Administration of high‐dose interleukin‐2 in a 2‐year‐old with metastatic melanoma

Malignant melanoma is rare in pediatrics, and therapies for patients with disseminated disease have not been well studied. This report describes our experience with the use of high‐dose interleukin 2 (aldesleukin, IL‐2) in a 2‐year‐old child with metastatic melanoma and describes our approach for the administration of this agent to young patients. Pediatr Blood Cancer 2009; 53:1346–1348. © 2009 Wiley‐Liss, Inc.     

Isolated central nervous system relapse of testicular cancer.

Central nervous system involvement with testicular cancer usually occurs with advanced systemic disease. Isolated CNS disease at relapse is rare. We report a patient who developed a solitary brain metastasis with no other systemic disease after having achieved a complete response to frontline therapy. After combined modality therapy for the CNS disease, the patient has remained disease-free for more than 3 years. The literature regarding brain metastases in relapsed testicular cancer is reviewed, including nine cases of isolated brain metastases. The CNS can be a "sanctuary" site for testicular cancer, and in the unusual subset of patients with isolated brain relapse, long-term remission is possible with aggressive therapy.     

Isolated central nervous system relapse of testicular cancer

Central nervous system involvement with testicular cancer usually occurs with advanced systemic disease. Isolated CNS disease at relapse is rare. We report a patient who developed a solitary brain metastasis with no other systemic disease after having achieved a complete response to frontline therapy. After combined modality therapy for the CNS disease, the patient has remained disease-free for more than 3 years. The literature regarding brain metastases in relapsed testicular cancer is reviewed, including nine cases of isolated brain metastases. The CNS can be a “sanctuary” site for testicular cancer, and in the unusual subset of patients with isolated brain relapse, long-term remission is possible with aggressive therapy.     

Position paper: Imaging methods for primary renal tumors of childhood: Costs versus benefits

The patterns of disease distribution at diagnosis and during follow-up were cataloged for the primary renal tumors of childhood. These data, derived from more than 1,500 patients, were used to define the most rewarding and cost-effective imaging methods required for patient management. The basic information needed prior to surgery includes whether there is a functioning kidney on the opposite side, and whether there are lung metastases or inferior vena cava thrombi. Simple X-ray examinations and ultrasonography (US) will provide the necessary data. Postoperatively, when the histology is known, examination of the brain (MRI or CT scan) is needed for patients with the rhabdoid tumor and clear cell sarcoma of the kidney (CCSK) who are prone to develop brain lesions; and the skeletal system (bone scan, X-ray skeletal survey) for CCSK and for renal cell carcinoma patients who tend to develop bone metastases. Continuing examination of the lung (chest films) is required for all histologies except perhaps for mesoblastic nephroma, which seldom metastasizes. The opposite kidney needs follow-up (US) for 5 or more years to exclude metachronous involvement if nephrogenic rests are present in either kidney. Sophisticated imaging studies, which cost five times or more than simple X-ray examinations or US, are not warranted routinely, and should be reserved for those cases where simpler, less expensive studies do not suffice for reaching patient management decisions. © 1993 Wiley-Liss, Inc.     

CENTRAL NERVOUS SYSTEM (CNS) TUMORS IN THE FIRST SIX MONTHS OF LIFE: The Childrens Hospital Los Angeles Experience, 1979–2005

Background: The authors report the experience at the Children's Hospital Los Angeles with brain tumors diagnosed before 6 months of age, describing the characteristics of the patients, their tumors, treatment strategies, and prognostic factors. Methods: Thirty-three children who were identified between 1979 and 2005 were included. Twelve were female (36%). There were 11 gliomas, 9 choroid plexus tumors, 8 medulloblastomas and supratentorial primitive neuroectodermal tumors (PNET), 2 atypical teratoid/rhabdoid tumors (ATRT), and 1 each of ependymoma, craniopharyngioma, and immature teratoma. Locations of primary tumors included 21 supratentorial (64%) and 7 posterior fossa, and 5 tumors involved both compartments. The treatment strategies included 5 patients with biopsy only, 18 less than gross total resections (<GTRx), and 9 GTRx. Fourteen children (42%) received chemotherapy. Three patients (9%) received irradiation, 1 at initial diagnosis and 2 at relapse. Nine patients (27%) demonstrated metastases, 6 at diagnosis and 3 at relapse. Results: The Kaplan Meier analysis of event-free survival (EFS) and overall survival (OS) for all patients is 21 ± 9% and 35 ± 9% at 5 years. For the glioma patients, the 4-year OS is 48 ± 17%, while the 5-year OS for the medulloblastoma/PNET/ATRT patients is 12 ± 11% (p = .39). The 5-year OS for children achieving a GTRx is 64 ± 21% and for those with <GTRx is 27 ± 10% (p = .08).     

Advanced small cell carcinoma of the ovary in a seventeen-year-old female, successfully treated with surgery and multi-agent chemotherapy

Advanced small cell carcinoma of the ovary (FIGO stage III or IV) is a rare and usually lethal tumor seen in adolescents and young women. In pediatric patients with advanced disease, there have been only two case reports of successful therapy, we report a third patient, diagnosed at 17 years of age, with an abdominal mass and metastatic disease to regional and distant lymph nodes, who was successfully treated with surgery and intensive multi-agent chemotherapy. Imatinib, thalidomide, and celecoxib were also administered for up to 24 months following initial chemotherapy. She remains in remission 3 years from diagnosis.     

Extensive brown tumors caused by parathyroid adenoma in an adolescent patient

Primary hyperparathyroidism is a rare endocrine disease in children and young adults. The early detection and treatment of primary hyperparathyroidism led to a marked decrease in classical bone and renal manifestations of the disease. Osteitis fibrosa cystica and brown tumors have become extremely rare clinical entities. Moreover, the skeletal involvement in primary hyperparathyroidism secondary to parathyroid adenoma is extremely rare. We report on an adolescent girl with multiple brown tumors and a history of recurrent fractures as the manifestation of primary hyperparathyroidism associated with a parathyroid adenoma. The patient’s clinical presentation mimicked parathyroid carcinoma. She had a large tumor associated with marked elevation in the parathyroid hormone and serum calcium levels. Skeletal manifestations were also atypical for benign primary hyperparathyroidism, with widespread brown tumors in the patient. None of the authors received financial support for this study.     

Follicle-derived thyroid cancer in young people: the Duke experience

Follicle-derived thyroid cancer is rare in the young. The authors examined a population with a low rate of radiation exposure and who were treated at a single institution. The records of 56 patients diagnosed before the age of 25 years were analyzed. The majority of patients presented with an asymptomatic thyroid mass. All patients were treated surgically and half received postoperative ablation with ¹³¹I. Recurrent disease was detected in 29%. The presence of local metastases at initial surgery was a predictor of recurrence. No patient presented with distant metastases and no patient died of thyroid cancer. Although radiation exposure remains a risk factor for thyroid cancer in the young, only a minority of patients with thyroid cancer have a known history of exposure. Patients who are diagnosed at a young age have a high rate of long-term recurrence, and should be followed closely throughout their lives.     

Mandibular and para-mandibular tumors in children

Sixteen cases of mandibular tumors or paramandibular soft tissue tumors with mandibular involvement are reported. These include such rare mandibular tumors or tumor-like conditions as melanotic progonoma, intraosseous haematoma secondary to von Willebrand's disease, post-irradiation osteosarcoma, monostotic eosinophilic granuloma, aneurysmal bone cyst and osseous hemangiopericytoma. Three cases of cherubism, one of fibrous dysplasia or aggressive fibromatosis and one of central giant cell reparative granuloma are also reported. The soft tissue tumors comprise round cell sarcoma, parotid adeno-carcinoma with generalised metastases, embryonal rhabdo-myo-sarcoma, neuro-fibro-sarcoma and congenital cystic hygroma. In all the cases the disease was well advanced when the patient presented for X-ray examination. The specific X-ray diagnosis of mandibular and paramandibular tumors in childhood is more difficult than that of similar tumors in other parts of the body.Presented at the 24-th Annual Meeting of the American Society for Paediatric Radiology, San Francisco, California, USA, March 22–27, 1981; Presented at the 18-th Annual Meeting of the European Society of Paediatric Radiology, Oslo, Norway, May 20–22, 1981 and at the 32-nd Annual General Meeting of the Royal Australasian College of Radiologists, Christchurch, New Zealand, September 20–25, 1981     

De Novo MYC and BCL2 Double-hit B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) in Pediatric and Young Adult Patients Associated With Poor Prognosis

MYC and BCL2 translocations in B-cell lymphomas are defined as “double-hit” associated with poor prognosis in adult patients. Such double-hit events are extremely rare in B-cell precursor acute lymphoblastic leukemia (BCP-ALL), especially in pediatric patients or young adults. This study is to investigate the clinical manifestation of de novo MYCyBCL2 double-hit BCP-ALL in young patients. Two pediatric and one young adult patients were identified after a retrospective data review and all without previous history of lymphoma. There were two females and one male aged 15, 18, and 24, respectively. All patients had an unremarkable medical history before presenting with extensive bone marrow and central nervous system involvement at diagnosis. Flow cytometry immunophenotypic analysis showed an immature B-cell immunophenotype (CD10+, CD19+, TdT+, surface Ig-) and immunohistochemistry showed high expression of MYC and BCL2 in all cases. All patients showed complex karyotypes associated with 8q24 abnormalities in the form of t(8;9)(q24;p13) or t(8;14)(q24;q32) and t(14;18)(q32;q21) and fluorescence in situ hybridization confirmed MYC and BCL2 rearrangements. Two patients died of refractory disease or disease progression 7 and 13 months after initial diagnosis, respectively, and the third patient was treated with protocol AALL0232 under the Children's Oncology Group study, achieved complete remission and remained in remission for 53 months at last follow-up. Our study showed that De novo MYCyBCL2 double-hit BCP-ALL is a rare disease that also occurs in pediatric and young adult patients and associated with complex karyotypes and poor prognosis. Younger patients may benefit from intensified chemotherapy.     

Late relapse of osteosarcoma: implications for follow-up and screening

Long-term disease-free survival in patients with localised osteosarcoma treated in large multicentre randomised trials is over 50%. Most relapses occur early, usually within 2-3 years. Relapse after 5 years is uncommon and has been infrequently described. Eight patients with osteosarcoma treated at The London Bone and Soft Tissue Tumour Service since 1986 developed recurrence of disease after 5 years, the latest 14 years after the initial diagnosis. Five patients developed pulmonary metastases, two patients isolated bone metastases and one patient intra-abdominal metastases. Although a second complete remission was achieved in six patients, four patients relapsed again, all with pulmonary metastases. Two patients had co-existent brain metastases. One of those with a second recurrence has achieved a further complete remission and remains well 50 months after the most recent treatment. A second patient is disease-free 24 months after complete excision of an isolated pulmonary metastasis and one further patient is disease-free 6 months after chemotherapy and pneumonectomy for pleural and pulmonary metastases. Five patients have died of disease with a median survival from the date of relapse of 17 months (2-68 months). Current data looking at long-term outcome of patients with osteosarcoma is limited. Reports of late relapse are rare as numbers are small, thus long-term surveillance of patients is essential. It is possible that sites of relapse are more unusual, and more extensive staging may be necessary when late relapse occurs.     

High-dose-rate brachytherapy in childhood sarcomas: A local control strategy preserving bone growth and function

The administration of external beam radiation therapy (EBRT) has been an integral part of the successful treatment of childhood sarcomas. However, EBRT has severe late morbidity in the developing child. In an attempt to deliver adequate tumoricidal radiation while preserving bone growth and organ function, 13 children with diverse sarcomas were treated with high dose rate brachytherapy (HDR). Seven patients had rhabdomyosarcoma and six patients had other soft tissue sarcoma variants. All patients were treated with disease-appropriate chemotherapy, usually according to the Intergroup Rhabdomyosarcoma Study. Eleven patients received fractionated 36 Gy HDR alone at a mean of 3.5 months from diagnosis. Two patients received 10–12.5 Gy intraoperative HDR brachytherapy and additional 27 Gy EBRT. Nine of 11 patients in first remission have had no recurrences. One died of recurrent pulmonary metastases. The other patient that did recur is disease-free 21 months post-recurrence. Two additional patients were treated with HDR after tumor recurrence. One patient with recurrent Ewing's sarcoma, relapsed and died. The second is disease free 3 months after autologous bone marrow transplant. Grade 1 morbidity occurred in 46%, Grade 2 in 15%, and Grade 3 in 8% of the children, while relatively good bone and organ growth was maintained. The combination of conservative surgery, chemotherapy, and HDR offers the potential for disease control in young children while preserving bone growth and organ function. © 1995 Wiley-Liss, Inc.     

Differentiated thyroid cancer

Objective: The retrospective analysis of the case files of children with differentiated thyroid carcinoma (DTC) was performed to define the disease by its presentation, clinical course and outcome of radioiodine therapy.Methods: Between 1967 to October 2002,1754 patients with thyroid cancer were treated in the Dept of Neuclear Medicine, AIIMS, out of which 122 (7%) were ≶ 20 years of age (71 girls and 51 boys). The mean age was 15.8 ± 3.6 years and the mean duration of follow-up was 90 ± 59.3 months. Mean tumor size was 4.4 cm. Histologically, 85% of the patients had papillary and rest follicular carcinoma. Cervical lymph node involvement was seen in 64%, and distant metastases, mainly pulmonary, in 23% of the patients. The presentation of the disease was very aggressive in the first decade of life with male preponderance. All but one patient in this age group had nodal and/or distant metastases; in 83.3% the disease had spread to the lymph nodes and 67% had metastases to the lungs. The post-surgery 48-hour mean radioiodine neck uptake was 10.5 ± 7.6%.Results: 94% of the residual thyroid, 88% of nodal metastases and 71% of pulmonary metastases were ablated requiring mean cumulative doses of 2.8 ± 2.7 GBq, 4.5 ± 2.7 GBq and 10.4 ± 7.9 GBq of¹³¹I, respectively. Average number of doses required for remnant, nodal and pulmonary metastases ablation were 1.3, 2.2 and 3.3, respectively. 80% of the patients with only remnant thyroid tissue and 50% with cervical lymph node metastases got ablated with a single dose of¹³¹I. Overall, 87% patients were currently free of disease. While, nine patients had nodal recurrence between surgery and radioiodine treatment, no recurrence was observed thereafter and 3 disease related deaths producing overall mortality of 2.5% (all in children ≶10 years of age) were seen in the mean follow-up of 7.5 years.Conclusion: Differentiated thyroid cancer in children and adolescents is rare but aggressive. The biological behavior differs from that in adults and is related to the age. Younger the age (≶10 years), more aggressive and widespread is the disease with male preponderance and high mortality. The Post-surgical radioiodine ablation/therapy is an important and effective adjuvant in the management of DTC in children and adolescents and even though they present with advance disease, long-term survival and overall prognosis is good.     

PET-CT in detection of meningeal metastasis in neuroblastoma

Neoplastic meningitis is being recognized with increasing frequency in patients with cancer: the common causes being adenocarcinomas originating from the lung, stomach, breast, ovary, malignant melanoma, leukemia, lymphoma, Ewings sarcoma, rhabdomyosarcoma, retinoblastoma and primary CNS malignancies. Meningeal metastases, though rare can be seen in advanced stages of neuroblastoma. Recognition of meningeal metastases is crucial for successful diagnosis and prompt treatment of these patients. Here, we present two patients of neuroblastoma in whom positron emission tomography-computed tomography (PET-CT) examination resulted in detection of meningeal metastases at diagnosis; thus, emphasizing the need of inclusion of brain imaging in PET-CT protocol in all cases of advanced neuroblastoma.     

The role of high‐dose chemotherapy and stem cell rescue in the treatment of malignant brain tumors: A reappraisal

Abstract: The outcome for children with malignant brain tumors has improved modestly in recent years. Notable is the improved 5‐yr disease‐free survival for those children with 'standard‐risk' medulloblastoma and other primitive neuro‐ectodermal tumors (PNET) (i.e. tumors without neuraxis dissemination at presentation). For other children with newly diagnosed malignant brain tumors, especially in the absence of radical surgical resection, the outcome remains poor despite surgery, irradiation and conventional chemotherapy. Patients whose tumors recur despite initial therapy continue to experience a dismal outlook with these conventional strategies of treatment. In an attempt to improve the outlook for such brain tumor patients with poor prognoses, strategies utilizing high‐dose (potentially myeloablative) chemotherapy with autologous stem cell rescue have been developed. These studies, conducted initially in patients with recurrent tumors, were then extended to patients with newly diagnosed malignant gliomas and brain‐stem tumors, as well as to young children with various malignant brain tumors at diagnosis in an attempt to avoid irradiation to the brain. The results of several of these studies are summarized, updating information reviewed in an earlier summary in 1996, demonstrating durable disease‐free survival for a proportion of patients with recurrent malignant gliomas and medulloblastomas/PNET, as well as encouraging data in some of those patients with newly diagnosed brain tumors.     

Bone and gallium scintigraphy in children with rhabdomyosarcoma: A 10-year review

Technetium-99m bone and Gallium-67 scintigraphy has been widely used in the management of children with solid tumors. A retrospective review of all patients with rhabdomyosarcoma (RMS) from January 1980 to December 1989 was undertaken in order to determine the sensitivity and specificity of scintigraphy in detection of metastatic disease and to determine optimum frequency of serial scans in follow up. Over the 10-year period, 40 patients were diagnosed and treated for RMS: 22 were newly diagnosed from 1980-1984 and of these 16 had a minmum 5-year disease-free period whilst 6 died of the disease, giving a cure rate of 73%. A total of 271 bone and 236 Gallium-67 scans were performed. With respect to detection of metastatic disease in all tissues, Gallium-67 scans had a sensitivity of 84%, specificity 95% and bone scans had a sensitivity of 70% and specificity 95%. Bone scan sensitivity and specificity for skeletal metastases were 100% and 95%, respectively. Considering only patients with Gallium avid primary tumors, the Gallium-67 scan sensitivity was 94%. Ten patients developed new metastatic disease or primary recurrence after starting therapy, 8/10 within 12 months of diagnosis. Frequent surveillance scanning in the treatment phase, 2 years post-diagnosis, is of value in the early detection of metastases and monitoring disease response to therapy. Surveillance scanning after completion of treatment is more difficult to justify.     

Occult trauma mimicking metastases on bone scans in pediatric oncology patients

Background. Tracer-avid osseous lesions are usually considered to represent metastases in pediatric oncology patients. However, sites of minor, clinically occult, skeletal trauma may be mistaken for osseous metastases. Objective. The objective of this study was to review our experience with skeletal scintigraphy in pediatric oncology patients to determine specificity for metastatic disease. Materials and methods. We reviewed 164 bone scans performed on 96 consecutive patients (ages 5 months to 23 years) at presentation with malignancy or during chemotherapy. Tumors included osteosarcoma (13), Ewing sarcoma (11), lymphoma (19), neuroblastoma (12), brain tumors (16), rhabdomyosarcoma (10), renal tumors (5), and miscellaneous neoplasms (10). Scintigraphic abnormalities were considered metastatic based on radiographic findings, subsequent tumor progression, or multiplicity of lesions. Lesions were considered benign when spontaneous resolution occurred without change in therapy or radiographs demonstrated a traumatic or other benign lesion. Results. Of the 96 patients, 51 had normal studies or showed only the primary lesion. Of the 45 patients with abnormal scintigraphy, 16 (35 %) had metastases and 29 (65 %) had one or more focal benign lesions. These lesions included abnormalities due to stress/trauma (25), benign neoplasm (2), infection (3), disuse (6), surgery (10) and artifacts (4). Conclusion. The majority of scintigraphic abnormalities have nonmalignant etiologies, most commonly stress reaction and trauma. In patients without known extraosseous metastases, one or two skeletal lesions should not be assumed to represent metastatic disease. Received: 11 December 1995 Accepted: 28 June 1996     

Isolated intracranial metastasis of neuroblastoma 2 years after completion of therapy

Metastatic neuroblastoma in the brain without evidence of intracranial or extracranial disease elsewhere, is a very rare event. The pattern of spread is believed to be via the hematogenous route or cerebrospinal fluid. A child with a cystic neuroblastoma mass in the right temporal lobe 23 months following completion of therapy for the initial disease is described here. Chemotherapy with the protocol ‘eight drugs in 1 day’ was initially effective for this patient.     

HIGH-DOSE BUSULFAN AND MELPHALAN AS CONDITIONING REGIMEN FOR AUTOLOGOUS PERIPHERAL BLOOD PROGENITOR CELL TRANSPLANTATION IN HIGH-RISK EWING SARCOMA PATIENTS: A Long-Term Follow-Up Single-Center Study

The aim of this retrospective study was to analyze the outcome and identify risk factors associated to progression-free survival (PFS) in 47 children with high-risk Ewing sarcoma who underwent autologous peripheral blood stem cell (PBSC) transplantation in the authors’ institution between 1995 and 2009. The conditioning regimen used in all patients consisted of high dose of busulfan and melphalan. Median age was 13 years (range: 4–21 years). Forty-three percent of patients had metastases at diagnosis. The probability of transplant-related mortality (TRM) was 6% ± 3%. Recurrence/progressive disease was observed in 17 patients. The probability of recurrence/progression was 39% ± 7%. With a median follow-up of 92 months (range: 6–168 months), the PFS was 56% ± 4% for the whole group. In multivariate analysis, localized disease at diagnosis and obtaining complete remission (CR) by 3 months after transplantation were variables associated to better outcomes. The probability of PFS was 78% ± 8% and 27% ± 10% for patients with localized and metastatic disease at diagnosis, respectively (P = .0001). This retrospective study shows a high long-term survival using high dose of busulfan and melphalan as conditioning regimen in children with high-risk Ewing tumors. Patients with localized disease at diagnosis and those with good response to treatment before or after transplant would benefit most.     

THYROID CANCER IN LEBANESE CHILDREN AND ADOLESCENTS: A 15-Year Experience at a Single Institution

Background and Aim: Thyroid carcinomas are rare in childhood and adolescence. Management of this entity remains controversial. The aim of this study is to review our experience with multidisciplinary management of papillary thyroid cancer in the pediatric population at a tertiary care specialized medical center in Lebanon. Procedure: The medical records of all patients with thyroid cancer younger than 20 years who presented to our center between January 1991 and January 2006 were reviewed. Results: Thirteen patients with papillary thyroid carcinoma (PTC) were identified. No patient had previous exposure to ionizing radiation. The mean age at diagnosis was 14.5 years. There were 8 females; all patients presented with a cervical mass. Ten patients underwent total thyroidectomy and three subtotal thyroidectomy. Eight patients (61.5%) had regional lymph node metastases, only one of whom (7.6%) had lung metastases. All received radioactive “131I” ablation postsurgical excision. Five (38.5%) had recurrences and needed multiple surgeries and/or “131I” ablation. At a median follow-up time of 8.3 years all patients are disease free. Conclusion: Pediatric thyroid cancer in Lebanon is a rare tumor that presents mainly as a primary malignancy. The main clinical presentation is a cervical mass with locoregional lymph nodes metastasis. The mainstay of therapy is total thyroidectomy with lymph node dissection when indicated and radioactive “131I” ablation. Despite recurrences the prognosis is excellent.