Myofibroma/myofibromatosis: a clinicopathologic analysis of 9 cases / 中华病理学杂志

Objective@#To investigate the clinical and histological features, diagnosis and differential diagnosis of myofibroma/myofibromatosis.@*Methods@#The clinical data and pathology features of nine cases of myofibroma/myofibromatosis were collected from August 2011 to November 2016 in Affiliated Drum Tower Hospital, Nanjing University Medical School and Children′s Hospital of Nanjing Medical University. Immunohistochemistry(IHC), PDGFRB molecular analysis and ETV6-NTRK3 gene fusion were performed and relevant literature reviewed.@*Results@#There were 7 males and 2 females, with age ranging from 3 days to 18 years (mean 5 years). The tumors were located in head and neck (eight cases) and trunk (one case). Clinically, the tumors presented as freely movable nodules. Microscopically, they appeared biphasic with alternating light- and dark-staining areas. The light-staining area consisted mainly of plump myoid spindle cells with eosinophilic cytoplasm arranged in nodules, short fascicles, or whorls.The dark-staining area was composed of round or polygonal cells with slightly hyperchromatic nuclei or small spindle cells arranged around a distinct hemangiopericytoma-like vascular pattern. IHC showed the tumor cells in the light-staining area were strongly positive for vimentin and SMA, while cells in dark-staining area were strongly positive for vimentin, and weakly for SMA. Tumor cells were negative for desmin, S-100 protein, h-Caldesmon, CD34 and STAT6. Analysis of PDGFRB mutations was performed in seven cases. Two cases showed 12 exon point mutation c. 1681 c>T(p.R561C), one case showed 14 exon point mutation c. 1998C>G (p.N666K). ETV6-NTRK3 gene fusion was not detected by fluorescence in situ hybridization in four patients under three years old. All cases were followed for 6 to 68 months, with two recurrences.@*Conclusions@#Myofibroma/myofibromatosis is an uncommon benign myofibroblastic tumor of infancy and childhood. The tumor can appear biphasic, and may show PDGFRB point mutation which is of potential diagnostic value.

Effect and mechanism of Imatinib mesilate on intimal hyperplasia of rabbit carotid artery after ballon injury / 天津医药

Objective To investigate the effect and mechanism of Imatinib mesilate (Imatinib) on intimal hyperplasia of rabbit carotid arteries after balloon injury. Methods Thirty adult Newzealand rabbits were randomly divided into three groups:group A, B and C. Their right carotid arteries were injuried then administered with 0, 25 or 50 mg/kg of Imatinib dai?ly for 14 consecutive days when the rabbits were sacrificed. The carotid arteries were harvested and sectioned for HE-stain?ing and immunohistochemisty staining. Real-Time PCR was used to examine transcription levels of PDGF-B and PDGFR-βmRNA. The plasma level of PDGF-BB was assayed by ELISA. Results Arterial intimal hyperplasia and stenosis following balloon injury were seen in three groups. Thickness and area of neointima, ratio of thickness of intima to media, ratio of area of intima to media and mRNA level of PDGF-β are all higher in group A than those in group B than those in group C (P<0.01). By contrast, the mRNA transcription level of PDGFR-β increased significantly in group C than that in group A (1.236±0.356 vs 0.708±0.372;t=2.91;P<0.01). Plasma level of PDGF-BB increased in all three groups after balloon injury than that in the baseline (P<0.01). The transcription level of PDGF-BB is higher in group A than that in group B and in group C (ng/L:23.464±3.542, 19.504±2.454, 16.588±1.207, F=17.322, P<0.05). There was no difference between group B and C. There was positive correlation between mRNA transcription level of PDGF-B and plasma level of PDGF-BB ( r=0.806, P<0.01). Conclusion Vascular injury can cause intimal hyperplasia and increased PDGF-B mRNA transcription. Imatinib mesilate could inhibit the intimal hyperplasia through down regulating PDGF-B mRNA transcription.

Functional analysis of platelet-derived growth factor-β receptor in self-renewal of neural stem cells / 中华神经科杂志

Objective To investigate the role of platelet-derived growth factor-β receptor (PDGFR-β) in self-renewal of neural stem cells (NSCs).Methods In this study,NSCs of subventricular zone were isolated and cultured from PDGFR-β knockout (PDGFR-β-/-) mice of postnatal day 1 (P1) and P28;the number and diameters of secondary neurospheres were calculated;using 5-bromo-2-deoxyuridine (BrdU) incorporation assay and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay,cell proliferation and survival rates were analyzed;gene expression profiles were determined by PCR-array analyses;the effect of brain-derived neurotrophic factor (BDNF) on secondary neurospheres formation was examined in these cells.Results In PDGFR-β-/-NSCs,stem cell activities,such as number (/well;P1:25.9±1.3vs117.6±3.6,t=4.236,P＜0.01;P28:13.8± 0.7vs 19.8±0.6,t=2.116,P＜0.01)and diameters (μm;P1:67.7±1.9 vs 69.1 ±2.0,t=3.211,P＜0.01;P28:33.4±0.8vs37.8±0.8,t=2.354,P ＜0.01) of secondary neurospheres,cell proliferation (％;P1:73.3 ± 2.7 vs 88.7 ± 3.6,t =2.773,P ＜ 0.05;P28:28.6 ± 9.6 vs 68.2 ± 4.5,t =6.302,P ＜ 0.05) and survival rates (％;P1:14.5 ±2.1 vs 9.3 ± 1.3,t =7.222,P ＜ 0.05),were significantly lower as compared with age-matched controls.In comparison of the same genotypic NSCs,the decrease of secondary neurosphere formation was more striking in P28 NSCs than in P1 NSCs.PCR Array analyses demonstrated that expressions of fibroblast growth factor2 and BDNF were decreased (-2.04 ± 0.25,t =2.653,P ＜ 0.05;-3.24 ± 0.37,t =1.324,P ＜ 0.05),and Noggin (2.31 ± 0.37,t =2.749,P ＜ 0.05) was increased in P1 PDGFR-β-/-NSCs as compared with P1 controls.Addition of BDNF rescued the number and diameter of secondary neurospheres in P1 PDGFR-β-/-NSCs to similar levels as controls.Conclusions PDGFR-β signaling may play a role in the selfrenewal and proliferation of NSCs.BDNF may be involved in the effects of PDGFR-β signaling in these cells.

Comparação de dois modelos experimentais de hipertensão pulmonar / Comparison of two experimental models of pulmonary hypertension

OBJETIVO: Comparar dois modelos de hipertensão pulmonar (monocrotalina e monocrotalina+pneumonectomia) em relação à gravidade hemodinâmica, estrutura de artérias pulmonares, marcadores inflamatórios (IL-1 e PDGF) e sobrevida em 45 dias. MÉTODOS: Foram utilizados 80 ratos Sprague-Dawley em dois protocolos de estudo: análise estrutural e de sobrevida. Os animais foram divididos em quatro grupos: controle, monocrotalina (M), pneumonectomia (P) e monocrotalina+pneumonectomia (M+P). Para a análise estrutural, 40 animais (10/grupo) foram cateterizados após 28 dias para a medição dos valores hemodinâmicos e sacrificados, obtendo-se tecidos cardíaco e pulmonar. O ventrículo direito (VD) foi dissecado do septo interventricular (SI), e a relação do peso do VD e do peso do ventrículo esquerdo (VE) com o SI foi obtida como índice de hipertrofia de VD. No tecido pulmonar, foram realizadas análises histológicas e dosados IL-1 e PDGF por ELISA. Para o estudo de sobrevida, 40 animais (10/grupo) foram observados por 45 dias. RESULTADOS: Os grupos M e M+P apresentaram hipertensão pulmonar em relação aos demais. Houve um aumento significativo da relação VD/VE+S no grupo M+P em relação aos demais. Não houve diferenças significativas entre os grupos M e M+P quanto à área da camada média das artérias pulmonares, dosagens de IL-1 e PDGF ou sobrevida. CONCLUSÕES: Baseados nos resultados, não podemos afirmar que o modelo de monocrotalina+pneumonectomia é superior ao modelo de monocrotalina.

OBJECTIVE: To compare two models of pulmonary hypertension (monocrotaline and monocrotaline+pneumonectomy) regarding hemodynamic severity, structure of pulmonary arteries, inflammatory markers (IL-1 and PDGF), and 45-day survival. METHODS: We used 80 Sprague-Dawley rats in two study protocols: structural analysis; and survival analysis. The rats were divided into four groups: control; monocrotaline (M), pneumonectomy (P), and monocrotaline+pneumonectomy (M+P). In the structural analysis protocol, 40 rats (10/group) were catheterized for the determination of hemodynamic variables, followed by euthanasia for the removal of heart and lung tissue. The right ventricle (RV) was dissected from the interventricular septum (IS), and the ratio between RV weight and the weight of the left ventricle (LV) plus IS (RV/LV+IS) was taken as the index of RV hypertrophy. In lung tissues, we performed histological analyses, as well as using ELISA to determine IL-1 and PDGF levels. In the survival protocol, 40 animals (10/group) were followed for 45 days. RESULTS: The M and M+P rats developed pulmonary hypertension, whereas the control and P rats did not. The RV/LV+IS ratio was significantly higher in M+P rats than in M rats, as well as being significantly higher in M and M+P rats than in control and P rats. There were no significant differences between the M and M+P rats regarding the area of the medial layer of the pulmonary arteries; IL-1 and PDGF levels; or survival. CONCLUSIONS: On the basis of our results, we cannot conclude that the monocrotaline+pneumonectomy model is superior to the monocrotaline model.

Eosinofilia reacional, leucemia eosinofílica crônica e síndrome hipereosinofílica idiopática / Reactive eosinophilia, chronic eosinophilic leukemia and idiopathic hypereosinophilic syndrome

A eosinofilia é freqüente na prática clínica, principalmente quando os valores estão entre 500 e 1000 eosinófilos/uL e indica a presença de doença parasitária, alérgica ou reação a medicamentos. Afora essas situações, a eosinofilia pode ser devida a doenças do tecido conjuntivo, infecções e, mais raramente, a doença hematológica maligna ou a tumores sólidos. Os critérios estabelecidos na década de 70 para a definição para a definição da síndrome hipereosinofílica idiopática se tornaram insuficientes para caracterizar todas as entidades albergadas sob o termo eosinofilia e, hoje, melhor compreendidas graças aos avanços na biologia celular e molecular, que proporcionaram a caracterização de doenças distintas e que envolvem células das linhagens mieloide e linfoide. Nesse contexto, as eosinofilias sanguíneas são categorizadas como reacionais, clonais e idiopáticas (SHE). O advento de terapia antitirosinoquinase (a exemplo do mesilato de imatinibe), eficaz para os casos com o rearranjo gênico FIP1L1/PDGFR, também abriu novas perspectivas para o controle ideal da leucemia eosinofílica crônica. Daí a importância do diagnóstico preciso e rápido para a indicação terapêutica ideal, antes que se instalem as complicações orgânicas, em especial cardíacas, que são irreversíveis. O presente manuscrito objetiva rever as situações de eosinofilia sanguínea e oferecer uma atualização da investigação diagnóstica e terapêutica.

Mild eosinophilia with values of less than 1000 eosinophils/µL is commonly seen in the clinical practice and can be secondary to parasitic, inflammatory or allergic diseases or to drug reactions. Additionally, eosinophilia may be due to connective tissue disorders, infections and occasionally to hematopoietic malignancies or solid tumors. The criteria established in the 1970s, for the definition of idiopathic hypereosinophilic syndrome is today unsatisfactory to characterize all conditions described as eosinophilia. Now these conditions are better understood due to the evolution of cellular and molecular biology. This knowledge has helped to characterize distinct disorders involving myeloid and lymphoid lineages. Hence, eosinophilia is categorized as reactive, clonal or idiopathic. With the introduction of anti-tyrosine kinase (imatinib mesylate) therapy, which is effective for the FIP1L1/PDGFRa rearrangement, there is a possibility to control or cure chronic eosinophilic leukemia. For this reason, precise and fast diagnosis is necessary for ideal therapeutic decisions before organic lesions that are irreversible, such as heart injury, become established. The aim of this manuscript is to review eosinophilia and offer an update on diagnostic and therapeutic investigations.

Expressão do P16 e do PDGFR-Beta no adenocarcinoma gástrico / Expression of P16 and PDGFR-Beta in gastric adenocarcinoma

OBJETIVO: Detectar a expressão imunoistoquímica do p16 e do PDGFR-beta no adenocarcinoma gástrico. MÉTODOS: Foram estudados 36 pacientes submetidos a cirurgia para adenocarcinoma gástrico entre 1998 e 2002 no Hospital da Santa Casa de Porto Alegre. As variáveis investigadas foram: idade, sexo, tamanho e localização do tumor, número de linfonodos dissecados, número de linfonodos metastáticos, tipo histológico, extensão da ressecção cirúrgica e estadiamento patológico. RESULTADOS: Não foi detectada expressão do PDGFR-beta nas peças cirúrgicas. Em relação ao p16, detectou-se perda de expressão menor que 10 por cento e menor que 1 por cento respectivamente em 89 por cento e 79 por cento das peças estudadas. CONCLUSÃO: Não houve correlação entre a perda de p16 e as variáveis estudadas.

OBJECTIVES: To detect immunohistochemistry expression of p16 and PDGFR-beta on gastric adenocarcinoma. METHODS: Thirty six patients submitted to surgery for gastric adenocarcinoma between 1998 and 2002 at Santa Casa de Porto Alegre Hospital have been studied. Variables investigated were: age, gender, tumour size and localization, number of dissected and metastatic nodes, histological type, surgical resection extension and pathological staging. RESULTS: No expression of PDGFR-beta has been detected on surgical specimens. Concerning to p16, loss of expression lower than 10 percent and 1 percent has been detected respectively on 89 percent and 79 percent of the specimens studied. CONCLUSION: There has been no correlation among p16 loss and variables studied.