RESUMEN
Frequent germline mutations of HAVCR2, recently identified in subcutaneous panniculitis-like T-cell lymphoma (SPTCL), are associated with an increased risk of hemophagocytic lymphohistiocytosis (HLH). However, SPTCL-HLH represents a challenge because of the difficulties in treatment with poor survival. Its malignant nature, specifically harbouring HAVCR2 mutations, has also been questioned. To better understand its pathology and treatment, we analysed the clinical data of six patients diagnosed at our centre. The median age at onset was 10.5 years (range, 0.8-12.4). Five patients presented with skin lesions of subcutaneous nodules/plaques and/or ulceration. All patients developed HLH; notably, one infant only had HLH without skin involvement. Histopathologically, only two patients were diagnosed with SPTCL and three were reported as panniculitis with no sufficient evidence of lymphoma. Genetically, germline homozygous mutation of HAVCR2 (p.Y82C) was identified in all patients, with a median diagnosis time of 4.6 months. All patients initially received corticosteroids, immunosuppressants or chemotherapy, achieving unfavourable responses. Strikingly, they responded well to ruxolitinib targeting inflammatory cytokines, allowing rapid disease resolution and/or long-term maintenance of remission. The excellent efficacy of ruxolitinib highlights this disease as an inflammatory condition instead of neoplastic nature and indicates novel agents targeting key inflammatory pathways as an encouraging approach for this disease entity.
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Linfohistiocitosis Hemofagocítica , Paniculitis , Niño , Preescolar , Humanos , Lactante , Mutación de Línea Germinal , Receptor 2 Celular del Virus de la Hepatitis A/genética , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Linfohistiocitosis Hemofagocítica/genética , Linfohistiocitosis Hemofagocítica/complicaciones , Paniculitis/tratamiento farmacológico , Paniculitis/genéticaRESUMEN
Background: Extraskeletal Ewing's Sarcoma (EES) may harbor more than one tumor-specific genetic abnormality, leading to diagnostic difficulties. Case report: We report a nine-year-old boy with recurrent mass of his right thigh. Tumor cells were round, with scant cytoplasm, finely dispersed chromatin, and inapparent, small nucleoli. The initial misdiagnosis was T-lymphoblastic lymphoma due to CD7 and TCR/Ig monoclonal rearrangement. As it expressed NKX2.2 and harbored an EWSR1-FLI1 fusion transcript, the diagnosis was changed to EES. The child underwent EES therapy with good initial response, but had a subcutaneous relapse at 22 months. Conclusion: In addition to typical genetic alterations, Ewing sarcoma can also express CD7 and TCR/Ig rearrangement, which are not limited to lymphoma.
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Leucemia-Linfoma Linfoblástico de Células Precursoras , Sarcoma de Ewing , Niño , Humanos , Inmunoglobulinas , Masculino , Recurrencia Local de Neoplasia , Receptores de Antígenos de Linfocitos T , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/genética , Sarcoma de Ewing/patologíaRESUMEN
In this study, we report on three immunocompetent children with pulmonary cryptococcosis presenting mediastinal lymphadenopathy as the prominent manifestation. All three children were otherwise healthy previously. Two children had a history of exposure to pigeons and poultry. All three presented persistent fever accompanied by mild cough. There were no obvious positive signs in the lungs. One patient had enlarged cervical lymph nodes. All three had elevated levels of white blood cells, neutrophil count, and C-reactive protein (CRP). The levels of IgG, IgM, IgA, IgE and T cell subsets were normal in all cases, and they were all tested negative for HIV antibody. Two children were tested positive for serum cryptococcal antigen (sCRAG). The chest X-ray and pulmonary CT findings of the three patients all demonstrated marked enlargement of mediastinal lymph nodes, and one patient had nodules in the parenchyma. Surgical biopsies of mediastinal lymph nodes were performed in two children and large numbers of capsule spores were found in the histological examination. In the three cases, definitive diagnosis of pulmonary cryptococcosis were made in two patients, and clinical diagnosis was made in the third patient. Two patients were treated with fluconazole alone. The other patient whose condition was complicated with spleen infection was treated with fluconazole combined with amphotericin B for the first month, and was then given fluconazole for maintenance treatment. The overall treatment course lasted 5-9 months and all three were cured eventually. In conclusion, immunocompetent children with pulmonary cryptococcosis may present mediastinal lymphadenopathy as a prominent or isolated manifestation, which should be considered in differential diagnosis. Treatment with fluconazole alone or in combination with amphotericin B when it was necessary showed good therapeutic outcomes.
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Criptococosis , Linfadenopatía , Niño , Tos , Criptococosis/complicaciones , Criptococosis/diagnóstico , Criptococosis/tratamiento farmacológico , Humanos , Pulmón , Ganglios LinfáticosRESUMEN
OBJECTIVE: To investigate the incidence, clinical and genetic characteristics of pediatric lymphoma patients of China with inborn errors of immunity (IEI)-related gene mutations, which have not been fully studied. METHOD: From Jan. 2020 to Mar. 2023, IEI-related genetic mutations were retrospectively explored in 108 children with lymphomas admitted to Beijing Children's Hospital by NGS. Genetic rule and clinical characteristics as well as treatment outcomes were compared between patients with or without IEI-related gene mutations. RESULTS: A total of 17 patients (15.7 %) harbored IEI-associated mutations, including 4 cases with X-linked lymphoproliferative syndrome (XLP), 3 cases had mutations in tumor necrosis factor receptor superfamily 13B (TNFRSF13B), 2 cases with Activated p110 syndrome (APDS). Patients with IEI all had alteration of immunocompetence with decreased levels of immunoglobulin and lymphocyte subsets. Recurrent infection existed in 41.2 % of patients. The 18-month event-free survival (EFS) and the overall response rate (ORR) of patients with IEI are significantly lower than those without IEI (33.86% vs. 73.26 %, p = 0.011; 52.94% vs. 87.91 %, p = 0.002, respectively). In addition, patients with IEI had a higher progression disease (PD) rate of 23.5 % than those without IEI of 4.4 % (p = 0.006). CONCLUSION: The present study demonstrated that IEI-associated lymphomas were much more common than originally appreciated in pediatric lymphomas, and those were insensitive to treatment and more likely to progress or relapse. The genomic analysis and a thorough review of the medical history of IEI can be used to distinguish them from pediatric lymphomas without IEI, which are beneficial for the early diagnosis and direct intervention.
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Linfoma , Mutación , Humanos , Masculino , Femenino , Estudios Retrospectivos , Niño , China/epidemiología , Linfoma/inmunología , Linfoma/genética , Preescolar , Lactante , Adolescente , Relevancia ClínicaRESUMEN
OBJECTIVE: To investigate the molecular genetic abnormalities of N-myc and C-myc, and their clinical pathological implications in pediatric neuroblastic tumors (NTs). METHODS: Abnormalities of N-myc were detected by interphase fluorescence in situ hybridization (FISH) technique in 246 cases of NTs, including neuroblastoma (NB,188 cases), ganglioneuroblastoma (GNB, 52 cases), ganglioneuroma (GN, 6 cases), and their association with the histological typing of the tumors and prognosis was analyzed. Abnormalities of C-myc were detected by FISH in 133 cases of NTs. RESULTS: Of the 246 cases of NTs, N-myc amplification was only found in 27 cases (11.0%, 27/246) of NB, but not in any cases of GNB or GN (P < 0.05). 89.0% (219/246) N-myc non-amplification were found in NTs, and it included N-myc gain in 175 cases (71.1%, 175/246) and normal N-myc in 44 cases (17.9%, 44/246). Univariate analysis indicated significantly (P = 0.012) poorer outcome in patients with N-myc amplification than N-myc non-amplification. However no significant difference was observed between N-myc gain cases and normal N-myc cases (P = 0.057). C-myc gain was found in 74 of 133 cases (55.6%) of NTs; no C-myc amplification or translocation was detected. Forty percent (6/15) of cases with N-myc amplification and 57.6% (68/118) of cases with N-myc non-amplification were accompanied by C-myc gain. The difference between N-myc amplification and non-amplification with C-myc gain was not significant (P > 0.05). Univariate analysis indicated that the outcome difference was not statistically significant between C-myc gain cases and normal C-myc cases (P = 0.357). CONCLUSIONS: The incidence of N-myc amplification only found in NB is low in pediatric NTs in China. Patients with N-myc amplification predict poorer outcome. No amplification or translocation of C-myc is detected in NTs, whereas C-myc gain is relatively common in NTs. There is no obvious association between N-myc amplification and C-myc gain.
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Neoplasias de las Glándulas Suprarrenales/patología , Amplificación de Genes , Genes myc , Neuroblastoma/patología , Neoplasias de las Glándulas Suprarrenales/genética , Niño , Preescolar , Femenino , Estudios de Seguimiento , Ganglioneuroblastoma/genética , Ganglioneuroblastoma/patología , Ganglioneuroma/genética , Ganglioneuroma/patología , Humanos , Hibridación Fluorescente in Situ , Lactante , Masculino , Neoplasias del Mediastino/genética , Neoplasias del Mediastino/patología , Neuroblastoma/genética , Tasa de SupervivenciaRESUMEN
OBJECTIVE: To investigate the clinical manifestations, pathological characteristics and treatment of primitive neuroectodermal tumor/Ewing's sarcoma (PNET/EWS) of the penis in children. METHODS: We analyzed the clinical data of a case of PNET/EWS and reviewed relevant literature. RESULTS: The patient was a 5-year-old boy, admitted for penis swelling with pain for 11 months. Biopsy showed a small round cell tumor, CD99 positive by immunohistochemical staining, with EWS translocation by fluorescence in situ hybridization on molecular biological examination. The tumor was confirmed to be PNET/EWS of the penis, and disappeared after 45 weeks of chemotherapy and local radiotherapy. CONCLUSION: PNET/EWS of the penis is an extremely rare disease, with no specific clinical symptoms except penis enlargement with pain. Immunohistochemistry and molecular biological examination contribute to its diagnosis.
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Tumores Neuroectodérmicos Periféricos Primitivos , Neoplasias del Pene , Sarcoma de Ewing , Preescolar , Humanos , MasculinoRESUMEN
In order to explore the characteristics of N2O emissions from winter wheat fields in the Loess Plateau under different farming methods and nitrogen levels, the dynamic changes in N2O emissions from rain-fed winter wheat fields were quantified using static box-gas chromatography. Winter wheat 'Xiaoyan22' was used as the material, and a two-factor split area design was adopted. The conventional tillage (CT), straw incorporated into soil (SM), and flat film mulching (FM) were assigned as the main plot, and three nitrogen fertilizer rates (no nitrogen fertilization, 20% nitrogen reduction (144 kg·hm-2), and conventional nitrogen application (180 kg·hm-2)) were assigned as a split plot. Taking CT as a control, the effects of FM and SM on soil N2O emissions under different nitrogen rates were assessed. Furthermore, the correlation between relevant environmental factors and N2O emission flux were analyzed, and N2 emissions were estimated using empirical formulas. The results showed the following:the N2O emissions from the soil of each nitrogen treatment occurred within 20 days, and N2O emission flux peaked within two weeks post-fertilization. The average N2O flux, the total N2O emissions, and the global warming potential of N2O were 1.92-22.75 µg·(m2·h)-1, 0.10-0.46 kg·hm-2, and 26.72-122.15 kg·hm-2, respectively. The N2O emission coefficient of fertilizer nitrogen was 0.05%-0.28%. The total N2 emissions ranged from 0.70-1.82 kg·hm-2. The N fertilization and film mulching significantly increased the N2O emission flux (P<0.05) and the cumulative N2O emissions (P<0.05); however, SM marginally reduced the total N2O emissions. The N2O emission coefficient and global warming potential of fertilizer nitrogen under FM were significantly higher than those under CT and SM (P<0.05). The N2O emissions without nitrogen treatment were only significantly positively correlated with soil water-filled pore spaces (WFPS) (P<0.05); the N2O emissions in the N fertilization condition were significantly positively correlated with WFPS, ω(NO3--N), ω(NH4+-N), and 0-5 cm soil layer temperature (P<0.05). Overall, under the condition of no fertilization, water was the main factor to control the nitrogen transformation and soil N2O emission; nevertheless, under the N fertilization condition, both nitrification and denitrification contributed to the N2O emissions in the rain-fed winter wheat fields. Film mulching practice and nitrogen application markedly increased the N2O emissions, fertilizer nitrogen emission coefficient, and global warming potential in the rain-fed winter wheat fields. Nonetheless, straw incorporated into the soil resulted in a marginal reduction in N2O emissions.
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Nitrógeno , Triticum , Agricultura/métodos , China , Fertilización , Fertilizantes/análisis , Nitrógeno/análisis , Óxido Nitroso/análisis , Suelo/químicaRESUMEN
BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm. A few LCH patients had Macrophage activation syndrome-hemophagocytic lymphohistiocytosis (MAS-HLH), a life-threatening, hyper-inflammatory syndrome. We retrospectively described the clinical-biological characteristics of a series of 28 pediatric LCH patients with MAS-HLH in a single center. We further analyzed the difference in treatment outcomes between second-line chemotherapy (cytarabine and cladribine) and targeted therapy (dabrafenib) for BRAF-V600E-positive patients. RESULTS: LCH patients with MAS-HLH were aged < 2 years, harbored high frequencies of risk organ, skin, or lymph nodes involvement, and most of them carried BRAF-V600E mutation in lesions (88.0%) or plasma (90.5%). Patients were firstly treated with the initial induction first-line therapy (vindesine-steroid combination), and most of them (26/28) failed to control the active MAS-HLH after one six-week course of induction treatment. Then they were shifted to second-line chemotherapy or targeted therapy dabrafenib. BRAF-V600E-mutant patients treated with dabrafenib had prompt resolution of MAS-HLH signs and symptoms with less toxicity than second-line chemotherapy. Moreover, the progression-free survival (PFS) rate for patients given dabrafenib was much higher than those treated with chemotherapy (4 year-PFS: 75% vs. 14.6%, P = 0.034). CONCLUSIONS: LCH patients with MAS-HLH harbored specific clinical-biology characteristics compared to the multisystem LCH without MAS-HLH. The BRAF inhibitor dabrafenib provides a promising treatment option for LCH with MAS-HLH.
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Histiocitosis de Células de Langerhans , Linfohistiocitosis Hemofagocítica , Síndrome de Activación Macrofágica , Niño , Preescolar , Histiocitosis de Células de Langerhans/diagnóstico , Histiocitosis de Células de Langerhans/tratamiento farmacológico , Humanos , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Síndrome de Activación Macrofágica/tratamiento farmacológico , Mutación , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: With current chemotherapy treatment, >90% of survival has been obtained for Burkitt lymphoma (BL). In this study, the demographic characteristics and treatment outcomes are presented for 78 children in China with central nervous system-positive (CNS+) BL. METHODS: This retrospective study consecutively enrolled 78 CNS+ BL patients in Beijing Children's Hospital (BCH) from 2007 to 2019 who received the BCH B-cell non-Hodgkin's lymphoma regimen (modified by French-American-British mature lymphoma B-cell 96 [FAB/LMB96] C1 arm ± rituximab). Clinical characteristics, methods of disease detection in the CNS, and outcomes were evaluated. Univariate and multivariate analyses were used to assess prognostic factors. RESULTS: The median age of 65 boys and 13 girls at the time of diagnosis was 5.7 years (ranging from 1 to 14 years). Patients were followed up for a median time of 34 months (ranging from 1 to 72 months). Bone marrow invasion was found in 38 (48.7%) patients. There were 48 (61.5%), 44 (56.4%), and 25 (32%) patients with cranial nerve palsy, intracerebral mass (ICM), and para-meningeal extension, respectively. Abnormal cerebrospinal fluid (CSF) morphology and CSF immunophenotype appeared in 15 (19.2%) and 15 (19.2%) patients, respectively. There were 69 (88.5%) patients treated with chemotherapy combined with rituximab, and nine patients were treated solely with chemotherapy. Finally, five patients died of treatment-related infection, recurrence occurred for 13, and one developed a second tumor. The 3-year overall survival and event-free survival rates were 78.9%â±â4.7% and 71.4%â±â6.0%, respectively. Treatment with chemotherapy only, ICM positivity, and >4 organs involved at diagnosis were independent risk factors. CONCLUSIONS: Rituximab combined with a modified LMB96 regimen has greatly increased the efficacy of treatment for Chinese children with CNS+ BL, and with the continuous collection of outcome data, treatment-related complications are decreasing. For further verification, a large sample multicentre randomized controlled study should be performed to explore a treatment scheme for Chinese children with even greater efficacy.
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Linfoma de Burkitt , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Burkitt/tratamiento farmacológico , Sistema Nervioso Central , Niño , Preescolar , China , Ciclofosfamida/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Humanos , Lactante , Masculino , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Rituximab/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Anaplastic lymphoma kinase-positive (ALK+) large B-cell lymphoma (LBCL) is a rare type of lymphoma with high invasiveness and rapid progression. It occurs in all age groups, but is extremely rare in children. The lesions mainly involve the lymph nodes and may present with extra-nodal involvement. Response to conventional chemotherapies and local radiotherapy is poor, with a 5-year overall survival of less than 40%. Recently, the use of ALK inhibitors for the treatment of this disease has been reported. CASE SUMMARY: We present a case of a 12-year-old boy diagnosed with ALK+LBCL. The patient had a 2-mo medical history of a calvarial mass, extensive systemic involvement, and positive bone marrow clathrin heavy chain (CLTC)-ALK fusion gene. Complete remission 1 (CR1) was achieved using the modified LMB89 Group C regimen followed by autologous stem cell transplantation. The patient relapsed 3 mo later. He then achieved CR2 with three short courses of chemotherapy (COP, reduced-dose ICE, low-dose Ara-c+VP16) and continuous alectinib targeted therapy. Afterward, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was performed. At 16 mo after the allo-HSCT, the patient was still in CR2. CONCLUSION: The modified LMB89 Group C regimen and ALK inhibitors are effective. Allo-HSCT should be performed after remission.
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INTRODUCTION: Pulmonary sequestration (PS) is a rare pulmonary congenital malformation characterized by disconnection with the tracheobronchial tree or the pulmonary arterial blood supply thus impeding the connection to the arterial blood supply from systemic circulation, ultimately resulting in a non-functional lung. PATIENT CONCERNS: A 73-day-old boy with rhabdomyomatoid hyperplasia was hospitalized for cough and fever 2 months after birth. DIAGNOSES: Routine B-ultrasound revealed a cystic malformation in the right lung. CT showed increased volume of the right lung accompanied with cystic low-density shadows of different sizes and a blood vessel leading from the abdominal aorta into the lesion lung. Thus, he was diagnosed with PS. INTERVENTIONS: The boy underwent an entire lobectomy of the lower lobe of the right lung. The operation field revealed several malformed blood vessels from the apposition to the right lower lobe. Most of the lung had cystic adenomatoid malformations. Other parts consisted of well-differentiated cystic dilated bronchus and striated muscles. Histopathological examination revealed rhabdomyus fibroblasts distributed throughout the bronchi. Nuclei were located at the margins of the cells. Striated muscle fibers observed as immunological markers (myogenin and desmin) of striated muscles were positively detected. OUTCOMES: The boy recovered uneventfully after his operation and no abnormal clinical findings were found at the 10-month follow-up. CONCLUSION: PS can not only accompany other developmental abnormalities, but can also associate with rhabdomyomatoid hyperplasia. This lesion is not a fatal congenital malformation and instead is a benign lesion affecting only a single lobe. It has a relatively good prognosis.
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Secuestro Broncopulmonar/diagnóstico por imagen , Secuestro Broncopulmonar/cirugía , Secuestro Broncopulmonar/complicaciones , Malformación Adenomatoide Quística Congénita del Pulmón/complicaciones , Malformación Adenomatoide Quística Congénita del Pulmón/diagnóstico por imagen , Malformación Adenomatoide Quística Congénita del Pulmón/cirugía , Humanos , Lactante , Pulmón/diagnóstico por imagen , Pulmón/cirugía , Masculino , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
BACKGROUND: The aberrant expression of the anaplastic lymphoma kinase (ALK) gene in ALK-positive (ALK+) anaplastic large cell lymphoma (ALCL) is usually due to t(2;5)/NPM-ALK. However, rarely, aberrant ALK expression can also result from a rearrangement of the ALK gene with various partner genes. Central nervous system (CNS) metastasis is very rare in ALK+ALCL. Patients with CNS involvement show an inferior prognosis. CASE SUMMARY: Here, we present the case of an 8-year-old girl diagnosed with ALK+ALCL. She presented with fever, skin nodules, leg swelling, and abdominal pain over the preceding 6 mo. She had extensive involvement and showed an extraordinary rare translocation, t(2;17)/CLTC-ALK, as demonstrated by RNA-seq. She underwent chemotherapy as per ALCL99, followed by vinblastine (VBL) maintenance treatment, and achieved complete remission. However, she developed CNS relapse during VBL monotherapy. The patient achieved a durable second remission with high-dose chemotherapy (including methotrexate 8 g/m2) and continuous treatment with alectinib and VBL. CONCLUSION: Alectinib showed significant and durable CNS effects in this patient. However, more cases are needed to prove the efficacy and safety of alectinib for pediatric ALK+ALCL patients.
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Abstract Objective: To investigate the incidence, clinical and genetic characteristics of pediatric lymphoma patients of China with inborn errors of immunity (IEI)-related gene mutations, which have not been fully studied. Method: From Jan. 2020 to Mar. 2023, IEI-related genetic mutations were retrospectively explored in 108 children with lymphomas admitted to Beijing Children's Hospital by NGS. Genetic rule and clinical characteristics as well as treatment outcomes were compared between patients with or without IEI-related gene mutations. Results: A total of 17 patients (15.7 %) harbored IEI-associated mutations, including 4 cases with X-linked lymphoproliferative syndrome (XLP), 3 cases had mutations in tumor necrosis factor receptor superfamily 13B (TNFRSF13B), 2 cases with Activated p110 syndrome (APDS). Patients with IEI all had alteration of immunocompetence with decreased levels of immunoglobulin and lymphocyte subsets. Recurrent infection existed in 41.2 % of patients. The 18-month event-free survival (EFS) and the overall response rate (ORR) of patients with IEI are significantly lower than those without IEI (33.86% vs. 73.26 %, p = 0.011; 52.94% vs. 87.91 %, p = 0.002, respectively). In addition, patients with IEI had a higher progression disease (PD) rate of 23.5 % than those without IEI of 4.4% (p = 0.006). Conclusion: The present study demonstrated that IEI-associated lymphomas were much more common than originally appreciated in pediatric lymphomas, and those were insensitive to treatment and more likely to progress or relapse. The genomic analysis and a thorough review of the medical history of IEI can be used to distinguish them from pediatric lymphomas without IEI, which are beneficial for the early diagnosis and direct intervention.
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OBJECTIVE: To investigate the correlation of Epstein-Barr virus (EBV) infection and childhood lymphoma. METHODS: Paraffin-embedded specimens of lymphoma collected between 1996 and 2005, including 36 Hodgkin lymphomas (HL) and 51 non-Hodgkin lymphomas (NHL), were included in this study. Paraffin-embedded specimens of reactive hyperplasia of lymph nodes (RL) collected during the same period were used as controls. Immunohistochemical (IHC) assay was used to detect EBV-LMP1 and in situ hybridization (ISH) to detect EBV-EBERs. RESULTS: EBV was detected in 72.2% (26/36) of the Hodgkin lymphomas, 15.7% (8/51) of the non-Hodgkin lymphomas and 33.3% (15/45) of the reactive hyperplasia of lymph nodes. There was a significant difference among Hodgkin lymphoma, non-Hodgkin lymphoma and RL (P = 0. 000). CONCLUSION: Childhood Hodgkin lymphoma is closely correlated with Epstein-Barr virus infection. However, the low rate of EBV infection detected in childhood non-Hodgkin lymphoma might be due to heterogeneous distribution of pathological types in this study.
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Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4/aislamiento & purificación , Enfermedad de Hodgkin/virología , Linfoma no Hodgkin/virología , Proteínas de la Matriz Viral/metabolismo , Niño , Preescolar , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/metabolismo , Femenino , Enfermedad de Hodgkin/complicaciones , Enfermedad de Hodgkin/metabolismo , Humanos , Linfoma no Hodgkin/complicaciones , Linfoma no Hodgkin/metabolismo , Masculino , Seudolinfoma/complicaciones , Seudolinfoma/metabolismo , Seudolinfoma/virología , ARN Viral/metabolismoRESUMEN
OBJECTIVE: To study the expression of anaplastic lymphoma kinase (ALK) and chromosome breakage of the anaplastic lymphoma kinase (ALK) gene retrospectively and to investigate their possible value as indicators of prognosis in primary systemic anaplastic large cell lymphomas (S-ALCL). METHODS: Twenty-eight cases of S-ALCL were collected from the Lymphoma Lab, the Department of Pathology, Peking University Health Science Center and Beijing Children's Hospital. The morphologic characteristics were studied under light microscope, and essential immunohistochemical staininings (IHC) were performed and reviewed to confirm the diagnosis of S-ALCL. ALK-1 monoclonal antibody was used to assess ALK fusion protein expression, and EnVision method was used in IHC. Locus specific interphase fluorescence in situ hybridization (LSI-FISH) was also performed on the neoplastic cells using paraffin-embedded tissues to detect ALK gene abnormality. RESULTS: ALK-1 protein was expressed in 19 of the 28 cases. In 14 ALCL cases, ALK gene breakage was detected by LSI-FISH, using a dual-color break-apart ALK gene DNA (LSI-ALK) probe. Of the other 14 cases which did not show ALK gene breakage, 5 showed 2 copies of ALK gene as normal, and 9 showed multi-copies of ALK gene. Of all the 28 cases, 22 had complete follow-up materials. Sixteen survived and 6 died, their survival time ranged from 0.5 to 36.0 months, and the survival time on average was 12.8 months, cumulative proportion survival rate was 73.9% in the 1st year. Those cases showing multi-copies of ALK gene might have the worst outcome, with only 47.6% of cumulative proportion survival rate in the 1st year. CONCLUSION: IHC detection for ALK fusion protein is important to the diagnosis of S-ALCL. ALK gene breakage detected by interphase LSI-FISH might not be always consistent with abnormal expression of ALK fusion protein. Complex abnormalities of ALK gene exist in S-ALCL cases, and different types of ALK gene might lead to different clinical outcome. Those cases with multi-copies of ALK gene probably have the poorest prognosis.
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Rotura Cromosómica , Linfoma Anaplásico de Células Grandes/genética , Proteínas Tirosina Quinasas/genética , Adolescente , Adulto , Quinasa de Linfoma Anaplásico , Niño , Preescolar , Humanos , Hibridación Fluorescente in Situ , Persona de Mediana Edad , Pronóstico , Proteínas Tirosina Quinasas/metabolismo , Proteínas Tirosina Quinasas Receptoras , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Estudios Retrospectivos , Adulto JovenRESUMEN
The most common causes of bronchiolitis obliterans organizing pneumonia (BOOP) are connective tissue diseases, organ transplantation, drug reaction, and infections. Although rare, BOOP due to gastroesophageal reflux (GER) has been reported in adults but not to date in pediatric patients. This study describes 2 pediatric patients who developed GER and BOOP. One patient had superior mesenteric artery syndrome and Helicobacter pylori infection, and the other had a gastroduodenal ulcer with reflux esophagitis. Respiratory symptoms occurred concurrently or after gastrointestinal symptoms. Monitoring of esophageal pH for 24 hours revealed pathologic acid reflux. Lung biopsy findings confirmed BOOP. No other causes of BOOP were observed in these 2 patients. Both patients were cured with antireflux therapy and corticosteroids. To our knowledge, this is the first case report to implicate GER as a reversible cause of BOOP in children.
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Neumonía en Organización Criptogénica/etiología , Reflujo Gastroesofágico/complicaciones , Niño , Humanos , MasculinoRESUMEN
OBJECTIVE: To investigate the expression of NPM- ALK fusion gene in bone marrow (BM) and peripheral blood (PB) in anaplastic large cell lymphoma (ALCL) patients and its prognostic significance. METHODS: NPM- ALK fusion gene of 21 BM and 15 PB samples from patients with NPM-ALK positive ALCL was detected by RT- PCR, and the relationship between NPM- ALK expression and prognosis and clinical characters was evaluated. RESULTS: Of the 21 patients, 12 cases were male and 9 case were female with a median age of 9 (range, 2-14) years old. The median follow- up was 31 months. Patients with a positive NPM-ALK expression in BM had a 3-years EFS of (35.6±18.6)%, compared with (91.7±8.0)% for patients with negative NPM-ALK (P=0.038). The incidence of positive expression in BM was significantly higher in patients who had more than 3 organs involved by tumor (P=0.032). 86.7% patients had a concordant results of NPM-ALK expression in PB and BM. CONCLUSION: We could evaluate the minimal disseminated disease of NPM-ALK positive ALCL patients by screening the NPM-ALK fusion gene in BM and PB by RT-PCR. The positive expression is associated with a poor prognosis and could be used for stratification of ALCL.
Asunto(s)
Linfoma Anaplásico de Células Grandes/genética , Proteínas Tirosina Quinasas/genética , Adolescente , Médula Ósea/metabolismo , Niño , Preescolar , Femenino , Humanos , Linfoma Anaplásico de Células Grandes/diagnóstico , Linfoma Anaplásico de Células Grandes/metabolismo , Masculino , Pronóstico , Proteínas Tirosina Quinasas/metabolismoRESUMEN
This study was purposed to analyze the relation of N-myc gene copy number with clinical staging, pathological types and tumor biological factors in children with neuroblastoma (NB), and to investigate the influence of chemotherapy on N-myc gene expression and explore the relationship of N-myc gene copies with prognosis of NB children. The newly diagnosed children with NB from 1 March 2007 to 31 January 2011 were enrolled in this study. The treatment was carried out by BCH-NB-2007 based on Hongkong NB-07 protocol, and the patients were follow up to 31 January 2012. The N-myc gene in NB children was detected by FISH. According to number of N-myc gene copies, the NB children were divided into 3 groups. A group (N-myc gene negative) had less than 2 copies, B group (N-myc gene gains) had 3 to 9 copies, and C group (N-myc amplification) had more than 10 copies. The results showed that the N-myc gene expression in 58 cases of NB was observed. There were 36 males and 22 females. NB children aged from 6.5 to 138 months (median age 47.5 months), all patients were followed up for 11 - 57 months with an average of 31.5 months. INSS stages I-IV were 1, 5, 8 and 44 cases, respectively. Twenty-five cases had primary post mediastinal tumor, thirty-three cases had retroperitoneal and pelvic tumor, three of which also companied with post mediastinal tumor. Thirty-five cases had bone metastasis (60.3%), thirty-two cases had bone marrow metastasis (55%). Of the 54 patients with fully known biologic features, seventeen cases had ganglioneuroblastoma, thirty-seven cases had neuroblastoma (15 displayed differentiated, 7 poorly differentiated or undifferentiated, 15 with pathological changes after chemotherapy), four cases had bone marrow metastasis only detected by bone marrow biopsy. Eleven cases had N-myc gene negative, forty-three had N-myc gains, four had N-myc amplification. The average copy number of N-myc gene copies in 58 cases was 5.96 ± 7.81 in which 28 children were non chemotherapy cases, their average copy number was 4.00 ± 1.88, thirty cases out of 58 cases received preoperation chemotherapy (chemotherapy group), and their average copy number was 7.80 ± 10.46, the difference is significant (P = 0.064). The clinic stage, the location of primary tumor, pathological classification, urine VMA and serum neurogenic specific enolase had no effects on the N-myc gene expression, but the serum LDH level had influence (P < 0.01). Single factor Kaplan-Meier analysis showed that the number of N-myc gene copies in NB patients were closely related with the poor prognosis. The more copies of N-myc gene, the more poor prognosis, the difference is statistically significant (P < 0.05). It is concluded that the number of N-myc gene copies correlates with the rapid growth of NB and its poor prognosis, detecting the N-myc amplification can help to estimate the prognosis and decide the program of treatment. Serum LDH, which correlated with the rapid growth of NB, had effect on the N-myc gene expression and is closely related with the poor prognosis of NB.
Asunto(s)
Genes myc , Neuroblastoma/genética , Neuroblastoma/patología , Niño , Preescolar , Femenino , Amplificación de Genes , Humanos , Lactante , Masculino , Estadificación de Neoplasias , Neuroblastoma/diagnóstico , PronósticoRESUMEN
OBJECTIVE: To analyze the clinical features and prognostic factors of children's anaplastic large cell lymphoma (ALCL), summarize the therapeutic effect and toxicities. METHOD: A total of 38 ALCL patients admitted to Beijing Children's Hospital from Jan. 2003 to Apr. 2010 were treated with BCH-ALCL-2003 regimen (modified from HK-ALCL-2000). RESULT: Thirty-four cases were ALK(+), male:female ratio = 2.16:1. The median age was 9 years; 86.8% had B symptoms. 94.7% evolved to Stage III and IV on admission. The median follow-up duration was 48 months (12 to 99 months). Median event-free survival (EFS) time was 43 months. Thirty-four patients (89.5%) achieved a remission. The disease relapsed in 3 patients within 20 months after diagnosis. Estimated 4-year EFS was (81.2 ± 6.4)%, estimated 4-year overall survival (OS) rate was (86.4 ± 5.7)%. Univariate analysis indicated that the unfavorable prognostic factors included: more than 3 extra nodal involvement, hepatosplenomegaly (> 3 cm), elevated lactate dehydrogenase (LDH), stage IV, hemophagocytosis in bone marrow, and age < 3 years. The major toxicity was myelosuppression and mucositis. no chemotherapy related death occurred. CONCLUSION: (1) Childhood ALCL patients often have B symptoms and extranodal involvement. (2) In the study, therapeutic effects was good. The disease relapsed mostly within the first 2 years, maintenance therapy with vinblastine is necessary. (3) The regimen is safe to patients.