Peripheral neuropathy associated with hypereosinophilia.

Three patients with hypereosinophilia showed different forms of peripheral neuropathy: severe polyneuropathy of prevalently sensory type (case 1), mild sensory neuropathy (case 2), acute mononeuropathy of the median nerve with subclinical polyneuropathy (case 3). Hypereosinophilia was probably idiopathic, however the presence of atypical findings suggested transition to vasculitides or collagen disease. Sural nerve biopsy in cases 1 and 2 showed features of axonopathy in both, although of different severity, reflecting the variability of clinical involvement and, probably, heterogeneous pathogenic mechanisms. Peripheral nerve involvement associated with hypereosinophilia may be related to neurotoxicity of eosinophils, or to vascular damage.     

Radiation effects on development of HER2-positive breast carcinomas.

PURPOSE: Neither hormone-related nor genetics risk factors have been associated with the development of highly proliferative HER2-positive breast carcinomas. Because the majority of HER2-positive tumors present the amplification of the oncogene, we asked whether genomic instability triggered by irradiation might be involved in the induction of HER2-overexpressing breast carcinomas. EXPERIMENTAL DESIGN: Sixty-six infiltrating breast carcinomas from patients treated with radiation therapy for Hodgkin's lymphoma or other pediatric solid tumors and a control series of 61 consecutive sporadic breast tumors were analyzed by immunohistochemistry for HER2 expression with HercepTest. A panel of antibodies against estrogen receptor, progesterone receptor, c-kit, cytokeratin 5/6, p53, and ki67 antigen was also used to identify differentiation subsets and molecular characteristics of the analyzed breast carcinomas. RESULTS: Although no differences between the two tumor series were found with respect to HER2 expression scored 2+ and 3+, the percentage of 3+ HER2-positive tumors was significantly higher in patients irradiated during breast maturation compared with patients irradiated after breast maturation (35.3% versus 12.5%, P = 0.046). In the latter group, 52.5% of the breast carcinomas showed basal-like differentiation (estrogen receptor, progesterone receptor, and HER2 negative) versus only 5.9% in the group irradiated during breast development (P < 0.0001). Analysis adjusted for age confirmed the significant increase in basal-like tumor development in patients irradiated within 4 years of menarche, but also showed that the differences between patients irradiated before and after puberty in HER2 3+ tumor frequencies are due to age-related differences in HER2 3+ tumor onset. CONCLUSION: Together, our data indicate that the development of HER2-positive tumors correlates with timing rather than type of carcinogenic hits and provide clear evidence that radiation is a risk factor for breast carcinomas showing basal-like differentiation.     

Intensive, very short-term chemotherapy for advanced Burkitt's lymphoma in children.

PURPOSE: To improve the 63% event-free survival (EFS) achieved before 1986 in Murphy's stage III to IV Burkitt's lymphoma (BL), both chemotherapy and supportive care were intensified. PATIENTS AND METHODS: From May 1987 to February 2001, 60 children, median age 9 years (range, 2.1 to 17 years), with advanced BL were enrolled onto two sequential institutional studies. From 1987 to 1992, 30 patients were stratified according to the absence (regimen IA, n = 19) or presence (regimen IB, n = 11) of bone marrow (BM) or CNS involvement. After 5-week cytoreductive chemotherapy consisting of vincristine, cyclophosphamide, doxorubicin, high-dose (HD) methotrexate (MTX), and intrathecal MTX or cytarabine, HD cytarabine and cisplatin were provided as a 4-day continuous infusion. Regimen IB was intensified by adding etoposide and HD ifosfamide and escalating MTX doses. Since 1992, regardless of BM or CNS status, 30 patients have been placed on regimen II, which is identical to IB but without ifosfamide. The scheduled duration of regimen II was 45 days. RESULTS: EFS and disease-free survival at 5 years are 81% +/- 5% and 87% +/- 5%, respectively, for 59 assessable patients (73% +/- 8% and 85% +/- 7% for regimen IA + IB, 89% +/- 6%, EFS and disease-free survival, for regimen II; median follow-up, 6.7 years; range, 0.6 to 13.5 years). Six patients, two of whom were receiving regimen II, died as a result of initial treatment failure or relapse, and five patients, none receiving regimen II, died as a result of treatment-related complications. CONCLUSION: This 45-day intensive chemotherapy program is the shortest schedule for disseminated BL and overcomes previously recognized risk factors such as BM and CNS infiltration.     

Malignant peripheral nerve sheath tumors in children: a single-institution twenty-year experience

A retrospective series of pediatric patients with localized malignant peripheral nerve sheath tumors (MPNST) treated during a 20-year period at one institution is reported. Between 1976 and 1996, 24 consecutive children were treated by a multimodality approach. Conservative surgery was the treatment of choice: primary radical surgery was performed in 10. Postoperative radiotherapy was administered in 12 and adjuvant chemotherapy in 19. Eight patients were alive without evidence of disease, six in first complete remission and two in second complete remission, after a median follow-up of 230 months. The 10-year event-free survival (EFS) and survival were 29% and 41%, respectively. Survival was 80% for the patients who underwent radical surgery, and 14% for the others; 71% for patients with tumors smaller than 5 cm, and 29% for those with tumors 5 cm or larger. Local recurrence was the major cause for treatment failure (13 of 17; 76%); the rate of local relapse was 33% v 75% in patients who either received or did not receive radiotherapy. Complete surgical excision remains the most effective treatment for MPNST and represents the main prognostic factor along with tumor size. Radiotherapy seems to play a role in achieving local control, whereas the role of chemotherapy is uncertain.     

Survival of adults treated for medulloblastoma using paediatric protocols

We retrospectively studied 26 consecutive adults treated for medulloblastoma using paediatric protocols. Between 1987 and 2003, patients 18 years old were given adjuvant chemotherapy consisting of one of two 'paediatric' regimens (depending on the time of presentation) and craniospinal local-boost radiotherapy: regimen A (n = 12), vincristine (VCR), intrathecal and/or intravenous methotrexate and conventional radiotherapy; or regimen B (n = 11) sequencing intensive doses of multiple agents followed by hyperfractionated accelerated radiotherapy (HART). A VCR-lomustine-based maintenance followed both regimens. Three additional patients received a tailored treatment due to their impaired neurological status after surgery. The median age at diagnosis was 26 years (range 18-41 years). With a median follow-up of 46 months, 5-year disease-free and overall survival rates were 65+/-11% and 73+/-10%, respectively, for the series as a whole. All patients who received regimen B (5 of whom had metastatic Chang M2-M3 disease) are alive with no evidence of disease at 39 months. Although the number of patients is limited, our data suggest that the sandwich sequential, moderately intensive chemotherapy in combination with HART is an effective treatment for medulloblastoma in adults, and this approach seems to overcome previously-recognised risk factors.     

Carcinoid tumor of the appendix in childhood: the experience of two Italian institutions

OBJECTIVES: Although rare, carcinoid tumor of the appendix is the most common neoplasm of the gastrointestinal tract in children and adolescents. It is usually an incidental finding after a laparotomy for appendectomy, with a frequency of 2 to 5 cases per 1000 appendectomies. The experience with 14 cases of carcinoid reported in the appendix is described. METHODS AND RESULTS: In six patients the tumor measured 1 cm or less; only in one patient did it measure 2 cm. In three patients the tumor measured between 1 and 2 cm and in four the size was not known. In five cases the lesion had invaded the mesoappendix and periappendiceal fat. All tumors were discovered by chance, and three patients underwent further surgery as a result of suspected involvement of the margins. All the patients were alive with no evidence of disease at 24 to 214 months from diagnosis. CONCLUSIONS: Traditionally, local invasiveness and size have been considered prognostic factors. In our experience, both patients with local invasiveness and the patient with a tumor larger than 2 cm had good outcomes. Ileocolectomy performed in the patient with a 2-cm tumor and in another two patients with smaller tumors did not demonstrate residual disease. Although the need for right hemicolectomy still remains controversial for tumors measuring more than 2 cm, the approach may be nonaggressive in case of tumors invading the serosa and the periappendiceal fat. Nonaggressive treatment has been suggested by some authors in cases of tumors larger than 2 cm; however, larger series need to be evaluated.