Blastoma

A blastoma is a type of cancer, more common in children, that is caused by malignancies in precursor cells, often called blasts. Examples are nephroblastoma, medulloblastoma, and retinoblastoma. The suffix -blastoma is used to imply a tumor of primitive, incompletely differentiated (or precursor) cells, e.g., chondroblastoma is composed of cells resembling the precursor of chondrocytes.

Molecular biology and treatment

Many types of blastoma have been linked to a mutation in tumor suppressor genes. For example, pleuropulmonary blastomas have been linked to a mutation of the coding for p53. However, the mutation which allows proliferation of incompletely differentiated cells can vary from patient to patient and a mutation can alter the prognosis. In the case of retinoblastoma, patients carry a visibly abnormal karyotype, with a loss of function mutation on a specific band of chromosome 13. This recessive deletion on the rb gene is also associated with other cancer types and must be present on both alleles, for a normal cell to progress towards malignancy. Thus, in the case of common blastomas, such as retinoblastomas, a practitioner may go directly into treatment, but in the case of rarer, more-genetically-linked blastomas, practitioners may karyotype the patient before proceeding with treatment.

Types of blastomas

Hepatoblastoma

Hepatoblastoma (HBL) is the first most common malignancy in children, often diagnosed during the first 3 years of life. In most cases, HBL is an sporadic pathology, although it has been sometimes associated with specific genetic abnormalities such as the Beckwith-Wiedemann syndrome and familial adenomatous polyposis. The incidence has increased over the last three decades, and the risk of developing HBL has been demonstrated to be higher for premature babies with a birth weight of less than 1 kilo. The fact that the survival rate for premature babies has increased might also account for the rise in HBL incidence. The most common signs used for diagnosis are abdominal distention and discomfort, generalized fatigue, loss of appetite and secondary anemia. The most important clinical marker for HBL is serum alpha-fetoprotein (AFP), except in the case of some rare variants of HBL and hepatocellular carcinoma that exhibit lower AFP levels.

Medulloblastoma

While leukemias are the most common type of malignancy to afflict the pediatric population, brain tumors are the most common solid tumors in this age group.[1] Medulloblastoma is the most common malignant brain tumor in children constituting nearly 20% of all pediatric brain tumors.[2] It is categorized as a primitive neuroectodermal tumor (PNET) of the cerebellum. Within the first few years of diagnosis, mortality approximates 15%; however, cure rates can reach as high as 60% with current therapeutic modalities.[3][4] Surgical resection, preceded and/or followed by radiation and chemotherapy, is the mainstay of therapy, with five-year survival rates of between 50% to 90%. This wide range is multifactorial, owing in part to age at diagnosis, the presence of metastases at diagnosis, and a histologic variant of medulloblastoma.[1][5] Regardless of long-term survival, treatment-related cognitive, neurologic, and endocrinologic effects remain a debilitating concern and an impetus for the search for further therapeutic modalities.

Nephroblastoma

Wilms tumor, or nephroblastoma, is the most common renal cancer in the pediatric age group.[1][2] It is also the most common pediatric abdominal cancer, and the fourth most common pediatric cancer overall.  Wilms tumor is typically found in children younger than five years old. The tumor is named after the German physician, Dr. Max Wilms, who first described it in 1899. The cause of Wilms tumor is not precisely known, but it is believed to be due to genetic alterations that deal with the normal embryological development of the genitourinary tract. Some of the genetic markers that have been associated with Wilms tumor include WT1, CTNNB1, and WTX gene alterations that have been found in about 1/3 of all Wilms tumors.  Other genes associated with Wilms tumor include TP53 and MYNC.  A poorer prognosis has been linked to TP53 and with the loss of heterozygosity at chromosomes 1p, 1q, 11p15 and 16q.[3][1]

Neuroblastoma

Neuroblastoma is the most common extra-cranial solid tumor in infants and children, representing 8%-10% of all childhood tumors. It accounts for approximately 15% of all cancer-related deaths in the pediatric population.1 The incidence of neuroblastoma is 10.2 cases per million children under 15 years of age,2 and nearly 500 new cases are reported annually. While 90% of cases are diagnosed before the age of 5, 30% of those are within the first year. The median age of diagnosis is 22 months.3 Rarely does it present in adolescence and adulthood, but outcomes are much poorer in this age group. There does not appear to be an increased prevalence among races, but there is a slight predilection for males (1.2:1)

Prognosis correlates with age and the degree of differentiation, and thus, outcomes vary from high rates of survival (with even possible tumor regression) to recurrence and mortality. While the standard of treatment is chemotherapy, radiation, and/or surgical resection, there is growing evidence that aggressive neuroblastomas are resistant to our therapies. To this end, research has been focused on the molecular mechanisms behind differentiation, cell survival and apoptosis, angiogenesis, and metastasis to elucidate where the process goes awry. The basis of this research has led to the development of novel therapies that are directed towards key targets, some of which are quite promising. While discussing clinical background, this article aims to provide a synopsis of the latest, up and coming developments in the field of neuroblastoma.

Pleuropulmonary blastoma

Childhood tumors of the lung are rare malignant tumors accounting for 0.5% to 1% of all primary malignant lung tumors. These tumors are subdivided into 3 subtypes: pulmonary blastoma, fetal adenocarcinoma, and pleuropulmonary blastoma. An epithelial malignant and immature component characterizes fetal adenocarcinoma. A malignant immature mesenchymal proliferation characterizes the pleuropulmonary blastoma. Biphasic components define the blastoma; a mesenchymal and an epithelial malignant and immature components that look like a 10- to 16-week gestational lung. In the 2015 World Health Organization Classification, fetal adenocarcinoma belongs to the group of adenocarcinomas, pulmonary blastoma belongs to the group of sarcomatoid carcinoma, and pleuropulmonary blastoma belongs to the group of mesenchymal tumors. Pleuropulmonary blastomas are rare tumors which present non-specific symptoms. Although the importance of the radiologic features to suspect the diagnosis, the positive diagnosis remains based on the microscopic features.[1][2] Many synonyms of pleuropulmonary tumors exist in the literature including:

• Cystic mesenchymal hamartoma
• Mesenchymal cystic hamartoma
• Pediatric pulmonary blastoma
• Pneumoblastoma
• Pulmonary rhabdomyosarcoma
• Rhabdomyosarcoma in lung cyst

Retinoblastoma

Retinoblastoma is a rare eye tumor of childhood that arises in the retina. It is the most common intraocular malignancy of infancy and childhood; with an incidence of 1/15,000–20,000 live births. The two most frequent symptoms revealing retinoblastoma are leukocoria and strabismus. Iris rubeosis, hypopyon, hyphema, buphthalmia, orbital cellulites and exophthalmia may also be observed. Sixty per cent of retinoblastomas are unilateral and most of these forms are not hereditary (median age at diagnosis two years). Retinoblastoma is bilateral in 40% of cases (median age at diagnosis one year). All bilateral and multifocal unilateral forms are hereditary. Hereditary retinoblastoma constitutes a cancer predisposition syndrome: a subject constitutionally carrying an RB1 gene mutation has a greater than 90% risk of developing retinoblastoma but is also at increased risk of developing other types of cancers. Diagnosis is made by fundoscopy. Ultrasound, magnetic resonance imaging (MRI) and computed tomography (CT) scans may contribute to diagnosis. Management of patients with retinoblastoma must take into account the various aspects of the disease: the visual risk, the possibly hereditary nature of the disease, the life-threatening risk. Enucleation is still often necessary in unilateral disease; the decision for adjuvant treatment is taken according to the histological risk factors. Conservative treatment for at least one eye is possible in most of the bilateral cases. It includes laser alone or combined with chemotherapy, cryotherapy and brachytherapy. The indication for external beam radiotherapy should be restricted to large ocular tumors and diffuse vitreous seeding because of the risk of late effects, including secondary sarcoma. Vital prognosis, related to retinoblastoma alone, is now excellent in patients with unilateral or bilateral forms of retinoblastoma. Long term follow-up and early counseling regarding the risk of second primary tumors and transmission should be offered to retinoblastoma patients.

Glioblastoma multiforme

Glioblastoma multiforme is a central nervous system tumor of grade IV histological malignancy according to the WHO classification. Over 90% of diagnosed glioblastomas multiforme cases are primary gliomas, arising from normal glial cells through multistep oncogenesis. The remaining 10% are secondary gliomas originating from tumors of lower grade. These tumors expand distinctly more slowly. Although genetic alterations and deregulations of molecular pathways leading to both primary and secondary glioblastomas formation differ, morphologically they do not reveal any significant differences. Glioblastoma is a neoplasm that occurs spontaneously, although familial gliomas have also been noted. Caucasians, especially those living in industrial areas, have a higher incidence of glioblastoma. Cases of glioblastoma in infants and children are also reported. The participation of sex hormones and viruses in its oncogenesis was also suggested. Progression of glioblastoma multiforme is associated with deregulation of checkpoint G1/S of a cell cycle and occurrence of multiple genetic abnormalities of tumor cells. Metastases of glioblastoma multiforme are rarely described. Treatment of glioblastoma multiforme includes tumor resection, as well as radiotherapy and chemotherapy. Drugs inhibiting integrin signaling pathways and immunotherapy are also employed. Treatment modalities and prognosis depend on the tumor localization, degree of its malignancy, genetic profile, proliferation activity, patient's age and the Karnofsky performance scale score. Although the biology of glioblastoma multiforme has recently been widely investigated, the studies summarizing the knowledge of its development and treatment are still not sufficient in terms of comprehensive brain tumor analysis.