Publications - Volume 12

Indranil Ghosh, MD and Sameer Bakhshi, MD

Tumour Markers in Paediatric Uro-malignancies              

 

Alfa-fetoprotein (AFP), beta-subunit of human chorionic gonadotrophin (ß-hCG) and lactate dehydrogenase (LDH) are useful serum tumor markers for pediatric germ cell tumors Methods have been suggested to distinguish between AFP of tumor or hepatic origin. A high AFP to concanavalin binding ratio (>10%) may favor a germ cell tumor origin rather than hepatic. Subfractionation of AFP has also been suggested as a measure to identify the source and also to predict the occurrence of malignant component in a tumor. Human chorionic gonadotropin (hCG) is a glycoprotein hormone produced in pregnancy that is made by the developing embryo soon after conception and later by the syncytiotrophoblast. False-positivity can result from cross-reactivity with LH (hypogonadism) or from ß-hCG released from host of other tumors like hepatic, renal, adrenal, and leukemia, lymphoma, as well as benign causes like hepatic necrosis, skeletal muscle disease and renal disease. Serum LDH is a non-specific marker of tumor burden and may be elevated in any histology. Serum LDH levels and its isoenzyme pattern have been suggested as useful tumor markers for diagnosis and post-therapy surveillance in patients with ovarian dysgerminomas. Neuroblastoma is the second most common solid malignancy in childhood and the most common malignancy in infants. Majority of neuroblastoms possess enzymes necessary for synthesis of catecholamines (dopamine, norepinephrine and epinephrine) and their degradation, which gives rise to metabolites like VMA and HVA. HVA is the major metabolite of dopamine, while VMA is the major metabolite of epinephrine and norepinephrine. Using combination of two or more metabolites in urine, sensitivity approaches 90% at diagnosis while it decreases to ~50% for detection of recurrent disease.second most common solid malignancy in childhood and the most common malignancy in infants. Majority of neuroblastoms possess enzymes necessary for synthesis of catecholamines (dopamine, norepinephrine and epinephrine) and their degradation, which gives rise to metabolites like VMA and HVA. HVA is the major metabolite of dopamine, while VMA is the major metabolite of epinephrine and norepinephrine. Using combination of two or more metabolites in urine, sensitivity approaches 90% at diagnosis while it decreases to ~50% for detection of recurrent disease.

 

Vivek Subbiah, MD and Winston W. Huh, MD

Genitourinary Rhabdomyosarcomas                              

 

Rhabdomyosarcoma is the most common soft tissue sarcoma in children and young adults. Improvements in diagnosis, classification, surgery, radiation therapy and chemotherapy have increased the overall survival to greater than 70 % for certain subgroups of patients. The genitourinary region represents the primary site for approximately 30% of RMS cases, with most patients having the embryonal subtype. Due to concerns about long-term morbidities, coordinated multidisciplinary care with accurate pre-treatment staging is pivotal in this challenging group of patients. Overall the prognosis for most patients with genitourinary RMS (GU RMS) is very good, but challenges remain with respect to limiting the incidence of long-term side effects of therapy. In this review, we discuss the clinical characteristics, presentation, and current standard-of-care therapies for patients with GU RMS.

 

Chetan Dhamne MD, Kunal Sawale MD and Peter Anderson MD

Treatment of Wilms' Tumour                                         

 

Wilms tumor also known as nephroblastoma is the most common primary malignant renal tumor of childhood. About 500 new cases are diagnosed every year in the US1. Over the last three decades the treatment of Wilms tumor has evolved to give >90% event free survival rates because of the collaborative efforts between surgeons, pathologists, oncologists and radiation therapists in The National Wilms Tumor Study Group now Children’s Oncology Group(COG), International Society for Pediatric Oncology (SIOP) and UK Children’s Cancer Study Group2. The SIOP and NWTSG use the same chemotherapeutic agents but the SIOP group recommends chemotherapy first, prior to surgery while the NWTSG recommends surgery followed by chemotherapy. Both approached have yielded comparable results and either system can be followed as per institutional preference3. Molecular studies should be done to assign the appropriate treatment strategy whenever available. In this section we will discuss the chemotherapy used for primary and relapsed Wilms tumor patients. The surgical aspects and pathology are discussed in a separate section.

 

Cynthia E. Gonzales, MD and Trib S. Vats, MD

Adrenocortical Tumours                                                

 

Approximately 5-15% of autopsies conducted in the adult population harbor silent adrenal masses, however, adrenocortical tumors (ACTs) are rare in children and adolescents. In older literature, over half of ACTs in children are diagnosed at > 3 years of age and 80% of cases occur in children < 8 years of age with a female to male ratio of approximately 3:1. Data from the National Cancer Insitute’s Surveillance Epidemiology and End Results (SEER) monograph gives an average annual incidence of adrenal carcinoma in children under the age of 9 of 0.25 per million. Several constitutional chromosomal aberrations have been described that explain the pathogenesis of these tumors. Constitutional p53 mutation is the most common reported finding in young children. The majority of children have functioning tumors and the most common symptoms are virilization and excess secretion of cortisol resulting in Cushing syndrome. 50-60% of  patients present with large tumors and with regional or metastatic involvement. Currently, the prognosis is grim for children with unresectable or metastatic tumors, hence, the mainstay of therapy has been complete surgical resection with care to avoid tumor spillage. Multi-agent chemotherapy is currently reserved for this subset of patients. Children with ACTs and other rare tumors must be encouraged to enroll in cooperative international trials to gain better insight into the biology of this tumor, determine the best treatment options and pave the way for the development of novel agents against oncogenic targets.

 

Philip Corbett, MD and Feilim Liam Murphy, FRSCI

Testicular Tumours in Children and Adolescents              

 

Prepubertal testicular tumours account for 2% of all childhood malignancies with an incidence of 0.3-2 per100,000 children. Overall they account for 2% of all childhood malignancies with an incidence of 0.3-2 per100,000 children. This review is to identify the key points of difference in pre pubertal testicular tumours relative to their diagnosis, treatment and outcome and to describe all the common and less common testicular neoplasms in order for the surgeon to al develop a clear management for every testicular tumour prior to surgery. Prepubertal testicular tumours are dramatically different from their adult counterparts. The epidemiology is unclear except for a strong familial cancer risk. Clinically the vast majority of the tumours present in the preschool child with a painless testicular mass and occasionally, as a trap for the unwary, with a hydrocoele. In the first 6 months of life juvenile granulosa cell tumours, sertoli cell tumours and teratomas commonly present as painless benign enlarged testes. In the first year multicystic dysplastic testes and excised Gonadoblastomas present. Between six and thirty six months of life yolk sac tumours, then teratomas peak in incidence. Clinical differentiations of the tumours can challenging as AFP can be physiologically raised and ultrasound of the scrotum can lack in specificity. However the tumours are can easily be identified on histology and the prognosis is excellent with teratomas being benign and yolk sac tumours presenting in clinical stage I. Between five and twelve years Leydig cells occur associated with precious puberty while the incidence of yolk sac tumours dramatically falls after age of four. In boys older than twelve the incidence of teratoma and the key issue at this age is to identify the onset of puberty as they should be evaluated and managed as for adults with malignant germ cell tumours. In order that we can improve our data on the incidence and demographics of testicular tumours all testicular tumours benign or malignant, enucleated or excised should be centrally reported to the appropriate tumour registry. If no suitable registry exists in your region we hope that this review prompts its creation.

 

Joy M. Fulbright, MD and Winston W. Huh, MD

Germ Cell Tumours of Gonadal/Sacrococcygeal Area      

 

Germ cell tumors (GCTs) constitute 2-3% of childhood malignancies. GCTs occur in a bimodal distribution in infants and adolescents. There are 4.9 cases of germ cell or other gonadal tumors per million children less than 15 years of age and 26 cases per million children age 15-19 years. The major risk factor for developing a gonadal GCT is gonadal dysgenesis, with incidence up to 30 percent in these patients. GCTs also occur in 5-10% of patients with undervirilization syndromes. Risk is thought to increase with age, therefore a gonadectomy during early childhood is recommended. In males with cryptorchidism, there is a 3-9 fold increase risk for GCTs compared to the normal male population. There are several subtypes of GCTs, but all are thought to have a common cell of origin, the primordial germ cell. Many of the tumor characteristics depend upon when in development the tumor occurs, the gender of the patient, and specific genetic aberrations. Even though gonadal GCTs are rare in the pediatric population they are important to diagnose and fully stage. With the addition of platinum based therapy to surgical resection gonadal and sacrococcygeal GCTs, even at advanced stages, have a good outcome. Current trials are now evaluating if decreasing low risk patient’s exposure to platinum based chemotherapy is feasible without compromising their outcome.

 

Chetan Dhamne, MD and Peter Eric Zage, MD

Neuroblastoma                                                            

 

Neuroblastoma is the most common solid tumor of infancy and the most common extracranial solid tumor of childhood. It is known for its heterogeneous clinical presentation and unpredictable behavior, including tumors that regress spontaneously without treatment or progress despite aggressive multi-modal therapy. Our improved understanding of molecular and genetic features of this tumor has shed some light on its diverse clinical behavior.1 It can be classified into high risk, intermediate risk, and low risk groups based on clinical and biological criteria that can predict prognosis. Although children with low risk neuroblastoma have very good outcomes and excellent long term survival, children with high-risk neuroblastoma continue to do poorly despite significant intensification of conventional treatment. Current trials continue to refine risk stratification based on newer biological variables, to continue the attempts to define the minimal therapy needed to maintain excellent outcomes and minimize long term side effects. However, even with aggressive treatment regimens, the overall survival for children with high-risk neuroblastoma remains poor, and newer agents hold promise for improved survival in children with high-risk neuroblastoma.

 

Rakesh Kumar, MD and Tushar Mohapatra, MD

Nuclear Medicine Investigations in Urinary System Malignancies in Children

 

In this chapter, the authors describe the role of various nuclear medicine investigations used for the management of urinary system pediatric malignancies. As of now, there is no single imaging modality which can provide all information like early diagnosis, correct initial staging, treatment response evaluation and detection of recurrent disease. Most of these investigations are complementary to each other. Various nuclear medicine investigations play important role in the management of urinary malignancies in children as these provide functional and metabolic status of tumors. Recent introduction of PET-CT has revolutionized non-invasive imaging as it provides structural and functional details in one setting. PET and PET/CT has been found to be useful in urinary system malignancies in children. PET/CT has limited role in early diagnosis, however, it plays an important role in initial staging, treatment response evaluation and detection of metastatic disease in these cancers. At present, there are few radiotracers in PET imaging under active research like 11C-methionine, 11C-choline, 11C-acetate etc, which characterize tumor biology other than glucose metabolism.

 

Nina Tatevian MD and Sagar Dhamne MD

Paediatric Renal Tumours: A Pathologist’s Perspective    

 

Pediatric renal tumors have been systematically targeted since the inception of groups like Childrens Oncology Group (COG) and have resulted in definition of new entities, reclassification of existing entities, and development of treatment protocols dramatically improving the outcome for these tumors. Though started out to specifically target Wilms’ tumor, over the last four decades more and more pediatric tumors have been included in the protocols. It is important for the oncologists as well as the pathologists to remain abreast with the latest developments in the classification and treatment protocols. Here we discuss the latest recommendations of the COG and also review briefly the pathology of important pediatric renal tumors.

 

Dr. Venkateswaran K Iyer, MD

Fine Needle Aspiration Cytology Diagnosis in Paediatric Uro-oncology

 

This review article describes the value of fine needle aspiration cytology (FNAC) in the diagnosis of tumors of the paediatric kidney. The merits, demerits, methods, complications, diagnostic techniques, cytologic features, immunocytochemistry and differential diagnostic considerations are elaborated. The main role of FNAC is the correct typing of tumor for selection of chemotherapy, which is specific for Wilms tumor, anaplastic Wilms tumor, clear cell sarcoma and rhabdoid tumor of kidney. FNAC also helps to differentiate Wilms tumor from neuroblastoma, the main differential diagnosis. FNAC diagnosis is important in India where over three fourths of cases present in stage 3 or above, requiring pre-operative chemotherapy.

 

Prabudh Goel,MCh and Minu Bajpai, MS, MCh, PhD, DNB, Fulbright Scholar

Germ Cell Tumors in the Intersex Gonad                        

With recent advances in the fields of genetic medicine, pathology, paediatric endocrinology, andrology, oncology, urology, pediatric surgery and epidemiology, the scientific understanding of the pathogenesis of the various Disorders of Sex Development (DSD) has increased greatly. The optimal management of these patients has always been a matter of controversy and the discussion and opinions have changed over time towards more conservative approaches in an effort towards preserving the normal and native tissues. However, the dysgenetic gonad has a potential for malignant transformation and this possibility has been the biggest obstacle to worldwide acceptance of conservative protocols that call for watchful waiting. The International consensus concluded on the management of these patients with regard to gonadectomy. However, information is inadequate due to the limited number of patients studied. Therefore, sufficient data are not available to draw guidelines for the establishment of safe, scientific and evidence based protocols for definitive management of these patients. An intense and multicentre collaboration is the need of the day.

 

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