DNAJB1‐PRKACA–positive metastatic fibrolamellar carcinoma with unknown primary in a pediatric patient

Fibrolamellar carcinoma (FLC) is a rare variant of hepatocellular carcinoma, occurring in children and young adults without underlying liver disease. The diagnosis is based on morphological characteristics of the tumor, supplemented by immunohistochemistry and/or genetic testing. Recently, the presence of a characteristic DNAJB1‐PRKACA fusion gene has been associated with FLC. Herein, we report a case of FLC presenting as peritoneal carcinomatosis in a 14‐year‐old female. Interestingly, no liver tumor was seen on imaging, and an alternative possibility is that the tumor arose outside the liver as a hepatoid carcinoma with fibrolamellar features.     

Pilocytic astrocytoma in a child with Noonan syndrome

Noonan syndrome (NS; MIM 163950) is an autosomal dominant dysmorphic syndrome characterized by distinct facial features, cardiac anomalies, short stature, and motor delay. Activating mutations in PTPN11, encoding the protein tyrosine phosphatase SHP2, are associated with about 50% of cases. Mutations in other genes in the RAS/mitogen‐activated protein kinase signaling pathway are responsible for many of the remainder of cases. While mutations in this pathway are found in a variety of malignancies, including solid tumors, there are few reports of solid tumors in individuals with NS. We report here a patient with PTPN11 mutation‐associated NS and a pilocytic astrocytoma. Pediatr Blood Cancer 2009;53:1147–1149. © 2009 Wiley‐Liss, Inc.     

Systemic mastocytosis in a child with t(8;21) acute myeloid leukemia

Mastocytosis is primarily limited to the cutaneous variant in pediatric patients. Systemic mastocytosis (SM) has been associated with t(8;21) acute myeloid leukemia (AML) in adults. We provide the first report of a child with t(8;21) AML, diagnosed with asymptomatic SM following four cycles of chemotherapy. Unlike most adults with SM/AML, she was not found to have a c-KIT (D816V) mutation. SM persisted in the bone marrow after completion of chemotherapy, and her AML relapsed 9 months off-treatment. Although she achieved a second remission, mastocytosis persists in the marrow. Pediatric patients with t(8;21) AML/SM may represent a high-risk group despite favorable cytogenetics.     

Perception and management of cancer predisposition in pediatric cancer centers: A European-wide questionnaire-based survey

The European Union-funded COST Action (LEukaemia GENe Discovery by data sharing, mining, and collaboration) LEGEND was an international and multidisciplinary collaboration between clinicians and researchers that covered a range of aspects of genetic predisposition in childhood leukemia. Within this framework, we explored the perception and handling of genetic predisposition in the daily practice of European treatment centers. Herein, we present the results of our questionnaire-based survey. We found that the overall awareness is quite high, and respondents remarked that identification and treatment of the most common predisposition syndromes were present. Nevertheless, high demand for continuous education and routinely updated resources remains.     

BCOR‐CCNB3 fusion‐positive clear cell sarcoma of the kidney

Clear cell sarcoma of the kidney (CCSK) is the second most common malignant pediatric renal tumor. Two of the recurrent somatic alterations reported in CCSK are BCL‐6 corepressor (BCOR) internal tandem duplication (ITD) and YWHAE‐NUTM2B/E gene fusion. A minority of patients with CCSKs have other rare somatic alterations. We report two patients with CCSK showing BCOR‐CCNB3 (where CCNB3 is cyclin B3) fusion, who had similar clinical presentation of a large renal mass with tumor thrombus extending through the inferior vena cava into the right atrium and a favorable response to chemotherapy. We recommend BCOR‐CCNB3 fusion testing for all patients with CCSK who lack BCOR‐ITD or YWHAE‐NUTM2B/E gene fusions.     

A case of luteinizing thecoma with sclerosing peritonitis: Revisiting a link with anti‐epileptic drugs

Luteinizing thecoma with sclerosing peritonitis (LTSP) is a rare ovarian tumor of unclear etiology and pathogenesis. The diagnostic entity was proposed in 1994, but a number of earlier reports described possible cases, and some suggested an association with anti‐epileptic drugs (AEDs). In presenting a new case we review the literature of previous cases to evaluate the possibility of such a link. When cases in reproductively immature patients are considered, evidence for an association between LTSP and AEDs is strongly suggested despite the rarity of the condition. Pediatr Blood Cancer 2010;54:470–472. © 2009 Wiley‐Liss, Inc.     

Optimal care for the child with cancer: A summary statement from the SIOP working committee on psychosocial issues in pediatric oncology

Since its foundation in 1991, the SIOP Working Committee on Psychosocial Issues in Paediatric Oncology 1 has developed and published 12 sets of Guidelines for health‐care professionals treating children with cancer and their families. Those elements considered essential in the process of cure and care of children with cancer are summarized in this document as a formal statement, developed at the 2007 SIOP annual meeting in Mumbai. Elaboration of the concepts with detailed strategies for practice can be found in the referenced guidelines [1–12] and in a companion publication [13]. This article is a summary of what practitioners considered critical elements in the optimal care of the child with cancer, with the goal of stimulating a broader application of these elements throughout the SIOP membership. Pediatr Blood Cancer 2009;52:904–907. © 2009 Wiley‐Liss, Inc.     

Clinical,histologic, and genetic features of mesothelioma in a 7‐Year‐old child

Malignant mesothelioma (MM) is a highly aggressive malignancy that is extremely rare in children. This case report documents a 7‐year‐old male without previous asbestos exposure with peritoneal MM that initially responded to chemotherapy with cisplatin and gemcitabine but ultimately metastasized to his chest. He was diagnosed with MM based on histology, extensive immunohistochemical analyses, and an elevated serum CA‐125 level. Cytogenetics and comparative genomic hybridization (CGH) analysis of his tumor identified a single extra copy number of chromosome 11 with few other changes noted. Pediatr Blood Cancer 2013; 60: 146–148. © 2012 Wiley Periodicals, Inc.     

A strategy to improve treatment‐related mortality and abandonment of therapy for childhood ALL in a developing country reveals the impact of treatment delays

Background

Treatment‐related mortality and abandonment of therapy are major barriers to successful treatment of childhood acute lymphoblastic leukemia (ALL) in the developing world.

Procedure

A collaboration was undertaken between Instituto Nacional de Cancerologia (Bogota, Colombia), which serves a poor patient population in an upper‐middle income country, and Dana‐Farber/Boston Children's Cancer and Blood Disorders Center (Boston, USA). Several interventions aimed at reducing toxic deaths and abandonment were implemented, including a reduced‐intensity treatment regimen and a psychosocial effort targeting abandonment. We performed a cohort study to assess impact.

Results

The Study Population comprised 99 children with ALL diagnosed between 2007 and 2010, and the Historic Cohort comprised 181 children treated prior to the study interventions (1995–2004). Significant improvements were achieved in the rate of deaths in complete remission (13% to 3%; P = 0.005), abandonment (32% to 9%; P < 0.001), and event‐free survival with abandonment considered an event (47% to 65% at 2 years; P = 0.016). However, relapse rate did not improve. Medically unnecessary treatment delays were common, and landmark analysis revealed that initiating the PIII phase of therapy ≥4 weeks delayed predicted markedly inferior disease‐free survival (P = 0.016). Conversely, patients who received therapy without excessive delays had outcomes approaching those achieved in high‐income countries.

Conclusions

Implementation of a twinning program was followed by reductions in abandonment and toxic deaths, but relapse rate did not improve. Inappropriate treatment delays were common and strongly predicted treatment failure. These findings highlight the importance of adherence to treatment schedule for effective therapy of ALL. Pediatr Blood Cancer 2015;62:1395–1402. © 2015 Wiley Periodicals, Inc.     

Addressing implicit bias in pediatric hematology‐oncology

Although awareness of implicit bias and its influence on providers and patients is increasing, the effects of implicit bias on the field of pediatric hematology‐oncology are less clear. This Special Report reviews the literature on implicit bias in pediatrics and medical oncology and further provides case examples and suggestions on what can be done to address implicit bias. There is a need for further research on how implicit bias impacts the complex care of pediatric hematology‐oncology patients.     

Hepatoblastoma in a Noonan syndrome patient with a PTPN11 mutation

Although Noonan syndrome (NS) is occasionally associated with embryonal solid tumors, there has been no report of hepatoblastoma in NS. We identified hepatoblastoma spreading into bilateral hepatic lobes in a 1-month-old NS patient with a heterozygous PTPN11 mutation (Asn308Asp). This finding suggests the potential relevance of constitutively activated RAS/MAPK signaling in the development of hepatoblastoma.     

Successful treatment of metachronous contralateral intratubular germ cell neoplasia with partial orchiectomy and low‐dose radiation in a patient previously treated for testicular carcinoma

Intratubular germ cell neoplasia (ITGCN) of the testis is a precursor to testicular germ cell tumor (TGCT), which can lead to the development of invasive cancer. In patients with a history of previously treated unilateral TGCT, treatment for ITGCN of the contralateral testis needs to be balanced with the risks of subsequent infertility. Here, we present a 17‐ year‐ old patient with ITGCN diagnosed after treatment of contralateral nonseminomatous TGCT who was successfully treated with a partial orchiectomy followed by low‐dose radiation with preservation of his testosterone production.      

Successful diuretics treatment of protein‐losing enteropathy in Noonan syndrome

There are few reports on successful high‐dose spironolactone treatment of refractory protein‐losing enteropathy (PLE) caused by Fontan procedure. We report successful diuretics treatment with spironolactone and furosemide at standard dose, of refractory PLE in a patient with Noonan syndrome and repaired congenital heart disease. This is the first successful application of diuretics treatment in a patient with refractory PLE without Fontan procedure. This case illustrates that diuretics treatment can be the first‐line treatment of PLE regardless of the causative physiology, and can be effective in refractory PLE with Noonan syndrome.