Pediatric Core Needle Biopsy: Strengths and Limitations in Evaluation of Masses

Needle core biopsies (NCB) are widely used in adults but are less often used for the evaluation of pediatric tumors. To determine the diagnostic utility of NCB for pediatric tumors, we performed a retrospective analysis. Fifty NCB of masses from 1992 to 1998, subsequent pathologic specimens, and medical records were reviewed. All patients were less than 21 years of age. Of the NCB 78% (39/50) were diagnostic of a neoplasm, 8% (4/50) were nondiagnostic in cases where a tumor was subsequently diagnosed, and 14% (7/50) revealed inflammatory or reactive lesions, with no subsequent diagnosis of a neoplasm according to medical record review. In cases in which a neoplasm was present, NCB was diagnostic in 91% (39/43). For cases in which there was a previous diagnosis of a tumor, 100% (9/9) of NCB were diagnostic of a recurrence or metastasis. In cases of NCB for primary tumor diagnosis, 88% (30/34) were diagnostic. The most common problems encountered were related to specimen adequacy, such as insufficient tissue, crush artifact, and tumor necrosis. Tumor diagnoses were as follows: primitive neuroectodermal tumor (PNET)/Ewing sarcoma (12), malignant lymphoma/Hodgkin's disease (8), rhabdomyosarcoma (4), germ cell tumor (3), Wilms' tumor (3), neuroblastoma (1), sarcoma, not otherwise specified (4), and other neoplasms (8). There were no complications of the procedure. NCB of pediatric tumors is an effective diagnostic tool and can be used to obtain diagnostic material quickly and safely. NCB was diagnostic in 90% of cases in this series. When NCB provide sufficient material for immunohistochemical, cytogenetic, flow cytometric, and other ancillary studies, the diagnostic efficacy is enhanced. The major limitations in this series were related to sampling problems and specimen adequacy for comprehensive pathologic evaluation. Received January 25, 2000; accepted March 17, 2000.     

Fungal infection by Paracoccidioides brasiliensis mimicking bone tumor

Paracoccidioides brasiliensis infection causes a systemic mycosis originally described in Latin America but with current reports of worldwide distribution. The clinical presentation of paracoccidiodomycosis as an isolated long-bone lesion in children is quite unusual. This article describes a 10-year-old male with a lytic femoral bone lesion caused by P. brasiliensis infection that was first suspected of being of neoplasic etiology. The text also emphasizes the importance of including endemic fungal infections in the differential diagnosis of bone lesions.     

Primary hemangiosarcoma of the spleen: Report of four cases

Four cases of primary splenic hemangiosarcoma are described. The most common presenting symptoms were recurrent fever, malaise, and abdominal pain. Three patients also had complaints referable to the urinary tract. Severe hemo-lytic anemia with bizarre or fragmented red blood cells on peripheral smear was noted in three patients, in two cases, for more than 1 year before diagnosis. Two patients had been treated for mammary carcinoma with ionizing radiation 10 years before developing hemangiosarcoma of the spleen. One patient had multiple congenital hemangiomas present from birth, and is thought to have developed hemangiosarcoma in a previously existing benign hemangi-oma. None of our patients survived more than 7 months after the diagnosis of hemangiosarcoma. The importance of early detection and treatment of this tumor is discussed.     

Prolonged 14‐day continuous infusion of high‐dose ifosfamide with an external portable pump: Feasibility and efficacy in refractory pediatric sarcoma

Background

Ifosfamide is currently used to treat pediatric sarcomas and increasing its dosage may be associated with a better response rate. Prolonged continuous infusion seems an attractive administration modality.

Methods

Ifosfamide 14 g/m² (with mesna 14 g/m²) was administered through an ambulatory portable pump over 14 days as a continuous infusion, starting every 3 weeks, in 14 patients with relapsing sarcomas. No growth factors were given.

Results

Acute grade 3 hematological toxicity was observed in only 13/66 cycles and red cell transfusions were given in two patients. Hematuria and dysuria occurred in three cases. The response rate was: five partial responses, five stable disease. The median time to progression was 3 months (range: 2–19 months). The best response rate was seen for synovial sarcoma and Ewing sarcoma.

Conclusion

Prolonged 14‐day continuous infusion of high‐dose ifosfamide is well tolerated. Potentially interesting preliminary responses in pediatric patients already treated with ifosfamide are reported. Pediatr Blood Cancer. 2010;55:617–620. © 2010 Wiley‐Liss, Inc.     

Primary cerebral rhabdomyosarcoma

Primary intracranial rhabdomyosarcomas are extremely rare tumors; those in the supratentorial location are commoner in adults. A 10 year old girl with primary cerebral rhabdomyosarcoma is presented.     

The role of adjuvant chemotherapy in children and adolescents with surgically resected, high-risk adult-type soft tissue sarcomas

PURPOSE: This analysis evaluates whether adjuvant chemotherapy can be recommended for high-risk, surgically-resected, adult-type non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) within the new European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) protocol. The Italian and German Cooperative Groups reviewed their data-bases, analyzing patients classified as group I-II, with high-grade tumor (G3) larger than 5 cm in size. METHODS: The analysis included 36 patients, and compared the clinical features and outcome of the group of 21 patients who received chemotherapy versus the group of 15 patients treated with local therapies only. RESULTS: For the series as a whole, 5-year event-free survival (EFS), metastasis-free survival (MFS), and overall survival (OS) were 26.2%, 34.0%, and 37.5%, respectively. In patients treated with chemotherapy, MFS and OS were 49.5% and 41.5% (median time to relapse: 13 months). In patients who did not receive chemotherapy, MFS and OS were 0% and 23.8% (median time to relapse: 3 months). CONCLUSION: The role of adjuvant chemotherapy in NRSTS is still uncertain, however, the current retrospective analysis showed that: (1) despite the globally good prognosis of grossly-resected cases, patients with G3 and large-size have a high-risk of metastatic spread, and (2) MFS appears to be better in patients who had chemotherapy. Based in part on these results, and in accordance with recent suggestions coming from the literature on adult sarcomas, the EpSSG NRSTS protocol will recommend adjuvant chemotherapy in high-risk surgically-resected patients.     

Ifosfamide, carboplatin, and etoposide (ICE) reinduction chemotherapy in a large cohort of children and adolescents with recurrent/refractory sarcoma: the Children's Cancer Group (CCG) experience

BACKGROUND: The prognosis for children with recurrent/refractory sarcomas is poor. We determined the overall response rate (ORR) and overall survival (OS) of children with recurrent/refractory sarcomas who were given ifosfamide, carboplatin, and etoposide (ICE) in three Children's Cancer Group (CCG) phase I/II trials. PROCEDURE: Children with recurrent/refractory sarcoma were treated with ifosfamide (1,800 mg/m2/day on day 0-4), carboplatin (400 mg/m2/day on day 0-1), etoposide (100 mg/m2/day on day 0-4) and either rhG-CSF (10 microg/kg/day vs. 5 microg/kg/day, CCG-0894, 71 patients), PIXY321 (500-1,000 microg/m2/day, CCG-0924, 14 patients), or rhG-CSF (5 microg/kg/day) and IL-6 (2.5-5 microg/kg/day, CCG-0931, 12 patients). RESULTS: Ninety-seven patients were evaluable for tumor response, 56 male and 41 female, median age 14.1 years (range 2.8-22.5 years). Tumor types were osteosarcoma (OTS) (n = 34), rhabdomyosarcoma (n = 27), Ewing sarcoma (EWS) (n = 21), soft tissue sarcoma-not otherwise specified (n = 5), undifferentiated sarcoma (n = 6), fibrosarcoma (n = 2), peripheral primitive neuroectodermal tumor (n = 1), and extraosseous Ewing (n = 1). The ORR was 51% (27% complete response [CR]). OS at 1 and 2 years was 49% and 28%, respectively. Patients with CR or partial response (PR) had significantly increased 1- and 2-year OS, 71% and 41%, respectively, (P < 0.001). Rhabdomyosarcoma patients with embryonal histology had significant improvement in 1- and 2-year OS: 82% and 46%, respectively, compared with other histologies, (P < 0.005). CONCLUSIONS: The ORR to ICE reinduction chemotherapy in children with recurrent/refractory sarcoma was 51%. OS of 1 and 2 years appeared significantly improved in patients who had CR or PR following ICE reinduction therapy or who had rhabdomyosarcoma with embryonal histology.     

Are serum levels of CD44 relevant in children with pediatric sarcomas?

BACKGROUND: Variation in serum levels of CD44, which acts as an adhesion receptor involved in lymphocyte migration and binding, have been reported in some malignancies. The aim of this study is to compare serum levels of CD44 in children with sarcomas with those in healthy children. PROCEDURE: CD44 levels were measured by enzyme-linked immunosorbent assay (ELISA) in serum samples taken at diagnosis from 55 children with sarcomas and from 27 healthy children of similar age, sex, and socioeconomic status. RESULTS: There was no statistically significant difference between CD44 serum levels of children with sarcomas and those of healthy children. No significant difference was observed between CD44 serum levels of each patient group and those of control group (P > 0.05). There was no significant difference among CD44 serum levels of patient groups according to stage or outcome. CONCLUSIONS: In this study, serum CD44 levels were not found to be of value in the diagnosis or prognosis in children with sarcomas.     

Positron emission tomography/computed tomography with 18fluoro-deoxyglucose in the detection of local recurrence and distant metastases of pediatric sarcoma

BACKGROUND: Combined positron emission tomography with (18)fluoro-deoxyglucose and computed tomography (FDG-PET/CT) has been used in the diagnosis and staging of various malignancies, but their use in the management of pediatric sarcomas is less well defined. The potential role of FDG-PET/CT in the diagnosis of local recurrence and distant metastases of pediatric sarcomas was investigated. PROCEDURE: Nineteen children (aged 2-21) with sarcoma (9 Ewing sarcoma, 3 osteogenic sarcoma, 7 rhabdomyosarcoma) were evaluated between January 2000 and December 2005 by FDG-PET/CT for suspected local relapse or distant metastases. The results of 21 FDG-PET studies, 16 CT scans, 9 magnetic resonance imaging (MRI) studies, and 7 bone scans (BSs) were compared with surgical pathology or clinical follow-up for at least 3 months. RESULTS: FDG-PET detected local relapse in all seven patients and distant metastases in 10/13 (77%). FDG-PET/CT and CT/MRI/BS results were discordant in eight patients. FDG-PET/CT was the only modality that detected distant metastases in two patients. PET/CT was true negative and excluded disease in three patients with abnormal CT/BSs and was false negative in three patients with distant metastases. CONCLUSION: FDG-PET/CT may be useful and complementary to other imaging modalities for the detection of recurrent pediatric sarcomas, especially at the primary site. Its potential advantages and limitations compared with conventional imaging modalities need to be further investigated in larger homogenous patient groups.     

Intraoperative radiotherapy in the multidisciplinary treatment of bone sarcomas in children and adolescents

From September 1984 to December 1989, 38 patients of pediatric age with localized bone sarcomas received intraoperative radiotherapy (IORT) as part of a multidisci plinary treatment program. The age ranged from 6 to 21 years. The tumor histologies were 22 osteosarcomas and 16 Ewing's sarcomas. Thirty-four had initial primary disease (90%) and 4 were treated for local recurrence (10%). IORT was used on 32 untreated patients and in 6 previously treated with external beam radiotherapy (EBR). The IORT field included the surgically exposed tumor bed area. Single radiation doses ranging from 10 to 20 Gy were delivered, using 6–20 MeV electron beams. The median follow-up time for the entire group is 25 months (2–65+ months). The projected 5-year disease-free and overall survival rates are 65% and 69%, respectively. One patient developed a local recurrence in each histological group: one chondroblastic osteosarcoma and one cervical Ewing's sarcoma. Six patients died from metastatic progression: 3 initially recurrent tumors and three primary disease cases. Severe neuropathy and soft tissue necrosis were seen in some patients as IORT related complications. IORT is a feasible technique to be integrated in multidisciplinary programs that may promote local control in pediatric and adolescent patients with bone sarcomas. Peripheral nerves are dose-limiting tissue structures for IORT.