OBJECTIVETo study the clinicopathologic features of Hodgkin lymphoma (HL) occurring in northern China, association with Epstein-Barr virus (EBV) infection and concordance between EBV protein immunohistochemistry (IHC) and in-situ hybridization (ISH).

METHODSTwo hundred and thirty-five cases were collected and their HE and IHC slides were reviewed to confirm the diagnosis and sort of HLs. All cases were performed with IHC staining for LMP-1 protein and ISH of EBV-encoded RNAs (EBER) was done in 101 cases to detect the existence of EBV.

RESULTSThe incidence peak was between age 25 and 35 years, followed by another peak between age 56 to 60 years. There were 135 males and 100 females. The tumor involved lymph nodes in 217 cases, and extranodal sites in 18 cases. There were 3 cases of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and 232 cases of classical Hodgkin lymphoma. All tumors were stained for CD30, CD20, CD3. CD30 was expressed in 227 cases (96.6%), CD20 was expressed in 53 cases (22.5%) with different level of intensity. CD3 was expressed only in 1 case (0.4%). CD15 staining was performed in 224 cases and 117 (52.2%) cases were positive. PAX-5 were performed in 213 cases and 160 (75.1%) cases showed weak to moderate expressions. Two hundred and thirty-five cases were immunohistochemically stained with LMP1 and 72 (30.6%) cases were positive. Meanwhile, EBER ISH were applied in 101 cases, and 40 cases (39.6%) were found positive. LMP1 was expressed in 30 cases among those EBER-positive cases, while LMP1 was only detected in 5 cases of the EBER-negative cases. There was no statistically significantce between LMP1 IHC and EBER ISH by pared chi-square test (P = 0.3), the overall concordance rate was 85.2%.

CONCLUSIONSThere was a bimodal age distribution in our group of HL cases from the northern part of China, with slight male predominance and mainly nodal involvement. Nodular sclerosis (NS) and mixed cellularity (MC) were major histologic subtypes. When it was compared with the EBER ISH method in detection EBV infection of HL, the more economical and convenient LMP1 IHC showed both high degree of consistency and overall concordance rate.

Adult ; Age Distribution ; Antigens, CD ; analysis ; China ; epidemiology ; Epstein-Barr Virus Infections ; complications ; epidemiology ; Female ; Herpesvirus 4, Human ; genetics ; isolation & purification ; Hodgkin Disease ; immunology ; pathology ; virology ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Incidence ; Male ; Middle Aged ; RNA, Viral ; analysis ; Sex Distribution

Increasing evidence suggests that multiple genes in the human leukocyte antigen(HLA) regions play an important role in development of cancers and immunity disorders. However, the biological mechanisms of the HLA associations are not well understood. We recently conducted a survey of all genome-wide association studies (GWAS) with significant findings in the HLA regions and concluded that diseases such as cancer and immune disorders are more likely to be associated with genetic variants located in the HLA regions than other diseases. This finding is suggestive for testing a hypothesis of a common etiology of infectious tumors and other immunity diseases.
Genetic Predisposition to Disease ; Genetic Variation ; Genome-Wide Association Study ; HLA Antigens ; genetics ; metabolism ; Herpesvirus 4, Human ; isolation & purification ; Humans ; Immune System Diseases ; genetics ; immunology ; virology ; Lymphoma, Non-Hodgkin ; genetics ; immunology ; virology ; Nasopharyngeal Neoplasms ; genetics ; immunology ; virology

The World Health Organization (WHO) recently defined systemic Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disorders (LPD) of childhood as a life-threatening illness. However, this rare disease has not been extensively studied. Here we report a case of systemic EBV-positive T-cell LPD in a previously healthy middle-aged man with a chief complaint of chronic diarrhea. The initial colon biopsy showed focal infiltration of EBV-positive small lymphocytes without any atypia. However, the disease rapidly progressed and the patient required a total colectomy due to severe gastrointestinal bleeding. Three and half months after admission, the patient died from a complication of disseminated intravascular coagulation. The resected colon showed diffuse infiltration of EBV-positive atypical lymphocytes with ischemic change. Most atypical lymphocytes were CD3+ or CD5+. The monoclonality of EBV was demonstrated by sequence variation analysis of the latent membrane protein 1 (LMP1) gene in the colectomy specimen as well as in the initial biopsy.
Chronic Disease ; Colonoscopy ; Diarrhea/*diagnosis ; Disseminated Intravascular Coagulation/diagnosis ; Epstein-Barr Virus Infections/complications/virology ; Feces/virology ; Gastrointestinal Hemorrhage ; Herpesvirus 4, Human/genetics/*isolation & purification ; Humans ; Lymphoproliferative Disorders/*diagnosis/immunology/virology ; Male ; Middle Aged ; RNA, Viral/analysis ; T-Lymphocytes/*immunology/pathology

Hypersensitivity to mosquito bites (HMB) is a disorder characterized by a necrotic skin reaction and generalized symptoms subsequent to mosquito bites. It has been suggested that HMB is associated with chronic Epstein-Barr virus (EBV) infection and natural killer cell leukemia/lymphoma. We describe here a Korean child who had HMB associated with chronic EBV infection and natural killer cell lymphocytosis. A 5-yr-old boy was suffered from necrotic skin lesions on the right ear lobe. Type A EB virus was detected from hlood cells and bone marrow biospy recognized hemophagocyrosis.
Animals ; Child, Preschool ; Culicidae/*immunology ; Epstein-Barr Virus Infections/complications/*diagnosis ; Herpesvirus 4, Human/genetics/isolation & purification ; Humans ; Hypersensitivity/complications/*diagnosis ; Insect Bites and Stings/complications/*immunology ; Killer Cells, Natural/immunology/*pathology ; Lymphocytosis/complications/*diagnosis ; Male ; Polymerase Chain Reaction

OBJECTIVETo study the clinicopathologic features of intravascular large B-cell lymphoma (IVLBCL).

METHODSTwo autopsy cases of IVLBCL were retrieved from the archival file. The clinicopathologic features, immunohistochemistry and molecular findings were studied.

RESULTSThe deceased were 70-year-old and 50-year-old males. Both of them had complained of a sudden onset of weakness and numbness of lower extremities. The clinical course deteriorated rapidly, with multi-organ failure. They died 85 days and 44 days after the presentation, respectively. Post-mortem examination did not reveal any mass lesion, except the presence of multiple skin and epicardium nodules, ranging from 0.5 cm to 2.5 cm in diameter, in the first patient. Pericardial effusion, ascites and pleural effusion were also observed. Histologically, neoplastic lymphoid cells filled up the small vessel lumina in many organs, including brain, hypophysis, spinal cord, spinal nerve roots, heart, lungs, kidneys, liver, spleen, digestive tract, pancreas, adrenal, thyroid, testes and lymph nodes. The tumor cells were relatively monotonous and of medium to large in size with round vesicular nuclei and 1 to 3 small basophilic nucleoli. Immunohistochemical study showed that the lymphoma cells expressed B-cell markers CD20 and CD79a, occasionally positive for CD5 and bcl-2 but negative for CD3, bcl-6, CD10, CD30, myeloperoxidase and cytokeratin. In-situ hybridization for Epstein-Barr virus-encoded RNA was negative. The proliferative index, as demonstrated by Ki-67 staining, was about 80%. Molecular study showed the presence of immunoglobulin heavy chain gene rearrangement in both cases, T-cell receptor-gamma gene rearrangement was not found.

CONCLUSIONSIVLBCL may present as neurological disturbance and carries distinctive morphologic characteristics, immunophenotype and molecular findings. The prognosis of this disease is often dismal.

Aged ; Antigens, CD20 ; analysis ; Autopsy ; B-Lymphocytes ; pathology ; virology ; CD79 Antigens ; analysis ; Herpesvirus 4, Human ; isolation & purification ; Humans ; Immunohistochemistry ; Lymphoma, B-Cell ; immunology ; pathology ; virology ; Lymphoma, Large B-Cell, Diffuse ; immunology ; pathology ; virology ; Male

OBJECTIVETo study the clinicopathologic features of inflammatory pseudotumor-like follicular dendritic cell tumor of spleen.

METHODSOne case of inflammatory pseudotumor-like follicular dendritic cell tumor of spleen was examined macroscopically and microscopically. Immunohistochemical study for CD21, CD23, CD35, clusterin, S-100 protein, vimentin, smooth muscle actin, CD1a, CD68, ALK protein, CD30, CD31, CD34, CD3 and CD20 was performed on formalin-fixed, paraffin-embedded sections by standard EnVision method. In-situ hybridization for Epstein-Barr virus (EBV)-encoded RNA was also carried out.

RESULTSMacroscopically, inflammatory pseudotumor-like follicular dendritic cell tumor was large in size, tan-colored, soft to rubbery in consistance and associated with central hemorrhage and necrosis. Histological examination showed scattered follicular dendritic cells admixed with abundant lymphocytes and plasma cells in the background, simulating inflammatory pseudotumor. On high-power magnification, the follicular dendritic cells possessed a moderate amount of pale to lightly eosinophilic cytoplasm, with indistinct cell borders. The nuclei were ovoid or spindly, with vesicular or stippled chromatin and small distinct, often centrally located, nucleoli. Some of the tumor cells showed nuclear pleomorphism and contained irregular foldings of nuclear membrane, coarse chromatin and prominent eosinophilic nucleoli. Mitotic figures were rarely identified. Immunohistochemical study showed that the tumor cells were positive for vimentin, clusterin, smooth muscle actin and CD68. They were weakly and focally positive for CD35 and S-100 protein, but negative for CD21, CD23, CD1a, ALK protein, CD30, CD31 and CD34. Most of the background lymphocytes were of T-lineage (CD3-positive) ,some were CD20 (B-cell marker)-positive. EBV RNA was demonstrated in the tumor cells by in-situ hybridization analysis.

CONCLUSIONSInflammatory pseudotumor-like follicular dendritic cell tumor is a rarely encountered low-grade malignancy with distinctive morphologic pattern. It is associated with EBV infection.

Adult ; Antigens, CD ; Antigens, Differentiation, Myelomonocytic ; Dendritic Cell Sarcoma, Follicular ; pathology ; physiopathology ; Dendritic Cells, Follicular ; pathology ; Female ; Granuloma, Plasma Cell ; etiology ; Herpesvirus 4, Human ; genetics ; immunology ; isolation & purification ; Humans ; Splenic Neoplasms ; pathology ; physiopathology

BACKGROUND: Fibrin-ring granuloma (FRG), which can be found in bone marrow or the liver, is a subtype of epithelioid granuloma characterized by a central fat vacuole and annular peripheral fibrinoid materials. FRG has been proven to be associated with many etiologies such as several infectious organisms (Coxiella burnett; Epstein-Barr Virus, EBV; cytomegalovirus, CMV; and hepatitis A virus), allopurinol induced hepatitis, Hodgkin's lymphoma, and peripheral T-cell lymphoma. METHODS: We retrospectively reviewed 24 patients diagnosed with FRG by bone marrow biopsy at a single institute between 1995 and 2004. We reviewed clinical symptoms and laboratory findings of the patients, classified them by etiology, and compared prognosis of each group. RESULTS: The most common cause of FRG was acute or chronic EBV infection. Chronic or acute EBV infection was associated with 41.4% of patients (10/24). Of the remaining patients, 33.3% (8/24) were leukemia or lymphoma patients after chemotherapy, 4.2% (1/24) was a patient with hepatic failure, and 20.8% (5/24) were diagnosed as fever of unknown origin. The most common symptom and clinical finding were fever and cytopenia. EBV-associated group comprised chronic active EBV infection, EBV-associated hemophagocytic histiocytosis, acute EBV infection, EBV-associated lymphoproliferative disease, and Langerhans' cell histiocytosis. The EBV-associated group showed a lower survival probability compared with the non-EBV group (P<0.05). CONCLUSIONS: Patients with bone marrow fibrin ring granuloma accompanied by fever require an active workup to find out the cause of infectious agents including EBV infection particularly due to their poor prognosis.
Adolescent ; Adult ; Aged ; Bone Marrow Diseases/diagnosis/*etiology/pathology ; Child ; Child, Preschool ; Epstein-Barr Virus Infections/*complications/diagnosis ; Female ; Fibrin/analysis ; Granuloma/diagnosis/*etiology/pathology ; Herpesvirus 4, Human/immunology/isolation & purification ; Humans ; In Situ Hybridization ; Male ; Middle Aged ; Polymerase Chain Reaction ; Prognosis ; Q Fever/diagnosis ; Retrospective Studies ; Survival Rate

OBJECTIVETo explore the relationship of Epstein-Barr virus (EBV) specific antibodies detection and the diagnoses of infectious mononucleosis (IM) caused by EBV.

METHODSSingle serum samples were collected from 220 inpatients with the diagnosis of IM between January 2005 and December 2006 in Beijing Children's hospital. The samples were detected for EBV-CA-IgM, EBV-CA-IgG, EBV-EA-IgG, EBV-NA-IgG and the avidity of EBV-CA-IgG by indirect immunofluorescent assay.

RESULTSThe positive rate of EBV-CA-IgG, EBV-CA-IgM, EBV-EA-IgG and EBV-NA-IgG were 100%, 95.9%, 79.5% and 4.1% respectively. Low-avidity EBV-CA-IgG was detected in 204 patients (92.7%) with positive EBV-CA-IgM and EBV-CA-IgG,negative EBV-NA-IgG, low-avidity EBV-CA-IgG were the main pattern of EBV antibody in IM patients (84.6%).

CONCLUSIONThe existence of EBV specific antibody (CA-IgG, CA-IgM, EA-IgG, NA-IgG and avidity of CA-IgG) could add more information to identify the stage of EBV infection so as to provide more reliable serological evidence for the diagnosis of IM.

Adolescent ; Antibodies, Viral ; blood ; Antibody Affinity ; Child ; Child, Preschool ; Epstein-Barr Virus Infections ; diagnosis ; immunology ; Female ; Fluorescent Antibody Technique, Indirect ; Herpesvirus 4, Human ; isolation & purification ; Humans ; Immunoglobulin G ; blood ; Infant ; Infectious Mononucleosis ; diagnosis ; immunology ; virology ; Male

OBJECTIVETo improve the clinical diagnostic standard and explore the mechanism of multiple clinical manifestation of Epstein-Barr virus (EBV) infection by studying the primary symptom and related disease spectrum in EBV infected children.

METHODSThe primary symptom, disease spectrum and prognosis of 190 EBV infected children whose serum EBV-VCA-IgM was positive detected by enzyme-linked immunosorbent assay (ELISA) were retrospectively reviewed.

RESULTSThe primary symptoms of EBV infection were diverse, the most common primary symptom was fever (66.8%), and followed by cough (14.2%), skin eruption (7.9%), lymphadenopathy (5.3%), eyelid edema (3.2%), pharyngalgia (1.6%), cardiac arrhythmia (1.6%), convulsion (1.6%), arthralgia (1.0%), gross hematuria (0.5%), etc. Most systems and organs were involved in the disease, including liver, spleen, lymph nodes, kidney, heart, lung, bone marrow, brain etc., which made the disease spectrum diverse. The most common disease caused by EBV infection was respiratory tract infection (40.5%), followed by infectious mononucleosis (17.9%), Kawasaki disease (6.3%), idiopathic thrombocytopenic purpura (5.8%), viral myocarditis (2.6%), viral encephalitis (2.6%), hemophagocytic syndrome (1.6%), rheumatoid arthritis (1.0%), acute lymphadenitis (1.0%), facial neuritis (1.0%), Evans syndrome (0.5%), systemic lupus erythematosus (0.5%), subacute necrotizing lymphadenitis (0.5%), non-Hodgkin's lymphoma (0.5%), acute aplastic anemia (0.5%), infantile hepatitis syndrome (0.5%), etc.; 9.5% of patients were ultimately diagnosed as EBV infection after long-term fever, and 10% of patients suffered from mixed infection. The prognosis of EBV infection was different due to involvement of different systems and organs. One patient died of hemophagocytic syndrome.

CONCLUSIONThe systems and organs impaired by EBV infection in children were diverse, and almost all the systems and organs were involved. Pediatricians should comprehensively analyze the clinical data and order corresponding laboratory examinations early to make the correct diagnosis and reduce the misdiagnosis rate and to treat appropriately.

Adolescent ; Age Factors ; Antibodies, Viral ; blood ; Child ; Child, Preschool ; Enzyme-Linked Immunosorbent Assay ; Epstein-Barr Virus Infections ; diagnosis ; pathology ; therapy ; Female ; Herpesvirus 4, Human ; immunology ; isolation & purification ; Humans ; Infant ; Infant, Newborn ; Male ; Prognosis ; Retrospective Studies ; Treatment Outcome

OBJECTIVESTo investigate the immunophenotypes of primary nasopharyngeal non-Hodgkin lymphoma (NPL) and their relationship to Epstein-Barr virus (EBV) infection.

METHODSThe clinical data and biopsies of 73 patients with NPL were collected in Guangzhou. In situ hybridization was performed to detect the EBV-encoded small non-polyadenylated nuclear RNAs (EBERs) on biopsy slides. Immunohistochemistry was used to classify the immunophenotypes of NPL and detect EBV antigen expression.

RESULTSForty-four (60.27%) of the 73 NPLs were of B cell lineage (CD79alpha(+)/CD3(-)/CD56(-)) while the 29 others (39.73%) were of non-B cell lineage. Seventy-three NPLs could be classified into 3 major immunophenotypes: B cell (CD79alpha(+)/CD3(-)/CD56(-), 44 cases), peripheral T cell (CD79alpha(-)/CD3(+)/CD56(-), 22) and NK/T cell (CD79alpha(-)/CD3(+)/CD56(+), 7). The percentages of EBV infection differed among the 3 major immunophenotypes (B cell: 11.36%, 5/44; peripheral T cell: 81.82%, 18/22; NK/T cell: 100%, 7/7). Both CD56(-) positive and CD56(-) negative immunophenotypes could further be divided into 4 subtypes: CD8(-)/CD4(-), CD8(+)/CD4(-), CD8(-)/CD4(+) and CD8(+)/CD4(+). All the CD8(-)/CD4(-) NPLs with CD56(-) positivity (7) or CD56(-) negativity (2) were infected with EBV. The neoplastic cells of a nasopharyngeal Burkitt's lymphoma expressed EBV nuclear antigen 1 (EBNA1) and EBV RNA (EBERs) only. In the other 29 EBV-infected NPLs, most of the lymphoma cells harboring EBV also expressed EBNA1 and EBERs; 21 of the 29 NPLs had a considerable number of neoplastic cells expressing latent membrane protein 1 (LMP1) (21/29, 72.41%) and 23 of 29 NPLs expressed latent membrane protein 2A (LMP2A) (23/29, 79.31%). A few lymphoma cells in 17 (17/29, 58.62%), 23 (23/29, 79.31%) and 22 NPLs (22/29, 75.86%) expressed Zta (Bam HI Z transactivator), viral capsid antigen (VCA) and membrane antigen (MA), respectively.

CONCLUSIONSThe prevalence ratio of the 3 immunophenotypes, namely, B cell, peripheral T cell and NK/T cell lymphoma, is about 6:3:1. However, the EBV infection ratio is reversed, 1:8:10. All the NK/T cell (CD56(+)) and peripheral immature T cell (CD3(+)/CD8(-)/CD4(-)) NPLs were EBV-infected. Except for one Burkitt's lymphoma, the EBV harbored in both B cell and non-B cell NPLs was mainly latent infection, type II, expressing EBNA1, LMP1 and LMP2A. However, the EBV found in a few lymphoma cells could become replicative, expressing lytic proteins.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; CD56 Antigen ; analysis ; Child ; Epstein-Barr Virus Infections ; complications ; Epstein-Barr Virus Nuclear Antigens ; analysis ; Female ; Herpesvirus 4, Human ; isolation & purification ; Humans ; Immunophenotyping ; Lymphoma, Non-Hodgkin ; etiology ; immunology ; virology ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; etiology ; immunology ; virology ; RNA, Viral ; analysis