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Objective: To study the clinicopathologic features, radiologic findings, treatment options and prognosis of dysembryoplastic neuroepithelial tumor (DNT)., Methods: The clinicopathologic and radiologic features were retrospectively analyzed in 10 cases of DNT., Results: Intractable partial seizure was the main presenting symptom in all patients. The tumor was located in temporal lobe (number = 5), frontal lobe (number = 3) or parietal lobe (number = 2). CT scan displayed a hypodense lesion. MRI scan revealed the tumor was non-enhancing T1WI hypointense and T2WI hyperintense, with internal septation and hyperintense ring around the tumor seen on FLAIR image. There was neither peritumoral edema nor mass effect. Histologically, the tumor showed the presence of glioneuronal element, with oligodendrocyte-like cells, floating neurons, astrocytes and associated microcystic changes. Immunohistochemical study demonstrated positivity for NeuN and synaptophysin in the neurons and some oligodendrocyte-like cells. Olig2 and S-100 protein were also expressed in the oligodendrocyte-like cells. Ki-67 index were lower than 1% in all cases. Nine cases were treated by complete surgical excision and the remaining case was subtotally excised. No post-operative chemotherapy or radiotherapy was given. One of the 10 cases recurred on follow up., Conclusions: Correct diagnosis of DNT requires correlation with clinicopathologic, radiologic and immunohistochemical findings. Complete resection of the tumor and epileptogenic foci is the mainstay of treatment for DNT, with intraoperative EEG monitoring. Post-operative chemotherapy or radiotherapy is not required.

Objective: To examine the cellular components at different stages of the crescent formation in four most common types of human crescentic glomerulonephritis (CGN), including anti-GBM disease (GBM-CGN), crescentic IgA nephropathy (IgA-CGN), ANCA associated pauci-immune CGN (ANCA-CGN) and crescentic lupus glomerulonephritis (LN-CGN)., Methods: Renal biopsy specimens of patients with GBM-CGN (n = 10), IgA-CGN (n = 12), ANCA-CGN (n = 12), and LN-CGN (n = 11) were selected. Immunohistochemistry was adopted to identify the cellular components using different cell markers including cytokeratin (PEC), CD68 (macrophage), nestin (podocyte), podocalyxin (podocyte), CD3 (lymphocyte), CD15 (neutrophil) and PCNA., Results: There were different subtypes of cell components identified during the formation of a cellular crescent in 4 different types of human CGN. Mainly of PEC 11.4 (0.0, 95.0)%, macrophage 8.0 (0.0, 35.0)% and podocyte 5.5 (0.0, 22.0)% and their constitutive percentages were different among various CGNs (P < 0.01). In all the CGNs studied, there were 50% of cells were negative to all the cell markers adopted for this expeiment. Podocalyxin positive cells 0.5 (0.0, 9.6)% were significantly less than nestin positive cells 5.5 (0.0, 22.0)% in all CGNs. PCNA positive cells were 44.7 (16.7, 83.3)% in the cellular crescent of all CGNs and co-localized with nestin (38/45 cases), CK (42/45 cases) or CD68 (24/45 cases)., Conclusions: PEC, macrophage and podocyte might play important roles in the formation of crescents. The staining disparity of nestin and podocalyxin indicates that podocyte dedifferentiation may occur during the crescent formation. PEC, podocytes and macrophages may participate in the formation of crescent in common CGNs through active cellular proliferation.

Objective: To study the clinicopathologic features of membranous nephropathy coexisting with IgA nephropathy., Methods: The renal biopsies performed in Peking University First Hospital during the period from January, 1998 to April, 2006 were retrospectively reviewed. The clinicopathologic features of 11 cases of membranous nephropathy coexisting with IgA nephropathy were studied. Electron microscopy with immunogold labeling for IgG and IgA were also performed., Results: The mean age of patients was 39.9 years. The male-to-female ratio was 1:2.9. The patients mainly presented with proteinuria. Proteinuria of nephrotic level was seen in 7 cases (63.6%). Seven cases also had associated microscopic hematuria. None of them showed evidence of renal insufficiency. Cases with secondary diseases, such as hepatitis virus infection and systemic lupus erythematosus, were excluded from the study. Histologically, vacuolation and thickening of glomerular basement membrane was seen. There was also mild mesangial hypercellularity and increase in mesangial matrix. Occasional glomeruli with crescent formation were identified in 2 cases. Immunofluorescence study showed granular staining for IgG and C3 along glomerular capillary walls, in addition to clumps of IgA deposits in mesangium. Electron microscopy revealed subepithelial and mesangial electron-dense deposits. Immunogold labeling showed IgG and IgA localized in the subepithelial and mesangial deposits respectively., Conclusion: Membranous nephropathy coexisting with IgA nephropathy possesses the clinicopathologic features of both components. It might be caused by independent occurrence of the two entities.

Objective: To study the clinicopathologic features of different variants of primary focal segmental glomerulosclerosis (FSGS)., Methods: One hundred and two cases of FSGS were retrieved from the archival files of Peking University First Hospital during the past 6-year period. The pathologic findings were reviewed and the degrees of active and chronic changes were assessed by morphometric analysis. The histopathologic patterns were then correlated with clinical manifestations., Results: Amongst the 102 cases of primary FSGS studied, 55.9% belonged to the NOS (not other specified) variant, while the perihilar, cellular, tip and collapsing variants accounted for 6.9%, 25.5%, 4.8% and 6.9% respectively. The level of proteinuria in the cellular and tip variants were much higher than that in the NOS variant; and the incidence of nephrotic syndrome in the tip and collapsing variants was higher than that in the other three variants (chi(2) = 12.23, P < 0.05). The activity score of the cellular and collapsing variants was also higher than that of the other three variants (P < 0.05). The interval between disease onset and renal biopsy diagnosis in the perihilar variant was longer than that in the other variants. The chronicity score of this variant was higher than that of the tip and NOS variants (P < 0.05). On the other hand, the total scores of active and chronic changes of the tip variant was lower than that of the cellular and collapsing variants (P < 0.05); and its chronic score was lower than that of the NOS and perihilar variants (P < 0.05)., Conclusions: The NOS variant is the commonest morphologic pattern seen in primary FSGS. The cellular and collapsing variants are the patterns associated with active lesions, while perihilar variant is the pattern associated with chronic lesions. The tip variant shows mild pathological changes compared with the other patterns.

Objective: Severe acute respiratory syndrome (SARS) is an emerging infectious disease that first manifested in humans in November 2002. The SARS-associated coronavirus (SARS-CoV) has been identified as the causal agent, but the pathology and pathogenesis are still not quite clear., Methods: Post-mortem lung samples from six patients who died from SARS from April to July 2003 were studied by light and electron microscopy, Masson trichromal staining and immunohistochemistry. Evidence of infection with the SARS-CoV was determined by reverse-transcription PCR (RT-PCR) , serological examination and electron microscopy., Results: Four of six patients had serological and RT-PCR evidence of recent infection of SARS-CoV. Morphologic changes are summarized as follows: (1) Diffuse and bilateral lung consolidation was seen in all patients (6/6) with increasing lung weight. (2) Diffuse alveolar damage was universal (6/6) with hyaline membrane formation (6/6), intra-alveolar edema/hemorrhage (6/6), fibrin deposition (6/6), pneumocyte desquamation (6/6). A marked disruption in the integrity of the alveolar epithelium was confirmed by immunostaining for the epithelial marker AE1/AE3 (6/6). (3) Type II pneumocytes, with mild hyperplasia, atypia, cytomegaly with granular amphophilic cytoplasm and intracytoplasmic lipid accumulation (5/6). (4) Giant cells in the alveoli were seen in five of 6 patients (5/6) , most of which were positive for the epithelial marker AE1/AE3 (5/6), but some cells were positive for the macrophage marker CD68(2/6). (5) A pronounced increase of macrophages were seen in the alveoli and the interstitium of the lung (6/6), which was confirmed by histological study and immunohistochemistry. (6) Haemophagocytosis was present in five of the 6 patients(5/6). (7) Lung fibrosis was seen in five patients(5/6), with alveolar septa and interstitium thickening(5/6), intraalveolar organizing exudates (6/6) and pleura thickening (4/6). Proliferation of collagen was confirmed by Masson trichromal staining, most of which was type III collagen by immunostaining. The formation of distinctive fibroblast/myofibroblast foci was seen in five patients (5/6) by light microscopy and immunochemistry. (8) Squamous metaplasia of bronchial mucosa was seen in five patients(5/6). (9) Thrombi was seen in all patients(6/6). (10) Accompanying infection was present in two patients, one was bacteria, the other was fungus. In addition, electron microscopy revealed viral particles in the cytoplasm of alveolar epithelial cells and endothelial cells corresponding to coronavirus., Conclusion: Direct injury of SARS-CoV on alveolar epithelium, prominent macrophage infiltration and distinctive fibroblast/myofibroblast proliferation may play major roles in the pathogenesis of SARS.

Objective: To study the morphologic changes of collagen type III glomerulopathy and to investigate the possible cellular origin for collagen III production., Methods: Light microscopy, immunofluorescent staining, immunohistochemistry (for collagen I, III and IV and alpha-SMA) and electron microscopy studies on 3 renal biopsy cases of collagen type III glomerulopathy were performed., Results: Two cases presented with nephrotic syndrome, one of which was associated with systemic hypertension. The third case showed renal impairment and renal hypertension. None had any known family history of renal diseases. Light microscopy showed diffuse thickened glomerular basement membrane and expanded mesangium with deposition of weakly PAS-positive homogeneous material not associated with mesangial cell proliferation. Electron microscopy revealed massive collagen fiber deposits in the subendothelial spaces and mesangium. The mesangial cells also contained bundles of microfilaments in the subplasmalemmal regions. Immunohistochemically, the diffuse positivity for type III collagen corresponded to the homogeneous material seen under light microscopy. The staining for type I and IV collagens was negative. Alpha-SMA was expressed in many mesangial cells., Conclusions: The diagnosis of collagen type III glomerulopathy can be made on the basis of detailed morphologic examination and ancillary investigations. It is possible that activated mesangial cells may be the cellular origin of collagen III.

Objective: To clarify the regulation of p53 through telomere pathway by investigating the molecular interaction between p53 and the main telomere-associated protein Telomeric Repeat Factor 2 (TRF2) in vitro., Methods: Four different p53-GST (glutathione S-transferase) fusion proteins and GST were expressed in E. coli and purified through glutathione sepharose 4B beads. The human recombinant p53s included wild type p53 (1-393), N terminus-truncated form p53 2C (95-393), C terminus-truncated form p53 N5 (2-293) and single amino acid mutant p53 R175H (175 arginine to histidine). Purified p53-GST fusion proteins and GST were mixed with cellular protein extracts of human breast cancer cells MCF-7 in vitro by pull down. The molecular interaction between p53 and TRF2 were detected by Western blot., Results: SDS-PAGE and Coomassie brilliant blue staining showed that the molecular weights of all purified proteins were as expected, with purities over 90%. Western blot of TRF2 indicated that both wild type p53 and p53 R175H could bind with TRF2 of MCF-7 cells in similar capacity, while GST alone failed to do so. The molecular interaction between p53 2C and TRF2 was enhanced. In contrast, the interaction between p53 N5 and TRF2 was significantly reduced., Conclusions: p53 can interact with TRF2 directly and specifically in vitro, with C terminus of p53 (293-393) being the binding region for their interaction. This C terminus-dependent interaction between p53 and TRF2 may be related to the cellular activities induced by telomere alterations.

Objective: To study the pathologic features, differential diagnosis and role of open lung biopsies (OLB) in usual interstitial pneumonia (UIP)., Method: The authors reviewed the pathologic, clinical and radiologic features of five cases of UIP (one autopsy case and four OLB cases), with follow-up information., Results: The typical histologic features were a non-uniform distribution of alveolar inflammation, fibroblastic foci, interstitial fibrosis and honeycomb change. There also was associated metaplasia of bronchiolar epithelium, type II pneumocyte hyperplasia and accumulation of alveolar macrophages., Conclusions: Characteristically, UIP exhibits temporal heterogeneity under low-power light microscopy, which includes changes in both the early and end stages. Open lung biopsy is an important diagnostic adjunct for suitable patients with atypical radiologic features on computerized tomography. Correlation between clinical, radiologic and pathologic findings is also essential for a correct diagnosis.

Objective: To study the possible role of hTERT and c-myc in endometrial carcinogenesis., Methods: The expression of hTERT and c-myc mRNA was examined by in situ hybridization of endometrial samples from 14 cases with simple hyperplasia, 10 with complex hyperplasia, 8 with atypical hyperplasia and 42 with endometrioid carcinoma., Results: Expression of hTERT was demonstrated in samples with simple hyperplasia, complex hyperplasia, atypical hyperplasia and carcinoma at frequencies of 2/14, 4/8, 8/10 and 39/42 (92.9%), respectively. The prevalence and intensity of the hTERT signal was greater in the carcinomas and lesions with atypical hyperplasia than those with simple or complex hyperplasia (P < 0.05). The expression of c-myc was demonstrated in samples with simple hyperplasia, complex hyperplasia, atypical hyperplasia and carcinoma at frequencies of 3/14, 1/8, 5/10 and 23/42 (54.8%), respectively. The frequency of c-myc expression was higher in carcinomas and hyperplastic lesions with atypia than those in lesions with simple or complex hyperplasia without atypia (P < 0.05). The expression of hTERT was shown to be correlated with the level of differentiation (P < 0.05), while the c-myc expression appeared to be associated with the depth of myometrial invasion (P < 0.05). The expression levels of hTERT and c-myc were not found to be correlated with each other in the tissues examined (P > 0.05)., Conclusions: The expression of hTERT and c-myc may be involved in the progression from the endometrial aypical hyperplasia to invasive carcinoma. The correlation between hTERT and c-myc in endometrial hyperplasia and carcinoma are not found.

Objective: To investigate the pathologic features and diagnostic algorithm of light chain nephropathy (LCN)., Methods: Seven cases of LCN were studied by light microscopy, electron microscopy and immunolabeling of light chains (kappa, lambda) by immunofluorescence and immunoelectron microscopy., Results: The histopathology of 7 cases by light microscopy was variable, with 3 cases showing nodular glomerulosclerosis, 1 case showing mild to moderate mesangial proliferation, and 3 cases showing cast nephropathy with minimal glomerular change. Immunofluorescence study revealed positive staining of a single type of light chain in mesangium (nodular pattern) or along glomerular basement membrane (linear), along tubular basement membrane and around arteriolar walls in all the 7 cases. Ultrastructurally, electron-dense granular deposits were identified in mesangium, subendothelial aspect of glomerular basement membrane, outer aspect of tubular basement membrane and arteriolar walls. Immunogold labeling of light chains showed distinct labeling of a single type light chain in the granular electron-dense materials (5 cases being kappa-positive and 2 being lambda-positive)., Conclusions: LCN typically shows nodular glomerulosclerosis. The ultrastructural change is characteristic and important for diagnosis. Immunolabeling of light chains by immunofluorescence and immunoelectron microscopy carries further diagnostic value, especially in cases with minimal light microscopic change.

Objective: To study the pathogenesis and the differential diagnosis of Castleman's disease., Methods: Histopathology, immunohistochemical staining and clinical courses of 26 cases of Castleman's disease (CD) were studied with follow-up study of 16 cases., Results: The present study included 6 cases of multicentric type, 20 cases of localized type in the clinical aspects and 19 cases with hyaline vascular type, 4 cases with plasma cell type, 3 cases with mixed type in the histologic aspect. The Multicentric type presented systemic lymphadenopathy, anemia, hyperglobulinemia, hepatosplenomegaly, skin changes, and lung disorder and kidney disfunction, of which 1 case died of respiratory and renal insufficiency. 13 of the 20 localized cases were of the hyaline vascular type, and with good prognosis. 7 of the 20 cases showed paraneoplastic pemphigus associated with hyperglobulinemia (4/7) and lung disease (5/7). The pathologic features composed of proliferation of the mantle zone B cell, follicular dendritic cell, plasma cell and small vessels. In immunohistochemical staining, kappa and lambda light chains were detected in each CD case., Conclusions: Many diseases are similar to CD clinicopathologically. It is important to make differential diagnosis through pathological study. Castleman's disease is a lymphoproliferative disorder. The pathogenesis of this multicentric disorder may be associated with autoimmune disease.

Objective: To observe the transdifferentiation of renal tubular epithelial cells in tubulointerstitial fibrosis., Methods: The renal tubulointerstitial fibrosis model in Wistar rats was established by unilateral renal vein ligature. The rats were kept 25 days after renal vein ligature. The kidneys were dissected every 5 days by killing 5 rats. The morphological changes of the kidney were observed by light microscopy, electron microscopy, polarizing microscopy and immunohistochemistry method., Results: The histological changes showed tubular atrophy and disappearance, widening of intertubular spaces with increased lymphocytes and mononuclear cells infiltration and fibrosis. The CK marker in injured and atrophic epithelial cells gradually weakened, but the alpha-SMA, vimentin, TGF-beta(1), collagen I and III showed gradually stronger positivity for immunohistochemistry. Some interstitial cells became positive for CK. Electron microscopy revealed decreased mitochondria, increased endoplasmic reticulum and microfilament of the tubular epithelial cells which merged into the interstitium. During the early stage of tubulointerstitial fibrosis, there was proliferation of type III collagen and then followed by type I collagen at later stage when observing the Sirius Red stained sections under the polarizing microscope., Conclusion: Tubular epithelial cells can transdifferentiate to fibroblasts during the process of tubulointerstitial fibrosis.

Objective: To investigate the clinicopathological manifestations of early renal amyloidosis (AL) and its diagnostic criteria., Methods: Fifteen cases with early renal amyloidosis admitted from 1994 to 2001 were collected from the hospital, and their clinical and pathological features were reviewed. Of them, the initial diagnoses were not made by depending findings from the light microscopy (LM) and immunofluorescense (IF), but confirmed by electron microscopy (EM) afterwards. Immuno-electron microscopy (IEM) were applied for amyloidosis typing., Results: Most patients of early renal AL were in the middle to old age. Nephrotic syndrome was the most prominent symptoms and signs accompanying with rare microscopic hematuria and hypertension. Most of them had a normal renal function. Pathological examinations of renal biopsies using LM and IF showed mild mesangial proliferation and mild thickening of glomerular basement membrane (GBM). Immunoglobulins and complements were negative or only scanty in certain cases, but in all cases there was a light chain protein deposition homogeously. There were 4 cases of minimal change glomerulopathy, 5 cases of mild mesangial proliferative glomerulonephritis, 5 cases of stage I membranous nephropathy, and 1 case of cast nephropathy diagnosed with LM. The amyloid fibrils (diameter 8 - 10 nm) were randomly distributed in the mesangium, along GBM and at the arteriolar wall under EM. Additionally, Congo red staining was positive. IEM demonstrated that amyloid fibrils labeled with colloid gold was combined with a kind of light chain protein which was confirmed as the light chain type of AL., Conclusions: The diagnosis of early renal AL was occasionally neglected by depending only findings of LM and LF. However, special amyloid fibrils can be detected using EM. EM observation is an indispensable technique for the diagnosis of early renal AL and the typing of AL may further be determined by using IEM.

Objective: To investigate expression of tissue transglutaminase (tTG) protein and its role in carcinogenesis of brain tumors., Methods: tTG protein was detected by immunohistochemical method in 62 astrocytomas, 18 oligodendrogliomas, 30 benign meningiomas, 30 pituitary adenomas and 10 normal brain tissues., Results: (1) In brain tumors, tTG protein expression was heterogeneous locating in tumor and endothelial cells. (2) Immunoreactivity of tTG protein was significantly different between different grades of astrocytomas. (3) Expression intensity of tTG protein in glioma was higher than that in benign brain tumors. (4) Strong expression of tTG protein in tumor cell was obtained around the necrosis foci and apoptotic cells in astrocytomas., Conclusions: tTG protein expression contributed to tumor malignant progression in malignant brain tumors.