytogenetics (48%), among which complex karyotype was a distinctive feature. Moreover, as recently found, 25 no patients had NPM1 mutations. Of interest, among 14 cases examined in our series, three had FLT3-ITD mutations.…”

Cytomorphological features of blastic plasmacytoid dendritic cell neoplasm on FNA and cerebrospinal fluid cytology: A review of 6 cases

“…9,10 BPDCN affects predominantly elderly males, with the median age of affected patients reported to be in the sixth decade. [11][12][13] It is characterized by the simultaneous occurrence of cutaneous and extracutaneous (bone marrow, lymph node, and peripheral blood) involvement. [14][15][16] Cutaneous involvement (either in the form of isolated purple nodules or macules or disseminated lesions) is estimated to occur in 85% of patients.…”

Treatment of blastic plasmacytoid dendritic cell neoplasm

“…As pictured in Figure 1C, chromatin is typically dispersed, and nuclear membranes are irregular with prominent nucleoli and increased mitotic activity. [17][18][19] The clinical and histologic presentation are most similar to myelomonocytic (M4) or monoblastic/monocytic (M5) leukemia with skin involvement, typically referred to as LC, aleukemic myeloperoxidase LC (MPO-LC), 17,20 or more rarely CD4…”

“…21,22 Thus, multiple recent case reports have further defined both immunophenotypic and cytogenetic profiles by which to differentiate BPDCN from other similar appearing myeloid-derived malignancies. 10,17,20,23 Immunophenotype Figure 1D shows the shared and unique immunohistochemical markers that allow BPDCN to be accurately differentiated from AML or AML-associated LC or myeloid sarcoma. For BPDCN originating as isolated cutaneous lesions without organ involvement, immunohistochemistry is of particular importance, because biopsy specimens may not yield sufficient cells for differentiation via flow cytometric analysis.…”