Burkitt's lymphoma in a child with AIDS

Few systemic lymphomas have been reported in children with AIDS. We report a case of disseminated Burkitt's lymphoma with lung involvement occurring in a 33-month-old child with acquired immunodeficiency syndrome. Lymphoid interstitial pneumonia was diagnosed by lung biopsy at 23 months of age, but lymphoma was not diagnosed before autopsy.     

Alectinib is effective,safe and tolerable in an adolescent with stage IVB ALK-rearranged adenocarcinoma of the lung

Abstract

Anaplastic lymphoma kinase (ALK) inhibitors such as crizotinib and alectinib have been shown to have significant activity in ALK-rearranged non-small cell lung cancers (NSCLC). There are no data for alectinib’s safety or efficacy in younger patients, though it is superior to crizotinib in adult trials. We present a 14-year old girl diagnosed with stage IV-B ALK-positive adenocarcinoma of the lung after presenting with cough and fever. She was commenced on alectinib at adult dose and has had sustained complete metabolic remission for 9?months. She is the youngest patient with lung adenocarcinoma to be treated with alectinib.     

Refractoriness to rituximab monotherapy in a child with relapsed/refractory Burkitt non-Hodgkin lymphoma

The authors describe a 6-year-old boy diagnosed with mediastinal Burkitt lymphoma with tumor invasion into bone marrow and both kidneys. After receiving chemotherapy according to NHL BFM-95 protocol for the high-risk disseminated lymphoma, the patient reached complete remission. He relapsed in the mediastinum at 5 months from the diagnosis. He underwent thoracotomy and tumor mass was removed by inferior lobectomy of right lung. Residual tumor progressed rapidly. Autologous stem cell transplantation could not be performed because of unresponsiveness to cytoreductive chemotherapy. Twenty-three days after the last chemotherapy course, he received rituximab at a dose of 375 mg/m ² by intravenous infusion weekly, for a total of 8 dose. However, multiple intra-abdominal metastatic lesions were detected at the end of the therapy. Palliative radiotherapy was applied to these sites. He died because of disease progression, 11 months after the diagnosis.     

Primary renal lymphoma presenting with hypertension

Primary renal lymphoma (PRL) is a rare lymphoma which usually presents with hematuria, flank pain, abdominal mass, and weight loss. PRL is more diagnosed in adults than children. We describe an asymptomatic child who presented with hypertension and was subsequently diagnosed with primary renal lymphoma. This case represents an atypical presentation for PRL.     

REFRACTORINESS TO RITUXIMAB MONOTHERAPY IN A CHILD WITH RELAPSED/REFRACTORY BURKITT NON-HODGKIN LYMPHOMA

The authors describe a 6-year-old boy diagnosed with mediastinal Burkitt lymphoma with tumor invasion into bone marrow and both kidneys. After receiving chemotherapy according to NHL BFM-95 protocol for the high-risk disseminated lymphoma, the patient reached complete remission. He relapsed in the mediastinum at 5 months from the diagnosis. He underwent thoracotomy and tumor mass was removed by inferior lobectomy of right lung. Residual tumor progressed rapidly. Autologous stem cell transplantation could not be performed because of unresponsiveness to cytoreductive chemotherapy. Twenty-three days after the last chemotherapy course, he received rituximab at a dose of 375 mg/m ² by intravenous infusion weekly, for a total of 8 dose. However, multiple intra-abdominal metastatic lesions were detected at the end of the therapy. Palliative radiotherapy was applied to these sites. He died because of disease progression, 11 months after the diagnosis.     

Intensive chemotherapeutic regimens against acute leukemia transiently suppress asthma symptoms but do not lead to long-term relief

In some very rare cases children suffer from a combination of asthma and a malignant disease. This study investigated whether intensive chemotherapy might have a positive effect on asthma in these special cases and whether asthma generally relapses after completion of chemotherapy. The authors monitored clinical outcome and lung function of 43 children with acute lymphoblastic leukemia and non-Hodgkin lymphoma who received chemotherapy at the University Children's Hospital of Greifswald between 1993 and 1998. Cytostatic chemotherapy was administered according to the German treatment protocols. Two of the 43 patients had asthma before leukemia was diagnosed. During the course of chemotherapy, asthma symptoms diminished promptly after beginning of chemotherapy but asthma was rediagnosed after completion of chemotherapy in both cases. The third patient developed asthmatic symptoms shortly after completion of chemotherapy for the first time. It can be stated that chemotherapy does not essentially cure asthma. Therefore, it seems mandatory to perform follow-up lung testings after chemotherapy, especially in patients with asthma.     

INTENSIVE CHEMOTHERAPEUTIC REGIMENS AGAINST ACUTE LEUKEMIA TRANSIENTLY SUPPRESS ASTHMA SYMPTOMS BUT DO NOT LEAD TO LONG-TERM RELIEF

In some very rare cases children suffer from a combination of asthma and a malignant disease. This study investigated whether intensive chemotherapy might have a positive effect on asthma in these special cases and whether asthma generally relapses after completion of chemotherapy. The authors monitored clinical outcome and lung function of 43 children with acute lymphoblastic leukemia and non-Hodgkin lymphoma who received chemotherapy at the University Children's Hospital of Greifswald between 1993 and 1998. Cytostatic chemotherapy was administered according to the German treatment protocols. Two of the 43 patients had asthma before leukemia was diagnosed. During the course of chemotherapy, asthma symptoms diminished promptly after beginning of chemotherapy but asthma was rediagnosed after completion of chemotherapy in both cases. The third patient developed asthmatic symptoms shortly after completion of chemotherapy for the first time. It can be stated that chemotherapy does not essentially cure asthma. Therefore, it seems mandatory to perform follow-up lung testings after chemotherapy, especially in patients with asthma.     

Malignant B-cell lymphoma following and associated with infectious mononucleosis. A comparison of two cases

The present report describes two young males with clinically diagnosed infectious mononucleosis (IM) who subsequently were diagnosed as having malignant B-cell lymphoma (i.e., immunoblastic sarcoma of B-cells). Despite these apparent similarities, there were fundamental differences between the two cases. The first patient, who lymphoma was diagnosed 9 months after IM, was one of a well-described kindred with the X-linked lymphoproliferative syndrome (XLP) in which affected young males lack the ability to mount an effective immune response to primary infection with the Epstein-Barr virus (EBV) (i.e., infectious mononucleosis), and subsequently develop fatal lymphoproliferative disorders of the B-cell type. This was in contrast to a second patient, also a young male, who did not have the X-linked lymphoproliferative syndrome, who did develop specific antibodies to the Epstein-Barr virus and whose malignant lymphoma was closely associated in time (i.e., 5 weeks) with the clinical diagnosis of infectious mononucleosis. The comparative immunologic and virologic features are discussed as well as the importance of careful clinicopathologic correlation in young adults and children developing malignant lymphoma both following and in association with infectious mononucleosis.     

Anti-CD20 Monoclonal Antibody (Rituximab) for Therapy of Mediastinal CD20-Positive Large B-Cell Non-Hodgkin Lymphoma with a Local Tumor Extension into the Lung of a 10-Year-Old Girl

Intravenous therapy with the anti-CD20 antibody Rituximab has been recently approved for the treatment of CD20 positive non-Hodgkin's lymphoma (NHL) in adults but not in children. The authors present the benefits of its application for mediastinal NHL CD 20+ with a local extension into the lung of a 10-year-old-girl. Receiving the chemotherapy according to study NHL-BFM-95 for high-risk lymphoma the girl did not reach complete remission. Before the last chemotherapy block was started, a computed tomography scan of the thorax showed residue in the right lung. Twenty-five days after the last chemotherapy she received Rituximab at a dose of 375 mg/m 2 by intravenous infusion once a week for a total of four doses without the adverse reactions. Complete remission was achieved. The patient was high risk with lung involvement of lymphoma suggesting a pure prognosis. The results suggest that Rituximab may improve the outcome in high-risk patients and appeared to be safe and effective in children also.     

Anti-CD20 monoclonal antibody (Rituximab) for therapy of mediastinal CD20-positive large B-cell non-Hodgkin lymphoma with a local tumor extension into the lung of a 10-year-old girl

Intravenous therapy with the anti-CD20 antibody Rituximab has been recently approved for the treatment of CD20 positive non-Hodgkin's lymphoma (NHL) in adults but not in children. The authors present the benefits of its application for mediastinal NHL CD 20+ with a local extension into the lung of a 10-year-old-girl. Receiving the chemotherapy according to study NHL-BFM-95 for high-risk lymphoma the girl did not reach complete remission. Before the last chemotherapy block was started, a computed tomography scan of the thorax showed residue in the right lung. Twenty-five days after the last chemotherapy she received Rituximab at a dose of 375 mg/m(2) by intravenous infusion once a week for a total of four doses without the adverse reactions. Complete remission was achieved. The patient was high risk with lung involvement of lymphoma suggesting a pure prognosis. The results suggest that Rituximab may improve the outcome in high-risk patients and appeared to be safe and effective in children also.     

Linfoma anaplásico de células grandes endobronquial en la infancia

Anaplastic large cell lymphoma is a very rare disease in childhood. The most common location of this lymphoma is lymph node and skin, with endobronchial involvement being extremely rare. We report a case of a 10-year-old boy diagnosed by chance with an endobronchial anaplastic large cell lymphoma, while he was being investigated for a a benign bone disease, due to the initial absence of respiratory symptoms.     

Diagnosis and treatment of post-transplantation lymphoproliferative disorder in pediatric heart transplant patients

PTLD is a severe complication in transplant recipients. Detection of increased EBV load in the peripheral blood acts as a surrogate marker for increased risk of PTLD development. We analyzed the time course of the disease, its severity, the organs involved, and mortality rates in our institutional experience of pediatric heart transplantation. This paper identifies risk factors for PTLD and describes the different ways of diagnosing and treating the disease. PTLD was screened for in 146 pediatric heart transplant patients using a retrospective analysis in patients who received transplantation before 1998. Prospective determination was performed in 72/146 patients transplanted after 1998 within the post-transplant follow-up. The occurrence of PTLD with all interventions, including tapering of immunosuppression, surgery, viral monitoring, and antiviral interventions, was recorded. PTLD was diagnosed in 12/147 (8.2%) children at a mean age of 7.2 +/- 3.3 yr after a mean post-transplant period of 3.2 +/- 2.2 yr. PTLD manifested in: lymph nodes (n = 4), intestine (n = 3), tonsils and adenoids (n = 2), eye (n = 2), and lung (n = 1). It was diagnosed in 7/12 as a monomorphic B-cell lymphoma and in four patients as a monomorphic Burkitt lymphoma, a polymorphic B-cell lymphoma, a T-cell rich or angiocentric lymphoma (Liebow) and as reactive plasmacytic hyperplasia (early lesion), respectively. Histology was not possible in one patient with ocular manifestation. EBV association was 83%. Risk factors in the comparison with patients without PTLD were age at time of Tx, primary EBV infection after Tx, use of Azathioprine and >or=3 doses of ATG. CMV mismatch and CMV infection, rejection episodes and steroids were not risk factors. Despite reduction of immunosuppression, treatment consisted of surgical procedures to remove tumor masses (n = 6), Rituximab (n = 5), polychemotherapy (n = 3), antiviral (n = 1) and autologous T-cell therapy (n = 1). All patients demonstrated full remission without death related to PTLD or treatment at 3.9 (1.3-6.2) yr median follow-up time. The manifestation of PTLD in pediatric heart transplant recipients is associated with EBV infection and is predominantly in the form of a B-cell lymphoma. A tight and specific follow-up including early assessment of immunity status and specific therapeutic intervention to improve cellular immunity is warranted and may contribute to a significant reduction of PTLD-related morbidity and mortality.     

小儿原发性胃肠道非霍奇金淋巴瘤的临床病理分析

目的探讨小儿原发性胃肠道非霍奇金淋巴瘤（primary gastrointestinallymphoma,PGIL）的临床病理特征及免疫表型。方法对10例小儿PGIL采用sP法行CD45、CD3、CD3e、CD5、CD10、CD15、CD20、CD30、CD45R01CD56、CD68,CD99、Bcl-2、Bcl-6、ALK、CyelinD1、Mum-1、MPO、PAX-5、TdT、TIA-1、Ki-67及细胞角蛋白（CK）免疫组织化学染色,运用原位杂交检测Epstein—Barr病毒编码的早期RNA（EBER）,按2008年WHO淋巴造血系统肿瘤分类标准进行分类。结果①10例瘤细胞均表达CIM5、Ki-67,无一例表达CK;10例均经病理、免疫组化及原位杂交检测等确诊为不同类型PGIL;②临床表现为腹痛、腹泻、腹部包块、发热、贫血和消瘦等。发生在小肠5例、回盲部2例、结肠1例、直肠2例。6例为溃疡型,4例为隆起型;③B细胞性NHL7例,其中伯基特淋巴瘤5例,B淋巴母细胞性淋巴瘤1例,弥漫性大B细胞淋巴瘤1例;T细胞NHL3例,其中NK／T细胞淋巴瘤1例,肠病相关T细胞淋巴瘤1例,ALK阳性间变性大细胞淋巴瘤1例。结论小儿PGIL临床症状无特异性,以B细胞淋巴瘤多见,T细胞淋巴瘤少见,预后差,须与其他胃肠道恶性肿瘤相鉴别。     

Diffuse cavitary lung lesions

An 11-year-old girl presented with a 2-month history of progressively worsening cough, daily fevers, and weight loss. A chest radiograph revealed multiple cystic cavitary lung lesions. An extensive infectious work-up was negative. Chest CT verified multiple cavitary lung lesions bilaterally, and [F-18]2-fluoro-2-deoxy-D-glucose (¹⁸F-FDG) positron emission tomography with CT (PET/CT) showed increased uptake in the lung lesions as well as regional lymph nodes. Subsequent biopsy of an involved lymph node confirmed classical Hodgkin lymphoma, nodular sclerosis type. This case represents an unusual presentation for a child with Hodgkin lymphoma and demonstrates a role for ¹⁸F-FDG PET/CT in evaluating a child with cavitary lung lesions.     

Autoimmune hemolytic anemia as presenting manifestation of primary splenic anaplastic large cell lymphoma

Autoimmune hemolytic anemia (AIHA) is an unusual complication of malignancy. We diagnosed primary splenic anaplastic large cell lymphoma (ALCL) in a patient. A seven-year-old boy presented with Coombs test-positive hemolytic anemia. After a course of prednisolone therapy, a complete response for anemia was achieved. Twenty months later, in addition to severe hemolytic anemia, the patient was diagnosed with ALCL after splenectomy and pathologic examination of the sample. The recognition of this clinical picture as a complication of non-Hodgkin's lymphoma has important implications. The most effective management of AIHA in the setting of cancer is to treat the underlying malignancy.     

Burkitt's lymphoma of the skull base presenting as cavernous sinus syndrome in early childhood

Primary non-Hodgkin's lymphoma of the skull base presenting with neuro-ophthalmologic abnormalities or cavernous sinus involvement is very rare in children. We have found only 13 reported cases of cavernous sinus involvement by lymphoma [1]. We report the case of the youngest child diagnosed with Burkitt's lymphoma of the cavernous sinus and sphenoid sinus, whose first presentation was cavernous sinus syndrome with neuro-ophthalmologic findings.     

Risk factors for reduced pulmonary function after malignant lymphoma in childhood

The aim was to study pulmonary function after Hodgkin disease or non-Hodgkin lymphoma in childhood and to evaluate if younger age at diagnosis and therapy is a risk factor for reduced pulmonary function. We studied a population-based sample of survivors of Hodgkin disease (n = 22) or non-Hodgkin lymphoma (n = 19) in childhood. Pulmonary function test results were compared with reference values for our laboratory, generated by adjusting published reference values to fit 348 healthy never-smokers from a local population study. Data were analysed as standardised residuals, which are [observed minus predicted value] divided by the residual standard deviation of the reference equations. At a median of 11 years after diagnosis (range 2 to 24), the participants had significantly reduced lung volumes and transfer factor, unrelated to the few pulmonary symptoms. On average, the total lung capacity was reduced to −0.9 standardised residual and the transfer factor was reduced to −1.3 standardised residual. Young age at therapy seemed to be a risk factor for reduced lung function, especially when treatment included thoracic irradiation. No significant toxic synergism was observed between smoking and previous cancer therapy. Therapy without thoracic irradiation but with doxorubicin and cyclophosphamide was almost as toxic to lung function as therapy with thoracic irradiation but without doxorubicin and cyclophosphamide. This suggests a pulmonary toxicity of doxorubicin or cyclophosphamide. In conclusion, lung volumes and transfer factor were reduced several years after childhood Hodgkin disease or non-Hodgkin lymphoma, with young age at therapy as a risk factor, especially when combined with thoracic irradiation. Med. Pediatr. Oncol. 30:240–248, 1998. © 1998 Wiley-Liss,Inc.     

Coexistence of Hodgkin lymphoma and cyst hydatic disease of the liver

Although both Hodgkin lymphoma and cyst hydatic disease in children have been seen with an increased frequency, there is no previously reported case of Hodgkin lymphoma associated with cyst hydatic disease from Turkey. The authors report such a case of Hodgkin lymphoma. Intrahepatic cystic masses were diagnosed during ultrasound examination for clinical staging on admission. The diagnosis of cyst hydatic of the liver was confirmed by surgery. Although there was no residual and/or new cyst formation on radiologic follow-up, elevated antibody titers (indirect hemagglutination test) persisted following surgical excision at least for 2 years of follow-up.     

The inter-regional epidemiological study of childhood cancer (IRESCC): a case control study of aetiological factors in leukaemia and lymphoma.

The inter-regional epidemiological study of childhood cancer analysed data on 234 children diagnosed with leukaemia or lymphoma and 468 controls matched for age and sex. A wide range of potential risk factors was examined, including prenatal exposure to x rays, maternal drug ingestion and smoking, child''s medical history, and parental medical conditions and occupation. Calculations were completed for leukaemia or lymphoma and diagnostic subgroups, as defined by laboratory confirmed cell type. In utero exposure to narcotic analgesics was weakly associated with leukaemia or lymphoma but no other antenatal factors gave significant risks. New associations were identified for skin diseases in both parents and congenital abnormalities in the mothers of children with leukaemia. For past medical conditions in the child, viral disease occurring under 6 months of age increased the risk for acute lymphoblastic leukaemia. Fewer children in the leukaemia or lymphoma group had been immunised compared with the control groups. Case children diagnosed over the age of 9 years were more likely than controls to have had four or more previous episodes of illness. Overall, these results indicate that prenatal factors may be less important than postnatal or genetic influences in the development of leukaemia or lymphoma in children.     

B cell non-Hodgkin's lymphoma in a girl with the DiGeorge anomaly.

The DiGeorge anomaly (DGA) is occasionally associated with cellular immunodeficiency. We report a female infant diagnosed with complete DGA, who developed fatal, high grade, non-Hodgkin's lymphoma that expressed Epstein-Barr virus (EBV). Non-Hodgkin's lymphoma should be considered in children with DGA.