17 yrs old male with multiple THREPINE BIOPSIES (2003,2004,2005,2006) and liver/spleen/lymph node biopsies (2004).  
HISTOLOGY: BM B06-1140 (2006) erythroid depression and reactive central limfoid follicle in BM (on the slides).  
BM B04-27041 (2004): the same changes. The erythroid precursors are unvisible in HE. The reticulin fibrosis and Fe deposits are absent. Perivascular interstitial and cewntral lymphoid follicles/infiltrates are obvious (CD3+>CD20+). The slightly elevated amount of TdT+ > CD34+ precursors. The single CD57+>CD56/GranB+ small lymphocytes. CD8+>>CD4+.  
BM B05-22799 (2005): The same changes. Focal I reticulin fibrosis appears. The prominent central follicles, interstitial and peritrabecular? lymphoid infiltrates. The slight eosinophilia is present.  
SUMMARY of BM changes: Erythroid depression, lymhoid infiltrates, most probably reactive, slight architectural distortion and eosinophilia. Focal I reticulin fibrosis.  
LYMH NODE B04-3220: Reactive lymphadenopathy.  
LIVER B04-3220: There are mononuclear portal and intrasinusoidal infiltration with some nuclear irregularities in parenchyma. Intrasinusoidal atypical lympho's: LCA+, CD20-, CD3-, CD4/CD8-, GranzymB-: lymphoid (NK?)proliferation, uncertain behaviour?.  
SPLEEN B04-3220: Follicular hyperplasia and some small lymphocytic CD3+ > GranzymB+, CD8+ slightly > CD4+, CD56/CD57(-) intrasinusoidal and interstitial infiltration: tends to be REACTIVE CHANGES.  
CLINICAL INFO (dr.Laimonas Griškevicius). The patient was first evaluated for anemia by a child hematologist at the age of 15 in October 2003. HB count was 62 g/l (normocytic, low reticulocytes), PLT, WBC normal. On presentation spleen was 3 cm below costal margin. BM biopsy revealed absent erythropoiesis. PRCA was diagnosed, the patient was treated with prednisolone and CsA with a good response: rising Hb and reticulocytes. During the course of disease, liver, spleen and multiple bone marrow biopsies were obtained (see pathology report). On discontinuation of prednisolone the patient repeatedly developed transfusion dependent anemia and was treated with 2 courses of ATG and CsA. The Hb count was not sustainable and chronic prednisolone therapy had to be continued. The patient was refered to adult hematology at the age of 18 in June 2006. At presentation, Cushingoid features due to chronic prednisolone treatment were noted. There was no peripheral lympadenopathy, spleen was palpable at 5 cm BCM, liver was not enlarged. Chest X ray normal. Abdominal sonoscopy: spleen 157 mm. WBC: 5.26 x109/l, normal differential, normal small lymphocytes, Hb 67 g/l, retic. 0.1%, MCV 84, PLT 378 x 109/l. Peripheral FC (obtained on chronic prednislone treatment) (CD16 positive NK cells 41% - 390/mkl): CD45+, CD2+, CD7+, CD11c+, CD16+, HLA-DR+, CD38+, CD3-, CD4-, CD5-, CD8-, CD25-, CD56-, CD57-, TCRab-, TCRgd-, cCD3-. The same phenotype was observed in June 2005, NK count was 1835/mkl in bone marrow. Coombs direct and indirect negative. Since NK cells have TCR genes in nonarranged germline postition, TCR clonality studies were considered noninformative and not performed. LDH 221 U/l (normal < 190 U/l) on CsA treatment. Beta2 microglobulin 4,17 mg /l (normal < 3 mg/l), creatinine 110 mkmo/l (slightly increased due to CsA).  
Given the splenomegaly, continuosly increased NK numbers with aberrant immunophenotype (CD56-), absent erythropoiesis and good response to prednisolone, the proposed diagnosis is:  
CHRONIC NK CELL LEUKEMIA. PURE RED CELL APLASIA.  
QUESTION: DIFFERENTIAL WITH REACTIVE NK LYMPHOCYTOSIS.