Diseases of Infancy and Childhood: Tumors and Tumor-like Lesions of Infancy and Childhood Flashcards
What does heterotopia (choristoma) refer to?
microscopically normal cells in abnormal location
what does hamartoma refer to?
excessive focal overgrowth of tissue native to the organ
What is a common example of a hamaratoma?
hemangiomas
What is the most common tumor of infancy?
hemangioma
the most common neoplasms of childhood are what derived?
soft-tissue mesenchymal derivation
hemangiomas may enlarge along with the growth of the child, but in many instances they?
spontaneously regress
in addition to their cosmetic significance, hemangiomas can represent one facet of the hereditary disorder _____?
von Hippel-Lindau disease
What are lymphatic tumors known as?
lymphangioma and lymphangiectasia
Teratomas exhibit two peaks in incidence: what are these peaks?
the first at approximately 2 years of age and the second in late adolescence or early adulthood
What are the most common teratomas of childhood?
sacrococcygeal teratomas (4x more common in females)
the most frequent childhood cancers arise in what?
the hematopoietic system, nervous tissue (including the central and sympathetic nervous system, adrenal medulla, and retina), soft tissue, bone, and kidney
In general, what are the characteristics of the malignant nonhematopoietic pediatric neoplasms?
they tend to have a more primitive (embryonal) undifferentiated appearance, often characterized by sheets of cells with small round nuclei
because of their primitive appearance, many childhood tumors have been collectively referred to as what?
small round blue cell tumors
neuroblastic tumors include tumors of what?
the sympathetic ganglia and adrenal medulla that are derived from primordial neural crest cells populating these sites
what is the most frequently diagnosed tumor of infancy?
neuroblastoma
What is the median age of diagnosis of neuroblastoma, but when are 40% of cases diagnosed?
median age is 18 months, but 40% of cases are diagnosed in infancy
most neuroblastomas occur sporadically, but 1-2% are familial due to what?
germline mutations in the anaplastic lymphoma kinase (ALK) gene
what are some characteristic features of neuroblastomas?
spontaneous or therapy-induced differentiation of primitive neuroblasts into mature elements, spontaneous tumor regression, and a wide range of clinical behavior and prognosis
What is the classical clinical presentation of a patient with a neuroblastoma?
they will be younger than 2 years old with a large abdominal mass, +/- weight loss
In childhood, about 40% of neuroblastoma arise where?
in the adrenal medulla
Besides the adrenal medulla, the remainder of neuroblastomas occur where?
anywhere along the sympathetic chain, with the most common locations being the paravertebral region of the abdomen and posterior mediastinum
In neonates, disseminated neuroblastomas may present how?
with multiple cutaneous metastases that cause deep blue discoloration of the skin (blueberry muffin baby)
In children older than 2 years, how might neuroblastoma present differently?
they may not come to attention until metastases produces manifestations such as bone pain, respiratory symptoms, or GI complaints; proptosis and ecchymosis may also be present as the periorbital region is a common metastatic site
about 90% of neuroblastomas, regardless of location, produce what?
catecholamines
how are the catecholamines produced by neuroblastomas used as a diagnostic feature?
elevated blood levels of catecholamines and elevated urine levels of the metabolites VMA and HVA
what does HVA come from?
the degradation of dopamine
what is responsible for breaking down dopamine into HVA?
Monoamine oxidase (MAO) and COMT
where does VMA come from?
the degradation of norepinephrine
what is responsible for breaking down norepinephrine into VMA?
monoamine oxidase (MAO) and COMT
what are in aitu lesions?
minute nodules- the great majority of these silent lesions regress leaving only a focus of fibrosis or calcification in the adult
histologically, classic neuroblastoma are composed of what?
small, primitive appearing cells with dark nuclei, scant cytoplasm, and poorly defined cell borders growing in solid sheets
what is a histological feature of neuroblastomas?
typically Homer-Wright pseudoresettes can be found in which tumor cells are concentrically arranged about a central space filled with neuropil
at what stage do most children first get diagnosed with neuroblastoma?
stage 3 or 4
What stages are considered fvorable for prognosis of neuroblastoma?
stages 1, 2A, 2B, and 4s
what are the favorable prognostic factors in neuroblastomas?
age: less than 18 months old; histology: ganglionic differentiation is present (mature), and there is not a lot of mitosis-karyorrhexis; MCYN: not amplified
what are the unfavorable prognostic factors in neuroblastomas?
Age: older than 18 months; Histology: no ganglionic differentiation and high mitosis-karyorrhexis index; MCYN: amplified
How can you test to see if MYCN is amplified or not?
by using FISH; used to test for gene amplification
One peculiar form of segmental aberration described recently in aggressive neuroblastoma is called what?
chromothripsis
what is chromothrupsis characterized by?
extensive genomic rearrangements and an oscillating pattern of DNA copy levels
What is the most common primary renal tumor of childhood?
Wilms tumor
when is the peak incidence of wilms tumor?
age 2-5 years old (but can occur up to 10 years old)
If you have bilateral wilms tumors and earlier presentation, what is most likely going on?
there was a germline mutation
How do children present when they have a Wilms tumor?
with a large abdominal mass that may extend down into the pelvis; hematuria, pain in the abdomen, intestinal obstruction, and the appearance of hypertension
Do Wilms tumors produce catecholamines?
NO THEY DO NOT
What type of metastases is commonly found at the time of primary diagnosis of Wilms tumors?
pulmonary metastases
What are the histological characteristics of Wilms tumors?
they have a classic triphasic combination of blastemal, stromal, and epithelial cell types
What do the blastemal cell types look like in the Wilms tumors?
they are the small blue cells
What is the epithelial differentiation of Wilms tumors usually in the form of?
abortive tubules or glomeruli
What is a key feature of Wilms tumors that has prognostic significance or is associated with chemotherapy resistance?
approximately 5% of these tumors have anaplasia; the presence of anaplasia correlates with the presence of TP53 mutations and the emergence of resistance to chemotherapy
what is anaplasia defined as?
the presence of large, hyperchromatic, pleomorphic nuclei and abnormal mitoses
The risk of Wilms tumor is increased with at least 3 recognizable groups of congenital malformations associated with distinct chromosomal loci. What are these groups/syndromes?
WAGR/WAGI syndrome, Denys-Drash syndrome, and Beckwith-Wiedeman syndrome
if you have WAGR/WAGI syndrome, what is your lifetime risk for getting Wilms tumor?
33%
what all occurs in WAGR/WAGI syndrome?
Wilms tumor, aniridia, genital anomalies, mental retardation (intellectual disability)
what is aniridia?
the absence of an iris (color in the eye)
what causes WAGR/WAGI syndrome?
a germline deletion of 11p13
what was the first wilms-tumor associated gene identified?
WT1
what causes aniridia specifically?
deleted autosomal dominant gene for aniridia PAX6
If you have Denys-Drash syndrome, what is your lifetime risk for getting Wilms tumor?
90%!!!!!!!
What is Denys-drash syndrome characterized by?
gonadal dysgenesis, early onset neuropathy leading to renal failure
What are Denys-Drash patients also at risk for besides Wilms tumor?
gonadoblastoma
What is the genetic abnormality associated with Denys-Drash syndrome?
the genetic abnormality is a dominant-negative missense mutation in the zinc-finger region of the WT1 protein that affects its DNA binding properties
What is Beckwith-Wiedmann syndrome characterized by?
organomegaly, macroglossia, hemihypertrophy, omphalocele, adrenal cytomegaly
Beckwith-Wiedmann syndrome has served as a model for tumorigenesis associated with what?
genomic imprinting
What is the chromosomal region implicated in beckwith-wiedmann syndrome?
it has been localized to band 11p15.5
What do some patients with beckwith-wiedmann syndrome have?
a CDKN1C mutation
what is the normal function of CDKN1C?
it is a cell cycle regulator that broadly inhibits multiple CDKs- so if it is mutated, the cell cycle will continue unchecked
besides wilms tumors, what are those with beckwith-wiedmann syndrome at increased risk for?
hepatoblastoma, pacreatoblastoma, adrenal cortical tumors, and rhabdomyosarcoma
