Clinical significances of TTF-1, neuroendocrine (chromogranin, synaptophysin, CD56), and keratin (pancytokeratin, CK7, CK5/6) marker immunostaining in small cell lung cancer.

PURPOSE: Immunohistochemistry (IHC) markers have established a role in the pathological diagnosis of small cell lung cancer (SCLC) and especially neuroendocrine markers help to differentiate SCLC from other tumors. The study aimed to evaluate the clinical role of different IHC markers in SCLC patients. METHODS: A total of 378 SCLC patients were enrolled in the study and analyzed retrospectively. TTF-1, neuroendocrine markers (chromogranin, synaptophysin, and CD56), and keratin markers (pancytokeratin, CK7 and CK5/6) were assessed. RESULTS: CD56 had the highest expression (92.3%) followed by pancytokeratin (82.8%), TTF-1 (74.8%), synaptophysin (72.7%), chromogranin (55.6%), CK7 (54.8%), and CK5/6 (9%). No differences were observed in the expression of all markers according to the stage of the disease. Extended disease SCLC (ED-SCLC) patients with synaptophysin expression had a higher response to chemotherapy compared to those without staining (p = 0.01); on the other hand, the chemotherapy response of these patients was not significantly different when they expressed CK7 (p = 0.06). Pancytokeratin expression was associated with favorable survival in both limited disease SCLC (LD-SCLC) (p = 0.02) and ED-SCLC (p = 0.005) patients. Similarly, ED-SCLC patients with CD56 staining lived longer than those without expression (p = 0.001). The lack of synaptophysin expression in LD-SCLC patients (p = 0.06) and TTF-1 expression in ED-SCLC patients (p = 0.06) were correlated with better survival rates. CONCLUSION: We conclude that IHC markers, used frequently in the diagnosis of SCLC, might also be used in clinical decision-making, since they are correlated with predictive and prognostic factors for the disease.

[Neuroendocrine expression markers in triple-negative, luminal-A, luminal-B and HER2neu breast cancer]. / Expresión de marcadores neuroendócrinos en cáncer de mama triple-negativo, luminal-A, luminal-B y HER2neu.

Background: Primary breast tumors with neuroendocrine (NE) differentiation are a heterogeneous tumor group with diversity of biological behavior, with poorly defined prevalence and prognosis. Objective: To evaluate the chromogranin, synaptophysin, CD56, INSM1 markers expression prevalence and the association between NE differentiation and tumor molecular type. Material and methods: Observational, cross-sectional study which included 110 breast tissue samples with primary invasive carcinoma. Immunohistochemistry was performed for chromogranin, synaptophysin, CD56 and INMS1 markers. NE differentiation was considered with 10-90% positive cells, and NE tumor with > 90% positive cells. Results: 26.3% showed neuroendocrine differentiation. Out of these, 48.2% were luminal-A type, 24.1% luminal-B, 11.5% HER2neu, 17.2% triple-negative; 1.8% were NE tumors. Tumors were marker positive, and out of these to chromogranin in 24.5%, synaptophysin in 28.2%, CD56 in 2.7%, INSM1 in 16.4%. Synaptophysin was expressed in 17.3% luminal-A type, 6.4% luminal-B, 0.9% HER2neu, 3.6% triple-negative. NE differentiation showed association with synaptophysin expression (r = 0.586, p = 0.0001). Conclusion: The NE differentiation prevalence was 26.3% in primary invasive breast cancers, with luminal-A molecular type predominance.

Introducción: los tumores primarios de mama con diferenciación neuroendócrina (NEBC por sus siglas en inglés) son un grupo heterogéneo de tumores con diversidad de comportamiento biológico, con prevalencia y pronóstico poco definido. Objetivo: evaluar la prevalencia de la expresión los marcadores cromogranina, sinaptofisina, CD56, INSM1 y la asociación entre la diferenciación neuroendócrina y el tipo molecular del tumor. Material y métodos: estudio observacional, transversal que incluyó 110 muestras de tejido mamario con carcinoma invasor primario. Se realizó inmunohistoquímica para los marcadores cromogranina, sinaptofisina, CD56 y INMS1. La presencia 10-90% de células positivas se consideró diferenciación neuroendócrina y tumor neuroendócrino con > 90% de células positivas. Resultados: el 26.3% mostró diferenciación neuroendócrina. De estos, 48.2% fueron tipo luminal-A, 24.1% luminal-B, 11.5% HER2neu y 17.2% triple-negativo; 1.8% resultaron tumores neuroendócrinos. Los tumores presentaron marcadores positivos y de estos, 24.5% fueron a cromogranina, 28.2% a sinaptofisina, 2.7% a CD56 y 16.4% a INSM1. La sinaptofisina se expresó en 17.3% del tipo luminal-A, 6.4% luminal-B, 0.9% HER2neu, 3.6% triple-negativo. La diferenciación neuroendócrina mostró asociación con la expresión de sinaptofisina (r = 0.586, p = 0.0001). Conclusión: la prevalencia de la diferenciación neuroendócrina fue del 26.3% en los cánceres invasores primarios de mama, con predominio en el tipo molecular luminal-A.

Immunostaining of stromal CD56 cells in ovarian malignancies

SUMMARY OBJECTIVES: The aim of this study was to evaluate CD56 immunostaining in the stroma of benign and malignant ovarian epithelial neoplasms and associate the CD56 immunostaining with prognostic factors and survival in ovarian cancer. METHODS: Patients with ovarian epithelial neoplasia (n=77) were studied with a prospective cohort. The CD56 immunostaining was evaluated in the peritumoral stroma. Two groups were evaluated: benign ovarian neoplasms (n=40) and malignant ovarian neoplasms (n=37). Data were recorded for histological type and grade, International Federation of Gynecology and Obstetrics staging, molecular subtype, and lymph node metastases. Fisher's exact test and Kaplan-Meier survival curves were used, with a significance level of ≤0.05. RESULTS: We found greater CD56 stromal immunostaining in malignant neoplasms when compared to the group of benign neoplasms (p=0.00001). There was no significant difference in relation to the prognostic factors and survival. CONCLUSION: Malignant ovarian neoplasms showed higher stromal CD56 immunostaining. As the prognostic value of natural killer in ovarian cancer is controversial, knowing the specific function of each cell present both in the tumor tissue and systemically may help guide successful immunotherapies in the near future.

Precursor B-lineage acute lymphoblastic leukemia patients with aberrant natural killer cell and T cell - lineage antigen expression: experience from a tertiary cancer care center

Abstract Introduction Flow cytometric immunophenotyping (FCI) plays a major role in diagnosing hematologic malignancies. In patients diagnosed with precursor B-lineage acute lymphoblastic leukemia (B-ALL), expression of certain non-lineage/cross lineage antigens is of prognostic and cytogenetic relevance. There is a paucity of studies that have comprehensively analyzed the clinical and laboratory profiles of B-ALL patients showing aberrant T/natural killer (NK) cell antigen expression. Materials and methods This is a prospective study where 152 consecutive B-ALL patients were analyzed for aberrant expression of T/NK cell antigens (CD1a, CD5, CD4, CD7, CD8 and CD56) by FCI. The clinical and laboratory profile of these T/NK-cell antigen-expressing B-ALL patients was statistically analyzed against conventional B-ALL patients. Results In our B-ALL cohort, CD5, CD7 and CD56 expression were observed in one, six and nine patients, respectively. CD56-expressing B-ALL patients were predominantly children (89%) and presented as standard clinical risk (p = 0.010) disease with frequent ETV6-RUNX1 fusion (p = 0.021) positivity. On the contrary, CD7-expressing B-ALL patients were adolescent-young adult/adult-age skewed (83%) and had an adverse cytogenetic profile (p = 0.001), especially for the frequent presence of BCR-ABL1 fusion (p = 0.004) and KMT2A rearrangement (p = 0.045). CD7-expressing B-ALL patients had inferior event-free survival (p = 0.040) than their CD56-expressing counterparts, but there was no significant difference in the overall survival (p = 0.317). Conclusion In comparison to conventional B-ALL patients, there are significant differences in the age, cytogenetic profile and event-free survival of T/NK-cell antigen-expressing B-ALL patients.

Precursor B-lineage acute lymphoblastic leukemia patients with aberrant natural killer cell and T cell - lineage antigen expression: experience from a tertiary cancer care center.

INTRODUCTION: Flow cytometric immunophenotyping (FCI) plays a major role in diagnosing hematologic malignancies. In patients diagnosed with precursor B-lineage acute lymphoblastic leukemia (B-ALL), expression of certain non-lineage/cross lineage antigens is of prognostic and cytogenetic relevance. There is a paucity of studies that have comprehensively analyzed the clinical and laboratory profiles of B-ALL patients showing aberrant T/natural killer (NK) cell antigen expression. MATERIALS AND METHODS: This is a prospective study where 152 consecutive B-ALL patients were analyzed for aberrant expression of T/NK cell antigens (CD1a, CD5, CD4, CD7, CD8 and CD56) by FCI. The clinical and laboratory profile of these T/NK-cell antigen-expressing B-ALL patients was statistically analyzed against conventional B-ALL patients. RESULTS: In our B-ALL cohort, CD5, CD7 and CD56 expression were observed in one, six and nine patients, respectively. CD56-expressing B-ALL patients were predominantly children (89%) and presented as standard clinical risk (p=0.010) disease with frequent ETV6-RUNX1 fusion (p=0.021) positivity. On the contrary, CD7-expressing B-ALL patients were adolescent-young adult/adult-age skewed (83%) and had an adverse cytogenetic profile (p=0.001), especially for the frequent presence of BCR-ABL1 fusion (p=0.004) and KMT2A rearrangement (p=0.045). CD7-expressing B-ALL patients had inferior event-free survival (p=0.040) than their CD56-expressing counterparts, but there was no significant difference in the overall survival (p=0.317). CONCLUSION: In comparison to conventional B-ALL patients, there are significant differences in the age, cytogenetic profile and event-free survival of T/NK-cell antigen-expressing B-ALL patients.

Loss of expression of the Neural Cell Adhesion Molecule 1 (NCAM1) in atypical teratoid/rhabdoid tumors: a new diagnostic marker?

Background: Atypical teratoid/rhabdoid tumors (AT/RT) are aggressive embryonal tumors of the central nervous system. They are largely characterized by inactivating mutations of the SMARCB1 tumor suppressor gene. AT/RT patients have a very poor prognosis and no standard therapeutic protocol has been defined yet. Recently, multimodal therapy with multiple drug combinations has slightly improved the overall survival, however drug toxicity remains high. In this scenario, a better understanding of the pathophysiology of the disease is needed. Methods: We evaluated the gene expression profile of AT/RT samples to find new genetic factors contributing to the pathophysiology of the disease. We found target genes significantly differentially expressed between AT/RT and medulloblastoma (MB), the most common embryonal brain tumor. The mRNA expression was validated by quantitative real-time PCR and, at the protein level, expression was validated by immunohistochemistry in an independent set of tumors. Results: The Neural cell adhesion molecule 1 (NCAM1) gene was found to be consistently downregulated in AT/RT samples when compared to MB and normal brain tissue. Immunohistochemistry showed that the expression of NCAM1 in AT/RT was significantly lower than that of MB. Conclusion: NCAM1 is an important molecule involved in neuron-to-neuron and neuron-to-muscle adhesion during development. Downregulation of NCAM1 has been implicated in several human cancers suggesting that it might have a tumor repressor role. In this study we found a significantly reduced expression of NCAM1 in AT/RT when compared to MB and we suggest that this feature can be used as a diagnostic marker, along with demonstration of SMARCB1 (INI1) or SMARCA4 (BRG1) inactivation. The roles of NCAM1 in the pathophysiology of AT/RT are still to be determined (AU)

Enfermedad celíaca vs. atrofia villositaria serológicamente negativa: similitudes y diferencias histológicas y en el perfil inmunohistoquímico de linfocitos CD3, CD4, CD8 y CD56 / Celiac disease and negative serology villous atrophy: histological comparison and immunohistochemical study of CD3, CD4, CD8 and CD56 lymphocytes

Existe un grupo de enteropatía conocidas como AVSN que pueden simular enfermedad celíaca. Objetivo: El objetivo de este estudio es describir los hallazgos histológicos y de inmunohistoquímica en pacientes con enfermedad celíaca y AVSN. Material y métodos: 15 biopsias de pacientes con enfermedad celíaca y 19 biopsias con AVSN fueron reexaminados. Se estudió características histológicas tales como atrofia severa, hiperplasia de criptas, número de células plasmáticas, número de eosinófilos y presencia de neutrófilos. Asimismo, a través de inmunohistoquímica se estudió la presencia de linfocitos CD4, CD8, CD3, CD56. Resultados: Se encontró diferencia significativa en la mayor presencia de hiperplasia de criptas (p=0,0348) y mayor número de células plasmáticas (p=0,0348) en las biopsias de enfermedad celíaca que en las catalogadas como AVSN. El número de linfocitos CD8, CD4, CD56 y su distribución fue similar en ambos grupos. El porcentaje de linfocitos intraepiteliales CD3 positivos (p=0,0144) fue mayor en pacientes con AVSN. Conclusión: Los hallazgos histológicos e inmunohistoquímicos muestran más similitudes que diferencias. La diferencia hallada en nuestro estudio sugiere mayor respuesta inmune humoral en pacientes con enfermedad celiaca que en AVSN...

There is a group of enteropathies recently known as seronegative villous atrophy (SNVA), which can simulate celiac disease. Objective: The aim of this study was to describe histological and immunohistochemical differences between a group of Celiac disease and SNVA patients. Material and methods: Microscopy reexamination and Immunohistochemistry study were performed for a group of 15 celiac patients and 19 SNVA patients. Histological features as severe atrophy, crypt hyperplasia, plasma cells number, eosinophils number, neutrophils presence were studied; CD4, CD8, CD3, and CD56 markers were studied through immunohistochemistry. Results: There was a significant difference between the frequency of observation of crypt hyperplasia (p=0.0348) and plasma cells (p=0.0348) in celiac disease patients than SNVA patients. In celiac disease was bigger. The number and distribution of CD 8, CD4 and CD56 lymphocytes was similar in both groups. The percentage of CD3 positive intraepithelial lymphocytes (p=0.0144) was higher in SNVA. Conclusion: Histological and immunohistochemical evaluation shows more similarities than differences. The differences found in this study suggest more humoral immune response in celiac disease than in SNVA...

Adaptive Memory of Human NK-like CD8+ T-Cells to Aging, and Viral and Tumor Antigens.

Human natural killer (NK)-like CD8+ T-cells are singular T-cells that express both T and NK cell markers such as CD56; their frequencies depend on their differentiation and activation during their lifetime. There is evidence of the presence of these innate CD8+ T-cells in the human umbilical cord, highlighting the necessity of investigating whether the NK-like CD8+ T-cells arise in the early stages of life (gestation). Based on the presence of cell surface markers, these cells have also been referred to as CD8+KIR+ T-cells, innate CD8+ T-cells, CD8+CD28-KIR+ T-cells or NKT-like CD8+CD56+ cells. However, the functional and co-signaling significance of these NK cell receptors on NK-like CD8+ T-cells is less clear. Also, the diverse array of costimulatory and co-inhibitory receptors are spatially and temporally regulated and may have distinct overlapping functions on NK-like CD8+ T-cell priming, activation, differentiation, and memory responses associated with different cell phenotypes. Currently, there is no consensus regarding the functional properties and phenotypic characterization of human NK-like CD8+ T-cells. Environmental factors, such as aging, autoimmunity, inflammation, viral antigen re-exposure, or the presence of persistent tumor antigens have been shown to allow differentiation ("adaptation") of the NK-like CD8+ T-cells; the elucidation of this differentiation process and a greater understanding of the characteristics of these cells could be important for their eventual in potential therapeutic applications aimed at improving protective immunity. This review will attempt to elucidate an understanding of the characteristics of these cells with the goal toward their eventual use in potential therapeutic applications aimed at improving protective immunity.

Linfoma T intestinal monomórfico CD56+. Primer caso informado en Colombia y revisión de la literatura / Monomorphic Intestinal T-Cell Lymphoma. First reported case in Colombia and review of the literature

Se informa el caso de una mujer de 80 años con hallazgo incidental de masa abdominal en mesogastrio. Se le realiza resección de intestino delgado por sospecha de absceso con síndrome adherencial. El estudio patológico de la pieza quirúrgica demostró compromiso por linfoma no Hodgkin T monomórfico CD56+. Los linfomas T del tubo digestivo son inusuales; corresponden al 5% de las neoplasias linfoides de esta localización. El linfoma intestinal T monomórfico CD56+ corresponde a 10-20% de los linfomas T intestinales. Se presenta en regiones donde la enfermedad celiaca es infrecuente y no se asocia a enteropatía. Su curso es agresivo y habitualmente se manifiesta como una emergencia quirúrgica por obstrucción o perforación intestinal.

80 year old woman with incidental finding of abdominal mass in midgut, in which small bowel resection is performed for suspected abscess associated to surgical adhesions. Pathological examination of the surgical specimen showed a monomorphic CD56+ T cell lymphoma. T-cell lymphomas of the digestive tract are rare, accounting for 5% of all lymphoid neoplasms in this location. Monomorphic CD56+ intestinal T cell lymphoma corresponds to 10 - 20% of T cell intestinal lymphomas. This tumor occurs in regions where celiac disease is rare and it is not associated with enteropathy. Its course is aggressive and usually manifests as a surgical emergency by intestinal obstruction or perforation.

As mucinas e o NCAM (CD56) na colangiocarcinogênese intra-hepática / Mucins and NCAM (CD56) in intrahepatic cholangiocarcinogenesis

Introduction: Cholangiocarcinoma is the second most common malignant neoplasm of the hepatobiliary system. During cholangiocarcinogenesis phenotypic changes occur in the ductal epithelium, including the expression of mucins (MUC). However, the evaluating studies of the expression of mucins in the different stages of cholangiocarcinogenesis are scarce. CD56 has also contributed in differentiating benign ductal proliferation and cholangiocarcinoma; however, its expression has not been evaluated in dysplastic epithelium of the bile duct yet. Objective: To assess immunohistochemical profile of (MUC) 1, 2, 5, 6, and CD56 in cholangiocarcinoma, pre-neoplastic and reactive lesions in the epithelium of intrahepatic bile ducts. Material and methods: Immunohistochemical expression of MUC 1, 2, 5, 6, and CD56 were studied for 11 cases of cholangiocarcinoma and 83 intrahepatic bile ducts (67 reactive and 16 dysplastic). Variables were considered significant when p < 0.05. Results: The expression of MUC1 occurred in about 90% of the cholangiocarcinomas, contrasting with the low frequency of positive cases in reactive and dysplastic bile ducts (p < 0.001). However, there was no statistically significant difference in the expression of MUC5, MUC6 and CD56 between the reactive or dysplastic lesions and cholangiocarcinoma. The anti-MUC2 antibody was negative in all cases. Conclusions: MUC1 contributed for the differential diagnosis between cholangiocarcinoma and pre-neoplastic and reactive/regenerative lesions of intrahepatic bile ducts, and it should compose the antibodies panel aiming at improvement of these differential diagnoses. In contrast, MUC2, MUC5, MUC6 and CD56 were not promising in differentiating all the phases of cholangiocarcinogenesis...

Introdução: O colangiocarcinoma é a segunda neoplasia maligna mais comum do sistema hepatobiliar. Durante a colangiocarcinogênese podem ocorrer alterações fenotípicas do epitélio ductal, incluindo a expressão de mucinas. Entretanto, os estudos que avaliam a expressão das mucinas nas diferentes etapas da colangiocarcinogênese são escassos. O CD56, apesar de contribuir na diferenciação entre as proliferações ductais benignas e o colangiocarcinoma, ainda não teve a sua expressão avaliada no epitélio displásico dos ductos biliares. Objetivos: Analisar o perfil das mucinas (MUC) 1, 2, 5, 6 e do CD56 no colangiocarcinoma, nas lesões pré-neoplásicas e reacionais de ductos biliares intra-hepáticos. Material e métodos: A expressão imuno-histoquímica da MUC 1, 2, 5, 6 e do CD56 foram avaliadas em 11 colangiocarcinomas e 83 ductos biliares intra-hepáticos (67 reativos e 16 displásicos). As variáveis foram consideradas como significativas quando p < 0,05. Resultados: A expressão da MUC1 ocorreu em cerca de 90% dos colangiocarcinomas, contrastando com a baixa frequência de casos positivos nos ductos biliares reativos ou displásicos (p < 0,001). Não houve diferença estatisticamente significativa na expressão de MUC5, MUC6 e CD56 entre as lesões reativas, displásicas e o colangiocarcinoma. O anticorpo anti-MUC2 foi negativo em todos os casos. Conclusão: A MUC1 contribuiu no diagnóstico diferencial entre o colangiocarcinoma e as lesões pré-neoplásicas e reacionais/regenerativas dos ductos biliares intra-hepáticos, e deve compor o painel de anticorpos a ser empregado visando o aprimorando destes diagnósticos diferenciais. Contrariamente, a MUC2, MUC5, MUC6 e o CD56 não se mostraram promissoras na diferen...

Blastic plasmacytoid dendritic cell neoplasm / Neoplasia blastica de celulas dendriticas plasmocitoides

Blastic plasmacytoid dendritic cell neoplasm is a rare and aggressive hematodermic neoplasia with frequent cutaneous involvement and leukemic dissemination. We report the case of a 76-year-old man with a 2 month history of violaceous nodules and a tumor with stony consistency, located on the head, and mandibular, cervical and supraclavicular lymphadenopathies. Multiple thoracic and abdominal adenopathies were identified on computerized tomography. Flow cytometry analysis of the skin, lymph node and bone marrow biopsies demonstrated the presence of plasmocytoid dendritic cell neoplastic precursor cells (CD4+, CD45+, CD56+ and CD123+ phenotype). After initial clinical and laboratorial complete remission with chemotherapy, the patient died due to relapse of the disease associated with the appearance of a cervical mass with medullary compromise.

A neoplasia blástica de células dendríticas plasmocitóides é uma neoplasia hematodérmica rara, agressiva, com frequente envolvimento cutâneo e disseminação leucêmica. Relatamos o caso de um homem de 76 anos com quadro clínico com 2 meses de evolução caracterizado por nódulos e tumor de tonalidade violácea, de consistência pétrea, localizados na cabeça, e linfadenopatias mandibular, cervicais e supraclaviculares. Identificaram-se múltiplas adenopatias torácicas e abdominais em tomografia computorizada. A análise por citometria de fluxo de biópsias cutânea, ganglionar e óssea demonstrou a presença de precursores neoplásicos das células dendríticas plasmocitóides (fenótipo CD4+, CD45+, CD56+ e CD123+). Após remissão clínica e laboratorial completa inicial com quimioterapia, veio a falecer por recaída da doença associada ao aparecimento de massa cervical com compromisso medular.

Efecto comparado de dosis inmunoestimulantes de fracciones ribosomales y proteoglicanos de membrana sobre la activación de subpoblaciones de células mononucleadas humanas de sangre periférica / Compared effect of immunostimulatory dose of ribosomal fractions and membrane proteoglycans on the activation of human mononuclear cell subsets from peripheral blood

Antecedentes. La población mexicana presenta una alta prevalencia de infecciones recurrentes de vías respiratorias altas. Objetivos. Comparar el efecto de dosis inmunoestimulantes de ribosomas bacterianos y proteoglicanos de membrana Ribovac® sobre células mononucleadas. Material y métodos. La expresión de IL-6 de células mononucleadas en cultivo, se midió a concentraciones y tiempos variables por la técnica de ELISA, mientras que el efecto de Ribovac® en poblaciones de células mononucleadas fue analizado por citometría de flujo. Resultados. Ribovac® tiene un efecto dependiente de dosis y tiempo de exposición sobre la expresión de IL-6 por células mononucleadas; las concentraciones de IL-6 fueron máximas a las 6 horas de tratamiento con Ribovac®. La expresión de CD3+ fue mayor cuando las células mononucleadas se trataron con 125 µg/ml por 72 horas (p=0,010) respecto a aquellas que se trataron a mitad de esa concentración en igual tiempo, a diferencia de la expresión de CD19, que fue mayor en células mononucleadas tratadas con 62,5 µg/ml por 72 horas que en aquellas tratadas con 125 µg/ml por 72 horas (p=0,021). No se encontraron disminuciones estadísticamente significativas en el número de células CD16+CD56+ ni en la coexpresión de los marcadores CD45 y CD19 cuando se compararon tanto tiempos de administración como concentraciones de Ribovac®. Conclusiones. La expansión de poblaciones linfoides y la maduración de éstas a fenotipos con mayor capacidad efectora son efectos inducibles y deseables de Ribovac®, que deben tenerse en cuenta al decidir su tiempo e intervalos de administración.(AU)

Background. The Mexican population has a high prevalence of recurrent infections of upper respiratory tract. Objective. To compare the effect of immunostimulatory dose of bacterial ribosomes and membrane proteoglycan Ribovac® on mononuclear cells. Methods. The expression of interleukin 6 from mononuclear cells in culture was measured at varying concentrations and times by ELISA, while the effect of R in populations of mononuclear cells was analyzed by flow cytometry. Results. Ribovac® has an dose-dependent and exposure time effect on the expression of IL-6 by mononuclear cells, concentrations of IL-6 were maximal at 6 hours of treatment with Ribovac®. The expression of CD3+ was higher when mononuclear cells weretreated with 125 µg/ml for 72 hours (p=0,010) than those who were treated to half that concentration in the same time, unlike the expression of CD19 which was higher in mononuclear cells treated with 62,5 µg/ml for 72 hours than those that were treated with 125 µg/ml for 72 hours (p=0,021). There were no statistically significance in the decrease in the number of CD16+CD56+ cells and in the coexpression of CD45 and CD19 markers neither; when comparing both times of administration and evaluated concentrations of Ribovac®. Conclusions. The lymphoid population expansion and their maturation to better effector phenotypes effector are inducible and desirable effects of Ribovac® and these important when deciding the time and intervals of administration.(AU)

The expression of CD56 antigen is associated with poor prognosis in patients with acute myeloid leukemia

BACKGROUND: The expression of CD56 is considered a bad prognostic factor for overall survival, lower rates or short complete remission and extramedullary invasion but the results are controversial. The importance of validating new prognostic parameters in acute leukemias was the reason to investigate the CD56 expression in blast cells of patients with acute myeloid leukemia. METHODS: A cohort of 48 patients treated at Hospital de Clinicas de Porto Alegre and diagnosed with acute myeloid leukemia as classified by the French-American-British group (FAB) criteria using cell morphology, cytochemistry and flow cytometry were evaluated. RESULTS: Eight cases (16.7 percent) were CD56 positive without correlation to age or gender. The highest incidence of CD56 positivity was in FAB subtypes M4 and M5. The death rate during induction was not significantly different between patients with and without CD56 expression (62.5 percent vs. 27.5 percent; p-value = 0.097). However, patients that expressed CD56 had significantly lower overall survival than those who did not (mean 4.0 months vs. 14.5 months; p-value = 0.03). CONCLUSIONS: The data suggest that expression of CD56 in acute myeloid leukemia may be indicative of poor prognosis because it is associated with a shorter overall survival. The death rate during induction was not significantly different despite an apparent difference in proportions between groups.

The expression of CD56 antigen is associated with poor prognosis in patients with acute myeloid leukemia.

BACKGROUND: The expression of CD56 is considered a bad prognostic factor for overall survival, lower rates or short complete remission and extramedullary invasion but the results are controversial. The importance of validating new prognostic parameters in acute leukemias was the reason to investigate the CD56 expression in blast cells of patients with acute myeloid leukemia. METHODS: A cohort of 48 patients treated at Hospital de Clinicas de Porto Alegre and diagnosed with acute myeloid leukemia as classified by the French-American-British group (FAB) criteria using cell morphology, cytochemistry and flow cytometry were evaluated. RESULTS: Eight cases (16.7%) were CD56 positive without correlation to age or gender. The highest incidence of CD56 positivity was in FAB subtypes M4 and M5. The death rate during induction was not significantly different between patients with and without CD56 expression (62.5% vs. 27.5%; p-value = 0.097). However, patients that expressed CD56 had significantly lower overall survival than those who did not (mean 4.0 months vs. 14.5 months; p-value = 0.03). CONCLUSIONS: The data suggest that expression of CD56 in acute myeloid leukemia may be indicative of poor prognosis because it is associated with a shorter overall survival. The death rate during induction was not significantly different despite an apparent difference in proportions between groups.

Neoplasia hematodérmica CD4+ CD56+ en la infancia / Hematodermic CD4+ CD56+ neoplasm in childhood

La neoplasia hematodérmica CD4+ CD56+ con fenotipo de célula dendrítica plasmocitoide es una rara y agresiva neoplasia recientemente reconocida por la WHO-EORTC classification. Afecta adultos de edad media y ancianos, siendo muy pocos los casos descriptos en niños. Presentamos el caso de una niña de 12 años con grave retraso mental, estigmas genéticos y múltiples lesiones cutáneas localizadas en miembros inferiores y superiores. Histológicamente se observó un infiltrado dérmico difuso de células pequeñas y medianas con expresión de CD4, CD56, CD43 y S100 así como de marcadores dendríticos plasmocitoides: CD 123 y BDCA-2 confirmados por citometría de flujo, sin compromiso de sangre periférica ni médula ósea. Cumpliendo dos semanas de tratamiento para leucemia linfoblástica aguda evolucionó con remisión clínica de las lesiones cutaneas.

Hematodermic CD4+ CD56+ neoplasm with plasmacytoid dendritic cell phenotype is a rare and aggressive neoplasm recently recognized by the WHO-EORTC classification. It generally appears in elderly adults, exceptionally in childhood. We present a 12-year-old girl with severe mental retardation, genetic clinical features and multiple nodular cutaneous lesions on legs and arms. Histologically the nodules showed diffuse dermal infiltrate of medium and small cells and expression of CD4, CD56, CD43, S100 and plasmacytoid dendritic markers: CD123, BDCA-2 under flow cytometry study. Peripheral blood and bone marrow were not involved. Clinical remission of cutaneous lesions was observed after two weeks of acute lymphoblastic leukemia therapy.

Infiltração cutânea na leucemia megacariocítica aguda com expressão de CD56 / Cutaneous infiltration in acute megakaryocytic leukemia with CD56 expression

A LMA-M7 é um subtipo raro de leucemia mielóide aguda (LMA). Está freqüentemente associada a mielofibrose e representa um subtipo de mau prognóstico. Raramente apresenta infiltração em sítios extramedulares. O aspirado de medula óssea ou biópsia mostra uma população de células pleomórficas e basofílicas, que podem apresentar projeções citoplasmáticas. A utilização da imunofenotipagem é essencial para o diagnóstico de LMA-M7. O imunofenótipo característico apresenta uma população de células leucêmicas com ausência da maioria dos marcadores linfóides e mielóides de superfície, porém com expressão para os antígenos da linhagem megacariocítica: CD41a (complexo glicoprotéico IIb/IIIa), CD42b (glicoproteína Ib) e/ou CD61 (glicoproteína IIIa), ou antígeno relacionado ao fator VIII. Freqüentemente, a coloração citoquímica Sudan Black para os blastos megacariocíticos é negativa; neste caso, foi positiva para 40 por cento das células analisadas. A presença de CD56, cuja expressão aberrante em algumas leucemias mielóides é indicativo de mau prognóstico, pode estar associada à infiltração da pele.

AML-M7 is a rare subtype of acute myeloid leukemia (AML). It is frequently associated with myelofibrosis and corresponds to a poor prognosis subtype. It rarely presents with infiltration at extramedullary sites. The bone marrow aspirate or biopsy identifies pleomorphic and basophilic cell populations that may present with cytoplasmatic projections. The use of immunophenotyping is essential for the diagnosis of AML-M7. The characteristic immunophenotype presents a leukemic cell population without most lymphoid and myeloid surface markers, but with an expression of the megakaryocytic antigens: CD41a (glycoprotein complex IIb/IIIa), CD42b (glycoprotein Ib) and/or CD61 (glycoprotein IIIa), or the factor VIII-related antigen. The cytochemical stain Sudan Black is frequently negative for megakaryocytic blasts; in this case, it was positive in 40 percent of the analyzed cells. The presence of CD56, whose aberrant expression in some myeloid leukemias indicates poor prognosis, might be associated with skin infiltration.