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.

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.

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.

Immunohistochemical differentiation between type B3 thymomas and thymic squamous cell carcinomas.

Type B3 thymomas and thymic squamous cell carcinomas have some overlapping histological features, so it is difficult to make the differential diagnosis between these two entities, especially when the biopsy specimen is small. Only a few markers such as CD5 and CD 117 were applied to the differential diagnosis, the purpose of this study is to identify other diagnostic markers to help making the differential diagnosis more accurate. GLUT-1, MUC-1, CD117, CD5, CEA, P63, CK19, CK5/6, CD1a and TdT were evaluated using 16 cases of type B3 thymoma and 20 cases of thymic squamous cell carcinoma. Staining scores were obtained by calculating the percentage of positive cells. The sensitivity of GLUT-1 or MUC-1 for thymic squamous cell carcinomas was highest (100%), followed by CK5/6 (95%), CD117 (90%), P63 (85%), CD5 (80%) and CEA (75%). The specificities of CD5, CD117 and CEA for thymic squamous cell carcinomas all were 100%, next was MUC-1 (56.3%), followed by GLUT-1 (50%), P63 (25%), CK5/6 (12.5%). The sensitivities of CK19, TdT, and CD1a for type B3 thymomas were 100%, 93.8% and 87.5%, respectively. The specificity of CD1a for type B3 thymomas was highest (100%), followed by TdT (95%), CK19 (10%). The reactivity of GLUT-1, MUC-1, CD117, CD5, CEA, CD1a and TdT in thymic squamous cell carcinomas and type B3 thymomas had significant difference. Usually a panel of markers is needed, if we combine GLUT-1 or MUC-1 which sensitivity for thymic squamous cell carcinomas is highest with CD5, CD117, CEA, CD1a or TdT which have high specificity, we can make the differential diagnosis effectively.

[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.

Immunohistochemical screening and fluorescence in situ hybridization confirmation of ALK translocation in lung adenocarcinoma and its clinicopathological significance: a single-center large-scale investigation of Chinese patients.

Anaplastic lymphoma kinase (ALK) translocation-positive adenocarcinoma of the lung is a newly recognized molecular subgroup. Limited data on the clinicopathological features of this entity in the Chinese population are available. We performed immunohistochemical staining for the ALK protein and fluorescence in situ hybridization detection of the ALK translocation. We enrolled 793 Chinese patients with lung adenocarcinoma and identified 54 ALK translocation-positive patients (6.8%) in the group. Compared with the entire group of patients, ALK translocation-positive patients were younger (P < .01) and more likely to be nonsmokers (P = .017), but presented with a higher percentage of advanced-stage disease (P = .022) and lymph node metastases (P = .006). ALK translocation-positive patients more commonly exhibited poorly differentiated tumor histology and a predominantly solid tumor growth pattern relative to the ALK translocation-negative patients. Morphologically, ALK translocation was associated with extracellular mucus secretion, a mucinous cribriform structure, and signet ring cell (SRC) components. ALK translocation was present in 42.5% and 34.0% of adenocarcinomas with SRC components or wild-type EGFR, respectively. ALK translocation, occurring at a frequency of 6.8% in Chinese patients, defines a unique molecular subgroup of lung tumors. Fluorescence in situ hybridization should be performed in each case of lung adenocarcinoma with SRC components or wild-type EGFR to identify ALK translocation-positive patients.

Aggressive natural killer-cell leukemia with jaundice and spontaneous splenic rupture: a case report and review of the literature.

Aggressive natural killer cell leukemia/lymphoma (ANKL) is a rare aggressive form of NK-cell neoplasm. We report an uncommon case of 36-year-old male who showed jaundice and spontaneous splenic rupture. The diagnosis was established by the biopsy of liver and spleen. The monomorphous medium-size neoplastic cells infiltrated into portal areas and sinus of liver as well as the cords and sinus of the spleen. Necrosis, mitotic figures and significant apoptosis could be seen easily. These neoplastic cells demonstrated a typical immunophenotype of CD3ε+, CD56+, CD16+, Granzyme B+, TIA-1+. T-cell receptor γ (TCR-γ) gene rearrangement analysis showed germline configuration and the result of in situ hybridization for Epstein-Barr virus-encoded RNA (EBER-ISH) was positive. The patient has undergone an aggressive clinical course and died of multi-organ function failure 14 days later after admission. To the best of our knowledge, this is the first case of ANKL with spontaneous splenic rupture, and we should pay more attention to recognize it. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2048154883890867.

[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.

[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.

Suppression of human MDA-MB-435S tumor by U6 promoter-driven short hairpin RNAs targeting focal adhesion kinase.

PURPOSE: Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase implicated in cancer cell survival, proliferation, and in various steps in the metastatic cascade. In the present study, we took advantage of a cationic liposome as gene carrier and targeted FAK function through both in vitro and in vivo approaches. METHODS: We utilized a plasmid-encoded hairpin RNA targeting the human FAK mRNA (pGensil2-shRNA/FAK), as a means to inhibit FAK expression for evaluating its anti-tumor effect in vitro and in vivo. Human MDA-MB-435S breast cancer cells were transfected with pGensil2-shRNA/FAK and examined for apoptosis by propidium iodide staining, DNA ladder, and flow cytometric analysis. For in vivo study, subcutaneous breast carcinomatosis models in nude mice were established to evaluate the therapeutic potential of pGensil2-shRNA/FAK. Assessments of proliferation (Ki-67), apoptosis (TUNEL) and angiogenesis (CD31) were done using immunohistochemical analysis. RESULTS: Transcripts expressed from plasmid both in vitro and in vivo were identified by northern blot analysis. pGensil2-shRNA/FAK effectively down-regulated the expression of FAK as demonstrated in vitro by real time RT-PCR and western blot analysis, whereas by real time RT-PCR and IHC staining of MDA-MB-435S tumors growing subcutaneously. Breast cancer cells lacking FAK expression undergo apoptosis in vitro. Systemic delivery of cationic liposome-complexed plasmids targeting FAK, resulted in the diminishment of subcutaneous tumor growth beyond the effects observed with liposomes carrying a non-specific shRNA. This diminishment in growth was associated with elevated levels of apoptosis (TUNEL staining), decreased cell proliferation (Ki-67 staining) and diminished endothelial cell density (CD31 staining). CONCLUSION: These results indicate that the systemic delivery of plasmid DNA targeting FAK function using cationic liposome as a gene carrier, represents a promising avenue for breast cancer therapy.

[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.

[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.

[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.

[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.

[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.