[A clinicopathologic and prognosis study of Epstein-Barr virus positive diffuse large B-cell lymphoma in west-southern China].

OBJECTIVE: To investigate the clinicopathologic features, immunophenotype, and the prognosis related factors of Epstein-Barr virus (EBV) positive diffuse large B-cell lymphoma (DLBCL) in west-southern China. METHODS: There were 42 cases of EBV+ DLBCL in a total 586 DLBCL, the clinical and pathologic profiles of these patients were evaluated. Immunohistochemical study and in situ hybridization (ISH) of EBER1/2 were performed on formalin fixed tissues by tissue chips. The prognosis related factors were analyzed. RESULTS: The median age of these 42 EBV+ DLBCL patients was 62.5 years. The male-to-female ratio was 2.23 : 1. The site of occurrence included lymph node (69.05%) and spleen, stomach, tonsil, nasal cavity and nasopharynx. The mostly common initial clinical presentations were non-specific symptoms, such as lymphadenopathy, splenomegaly, hepatomegaly, fever, and fatigue. Morphologically, the majority (90.48%, 38/42) were pleomorphic subtypes and only 4 cases (9.52%) were simplex subtypes. Immunophenotype showed non-GCB type of DLBCL was predominance (83.33%, 35/42) by Hans classification. The expression of CD30, CD5, BCL-2, P53 and NF-kappaB/ P65 were 52.38% (22/42), 54.76% (23/42), 54.76% (23/42), 87.5% (35/40) and 0% (0/40) respectively. Follow-up data was available in 23 (54.76%) patients, 14 (60.87%) patients died of the tumor. 5-years overall survival was 16.5%. The median survival time was 40 months. The expression of BCL-2, increased LDH level and starry-sky morphologic character were associated with a poor prognosis. CONCLUSION: EBV positive DLBCL is not uncommon. Most lesions locate in lymph nodes. Pleomorphic histologic subtype is predominant. The tumor has worse prognosis with increased LDH level, starry-sky morphologic character and BCL-2 expression.

[Langerhans cell histiocytosis: a clinicopathologic and immunohistochemical analysis of 258 cases].

OBJECTIVES: To observe the clinicopathologic features of Langerhans cell histiocytosis (LCH), and to evaluate the values of langerin, CD1a and S-100 protein expression in diagnosis of the tumor. METHODS: Total 258 cases of Langerhans cell histiocytosis in the past 18 years (from 1992 to 2008) were collected, morphologic review and immunohistochemical staining were performed. RESULTS: In all 258 cases, the ages of patients older than 16 years or younger than 2 years were 126 (48.8%) and 37 (14.3%), respectively, in the remaining 95 (36.8%) of the cases, the age of the patients ranged from 2 to 16 years. For all of 258 cases, there were 364 diseased sites. Bony lesions accounted for 77.2% (281 cases), especially the skull (112 cases, 39.9%), followed by lymph node (25 cases, 6.9%) and skin (14 cases, 3.8%). Clinically, unisystem or unifocal disease was predominant (201 cases, 77.9%), followed by unisystem and multifocal disease (21 cases, 8.1%), multi-system disease (26 cases, 10.1%), isolated pulmonary LCH (2 cases, 0.8%), and unclassified (8 cases, 3.1%). Histologically, variable number of Langerhans cells was present in 265 samples of 258 cases. Multinucleated giant cells were found in 166 (62.6%) of the samples. Eosinophils were the major infiltrating non-neoplastic cells, and eosinophilic abscess was seen in 57 cases (21.5%). Coagulative necrosis and dead bone were detected in 29 (10.9%) and 124 (46.8%) of the cases, respectively. Immunohistochemically, the expression of S-100 protein, CD1a and langerin was 99.1% (209/211), 100% (206/206) and 98.5% (193/196), respectively, and the sensitivity of them had no statistical difference. CONCLUSIONS: In this group of LCH cases, the ratio of adult patients is high, but the proportion of multi-organ lesion is low. No significant difference of the sensitivity is found among langerin, CD1a and S-100 expression in diagnosis of LCH.

Honokiol attenuate the arsenic trioxide-induced cardiotoxicity by reducing the myocardial apoptosis.

Despite advantages of arsenic trioxide (ATO) in oncological practice, its clinical applications have been hampered by severe cardiotoxicity. The general mechanism of ATO-induced cardiotoxicity has been attributed to its damage to mitochondria, resulting in cardiac remodeling. Honokiol (HKL) is a naturally occurring compound derived from Magnolia bark. Previous studies have demonstrated that HKL exerts cardio-protective effects on ischemia/reperfusion (I/R) or chemical-induced cardiotoxicity by counteracting the toxic effects on mitochondria. The present study was conducted to investigate whether HKL pretreatment protects against ATO-induced cardiac oxidative damage and cell death. For the in vitro study, we evaluated the effects of ATO and/or Honokiol on reactive oxygen species (ROS) production and apoptosis induction in primary cultured cardiomyocytes; for the in vivo study, BALB/c mice were administrated with ATO and/or HKL for a period of 4 weeks, myocardial apoptosis, cardiac function, and cardiac remodeling (cardiac hypertrophy and cardiac fibrosis) were assessed at the end of administration. Our results demonstrated Honokiol pretreatment alleviated the ATO-induced boost in ROS concentration and the following apoptosis induction in primary cultured cardiomyocytes. In the mouse model, Honokiol pretreatment ameliorated ATO-induced myocardial apoptosis, cardiac dysfunction, and cardiac remodeling. Collectively, these results indicated that Honokiol provide a protection against ATO-induced cardiotoxicity by reducing mitochondrial damage. In addition, given that Honokiol has shown considerable suppressive effects on leukemia cells, our data also imply that ATO and Honokiol combination may possibly be a superior avenue in leukemia therapy.

[Clinicopathologic and immunohistochemical study of 23 cases of mesenchymal chondrosarcoma].

OBJECTIVE: To study the clinicopathologic and immunohistochemical features of mesenchymal chondrosarcoma. METHODS: The clinical and histologic features of 23 cases of mesenchymal chondrosarcoma were analyzed. Immunohistochemical study was also performed in 14 of the cases. RESULTS: The age of patients ranged from 12 to 47 years. Fourteen of them occurred in males. Thirteen cases involved the bony skeleton and 5 cases affected the soft tissue. The patients presented with pain and/or swelling. Histologically, the tumor consisted of a mixture of undifferentiated small round cells and hyaline cartilage. Transition between the two components was demonstrated and growth plate-like cartilage was observed. Immunohistochemical study showed that the small round cells were positive for Sox9 (14/14), CD99 (12/14), vimentin (6/14), CD56 (4/14), CD57 (4/14), neuron-specific enolase (3/14) and desmin(1/14). They were negative for Coll-II, S-100 protein, epithelial membrane antigen, pan-cytokeratin, synaptophysin, chromogranin A, CD34 and c-erbB2. CONCLUSIONS: Mesenchymal chondrosarcoma is a rare malignant tumor. Thorough histologic examination, when coupled with immunohistochemical findings, is helpful in arriving at a correct diagnosis.

[Roles of histologic examination and polymerase chain reaction in diagnosis of toxoplasmic lymphadenitis].

OBJECTIVE: To study the roles of histologic examination and polymerase chain reaction in diagnosis of toxoplasmic lymphadenitis (TL). METHODS: Forty-six archival cases of histologically diagnosed TL, encountered during the period from April, 1999 to September, 2009 and with the paraffin-embedded lymph node tissue blocks available, were enrolled into the study. The presence of genome fragments of Toxoplasma gondii (T. gondii) was analyzed using semi-nested polymerase chain reaction (PCR). Thirty cases of one or two histopathologic triad of TL as the controls. RESULTS: The positive rate of PCR in TL group was 76.1% (35/46), as compared to 10.0% (3/30) in the control group. The difference was of statistical significance. The sensitivity and specificity of the histologic triad in diagnosing TL was 92.1% (35/38) and 71.1% (27/38), respectively. The predictive value of positive and negative PCR results was 76.1% (35/46) and 90.0% (27/30). respectively. CONCLUSIONS: The high specificity but low sensitivity of applying the histologic triad in diagnosing TL cases may be due to the occurrence of atypical histologic pattern. The sensitivity is improved with the use of semi-nested PCR in detecting T. gondii DNA.

[Application of Warthin-Starry stain, immunohistochemistry and transmission electron microscopy in diagnosis of cat scratch disease].

OBJECTIVE: To evaluate the diagnostic utility of Warthin-Starry silver stain, immunohistochemistry and transmission electron microscopy in the detection of human Bartonella henselae infection and pathologic diagnosis of cat scratch disease (CSD). METHODS: The paraffin-embedded lymph node tissues of 77 histologically-defined cases of cat scratch disease collected during the period from January, 1998 to December, 2008 were retrieved and studied using Warthin-Starry silver stain (WS stain) and mouse monoclonal antibody against Bartonella henselae (BhmAB stain). Five cases rich in bacteria were selected for transmission electron microscopy. RESULTS: Under electron microscope, the organisms Bartonella henselae appeared polymorphic, round, elliptical, short rod or bacilliform shapes, ranged from 0.489 to 1.110 microm by 0.333 to 0.534 microm and often clustered together. Black short rod-shaped bacilli arranged in chains or clumps were demonstrated in 61.0% (47/77) of CSD by WS stain. The organisms were located outside the cells and lie mainly in the necrotic debris, especially near the nodal capsule. In 72.7% (56/77) of the cases, dot-like, granular as well as few linear positive signals were observed using BhmAB immunostain and showed similar localization. Positive results for both stains were identified in 59.7% (46/77) of the cases. When applying both stains together, Bartonella henselae was observed in 74.0% (57/77) of the case. The difference between the results obtained by WS stain and BhmAB immunostain was of statistical significance (P < 0.05). CONCLUSIONS: Bartonella henselae is the causative pathogen of cat scratch disease. WS stain, BhmAB immunostain and transmission electron microscopy are helpful in confirming the histologic diagnosis. Immunostaining using BhmAB can be a better alternative than WS stain in demonstrating the organisms.

[Effects of urokinase intervention on endotoxin-induced DIC in Wistar rat model].

OBJECTIVE: To study the effects of urokinase intervention on endotoxin-induced DIC in Wistar rats model. METHODS: Wistar rats were randomly assigned into 4 groups: normal saline (NS) group, urokinase (UK) group, endotoxin (LPS) group and LPS+ UK group. These agents were given to the rats by the tail vein intravenous infusion, NS group was treated with NS 2.5 mL/h x 4 h; UK group with NS 2.5 mL/h, 1 h later UK 4 IU/(g x h) x 3 h; LPS group with LPS 3 mg/(kg x h) x 4 h; LPS+UK group with LPS 3 mg/(kg x h) firstly, 1 h later UK 4 IU/(g x h) ) < 3 h. After the intervention, the function of coagulation and fibrinolysis, the indicators of organ damage and microcirculation fibrin micro-clots were evaluated. RESULTS: One hour after the infusion of 3 mg/(kg x h) of LPS, DIC signs began to appear, and became more apparent over time. After the intervention of urokinase, the values of clotting time (PT), activated partial thromboplastin time (APTT) were significantly shorter, but the platelet count (PLT), the amount of fibrinogen (FIB) changed little. Plasminogen activator inhibitor-1 (PAI-1) level decreased, while the D-dimer level increased. Serum creatinine (Cr), alanine aminotransferase (ALT) also decreased significantly. The biopsy of liver, kidney, and lung showed tissue damage became better, and the organ microcirculation fibrin micro-clots decreased significantly. CONCLUSION: The concentration of 3 mg/(kg x h) endotoxin can successfully induce DIC model in Wistar rats. Urokinase could play a positive role to prevent the LPS-induced DIC.

[Expressions of APC and c-Myc and its implication on non-small cell lung cancer].

OBJECTIVE: To investigate the expressions of adenomatous polyposis coli (APC) protein and c-Myc protein in non-small cell lung cancer (NSCLC) and their lymph node metastases. METHODS: APC and c-Myc proteins were detected in 270 cases of primary NSCLC, 55 cases of lymph node metastatic tissues and 46 cases of adjacent normal lung tissues by EliVision and EnVision methods of immunohistochemical staining. RESULTS: Higher rates of the expressions of both APC and c-Myc proteins in NSCLC primary foci were found compared with those in lymph node metastases (P < 0.05). Furthermore, the expressions of APC and c-Myc proteins varied with histological types, TNM stagings and metastasis of the NSCLC (P < 0.05). The Spearman correlation analysis showed that the expressions of APC and c-Myc proteins were positively correlated (r(s) = 0.376, P = 0.000). The Kaplan-Meier survival analysis revealed that the survival rate was lower in patients with positive expressions of APC and c-Myc proteins than in patients with negative expressions (P < 0.05). Histological type, pathologic grading, metastasis and c-Myc were identified as independent risk factors with related to the prognosis of NSCLC patients in the multivariate Cox regression model (P < 0.05). CONCLUSION: APC and c-Myc may play an important role in the progression of NSCLC.

Chidamide plus decitabine synergistically induces apoptosis of acute myeloid leukemia cells by upregulating PERP.

Acute myeloid leukemia (AML) is a malignant clonal disease that originates from hematopoietic stem cells. Because AML has a generally unsatisfactory long-term prognosis, new therapeutic options are required. To this end, we explored the effects of chidamide and decitabine alone or in combination on the AML cell lines THP-1, MV4-11, HL60, and Kasumi-1. Notably, the two drugs exhibited a synergistic effect against these cell lines. Similarly, we also found potential synergistic effects in primary cells of relapsed/refractory (r/r) AML. A transcriptome sequencing analysis performed to elucidate the underlying molecular mechanism revealed differentially expressed genes and regulatory pathways, particularly with regard to apoptosis, when comparing cells subjected to single and combination treatments. We identified PERP as a downstream target gene of the transcription factors P53 and P63, and it was expressed at considerably higher levels in combination-treated cells relative to monotherapy-treated cells. We further used a lentivirus-mediated small interfering RNA to inhibit the endogenous expression of PERP in AML cell lines and observed a significant increase in cell proliferation. Collectively, our results demonstrate, for the first time, the role of PERP in the response of AML to a combination drug regimen, providing a new potential treatment protocol and target in this context.

[Investigation on clinicopathologic features of lymphomatoid papulosis].

OBJECTIVE: To investigate the clinicopathologic features, immunophenotype and prognosis of lymphomatoid papulosis (LyP). METHODS: Clinicopathologic analysis, immunohistochemical staining (LSAB and EliVision method) and in situ hybridization for EBER were undertaken in this study. RESULTS: Thirteen cases of LyP were studied, derived from six male and seven female patients with a median age of 26.4 years. The most common presentation was multiple symptomless papules or nodules, involving predominately the extremities and trunks. Histologically, the tumor primarily involved the dermis and subcutaneous layer. Six tumors were type A, one was type B and six were type C. The main infiltration patterns were wedge-shaped, band-like, sheet-like or nodular. There was epidermotropism in eight cases. Immunohistochemical staining showed that the large tumor cells in all 12 types A and C cases expressed CD30. All 13 cases expressed two to three T-cell associated antigens (CD3, CD5 or CD45RO) and one to three cytotoxic granule associated antigens (TIA-1, GrB or Perforin). All cases expressed CD4, four expressed CD8, and one expressed CD15. Only one case expressed CD20; and all cases were negative for ALK-1. The tumor cells showing epidermotropism had CD3(+), CD4(+) and CD8(-) phenotype in most cases. Only one case was EBER1/2 positive. Follow up information was available in 12 patients; all were alive at the end of the follow up period. CONCLUSIONS: LyP has distinctive clinicopathologic features and immunophenotype with favorable prognosis. In types A and C, the atypical cells showing epidermotropism were similar to those in MF, these cells possess cerebriform and hyperchromatic nuclei. The epidermotropic tumor cells and the CD30(+) large cells may be derived from different clones. EB virus may not be correlated with LyP.

[Intralaboratory reproducibility of HER2 testing in breast cancer by immunohistochemistry and comparison of results obtained by different assays].

OBJECTIVES: To investigate the intralaboratory reproducibility of immunohistochemistry (IHC) testing for HER2 status in breast cancer, and to evaluate the factors which influence the reproducibility. The concordance between monoclonal antibody CB11 and HercepTest was also assessed. METHODS: HER2 overexpression on paraffin sections from thirty-seven cases of breast invasive ductal carcinoma was evaluated using CB11 and the evaluation procedure had been repeated for five times scored the tests together according to the HercepTest and new American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) grading schemes by 2 experienced pathologists together. Reproducibility rates of the five rounds were assessed using Kappa statistic, and the results from two scoring systems were compared. HercepTest kit was applied to the same cases afterward and the results were compared with CB11. RESULTS: Substantial intralaboratory reproducibility was achieved among 5 rounds tests. Excluding the influence effect of changing antibody lots, the intralaboratory reproducibility was closed to the perfect threshold (Kappa = 0.7858, HercepTest scheme). The results derived from the two grading schemes had an almost perfect agreement (Kappa = 0.8549). The concordance (positive vs. negative) between CB11 and HercepTest was 83.78%. CONCLUSIONS: Laboratory work with strict supervision and more experience will ensure a reliable testing consistency. Reproducibility analysis could be adopted to evaluate the intralaboratory staining quality on HER2 testing. Different antibody lots bring some influence to the intralaboratory reproducibility, but not significant. CB11 could be accepted to screen HER2 status in routine practice after testing validation.

[Lymphoplasmacytic lymphoma with Waldenström's macroglobulinemia: a clinicopathological and immunophenotypic study of 40 Chinese patients].

OBJECTIVE: To investigate the clinicopathologic features of lymphoplasmacytic lymphoma (LPL) with Waldenström's macroglobulinemia (WM) and to evaluate the usefulness of immunophenotype analysis in diagnosis and differential diagnosis of the tumor. METHODS: A total of 40 cases of LPL with WM diagnosed according to the 2008 World Health Organization classification of tumors of hematopoietic and lymphoid tissues were analyzed using immunophenotype and follow-up information. RESULTS: The mostly common initial clinical presentations were non-specific symptoms, such as fatigue, anemia and hemorrhage. Lymphadenopathy, splenomegaly and hepatomegaly were found in 42.5%, 20.0% and 12.5% of the patients respectively. The pattern of bone marrow involvement included mixed type (47.2%), diffuse type (41.7%) and interstitial type (11.1%). The nodal architecture was completely destroyed in one case and partially effaced with residual germinal centers and dilated sinuses in 8 cases. All of the neoplastic cells expressed CD20 and CD79a. Neoplastic plasma cells were positive for CD138 and CD79a. No cases expressed CD5. Four cases weakly expressed CD23. No significant prognosis related factors were identified in the survival analysis. CONCLUSIONS: LPL with WM is a rare indolent small B-cell lymphoma, which is commonly seen, in older male patients. The tumor frequently involves bone marrow and shows various clinical manifestations. Combination analyses of the bone marrow biopsy histology, immunophenotypic study and clinical data, especially the serum examination are important for the diagnosis of LPL with WM.

[Extramedullary infiltration of acute monocytic leukemia/monoblastic sarcoma: a clinicopathologic and immunophenotype analysis of 5 cases].

OBJECTIVE: To study the clinicopathologic features, diagnosis and differential diagnosis of extramedullary infiltration of acute monocytic leukemia/monoblastic sarcoma. METHODS: Five cases of extramedullary infiltration of acute monocytic leukemia/monoblastic sarcoma were selected from 102 cases of myeloid sarcoma diagnosed during the period from 1990 to 2006. The clinicopathologic findings and followup data were retrospectively analyzed. Immunohistochemical study was also carried out with SP method. RESULTS: Among the 5 cases studied, 3 were males and 2 were females, including 2 children and 3 adults. Generalized lymphadenopathy was found in 4 patients and skin lesions were observed in 2 patients. The tumor cells in all cases were positive for CD68 (KP1), CD68 (PGM1), lysozyme and CD45. They were negative for MPO, CD15, CD163, TdT, CD117, T and B cell markers. The Ki-67 index ranged from 40% to 80%. Follow-up data were available in all the 5 patients. Four of the 5 patients died of the disease, with the average survival time being 6.25 months. CONCLUSIONS: Monoblastic sarcoma is a rare disease with poor prognosis. It is almost impossible to distinguish monoblastic sarcoma from granulocytic sarcoma and other types of small round cell tumors on the basis of morphologic examination alone. Immunohistochemistry is mandatory for a correct diagnosis.

[Intravascular large B-cell lymphoma: report of two autopsy cases with literature review].

OBJECTIVE: To study the clinicopathologic features of intravascular large B-cell lymphoma (IVLBCL). METHODS: Two autopsy cases of IVLBCL were retrieved from the archival file. The clinicopathologic features, immunohistochemistry and molecular findings were studied. RESULTS: The 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. CONCLUSIONS: IVLBCL may present as neurological disturbance and carries distinctive morphologic characteristics, immunophenotype and molecular findings. The prognosis of this disease is often dismal.

[Activity detection and immunohistochemistry study on xanthine oxidase in pathological scars].

OBJECTIVE: To study the change of xanthine oxidase in pathological scars. METHODS: The tissues of hypertrophic scar (10 cases), keloid (10 cases) and normal skin (8 cases) were collected for this project, in which the content of malonaldehyde, the activity of xanthine oxidase and total of antioxidant capacity were detected by spectrophotometric method. The expression of xanthine oxidase was evaluated by immunohistochemistry technique. RESULTS: Compared with normal skin tissue, the content of malonaldehyde and xanthine oxidase activity were significantly higher in pathological scars (P < 0.05), but no significant difference was observed in the decrease of total antioxidant capacity. Differences in above-mentioned indexes all were not remarkable between hypertrophic scars and keloids. Immunohistochemical study indicated that the expressions of xanthine oxidase in the epidermal keratinocytes and dermal fibroblasts of pathological scars increased markedly in contrast with normal skin (P < 0.05). CONCLUSION: The xanthine oxidase activity shows to be increased in pathological scars, and the xanthine oxidase expressions are enlarged in epidermal keratinocytes and dermal fibroblasts of pathological scars, which may be a reason resulting in the increase of free excessive growth of scar tissues. radical level, and may play a role in pathogenesis of excessive growth of scar tissues.

[Rosai-Dorfman disease: clinicopathologic, immunohistochemical and etiologic study of 16 cases].

OBJECTIVES: To study the clinicopathologic features of Rosai-Dorfman disease (RDD), expression of various antigens, human herpes virus type 8 (HHV8), human papillomavirus (HPV)-DNA and Epstein-Barr virus (EBV)-mRNA, and compare the findings with those in the literature. METHODS: The clinicopathologic findings of 16 Rosai-Dorfman disease cases were retrospectively reviewed. Immunohistochemical study for S-100 protein, CD68 (PG-M1), CD163, CD21, CD1a, CD20, CD45RO, CD4, CD8, M-CSF and HHV8 was carried out in 9 of the 16 cases. In-situ hybridization for EBV-mRNA and HPV-DNA was also performed. RESULTS: The male-to-female ratio of the patients was 4.33:1. Amongst the 16 cases studied, 62.5% (10/16) presented nodal RDD, with cervical lymph node predominantly involved. Half of these cases had affected lymph nodes in more than one anatomic site. Extranodal RDD represented 37.5% (6/16) of the cases. The relapse rate of extranodal RDD was higher than that of nodal RDD. Histologically, nodal RDD was characterized by dilated sinuses filled with large polygonal histiocytes which contained lymphocytes and plasma cells. For extranodal lesions, various degrees of stromal fibrosis were seen in association with mixed inflammatory cells (especially plasma cells). The large polygonal histiocytes varied in number and were distributed in clusters or patches. Immunohistochemical study showed that the abnormal histiocytes were strongly positive for S-100 protein. They also expressed CD68, CD163 and M-CSF, but were negative for CD1a, CD21 and HHV8. The lymphocytes in cytoplasm of these histiocytes were positive for both T and B cell markers (with T cell predominance, including a mixture of CD4- and CD8-positive cells). HPV-DNA and EBV-mRNA were not detected by in-situ hybridization. To date, 62 cases of RDD have been reported in mainland China, including 34 cases of nodal RDD and 18 cases of extranodal RDD. The remaining 10 cases involved both lymph nodes and extranodal sites. Compared with overseas reports, RDD occurring in China tended to affect older patients and with slight male predilection. CONCLUSIONS: Rosai-Dorfman disease is relatively rare in China. Pathologic diagnosis of extranodal RDD may be difficult. The demographic data of RDD in China, including age and sex of patients, are different from those in the literature.

Overexpression of Rad51 Predicts Poor Prognosis in Colorectal Cancer: Our Experience with 54 Patients.

BACKGROUND: Aberrant Rad51 expression is implicated in the progression of human malignancies. However, the role of Rad51 in colorectal cancer (CRC) remains undefined. This study aimed to establish a relationship between Rad51 and clinicopathologic features of CRC. METHODS: We retrospectively examined the paraffin-embedded tissue samples obtained from 54 patients with CRC who had received surgical therapies at our institution during 2006-2008. Rad51 expression in adenocarcinoma, paracancerous tissue, and normal colonic tissue was determined by immunohistochemistry. The correlation between Rad51 immunoreactivity and clinicopathologic features of these patients was evaluated. RESULTS: Rad51 immunoreactivity was detected in 67% of adenocarcinoma, 48% of paracancerous tissue, and 27% of normal colonic mucosa. Rad51 expression in adenocarcinoma was significantly higher than normal colonic tissue (p < 0.05). Rad51 was also overexpressed in poorly differentiated tumors and tumor samples from patients with lymph node metastasis (p < 0.05). Patients with Rad51 overexpression had a 69% two-year survival, 49% three-year survival, and 16% five-year survival, considerably worse than patients with negative Rad51 expression (p < 0.05). CONCLUSION: Our data suggest that Rad51 overexpression is correlated with malignant phenotypes of CRC and may predict poor prognosis for these patients.

[Diffuse large B-cell lymphoma with expression of anaplastic lymphoma kinase protein: clinicopathologic and immunohistochemical study of 5 cases].

OBJECTIVE: To study the clinicopathologic features of diffuse large B-cell lymphoma (DLBCL) with expression of anaplastic lymphoma kinase (ALK) protein. METHODS: Nine hundred and forty-five (945) cases of DLBCL (including 177 consultation cases) diagnosed according to the 2001 World Health Organization classification of tumors of hematopoietic and lymphoid tissues were enrolled into the study. Immunohistochemical study for anti-ALK-11 was performed using LSAB technique. The ALK-positive cases were further confirmed by immunohistochemical study using EnVision technique. Only ALK-positive cases by EnVision technique were further analyzed by immunostaining for antigens including CD20, CD3, CD30, EMA, granzyme-B, TIA-1 and PC. Immunoglobulin heavy chain gene rearrangement study was also performed and follow-up data collected. RESULTS: There were altogether 5 (4 males and 1 female) cases of DLBCL showing expression of ALK protein. The age of the patients ranged from 34 to 72 years. All were primary nodal DLBCL. One case belonged to clinical stage I, 2 in stage II and 2 in stage III. The duration of follow up ranged from 4 to 32 months. Three patients subsequently died and the longest survival was 32 months. Morphologic subtypes included centroblastic 2, anaplastic 1, immunoblastic with plasmacytoid differentiation 1 and plasmablastic 1. Immunohistochemically, 4 cases were CD20 positive (including 2 centroblastic, 1 anaplastic and 1 immunoblastic cases). The plasmablastic case expressed kappa light chain and was negative for CD20. Rearrangement of immunoglobulin heavy chain gene was demonstrated in all 5 cases studied. As for ALK protein staining, a mixed membranous and cytoplasmic (1 immunoblastic case), granular cytoplasmic (2 centroblastic and 1 anaplastic cases) and mixed nuclear and cytoplasmic (1 plasmablastic case) patterns were observed. CONCLUSIONS: Expression of ALK protein is a rare phenomenon in DLBCL and can be seen in centroblastic, anaplastic, immunoblastic and plasmablastic subtypes. It is often associated with aggressive clinical behavior and worse prognosis. A new pattern of ALK protein expression, mixed membranous and cytoplasmic, is reported.