PMC5651110_01
(a) Low-power view shows the tumor cells in a diffuse growth pattern in lung parenchyma and background of uninvolved alveoli (H&E, x100 magnification). (b) High-power view shows the morphology of the tumor cells in the lung parenchyma (H&E, x400 magnification). (c) Intermediate power of the tumor cells involving the blood vessel walls with angioinvasion (H&E, x200 magnification). (d) An intermediate-power view shows the tumor cells with focal necrosis (H&E, x200 magnification).
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Mayo Clinic Medical Laboratories). Three lung biopsy specimens were obtained and all revealed a diffuse proliferation of large atypical cells lacking any significant architectural pattern (Figure 1(a)). Many of these cells had large irregular nuclei with occasional prominent nucleoli (Figure 1(b)). Angioinvasion of the blood vessels was present (Figure 1(c)) along with areas of necrosis (Figure 1(d)).
(a) High-power view shows the tumor cells diffusely positive for CD20 (IHC stain with hematoxylin counterstain, x400 magnification). (b) High-power view shows the tumor cells partially positive for CD10 (IHC stain with hematoxylin counterstain, x400 magnification). (c) High-power view shows the tumor cells diffusely positive for EBER (ISH stain with eosin counterstain, x400 magnification). (d) High-power view shows the tumor cells positive for EBNA2 (IHC stain with hematoxylin counterstain, x400 magnification).
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Tucson, AZ) (Figure 2(a)). The large atypical lymphoid cells were positive for CD10 (SP67, Ventana) (Figure 2(b)) and MUM1 (MRQ-43, Cell Marque) and negative for BCL-6 (GI191E/A8, Cell Marque) and had a high 90% proliferation index by Ki-67 (30-9, Ventana) immunostain. EBV by in situ hybridization using Epstein-Barr virus-encoded small RNA (EBER) probe (EBER 1 DNP Probe, Ventana) was diffusely positive in about 80% of tumor cells (Figure 2(c)). Santa Clara, CA) (performed at Center for Cancer Research, National Institutes of Health, Bethesda, MD), and EBV nuclear antigen 2 (EBNA2) (PE2, Novocastra) (Figure 2(d)), but they were CD15-immunonegative (MMA, Ventana). Special stains for acid-fast bacillus (AFB), AFB-Fite, and Grocott's methenamine silver (GMS) were negative for microorganisms.
(a) Flow cytometry histogram of forward scatter versus side scatter with a population of large cells gated. (b) Flow cytometry histogram of side scatter versus CD45. (c) Flow cytometry histogram of CD19 versus surface kappa light chain with CD19+ large B-cells highlighted in green events. (d) Flow cytometry histogram of CD19 versus surface lambda light chain with CD19+ large B-cells highlighted in green events.
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Flow cytometric analysis of lung biopsy specimens showed a monoclonal large B-cell population with a kappa restriction comprising about 2.8% of total cells (Figures 3(a)-3(d)).