Update on lymphoma

Lymphoma comprises ∼10% of childhood cancers and 17% of cancer in teenagers. It is divided into Hodgkin and non-Hodgkin lymphoma; most of the latter in children are Burkitt lymphoma, lymphoblastic lymphoma and anaplastic large cell lymphoma. Lymphoma commonly presents with painless lymphadenopathy, usually cervical. ‘B’ symptoms are associated with advanced disease. The diagnosis is made by histological examination of an excised lymph node, but can be made on pleural fluid or a bone marrow aspirate. Emergency management, particularly of the airway, may be necessary, particularly in non-Hodgkin lymphoma. Lymphomas are treated with multi-drug chemotherapy regimens, stratified by risk group, with radiotherapy in selected cases. In Hodgkin lymphoma, PET is prognostic after two cycles of chemotherapy. The high cure rate for lymphomas (greater than 90% for Hodgkin and Burkitt lymphoma) and the need to reduce late effects has led to the drive to tailor treatment according to risk groups and response to initial therapy.     

An update on lymphoma in children and young adults

Lymphoma accounts for approximately 10% of childhood cancers, but 17% in teenagers. It is divided into Hodgkin and non-Hodgkin lymphoma, with the vast majority of non-Hodgkin lymphoma in children being Burkitt lymphoma, lymphoblastic lymphoma and anaplastic large cell lymphoma. Lymphoma usually presents with painless lymphadenopathy, most commonly in the cervical region. ‘B’ symptoms are associated with more advanced disease. The diagnosis is usually made by histological examination of an excised lymph node, but can be made on pleural fluid or a bone marrow aspirate. Emergency management, particularly of the airway, may be necessary, especially in non-Hodgkin lymphoma. Lymphomas are treated with multi-drug chemotherapy regimens, stratified by risk group, with radiotherapy in selected cases. Rituximab (anti-CD20 monoclonal antibody) is used in conjunction with chemotherapy for poorer risk groups and in the relapse setting. In Hodgkin lymphoma, positron emission tomography scans are prognostic at assessment of response to therapy. The high cure rate for lymphomas (more than 90% for Hodgkin and Burkitt lymphoma) and the need to reduce late effects in children and adolescents has led to the current drive to tailor treatment according to risk group and response to initial therapy.     

Seasonal variation in month of birth and diagnosis in children and adolescents with Hodgkin disease and non-Hodgkin lymphoma

PURPOSE: Infections have been hypothesized to be a risk factor for Hodgkin disease and non-Hodgkin lymphoma. Because infections usually occur seasonally, the authors looked at the seasonal pattern of occurrence of these diseases, since seasonal variation in occurrence would lend support to the hypothesis of an etiologic link between infection and lymphoma. METHODS: The authors identified 575 patients with Hodgkin disease and 498 with non-Hodgkin lymphoma under the age of 20 years in the Danish Cancer Registry from 1943 to 1994. A periodic regression model was used to evaluate the seasonal distribution of month of diagnosis and month of birth. RESULTS: For the month of diagnosis of Hodgkin disease, the peak month of occurrence was March. The peak-to-trough ratio (the estimated incidence in the month of the peak divided by the estimated incidence in the month of the trough) was 1.57. For birth date, the ratio of case births at the peak month to case births at the trough month was 1.21, with a peak in July. There was no meaningful seasonal variation in the diagnosis or month of birth of children with non-Hodgkin lymphoma. CONCLUSIONS: These data corroborate a previously reported March peak in the diagnosis of Hodgkin disease.     

Thymic and adenotonsillar enlargement after successful treatment of malignancies

Anterior mediastinal and adenoid masses in children after cessation of chemotherapy for malignant disease often cause a diagnostic problem. Differential diagnosis of thymic enlargement and adenoid hyperplasia from recurrence frequently poses a challenge both for the radiologist and the physician. In this study the authors evaluated 491 patients with different malignant tumors for thymic and adenoid hyperplasia. Thymic hyperplasia was seen in 18 patients (5 Hodgkin disease (HD), 5 non-Hodgkin lymphoma (NHL), 4 Wilms tumor, 2 germ cell tumor, 1 Ewing sarcoma, and 1 neuroblastoma), only adenotonsillar hyperplasia was seen in 6 patients, all with NHL, and both thymic and adenotonsillar hyperplasia were seen in 3 patients (1 HD, 2 NHL). In 5 patients, adenoid hyperplasia was proven by biopsy; 1 patient underwent to adenoidectomy. Their histopathologic investigation showed polyclonal follicular hyperplasia. The authors recommend that patients with thymic and/or adenotonsillar enlargement after successful treatment of their primary malignancy should be evaluated cautiously before an invasive procedure is planned.     

Pulmonary involvement in pediatric lymphoma

Background The prevalence of pulmonary lymphoma in the pediatric age group is not documented in the literature.Objective This study was designed to assess the prevalence of pulmonary parenchymal lymphoma in children with Hodgkin disease (HD), non-Hodgkin lymphoma (NHL) and post-transplant lymphoproliferative disorder (PTLD).Materials and methods A 10-year retrospective analysis of 161 lymphoma patients (62 girls and 99 boys), mean age of 12.4 years, was performed. The definition of pulmonary lymphoma excluded those with isolated pleural disease and/or mediastinal adenopathy.Results Eighty-two patients had HD, 65 had NHL, and 14 had PTLD. Overall prevalence of pulmonary parenchymal involvement was 13% (21/161), including 12% of patients with HD, 10% of patients with NHL, and 29% of patients with PTLD. CT findings included: pulmonary nodules (90%) or mass (38%); interstitial (9%) or alveolar (9%) disease; cavitation (9%); and pleural based mass (9%).Conclusions Pulmonary parenchymal disease in our pediatric lymphoma population was more prevalent than expected (13%). This is significant for patient management. New pulmonary lesions in patients with known lymphoma should be regarded with suspicion. In the setting of immune suppression, pulmonary lesions treated as infection may actually represent lymphoma. Expeditious biopsy of lesions failing to respond promptly to antibiotic therapy should be considered.     

MALIGNANT SOLID TUMORS ASSOCIATED WITH CONGENITAL IMMUNODEFICIENCY DISORDERS

This objective of this study was to evaluate patients with immunodeficiency syndromes who had developed malignant solid tumors and to examine survival rates and prognosis with respect to type of immunodeficieny disease. Twenty-two patients who were diagnosed with malignant solid tumors and immunodeficiency syndromes between January 1972 and February 2003 were analyzed retrospectively. There were 12 (55%) patients with non-Hodgkin lymphoma, 8 (37%) with Hodgkin disease, 1 (5%) with mucinous adenocarcinoma of the colon, and 1 (5%) with brain stem glioma. Fifteen (68%) patients had ataxia-telangiectasia, 3 (14%) had common variable immunodeficiency disease, 2 (9%) had Bloom syndrome, 1 (5%) had combined immunodeficiency, and 1 (5%) had selective immunoglobulin A deficiency. Out of the 15 patients with ataxia–telangiectasia 9 patients had non-Hodgkin lymphoma, 5 had Hodgkin disease, and 1 had brain stem glioma. Two patients with common variable immunodeficiency disease had non-Hodgkin lymphoma and 1 had Hodgkin disease. One of the patients with Bloom syndrome had Hodgkin disease and 1 had colon carcinoma. The overall survival for the whole group was 24%. Overall survival rates in non-Hodgkin lymphoma, Hodgkin disease, colon carcinoma, and brain stem glioma were 17, 44, 0, and 0% (=. 25), respectively. Overall survival in ataxia-telangiectasia patients was 20%. In this series, most of the patients had ataxia-telangiectasia (68%). The survival rates of the malignant diseases were very poor in immunodeficiency. Overall survival in non-Hodgkin lymphoma patients was relatively worse than Hodgkin disease patients.     

Malignant solid tumors associated with congenital immunodeficiency disorders

This objective of this study was to evaluate patients with immunodeficiency syndromes who had developed malignant solid tumors and to examine survival rates and prognosis with respect to type of immunodeficiency disease. Twenty-two patients who were diagnosed with malignant solid tumors and immunodeficiency syndromes between January 1972 and February 2003 were analyzed retrospectively. There were 12 (55%) patients with non-Hodgkin lymphoma, 8 (37%) with Hodgkin disease, 1 (5%) with mucinous adenocarcinoma of the colon, and 1 (5%) with brain stem glioma. Fifteen (68%) patients had ataxia-telangiectasia, 3 (14%) had common variable immunodeficiency disease, 2 (9%) had Bloom syndrome, 1 (5%) had combined immunodeficiency, and 1 (5%) had selective immunoglobulin A deficiency. Out of the 15 patients with ataxia-telangiectasia 9 patients had non-Hodgkin lymphoma, 5 had Hodgkin disease, and 1 had brain stem glioma. Two patients with common variable immunodeficiency disease had non-Hodgkin lymphoma and 1 had Hodgkin disease. One of the patients with Bloom syndrome had Hodgkin disease and 1 had colon carcinoma. The overall survival for the whole group was 24%. Overall survival rates in non-Hodgkin lymphoma, Hodgkin disease, colon carcinoma, and brain stem glioma were 17, 44, 0, and 0% (p =.25), respectively. Overall survival in ataxia-telangiectasia patients was 20%. In this series, most of the patients had ataxia-telangiectasia (68%). The survival rates of the malignant diseases were very poor in immunodeficiency. Overall survival in non-Hodgkin lymphoma patients was relatively worse than Hodgkin disease patients.     

Diagnostic and therapeutic problems posed by malignant non Hodgkin lymphoma of renal origin in children. Apropos of 7 cases]

BACKGROUND. The kidneys of non Hodgkin lymphoma patients frequently contain lymphoma cells, but these tumors rarely arise in the renal tissue and are rarely located there. PATIENTS. A diagnosis of non Hodgkin lymphoma of renal origin or predominantly located in kidneys was made in 7 patients aged 2-14 years old. These patients formed part of a total of 450 patients with non Hodgkin lymphomas seen from 1974 to 1987. The first manifestation in these 7 children was an abdominal mass associated with hypertension in 3 cases; 2 of whom presented with acute kidney failure. Ultrasonography showed hypoechogenous masses in one (2 cases) or both kidneys (5 cases). The diagnosis of malignant lymphoma was made directly in only one patient who also presented with mediastinal and abdominal lymph node enlargement. In the others, the first diagnosis was Wilms tumor (5 cases) and polycystic disease of the kidney (1 case); the correct diagnosis of malignant lymphoma was later made from biopsies of renal (4 patients) or extrarenal involved tissue (2 patients). Six of the 7 cases were Burkitt lymphomas, and all 7 were in stage III (3 patients) and IV (4 patients). 6 patients (3 stage III and 3 stage IV) were successfully treated by chemotherapy with a median follow-up of 9 years. CONCLUSIONS. Differential diagnosis between non Hodgkin lymphomas of renal origin and a Wilms tumor may be difficult even though kidney failure is more frequent in lymphoma. Sonography is the best method for diagnosis showing typical hypoechogenous masses and diffuse homogeneous infiltration of the kidneys. In the absence of extrarenal (meningeal, testis, bone marrow) dissemination, definite evidence of lymphoma depends on the histological examination of tumoral tissue obtained by surgical biopsy.     

Spindle cell lesions of the head and neck mimicking rhabdomyosarcoma in children

Malignancies of head and neck are uncommon among children. The most commond solid tumors to occur in this region are rhabdomyosarcoma, Hodgkin disease, and non-Hodgkin lymphoma. Two children are described who presented with signs and symptoms consistent with rhabdomyosarcoma, but who were found to hav e benign spindle cell lesions. These rare lesions should bepart of the differential of children with a head and neck mass.     

Degree of fatness after treatment of malignant lymphoma in childhood

BACKGROUND: Sex hormone deficiency or growth hormone deficiency may cause excess fatness after treatment for childhood malignant lymphoma. Previous studies of the body composition after treatment for childhood cancer included few survivors of malignant lymphoma who were not analysed separately. PROCEDURE: We measured the whole-body percent fat by dual energy X-ray absorptiometry (DXA) and the body-mass index (weight/height(2) (kg/m(2)), BMI) in survivors of childhood Hodgkin disease (n = 23) or non-Hodgkin lymphoma (n = 21) a median of 11 years after diagnosis (range 2-25). Results were compared with local data on 463 healthy controls. RESULTS: Adjusted for sex and age, the mean BMI did not differ from that of local controls, but the mean whole-body percent fat was significantly increased (0.8 SD above predicted, P = 0.0001). Sixteen of 44 participants had a percent fat above the 90 percentile of the reference values, which indicates excess fatness. Adjusted for sex and age, percent fat was significantly higher in persons treated for non-Hodgkin lymphoma. Controlled for this, the whole-body percent fat was not significantly related to sex, age at diagnosis, length of follow-up, sex hormone therapy at follow-up or the cumulative dose of corticosteroids or doxorubicin. CONCLUSIONS: Eleven years after diagnosis of childhood Hodgkin disease or non-Hodgkin lymphoma, the whole-body percent fat was increased whereas the BMI was like that of the controls. This indicates a reduced lean body mass.     

A kinetically designed chemotherapeutic regimen for advanced refractory lymphoma patients.

Three patients with Hodgkin disease, eight with non-Hodgkin lymphoma, and one with chronic lymphocytic leukemia refractory to conventional combination chemotherapy were treated for remission induction with a new kinetically designed four-drug combination consisting of bleomycin, vincristine, adriamycin, and prednisone and given the acronym "BOAP." Eight patients had prior radiotherapy, included two who had total nodal irradiation. Eight patients (all three with Hodgkin disease and five of eight with non-Hodgkin lymphoma) achieved complete remission (73% of the lymphoma patients). An additional two patients with non-Hodgkin lymphoma sustained partial remissions, for an overall response rate of 91%. Toxicity caused the interruption of therapy in three patients and an additional patient might have sustained a drug-related death. This study compares favorably with other studies investigating primary or secondary combination chemotherapy of advanced lymphomas.     

A kinetically designed chemotherapeutic regimen for advanced refractory lymphoma patients

Three patients with Hodgkin disease, eight with non-Hodgkin lymphoma, and one with chronic lymphocytic leukemia refractory to conventional combination chemotherapy were treated for remission induction with a new kinetically designed four-drug combination consisting of bleomycin, vincristine, adriamycin, and prednisone and given the acronym “BOAP.” Eight patients had prior radiotherapy, including two who had total nodal irradiation. Eight patients (all three with Hodgkin disease and five of eight with non-Hodgkin lymphoma) achieved complete remission (73% of the lymphoma patients). An additional two patients with non-Hodgkin lymphoma sustained partial remissions, for an overall response rate of 91%. Toxicity caused the interruption of therapy in three patients and an additional patient might have sustained a drug-related death. This study compares favorably with other studies investigating primary or secondary combination chemotherapy of advanced lymphomas.     

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.     

Imaging recommendations in pediatric lymphoma: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper

Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) are both malignancies originating in the lymphatic system and both affect children, but many features differ considerably, impacting workup and management. This paper provides consensus-based imaging recommendations for evaluation of patients with HL and NHL at diagnosis and response assessment for both interim and end of therapy (follow-up).     

Diagnosis of anterior mediastinal mass lesions using the Chamberlain procedure in children

The mediastinum is the most common site for primary intra-thoracic pathology in childhood. This paper describes the versatility of the Chamberlain operation in establishing tissue diagnosis and guiding definitive treatment in children with mediastinal mass lesions. During 1999-2006, 28 consecutive patients were referred to a National Oncology Center with anterior mediastinal pathology. Eleven underwent the Chamberlain procedure. Demographic data, diagnostic sensitivity, operating time and morbidity were recorded. All patients had preoperative chest X-ray and computed tomography scans. The Chamberlain operation was deployed in only those children without other ways of accurately establishing their diagnosis. Others with mediastinal pathology had a diagnosis established by lymph node biopsy, thoracentesis or other method(s). Eleven patients (nine male, two female; age range 2-13 years) underwent the Chamberlain procedure. In these children, there was no pre-existent diagnosis and this was the primary procedure employed. Diagnostic accuracy was 100%. Three patients had pleural disruption and chest tubes were placed at the time of surgery. No patient required a thoracotomy. Average operating time was 1.3 h. Five patients were diagnosed with Hodgkin's lymphoma, four had non-Hodgkin's lymphoma and two children thymic hyperplasia. The Chamberlain operation provides excellent access to the antero-superior mediastinum for biopsy of obscure mediastinal mass lesions in childhood. Complications from this procedure are very rare.     

Natural history of thyroid nodules in survivors of pediatric Hodgkin lymphoma

BACKGROUND: Survivors of Hodgkin lymphoma and other patients who receive neck irradiation are at increased risk of thyroid cancer. Ultrasonography provides an inexpensive and non-invasive method of thyroid screening, but the clinical significance of thyroid nodules detected by ultrasound screening is uncertain. PROCEDURE: We reviewed the demographics, clinical characteristics, method of detection, and outcome of patients who developed thyroid nodules after treatment for pediatric Hodgkin lymphoma at our institution. One radiologist reviewed all imaging studies. RESULTS: Sixty-seven children treated for Hodgkin lymphoma from 1962 to 2001 developed thyroid nodules. The study group represented 9,024 person-years of follow-up after the diagnosis of Hodgkin lymphoma and 581 person-years after diagnosis of a thyroid nodule. A median of 10.5 years (range, 0.2-24.8 years) elapsed between the diagnoses of Hodgkin lymphoma and thyroid nodule(s). All but one patient had received neck irradiation for Hodgkin lymphoma, with a median thyroid radiation dose of 35 Gy (range, 12-45 Gy). Thyroid nodules were found to be malignant in seven patients (10%), at a median of 16.2 years (range, 8.4-23.7 years) after diagnosis of Hodgkin lymphoma. Only one malignancy was found through screening ultrasonography. All patients with thyroid cancer remained disease-free at 0.4-16.2 years of follow-up. CONCLUSIONS: Thyroid nodules are common in Hodgkin lymphoma survivors treated with neck irradiation, but the majority of these lesions have an indolent clinical course and do not undergo malignant transformation. Only patients with a palpable mass or clinical symptoms need more extensive evaluation, including Doppler-flow ultrasonography and fine-needle aspiration.     

Childhood leukemia and lymphoma: correlation of clinical features with immunological and morphological studies

Malignant cells from 49 children with lymphoid neoplasms other than Hodgkin disease were evaluated by surface marker and morphologic studies. We classified the patients into three groups: 36 patients (74%) with acute lymphocytic leukemia; 7 (14%) classified as convoluted lymphocytic lymphoma/leukemia; and 6 (12%) with small noncleaved follicular center cell lymphoma/leukemia. Diffuse marrow involvement was present at diagnosis in some patients in the latter two groups, but their clinical course was not characteristic of the patients with acute lymphocytic leukemia. Male predominance, poor prognosis, and high incidence of central nervous system disease characterized patients in the convoluted lymphocytic and follicular center cell lymphoma/leukemia groups. Clinical presentation in these two groups differed. Proliferations of convoluted lymphocytes were associated with mediastinal masses and proliferations of follicular center cells with intraabdominal tumors. The high incidence of CNS disease in children with neoplasms of convoluted lymphocytes and follicular center cells suggests that these processes have a predilection for the CNS and that patients with them may benefit from CNS prophylaxis.     

经支气管针吸活检术在现代儿科介入呼吸病学的应用

经支气管针吸活检术(transbronchial needle aspiration,TBNA)是一项重要的呼吸内镜介入诊疗技术,它在纵隔、肺门、肺部外周结节病变的性质诊断,以及肺癌的分型分期等方面发挥了非常重要的作用。相较于纵隔镜及开胸探查术,TBNA具有操作简便、创伤小、费用低及并发症少等特点,在成人呼吸系统疾病得到广泛应用。但儿童因自身特点,对TBNA的技术、器材、麻醉等要求较高,应用TBNA时面临更多的挑战。随着技术的不断改进,以及儿童呼吸介入医师的不断探索,TBNA在儿童中运用也越来越多,填补了常规诊治过程中的空白,为纵隔或肺门病变患儿带来新的诊断理念和方法。     

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.     

Bone mass after treatment of malignant lymphoma in childhood.

BACKGROUND: Sex hormone deficiency, growth hormone deficiency, skeletal irradiation, and treatment with corticosteroids or methotrexate may all cause reduction in bone mass after treatment for childhood malignant lymphoma. Previous studies of the bone mass of childhood cancer survivors often lacked adequate local reference data, and survivors of malignant lymphoma were never analyzed separately. PROCEDURE: The bone mass of survivors of childhood Hodgkin disease (n = 23) or non-Hodgkin lymphoma (n = 21) was measured by dual-energy X-ray absorptiometry a median of 11 years after diagnosis (range 2-25). Results were compared with local data on 463 healthy controls. RESULTS: Adjusted for gender and age, the mean whole-body bone mineral content and bone mineral areal density were slightly, but significantly, reduced (0.5 and 0.4 SD lower than predicted). The reduced bone mineral content was associated with a significantly reduced height, whereas the size-adjusted bone mass (bone mineral content for bone area) did not differ significantly from that of controls. Lower height was related to male gender and to cranial, thoracic, and lumbar spine irradiation. Whole-body bone mineral content and bone mineral density were lower in persons treated with lumbar spine irradiation and whole-body bone mineral content was higher in nine women receiving sex hormone replacement therapy or oral contraceptives. Whole-body bone mass was not related to the cumulated doses of corticosteroids or methotrexate. CONCLUSIONS: Eleven years after diagnosis of childhood Hodgkin disease or non-Hodgkin lymphoma, the whole-body bone mass of survivors was only slightly reduced and the size-adjusted bone mass was normal.