Childhood non-Hodgkin malignant lymphomas: A clinicopathologic retrospective study

Between 1968 and 1975, 44 evaluable children under 16 years of age with the histologic diagnosis of non-Hodgkin malignant lymphoma (ML) were treated at the Istituto Nazionale Tumori of Milan. Histologic diagnoses were reclassified as follows: 13 lymphoblastic (others) ML, 15 convoluted cell type lymphoblastic ML, 9 Burkitt type ML, and 7 immunoblastic ML. Only 36% of the patients had stage I and II disease. At diagnosis 25% showed malignant cells in the bone marrow smears. Bone marrow infiltration was particularly frequent in the convoluted cell type lymphoblastic ML and in the lymphoblastic (others) ML subgroups. Burkitt type ML frequently was associated with abdominal lesions and subsequently a high incidence of central nervous system involvement. Patients with stage I and II ML were encountered mostly in the immunoblastic ML subgroup. After 1973 more intensive chemotherapy plus radiotherapy seems to have slightly improved the survival of the patients, except in the Burkitt type ML subgroup.     

Fine Needle Aspiration Cytology (FNAC) of the Testes in Childhood Acute Lymphoblastic Leukemia and Non-Hodgkin's Lymphoma: Preliminary Report

Eighteen patients with childhood acute lymphoblastic (ALL) or non-Hodgkin's lymphoma (NHL) in remission and 2 patients with ALL in suspected testicular relapses were studied by testicular fine needle aspiration cytology (FNAC). Well-preserved testicular cells, both singly and in small clusters, were considered indicative of an adequate aspiration. Of 18 patients in remission, 17 had at least one adequate sample from each testis and one showed evidence of leukemic infiltrate. None of these patients experienced a relapse during a median follow up of 4 years. In 2 other patients with clinically suspected testicular relapses, the smears from fine needle aspirates contained numerous malignant lymphoid cells that could be readily distinguished from seminiferous tubular cells. The observations indicate that FNAC is a promising new approach to study testicular conditions in childhood ALL and NHL. A larger prospective study and accumulation of additional follow-up data is required before a definitive evaluation of the technique can be made.     

Cytogenetic studies of pediatric brain and spinal cord tumors.

Seventy pediatric patients with brain and spinal cord tumors had cytogenetic analysis of 99 samples of their tumors. Successful analysis was accomplished in 95%. Tumors included 43 gliomas, 9 medulloblastomas and a variety of other lesions. Forty-three patients had normal chromosomes; 28 of these had benign tumors and good outcomes. Of 11 patients with malignant tumors and normal chromosomes, 8 have no disease or stable disease during the period of follow-up. Outcomes of the 23 patients with abnormal chromosomes were poor; 17 had malignant pathology. Six patients with 'benign' disease and abnormal chromosomes died or have progressive disease. A relationship between outcome and pathologic diagnosis is often enhanced by cytogenetic findings. The study indicated specific chromosome abnormalities in certain pediatric brain tumors, such as chromosome 1 abnormalities in gliomas and isochromosome 17 abnormalities in medulloblastomas. It is recommended that cytogenetic studied be included in cooperative therapeutic trials. The clastogenic effects of treatment on the cytogenetic characteristics of tumors sequentially studied were demonstrated, as was the role of sampling variations. Attention to the treatment history of tumor samples, as well as evaluation of multiple samples from each tumor, may improve the reliability of cytogenetic studies.     

Peripheral lymphadenopathy in childhood. Ten-year experience with excisional biopsy

We reviewed our experience with excisional lymph node biopsy over a ten-year period in an attempt to determine which clinical features, if any, were predictive of histologic diagnosis. A total of 75 patients, aged 8 months to 17 years, were available for review. Of these patients, 41 (55%) had nodes with nondiagnostic hyperplasia, 16 (21%) had noncaseating granulomatous lymphadenitis, 5 (7%) showed the caseating lesion of tuberculosis, while 13 (17%) showed a lymphoreticular malignant neoplasm. While patients with lymphoma more frequently had a history of weight loss or arthralgia, no one clinical feature, by either its presence or absence, could predict the biopsy diagnosis. All five patients with supraclavicular lymhadenopathy were found to have mediastinal disease. Of the 41 patients initially found to have nondiagnostic reactive hyperplasia, seven (17%) ultimately proved to have a specific pathologic process.     

Ovarian masses in children.

We evaluated the outcome of children with ovarian mass operated on at our Center over an 8-year period. Thirty-four girls aged 1 day to 17 years were included in the study. Mean duration of follow-up was 39.5 months. Eighteen had a nonneoplastic mass and 16 a neoplastic mass, eight of which were malignant. Patients with a malignant tumor underwent adnexectomy of the affected side and appendectomy, without removal of the uterus or the other ovary and without partial omentectomy; only the one girl with bilateral malignant disease had bilateral adnexectomy. Five of the eight patients with malignant disease received chemotherapy. All patients are alive with no evidence of disease. Pediatric ovarian masses are rare but have a relatively high rate of malignancy. They differ from adult malignant tumors in many aspects. Conservative surgery should be applied to preserve fertility and combined, if necessary, with aggressive chemotherapy. A good prognosis may be expected in most cases, even with progressive disease.     

Malignant mesothelioma in children: report of seven cases and review of the literature

Seven children with malignant mesothelioma have been seen at Memorial Hospital since 1953. In six, the origin was at the pleura and in one at the peritoneum. None of the patients related a history of exposure to asbestos. Two patients lived more than five years. The other five patients died within two years of the diagnosis. Distant metastases were seen in four of the patients, including three who had metastases to brain. Surgery or radiotherapy were not effective in controlling the disease in most of the patients. One patient had a complete response to a combination of Adriamycin, cyclophosphamide, and vincristine and has remained free of disease for 5 1/2 years. The seven cases are reviewed, as are the other 42 cases of malignant mesothelioma in children reported in the literature.     

Neutrophil-rich Anaplastic Large Cell Lymphoma of the Skull Presenting after Head Trauma

The presentation of anaplastic large cell lymphoma in bone is uncommon. We report a case of anaplastic large cell lymphoma of the skull that was diagnosed after head trauma. Biopsy revealed significant destruction of the outer table of the frontal bone. Histopathologically, the initial evaluation suggested osteomyelitis because of a mixed inflammatory infiltrate with large numbers of neutrophils. However, several clusters and individual mononuclear cells were atypical. The tumor cells had large, pleomorphic nuclei; these cells stained positively with antibodies to Ki-1 (CD 30), ALK-1, and EMA. Fluorescence in situ hybridization (FISH) showed rearrangement of the ALK gene, which usually results from the t(2;5) translocation, present in most anaplastic large cell lymphomas. There was no evidence of systemic disease. The patient has tolerated chemotherapy and is free of disease 12 months later. Received April 24, 2000; accepted October 25, 2000.     

Coexistence of myeloid and lymphoid neoplastic subpopulations in chronic myelogenous leukemia

Serial cytogenetic studies have been performed on a child with Philadelphia chromosome (Ph¹)-positive chronic myelogenous leukemia (CML) and correlated with clinical, morphologic, and cytochemical data in an attempt to elucidate further the natural history of leukemic progression observed in this disease. Once the initial blast crisis had occurred, two genetically different leukemic clones of cells, one presumably having arisen from the other, coexisted throughout the remainder of the patient's course. The initial clone comprised diferentiating myeloid cells, while the second clone appeared on morphologic and cytochemical grounds to be lymphoid and blastic. A dynamic equilibrium existed between these two populations of cells, with the balance altered by chemotherapy and/or other selective pressures. The leukemic progression demonstrated in this case is consistent with the concept of clonal evolution of malignant cell populations. In planning therapy, it may be necessary to consider each of these coexistent clones and their different therapeutic requirements.     

Serum levels and differential expression of CD44 in childhood leukemia and malignant lymphoma: Correlation with prognostic criteria and survival

BACKGROUND: The CD44, a cell surface proteoglycan, participates in a variety of function including tumor dissemination and metastasis. However, there are no available data on the prognostic significance of CD44 expression of tumor tissue correlated with serum sCD44 level in childhood leukemias and lymphomas. METHODS: Serum levels and leukemic cell tumor tissue expression of CD44 were detected in 54 children with acute leukemia and malignant lymphoma. Serum samples were obtained from all patients before treatment and during remission. Twelve age-matched healthy children were included as a control group. RESULTS: The serum CD44 levels were significantly higher in patients with Hodgkin's disease (HD), non-Hodgkin's lymphoma (NHL), Burkitt's lymphoma (BL) and acute lymphoblastic leukemia (ALL) than those in the control group. The median values were 1627.0, 1336.0, 1318.5, 1730.4, 902.7 ng/mL, respectively, and P<0.001, P<0.01, P<0.01, P<0.05 in comparisons, respectively. However, there was no significant difference between acute myeloid leukemia (AML) and the control group (median values: 900.3 and 902.7 ng/mL, respectively, P>0.05). Serum sCD44 levels significantly declined in HD, NHL and ALL patients who were in complete remission (median values: 684.0, 573.8 and 1101.1 ng/mL, respectively, P<0.05 in each comparison). Patients with HD had higher levels of serum sCD44 and correlated well with higher erythrocyte sedimentation rate (ESR), B-symptoms and advanced-stage disease (P<0.05, P<0.05 and P<0.01, respectively). Expression of CD44 was significantly high in patients with HD and NHL who were in advanced stages of disease. High serum CD44 level was also associated with high tumor tissue expression of CD44 in patients with HD and BL. In addition, patients with higher levels of serum sCD44, had a poorer outcome and survival than those with lower sCD44 levels in HD and NHL groups. CONCLUSIONS: A high serum sCD44 level and/or tumor tissue expression at diagnosis is associated with poor prognostic criteria and/or unfavorable outcome in childhood leukemias and lymphomas.     

Detection of multidrug-resistant protein,P-glycoprotein in childhood leukaemia and lymphoma

Flow cytometric detection of surface P-glycoprotein, a multidrug-resistant gene product, with a monoclonal antibody, MRK 16, was performed on cells obtained from 18 children with leukaemia and lymphoma. Of 18 patients examined, 1 with malignant lymphoma at relapse showed a significant increase in P-glycoproteinpositive cells and a strong resistance to chemotherapy. Overexpression of P-glycoprotein in a case with B-cell type malignant lymphoma was confirmed by immunoprecipitation and Northern hybridization analysis. The present study suggests that an increased expression of surface P-glycoprotein might be involved in multidrug resistance at least in a certain case of childhood leukaemia and lymphoma.     

以肾小管酸中毒为首发表现的儿童恶性淋巴瘤

原发性肾淋巴瘤是原发于淋巴结以外的一种恶性淋巴瘤,罕见于儿童。该文报道2例以肾小管酸中毒为首发表现,以肾组织穿刺病理确诊的儿童原发性肾淋巴瘤。2例皆以“多饮、多尿、乏力、呕吐、贫血”为主要症状,双肾肿大,伴低钾、低钙、低磷,代谢性酸中毒等。1例放弃治疗,另外1例经泼尼松、长春新碱、阿糖胞苷＋L-天冬氨酰胺酶(PVA+L-ASP)方案化疗,联合氨甲喋呤、地塞米松、阿糖胞苷鞘内注射、纠酸、补钾、输血及对症支持治疗后,多饮多尿症状缓解,内环境稳定, 复查肾B超无异常发现。一旦怀疑该型恶性淋巴瘤,应尽快肾组织穿刺病理确诊,早期采取综合治疗,包括手术、化疗与放疗、支持疗法等。     

以骨质破坏为主的儿童恶性淋巴瘤临床及影像学特点

为初步探讨表现为骨质破坏的儿童恶性淋巴瘤临床及影像学特点、方案选择、疗效和预后,对6例表现为骨质破坏的儿童恶性淋巴瘤进行影像学检查、免疫组化检查、病理分型及选择方案化疗和放疗并长期随访。结果显示6例患儿CT和MRI检查均有不同骨质破坏,免疫分型为B型;采用MCP方案化疗后1例死亡,5例长期无病生存。提示表现为骨质破坏的恶性淋巴瘤临床少见报道,应通过影像学和病理检查及早确诊,可采用常规化疗方案结合放疗治疗,预后与临床分期相关。     

Malignant phaeochromocytoma in children: A case with neurofibromatosis and review of the literature

A boy of 13 with familial neurofibromatosis developed a malignant adrenal phaeochromocytoma, presenting with growth failure and an abdominal mass but no hypertension, with metastases in lungs, lymph nodes and liver, producing dopamine, noradrenaline and adrenaline. Postoperative hypotension and pulmonary oedema proved fatal. Twenty-four case reports of children with malignant phaeochromocytoma were found. Diagnosis, treatment, prognostic and malignancy risk factors are discussed. Malignancy was associated with extraadrenal primary tumour, other inherited or congenital disease especially neurofibromatosis, labile hypertension and females. Two clinicopathologic groups emerged. Cases with widespread metastases had a high incidence of associated inherited or congenital disease, poor response to treatment and poor survival. Cases with metastases confined to lung or local/ regional lymph nodes rarely had associated disease, had good response to treatment and good survival; the possibility that they are really extra-adrenal benign tumours and possible healing factors are discussed, also a link between neurofibromatosis and dopamine secretion. Child, neoplasm metastases, neurofibromatosis, pheochromocytoma     

钙视网膜蛋白在肠无神经节细胞症诊断中的应用

目的分析钙视网膜蛋白在小儿肠无神经节细胞症诊断中的应用意义。方法回顾性分析本院自2011年1月1日至2014年12月31日收治的确诊小儿肠无神经节细胞症、肠神经节细胞发育异常症患儿术前直肠黏膜活检标本中钙视网膜蛋白的表达情况和HE染色结果、根治术或造瘘术后病变段钙视网膜蛋白表达情况和病理检查HE染色结果。结果①肠无神经节细胞症中术前直肠黏膜活检检查钙视网膜蛋白的表达在所有病例中阴性表达11 1/114例,HE染色未见神经节细胞112/114例;根治手术后痉挛段肠壁中钙视网膜蛋白均呈阴性表达133/133例,HE染色未见神经节细胞133/133例,而在扩张段的肠壁中钙视网膜蛋白的表达均呈阳性表达133/133例,HE染色可见发育正常的神经节细胞133/133例;②肠神经节细胞发育异常症中术前直肠粘膜活检钙视网膜蛋白表达阴性4/4例,HE染色见到发育不良神经节细胞1/4例,其余3例均未见到神经节细胞;根治术或造瘘术后病变段钙视网膜蛋白表达阳性42/42例,HE染色见到神经节细胞发育异常或减少42/42例。结论钙视网膜蛋白染色可以作为肠无神经节细胞症的诊断依据之一,但仍然有假阳性及假阴性结果可能,特别是在术前直肠粘膜活检的应用中。     

Leukemic phase of malignant histiocytosis (arguments in favour of the histiomonocytic origin of the abnormal cells)

A 15-year-old female was treated for malignant histiocytosis. The occurrence of a leukemic phase (178,000 blasts/cu mm) during the follow up provided the opportunity of studying a large number of malignant cells by cytochemical, electron microscopic, and cell membrane markers techniques. Acid phosphatase reaction was strongly positive and totally inhibited by tartaric acid. Nonspecific esterase reaction was moderately positive with inhibition by sodium fluorid. Electron microscopy revealed the presence of surface membrane pseudopods and the phagocytic activity of the cells. The leukemic cells had a receptor for the Fc fragment of IgG. These findings support the histiomonocytic origin of the abnormal cells in malignant histiocytosis.     

儿童先天性体动脉-肺动脉瘘4例并文献复习

目的总结临床表现为大量咯血的先天性体动脉-肺动脉瘘患儿的临床特点及诊治经 验。方法回顾性收集首都医科大学附属北京儿童医院2007年3月至2008年2月诊断为先 天性体动脉-肺动脉瘘4例患儿的临床资料,总结其临床表现、胸部X线片、胸部64 排CT增强扫描三维容积再现(3D-VR)、数字减影血管造影（DSA）、治疗及随访情 况。结果男1例,女3例,最大发病年龄为11岁,最小发病年龄为2个月,主要表现为咯 血。1例有杵状指,3例未见特异性体征。胸部X线片检查：3例未见异常,1例示肺 间实质浸润。胸部64排CT增强扫描3D-VR检查：1例提示支气管动脉迂曲,但未见 异常交通;1例导管栓塞治疗（TCE）后示右侧支气管动脉扩张迂曲,并与肺动脉 相通可能性大,考虑支气管动脉-肺动脉瘘;1例提示支气管动脉-肺动脉瘘;1例 未见异常。3例DSA提示为支气管动脉-肺动脉瘘,病变部位均位于右下肺,并行 TCE。随访至2009年2～5月,1例复发,表现为痰中带血,胸部64排CT增强扫描未 见异常,余3例未复发。3例怀疑为遗传性出血性毛细血管扩张症(HHT),1例考虑 为HHT高度危险者。结论体动脉-肺动脉瘘可造成大量咯血。胸部X线片一般无特异性表现,胸部64排 CT增强扫描3D-VR可显示病变部位,明确诊断需行DSA。可采用TCE治疗。TCE远期 效果应进行长期随访予以明确。     

Gene expression profiling reveals intrinsic differences between T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma

BACKGROUND: T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LL) and are often thought to represent a spectrum of a single disease. The malignant cells in T-ALL and T-LL are morphologically indistinguishable, and they share the expression of common cell surface antigens and cytogenetic characteristics. However, despite these similarities, differences in the clinical behavior of T-ALL and T-LL are observed. PROCEDURE: We analyzed the gene expression profiles of T-ALL and T-LL samples obtained from Children's Oncology Group (COG) tumor banks using DNA arrays. Immunohistochemistry was also performed to validate the expression of selected targets. RESULTS: Unsupervised hierarchical clustering of all samples showed complete segregation of T-ALL and T-LL into distinct clusters. Next, we identified the top 201 genes that best differentiated T-ALL from T-LL using significance analysis of microarrays (SAM), a supervised statistical approach. Genes representing several functional groups were differentially expressed in T-LL and T-ALL. Prediction analysis of microarrays (PAM) identified a subset of genes, which accurately classified all 19 T-ALL and T-LL samples with an overall misclassification error rate of 0. Immunohistochemical validation of protein expression of selected genes identified by microarray analysis confirmed overexpression of MLL-1 in T-LL tumor cells compared to T-ALL and CD47 in T-ALL tumors cells when compared to T-LL. CONCLUSIONS: Despite significant similarities between the malignant T-cell precursors, clear differences in the gene expression profiles were observed between T-ALL and T-LL implying underlying differences in the biology of the two entities.     

Interferon-γ production by cord-blood mononuclear cells is reduced in newborns with a family history of atopic disease and is independent from cord blood IgE-levels

For newborn children both elevated serum IgE levels in the cord blood and a positive family history of atopic disease have been shown to be risk factors for the manifestation of atopic diseases. In adult patients with atopic dermatitis, in vitro interferon-γ (IFN-γ) production is reduced and a negative correlation with serum IgE levels has been shown. We have now raised the question if newborn infants at risk for the development of atopic disease have similar abnormalities of cytokine production at birth. In vitro production of interleukin 2, interleukin 6 and interferon-γ by peripheral blood mononuclear cells was measured in 53 newborns: 21 had cord blood IgE levels above 0. 9 kU/1, 21 had a positive family history, 7 had both elevated IgE and a positive family history; 18 newborns with no identitiable risk for atopic disease served as controls. Umbilical cord blood mononuclear cells were stimulated with PHA or monoclonal antibody OKT3. In vitro production of interleukin 2 and 6 was comparable in all groups. Compared to controls IFN-γ production of peripheral mononuclear cells (PBMC) from newborns with elevated cord blood IgE was not different, but PMBC from newborns with a familial risk showed a significant decrease in PHA induced IFN-γ production (p < 0.005, U-test). No correlation between umbilical cord blood IgE and diminished IFN-γ production was found in newborns with or without a positive family history. We conclude that immunoregulatory abnormalities in newborns of atopic families are detectable already at birth and are unrelated to cord blood IgE.     

Cerebral Malignant Nerve Sheath Tumor,Triton Tumor Variant: Case Report

A case of a cerebral malignant triton tumor in a 3-year-old boy with a 2-month history of frontal headache and no clinical evidence of neurofibromatosis is reported. The computed tomography (CT) scan showed a large, irregular tumor in the right parietooccipital lobe. A partial surgical resection was performed. Histologically, the tumor was highly cellular and consisted of spindle cells with hyperchromatic and pleomorphic nuclei. Focally, neoplastic cells with rhabdomyoblastic features were found. The immunohistochemical study showed that tumor cells were positive for S-100 protein and CD57, and the rhabdomyoblasts expressed desmin, Myo-D1, and myoglobin. During the postoperative period, a massive intraparenchymal hemorrhage was identified and surgical drainage was performed. The patient worsened and died 10 days after the first surgery. Postmortem study was not authorized. Six cases of cerebral malignant nerve sheath tumor have been described; however, primary intraparenchymal malignant triton tumor has not been previously described.     

The clinical significance of pseudouridine determination of the urine in children and adolescents

A HPLC-method is described to determine the Pseudouridine/creatinine ratio in spontaneous urine samples in infancy and childhood. The urines of 74 healthy children between 1 and 18 years of age and of 231 children with different diseases were examined for this ratio, making 1097 measurements. 157 children suffered from a malignant disease, 66 of them having an acute leukemia. Those patients, who remain in remission of the leukemia showed normal values, whereas the others had elevated ratios, reflecting the activity of the leukemia, when they were followed up by multiple determinations. Perhaps it is also possible to detect preclinical stages of leukemia by measuring the pseudouridine/creatinine ratio routinously over a long period of time. Today no strict correlation between the prognosis of leukemia and the level of this ratio can be drawn. Similar behaviour of the pseudouridine/creatinine ratio is seen in other malignant diseases with exception of brain tumors. The difference to leukemias is, that all other malignant tumors show more often normal values in patients with a remaining tumor. A pathological value of pseudouridine may also be seen in others than malignant diseases.