Clinical and laboratory features compared between JAK2 exon12 and JAK2 V617F mutated polycythemia vera / 中华血液学杂志

Objective: To compare clinical and laboratory features between JAK2 exon12 and JAK2 V617F mutated polycythemia vera (PV) . Method: We collected data from 570 consecutive newly-diagnosed subjects with PV and JAK2 mutation, and compared clinical and laboratory features between patients with JAK2 exon12 and JAK2 V617F mutation. Results: 543 (95.3%) subjects harboured JAK2 V617F mutation (JAK2 V617F cohort) , 24 (4.2%) harboured JAK2 exon12 mutations (JAK2 exon12 cohort) , and 3 (0.5%) harboured JAK2 exon12 and JAK2 V617F mutations. The mutations in JAK2 exon12 including deletion (n=10, 37.0%) , deletion accompanied insertion (n=10, 37.0%) , and missense mutations (n=7, 25.9%) . Comparing with JAK2 V617F cohort, subjects in JAK2 exon12 cohort were younger [median age 50 (20-73) years versus 59 (25-91) years, P=0.040], had higher RBC counts [8.19 (5.88-10.94) ×10(12)/L versus 7.14 (4.11-10.64) ×10(12)/L, P<0.001] and hematocrit [64.1% (53.7-79.0%) versus 59.6% (47.2%-77.1%) , P=0.001], but lower WBC counts [8.29 (3.2-18.99) ×10(9)/L versus 12.91 (3.24-38.3) ×10(9)/L, P<0.001], platelet counts [313 (83-1433) ×10(9)/L versus 470 (61-2169) ×10(9)/L, P<0.001] and epoetin [0.70 (0.06-3.27) versus 1.14 (0.01-10.16) IU/L, P=0.002] levels. We reviewed bone marrow histology at diagnosis in 20 subjects with each type of mutation matched for age and sex. Subjects with JAK2 exon12 mutations had fewer loose megakaryocyte cluster (40% versus 80%, P=0.022) compared with subjects with JAK2 V617F. The median follow-ups were 30 months (range 4-83) and 37 months (range 1-84) for cohorts with JAK2 V617F and JAK2 exon12, respectively. There was no difference in overall survival (P=0.422) and thrombosis-free survival (P=0.900) . Conclusions: Compared with patients with JAK2 V617F mutation, patients with JAK2 exon12 mutation were younger, and had more obvious erythrocytosis and less loose cluster of megakaryocytes.

Clinical features of childhood refractory cytopenia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the clinical features of patients with refractory cytopenia of childhood (RCC).</p><p><b>METHODS</b>The clinical data of 1 420 children (0-14 years old) with an initial diagnosis of non-severe aplastic anemia between January 1990 and June 2013 were retrospectively analyzed. Bone marrow cell morphology and histopathology were re-evaluated, and the patients were re-classified using the criteria proposed in the 2008 edition of the World Health Organization classification of RCC in hematopoietic and lymphoid tumor tissues. The clinical outcomes were followed up every 3-6 months.</p><p><b>RESULTS</b>Among all the 1 420 cases, 152 (10.7%) were reassessed as RCC. Patients with RCC had a lower level of hemoglobin and a higher percentage of fetal hemoglobin than those with non-severe aplastic anemia. Of the patients with RCC, 21.5% showed abnormal karyotypes at diagnosis. The median follow-up period for all patients was 36 months (ranging from 1 to 283 months). The rates of complete response, partial response, and no response to cyclosporine and androgen treatment in RCC patients were 19.0%, 26.7%, and 54.3%, respectively. The 5- and 10-year prospective overall survival rates of RCC patients were 87.9% and 72.4%, respectively. The 5- and 10-year prospective clonal evolution rates were 15.3% and 20.0%, respectively. The 2-year prospective incidence of newly diagnosed karyotype abnormality after the initial diagnosis was 3.6%. The 5- and 10-year prospective leukemia transformation rates were 10.0% and 20.0%, respectively.</p><p><b>CONCLUSIONS</b>RCC shows clinical features similar to adult myelodysplastic syndrome. Children with RCC have a poor prognosis, an increased risk of transformation to leukemia, and a low response rate to cyclosporine treatment.</p>

Expression of SIRT1 in bone marrow biopsy tissues and its clinical significance among children with acute myeloid leukemia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To determine the expression level of silent mating-type information regulation 2 homologue 1 (SIRT1) in bone marrow biopsy tissues among children with acute myeloid leukemia (AML) and analyze its relationship with the prognosis of AML patients.</p><p><b>METHODS</b>A retrospective analysis was performed on the clinical data of 54 children who were diagnosed with AML between July 2009 and April 2012 and who underwent bone marrow biopsy at diagnosis. The expression of SIRT1 in bone marrow was measured by immunohistochemistry. The 54 patients were divided into two groups according to the expression of SIRT1: SIRT1-negative (n=10) and SIRT1-positive (n=44). The SIRT1-positive group was further divided into three subgroups: SIRT1(+) (n=8), SIRT1(++) (n=7) and SIRT1(+++) (n=29) according to the expression levels of SIRT1. Cox multivariate regression analysis was used to determine the unfavorable factors for long survival in children with AML.</p><p><b>RESULTS</b>The SIRT1(+++) subgroup had a significantly higher mortality than the SIRT1-negative group (P<0.05). Compared with the SIRT1-negative group, the SIRT1-positive group had a significantly lower 2-year overall survival rate (P<0.05) and a significantly lower 2-year event-free survival rate (P<0.05). Cox multivariate regression analysis showed that positive expression of SIRT1 was an unfavorable factor for long-term survival in children with AML, with a risk coefficient of 2.071 (95% CI: 1.017-4.219; P=0.045).</p><p><b>CONCLUSIONS</b>SIRT1 is overexpressed in some of pediatric AML patients, and the overexpression of SIRT1 is associated with poor prognosis.</p>

Treating chronic persistent bronchial asthma children with abnormal myocardial enzyme spectrum by Yupingfeng powder: an efficacy observation / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the clinical efficacy of treating chronic persistent bronchial asthma (CPBA) children with abnormal myocardial enzyme spectrum (AMES) by Yupingfeng Powder (YP) combined routine therapy.</p><p><b>METHODS</b>From January 2010 to December 2012, 156 CPBA children patients with AMES were randomly assigned to the treatment group (80 cases) and the control group (76 cases). All patients received routine treatment (inhaled corticosteroids and/or leukotriene regulator). Besides, those in the treatment group took YP. The treatment duration was 3 months. The scores of children asthma control test (C-ACT), pulmonary function (FEV,% and PEF%), myocardial enzyme spectrum were observed before and after treatment, and 3 months before and after treatment. The myocardial enzyme spectrum of 40 healthy children at the baby clinics during the same period were recruited as the control.</p><p><b>RESULTS</b>Compared with the control group, creatine kinase isoenzyme (CK-MB), creatine kinase(CK), and lactate dehydrogenase (LDH) increased in the two treatment groups (P <0.01), but there was no statistical difference in AST (P >0.05). Compared with before treatment in the same group, CK-MB, CK, LDH, and AST decreased in the treatment group after treatment and 3 months after treatment (P <0.01). CK-MB, CK, LDH, and AST decreased in the control group 3 months after treatment (P <0.01, P <0.05).Compared with after treatment, CK decreased in the control group 3 months after treatment (P <0.01). C-ACT score, FEV(1),%, and PEF% all increased in the two groups after treatment and 3 months after treatment (P <0.01, P <0.05). Compared with after treatment in the same group, CK decreased in the control group 3 months after treatment (P <0. 01). Compared with the control group in the same period, post-treatment CK-MB and CK decreased (P <0. 01, P <0. 05), while post-treatment C-ACT score, FEV, %, and PEF% increased (P <0.05) in the treatment group (P <0.05).</p><p><b>CONCLUSION</b>YP could strengthen specific and non-specific immunity of the organism, and improve clinical symptoms and the level of myocardial enzyme spectrum.</p>

Clinical features of cytopenia with bone marrow hypoplasia in children: an analysis of 100 cases / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To summarize the clinical features of cytopenia with bone marrow hypoplasia in 100 children and to investigate an effective treatment regimen for myelodysplastic syndrome (MDS) in children.</p><p><b>METHODS</b>A retrospective analysis was performed on the clinical data of 100 children non-randomly selected from Japan and China who were diagnosed with cytopenia with bone marrow hypoplasia between 2006 and 2011. The data of patients from China were subjected to prognostic analysis.</p><p><b>RESULTS</b>There was no significant difference in the proportion of MDS cases and acquired aplastic anemia (AA) cases between the Japanese and Chinese children. Of the 100 patients, there were 29 cases of acquired AA, 58 cases of refractory cytopenia of childhood (RCC) and 13 cases of refractory cytopenia with multilineage dysplasia (RCMD). There were significant differences in reticulocyte absolute value in peripheral blood and degree of bone marrow proliferation among the three patient groups (P<0.05). The patients from China were followed up for 16-70 months (median, 41 months). After being treated with cyclosporine (CsA) combined with stanozolol, the patients with AA had response rates of 25% and 75%, the patients with RCC had response rates of 47.1% and 82.4%, and the patients with RCMD had response rates of 60% and 60% respectively at 3 and 6 months after treatment.</p><p><b>CONCLUSIONS</b>There are significant differences in reticulocyte absolute value in peripheral blood and degree of bone marrow proliferation among patients with RCC, RCMD and acquired AA. CsA combined with stanozolol has a good therapeutic efficacy in the treatment of acquired AA and hypoplastic MDS in children, but studies of more cases and a longer follow-up duration are needed.</p>

Retrospective analysis of treatment strategy and prognosis in childhood myelodysplastic syndromes from China and Japan / 中国实验血液学杂志

This study was aimed to retrospectively analyse the prognosis of childhood myelodysplastic syndromes (MDS-RCC ) from China and Japan. Two hematologists and one pathologist from China and Japan constituted a diagnosis group. According to the criteria of 2008 WHO, 33 children with MDS-RCC from 50 chinese children diagnosed as acquired bone marrow failure syndrome from 2009 to 2011, and 74 Japanese children with MDS-RCC in a prospective registration group conducted by the Japanese Society of Pediatric Hematology were enrolled in this study. The outcome of total 107 childhood MDS-RCC treated with different treatment strategies was analyzed retrospectively. The results indicated that: (1) the 3 and 5-year overall survival rates (OS) for all patients were 93.8% and 79.7% respectively. (2) All 107 patients with MDS-RCC were further subclassified into 2 groups: transfusion dependent group and transfusion independent group. The 3 and 5-year overall survival rates (OS) for transfusion dependent group were 89.9% and for transfusion independent group were 70.6% respectively, the 5-year overall survival rate (OS) for transfusion independent group was 100.0%. (3) Treatment strategy: patients from transfusion dependent group were treated with immunosuppression therapy (IST), in which CsA combined with or without ATG and patients were treated with HSCT. The 5-year overall survival rate (OS) was 100% for IST group. The 3 and 5-year overall survival rates (OS) for HSCT patients were 82.9% and 30.6%, respectively. All the patients from transfusion independent group were alive till the last follow up. (4) Compared with patients from our hospital and Japan, the 5-year overall survival rate (OS) for patients in our hospital was 100.0%, the 3-and 5-year overall survival rates (OS) for patients in Japan were 93.7% and 75.0%, respectively. It is concluded that children with MDS-RCC are seldom progressive. The observation and wait strategy is applicable for patients with MDS-RCC who have no transfusion dependent. IST therapy is recommended to those who have transfusion-dependent.

Expression of survivin in patients with acute myeloid leukemia / 中国实验血液学杂志

Objective of this study was to detect the expression of Survivin in acute myeloid leukemia (AML) and investigate the relationship of its expression levels with clinical variates and its correlations with BCL-2 ,Bcl-xL and MCL-1. The expression of Survivin, BCL-2, Bcl-xL and MCL-1 were measured by immunohistochemistry in bone marrow biopsy of 63 newly diagnosed AML patients, and the relationship between its expression level and clinical parameters (age, sex, WBC count, diagnosis, prognosis), especially fusion protein AML1/ETO was investigated. The results showed that the expression level of Survivin in newly diagnosed AML patients was higher than that of normal controls (P < 0.01), the expression levels of Survivin did not correlate with age, sex, and WBC counts of patients and so on. There was no significant difference of Survivin expression between different NCCN prognosis groups, either between patients with AML1/ETO or FLT3-ITD mutation and the other patients. Survivin positive patients were got to have lower CR rate but higher relapse rate, however that was not significant in statistics. Indeed, the cumulative survivin rate of Survivin positive patients were lower than that of Survivin negative patients (P = 0.04). Finally, positive correlation between Survivin and MCL-1 was also observed (r = 0.639, P = 0.000). It is concluded that overexpression of Survivin are closely related with occurrence and development of acute leukemia, and may be used as an indicator of prognosis evaluation. In addition, Survivin and MCL-1 may have a relationship of cooperation or interaction.

Determination and clinical significance of serum surfactant proteins A and D in children with bronchiolitis / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the variation and clinical significance of serum levels of surfactant proteins A (SP-A) and D (SP-D) among children with different degrees of bronchiolitis.</p><p><b>METHODS</b>Seventy children with bronchiolitis were divided into acute (n=42) and recovery phase groups (n=28). According to the severity of symptoms, the acute phase group was further divided into severe (n=12) and mild subgroups (n=30). Another 26 children who were hospitalized in the same period due to non-infectious diseases and had not undergone surgery were used as the control group. Competitive enzyme-linked immunosorbent assay was performed to measure serum levels of SP-A and SP-D in each group.</p><p><b>RESULTS</b>The acute phase group had significantly higher serum levels of SP-A and SP-D compared with the recovery phase (P<0.01) and control groups (P<0.01). Compared with the control group, the recovery phase group had elevated levels of SP-A and SP-D (P<0.01). Within the acute phase group, serum levels of SP-A and SP-D in the severe subgroup were significantly higher than in the mild subgroup (P<0.01).</p><p><b>CONCLUSIONS</b>Serum levels of SP-A and SP-D are significantly elevated in children with acute bronchiolitis, and severe cases have higher serum levels of SP-A and SP-D than mild cases. Even after the relief of clinical symptoms, serum levels of SP-A and SP-D remain high. These findings suggest that serum levels of SP-A and SP-D might be useful biomarkers for evaluating the severity of bronchiolitis among children.</p>

Clinicopathologic features and differential diagnosis of splenic B-cell marginal zone lymphoma involving bone marrow / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features and differential diagnosis of splenic B-cell marginal zone lymphoma (SMZL) involving bone marrow.</p><p><b>METHODS</b>The clinical and pathologic features of 22 patients with SMZL were retrospectively studied. Immunophenotypic analysis was carried out by flow cytometry and immunohistochemistry. Immunoglobulin heavy chain rearrangement study was performed using polymerase chain reaction-based method.</p><p><b>RESULTS</b>Villous lymphocytes were found in peripheral blood smears of 11/18 of the patients. In bone marrow aspirates, lymphocytosis (> 20%) was demonstrated in 15 cases (15/18) and villous lymphocytes in 6 cases (6/18). Flow cytometry showed CD19(+) CD20(+) FMC7(+) CD22(+) CD10(-) CD2(-) CD3(-) CD7(-) in 18 cases. Bone marrow biopsies of all the 22 patients revealed various degrees and patterns of neoplastic infiltration, as follows: mild (4 cases, 18.2%), moderate (11 cases, 50.0%) or severe (7 cases, 31.8%); intrasinusoidal (16 cases, 72.7%), interstitial (14 cases, 63.6%), nodular (11 cases, 50.0%) or diffuse (1 case, 4.5%). Reactive germinal center formation (CD23(+) bcl-2(-)) was found in 2 cases (91.0%). Immunohistochemical study showed the following results: CD20(+) PAX5(+) CD3(-) CD5(-) CD10(-) cyclin D1(-) CD23(-) CD43(-) Annexin A1(-) CD11C(-) CD25(-) in all the 22 cases, CD38(+) in 2 cases (9.1%) and CD138(+) in 2 cases (9.1%).</p><p><b>CONCLUSIONS</b>Different and overlapping patterns of bone marrow involvement are observed in SMZL. As the histologic and immunophenotypic features are not specific to SMZL, distinction from other types of mature B-cell lymphomas is necessary.</p>

Analysis of clinical features and prognosis of primary myelodysplastic syndromes with myelofibrosis patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the clinical features and prognosis of the primary myelodysplastic syndrome with myelofibrosis (MDS-MF) patients and to improve the cognition of MDS-MF.</p><p><b>METHODS</b>Four hundred and sixty-six primary MDS patients with bone marrow (BM) biopsy were divided into two groups according to whether BM associated with fibrosis, the clinical features and prognosis of the two groups were analyzed retrospectively.</p><p><b>RESULTS</b>167 (35.8%) MDS cases revealed myelofibrosis, of which MF-1 123 cases (26.4%), MF-2 40 cases (8.6%), MF-3 4 cases (0.9%). The proportion of hepatosplenomegaly in MDS-MF group was significantly higher than in MDS without MF group, the difference had statistical significance (P = 0.031). The proliferation of BM biopsy in MDS-MF group was significantly more active than in MDS without MF group. The number of blasts, megakaryocytes and abnormal megakaryocytes in MDS-MF group were significantly higher than in MDS without MF group, the differences had statistical significance (P < 0.05). Among the 345 patients who had available results of cytogenetic analysis, 121 cases were MDS-MF patients, the proportion of middle and high-risk prognostic group according to IPSS karyotype prognosis groups in MDS-MF group were significantly higher than in MDS without MF group, the differences had statistical significance (P = 0.047). The median survival was 17 (1 - 60) months in MDS-MF group, and was 32 (1 - 62) months in MDS without MF group. The difference had statistical significance (P = 0.001). Myelofibrosis had independent prognostic significance by multi-variable analysis (P = 0.019).</p><p><b>CONCLUSION</b>The myelofibrosis in MDS is main the proliferation of reticular fiber. The proliferation of reticular fiber is closely related with the number of blast cells, the proliferation and developmental abnormalities of megakaryocytes and the karyotype. The prognosis of MDS-MF patients is poor.</p>

Hematopathologic features of T-cell large granular lymphocytic leukemia / 中华病理学杂志

<p><b>OBJECTIVE</b>To explore the hematopathologic features of T-cell large granular lymphocytic leukemia (T-LGLL).</p><p><b>METHODS</b>A retrospective analysis of the clinical presentation, bone marrow morphology, immunophenotyping and T-cell receptor gene rearrangement status were performed in 19 patients with T-LGLL.</p><p><b>RESULTS</b>Of 19 patients, the most frequent hematological abnormalities were anemia and neutropenia (16/19 and 17/19 patients, respectively). Large granular lymphocytes (LGLs) were observed in 17 of 19 peripheral blood smears and 15 of 19 bone marrow aspirate specimens. Lymphocytosis (> 0.2) was present in 17 of 19 patients in their bone marrow aspirate specimens. Bone marrow biopsy specimens revealed lymphocytosis in 16 cases, with a mild to moderate increase of lymphocytes observed in 12 cases (12/16). The pattern of lymphoid distribution was interstitial in bone marrow sections. Intravascular distribution was seen in 8 cases. Lymphoid nodules were present in 4 cases. Flow cytometery showed an immunophenotype of CD3(+) CD4(-) CD8(+) CD56(-) CD57(+) of the tumor cells in 13 cases. Of the other 6 cases, the immunophenotypes included CD8(-) (1 case), CD56(+) (2 cases) and CD57(-) (3 cases). Immunohistochemistry showed CD3+ (10/10), CD57+ (3/3), CD8+ (6/7), TIA-1+ (6/7), granzyme B+ (4/7), perforin + (1/7), CD4- (4/4) and CD56- (9/9). Clonal T-cell receptor γ gene rearrangement by PCR was detected in 12 cases (12/17).</p><p><b>CONCLUSIONS</b>Hematopathologic features of most T-LGLL are distinct. Morphologic, immunophenotypic and molecular analysis of both peripheral blood and bone marrow specimens are essential and complementary in the diagnosis and differential diagnosis of T-LGLL.</p>

The role of bone marrow pathology in diagnosis and differential diagnosis of refractory cytopenia of children / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the diagnosis and differential diagnosis of refractory cytopenia of children (RCC) according to WHO classification, and discuss the relationship between the cytology reviewed by hematologists and histology reviewed by pathologists.</p><p><b>METHODS</b>We selected 50 non-severe aplastic anemia cases from 2007 - 2010 in our hospital and collected clinical data. Experienced hematologists and pathologists evaluated bone marrow biopsy and smear respectively.</p><p><b>RESULTS</b>Of 50 cases, 23 were male and 27 female (M:F = 1:1.17), the median age at diagnosis was 9 years (ranged from 3 to 14 years). 5 patients had disagreement of diagnosis between hematologists and pathologists. In 3 cases hematologists diagnosed as aplastic anemia (AA) and pathologists as RCC, 2 cases vice versa. The final diagnoses of 50 patients reached consensus between hematologists and pathologists were AA 16 cases, RCC 34 cases including 8 refractory cytopenias with multilineage dysplasia (RCMD) cases. All 16 cases AA showed severe hypocellularity. Only 4 cases (25.00%) RCC showed severe hypocellularity, 19 cases (73.08%) RCC showed mild hypocellularity and 3 cases (11.54%) RCC were normal hypocellularity.</p><p><b>CONCLUSION</b>Our results suggests that RCC was not rare in China. The main feature of RCC was dysplasia because of absence of increased blast. RCC was easily confused with AA. The main points of differential were present dysplastic changes of megakaryocyte best appreciated by the hematologists and morphologists and abnormal location of hematopoietic easily observed by pathologists. Overall, cytology and histology were complementary in the investigation of RCC and AA, because of sometimes one might give information that not be given from the other.</p>

Clinicopathologic features of aggressive natural killer cell leukemia / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features of aggressive natural killer cell leukemia (ANKL).</p><p><b>METHODS</b>The clinical and pathologic features were analyzed in 10 patients with ANKL. The complete blood count, peripheral blood smears, bone marrow aspirates and bone marrow biopsies were studied. Immunophenotypic analysis was carried out by flow cytometry and immunohistochemistry. T-cell receptor (TCR) γ gene rearrangement was studied by PCR method.</p><p><b>RESULTS</b>The most frequent hematologic abnormalities observed were anemia (7 cases) and thrombocytopenia (9 cases). Large granular lymphocytes were found on peripheral blood smears of 6 patients. In bone marrow aspirates, lymphocytosis (> 20.0%) was demonstrated in 8 cases and large granular lymphocytes in 6 cases. Bone marrow biopsies revealed various degrees of neoplastic infiltration, as follows: mild (5 cases), moderate (3 cases) and severe (2 cases). The neoplastic cells were mainly interstitial in distribution in 8 cases and diffuse in 2 cases. Hemophagocytosis was observed in 4 cases. Flow cytometry showed CD2+ sCD3- CD4- CD56+ CD57- in all cases, CD7+ in 9 cases, CD16+ in 5 cases, CD8+ in 4 cases and CD5+ in 1 case. Immunohistochemistry performed in 8 cases showed the following results: cCD3+ in 4 cases, CD56+ in 6 cases, TIA-1+ in 6 cases, granzyme B+ in 4 cases and perforin+ in 2 cases. PCR study revealed germline TCRγ gene configuration in all cases.</p><p><b>CONCLUSIONS</b>ANKL is a highly aggressive NK cell-derived lymphoid neoplasm. Comprehensive morphologic, immunophenotypic and molecular analysis are essential in arriving at a correct diagnosis. ANKL needs to be distinguished from other types of NK-cell and T-cell lymphomas.</p>

Clinicopathologic features of lymphoplasmacytic lymphoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To explore the clinicopathologic features of lymphoplasmacytic lymphomas (LPL).</p><p><b>METHODS</b>Routine histological examination was performed on hematoxylin-eosin stained sections of 24 bone marrow biopsies and available 6 concurrent lymph node specimens. Immunohistochemistry study was performed using EliVision methods.</p><p><b>RESULTS</b>Among 24 cases, the male-to-female ratio was 2.4:1 and the median age was 59.5 years (42 - 75). The most common symptom was weakness (83.3%, 20/24). Hyperviscosity and "B" symptoms occurred in 20.8% (5/24) and 8.3% (2/24) respectively. 41.7% (10/24) patients presented with lymphadenopathy. Anemia, leukocytosis and thrombocytopenia were seen in 79.2% (19/24), 8.3% (2/24) and 37.5% (9/24) respectively. Monoclonal Ig light chain expression was detected by serum immunofixation electrophoresis in 23 cases (95.8%), including IgM (20 cases), IgG (2 cases) and IgA (1 case). Basing on the histology and immunohistochemistry findings, the diagnosis was made in 22 bone marrow and 2 lymph node biopsies, respectively. Histologically, the bone marrow and lymph node specimens composed of small lymphocytes, plasmacytoid lymphocytes and plasma cells. The most frequent pattern of bone marrow involvement was diffuse in appearance (63.6%, 14/22), while nodular and interstitial patterns were less common (22.7%, 5/22 and 13.6%, 3/22, respectively). Lymph node involvement was also to be diffuse in pattern. The proliferative cells expressed Pax5, CD20, CD38 and CD138, but were negative for CD5, CD10, CD23, CyclinD1, CD3, CD7 and MPO.</p><p><b>CONCLUSIONS</b>LPL has distinct clinicopathological features. Histological and immunohistochemistry findings are important for its differential diagnosis with chronic lymphocytic leukemia/small lymphocytic lymphoma, splenic marginal zone lymphoma and follicular lymphoma. Waldenström macroglobulinemia is LPL.</p>

Clinicopathologic study of 15 splenectomy specimens of patients with hairy cell leukemia / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathologic features, diagnosis, differential diagnosis and the prognosis of hairy cell leukemia (HCL).</p><p><b>METHODS</b>Fifteen splenectomy specimens of HCL patients were investigated retrospectively using HE and immunohistochemistry in correlation with the follow-up information.</p><p><b>RESULTS</b>(1) The male to female ratio was 2.75:1, age ranged from 36 to 68 years with a median of 47 years. The most consistent clinical feature at presentation was marked splenomegaly (100%). Other symptoms included anemia (80.0%), thrombocytopenia (60.0%), leucocytosis (53.3%), pancytopenia (20.0%) and the absence of B-symptom. (2) The proportion of hairy cells was (14.6 +/- 7.2)% in periphery blood and (47.3 +/- 23.8)% in bone marrow. The positive rate of TRAP assay was 62.5% in bone marrow; 85.7% for TPA test and the detection rate for RLC was 25% by transmission electric microscopy. The frequency of bone marrow involvement was 100%. (3) The average weight of 15 spleens was (3012 +/- 1974) g. The size of 6 spleens ranged from 16 cm x 10 cm x 5 cm to 32 cm x 20 cm x 14 cm. The white pulp of spleen showed a characteristic atrophy feature or even absent due to leukemic infiltration, predominantly involving the red pulp with some sinusoidal pattern. "Blood pool" change was an infrequent feature (3/15 cases). The nuclei of leukemic cells were round (13 cases) or bean-shaped (2 cases), nucleoli inconspicuous or disappeared. The abundant cytoplasm and prominent cell border resulted in a "fried egg" appearance. By immunohistochemistry, leukemic cells were positive for CD45RA, CD20, PAX-5, CD25, CD11c, Annexin A1 and cyclinD1, but negative for CD3 and CD43. (4) 13 cases (86.7%) have been followed-up and all are alive. Among them, 9 cases are living well more than 5 years and 7 more than 10 years.</p><p><b>CONCLUSIONS</b>Splenomegaly is frequently the first manifestation of patients with HCL and occurred predominantly in the middle to elderly adults. Definite diagnosis of HCL requires a combined histological and immunohistochemical assessment of the splenectomy specimen, bone marrow biopsy and aspirate.</p>

Clinical significance of ZAP-70 protein expression in chronic lymphocytic leukemia/small lymphocytic lymphoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features and prognostic significance of ZAP-70 protein expression in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).</p><p><b>METHODS</b>The histologic features of 52 cases of CLL/SLL with lymph node and/or bone marrow biopsies performed were retrospectively reviewed. Immunohistochemical study using EliVision for ZAP-70 protein was adopted.</p><p><b>RESULTS</b>The lymph nodes of the 12 cases studied showed effacement of the nodal architecture and was replaced by a monotonous infiltration of small lymphoid cells. Among them, proliferation centers were identified in 6 cases. Similar morphologic pattern was seen in the 40 bone marrow biopsy samples, but no proliferation center formation obtained. The infiltration pattern of tumor cells in the bone marrow were further subdivided into nodular (n = 9), interstitial (n = 3), mixed (n = 9) and diffuse types (n = 19). There was no significant difference found on survival rates between the diffuse infiltration and non-diffuse infiltration groups (Fisher's exact test, P = 0.199). ZAP-70 protein was mainly located in the cytoplasm and nuclei of lymphoma cells. There were 21 cases (40.4%) positive for ZAP-70 and among them, 11 died of this disease or the related infections. On the other hand, ZAP-70 was negative in 31 cases (59.6%) and only 4 of them died of this disease or related infections. The overall survival in ZAP-70-negative group was higher than that of the ZAP-70-positive group (59 months versus 39 months, chi(2) = 6.991, P = 0.008). Follow-up information was available in 51 patients. Among the 21 dead cases, 15 died of CLL/SLL or the related infection.</p><p><b>CONCLUSION</b>A positive expression of ZAP-70 protein in CLL/SLL suggests a poor prognosis.</p>

Nodal versus extranodal diffuse large B-cell lymphoma: comparison of clinicopathologic features, immunophenotype and prognosis / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features and outcome of patients with diffuse large B-cell lymphoma (DLBCL), and to compare the differences between DLBCL of nodal and extranodal origins.</p><p><b>METHODS</b>One hundred and forty-two cases of de novo DLBCL collected during a 10-year period were reviewed. The clinicopathologic features and follow-up (2 - 108 months) data were analyzed. Tissue microarray blocks were performed and immunohistochemical studies using antibodies against CD10, bcl-6 and MUM1 were carried out. The cases were then further categorized into germinal center B cell-like (GCB) and non-GCB subtypes.</p><p><b>RESULTS</b>Primary gastrointestinal DLBCL often presented as early-stage disease (stage I or II) and was associated with low international prognostic index. They showed better prognosis than DLBCL of nodal and other extranodal origins. The positivity rates of CD10, bcl-6 and MUM1 were 19%, 51% and 58%, respectively. 36% of the cases belonged to GCB, while the remaining 64% were non-GCB. In general, DLBCL of extranodal origin showed more frequent bcl-6 expression than nodal DLBCL. As for extranodal DLBCL, GCB immunophenotype was often seen in thyroid and breast tumors, while testicular DLBCL usually carried a non-GCB immunophenotype.</p><p><b>CONCLUSIONS</b>DLBCL of various origins show a diversified GCB and non-GCB differentiation. Nodal and extranodal DLBCL, as well as extranodal DLBCL from different primary sites, carry different biologic characteristics and prognostic implications.</p>

Detection of t (14; 18) chromosomal translocation in paraffin-embedded tissues of follicular lymphoma and its clinical significance / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the genetic aberrations and their pathologic significance in follicular lymphoma (FL).</p><p><b>METHODS</b>Paraffin-embedded tissue samples of 55 cases of FL, 28 cases of other small B-cell lymphomas and 10 cases of reactive follicular hyperplasia were retrieved. Nested polymerase chain reaction (PCR) was used to detect clonal rearrangement of immunoglobulin heavy chain gene (IgH) in FL and other small B-cell lymphomas. The translocation t (14; 18) was studied by PCR and dual-color fluorescence in-situ hybridization (FISH) in FL. Cases of reactive follicular hyperplasia were used as controls.</p><p><b>RESULTS</b>Amongst the 55 cases studied, 49 cases were nodal and 6 cases were extranodal. There were 33 males and 22 females. The male-to-female ratio was 1.5:1. The median age of the patients was 57 years. Twenty-five cases belonged to histologic grade 1, while 19 cases were grade 2 and 11 cases were grade 3. Beta-actin DNA was detected in 50 cases of FL. Amongst those 50 cases, clonal IgH rearrangement was present in 34 (68%). Twenty-four cases (48%) and 25 cases (50%) were positive for FR3A and FR2 respectively. Fifteen cases (30%) showed dual positivity for both FR3A and FR2. Thirty-four cases (68%) demonstrated clonal IgH rearrangement. As for other small B-cell lymphomas, 25 cases were positive for beta-actin. FR3A and FR2 were detected in 18 and 17 cases respectively. Clonal IgH rearrangement was demonstrated in 24 cases. In contrast, none of the 4 cases of reactive follicular hyperplasia showed the clonal rearrangement pattern. Amongst the 44 cases of nodal FL analyzed, t (14; 18) was detected in 15 cases (with 14 cases in MBR and 1 case in mcr). In general, FISH was superior to PCR in detecting t (14; 18) using paraffin-embedded tissue samples.</p><p><b>CONCLUSIONS</b>The detection rate of clonal IgH rearrangement in FL is lower than that in other small B-cell lymphomas. Demonstration of t (14; 18) in paraffin-embedded tissue samples by FISH helps in diagnosis of FL. FISH is superior to PCR, as the technique is more sensitive and less labor intensive.</p>

Loss of heterozygosity in esophageal squamous cell carcinoma and its precursor lesion / 中华病理学杂志

<p><b>OBJECTIVE</b>To detect the loss of heterozygosity (LOH) in esophageal squamous cell carcinoma and adjacent high-grade squamous dysplasia, and to evaluate possible tumor suppressor genes in the development and progression of invasive malignancy.</p><p><b>METHODS</b>LOH was detected in normal esophageal mucosa, high grade squamous dysplasia and esophageal squamous cell carcinoma using microdissection and polymerase chain reaction technology. The changes of LOH at seven microsatellite markers and the relationship between LOH rate and clinicopathologic parameters were analyzed.</p><p><b>RESULTS</b>In high grade squamous dysplasia, LOH was detected at D13S802 (40%), D13S267 (32%), D13S221 (31%), D9S942 (30%), D17S520 (24%) and D9S171 (33%). However, D17S1798 LOH was not detected. In invasive squamous cell carcinoma, LOH was detected as follows: D13S267 (71%), D13S802 (58%), D17S520 (55%), D13S221 (45%), D9S942 (43%), D9S171 (33%) and D17S1798 (11%). The frequency of LOH in the seven microsatellite markers, the pathologic grade, clinical stage and occurrence of lymph node metastasis did not show any statistically significant correlation (P > 0.05).</p><p><b>CONCLUSIONS</b>The progression from normal squamous epithelium to high grade squamous dysplasia and subsequently to invasive squamous cell carcinoma of the esophagus was associated with accumulation of genetic errors. Possible tumor suppressor genes related to the development of esophageal squamous cell carcinoma may exist near D13S802 (13q12.12). Possible tumor suppressor genes near D13S267 (13q13.1), D17S1798 (17p13.3) and D17S520 (17p13.1) may be related to the progression of esophageal squamous cell carcinoma.</p>