Xeroderma pigmentosum in four siblings with three different types of malignancies simultaneously in one

Xeroderma pigmentosum (XP) is a rare autosomal recessive disease characterized by marked sensitivity to ultraviolet radiation that leads to the development of multiple skin malignancies. The authors describe four XP siblings in a consanguineous Pakistani family. The first patient was a boy who died at age 2 years. The second and third siblings were girls who died at age 2 and 7 years, respectively. The fourth sibling, the propositus, was a boy diagnosed with XP at age 7 years. He developed three different types of malignancies simultaneously and died at age 13. The authors conclude that it is important to be aware of multiple malignancies of different types in the same patient with XP.     

Dramatic response to nivolumab in xeroderma pigmentosum skin tumor

We report the case of a 6‐year‐old female with xeroderma pigmentosum (XP) who developed a nonoperable scalp tumor, treated with anti‐programmed cell death protein 1 (anti‐PD‐1) therapy (nivolumab). She presented with a sarcomatoid carcinoma of the scalp with bone lysis as well as vascular and meningeal contact. Nivolumab was initiated because it has emerged as a promising immunotherapy. We observed a dramatic tumor response with excellent tolerance. However, while on nivolumab therapy she developed two large skin melanomas and several squamous cell carcinomas, which have been resected. These results demonstrate that cancer immunotherapy in patients with XP can be impressive but complex and warrants further investigation.     

Bronchioloalveolar carcinoma as a second malignancy in osteosarcoma survivors

Second malignancies occur in 2–3% of survivors of pediatric osteosarcoma; treatment‐related hematologic and solid malignancies have both been described. We present two cases of patients with pulmonary nodules that developed more than 2 years after treatment of osteosarcoma. Both lesions were completely resected and pathology revealed bronchioloalveolar carcinoma (BAC). Primary BAC is extremely rare in children; however, cases of this malignancy have been described in survivors of pediatric cancer. BAC may present as a solitary pulmonary nodule indistinguishable from a metastatic lesion and should be included in the differential diagnosis of pulmonary nodules in survivors of pediatric cancer. Pediatr Blood Cancer 2009;53:499–501. © 2009 Wiley‐Liss, Inc.     

Primary epithelial lung malignancies in the pediatric population

BACKGROUND: Primary epithelial lung malignancies are rare in childhood and adolescence. We reviewed the Memorial Sloan-Kettering Cancer Center experience with these tumors to better understand their histology, time to diagnosis, treatment, and outcome. PROCEDURE: A retrospective review was performed on all patients 21 years of age or younger at diagnosis, treated for primary epithelial lung malignancies at Memorial Sloan-Kettering Cancer Center between 1980 and 2001. RESULTS: We identified 11 patients with primary epithelial lung malignancy. The median age at diagnosis was 19 (range: 12-21) years. The most common radiographic abnormality was a mass (55%) on chest imaging. Seven patients (64%) were initially diagnosed as having pneumonia which contributed to a delay in diagnosis. Final pathologic diagnoses included adenocarcinoma (four), carcinoid tumor (three typical, one atypical), basaloid carcinoma (two), and mucoepidermoid carcinoma (one). A majority of patients presented with advanced disease (two stage III, four stage IV). Patients with localized disease were treated with surgical resection and all but one remains disease free with a median follow-up of 60 months (range: 13-286). Patients with either advanced locoregional or distant metastatic disease were treated with multimodal therapy and a majority had rapid progression of disease. CONCLUSIONS: When children and adolescents present with primary epithelial lung malignancy a majority will have advanced disease and experience a delay in diagnosis. The histologic types of tumors encountered are similar to lung tumors occurring in adults, although the frequency of the various types differs. Carcinoid tumors are more frequent, and less common subtypes of bronchogenic carcinoma are also more prevalent in the pediatric age group. Similar to the adult population, the prognosis of these tumors is dependent on histology and stage. Patients with carcinoid tumors seem to have the best prognosis, followed by adenocarcinoma. The highly aggressive basaloid carcinoma has the worst.     

Cis-diamminedichloroplatinum (NSC-119875) in childhood malignancies: A southwest oncology group study

Children with malignancies resistant to conventional therapy were treated with cis-diamminedichloroplatinum (PDD), 1 5 to 20 mg/m², given daily by rapid intravenous infusion for 5 days at 3-wk intervals. Eleven of 24 children with acute lymphocytic leukemia (ALL) received two or more courses; among these no remissions occurred. Fifty-four children with solid tumors were treated: 25 neuroblastoma, 9 rhabdomyosarcoma, 4 Ewing sarcoma, 2 testicular embryonal carcinoma, 2 retinoblastoma, and 12 miscellaneous tumors. One complete remission, 3 partial remissions, and 2 improvements were observed in children with neuroblastoma. One girl with metastatic osteogenic sarcoma achieved a partial remission. One child with metastatic testicular embryonal carcinoma showed improvement. The side effects were vomiting controlled by antiemetics in 26 children and transient elevations of serum creatinine and BUN in 14 children. Nineteen of 39 children with solid tumors, who received more than one course of PDD, had moderately severe myelosuppression caused by PDD. In summary, PDD is a promising agent in neuroblastoma, osteogenic sarcoma, and testicular embryonal carcinoma, and an ineffective agent in ALL. The effect of PDD on other types of solid tumors should be evaluated in the future.     

Imaging of pediatric liver tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper

Primary hepatic malignancies are relatively rare in the pediatric population, accounting for approximately 1%–2% of all pediatric tumors. Hepatoblastoma and hepatocellular carcinoma are the most common primary liver malignancies in children under the age of 5 years and over the age of 10 years, respectively. This paper provides consensus-based imaging recommendations for evaluation of patients with primary hepatic malignancies at diagnosis and follow-up during and after therapy.     

Bloom Syndrome in Sibs: First Reports of Hepatocellular Carcinoma and Wilms Tumor with Documented Anaplasia and Nephrogenic Rests

The triad of small body size, immunodeficiency, and sun-sensitive facial erythema characterizes the phenotype Bloom syndrome (BS), a rare autosomal recessive disorder with a striking predisposition to multiple types of cancers that arise earlier than expected in the general population. Here we report two sibs with BS. The older, a 15-year-old-girl, developed a hepatocellular carcinoma, a neoplasm not yet reported in association with BS. Her younger brother developed an anaplastic Wilms tumor (WT) associated with nephrogenic rests at the age of 31/2 years, and this was followed by a myelodysplastic syndrome. Complex cytogenetic abnormalities were identified in all three neoplasms. These examples expand the spectrum of malignancies occurring in BS to include liver cell neoplasms, and confirm the association of nephrogenic rests with WT, even in the setting of BS. Received December 12, 2000; accepted April 25, 2001.     

Multivisceral transplantation for abdominal tumors in children: A single center experience and review of the literature

Standard management of intra‐abdominal pediatric solid tumors requires complete resection. However, tumors with multiple organ and vascular involvement present a unique surgical challenge. We conducted a retrospective chart review of four patients, aged 2‐14 years, undergoing MVT for intra‐abdominal tumors with significant involvement of the visceral arteries and/or portomesenteric venous system at our institution. Indications for MVT included hepatocellular carcinoma, inflammatory myofibroblastic tumor, and two cases of hepatoblastoma. Grafts included liver, stomach, small bowel, and pancreas in all patients, with two patients also receiving spleens, and one, a partial esophageal transplant. Median hospital stay was 80 days. Postoperative complications included reoperation for abdominal hematoma and bowel obstruction, steroid responsive intestinal rejection, wound dehiscence, fungemia, seizures, and chyle leak with pleural effusion. One patient developed Epstein‐Barr virus‐associated complications which responded well to treatment. On follow‐up (range 2.8‐7.8 years), all patients have satisfactory graft function and no evidence of recurrent disease. MVT is an effective means of achieving complete gross resection of intra‐abdominal malignancies in patients with multiple organ and vascular involvement.     

Malignancies in Down Syndrome

Down Syndrome (DS) is associated with an increased incidence of malignancies, especially leukaemias. We came across 8 DS children presenting with malignancies and having trisomy 21 as the sole cytogenetic abnormality. Of these 8 DS cases, 4 presented with acute lymphocytic leukaemia, 2 with acute myeloid leukaemia and one case each with Hodgkin’s disease and Wilms’ tumour. There are contradictory reports regarding the distribution of myeloid versus lymphoid malignancies in DS children and their response to therapy. The exact mechanism by which patients with DS are predisposed to develop malignancies is unclear. However, presence of the extra chromosome no. 21 is presumed to disrupt the genetic balance which increases generalized susceptibility to genetic and environmental trauma. Furthermore, an increased methotrexate toxicity observed irv these patients should also be taken into consideration in designing treatment for DS children with malignancies.     

A method to overcome the inability to draw blood from central venous lines in children

The insertion of central venous catheters has become an established practice in the management of children with different types of malignancies for the administration of chemotherapeutic agents, antibiotics, blood and blood products, as well as drawing blood for various investigations. A commonly encountered problem is that despite the catheter being patent it may be impossible to draw blood from it. We believe this is related to the cut of the catheter tip. To overcome this problem, a technique for cutting the tip of the catheter is described. Accepted: 23 February 1999     

Colorectal adenocarcinoma as a second malignant neoplasm following Wilms' tumor and rhabdomyosarcoma

Colorectal carcinoma is one of the most common primary malignancies in adults and occurs in older patients after pelvic radiation. It is rare in children and young adults. We report two cases of colonic adenocarcinoma which were second malignant neoplasms following treatment for early childhood malignancies. One child had Wilms' tumor at 9 months of age treated with preoperative radiation and surgery. He developed radiation colitis and multifocal intestinal adenocarcinomas 42 years later and died with abdominal carcinomatosis. The second child had retroperitoneal embryonal rhabdomyosarcoma at age 1 year and was treated with preoperative radiation, surgery, and chemotherapy. At age 2 years he had radiation colitis; at age 11 years he had rectal adenocarcinoma associated with adenomatous polyps, focal adenomatous change and radiation colitis. Immunohistochemical studies revealed p53 positivity in both adenocarcinomas and in adenomas from the second patient, suggesting that p53 mutation was involved in carcinogenesis. The history of high-dose radiation in early childhood and the multifocal lesions suggest the adenocarcinomas in both patients were second malignant neoplasms, with associated reactive and benign neoplastic and premalignant lesions well documented in one case. These two cases document the phenomenon of early onset of adult type tumors in survivors of childhood cancer and emphasize the need for continued clinical evaluation of patients at risk for second malignant neoplasms. © 1996 Wiley-Liss, Inc.     

Laparoscopic ovariopexy for paediatric pelvic malignancies

Ovariopexy can prevent radiation damage to the ovaries in children undergoing pelvic irradiation, and should be considered prior to radical curative radiotherapy. We report two children who have had successful laparoscopic ovariopexy, and advocate its use in conjunction with local radiotherapy in childhood malignancy. It reduces iatrogenic trauma significantly and assists with staging and managing paediatric pelvic malignancies. Correspondence to: H. L. Tan     

Mucoepidermoid Carcinoma of the Parotid Gland in Childhood Survivor of Acute Lymphoblastic Leukemia With Need of Radiotherapy for Treatment and Review of the Literature

Diagnosis of secondary malignancies began with the increasing survival in childhood cancer. Children treated for acute lymphoblastic leukemia (ALL) have an increased risk for developing mucoepidermoid carcinoma (MEC) of the parotid gland. The latent period ranges from 5 to 16 years. A 2 6/12-year-old girl was treated for pro-B ALL. Treatment included multidrug chemotherapy, prophylactic intrathecal methotrexate, and cranial radiotherapy. MEC of the left parotid gland was diagnosed at the age of 8 years, 3 years after completing treatment. She was treated with multiple surgery and radiotherapy. The authors aimed to emphasize the need for concern about second cancers of the parotid gland in children treated for ALL.     

Assessment of extrahepatic abdominal extension in primary malignant liver tumours of childhood

Imaging is a crucial part of the evaluation of children with primary liver malignancies. In addition to staging the intrahepatic extent of the tumour, the 2005 revision of the PRETEXT system specifies certain criteria for assessment of extrahepatic disease. This article reviews the imaging findings of two of these criteria: direct extrahepatic extension of the tumour (E1, E1a, E2, E2a) and tumour rupture at diagnosis (H1).     

Cutaneous squamous cell carcinoma in two pediatric lung transplant patients on prolonged voriconazole treatment

Oral voriconazole is commonly used for treatment and prophylaxis of invasive fungal disease post‐LTx. Development of cutaneous SCC has been described in adult LTx recipients, although it is extremely rare in children. We describe two Caucasian children who developed cutaneous SCC beyond three yr post‐LTx. Both developed severe photosensitivity, actinic keratosis and required curative surgical excision of the cutaneous SCC lesions. Neither patient developed metastatic lesions nor had allograft dysfunction as a result of the SCC or the change in medical treatments. The effect of voriconazole on the development of malignant skin lesions is discussed and a recommendation on dermatologic surveillance, preventive measures against phototoxicity and early treatment of SCC are provided.     

Hyponatremia and Renal Sodium Wasting in patients receiving cisplatinum

Three children with malignant solid tumors developed hyponatremia with renal sodium wasting associated with other signs of tubular dysfunction, such as hypokalemia or hypomagnesemia, a few days after cisdiammine dichloroplatinum (CDDP) administration. The normalization of serum electrolyte disturbances was obtained with increased parenteral intakes in fluids and electrolytes, and renal sodium wasting stopped by itself a few days later     

Carcinoma of the Tongue in a Long-Term Survivor of Clear Cell Sarcoma of the Kidney

Squamous cell carcinoma (SCC) of the tongue in persons younger than 30 years of age is an extremely rare neoplasm. We report an unusual case of SCC of the tongue as a second malignancy in a young adult with a history of a stage III clear cell sarcoma of the kidney (CCSK) treated 19 years earlier. Review of the literature reveals a spectrum of cytogenetic abnormalities in SCC; however, aberrations involving the long arm of chromosome 10 have been reported in both SCC and CCSK. Long-term follow-up, with particular attention to the head and neck, may be warranted in children with CCSK.     

Treatment of invasive aspergillosis in children with hematologic malignancies

The respiratory tract is the most common organ involved with Aspergillosis in children with hematologic malignancies. AlsoAspergillus species tend to invade blood vessels resulting in systemic dissemination to multiple organs. Early diagnosis and treatment are pivotal to the patient’s outcome. A high index of suspicion should be maintained in children who have profound neutropenia and present with prolonged fever that is unresponsive to systemic antibiotics. Several diagnostic modalities should be used simultaneously in order to confirm the diagnosis in an expedited manner. Combination and sequential antifungal therapy have been shown to be of added benefit. Surgical intervention is associated with a high mortality rate, but may be indicated in children with a localized disease. In this article the authors review the epidemiology, microbiology, pathology, and clinical manifestations of invasive aspergillosis in children with hematologic malignancies. Current diagnostic approach, medical, and surgical treatment options are discussed.     

Prevention of indwelling central venous catheter sepsis

In an attempt to decrease the incidence of central venous catheter sepsis in children with cancer, we conducted a study to evaluate the benefit of adding broad-spectrum antibiotics to the catheter “flush solution.” In a prospective, placebo-controlled, double-blinded, randomized trial, 69 children with different types of malignancies were studied. The central venous catheters in these children were flushed with either the standard solution (normal saline + 100 U/ml of heparin) or the study solution (25 μg/ml of both amikacin and vancomycin added to the standard solution). At the conclusion of the study, 64 children with a total of 67 indwelling central venous lines were assessable. The total catheter days on study were 20,700 days, with a median of 323 catheter days per patient. We documented 10 events of catheter-related infections (0.49 events/1,000 catheter days at risk). Five of these events were catheter-related sepsis (0.24 sepses/1,000 catheter days): two were fungal and three were bacterial. Due to the low incidence of catheter-related sepsis in this study, no statement regarding the prophylactic use of antibiotics could be made. The extremely low rate of catheter-related sepsis reported herein may be retrospectively attributed to continuous staff education regarding aseptic techniques in handling these catheters. Staff education is essential, and probably the most effective factor in preventing catheter-related sepsis. © 1996 Wiley-Liss, Inc.     

Cabozantinib for relapsed neuroblastoma: Single institution case series

Relapsed high‐risk neuroblastoma has few effective therapies currently available or in development. Cabozantinib is an Food and Drug Administration approved multitargeted tyrosine kinase inhibitor for select adult malignancies with preclinical data suggesting efficacy against neuroblastoma. A safe and tolerable dose has been identified for children, but its efficacy remains unknown. We describe four children with relapsed metastatic neuroblastoma treated with cabozantinib. All four patients had extended disease control (two complete responsesfor >12 months, 2 stable disease >6 months) with manageable predictable toxicities requiring dose reduction in two patients. We discuss the potential for the use of cabozantinib in neuroblastoma.