Childhood Malignant Thymoma: Clinical, Therapeutic, and Immunohistochemical Considerations

Malignant thymomas are among the least common mediastinal tumors in the pediatric age group. Thymomas are considered malignant on the basis of macroscopic and microscopic invasiveness. As only 20 well-documented cases involving children have been reported in the literature, the pattern of responsiveness to therapy and the value of prognostic signs is obscure. Two cases of malignant pediatric thymomas are reported with pathognomonic histoimmunological features of aggressive thymoma. One was cured, with a follow-up of 70 months, and one died while on therapy. Analysis of the histological features and the immunoperoxidase staining displays the complexity of pediatric thymomas and the inability to prognosticate the outcome, respectively.     

Clinical and laboratory manifestations of congenital dyserythropoietic anemia type I in young adults

OBJECTIVES: Congenital dyserythropoietic anemia (CDA) type I is a rare autosomal recessive macrocytic anemia whose natural history is not well documented. The aim of the present study was to evaluate the clinical picture of the disease in young adults. METHODS: The study sample consisted of 17 patients of mean age 11.9 +/- 5.4 yr (range 18-33 yr) and one older patient (age 44 yr), all Israeli Bedouins. The degree of anemia was evaluated as well as the extent of development of gallstones and iron overload. In each subject we determined the hemochromatosis gene mutations and the uridine dyphosphate-glucoronosyltransferase (UGT-1A) gene polymorphism associated with Gilbert's syndrome. RESULTS: The patients were found to have moderate anemia, with the women displaying lower mean hemoglobin levels than the men (8.2 +/- 0.9 g dL(-1) vs. 10 +/- 1.3 g dL(-1); P=0.0059). The majority of patients (59%) had received at least one blood transfusion, with the women having a significantly higher transfusion requirement. Although delayed puberty was noted, final height and weight were within normal limits, and eight patients had progeny. Biliary stones were found in three of 16 patients, two of whom were homozygous for UGT-1A gene polymorphism. None of the patients carried the common hemochromatosis gene mutation, although serum ferritin levels were moderately elevated (788 +/- 332 ng mL(-1)). CONCLUSIONS: CDA type I in young adults is characterized by moderate macrocytic anemia, more severe in women, and a tendency to cholelithiasis and secondary progressive iron overload. We suggest that iron overload in this patient population should be monitored and chelation therapy initiated when indicated to prevent organ damage     

Pregnancy outcome in congenital dyserythropoietic anemia type I

Objectives: Congenital dyserythropoietic anemia type I (CDA I) is a rare inherited disease characterized by moderate to severe macrocytic anemia and abnormal erythroid precursors with nuclear chromatin bridges and spongy heterochromatin. Moderate to severe maternal anemia is a recognized independent risk factor for low birth weight (LBW) and complicated delivery. The aim of the study was to review the outcome of pregnancies in women with CDA I. Methods: The clinical and laboratory records of 28 spontaneous pregnancies in six Bedouin women with CDA I were reviewed. The results were compared with findings from a retrospective review of a large population‐based registry including all pregnancies in Bedouin women during the same 15‐yr period. Results: Eighteen pregnancies in women with CDA I (64%) were complicated. One pregnancy was aborted spontaneously in the first trimester and one resulted in a non‐viable fetus (stillborn at 26 wk). Cesarean section (CS) was performed in 10 pregnancies (36%). Eleven of the 26 newborns (42%) had a LBW: six were born prematurely and five were small for gestational age. The odds ratio for CS in women with CDA I compared with healthy Bedouin women was 4.5 [95% confidence interval (CI) 1.2–10.3], and for a LBW infant, 5.5 (95% CI 2.4–12.3). Careful follow‐up was associated with significantly better fetal outcome (P = 0.05). Conclusions: Pregnancies in women with CDA I are at high risk for delivery‐related and outcome complications. To improve fetal outcome, women with CDA I should be carefully monitored during pregnancy.     

Iatrogenic hyperthyroidism does not promote weight loss or prevent ageing-related increases in body mass in thyroid cancer survivors

Context Thyroid cancer survivors represent a unique population in which the potential long‐term effects of brief periods of intentional thyroid hormone withdrawal and/or prolonged periods of iatrogenic hyperthyroidism on body weight and body mass were evaluated. Objectives The objectives of this study were to characterize body mass changes over several years in a cohort of thyroid cancer patients with iatrogenic hyperthyroidism and to compare these changes with the expected weight gain in age‐matched healthy control populations. We also evaluated the possibility that the method of preparation [thyroid hormone withdrawal (THW) vs recombinant human TSH (rhTSH)] for radioactive iodine remnant ablation may be associated with differences in body mass at the time of the final follow‐up. Design/Setting/Patients/Interventions A retrospective review identified 153 patients with thyroid cancer who underwent total thyroidectomy at one major medical centre. Of the 153 patients, 143 also had radioactive iodine remnant ablation: 70 after THW and 73 after rhTSH. Main Outcome Measures Change in weight and BMI at 1–2 and 3–5 years of follow‐up points were examined. Annualized weight variation within the cohort was compared with age‐matched population controls expressed in kilogram/year. Results Significant weight gain was noted for the full cohort after 3–5 years of follow‐up as compared to baseline (76 ± 21 kg at baseline vs 79 ± 23 kg at 3–5 years of follow‐up, P < 0·01), which represented a 3·2% increase. Female and male patients with thyroid cancer experienced 0·46 and 0·94 kg/year gain in weight, respectively, which is similar or somewhat higher than previously published age‐matched population controls (ranging from 0·23 to 0·34 kg/year). When expressed as per cent change and comparing the final weight to the pre‐operative baseline, the rhTSH group experienced approximately a 1·7% increase in weight compared with the 3·9% increase seen with THW patients (P = 0·02). When expressed as kg/year change, the rhTSH cohort had 0·34 kg/year change compared with the 0·64 kg/year change seen in the thyroid hormone withdrawal patients (P = 0·02). Conclusion In otherwise, healthy patients with differentiated thyroid cancer, significant weight gain occurred during the 3–5 years of follow‐up despite ongoing thyrotropin suppression. The data suggest that mild iatrogenic hyperthyroidism does not promote weight loss or prevent ageing‐related weight gain. Greater weight gain was seen in patients prepared for radioactive remnant ablation with THW than with rhTSH.     

Outcome and management of pregnancies in severe chronic neutropenia patients by the European Branch of the Severe Chronic Neutropenia International Registry

Long-term granulocyte-colony stimulating factor treatment has been shown to be safe and effective in severe chronic neutropenia patients. However, data on its use during pregnancy are limited. To address this issue, we analyzed all pregnancies reported to the European branch of the Severe Chronic Neutropenia International Registry since 1994. A total of 38 pregnancies in 21 women with chronic neutropenia (16 pregnancies in 10 women with congenital, 10 in 6 women with cyclic, 12 in 5 women with idiopathic neutropenia) were reported. Granulocyte-colony stimulating factor was administered throughout pregnancy in 16 women and for at least one trimester in a further 5 women. No major differences were seen between treated and untreated women with respect to pregnancy outcome, newborn complications and infections. In addition, we evaluated the genetic transmission of known or suspected genetic defects in 16 mothers having 22 newborns as well as in 8 men fathering 15 children. As a proof of inheritance, neutropenia was passed on to the newborn in 58% from female and in 62% from male patients with ELANE mutations, but also to some newborns from parents with unknown gene mutation. Based on our results, granulocyte-colony stimulating factor therapy has been shown to be safe for mothers throughout pregnancies and for newborns without any signs of teratogenicity. With an increasing number of adult patients, genetic counseling prior to conception and supportive care of mothers during pregnancy are crucial. The acceptance of having affected children may reflect the high quality of life obtained due to this treatment.     

T-cell acute lymphoblastic leukemia following therapy of rhabdomyosarcoma.

Multiple studies have documented an increased risk of secondary malignancies in patients receiving alkylating agents. Secondary leukemia following chemotherapy accounts for about 20% of all secondary neoplasms; most are acute nonlymphocytic. Secondary acute lymphoblastic leukemia has rarely been reported in either adult or childhood cancer. We report the development of acute T-cell lymphoblastic leukemia in a child following successful treatment of a paravertebral embryonal rhabdomyosarcoma (ERS). Southern blot analysis of DNA extracted from the T-cell lymphoblasts, using probes homologous to loci on the short arm of chromosome 11; P-calcitonin, P40.1 and H-ras, did not demonstrate the chromosomal loss of heterozygosity (LOH), a common feature of embryonal rhabdomyosarcoma. The data presented support the assumption that de novo leukemia emerged following treatment of the primary malignancy.