Childhood intrathoracic Hodgkin lymphoma with hypertrophic pulmonary osteoarthropathy: a case report and review of the literature

Hypertrophic osteoarthropathy (HOA) is characterized by clubbing, periosteal new bone formation and polyarthritis. The pathogenesis of clubbing involves an increased expression of platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) from the digitally lodged platelet clumps, which bypass the pulmonary capillary network as a result of various systemic disorders. Intrathoracic neoplasms are rare causes of HOA in children. We report here a 14-year-old boy with digital clubbing, who eventually received the diagnosis of intrathoracic Hodgkin lymphoma (HL) and HOA. Eight cases previously reported with these two diagnoses are reviewed to emphasize the prognostic significance of HOA in childhood HL. Conclusion: Given the pathogenesis of clubbing and the prognostic significance of HOA, intrathoracic disease should be considered when HOA is detected in a child with a known or suspected malignant disease, and the occurrence of HOA during follow-up should alert the physicians for possible recurrence of the neoplastic disease or intrathoracic involvement. There is no conflict of interest associated with this report nor any sponsors.     

Hypertrophic osteoarthropathy in two children with cholestatic hepatic disease

AIM: To describe two children with hypertrophic osteoarthropathy associated with cholestatic hepatic disease. Both patients suffered from chronic progressive cholestatic liver disease and developed digital clubbing, polyarthritis and periosteal reaction. In one of them, clinical and radiological features normalized after liver transplant. CONCLUSION: Hepatic hypertrophic osteoarthropathy is a rare disabling condition that responds poorly to conservative management, while liver transplantation appears to be the only effective therapeutic intervention.     

Hypertrophic osteoarthropathy,tuberculoma of brain and cyanotic heart disease

A nine year old girl with tetralogy of fallot was admitted with right sided focal seizures and tender, swollen right elbow and knee joints. During the hospital stay there was no improvement. The patient deteriorated and died 25 days following admission. Radiological survey showed characteristic features of hypertrophic osteoarthropathy. Brain biopsy showed granulomas consistent with tuberculoma. The association of hypertrophic osteoarthropathy and cyanotic congenital heart disease is being increasingly recognised. The association of hypertrophic osteoarthropathy with tuberculoma of brain has not been reported earlier.     

Pulmonary hypertrophic osteoarthropathy in a child with late-onset agammaglobulinemia

A case of hypertrophic osteoarthropathy is described in an 8-year-old child with late-onset agammaglobulinemia, bronchiectasis and clubbing of the fingers and toes. The child presented with pain of recent onset in the legs, ankles, and knees and a diagnosis of hypertrophic osteoarthropathy was made on the basis of the radiologic findings. Therefore the differential diagnosis of bone and joint pain in agammaglobulinemic subjects must take into account hypertrophic osteoarthropathy.     

Cardiac metastasis and hypertrophic osteoarthropathy in recurrent infantile fibrosarcoma

Cardiac metastasis and hypertrophic osteoarthropathy are both quite rare. We describe a patient presenting with hypertrophic osteoarthropathy as the first symptom of recurrent infantile fibrosarcoma (IF). During surgical resection of lung metastasis, the patient suffered sudden cardiac arrest. Autopsy demonstrated a metastatic lesion in the intraventricular septum of the heart, which is previously undescribed in the literature. This case demonstrates that IF can be aggressive despite its more typical benign course.     

Hypertrophic osteoarthropathy in primary liver rhabdomyosarcoma

Hypertrophic osteoarthropathy is a well-documented paraneoplastic phenomenon in adults. It is a rare, but important finding in children with malignant disease as it can indicate prognosis. We present a case of hypertrophic osteoarthropathy associated with primary liver rhabdomyosarcoma in a 14-year-old boy.     

Prognostic factors and treatment outcome in childhood Hodgkin disease

BACKGROUND: The goals of this study included: (1) Identification of factors prognostic for event-free survival (EFS) and overall survival (OS), and (2) Definition of risk groups for risk adapted therapy in children with Hodgkin disease (HD). PROCEDURE: From 1991 to 2003, 69 children with newly diagnosed, untreated biopsy-proven stage I-IV HD were treated with chemotherapy (CT) and low-dose involved field radiotherapy (LD-IFRT). The relationship of pretreatment factors to EFS and OS was analyzed by univariate and multivariate analysis. RESULTS: The 5-year EFS and OS for all patients were 90.77% and 96.22%, respectively with a median follow-up of 73 months (3-137 months). Male to female ratio was 3:1 and 21 children (32.3%) were less than 7 years of age. Mixed cellularity was the predominant histologic subtype (38.5%). Factors associated with inferior EFS by univariate analysis were extranodal disease, hemoglobin level <11 g/dl, number of involved lymph node regions and stage. By multivariate analysis only stage IV disease was significant. CONCLUSION: Our study confirms that excellent results are achievable with combined modality therapy in childhood HD. In order to use risk-adapted therapy in children with HD, clinical prognostic factors should be validated with large, multicentered prospective clinical studies.     

Primary hypertrophic osteoarthropathy: Another heritable disorder associated with patent ductus arteriosus

Summary Patent ductus arteriosus (PDA) is a congenital malformation that has been linked to diverse heritable and chromosomal disorders. Primary hypertrophic osteoarthropathy (HOA) is a rare heritable syndrome in which digital clubbing and periostosis become evident without any underlying illness.The objective of this article is to describe four patients with coexisting PDA and primary HOA. Surgical closure of the ductus showed no effect on the skeletal changes.Primary HOA should be included among the heritable disorders that may be associated with PDA.     

Endometrial carcinoma after Hodgkin disease in childhood

A 34-year-old patient developed metastatic endometrial carcinoma after Hodgkin disease in childhood. She had ovarian failure after abdominal irradiation and chemotherapy for Hodgkin disease, and received exogenous estrogens, a treatment implicated in the development of endometrial cancer in menopausal women. Young women on replacement estrogens for ovarian failure after cancer therapy may also have increased risk of endometrial carcinoma and should be examined periodically.     

Evaluation of left ventricular function in long-term survivors of childhood Hodgkin disease

BACKGROUND: Data on the presence of myocardial abnormalities in long-term Hodgkin disease survivors are contradictory. The purpose of this study was to determine if myocardial performance index (MPI) was capable of discovering cardiac abnormalities. PROCEDURE: Echocardiographic evaluation was performed in 31 survivors of Hodgkin disease (mean age 17.0 years), who received doxorubicin as part of chemotherapeutic treatment (median dose 164.8 +/- 42.5 mg/m(2)). Control group comprised 22 healthy subjects (mean age 16.7 years). RESULTS: Peak A velocity was increased (P = 0.004) and peak E/A velocity ratio was lower (P = 0.002) in patients compared to controls. Mean isovolumetric contraction time was longer in patients than in controls (P = 0.0001). Ejection time was significantly shorter in patients than in the controls (P = 0.001). Consequently, the MPI was significantly greater in the patients than in the controls (P = 0.0001). Abnormal MPI was found in 25/31 patients (83%). CONCLUSIONS: The Doppler-derived index of combined systolic and diastolic myocardial performance demonstrates the presence of subtle cardiac abnormalities in the majority of Hodgkin disease survivors.     

Results of Treatment of 18 Children With Hodgkin Disease With MOPP Chemotherapy as the Only Treatment Modality

Eighteen children with Hodgkin disease (16 previously untreated; two relapsed) were treated with MOPP chemotherapy (nitrogen mustard, vincristine, prednisone, procarbazine) only. Ten had clinical stage I and II disease, four had stage III, and four had stage IV. In ten patients, the clinical stage was confirmed by staging laparotomy. Six courses of MOPP were given to eight stage I and II patients and two stage IV patients. Between 7 and 12 courses were given to two stage I and II, and six stage III and IV patients. Dose reduction of 75-50% was required in 13% and delay of treatment in 22% of the first six courses of MOPP. Hematologic toxicity, minor and major viral infections, and nausea and vomiting were the major complications. Complete remission (CR) was obtained in 17 patients. Of these 17, there has been one death in CR, and one relapse. Sixteen patients have discontinued treatment and have been observed off treatment for 8 months to 7.5 years. The actuarial disease-free survival with a median follow-up of 28 months is 80% and overall survival is 92%.     

Long-term pulmonary function in survivors of childhood Hodgkin disease and non-Hodgkin lymphoma

BACKGROUND: The aim of our study was to evaluate the long-term effects of chemotherapy and/or radiotherapy on lung function in 75 childhood Hodgkin disease (HD) and non-Hodgkin lymphoma (NHL) survivors several years after treatment. PATIENTS AND METHODS: We studied 37 HD and 38 NHL survivors. These patients were divided into two groups according to the treatment protocols applied. Group I consisted of 23 patients who were treated with both chemotherapy and thoracic irradiation and Group II consisted of 52 patients who were treated with chemotherapy and no thoracic irradiation. A detailed history of smoking habits, respiratory symptoms, and diseases was recorded. Complete physical examinations and pulmonary function tests [PFT, including spirometry, lung volume, and diffusion capacity for carbon monoxide (DLCO)] were performed on all subjects. RESULTS: No patients reported acute or chronic respiratory symptoms or diseases. Pulmonary function abnormality (reduced lung volume and diffusion capacity) was found in 13% of patients at a median 5 years after diagnosis. The percentage of predicted normal value of forced expiratory volume in the 1st sec (FEV(1)), residual volume (RV), and DLCO were significantly lower in Group I than these values for Group II. There were no significant differences in PFT parameters between patients with HD and NHL (P > 0.05). It appears that the risk of reduced lung function was greater the younger the patient in therapy. CONCLUSION: Chemotherapy or chemo-radiotherapy-induced pulmonary sequalae in childhood may remain asymptomatic for many years.     

Hodgkin Disease and the Role of the Immune System

Hodgkin disease (HD) is a malignancy of primarily B lymphocytes that has the unique ability to cause immunodeficiency, as well as provide immune evasion mechanisms to avoid self-destruction. In this review, the authors discuss Hodgkin disease, its association with Epstein-Barr virus (EBV), the immune deficiency caused by HD, and tumor immune evasion mechanisms. Specifically, the authors closely evaluate the roles of regulatory T cells in HD, cytotoxic T cells, cytokine and chemokine secretion, down-regulation of Fas ligand, and indoleamine 2,3-dioxygenase (IDO) secretion.     

Osteosarcoma and acute myeloblastic leukemia after therapy for childhood Hodgkin disease - A case report

A child diagnosed with Stage IVB Hodgkin disease at nine and one-half years of age subsequently developed osteosarcoma and acute myelogenous leukemia ten years after her initial diagnosis. She received multiple courses of radiotherapy and several single chemotherapeutic agents for her Hodgkin disease. Therapy-induced multiple malignancies and intrinsic predisposition to carcinogenesis in this case is discussed.     

Male gonadal function in survivors of childhood Hodgkin and non-Hodgkin lymphoma

The aim of this study was to investigate the impact of therapy on long-term gonadal function of young people cured of childhood lymphomas and to assess whether a prepubertal state during the treatment protects the gonads from chemotherapy and/or radiotherapy late effects. Clinical evaluation, semen analysis, and endocrine status were studied in 20 survivors of childhood lymphomas. Five patients received Inverted Y radiotherapy, 2320 cGy (1550-4000); all 20 received chemotherapy as follows: MOPP/ABVD protocol, 9 patients; COMP protocol, 5 patients; MOPP protocol, 3 patients; other protocols, 3 patients. Semen analysis results were as follows: normal values, 4/20 patients; oligospermia, 8/20 patients; azoospermia, 8/20 patients; FSH above normal level, 10/20 patients; 4/5 who received Inverted Y irradiation were azoospermic and 1 was severely oligospermic. Treatment damage to the testis involves tubular germinal elements. Radiotherapy and chemotherapy combinations that included nitrogen mustard or cyclophosphamide were associated with high rates of oligospermia and azoospermia. MOPP/ABVD combination did not have a significant better outcome of sperm counts compared to MOPP alone. Age at chemotherapy did not correlate with the sperm count; hence a prepubertal state did not protect the gonad from the late effects of treatment.