Diseases of Infancy and Childhood: Tumors and Tumor-like Lesions of Infancy and Childhood

Question 1

What does heterotopia (choristoma) refer to?

Answer 1

microscopically normal cells in abnormal location

Question 2

what does hamartoma refer to?

Answer 2

excessive focal overgrowth of tissue native to the organ

Question 3

What is a common example of a hamaratoma?

Answer 3

hemangiomas

Question 4

What is the most common tumor of infancy?

Answer 4

hemangioma

Question 5

the most common neoplasms of childhood are what derived?

Answer 5

soft-tissue mesenchymal derivation

Question 6

hemangiomas may enlarge along with the growth of the child, but in many instances they?

Answer 6

spontaneously regress

Question 7

in addition to their cosmetic significance, hemangiomas can represent one facet of the hereditary disorder _____?

Answer 7

von Hippel-Lindau disease

Question 8

What are lymphatic tumors known as?

Answer 8

lymphangioma and lymphangiectasia

Question 9

Teratomas exhibit two peaks in incidence: what are these peaks?

Answer 9

the first at approximately 2 years of age and the second in late adolescence or early adulthood

Question 10

What are the most common teratomas of childhood?

Answer 10

sacrococcygeal teratomas (4x more common in females)

Question 11

the most frequent childhood cancers arise in what?

Answer 11

the hematopoietic system, nervous tissue (including the central and sympathetic nervous system, adrenal medulla, and retina), soft tissue, bone, and kidney

Question 12

In general, what are the characteristics of the malignant nonhematopoietic pediatric neoplasms?

Answer 12

they tend to have a more primitive (embryonal) undifferentiated appearance, often characterized by sheets of cells with small round nuclei

Question 13

because of their primitive appearance, many childhood tumors have been collectively referred to as what?

Answer 13

small round blue cell tumors

Question 14

neuroblastic tumors include tumors of what?

Answer 14

the sympathetic ganglia and adrenal medulla that are derived from primordial neural crest cells populating these sites

Question 15

what is the most frequently diagnosed tumor of infancy?

Answer 15

neuroblastoma

Question 16

What is the median age of diagnosis of neuroblastoma, but when are 40% of cases diagnosed?

Answer 16

median age is 18 months, but 40% of cases are diagnosed in infancy

Question 17

most neuroblastomas occur sporadically, but 1-2% are familial due to what?

Answer 17

germline mutations in the anaplastic lymphoma kinase (ALK) gene

Question 18

what are some characteristic features of neuroblastomas?

Answer 18

spontaneous or therapy-induced differentiation of primitive neuroblasts into mature elements, spontaneous tumor regression, and a wide range of clinical behavior and prognosis

Question 19

What is the classical clinical presentation of a patient with a neuroblastoma?

Answer 19

they will be younger than 2 years old with a large abdominal mass, +/- weight loss

Question 20

In childhood, about 40% of neuroblastoma arise where?

Answer 20

in the adrenal medulla

Question 21

Besides the adrenal medulla, the remainder of neuroblastomas occur where?

Answer 21

anywhere along the sympathetic chain, with the most common locations being the paravertebral region of the abdomen and posterior mediastinum

Question 22

In neonates, disseminated neuroblastomas may present how?

Answer 22

with multiple cutaneous metastases that cause deep blue discoloration of the skin (blueberry muffin baby)

Question 23

In children older than 2 years, how might neuroblastoma present differently?

Answer 23

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

Question 24

about 90% of neuroblastomas, regardless of location, produce what?

Answer 24

catecholamines

Question 25

how are the catecholamines produced by neuroblastomas used as a diagnostic feature?

Answer 25

elevated blood levels of catecholamines and elevated urine levels of the metabolites VMA and HVA

Question 26

what does HVA come from?

Answer 26

the degradation of dopamine

Question 27

what is responsible for breaking down dopamine into HVA?

Answer 27

Monoamine oxidase (MAO) and COMT

Question 28

where does VMA come from?

Answer 28

the degradation of norepinephrine

Question 29

what is responsible for breaking down norepinephrine into VMA?

Answer 29

monoamine oxidase (MAO) and COMT

Question 30

what are in aitu lesions?

Answer 30

minute nodules- the great majority of these silent lesions regress leaving only a focus of fibrosis or calcification in the adult

Question 31

histologically, classic neuroblastoma are composed of what?

Answer 31

small, primitive appearing cells with dark nuclei, scant cytoplasm, and poorly defined cell borders growing in solid sheets

Question 32

what is a histological feature of neuroblastomas?

Answer 32

typically Homer-Wright pseudoresettes can be found in which tumor cells are concentrically arranged about a central space filled with neuropil

Question 33

at what stage do most children first get diagnosed with neuroblastoma?

Answer 33

stage 3 or 4

Question 34

What stages are considered fvorable for prognosis of neuroblastoma?

Answer 34

stages 1, 2A, 2B, and 4s

Question 35

what are the favorable prognostic factors in neuroblastomas?

Answer 35

age: less than 18 months old; histology: ganglionic differentiation is present (mature), and there is not a lot of mitosis-karyorrhexis; MCYN: not amplified

Question 36

what are the unfavorable prognostic factors in neuroblastomas?

Answer 36

Age: older than 18 months; Histology: no ganglionic differentiation and high mitosis-karyorrhexis index; MCYN: amplified

Question 37

How can you test to see if MYCN is amplified or not?

Answer 37

by using FISH; used to test for gene amplification

Question 38

One peculiar form of segmental aberration described recently in aggressive neuroblastoma is called what?

Answer 38

chromothripsis

Question 39

what is chromothrupsis characterized by?

Answer 39

extensive genomic rearrangements and an oscillating pattern of DNA copy levels

Question 40

What is the most common primary renal tumor of childhood?

Answer 40

Wilms tumor

Question 41

when is the peak incidence of wilms tumor?

Answer 41

age 2-5 years old (but can occur up to 10 years old)

Question 42

If you have bilateral wilms tumors and earlier presentation, what is most likely going on?

Answer 42

there was a germline mutation

Question 43

How do children present when they have a Wilms tumor?

Answer 43

with a large abdominal mass that may extend down into the pelvis; hematuria, pain in the abdomen, intestinal obstruction, and the appearance of hypertension

Question 44

Do Wilms tumors produce catecholamines?

Answer 44

NO THEY DO NOT

Question 45

What type of metastases is commonly found at the time of primary diagnosis of Wilms tumors?

Answer 45

pulmonary metastases

Question 46

What are the histological characteristics of Wilms tumors?

Answer 46

they have a classic triphasic combination of blastemal, stromal, and epithelial cell types

Question 47

What do the blastemal cell types look like in the Wilms tumors?

Answer 47

they are the small blue cells

Question 48

What is the epithelial differentiation of Wilms tumors usually in the form of?

Answer 48

abortive tubules or glomeruli

Question 49

What is a key feature of Wilms tumors that has prognostic significance or is associated with chemotherapy resistance?

Answer 49

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

Question 50

what is anaplasia defined as?

Answer 50

the presence of large, hyperchromatic, pleomorphic nuclei and abnormal mitoses

Question 51

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?

Answer 51

WAGR/WAGI syndrome, Denys-Drash syndrome, and Beckwith-Wiedeman syndrome

Question 52

if you have WAGR/WAGI syndrome, what is your lifetime risk for getting Wilms tumor?

Answer 52

33%

Question 53

what all occurs in WAGR/WAGI syndrome?

Answer 53

Wilms tumor, aniridia, genital anomalies, mental retardation (intellectual disability)

Question 54

what is aniridia?

Answer 54

the absence of an iris (color in the eye)

Question 55

what causes WAGR/WAGI syndrome?

Answer 55

a germline deletion of 11p13

Question 56

what was the first wilms-tumor associated gene identified?

Answer 56

WT1

Question 57

what causes aniridia specifically?

Answer 57

deleted autosomal dominant gene for aniridia PAX6

Question 58

If you have Denys-Drash syndrome, what is your lifetime risk for getting Wilms tumor?

Answer 58

90%!!!!!!!

Question 59

What is Denys-drash syndrome characterized by?

Answer 59

gonadal dysgenesis, early onset neuropathy leading to renal failure

Question 60

What are Denys-Drash patients also at risk for besides Wilms tumor?

Answer 60

gonadoblastoma

Question 61

What is the genetic abnormality associated with Denys-Drash syndrome?

Answer 61

the genetic abnormality is a dominant-negative missense mutation in the zinc-finger region of the WT1 protein that affects its DNA binding properties

Question 62

What is Beckwith-Wiedmann syndrome characterized by?

Answer 62

organomegaly, macroglossia, hemihypertrophy, omphalocele, adrenal cytomegaly

Question 63

Beckwith-Wiedmann syndrome has served as a model for tumorigenesis associated with what?

Answer 63

genomic imprinting

Question 64

What is the chromosomal region implicated in beckwith-wiedmann syndrome?

Answer 64

it has been localized to band 11p15.5

Question 65

What do some patients with beckwith-wiedmann syndrome have?

Answer 65

a CDKN1C mutation

Question 66

what is the normal function of CDKN1C?

Answer 66

it is a cell cycle regulator that broadly inhibits multiple CDKs- so if it is mutated, the cell cycle will continue unchecked

Question 67

besides wilms tumors, what are those with beckwith-wiedmann syndrome at increased risk for?

Answer 67

hepatoblastoma, pacreatoblastoma, adrenal cortical tumors, and rhabdomyosarcoma