Diseases Of Infancy And Childhood Pt2

Question 1

What is heterotopia (choristoma)?

Answer 1

Microscopically normal cells/tissues in abnormal location

Question 2

What is a hamartoma?

Answer 2

Excessive focal overgrowth of tissue native to the organ (ex. hemangioma)

Question 3

What is the most common tumor of infancy?

Answer 3

Hemangioma

Question 4

Describe the growth of hemangiomas

Answer 4

May enlarge along with the growth of the child but in many instances they spontaneously regress
They can represent one part of the hereditary disorder von Hippel-Lindau disease

Question 5

A subset of CNS cavernous hemangiomas can occur in the familial setting and these families harbor mutations in one of which three genes?

Answer 5

KRIT1, CCM2 or PDCD10

Question 6

What are examples of lymphatic tumors?

Answer 6

Lymphangioma and lyphaniectasia

Question 7

What are the two types of hemangiomas?

Answer 7

Capillary and cavernous

Question 8

What are port wine stains?

Answer 8

Occurs in children with hemangiomas

Flat hemangioma that is a vascular ectasis

Question 9

Describe lymphangiomas

Answer 9

Characterized by cystic and cavernous spaces
Can occur in the skin but more likely in the deeper regions of the neck, axilla, mediastinal tissue, or retroperitoneal tissue
Histologically benign but can grow after birth due to the accumulation of fluid and the budding of pre-existing spaces

Question 10

Describe lymphangiectasia

Answer 10

Abnormal dilations of pre-existing lymph channels
Presents as a diffuse swelling of part of or all the extremity that can cause considerable distortion and deformation due to the spongy dilated subcutaneous lymphatic ducts

Question 11

Fibrous tumors can look like what?

Answer 11

Adult type fibrosarcoma but have a better outcome (aka excellent prognosis)
Associated with congenital infantile fibrosarcomas

Question 12

What chromosome translocation is unique to congenital infantile fibrosarcomas?

Answer 12

ETV6-NTRK3 fusion transcript

Diagnostic

Question 13

Describe teratomas

Answer 13

Benign, well differentiated cystic lesions (mature teratoma —> better prognosis) 
Lesions of interdeterminate potential (immature teratoma)
Malignant teratomas (admixed with another germ cell tumor component -> endodermal sinus tumor)

Question 14

What are the two peaks of incidence with teratomas?

Answer 14

2 years old (congenital neoplasms)

In late adolescence or early adulthood (slow growing, may be prenatal)

Question 15

What is the most common teratoma?

Answer 15

Sacrococcygeal teratoma
Greater in females than males
Mostly mature teratomas

Question 16

The most frequent childhood cancers arise where?

Answer 16

Hematopoietic system, nervous tissue including the CNS, SNS, adrenal medulla and retina, soft tissue, bone and kidneys

Question 17

Most neoplasms of children typically come from what?

Answer 17

Soft tissues of mesenchymal origin whereas in the adult they are from epithelial origin

Question 18

Describe the histology of malignant non-hematopoietic pediatric neoplasms

Answer 18

Tend to have a more primitive/embryo an undifferentiated appearance
Characterized by sheets of cells with small, round nuclei (referred to as small round blue cell tumors)
Frequently show organogenesis specific to site of tumor origin
Referred to by the suffix -blastoma

Question 19

What are common malignant neoplasms in infancy and childhood?

Answer 19

Leukemia, Rb, neuroblastoma, Wilms tumor, hepatoblastoma, soft tissue sarcoma, teratoma, central nervous system tumors, Ewing sarcoma

Question 20

What are neuroblastic tumors?

Answer 20

Includes tumors of the sympathetic ganglia and adrenal medulla that are derived from primordial NCCs populating these sites

Question 21

What is the most common extracranial solid tumor of childhood?

Answer 21

Neuroblastoma

Median age of diagnosis is 18 mo

Question 22

Germline mutations in which gene have been identified to confer a familial predisposition to neuroblastoma?

Answer 22

Anaplastic lymphoma kinase (ALK gene)

Question 23

What are characteristics features of a neuroblastoma?

Answer 23

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

Question 24

What is the clinical presentation of a neuroblastoma?

Answer 24

Less than 2 years old with large abdominal mass, fever, +/- weight loss
Infants with multiple cutaneous metastasis (blueberry muffin baby)
May present with Mets via blood and lymph to liver, lung, bone and bone marrow (periorbital region is a common metastatic site)

Question 25

40% of neuroblastoma arise where?

Answer 25

In the adrenal medulla

Question 26

What is an important diagnostic feature of neuroblastoma?

Answer 26

Regardless of location 90% of them will produce catecholamines (i.e. elevated blood levels of catecholamines and elevated urine levels of metabolites VMA and HVA)

Question 27

Histologically classic neuroblastomas are composed of what?

Answer 27

``` Small primitive appearing cells with dark nuclei, scant cytoplasm, and poorly defined cell borders growing in solid sheets Neuropil present (neuritic processes of immature neuroblasts) ```

Question 28

What is Homer-Wright pseudorosette?

Answer 28

Can be found in which the tumor cells are concentrically arranged about a central space filled with neuropil

Question 29

What is important in determining prognosis of a neuroblastoma?

Answer 29

The staging system

Question 30

When is MYCN amplified in neuroblastomas?

Answer 30

Not amplified in favorable prognosis, but amplified in unfavorable

Question 31

Ganglioneuromas are characterized by what?

Answer 31

Clusters of large cells with vesicular nuclei and abundant eosinophilic cytoplasm representing neoplasticism ganglion cells Spindle shaped Schwann cells are present in the background stroma (associated with favorable outcome)

Question 32

Regardless of the stage those diagnosed with neuroblastoma earlier than 18 months have what kind of prognosis?

Answer 32

Favorable prognosis (while those older than 18 mo will have unfavorable prognosis)

Question 33

What is FISH?

Answer 33

Uses DNA probes that recognize sequences specific to particular chromosomal regions Used to detect numeric abnormalities of chromosomes, subtle deletions or translocations, and gene amplification (e.g. NMYC amplification in neuroblastoma)

Question 34

What is chromothripsis?

Answer 34

Characterized by extensive genomic rearrangements and an oscillating pattern of DNA copy number levels all restricted to one or a few chromosomes Associated with aggressive neuroblastomas

Question 35

What is the most common primary renal tumor of childhood?

Answer 35

Wilms tumor | And the 4th MC pediatric malignancy in the US

Question 36

Describe Wilms tumor

Answer 36

Peak incidence 2-5 years of age Germline mutation leads to bilateral tumors and earlier presentation Some are a consequence of therapy mostly radiation administered to the cancer filed

Question 37

Most children with Wilms tumors present with what?

Answer 37

A large abdominal mass that may be unilateral or when very large may extend across the midline and down into the pelvis Hematuria, pain in the abd after some traumatic incident, intestinal obstruction and appearance of HTN are other patterns of presentation Pulmonary metastasis are present at the time of primary diagnosis

Question 38

Wilms tumors are characterized by what?

Answer 38

Recognizable attempts to recapitulate different stages of nephrogenesis

Question 39

What is the classic triphasic combination in Wilms tumors?

Answer 39

Blastemal, stromal and epithelial cell types observed in the vast majority of lesions (percent of each component varies)

Question 40

5% of Wilms tumors show what?

Answer 40

Anaplasia with TP53 mutation | Correlates with chemo resistance

Question 41

What are nephrogenic rests?

Answer 41

Putative precursor lesions of Wilms tumors and are seen in the renal parenchyma adjacent to approximately 25-40% of unilateral tumors Rises to nearly 100% in cases of bilateral tumors

Question 42

The risk of Wilms tumor is increased with at least 3 recognizable groups of what?

Answer 42

Congenital malformations associated with distinct chromosomal loci Includes WAGR syndrome, Denys-Drash syndrome and Beckwith-Wiedemann syndrome

Question 43

What is WAGR/WAGI syndrome?

Answer 43

Wilms tumor, Aniridia (no iris), Genital anomalies and mental Retardation/Intellectual disability Pax6 = makes protein that is involved in early development of the eyes, brain, SC and pancreas Germline WT1 deletion is first hit, second hit is frameshift or nonsense mutation in second allele 33% lifetime risk of Wilms tumor

Question 44

What is Denys-Drash syndrome?

Answer 44

90% risk of Wilms tumor Gonadal dysgenesis (male pseudohermaphrodism) Early onset nephropathy —> renal failure Increased risk of gonadoblastoma (germ cell tumors) Inactivation of WT1

Question 45

What is Beckwith-Wiedemann syndrome?

Answer 45

Characterized by organomegaly, macroglossia, hemihypertrophy, omphalocele, adrenal cytomegaly Ex of genomic imprinting (WT2-IGF2) Some have CDKN 1C mutation (a cell cycle regulatory p57 that readily inhibits multiple CDKs)

Question 46

Those with Beckwith-Wiedemann syndrome have increased risk for what?

Answer 46

Hepatoblastoma, pancreatoblastoma, adrenal cortical tumors, rhabdomyosarcoma