Diagnostic and therapeutic values of interphase fluorescence in situ hybridization in B-cell lymphomas: a clinicopathologic analysis of 604 cases / 中华病理学杂志

Objective@#To investigate the feasibility and value of interphase fluorescence in situ hybridization (FISH) in the pathological diagnosis, differential diagnosis and therapeutic assessment of B-cell lymphomas.@*Methods@#The cohort included 604 cases of B-cell lymphoma which were collected at West China Hospital from May 2010 to December 2016.And all were subjected to interphase FISH using 11 break apart or fusion probes (MYC, bcl-2, bcl-6, IRF4, MYC/IgH, bcl-2/IgH, CCND1/IgH, IgH, API2/MALT1, p53/ATM, and D13S319/CEP12).@*Results@#The median age of the 604 B-cell lymphoma patients was 47.7 (aged 2-90) years including 372 men and 232 women. All the cases was divided into 463 large B cell lymphomas(LBL) and 141 small B cell lymphomas, and the total interphase FISH positive rate was 59.8% (361/604). Among the 463 LBL, 12.5% (58/463), 9.5% (44/463) and 2.2% (10/463) of cases showed MYC, bcl-6 and bcl-2 gene rearrangements respectively; and 363 diffuse large B cell lymphoma (DLBCLs) were reclassified as germinal center B-cell (GCB) subtype (38.6%, 140/363) and non-GCB subtype (61.4%, 223/363) by Hans algorithm. The rearrangement rates in GCB and non-GCB DLBCL were 45.7%(64/140)and 21.5%(48/223; P=0.001), respectively. Compared to the non-GCB DLBCL, GCB DLBCL showed higher MYC and bcl-2 gene rearrangements (P=0.001). Eleven (2.4%, 11/463) cases had MYC and bcl-6 or bcl-2 gene rearrangement (double-hit lymphoma); one (0.2%, 1/463) case had MYC, bcl-6 and bcl-2 gene rearrangements (triple-hit lymphoma); two (0.4%, 2/463) cases had bcl-2 and bcl-6 gene rearrangements. MYC translocation and MYC/IgH fusion were detected in 94.2%(81/86) and 83.7%(72/86) cases of Burkitt lymphomas. IRF4 rearrangement was detected in two cases of IRF4+ LBCL. Genetic abnormalities were detected in 9/19, 100%(29/29), 30.8%(12/39) and 68.5%(37/54) cases of follicular lymphoma, mantle cell lymphoma, MALT lymphoma and chronic lymphocytic leukemia, respectively.@*Conclusions@#Interphase FISH can rapidly and accurately detect the genetic changes in B-cell lymphomas. Different genetic changes are specifically valuable to the diagnosis, differential diagnosis, prognosis evaluation and treatment guidance of various B-cell lymphomas.

Detection ofN-myc andALK abnormality in and clinicopathological analyses of 83 cases of neuroblastoma / 临床儿科杂志

ObjectivesTo retrospectively analyze the clinicopathological features of neuroblastoma (NB) and investigate the signiifcance of abnormality ofN-myc and anaplastic lymphoma kinase (ALK) gene copy number change as well asALKmu-tations in NB.Methods Eighty-three NB patients were collected and classiifed into different subgroups according to the clinical stage and histology. Fluorescence in situ hybridization (FISH) was performed to detect the abnormalities ofN-mycandALK genes. The extracted DNA was ampliifed by PCR and sequenced to investigate the point mutations of theALK gene. Follow-up data were collected and survival analysis was performed.ResultsFISH detection showed that the aberration ofN-mycgene copy number presented as gain and ampliifcation. The aberration ofALK gene presented as point mutation and gain. It was shown that 17 cases had the abnormality of bothN-myc andALK gene. Survival analysis showed that the prognostic factors included the clinical stage, age and abnormality ofN-myc genes.ConclusionDetection ofN-myc andALK abnormality in NB would be helpful for evaluating the prognosis and providing theoretical basis forALK target therapy.

Correlation of immunoglobulin variable heavy chain gene mutation status with prognosis in patients with mantle cell lymphoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the relationship between immunoglobulin variable heavy chain (IgVH) gene mutation status and clinical features, pathologic findings and biologic behavior of mantle cell lymphoma (MCL).</p><p><b>METHODS</b>IgVH gene was amplified in 60 cases of MCL with FR1-JH and FR2-JH primers in BIOMED-2. The sequence was determined by cloning. The IgVH somatic mutational status was analyzed using NCBI's Ig-Blast tool. The relationship between IgVH gene mutation status and clinicopathologic features was also analyzed.</p><p><b>RESULTS</b>Forty percent (24 cases, 28 functional Ig genes) of the MCL cases displayed somatically mutated VH genes (defined as > 2% mutated), whereas 60.0% (36 cases, 40 functional Ig genes) showed unmutated VH genes. The most widely used genes were VH3-21 (27.9%) and VH4-34 (19.1%). The former were mainly used by unmutated cases, while the later mainly by mutated cases.Intraclonal heterogeneity was noted in 19 cases. There was no correlation of VH mutation status and specific VH gene with survival (P > 0.05).</p><p><b>CONCLUSIONS</b>MCL comprises at least two subsets that do not correlate with morphology: one with unmutated VH genes and one with mutated VH genes. The biased use of VH3-21 and VH4-34 is noted. The nonrandom usage of IgVH segments suggests specific antigens may play a role in the pathogenesis and progression of MCL subsets. There is no correlation of IgVH mutation status and specific VH gene with survival.</p>

Clinicopathological features of pancreatic neuroendocrine neoplasms: a retrospective analysis of 64 cases / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the clinicopathological features of pancreatic neuroendocrine neoplasms (P-NENs).</p><p><b>METHODS</b>From January 2006 to December 2010, 64 patients with P-NENs were diagnosed in the Department of Pathology, West China Hospital, Sichuan University. Immunohistochemical staining of neuroendocrine markers, synaptophysin (Syn) and chromogranin A (CgA), were first made to determine whether the tumor had neuroendocrine properties, then the P-NENs were classified as neuroendocrine tumor (NET), neuroendocrine carcinoma (NEC) and mixed adenoneuroendocrine carcinoma (MANEC, G3) according to the morphological changes and proliferative activity (Ki 67 expression).</p><p><b>RESULTS</b>Of all the 64 cases detected, 60 were NETs and four were NEC. Most of the tumors were single solitary masses, and more than half of the tumors arose in the head of the pancreas, while about one third in the tail. The positive rates of CgA and Syn immunostaining were 96.9% and 95.3%, respectively. The tumor stages of the 64 patients were as follows: stage I, 44 cases; stage II, 11 cases; stage III, one case; and stage IV, 8 cases. The median age of patients in the study was 45.56 years. Of all the P-NENs, 38 cases were functional ones, presenting with characteristic clinical syndrome owing to hormone hypersecretion, while 26 cases were nonfunctional ones with no distinct clinical syndrome. 58 patients underwent surgical operation. The 5-year progression-free survival rate was 91.4%.</p><p><b>CONCLUSIONS</b>P-NENs may occur anywhere in the pancreas, and the clinical manifestations may not be easy to distinguish from other diseases. Diagnosis depends on pathological examination. Surgery is the major approach option, and the clinical prognosis is rather good. The tumor histological grade and distant metastasis are independent prognostic factors in P-NENs.</p>

Hepatic epithelioid angiomyolipoma: a clinicopathologic analysis of 25 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, immunophenotype, histological diagnosis and prognosis of hepatic epithelioid angiomyolipoma.</p><p><b>METHODS</b>Clinical data of 25 cases of hepatic epithelioid angiomyolipoma were collected along with follow-up study of the patients. The pathological features were documented and immunohistochemical study of various markers was performed with an emphasis on diagnosis and differential diagnosis.</p><p><b>RESULTS</b>Hepatic epithelioid angiomyolipoma was more commonly found in young women without characteristic clinical symptoms. Its morphological features were characterized by marked cytological atypia, relatively rare mitotic figures; radial distribution of tumor cells around the thin-walled blood vessels or muscular vessels; and the presence of common multinucleated giant cells and large ganglion-like tumor cells. The tumor cells expressed both melanoma cell markers (HMB45, MART-1) and smooth muscle cell markers (SMA). Tumor cells expressed various other markers including ER 16% (4/25), PR 32% (8/25), TFE3 24% (6/25) and p53 60% (15/25).</p><p><b>CONCLUSIONS</b>Hepatic epithelioid angiomyolipoma has variable morphological features and characteristic immunohistochemical phenotype. The differential diagnoses include a variety of tumors. The biological behavior of the tumor tends to be benign.</p>

Expressions of survivin and Ki67 and their significance in cutaneous extranodal NK/T-cell lymphoma,nasal type / 中华皮肤科杂志

Objective To investigate the expressions of survivin and Ki67 in cutaneous extranodal NK/T-cell lymphoma,nasal type and their significance.Methods Clinical data and laboratory test results were collected from 15 cases of cutaneous extranodal NK/T-cell lymphoma,nasal type with skin lesions as the initial manifestation.Immunohistochemical SP method was used to measure the expression of survivin and Ki67 in tissue sections from the lesions of these patients.To determine the percentage of survivin-or Ki67-positive cells,200 tumor cells were counted in a high power field (HPF) and 5 HPFs were observed in 1 section.Results There were 10 males and 5 females among the 15 patients,with the median age at diagnosis being 28.7 (range:9-62) years.Immunohistochemical study showed that the lesional tissue was positive for CD56 in 9 cases,CD3ε in 13 cases,T cell intracellular antigen (TIA)-1 in 15 cases,granzyme B in 10 cases,CD3 in 2 cases,βF1 in 1 case,but negative for CD4,CD5,CD8,CD20,and CD79α.All the 15 cases were positive for 1 or 2 T-cell associated antigens (CD2,CD7 or CD45RO).CD30 was observed in large tumor cells in 3 of the 15 cases.Monoclonal TCR-γ gene rearrangement was found in 3 of 14 cases.In situ hybridization for EBER1/2 was positive in all of the 15 cases.Survivin and Ki67 were expressed in 73.3％ (11/15) and 100％ (14/14,note:a tissue section was unavailable because of the detachment of tissue from the slide) of the specimens respectively,with the average percentage of positive cells being 23.97％ ± 18.35％ and 41.20％ ± 19.52％ for survivin and Ki67,respectively.Statistical differences were observed in the percentage of Ki67-expressing cells between the specimens with 0-2 mitotic figures per high power field from 9 cases and those with more than 2 mitotic figures from 6 cases (25.27％ ± 12.96％ vs.58.23％ ± 16.02％,F =19.14,P =0.001).No correlation was found between the expression of survivin and Ki67 in cutaneous extranodal NK/T-cell lymphoma,nasal type.Conclusion The high expressions of survivin and Ki67 may play a role in the occurrence and development of cutaneous extranodal NK/T-cell lymphoma,nasal type.

Experience on trial of virtual slides in experiment teaching of pathology / 中华医学教育探索杂志

Virtual slides were applied in experiment teaching of pathology on trial in clinic medicine college of Sichuan university.The resuhs from the Survey showed that students and teachers preferred virtual slides in learning microscopic lesions.Virtual Slides can help us save time,promote quality of observation,carry out discussion based teaching and manage teaching documents.It can be used in network teaching after marking the lesions.

Primary intestinal NK/T cell lymphoma: a clinicopathologic study of 25 Chinese cases

Primary intestinal NK/T cell lymphoma is extremely rare and early diagnosis is frequently difficult. The aim of this study is to investigate the clinicopathological findings, immunophenotype, and T cell receptor [TCR] gamma gene rearrangement of primary intestinal NK/T cell lymphomas in 25 Chinese cases. Clinical data of the 25 cases were analyzed. Immunohistochemistry for immunophenotype, in situ hybridization for EBER, and polymerase chain reaction for TCR y gene rearrangement were investigated. Survival curves according to clinical characteristics were analyzed. The median age was 33 years and the median survival was 7 months. The common symptoms consisted of abdominal pain, fever, marasmus, diarrhea, and hematochezia. Endoscopically, the tumors were mainly featured by focal, multifocal or diffuse irregular ulcers, which most frequently emerged in the ascending colon. Histologically, the tumors were characterized by the proliferation of pleomorphic atypical lymphoid cells [ALCs], necrosis, lympho-epithelial lesions, and mixed inflammatory infiltration. The positive frequency of CDepsilon was 88.2%, of CD56 was 84%, granzyme B was 90%, and EBER was 84.2%. A total of 12 out of 14 cases [85.7%] highly expressed Ki67. The negative prognostic factors for survival were Ann Arbor stage HIE or IVE [P = 0.039] and more than one extranodal site of disease [P = 0.019]. Primary intestinal NK/T cell lymphomas most frequently favor young people and have a poor prognosis. Due to the nonspecific clinical and endoscopic findings, it is difficult to distinguish intestinal NK/T cell lymphomas from inflammatory and infectious disorders. Histopathology, immunophenotype, and DNA study play key roles in differential diagnosis

A comparative study between subcutaneous panniculitis-like T-cell lymphoma and cutaneous extranodal nasal-type NK/T cell lymphoma / 肿瘤

Objective:To compare the difference between 20 cases of subcutaneous panniculitis-like T-cell lymphoma (SPTL) and 19 cases of cutaneous extra-nodal nasal-type NK/T-cell lymphoma (cutaneous NK/T-cell lymphoma). Methods:The two types of lymphoma were compared in clinical pathology, immunological marker, Epstein-Barr (EB) virus infection, and T-cell receptor (TCR) gene rearrangement. Results:Differentiated diagnosis of the two types of lymphomas was not easy based on their clinical manifestations,but the cutaneous NK/T-cell lymphoma was always followed by extracutaneous dissemination and had a poor prognosis. Histopathologically, SPTL was usually limited in subcutaneous fatty tissues while the cutaneous NK/T-cell lymphoma showed diffused infiltration around the dermis and it often infiltrated into the subcutaneous fat tissues. Coagulation necrosis, angiocentric infiltration and epidermotropism were often observed in cutaneous NK/T-cell lymphoma. When compared with immunophenotypes, SPTL often expressed βF1, membrane CD3 and CD8 but did not express CD4 and CD56, while most of the cutaneous NK/T-cell lymphomas expressed CD56 and cytoplasm CD3ε and only a few cases expressed CD3 and CD8. The differences in the expression of CD56, CD3, CD8, and βF1 were significant between the two types of lymphomas(P<0.05). The positive rate of EBER1/2 was 25% (5/20) in SPTL while it was 100% in cutaneous NK/T-cell lymphoma. The difference was statistically significant (P<0.05). Monoclonal TCR-γ gene rearrangement was found in 16 out of 20 cases of SPTL (80%) but only in 4 of 18 cases in the cutaneous NK/T-cell lymphoma (22.2%). The difference was significant(P<0.05). Conclusion:The key points to distinguish the two lymphomas are (1) extracutaneous dissemination, coagulation necrosis, angiocentric infiltration and epidermotropism; (2) the expressions of CD56, CD3, CD3ε, CD8, and βF1; (3) the positivity of in situ hybridization of EB virus; (4) detection of the monoclonal TCR-γ gene rearrangement. To make an acute differentiated diagnosis of the two lymphomas, comprehensive analysis is necessary to integrate the results of clinical manifestation, histopathology, immunophenotype, infection of EB virus and gene rearrangement.

A comparison of clinical and pathologic characteristics between Crohn's disease and intestinal tuberculosis / 中华内科杂志

Objective To search for the distinctive diagnostic features of Crohn's disease and intestinal tuberculosis in clinical manifestations with methods widely used clinically.Methods A retrospective study enrolled 33 Crohn's disease and 34 intestinal tuberculosis inpatients in West China Hospital of Sichuan University from 1996 to 2007.The clinical characteristics and key points of differential diagnosis were analyzed.All the pathological sections were studied again.Results The total duration of symptoms in patients with a diagnosis of Crohn's disease was longer than that in patients with intestinal tuberculosis ( P < 0.05 ).The incidence of eolectomy is significantly higher in Crohn' s disease than in intestinal tuberculosis because of intestinal obstruction or undefined diagnosis ( P < 0.05 ).Hematochezia,extra-intestinal manifestation and ileus occurred significantly more in Crohn's disease than in intestinal tuberculosis( P < 0.05 ).Night sweating and hypoalbuminemia occurred significantly more in intestinal tuberculosis than in Crohn's disease( P <0.05 ).The positive rate of serum antibodies to mycobacterium and increased erythrocyte sedimentation rate is higher in intestinal tuberculosis than in Crohn's disease(P < 0.05).Cobblestone sign and fissure-shape ulcers were only found in Crohn's disease,while circular ulcer occurred significantly more in intestinal tuberculosis( P <0.05).The involvement of stomach,jejunum or ileum was significantly more in Crohn's disease than in intestinal tuberculosis( P < 0.05 ).Granulomas were more common in intestinal tuberculosis than in Crohn's disease( P < 0.05 ) and the site of granulomas was valuable for differential diagnosis.In all the Crohn's disease specimens,lymphoid aggregates in the lamina propria or submucosa were significantly more in surgically reseeted specimens than in endoscopic biopsies (P <0.05).Conclusions There are definitely some different features between the two diseases.It is essential to review the whole clinical data of the patient.The frequency of granulomas and the distribution of chronic inflammation are identified as histological parameters that can be used to differentiate tuberculosis and Crolm's disease.

A clinicopathologic study of 9 cases of primary pulmonary extranodal marginal zone B-cell lymphoma / 中国肺癌杂志

<p><b>BACKGROUND</b>To study the clinicopathologic and immunohistochemical features of primary pulmonary extranodal marginal zone B-cell lymphomas (MALT lymphomas).</p><p><b>METHODS</b>Immunohistochemical staining for LCA, CD20, CD45RO, CD5, cyclinD1, Ki-67, immunoglobine light chain κ and λ, CK and NSE was carried out in 9 patients with primary pulmonary extranodal marginal zone B-cell lymphomas by the S-P methods.</p><p><b>RESULTS</b>According to the histological pattern and immunohistochemical features, all patients were diagnosed as primary pulmonary extranodal marginal zone B-cell lymphomas. There were four males and five females with a median age of 51.5 years (range from 37 to 64 years). The tumor cells were positive for LCA and CD20, however, the positive rates of Ki-67 were low. The tumor cells expressed immunoglobine light chain restriction λ in 5 cases , κ in 1 case, both λ and κ in 1 case, and neither of them in 2 cases. The tumor cells were negative for CD45RO, CD5, cyclineD1, CK, NSE in all patients.</p><p><b>CONCLUSIONS</b>Primary pulmonary extranodal marginal zone B-cell lymphomas are inert lymphomas which are easily misdiagnosed. The evaluation of pathologic features and immunohistochemistry are useful and practical in the diagnosis and differential diagnosis of primary pulmonary extranodal marginal zone B-cell lymphomas.</p>

Primitive study of the cell lineage and Epstein-Barr virus infection in so called malignant histiocytosis with tissue microarray technique / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the cell lineage and Epstein-Barr virus infection in previously diagnosed cases of malignant histiocytosis (MH) with tissue microarray technique.</p><p><b>METHODS</b>Using tissue-chips, immunohistochemical staining, in situ hybridization and PCR to analyze 5 autopsy cases of MH.</p><p><b>RESULTS</b>(1) In all 5 cases, positive reactions of CD45RO, CD3 epsilon, TIA-1, Granzyme B were detected in the neoplastic cells, whereas negative reactions were found with CD30, CD20, CD56. (2) All cases revealed EBER1/2 positivity in neoplastic cells.</p><p><b>CONCLUSION</b>Previously diagnosed malignant histiocytosis is an EBV-associated aggressive NK/T cell lymphoma.</p>

Analyzing of prognosis of intestinal T-cell lymphoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the roles of different clinicopathological features and expression of EBV genome in prognosis of intestinal T-cell lymphoma (ITCL).</p><p><b>METHODS</b>Polymerase chain reaction for TCR-gamma gene rearrangement, in situ hybridization for EBER1/2 and immunohistochemical staining for CD4, CD8, CD45RO, CD56, TIA-1 were investigated and all patients followed-up. The LMP-1 expression was determined in forty-two ITCLs cases. The relationship between clinical data, different clinicopathological features, expression of EBV genome and prognosis were analyzed by SPSS10.0 program.</p><p><b>RESULTS</b>(1) All 42 cases of ITCL had an extremely poor prognosis with a median survival of 3.0 months, of which the one year survival rate and two year survival rate being 30% and 22% respectively. (2) The patients without TCR-gamma gene rearrangements showed poorer prognosis than those with TCR-gamma gene rearrangements, and the patients who received operation and chemotherapy showed better prognosis than those who only received operation (P < 0.05). (3) No significant prognostic factor for ITCLs was determined.</p><p><b>CONCLUSION</b>The special clinicopathological features of ITCL could be due to the cytotoxic function and the role of EBV infection in the pathogenesis of ITCL.</p>

Clinicopathologic features of mantle cell lymphoma and the significance of cyclin D1 in diagnosis / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathologic features of mantle cell lymphoma (MCL) and the significance of immunostaining for cyclin D1 in diagnosis.</p><p><b>METHODS</b>Clinicopathologic observation and immunohistochemical staining for CD20, CD45RO, cyclin D1, bcl-2, Ki-67, CD5 for 8 cases of mantle cell lymphoma were performed.</p><p><b>RESULTS</b>The 8 cases of mantle cell lymphoma consisted of 6 males and 2 females, aged from 43 to 78 years (mean 57 years). Histopathologically, MCL demonstrated architectural destruction by a vaguely nodular monomorphic lymphoid proliferation with vaguely nodular, diffuse or mantle zone growth patterns. Analogous to centrocytes, the lymphoma cells with slightly to markedly irregular nuclear contours showed moderately dispersed chromatin and a low mitotic figure. Three cases were transformed into highly aggressive blastoid variants. The tumor cells were positive for CD20, CD5, bcl-2 and cyclinD1 in all 8 cases and negative for CD45RO.</p><p><b>CONCLUSIONS</b>The clinicopathological features and special immunophenotypes were present in mantle cell lymphoma. This tumor can be differentiated from other small B-cell lymphomas on the basis of histopathologic features and positive cyclin D1 immunophenotype. The blastoid variant should also be differentiated from other variants.</p>

Chromosome translocation t (11;18) and expression of BCL10 protein in gastric mucosa-associated lymphoid tissue lymphoma / 中华消化杂志

Objective To detect chromosome translocation t (11;18)(q21;q21) and expression of BCL10 protein in gastric mucosa associated lymphoid tissue (MALT) lymphoma. Methods We, combining clinical and pathological data, detected API2 MLT fusion by reverse transcriptase polymerase chain reaction (RT PCR)as well as the expressions of BCL10 protein and Ki 67 by immunohistochemistry in cases of gastric MALT lymphoma and follicular gastritis (FG) and analyzed the relationships among them. Results API2 MLT fusion was detected in three cases (2 low grade and 1 low to high grade) out of 14 cases of gastric MALT lymphoma, and no in 8 cases of FG. BCL10 protein was weakly expressed in cytoplasm of B cells of germinal center in lymph follicles of FG; but abundantly in cytoplasm of tumor cells in gastric MALT lymphoma; 42.5% of the latter showed weak expression in nucleus. The expression of Ki 67 was significantly higher in low to high and diffuse large B cell lymphoma cases than in low grade cases( P 0.05), the frequency of nuclear expression of BCL10 increased with the increased expression of Ki 67. Conclusions Both API2 MLT fusion and BCL10 nuclear expression are associated with transformation of gastric MALT lymphoma from LG to HG. RT PCR technique used to detect API2 MLT fusion may be an important tool in identification of t(11;18)(q21;q21).

A study of Epstein-Barr virus infection in intestinal T-cell lymphoma / 中华消化杂志

Objective To investigate the status of Epstein Barr virus (EBV) latent infection, the subtypes of EBV, and the expression of EBV genome in intestinal T cell lymphoma (ITCL). Methods In situ hybridization for EBER1/2 and polymerase chain reaction for EBV nuclear antigen gene (EBNA 3C) of two EBV subtypes were performed in forty two cases of ITCL. Some cases which were positive in both in situ hybridization and immunohistochemistry were detected by double staining. Amplified product of EBNA 3C gene was analyzed by DNA sequencing. For immunohistochemical staining, EBNA 2 and LMP 1 monoclonal were applied. Results EBV infection was detected in 41 of the 42 cases ( 97.6% ). Thirty eight cases ( 90.5% ) exhibited specific bands by polymerase chain reaction, in which 32 (84.2%) were EBV type A, 2 (5.3%) were type B and 4 ( 10.5% ) were mixtures of type A and B. There were seldom base insertion and base deletion in EBNA 3C gene. In 36 ( 85.7% ) cases, the tumor cells showed positive in EBER1/2 ISH, and they were demonstrated to express CD 45 RO, CD 4, CD 8, CD 56 , or TIA 1 by in situ hybridization immunohistochemistry double staining. The expression frequency of LMP 1 was 38.1% (16/42). None case presented EBNA 2 positive reaction. There were two patterns of EBV latent infection in ITCL, the more common one was type Ⅰ and the other was type Ⅱ. Conclusions A high level EBV latent infection is present in ITCL in China, and EBV type A frequently occurs. The patterns of EBV latent infection in ITCL are either type Ⅰ or type Ⅱ. ITCL and nasal NK/T cell lymphoma might belong to the same spectrum.

Epstein-Barr virus-associated and Epstein-Barr virus not-associated intestinal T-cell lymphomas:A clinicopathologic study / 临床与实验病理学杂志

Purpose　To investigate the clinicopathological and immunohistochemical features of Epstein-Barr virus-associated and Epstein-Barr virus not-associated primary intestinal T-cell lymphomas(ITCL) and to study their cell origins. Methods　In situ hybridization for EBER1/2 and immunohistochemical staining for immunophenotypes, LMP-1,TIA-1,bcl-2 and CD21 were performed in 32 cases. The clinical data were analyzed and all patients were followed-up. Results　(1) In 27 of the 32 cases, EBER1/2 were detected in the tumor cells, in which 11 presented LMP-1 positive reactions. (2) All 32 cases of ITCL revealed CD45RO positivity，in which 4（12.5%） expressed CD8，8（25.0%）expressed CD4, 9（28.1%）expressed CD56,and 31（96.9%）expressed TIA-1. There were 17（53.7%）cases with CD4-，CD8-，CD56- immunophenotype. None expressed bcl-2 and CD21. 32 ITCL were classified into pleomorphic medium and large cell(n=28), monomorphic medium-sized(n=2), pleomorphic small cell(n=2). Clinically, most patients with ITCL were young males with abdominal pain, hematochezia, fever and weight loss. The prognosis of patients with ITCL showed poor (survival median was 1.7 month). (3) The differences between EBV-associated and EBV not-associated ITCL lay in hematochezia, fever and the expression of CD3, CD8 and CD56. Conclusion　Most of Chinese ITCL are EBV-associated ones with unusual clinicopathological and immunohistochemical features，which are of different lineages of T-cell subtypes, including cytotoxic T-cell or NK cell.

Investigation of the Clinicopathologic Features of Cutaneous NK/T Cell Lymphoma and Epstein－ Barr Virus Infection / 中华皮肤科杂志

Objective To study the clinicopathologic features and immunophenotype of cutaneous NK/T cell lymphoma and the association with Esptein－ Barr virus (EBV) infection. Methods Five cases of cutaneous NK/T cell lymphoma were studied. Histologic sections of embedded tissues were immunohistochemically stained with CD45RO, CD3? , TIA－ 1, CD20, Ki－ B5, CD68 and LMP1 antibodies, and in situ hybridization for EBV－ encoded small nuclear RNAs－ EBER1/2 was also carried out. Results Cutaneous NK/T cell lymphoma accounted for 5.68％ in the cutaneous malignant lymphoma in the same period of observation. There were 4 male and 1 female patients, and the mean age was 34 years. The main clinical manifestations were asymptomatic nodules and masses, which were accompanied by ulcers in 2 cases. Histologically, the tumors were mainly located in the dermis and subcutaneous adipose tissue, the infiltrated lymphoid cells were pleomorphic, and angiocentricity and angiodestruction were found in almost all cases. Immunohistochemical stain showed that five cases were T cell phenotype and the expression rate of TIA－ 1 was 100％ (4/4). The EBV was present in three of four cases by in situ hybridization. Conclusions Cutaneous NK/T cell lymphoma presents with unique and diagnostic clinicopathologic features, and is strongly associated with EBV.