Interferon-induced transmembrane protein 3 in the hippocampus: a potential novel target for the therapeutic effects of recombinant human brain natriuretic peptide on sepsis-associated encephalopathy.

Objective: This study aims to explore whether interferon-induced transmembrane protein 3 (IFITM3) is involved in recombinant human brain natriuretic peptide (rhBNP)-mediated effects on sepsis-induced cognitive dysfunction in mice. Methods: The cellular localization and expression level of IFITM3 in the hippocampus were detected. The IFITM3 overexpression was achieved using an intracranial stereotactic system to inject an adeno-associated virus into the hippocampal CA1 region of mice. Field experiments, an elevated plus maze, and conditioned fear memory tests assessed the cognitive impairment in rhBNP-treated septic mice. Finally, in the hippocampus of septic mice, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining and Immunoblot were used to detect changes in the protein expression of cleaved Caspase-8 and cleaved Caspase-3 in apoptosis-related pathways, and toll-like receptor 4 (TLR4) and nuclear factor κB (NF-κB) p65 in inflammatory pathways. Results: Fourteen days after cecal ligation and puncture (CLP) surgery, IFITM3 localized in the plasma membrane and cytoplasm of the astrocytes in the hippocampus of septic mice, partially attached to the perivascular and neuronal surfaces, but not expressed in the microglia. The expression of IFITM3 was increased in the astrocytes and neurons in the hippocampus of septic mice, which was selectively inhibited by the administration of rhBNP. Overexpression of IFITM3 resulted in elevated anxiety levels and long-term learning and memory dysfunction, completely abolished the therapeutic effect of rhBNP on cognitive impairment in septic mice, and induced an increase in the number of neuronal apoptosis in the hippocampal CA1 region. The expression levels of cleaved Caspase-3 and cleaved Caspase-8 proteins were significantly increased in the hippocampus, but the expression levels of TLR4 and NF-κB p65 were not increased. Conclusion: The activation of IFITM3 may be a potential new target for treating sepsis-associated encephalopathy (SAE), and it may be one of the key anti-apoptotic mechanisms in rhBNP exerting its therapeutic effect, providing new insight into the clinical treatment of SAE patients.

Bladder paraganglioma after kidney transplantation: A case report.

BACKGROUND: Kidney transplantation is associated with an increased risk of tumors in the urinary bladder. Among all the pathological types of tumors in the bladder, paraganglioma, which arises from extra-adrenal paraganglia and consists of chromaffin cells, is rare. Paragangliomas might cause severe clinical symptoms due to catecholamine hypersecretion or mass compression. Bladder paragangliomas are rare, especially those appearing after kidney transplantation. Here, we report a case of bladder paraganglioma developing after kidney transplantation. CASE SUMMARY: A 63-year-old woman received a kidney transplant 12 years ago and took oral immunosuppressants (cyclosporine, mizoribine, and methylprednisolone) for regular post-transplant treatment. The patient felt no discomfort and she came to the hospital for a routine checkup. A mass located in the bladder was incidentally discovered by computed tomography, and she underwent surgical treatment. A 2 cm × 2 cm invasive mass was found in the trigone of the bladder and the mass was removed. The diagnosis of paraganglioma was confirmed by morphology and immunophenotyping. The patient had a good prognosis and is still alive. CONCLUSION: Paraganglioma can grow in the bladder, which might cause no clinical symptoms. The diagnosis mainly depends on morphology and immunophenotyping. Surgical resection is an important treatment option for such patients.

Roles of Proteoglycans in the Tumourigenesis and Development of Adenoid Cystic Carcinoma and Pleomorphic Adenoma of the Salivary Gland: A Systematic Review.

Salivary adenoid cystic carcinoma (ACC) and pleomorphic adenoma (PA) are the most common types of salivary gland tumours; the former is malignant and the latter is benign but with features of a border tumour. Proteoglycans (PGs) produced by neoplastic myoepithelial cells are ubiquitous in both types of tumours. However, normal myoepithelial cells of salivary glands do not have the ability to secrete PGs. When the synthesis of PGs is blocked, the pulmonary metastasis and perineural growth of salivary ACC as well as the implanting growth of salivary PA are inhibited, highlighting the important functions of PGs in the tumourigenesis and development of these two tumours. In this review, we summarise literature from the past 40 years, including more recent findings from our laboratory, to clarify the pivotal roles of PGs produced by neoplastic myoepithelial cells in both the histogenesis and biological behaviours of ACC and PA.

Human antigen R-regulated mRNA metabolism promotes the cell motility of migrating mouse neurons.

Neocortex development during embryonic stages requires the precise control of mRNA metabolism. Human antigen R (HuR) is a well-studied mRNA-binding protein that regulates mRNA metabolism, and it is highly expressed in the neocortex during developmental stages. Deletion of HuR does not impair neural progenitor cell proliferation or differentiation, but it disturbs the laminar structure of the neocortex. We report that HuR is expressed in postmitotic projection neurons during mouse brain development. Specifically, depletion of HuR in these neurons led to a mislocalization of CDP+ neurons in deeper layers of the cortex. Time-lapse microscopy showed that HuR was required for the promotion of cell motility in migrating neurons. PCR array identified profilin 1 (Pfn1) mRNA as a major binding partner of HuR in neurons. HuR positively mediated the stability of Pfn1 mRNA and influenced actin polymerization. Overexpression of Pfn1 successfully rescued the migration defects of HuR-deleted neurons. Our data reveal a post-transcriptional mechanism that maintains actin dynamics during neuronal migration.

Multimodality-imaging manifestations of primary renal-allograft synovial sarcoma: First case report and literature review.

BACKGROUND: Primary renal synovial sarcoma (PRSS) is an extremely rare tumor with a poor prognosis. Its imaging and immunohistochemical characteristics may overlap with other renal tumors, which renders its early diagnosis in a dilemma. The diagnosis of primary renal synovial sarcoma requires histopathology and the confirmation of SYT-SSX gene fusion using molecular techniques. Cases of primary renal synovial sarcoma have been previously reported in the literature. However, to our knowledge, primary renal allograft synovial sarcoma was never described. CASE SUMMARY: A 43-year-old male patient who underwent kidney transplantation 9 months ago came to our hospital for regular follow-up. Traditional ultrasonography revealed multiple hypo-echo neoplasms in the renal allograft. Contrast-enhanced computed tomography (CECT) showed slightly hyper-density masses with slow homogeneous enhancement. Ultrasound-guided biopsy was conducted for accurate pathological diagnosis. The neoplasms were diagnosed as synovial sarcoma by pathological, immunohistochemical, and genetic analyses. Positron emission tomography/CT showed no evidence of metastasis. At approximately one week post biopsy, contrast-enhanced ultrasound was conducted to eliminate active hemorrhage. One month later, CECT showed that the biggest neoplasm grew from 3.3 cm to 5.7 cm in diameter. Parametric imaging was conducted with SonoLiver CAP to conduct further quantitative analysis, which showed that the enhancement pattern was heterogeneous hyper-vascular enhancement. Radical surgical resection of the whole renal allograft and ureter was conducted without additional adjuvant chemotherapy or external radiotherapy. Anlotinib was chosen for targeted therapy with a good response. CONCLUSION: We propose multimodality imaging for accurate diagnosis of renal allograft synovial sarcoma especially when it is formed by spindle-shaped cells.

HuR in the Medial Prefrontal Cortex is Critical for Stress-Induced Synaptic Dysfunction and Depressive-Like Symptoms in Mice.

Chronic stress has been observed to increase the risk of developing depression and induce neuronal alterations of synaptic plasticity, yet the underlying molecular mechanisms remain unclear. Here, we found that the ubiquitously expressed RNA-binding protein HuR was up-regulated in the medial prefrontal cortex (mPFC) of mice following chronic stress. In adult mice, AAV-Cre-mediated knockout of HuR in the mPFC prevented anxiety-like and depression-like behaviors induced by chronic stress. HuR was also required for the stress-induced dendritic spine loss and synaptic transmission deficits. Moreover, HuRflox/flox;Nex-Cre mice, which induce HuR loss of function from embryonic development, exhibited enhanced synaptic functions. Notably, we ascertained RhoA signaling to be regulated by HuR and involved in the modulation of structural synaptic plasticity in response to chronic stress. Our results demonstrate HuR is a critical modulator for the regulation of stress-induced synaptic plasticity alterations and depression, providing a potential therapeutic target for the treatment of depressive disorders.

EGFR mutations subset in Chinese lung squamous cell carcinoma patients.

Research has identified that epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) possess large benefits for adenocarcinoma (ADC), although little benefit for squamous cell carcinoma (SCC). The aim of the present study was to investigate the percentage of patients with SCC with the EGFR mutations subset and the benefits of EGFR TKIs in SCC. In the present study, the EGFR mutations subset was detected with an amplification refractory mutation system in 1,359 clinical SCC tissues. The association of the EGFR mutations subset with clinicopathological parameters was evaluated using the Mann­Whitney U test, and Kruskal­Wallis H. Kaplan­Meier survival analysis was used to estimate the effect of the EGFR mutations subset on SCC patient survival rates. A total of 94 out of 1,359 SCC patients were identified as having EGFR mutations, an EGFR mutation rate of 6.92%. The EGFR mutations subset in the 94 cases was identified as follows: 37.2% (35/94) in exon 19; 39.4% (37/94) in L858R; 5.3% (5/94) in T790M; 4.3% (4/94) in G719X; 2.1% (2/94) in L861Q; and 11.7% (11/94) in other mutations. Kaplan­Meier survival analysis identified that the differentiation, pathological tumor, node, metastasis stage, lymph node metastasis and distant metastases were significantly associated with patients' survival (P>0.05; log­rank test), and no significant difference was observed between TKI therapy and chemotherapy in terms of patient survival rates (P>0.05). In addition, the overall discordant rate of the EGFR mutations subset in SCC patients was relatively low. Due to the non­significant difference between TKI therapy and chemotherapy in terms of patient survival and the lower discordance rate of the EGFR mutations subset in SCC patients, EGFR TKIs could be a recommended treatment for SCC.

Cholesterol polyps in the distal common bile duct: a case report.

RATIONALE: Cholesterol polyps are rare in the common bile duct and difficult to diagnose. PATIENT CONCERNS: The small polypoid lesions often go undetected when using routine imaging methods, such as ultrasonography. DIAGNOSES: We treated a patient with cholesterol polyps in the common bile duct. After failing to detect choleliths using ultrasonography, magnetic resonance cholangiopancreatography revealed mild dilation of the common bile duct. Choledochoscopy was performed during laparoscopic cholecystectomy, which revealed yellowish-white polyps circumferentially distributed across the luminal surface of the distal common bile duct. Histological examination of biopsy specimens indicated cholesterol polyps with characteristic foamy cells. INTERVENTIONS: The patient was treated with ursodeoxycholic acid, and the number of polyps was found to have been reduced at the 6-week follow-up based on T-tube choledochoscopic examination. OUTCOMES: Recovery was unremarkable, and the ursodeoxycholic acid treatment was discontinued at the 6-month follow-up. LESSONS SUBSECTIONS: Our findings suggest that this rare condition can be treated pharmacologically to avoid potential postsurgical complications following resection of the distal common bile duct.

[Clinical and pathologic features of tubulocystic carcinoma of kidney].

OBJECTIVE: To investigate clinicopathological features and differential diagnosis of tubulocystic carcinoma of the kidney. METHODS: The clinical features, histological and immunohistochemical findings were analyzed in 3 cases of tubulocystic carcinoma of the kidney, along with review of the related literatures. RESULTS: Three patients were males with a mean age of 59 years old (range from 44 to 71 years). All presented with no symptom and their tumors were found during routine examination. The tumor size ranged from 1.5 to 5.0 cm in greatest dimension. The tumors were grossly well-circumscribed without capsules and exhibited a spongy cut surface. Microscopically, all three tumors were composed of tubules and cysts of varying sizes separated by thin fibrous septa. The epithelial lining cells were flat, cuboidal and columnar, with often a hobnail-like appearance characterized by abundant eosinophilic cytoplasm with prominent nucleoli. Two cases showed focal clear cytoplasm. One of the three cases coexisted with a papillary renal cell carcinoma. Immunohistochemically, all 3 cases showed positivity for pan-CK, vimentin, CK19, CD10, P504S, and focal positivity for 34ßE12. Two cases showed focal positivity for CK7. CONCLUSIONS: Tubulocystic carcinoma of the kidney is a rare kidney neoplasm and occurs predominantly in males. The tumor is characterized by gross spongy appearance and microscopic cysts and tubules often lined by hobnail-like cells and separated by thin fibrotic stroma. The differential diagnosis mainly includes other lesions of the kidney that have a multicystic growth pattern.

[Clinicopathologic analysis of intestinal follicular lymphoma first presenting with gastrointestinal symptoms].

OBJECTIVE: To study the clinical features, endoscopic findings, pathologic diagnosis and treatment options of intestinal follicular lymphoma first presenting with gastrointestinal symptoms. METHODS: The clinical features, pathologic findings and follow-up data were retrospectively studied in 9 cases of intestinal follicular lymphoma. Immunohistochemical study for CD3, CD5, CD20, CD21, Ki-67, bcl-2, bcl-6, CD10 and cyclin D1 was carried out. RESULTS: Seven of the 9 patients were females and two were males. The age of patients ranged from 5 to 60 years (mean = 44 years). The clinical manifestations included abdominal pain (5 cases), blood in stool (3 cases) and abdominal distension (1 case). The commonest site of involvement was ileocecal region (6/9). Endoscopic examination had been carried out in 6 patients and all showed the presence of multiple polyps. Five cases had undergone endoscopic biopsy. Histologic examination of the endoscopic biopsies showed lymphoma cells located mainly in mucosal layer, forming vague nodules with ill-defined boundaries. Plasma cells and eosinophils were not conspicuous. Immunohistochemically, the tumor cells in all cases diffusely expressed CD20, CD10 and bcl-2. The staining for CD3, CD5 and cyclin D1 was negative. Lymphoid cells with weak CD10-positivity were identified in the interfollicular regions. Four cases were treated with surgical resection and chemotherapy. The other 3 cases received chemotherapy only and the remaining cases were treated conservatively. All of them were still alive on follow up. CONCLUSIONS: Primary intestinal follicular lymphoma affects predominantly elderly patients and has a female predilection. The commonest site of involvement is ileocecal region. Endoscopic examination shows polypoid changes. The disease often runs a relatively indolent clinical course. The prognosis is better than that of primary nodal follicular lymphoma.

Idiopathic phacodonesis in senile cataract patients in Qinghai, China.

AIM: To investigate the frequency of idiopathic phacodonesis (IP) in senile cataract subjects and the short-term clinical outcomes following cataract surgery. METHODS: This institutional case-control study included 1301 consecutive low-income cataract subjects from June to November 2009. Anterior segment were carefully evaluated with dilated pupil under slit-lamp. IP were screened and graded by a criteria set by the authors. Risk factors, surgical outcomes, and operative complications were analyzed. RESULTS: A total of 42 subjects (3.2%) with IP were diagnosed and classified as grade 1 (36 subjects), grade 2 (5 subjects) and grade 3 (1 subject). Harder lenses and intumescent cataracts were observed in the IP group than the control group (P<0.05). Logistics regression test also indicated the main risk factor was the hardness of the lens. The incidence of zonular dialysis during surgery was 23.8% (10 eyes), which was significantly higher than the controls (0.7%, P<0.001). Visual outcomes of the two groups were not statistically or clinically significant. CONCLUSION: Hard nucleus and intumescent cataract are related to IP in senile cataract subjects in Qinghai, China. With more care being taken, grade 1 and some of the grade 2 IP subjects achieved similar surgical outcomes as compared to controls.

[The differential expression of Stathmin in the spinal cord tissue of hens exposed to tri-o-cresyl phosphate].

OBJECTIVE: To screen the differently expressed proteins related to regulating the depolymerization of microtubules in the spinal cord of hens exposed to tri-o-cresyl phosphate (TOCP) and to provide target protein evidence for exploring the mechanisms of the delayed neurotoxicology (OPIDN) induced by organophosphorus compounds (OPs). METHODS: Forty two Roman hens were randomly divided into three groups, i.e. TOCP group treated with 1000 mg/kg TOCP; intervention group treated with 40 mg/kg phenylmethanesulfonyl fluoride (PMSF) before 1000 mg/kg TOCP treatment and control group treated with tap water. Four hens in each group were sacrificed on the 5th and 20th days after exposure, respectively. Spinal cords were separated and homogenates at low temperature, and the total proteins were extracted. The OPIDN symptoms observed and recorded in the remaining 6 hens in each group. The differently expressed proteins related to regulating the depolymerization of microtubules were screen by two-dimensional electrophoresis and mass spectroscopy (MS). RESULTS: The OPIDN symptoms appeared on the 5th day after exposure in TOCP group, which were gradually serious with time. The results by two-dimensional electrophoresis and MS showed that the Stathmin expression was downregulated 3.4 times and 2.8 times in TOCP group, respectively, as compared with the control and PMSF intervention groups. However, there was no significant difference of the Stathmin expression between control group and PMSF intervention group. CONCLUSION: The Stathmin expression in the spinal cord tissues of hens exposed to TOCP significantly downregulated. Moreover, the downregulated Stathmin expression may be related to excess polymerization of microtubules and the mechanism of OPIDN.

[Loss of pan-T cell antigens CD2, CD3, CD5 and CD7 in Kikuchi's disease].

OBJECTIVE: To study the possible loss of pan-T cell antigens CD2, CD3, CD5 and CD7 in Kikuchi's disease and to evaluate the role of T cell antigen loss in distinguishing benign from malignant T-cell lymphoid lesions. METHODS: Formalin-fixed and paraffin-embedded tissues of 33 cases of Kikuchi's disease and 15 cases of reactive lymphoid hyperplasia were studied by EliVision immunohistochemical staining for CD2, CD3, CD5 and CD7. RESULTS: Twenty-four of the 33 (72.7%) cases of Kikuchi's disease lost one or more of the pan-T cell antigens, including the loss of CD5 only (13 cases), CD7 only (1 case), CD2 only (1 case), CD2 and CD7 (2 cases), CD5 and CD7 (4 cases), CD2 and CD5 (2 cases), and CD2, CD7 and CD5 (1 case). Amongst these cases, the commonest antigen loss was CD5 (20 cases, 60.6%), followed by CD7 (8 cases, 24.2%) and CD2 (6 cases, 18.2%). Compared with the xanthomatous subtype of Kikuchi's disease, the loss of antigens was more commonly seen in the proliferative and necrotizing subtypes. Analysis of follow-up data showed that the loss of antigens in Kikuchi's disease was not significantly associated with the prognosis. In reactive lymphoid hyperplasia, the expression of CD2, CD3, CD5 and CD7 was seen in all cases with similar intensity, with no obvious pan-T cell antigen loss. CONCLUSION: Loss of one or more pan-T cell antigens in Kikuchi's disease is demonstrated in present study, suggesting that the immunophenotypic pattern is not unique in T cell lymphoma.

[Clinicopathologic study of juvenile granulosa cell tumor of ovary].

OBJECTIVE: To study the clinicopathologic features, diagnostic criteria and prognostic parameters of juvenile granulosa cell tumor of ovary. METHODS: The clinical and pathologic findings of 7 cases of juvenile granulosa cell tumor were retrospectively reviewed. Immunohistochemical study was carried out in 6 of these cases. The follow-up data were also analyzed. RESULTS: The mean age of the patients was 24 years (range=6 to 53 years). Four patients presented with hormonal disturbance, while 3 patients presented with abdominal pain or swelling. Six patients underwent unilateral salpingo-oophorectomy. Six cases were in stage IA and the remaining case in stage IC. Follow-up information was available in 6 patients and the duration of follow up ranged from 1 to 10 years (mean=4.3 years). Five patients remained healthy, with no evidence of tumor recurrence. One patient died of tumor metastasis one year after the diagnosis. Gross examination showed that the tumor masses ranged from 7 to 20 cm in the greatest dimension (average=13.4 cm). Four of the 7 tumors were mixed solid-cystic in appearance and 2 cases were unilocular cystic in nature. Microscopic examination showed diffuse atypical follicular structures formed by granulosa cells. The granulosa cells contained round hyperchromatic nuclei, without nuclear grooves or Call-Exner body formation (6/7). In one of the cases studied, minor foci resembling adult granulosa cell tumor were also demonstrated. The degree of cellular atypia varied (3 cases with severe atypia, 1 case with moderate atypia and 3 cases with mild atypia). The mitotic count ranged from 1 to more than 5 per 10 high-power fields. Immunohistochemical study showed diffuse positivity for vimentin (6/6). The staining for cytokeratin (AE1/AE3) and calretinin was negative. Four cases expressed CD99 and 1 case was positive for inhibin. CONCLUSIONS: Juvenile granulosa cell tumor is characterized by the presence of diffuse atypical follicular structures formed by small round cells, without nuclear grooves or Call-Exner bodies. Rare cases contain minor foci of adult granulosa cell tumor. They can be unilocular cystic in nature. The degree of nuclear atypia, mitotic activity and size of the tumor vary and do not correlate with the risk of recurrence and aggressive biologic behavior.

[Retrospective analysis of 4 cases of the so-called blastic NK-cell lymphoma, with reference to the 2008 WHO classification of tumours of haematopoietic and lymphoid tissues].

OBJECTIVE: To study the clinical and pathologic features of 4 cases of the so-called blastic natural killer (NK)-cell lymphoma, with reference to the 2008 WHO classification of tumours of haematopoietic and lymphoid tissues. METHODS: The clinical, pathologic and immunohistochemical findings (EliVision method) of 4 cases of blastic NK-cell lymphoma (previously diagnosed according to the 2001 WHO classification) were retrospectively analyzed and reclassified with a special reference to the 2008 WHO classification. RESULTS: The 4 cases of hematologic malignancy studied were characterized by the presence of medium-sized blastic lymphoma cells, CD56 expression, and absence of lineage-specific B-cell, T-cell and myeloid cell markers. According to the 2001 WHO classification, they fell into the category of blastic NK-cell lymphoma. Three of the cases presented with primary cutaneous lesions and expression of CD56, CD4 and CD123. They are likely derived from the plasmacytoid dendritic cells rather than NK cells. They were then, according to the 2008 WHO classification, reclassified as the blastic plasmacytoid dendritic cell neoplasm. The remaining case showed lymph node involvement, positive for CD56 and CD4, negative for CD123, and not accompanied with the cutaneous lesions. This case was provisionally classified as a ambiguous lineage leukemia-NK cell lymphoblastic leukemia/lymphoma. CONCLUSIONS: The so-called blastic NK-cell lymphomas in the 2001 WHO classification are rare and represent a heterogeneous group of lymphoproliferative disorders, with different clinical, pathologic and immunohistochemical features. It's suggested to have a precise category when applying the 2008 WHO classification to this kind of lesion.

[Histiocytic sarcoma: a clinicopathologic study of 6 cases].

OBJECTIVE: To study the morphologic features, immunophenotypes, differential diagnoses and prognosis of histiocytic sarcoma (HS). METHODS: The clinical and pathologic findings of 6 cases of HS were reviewed. Immunohistochemical assay (Elivision staining) was also performed. Follow-up information was available in 4 patients. RESULTS: There were altogether 3 males and 3 females. The age of patients ranged from 12 to 81 years old (median = 54.6 years). The sites of involvement included lymph node (number = 2 cases) and skin or soft tissue (number = 4 cases). The tumor was composed of sheets of large epithelioid cells with abundant eosinophilic cytoplasm, oval to irregular nuclei, vesicular chromatin and large nucleoli. Binucleated form was not uncommon. Two of the cases showed increased pleomorphism with multinucleated tumor giant cell formation. Focal cytoplasmic with foamy appearance was identified in 3 cases. One case demonstrated foci of spindly sarcomatoid appearance. Hemophagocytosis was identified in 2 cases. Mitotic figures were readily identified. The tumor cells were often accompanied by various numbers of inflammatory cells. Immunohistochemical study showed that all cases were diffusely positive for leukocyte common antigen, CD4, CD68 and CD163. Four of the 5 cases studied also expressed lysozyme. Amongst the 4 patients with follow-up information available, 3 died of the disease at 6 to 11 months interval after diagnosis. One patient, whose lesion was localized at the skin and soft tissue, survived for 3 years, with no evidence of tumor recurrence. CONCLUSIONS: Accurate diagnosis of the HS is based on the combination of morphologic examination and immunohistochemical assay. HS often presents with clinically advanced disease and pursues an aggressive clinical course, with a poor response to therapy. However, a subset of cases presenting with clinically localized lesion may carry a relatively favorable long-term outcome.

[Clinicopathological study on the follicular dendritic cell sarcoma].

OBJECTIVE: To investigate the clinicopathologic features and differential diagnostic methods for follicular dendritic cell sarcoma. METHODS: Histological and immunohistochemical examinations and EBER in situ hybridization were used to investigate the pathological features of 5 cases of follicular dendritic cell sarcoma, and related literature was reviewed. RESULTS: There were 3 males and 2 females with a median age of 54 years (range, 28 - 75 years). The location of lesions included lymph node (2 cases), tonsil (1 case), stomach (1 case), and liver (1 case). The growth patterns were fascicular or whorls and/or diffuse. The neoplastic cells were spindle or ovoid in shape with indistinct border and slightly eosinophilic cytoplasm. The nuclei were round, oval or spindle in shape with small distinct nucleoli. Warthin-Finkeldey-like multinucleated giant cells were detected in two cases. Mitotic figures were found in 1-22/10 HPF. Immunohistochemical staining showed that CD21 and CD23 (3 of 5), CD35 (4 of 5), D2-40 (4 of 4), and CXCL13 (3 of 4) were positive in neoplastic cells. EBER was detected in one of five cases by in situ hybridization. Four cases were followed-up for 6 approximately 25 months and no recurrence or death was observed yet. CONCLUSION: Follicular dendritic cell sarcoma is an extremely rare and should be considered as a moderately malignant tumor, and may present histological polymorphism with certain distinctive features. Immunohistochemistry is necessary in differential diagnosis to distinguish from other tumors.

[Morphologic and immunophenotypic analysis of angioimmunoblastic T-cell lymphoma].

OBJECTIVE: To study the morphologic and immunophenotypic features of angioimmunoblastic T-cell lymphoma (AITL), as well as the origin of the proliferative follicular dendritic cells (FDCs) in AITL. METHODS: Immunohistochemical study for CD10, CXCL13, bcl-6 and CD21 was performed on 29 cases of AITL. Double immunostaining for bcl-6/CD3, CD10/CD21 and CD10/CD20 were also carried out. Cases of peripheral T-cell lymphoma, unspecified, extranodal NK/T-cell lymphoma, nasal-type, enteropathy-type T-cell lymphoma, anaplastic large cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma and reactive lymphoid proliferation were selected as controls. RESULTS: Amongst the 29 cases of AITL studied, 75.9% (22/29) showed aberrant expression of CD10, while all except one of the controlled cases were negative, 82.8% (24/29) of the AITL cases expressed CXCL13, while all cases of peripheral T-cell lymphoma, unspecified were negative. As for bcl-6 staining, although the highest percentage of bcl-6-positive cells was observed in AITL, the expression pattern was not useful in differentiating AITL from peripheral T-cell lymphoma, unspecified and lymphoid reaction. Besides, all cases of AITL demonstrated the characteristic proliferation of follicular dendritic cells. Two of the cases, which contained obvious germinal centers, had the follicular dendritic cell meshwork extending beyond the lymphoid follicles. CONCLUSIONS: As compared with bcl-6, CD10 and CXCL13 are specific and sensitive markers in diagnosing AITL. Part of the proliferative FDCs in AITL may originate from the germinal centers.

[Clinicopathologic study of splenic marginal zone B-cell lymphoma].

OBJECTIVE: To study the clinicopathologic features, diagnosis and differential diagnosis of splenic marginal zone B-cell lymphoma (SMZL). METHODS: The clinical data, histologic findings and immunophenotype of 8 SMZL cases were studied. IgH gene rearrangement was performed in 1 case. Follow-up information was available in 4 patients. RESULTS: The median age of the patients was 61.5 years (range: 36 to 75 years). The male-to-female ratio was 1.7:1. All cases presented with massive splenomegaly. Five of six cases had abnormal blood counts: neutropenia and thrombocytopenia with two of them showing anemia. After splenectomy, the blood counts in 3/3 cases returned to normal levels. Post-operative fludarabine-based chemotherapy was given to 3 patients, two of them achieved complete remission and 1 case died during the course of chemotherapy. The average survival time was 21.5 months (range: 6 to 60 months). Histologically, all of the 8 cases showed micronodular white pulp lesions. Six of them exhibited the classic biphasic appearance with central aggregates of small B cells rimmed by a peripheral zone of atypical monocytoid B cells. The remaining 2 cases had a monomorphous appearance, consisting mainly of atypical monocytoid B cells. There was infiltration of tumor cells in the red pulp, sheets in appearance in all 8 cases. Immuno-histochemical staining showed CD20-positive (8/8), IgD-positive in 2 of the 4 cases (2/4), CD5-positive in 1 of the 4 cases (1/4), 6 of the 6 cases were bcl-2-positive, cyclin D1-negative and bcl-6/CD10-negative, CD43-negative in 5 of the 6 cases (5/6). The proliferation index, as highlighted by Ki-67 immunostaining, was low (< 15%). CONCLUSIONS: SMZL is an indolent B-cell non-Hodgkin lymphoma. The main clinical manifestations are splenomegaly and abnormalities in blood counts. The main modality of treatment is splenectomy. Adjuvant fludarabine-based chemotherapy helps to achieve complete remission. In general, the prognosis of this lymphoma type is good. The lymphoma cells predominantly grow in micronodular pattern, with atypical monocytoid B cells rimming around the small B cells, which aggregates in the center. The differential diagnosis includes other small B-cell lymphomas and lymphoid hyperplasia of spleen.