Interferon-α mediating the functional damage of CD56dimCD57+natural killer cells in peripheral blood of systemic lupus erythematosuss / 北京大学学报(医学版)

OBJECTIVE@#To investigate the regulatory effect of interferon-α (IFN-α) on the apoptosis and killing function of CD56dimCD57+ natural killer (NK) cells in systemic lupus erythematosus (SLE) patients, and to explore the specific mechanism.@*METHODS@#A total of sixty-four newly treated SLE patients and sixteen healthy controls (HC) enrolled in the Second Hospital of Dalian Medical University were selected as the research subjects. And the gene expression levels of molecules related to NK cell-killing function were detected by real-time quantitative polymerase chain reaction. CD56dimCD57+ NK cells were co-cultured with the K562 cells, and the apoptotic K562 cells were labeled with Annexin-Ⅴ and 7-amino-actinomycin D. Peripheral blood mononuclear cells were treated with 20, 40, and 80 μmol/L hydrogen peroxide (H2O2), and treated without H2O2 as control, the expression level of perforin (PRF) was detected by flow cytometry. The concentration of IFN-α in serum was determined by enzyme linked immunosorbent assay. The expression levels of IFN-α receptors (IFNAR) on the surface of CD56dimCD57+ NK cells were detected by flow cytometry, and were represented by mean fluorescence intensity (MFI). CD56dimCD57+ NK cells were treated with 1 000 U/mL IFN-α for 24, 48 and 72 h, and no IFN-α treatment was used as the control, the apoptosis and the expression levels of mitochondrial reactive oxygen species (mtROS) were measured by flow cytometry and represented by MFI.@*RESULTS@#Compared with HC(n=3), the expression levels of PRF1 gene in peripheral blood NK cells of the SLE patients (n=3) were decreased (1.24±0.41 vs. 0.57±0.12, P=0.05). Compared with HC(n=5), the ability of peripheral blood CD56dimCD57+ NK cells in the SLE patients (n=5) to kill K562 cells was significantly decreased (58.61%±10.60% vs. 36.74%±6.27%, P < 0.01). Compared with the control (n=5, 97.51%±1.67%), different concentrations of H2O2 treatment significantly down-regulated the PRF expression levels of CD56dimCD57+ NK cells in a dose-dependent manner, the 20 μmol/L H2O2 PRF was 83.23%±8.48% (n=5, P < 0.05), the 40 μmol/L H2O2 PRF was 79.53%±8.56% (n=5, P < 0.01), the 80 μmol/L H2O2 PRF was 76.67%±7.16% (n=5, P < 0.01). Compared to HC (n=16), the serum IFN-α levels were significantly increased in the SLE patients (n=45) with moderate to high systemic lupus erythematosus disease activity index (SLEDAI≥10) [(55.07±50.36) ng/L vs. (328.2±276.3) ng/L, P < 0.001]. Meanwhile, compared with HC (n=6), IFNAR1 expression in peripheral blood CD56dimCD57+ NK cells of the SLE patients (n=6) were increased (MFI: 292.7±91.9 vs. 483.2±160.3, P < 0.05), and compared with HC (n=6), IFNAR2 expression in peripheral blood CD56dimCD57+ NK cells of the SLE patients (n=7) were increased (MFI: 643.5±113.7 vs. 919.0±246.9, P < 0.05). Compared with control (n=6), the stimulation of IFN-α (n=6) significantly promoted the apoptosis of CD56dimCD57+ NK cells (20.48%±7.01% vs. 37.82%±5.84%, P < 0.05). In addition, compared with the control (n=4, MFI: 1 049±174.5), stimulation of CD56dimCD57+ NK cells with IFN-α at different times significantly promoted the production of mtROS in a time-dependent manner, 48 h MFI was 3 437±1 472 (n=4, P < 0.05), 72 h MFI was 6 495±1 089 (n=4, P < 0.000 1), but there was no significant difference at 24 h of stimulation.@*CONCLUSION@#High serum IFN-α level in SLE patients may induce apoptosis by promoting mtROS production and inhibit perforin expression, which can down-regulate CD56dimCD57+ NK killing function.

Comparative Study of the Two High-Efficient Strategies for in vitro Generation of Human Umbilical Cord Blood-derived Natural Killer Cells / 中国实验血液学杂志

OBJECTIVE@#To explore the similarities and variations of biological phenotype and cytotoxicity of human umbilical cord blood natural killer cells (hUC- NK) after human umbilical cord blood-derived mononuclear cells (hUC-MNC) activated and expanded by two in vitro high-efficient strategies.@*METHODS@#Umbilical cord blood mononuclear cells (MNC) from healthy donor were enriched by Ficoll-based density gradient centrifugation. Then, the phenotype, subpopulations, cell viability and cytotoxicity of NK cells derived from Miltenyi medium (denoted as M-NK) and X-VIVO 15 (denoted as X-NK) were compared using a "3IL" strategy.@*RESULTS@#After a 14-day's culture, the contents of CD3-CD56+ NK cells were elevated from 4.25%±0.04% (d 0) to 71%±0.18% (M-NK) and 75.2%±1.1% (X-NK) respectively. Compared with X-NK group, the proportion of CD3+CD4+ T cells and CD3+CD56+ NKT cells in M-NK group decreased significantly. The percentages of CD16+, NKG2D+, NKp44+, CD25+ NK cells in X-NK group was higher than those in the M-NK group, while the total number of expanded NK cells in X-NK group was half of that in M-NK group. There were no significant differences between X-NK and M-NK groups in cell proliferation and cell cycle, except for the lower percentage of Annexin V+ apoptotic cells in M-NK group. Compared with X-NK group, the proportion of CD107a+ NK cells in M-NK group were higher under the same effector-target ratio (E∶T) (P<0.05).@*CONCLUSION@#The two strategies were adequate for high-efficient generation of NK cells with high level of activation in vitro, however, there are differences in biological phenotypes and tumor cytotoxicity.

Expression and significance of CK5/6, P63, P40, CK7, TTF-1, NapsinA, CD56, Syn and CgA in biopsy specimen of squamous cell carcinoma, adenocarcinoma and small cell lung carcinoma / Expresión y significado de CK5/6, P63, P40, CK7, TTF-1, NapsinA, CD56 Syn y CgA en muestras de biopsia de carcinoma de células escamosas, adenocarcinoma y carcinoma de células pequeñas de pulmón

Nine tumor and various potential biomarkers were measured and combined the information to diagnose disease, all patients accepted fiber bronchoscopy brush liquid based cytologyand histopathology examination in order to reliably detect lung cancer. The samples from 314 Chinese lung cancer patients were obtained and CK5/6, P63, P40, CK7, TTF-1, NapsinA CD56, Syn and CgA were measured with the immunohistochemical SP method and analyzed correlation of the expression of these markers with pathological and clinical features of squamous cell carcinoma, adenocarcinoma, and small cell lung carcinoma. Squamous cell carcinoma, adenocarcinoma and small cell carcinoma were 61 cases, 114 cases and 139 cases,CK5/6 and P63 expression were more frequent in squamous cell carcinoma, with sensitivity and specificity of 77.05 % and 96.44 %, 83.61 % and 88.93 %,and compared with adenocarcinoma and small cell carcinoma difference was statistically significant (P<0.05), The incidences of a positive P40 expression were 100 % in squamous cell carcinoma, with specificity of 98.81 %.CK7, TTF-1 and NapsinA expression were more frequent in adenocarcinoma, with sensitivity and specificity of 85.09 % and 78.69 %, 79.82 % and 93.44 %, 56.14 % and 95.08 %, and compared with squamous cell carcinoma and small cell carcinoma difference was statistically significant (P<0.05). TTF-1, Syn, CgA and CD56 expression were more frequent in adenocarcinoma, with sensitivity and specificity of 86.33 % and 93.44 %, 89.21 % and 98.36 %, 74.10 % and 100 %, 96.40 % and 96.72 %. The combined detection of CK5/6, P63 and P40 were more useful and specific in differentiating squamous cell carcinoma. CK7, TTF-1 and NapsinA were more useful and specific in differentiating lung adenocarcinoma. The impaired CD56, TTF-1, Syn and CgA reflects the progression of small cell lung cancer.

Se midieron tumores y utilizaron nueve biomarcadores potenciales y se analizó la información para diagnosticar la enfermedad. A todos los pacientes se les realizó citología en líquido con broncoscopía de fibra y examen histopatológico para detectar de manera confiable el cáncer pulmonar. Se obtuvieron muestras de 314 pacientes chinos con cáncer de pulmón y CK5 / 6, P63, P40, CK7, TTF-1, Napsina A, CD56, Syn y CgA se midieron a través de histoquímica SP y analizaron la correlación de la expresión de estos marcadores con características patológicas y clínicas de carcinoma de células escamosas, adenocarcinoma y carcinoma de células pequeñas en el cáncer de pulmón. El carcinoma de células escamosas, el adenocarcinoma y el carcinoma de células pequeñas fueron 61 casos, 114 casos y 139 casos, respectivamente, la expresión de CK5 / 6 y P63 fueron más frecuentes en el carcinoma de células escamosas, con una sensibilidad y especificidad del 77,05 % y 96,44 %, 83,61 % y 88,93 %, y en comparación con el adenocarcinoma y el carcinoma de células pequeñas, la diferencia fue estadísticamente significativa (P <0,05). La incidencia de ap la expresión positiva P40 fue del 100 % en el carcinoma de células escamosas, con una especificidad del 98,81 %. La expresión de CK7, TTF-1 y NapsinA fueron más frecuentes en el adenocarcinoma, con una sensibilidad y especificidad del 85,09 % y 78,69 %, 79,82 % y 93,44 %, 56,14 % y 95,08 %, y en comparación con el carcinoma de células escamosas y la diferencia de carcinoma de células pequeñas fue estadísticamente significativa (P <0,05) .TTF-1, Syn, CgA y la expresión de CD56 fueron más frecuentes en adenocarcinoma, con sensibilidad y especificidad de 86.33 % y 93.44 %, 89.21 % y 98.36 %, 74.10 % y 100 %, 96.40 % y 96.72 %. La detección combinada de CK5 / 6, P63 y P40 fue más útil y específica en la diferenciación del carcinoma de células escamosas. CK7, TTF-1 y NapsinA fueron más útiles y específicos para diferenciar el adenocarcinoma de pulmón. El deterioro de CD56, TTF-1, Syn y CgA refleja la progresión del cáncer de pulmón de células pequeñas.

Melanotic neuroectodermal tumor of infancy: a clinicopathological case report

Abstract Melanotic neuroectodermal tumor of infancy (MNTI) is a rare neoplasm that affects mainly children under 1 year of age. A 4-month-old boy was referred for evaluation of a lesion with 1 month of evolution. Intra-oral examination detected a firm upon palpation submucosal nodular mass, measuring 1.5 cm in diameter, affecting the anterior maxillary alveolar ridge and covered by a slightly blue mucosa with evident telangiectasia. The patient underwent an incisional biopsy and histological and immunohistochemical analyses revealed nests of AE1/AE3 positive epithelioid cells with abundant melanin pigmentation. Other cell types, resembling neuroblasts, were also present and positive for CD56, synaptophysin and enolase. The diagnosis of MNTI was established and the patient was referred for treatment. Conservative surgical resection was performed along with 3 adjacent teeth under general anesthesia. The patient is in follow-up for 1,5 year without recurrence. Conservative surgical management of MNTI may be an alternative to maxillectomy, contributing to the patient´s quality of life.

Resumo Tumor neuroectodérmico melanótico da infância (TNMI) é um neoplasma raro que afeta principalmente crianças com idade abaixo de 1 ano. Um menino de 4 meses foi referenciado para avaliação de uma lesão com 1 mês de evolução. O exame intra-oral detectou uma massa nodular submucosa firme à palpação, medindo 1,5 cm de diâmetro, afetando rebordo alveolar anterior da maxila e recoberta por mucosa de coloração levemente azulada com telangiectasia evidente. O paciente foi submetido à biopsia incisional e as análises histológica e imunohistoquímica revelaram ninhos compostos por células com abundante pigmento de melanina, positivas para AE1/AE3. Outro tipo celular, semelhante à neuroblastos, também estava presente e foram positivas para CD56, sinaptofisina e enolase. O diagnóstico de TNMI foi estabelecido e o paciente encaminhado para tratamento. Ressecção cirúrgica conservadora sob anestesia geral ao longo de 3 dentes adjacentes foi realizada. O paciente está em acompanhamento há 1 ano e meio sem sinais de recorrência. O tratamento cirúrgico conservador do TNMI pode ser uma alternativa à maxilectomia, contribuindo para a qualidade de vida do paciente.

Acute Myeloid Leukemia With MLL Rearrangement and CD4+/CD56+ Expression can be Misdiagnosed as Blastic Plasmacytoid Dendritic Cell Neoplasm: Two Case Reports

No abstract available.

A Rare Case of Acute Leukemic Presentation of Blastic Plasmacytoid Dendritic Cell Neoplasm without Cutaneous Lesions

No abstract available.

A Case of Double Primary Neuroendocrine Tumor from Duodenum and Pancreas / 대한소화기학회지

Gastrointestinal neuroendocrine tumors arise from cells of the diffuse neuroendocrine system and can take place almost anywhere within the gastrointestinal tract. A 40-year-old man admitted to evaluate a duodenal subepithelial lesion which was incidentally found at health check-up. The polypoid duodenal subepithelial lesion, measuring about 7 mm, was removed by the endoscopic mucosal resection and the pathology confirmed a neuroendocrine tumor. Abdominopelvic computed tomography, done for staging work up, revealed a mass in the pancreatic head and the patient received pylorus preserving pancreaticoduodenectomy. Mass at the pancreas also found out to be neuroendocrine tumor but showed different histopathologic traits under immunohistochemical staining. The patient was also diagnosed as hyperparathyroidism and pituitary microadenoma. Finally, multiple endocrine neoplasia type 1 was confirmed, which was accompanied by duodenal neuroendocrine tumor.

A Case of Double Primary Neuroendocrine Tumor from Duodenum and Pancreas / 대한소화기학회지

Gastrointestinal neuroendocrine tumors arise from cells of the diffuse neuroendocrine system and can take place almost anywhere within the gastrointestinal tract. A 40-year-old man admitted to evaluate a duodenal subepithelial lesion which was incidentally found at health check-up. The polypoid duodenal subepithelial lesion, measuring about 7 mm, was removed by the endoscopic mucosal resection and the pathology confirmed a neuroendocrine tumor. Abdominopelvic computed tomography, done for staging work up, revealed a mass in the pancreatic head and the patient received pylorus preserving pancreaticoduodenectomy. Mass at the pancreas also found out to be neuroendocrine tumor but showed different histopathologic traits under immunohistochemical staining. The patient was also diagnosed as hyperparathyroidism and pituitary microadenoma. Finally, multiple endocrine neoplasia type 1 was confirmed, which was accompanied by duodenal neuroendocrine tumor.

Immunophenotypic Characterization and Quantification of Neoplastic Bone Marrow Plasma Cells by Multiparametric Flow Cytometry and Its Clinical Significance in Korean Myeloma Patients

Multiparametric flow cytometry (MFC) allows discrimination between normal and neoplastic plasma cells (NeoPCs) within the bone marrow plasma cell (BMPC) compartment. This study sought to characterize immunophenotypes and quantitate the proportion of NeoPCs in BMPCs to diagnose plasma cell myeoma (PCM) and evaluate the prognostic impact of this method. We analyzed the MFC data of the bone marrow aspirates of 76 patients with PCM and 33 patients with reactive plasmacytosis. MFC analysis was performed using three combinations: CD38/CD138/-/CD45; CD56/CD20/CD138/CD19; and CD27/CD28/CD138/CD117. The plasma cells of patients with reactive plasmacytosis demonstrated normal immunophenotypic patterns. Aberrant marker expression was observed in NeoPCs, with negative CD19 expression observed in 100% of cases, CD56+ in 73.7%, CD117+ in 15.2%, CD27- in 10.5%, CD20+ in 9.2%, and CD28+ in 1.3%. In PCM patients, more than 20% of NeoPCs/BMPCs were significantly associated with factors suggestive of poor clinical outcomes. Patients who were CD27- or CD56+/CD27-, demonstrated shorter overall survival than patients of other CD56/CD27 combinations. Our results support the clinical value of immunophenotyping and quantifying NeoPCs in PCM patients. This strategy could help to reveal poor prognostic categories and delineate surrogate markers for risk stratification in PCM patients.

Multiple Neuroendocrine Tumor of the Distal Ileum / 대한소화기학회지

No abstract available.

Diffuse Follicular Variant of Papillary Thyroid Carcinoma in a 69-Year-old Man with Extensive Extrathyroidal Extension: A Case Report

Diffuse follicular variant papillary thyroid carcinoma (DFVPTC) is a rare variant papillary thyroid carcinoma. DFVPTC typically occurs in young females, extensively involves one lobe or both lobes entirely with frequent nodal metastasis and vascular invasion. In contrast to the other subtypes of follicular variant, DFVPTC has biologically aggressive behavior. We present a case of DFVPTC arising in a 69-yr-old male patient. He presented hoarseness for a few months. Following diagnosis of malignancy on aspiration cytology, total thyroidectomy with neck dissection was performed. The tumor involved both lobes of thyroid, encroaching the surrounding structures including tracheal cartilage and esophagus. Multiple lymph node metastasis and vascular invasion were also found. The patient passed away due to the unexplained bleeding of surgical site.

Exophytic combined hepatocellular carcinoma and cholangiocarcinoma

No abstract available.

Immunophenotypic Features of Granulocytes, Monocytes, and Blasts in Myelodysplastic Syndromes / 대한진단검사의학회지

BACKGROUND: Despite the diagnostic utility of immunophenotyping for myelodysplastic syndromes (MDS), it has not been widely performed, and reports on this are absent in Korea. We aimed to evaluate the immunophenotypic features of non-blastic granulocytes, monocytes, and blasts in patients with MDS and non-clonal disorders using routine flow cytometry (FCM). Moreover, we evaluated the phenotypic abnormalities of mature cells in leukemic patients. METHODS: Marrow aspirates from 60 patients, including 18 with MDS, 18 with leukemia, and 24 with non-clonal disorders (control group), were analyzed using FCM. Blasts, non-blast myeloid cells, and monocytes were gated based on CD45 expression and side scatter (SSC). The phenotypes were then compared among the 3 groups. RESULTS: Compared to non-clonal disorders, the granulocytic lineages of MDS showed decreased SSC (P=0.005), increased CD45 intensity (P=0.020), decreased CD10-positive granulocytes (P= 0.030), and a higher CD56-positive rate (P=0.005). It is noteworthy that similar results were obtained in the leukemia group, and these findings were not related to the phenotypes of the leukemic cells. Using blast and monocytic gating, useful parameters for generating a differential diagnosis were not found. CONCLUSIONS: Gating the granulocytic region is a relatively easy method for MDS immunophenotyping. Among the parameters studied, SSC, CD10, and CD56 were the most useful for differentiating MDS from non-clonal disorders. While immunophenotypic changes in MDS appear to be useful for differentiating MDS from non-clonal disorders, these changes were also noted in the mature cells of leukemic patients.

A Case of Atypical Solid-pseudopapillary Tumor of the Pancreas / 대한소화기학회지

Solid-psudopapillary tumor is an uncommon pancreatic neoplasm of low malignant potential that most frequently affect young woman. Solid-psudopapillary tumor are histologically, clinically, and prognostically quite distinct from the more common ductal adenocarcinoma. Recently, we experienced a 36-year-old male who was suspected to have extrapancreatic tumor based on atypical radiologic imaging study, young age, and male sex, and finally diagnosed as solid-psudopapillary tumor on immunohistochemical stain examination. We report this case with review of the relevant literatures.

A Case of CD56+ Extranodal NK/T-cell Lymphoma, Nasal Type, Presenting as a Duodenal Ulcer Bleeding / 대한소화기학회지

Extranodal NK/T-cell lymphoma is a recently recognized distinct entity within the World Health Organization classification of lymphoid tumors. It is relatively prevalent in Asian and South American populations. It most commonly occurs in the nasal or paranasal areas and less frequently in the skin, the soft tissue, and the gastrointestinal tract. Among these, extranodal NK/T-cell lymphoma of the gastrointestinal tract has shown an aggressive clinical course. We report a case of CD56+ extranodal NK/T-cell lymphoma presenting as a duodenal ulcer bleeding. A 62-year-old male patient presented with melena and abdominal pain. Endoscopic examination of the upper gastrointestinal tract showed the duodenal ulcer covered by blood clot. Pathologic examination revealed the diffuse infiltration of atypical lymphocytes with an angiocentric growth pattern, which was positive for CD3, CD56, and granzyme. The patient showed rapid deteriorating clinical course and died on day 14 after admission. Thus, we report this case with the review of literatures.