OBJECTIVETo study the clinicopathologic features, diagnosis and differential diagnosis of systemic Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disease of childhood (CSEBV(+)T-LPD).

METHODSThirty cases of CSEBV(+)T-LPD were retrospectively studied by light microscopy, immunohistochemistry and in-situ hybridization for EBV-encoded RNA (EBER). The clinical information and follow-up data were analyzed.

RESULTSNineteen of the 30 patients were males and 11 females. The median age of disease onset was 9 years (range = 1.5 to 32 years). The average duration between disease onset and diagnosis was 14 months. The major clinical manifestations were fever (96.7%), lymphadenopathy (83.3%) and hepatosplenomegaly (66.7%). Cutaneous manifestations were not uncommon, which included hypersensitivity to mosquito bite (13.3%) and skin rash (20.0%). Six of the 20 patients died on follow up. Histologically, the lymph nodes showed expansion of T zone, with diminished or effaced lymphoid follicles. The lymphoid cells were of small to medium size. Scattered large lymphoid cells were also identified in the expanded T zone. Furthermore, the liver and spleen showed mild to marked sinusoidal infiltration. In some cases, various degrees of sinus histiocytosis with erythrophagocytosis were present. Skin biopsies showed mild to marked degree of lymphocytes infiltration in dermis. Immunohistochemical study and in-situ hybridization showed that the EBER-positive cells were of T lineage and CD3 positive. They also expressed cytotoxic molecules granzyme B and TIA-1. Seven of the 8 cases examined were CD8 positive, while the remaining case was mainly CD4 positive. Thirteen of 15 cases were shown to be CD56 negative. The number of EBER-positive cells ranged from 5 to more than 500 per high-power field. These cells included small to large lymphoid cells located mostly in the expanded T zone and sometimes in the germinal centers. Nine of the 30 cases, which consisted mainly of medium to large-sized lymphoid cells, were also EBER positive.

CONCLUSIONSSystemic EBV-positive T-cell lymphoproliferative disease of childhood occurs most often in children and young adults, with a median age of 9 years. It has a subacute or chronic clinical course. Most of the patients have evidence of systemic disease, often with lymph node, liver, spleen and skin involvement. It carries a poor clinical outcome and can be life-threatening. The disease is characterized by a clonal proliferation of EBV-infected T cells with cytotoxic immunophenotype. Definitive diagnosis requires correlation between clinical, pathologic and ancillary investigation findings.

Adolescent ; Adult ; CD3 Complex ; metabolism ; CD8 Antigens ; metabolism ; Child ; Child, Preschool ; Epstein-Barr Virus Infections ; genetics ; metabolism ; pathology ; virology ; Female ; Follow-Up Studies ; Gene Rearrangement, T-Lymphocyte ; Granzymes ; metabolism ; Herpesvirus 4, Human ; isolation & purification ; Humans ; Infant ; Lymph Nodes ; metabolism ; pathology ; Lymphoproliferative Disorders ; genetics ; metabolism ; pathology ; virology ; Male ; Poly(A)-Binding Proteins ; metabolism ; Prognosis ; RNA, Viral ; metabolism ; Retrospective Studies ; T-Cell Intracellular Antigen-1 ; T-Lymphocytes ; metabolism ; pathology ; virology ; Young Adult

OBJECTIVETo explore the expression of beta-catenin, Glut-1, PTEN in uterine endometrioid adenocarcinoma and their roles in tumorigenesis.

METHODSA total of 83 cases of endometrial hyperplasia were selected and reclassified according to EIN diagnostic criteria. Expressions of beta-catenin, Glut-1 and PTEN proteins were investigated by immunohistochemistry in 10 proliferative endometrium, 83 endometrial hyperplasia and 24 endometrioid adenocarcinoma.

RESULTS(1) 24 EIN (28.9%) lesions were reclassified among 83 previously diagnosed endometrial hyperplasia, of which, 16 of 24 EIN cases (66.7%) had a prior diagnosis of complex atypical hyperplasia. The relation between EIN diagnosis and grade of atypical hyperplasia was not obvious (P > 0.05). (2) Normal (membranous) expression of beta-catenin was present in 10 cases of proliferative endometrium. Abnormal (marked membranous/cytoplasmic, cytoplasmic and/or nuclear or negative) expression rates of beta-catenin in EIN lesions (50%, 12/24) and endometrioid adenocarcinoma (66.7%, 16/24) were significantly higher than that of benign hyperplasia (10.2%, 6/59) respectively (P < 0.01). However, the difference was not significant between EIN lesions and endometrioid adenocarcinomas (P > 0.05). (3) Low level expressions of Glut-1 was present in proliferative endometrium and benign hyperplasia. Overexpression of Glut-1 was present in 58.3% (14/24) of EIN and 70.8% (17/24) of endometrioid adenocarcinoma, respectively, and statistically not significant (P > 0.05). (4) Percentages of loss of PTEN expression showed no difference between EIN lesions (37.5%, 9/24) and proliferative endometrium (2/10), benign hyperplasia (28.8%, 17/59), endometrioid adenocarcinoma (62.5%, 15/24; P > 0.05). However, loss of PTEN expression in endometrioid adenocarcinoma was significantly higher than those in proliferative endometrium and benign hyperplasia (P < 0.05).

CONCLUSIONSAbnormal expression of beta-catenin and overexpression of Glut-1 may be the early events in tumorigenesis of endometrioid adenocarcinoma. The expression of both markers may be useful in distinguishing a benign hyperplasia from EIN and endometrioid adenocarcinoma. Lack of PTEN expression may be the earliest event in endometrial carcinogenesis. However, it can not be used yet as a diagnostic marker for the EIN lesion.

Adult ; Biomarkers, Tumor ; metabolism ; Carcinoma, Endometrioid ; metabolism ; pathology ; Endometrial Hyperplasia ; metabolism ; pathology ; Endometrial Neoplasms ; metabolism ; pathology ; Female ; Glucose Transporter Type 1 ; metabolism ; Humans ; Immunohistochemistry ; Middle Aged ; PTEN Phosphohydrolase ; metabolism ; beta Catenin ; metabolism

OBJECTIVETo study the clinicopathologic features, immunophenotype, differential diagnosis and prognosis of uterine epithelioid trophoblastic tumor(ETT).

METHODSFrom 2000 to 2007, 5 ETTs cases were diagnosed in the affiliated Women's Hospital, School of Medicine, Zhejiang University. The pathologic characteristics and immunophenotype of the tumors were analyzed by histological examination and immunohistochemistry of CK18, p63, inhibin-alpha, HCG, HPL, PLAP and Ki-67. The clinical prognostic factors were evaluated based on a following-up data with a period of 11 - 50 months.

RESULTSThe overall prevalence of ETT was 0.48% among all the gestational trophoblastic diseases patients received in the same period. Five ETT patients were in the reproductive ages with a median of 33 years. Histologically, the tumor showed an invasive, nodular growth consisting of uniform mononuclear trophoblastic cells. There were zones of hyaline material in the tumour nests. Necrosis was commonly seen with a characteristic geographic pattern. Immunohistochemically, all cases displayed a diffuse CK18 and p63 positivity, to be either positive focally or negative for HCG, HPL and PLAP staining. Inhibin-alpha staining was positive or negative either in the 5 cases. Two patients died of the tumour relapse: one died after 1 year with the tumor having a high mitotic activity (averagely 15 mitotic figures per 10 high-power fields), and the other died of lung metastasis 2 years after the diagnosis.

CONCLUSIONSETT is a rare trophoblastic disease with distinct clinicopathological features and immunostaining patterns. A high mitotic index and lung metastasis are indicators for an unfavorable prognosis.

Adult ; Alkaline Phosphatase ; metabolism ; Chemotherapy, Adjuvant ; Chorionic Gonadotropin ; metabolism ; Epithelioid Cells ; pathology ; Female ; Follow-Up Studies ; GPI-Linked Proteins ; metabolism ; Humans ; Hysterectomy ; Inhibins ; metabolism ; Isoenzymes ; metabolism ; Keratin-18 ; metabolism ; Ki-67 Antigen ; metabolism ; Lung Neoplasms ; secondary ; Membrane Proteins ; metabolism ; Middle Aged ; Neoplasm Recurrence, Local ; Placental Lactogen ; metabolism ; Pregnancy ; Trophoblastic Neoplasms ; drug therapy ; metabolism ; pathology ; secondary ; surgery ; Uterine Neoplasms ; drug therapy ; metabolism ; pathology ; surgery

OBJECTIVETo explore the existence of vasculogenic mimicry (VM) in ovarian carcinoma and its correlationship with the clinicopathologic features and prognosis of the tumor.

METHODSA total of 84 ovarian carcinoma cases were collected with complete clinical and prognostic data. CD31 immunohistochemistry and PAS special stain were used to investigate VM in the tumor tissue. Immunohistochemical staining of VEGF, MMP-2, MMP-9, E-cadherin, beta-catenin, and Vimentin were used to explore the pathogenesis of VM.

RESULTSTotally 36 of 84 cases exhibited evidence of VM. FIGO classification, pathologic grades and histological types were significantly different between the VM and non-VM groups. Expression of VEGF, MMP-2, MMP-9, E-cadherin and beta-catenin were higher in the VM group than in the non-VM group. Kaplan-Meier survival curve analysis showed that cases of the VM group had a lower survival rate than that of the non-VM group (P = 0.04).

CONCLUSIONSVasculogenic mimicry exists in ovarian carcinoma. Ovarian carcinomas with a high grade malignancy have a high incidence of VM formation, a higher incidence of metastases and a lower survival rate. High expression of MMP-2 and MMP-9 may contribute to the formation of VM in the ovarian cancer.

Cadherins ; metabolism ; Carcinoma, Endometrioid ; metabolism ; pathology ; Cystadenocarcinoma, Mucinous ; metabolism ; pathology ; Cystadenocarcinoma, Serous ; metabolism ; pathology ; Female ; Humans ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Middle Aged ; Neoplasm Metastasis ; Neovascularization, Pathologic ; metabolism ; pathology ; Ovarian Neoplasms ; metabolism ; pathology ; Survival Rate ; Vascular Endothelial Growth Factor A ; metabolism ; beta Catenin ; metabolism

OBJECTIVETo study the value of combined use of paternally imprinted gene product p57(KIP2) immunohistochemistry and flow cytometry in the differential diagnosis of placental hydropic diseases.

METHODSA total of 32 cases of hydropic placenta with DNA polymorphism information were collected, and the genetic results were used as basis for the diagnosis of complete hydatidiform moles (CHM), partial hydatidiform moles (PHM) or hydropic abortions. All cases were examined by histology, p57(KIP2) immunohistochemical staining (EnVision method) and flow cytometry DNA ploidy analysis. The p57(KIP2) immunohistochemical staining and DNA ploidy results were compared with the genetic results.

RESULTSIn CHM, p57(KIP2) negative rates were 95.2% (20/21), whereas all the 11 cases of non-CHM (7 cases PHM and 4 cases hydropic abortions) were positive (11/11). In 11 p57(KIP2) -positive cases, 7 cases with triploidy and 4 cases with diploidy by flow cytometry were proven to be PHM and hydropic abortions by genetic analysis, respectively. Overall, 96.9% (31/32) cases of hydropic placentas were correctly diagnosed by combined use of p57(KIP2) immunohistochemistry and flow cytometry.

CONCLUSIONSp57(KIP2) immunohistochemical negativity is a reliable index for the diagnosis of CHM. Combined flow cytometry DNA ploidy and p57(KIP2) immunohistochemistry are useful in the pathological differentiation of CHM, PHM and hydropic abortions.

Abortion, Spontaneous ; diagnosis ; genetics ; metabolism ; Adult ; Cyclin-Dependent Kinase Inhibitor p57 ; metabolism ; DNA, Neoplasm ; analysis ; Diagnosis, Differential ; Diploidy ; Female ; Flow Cytometry ; Humans ; Hydatidiform Mole ; diagnosis ; genetics ; metabolism ; Immunohistochemistry ; Middle Aged ; Pregnancy ; Triploidy ; Uterine Neoplasms ; diagnosis ; genetics ; metabolism ; Young Adult

Carcinoma in Situ ; pathology ; virology ; Carcinoma, Squamous Cell ; pathology ; virology ; Diagnosis, Differential ; Female ; Humans ; Paget Disease, Extramammary ; pathology ; virology ; Papillomavirus Infections ; Precancerous Conditions ; pathology ; virology ; Vulvar Neoplasms ; classification ; pathology ; virology ; Warts ; pathology ; virology

CD5 Antigens ; metabolism ; Chromosomes, Human, Pair 11 ; Chromosomes, Human, Pair 14 ; Chromosomes, Human, Pair 18 ; Cyclin D1 ; metabolism ; Diagnosis, Differential ; Humans ; Ki-67 Antigen ; metabolism ; Lymphoma, B-Cell, Marginal Zone ; genetics ; metabolism ; pathology ; Lymphoma, Follicular ; genetics ; metabolism ; pathology ; radiotherapy ; Lymphoma, Mantle-Cell ; genetics ; metabolism ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Pseudolymphoma ; metabolism ; pathology ; Translocation, Genetic

Burkitt Lymphoma ; classification ; genetics ; therapy ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; classification ; genetics ; therapy ; Lymphoma, B-Cell ; classification ; genetics ; therapy ; Lymphoma, Follicular ; classification ; genetics ; therapy ; Lymphoma, Large B-Cell, Diffuse ; classification ; genetics ; therapy ; Lymphoma, Mantle-Cell ; classification ; genetics ; therapy ; Prognosis

CA-19-9 Antigen ; metabolism ; Carcinoembryonic Antigen ; metabolism ; Carcinoma ; pathology ; Carcinoma in Situ ; etiology ; genetics ; metabolism ; pathology ; Chromosomes, Human, Pair 17 ; Chromosomes, Human, Pair 5 ; Diagnosis, Differential ; Gallbladder Diseases ; pathology ; Gallbladder Neoplasms ; etiology ; genetics ; metabolism ; pathology ; Humans ; Loss of Heterozygosity ; Microsatellite Instability ; Polyps ; pathology ; Precancerous Conditions ; etiology ; genetics ; metabolism ; pathology

Adenocarcinoma ; metabolism ; pathology ; surgery ; ultrastructure ; Aged ; Carcinoembryonic Antigen ; metabolism ; Carcinoma, Neuroendocrine ; metabolism ; pathology ; surgery ; ultrastructure ; Cardia ; Humans ; Ki-67 Antigen ; metabolism ; Male ; Microscopy, Electron, Transmission ; Stomach Neoplasms ; metabolism ; pathology ; surgery ; ultrastructure ; Synaptophysin ; metabolism