Path IX: neoplasia in infancy and childhood Flashcards
What is the typical presentation of cancer in adults?
epithelial cells that progress through sequential gene mutations within a single cell leading to a neoplastic clonal expansion of that cell.
What kinds of cells are typically invovled in pediatric tumors?
precursor cells, aka blastemal cells
in the organ or tissue invovled have the potential to differentiate into more than one cell line.
What is the children’s oncology group?
national organization that coordinates study protocols and research on the majority of pediatric tumors throughout the country
What is a common tumor of the kidney and what is the genetic mutation?
Wilms’ tumor (neuroblastoma)
WT1 mutation
What is a common adrenal tumor and genetic mutation?
neuroblastoma
N-myc amplification; ALK-1 mutation
What is a common pediatric CNS tumor?
medulloblastoma
What is Ewing’s sarcoma?
tumor of the soft tissue or bone caused by a t11;22 translocation
What is a tumor in the skeletal muscle called?
rhabdomyosarcoma
What are common signs of pediatric neoplasia, clinically?
failure to thrive, palpable mass on exam, fever, bone pain if metastatic
What are specific clinical signs of a renal tumor?
hematuria, oliguria, palpable flank mass
What are some clinical signs of an adrenal tumor?
hypertension if hormone secreting, hematuria if adrenal tumor invades kidney, palpable flank mass
What is a common clinical sign of hepatoblastoma?
elevated liver function tests
What is a common clinical sign of osteosarcoma?
pathologic fracture
What pediatric conditions might you see with a chest radiograph?
enlarged heart, lung infiltrates, pulmonary edema
What conditions would you see with an abdominal radiograph?
abnormal GI gas patterns, unusual calcifications and, with contrast, abnormal renal voiding patterns
What could you use an abdominal CT scan for?
defining intra-abdominal tumors: see if it involves kidney, adrneal gland, liver. Also tells you about consistency of the tumor.
When would MRI be particularly useful?
defining tissue planes btw soft tissue and bone as in osteosarcoma and Ewings sarcoma.
What is the origin of the neoplastic cell ion a neuroblastic tumor?
neuroblastic cells of the sympathetic autonomic system in either the adrenal medulla or sympathetic ganglia of the retroperitoneum
What is anew mutation recently found in neuroblastam and why is it important?
ALK1 mutation
may allow the addition of anti-tyrosine kinase chemocherapy
How are neuroblastoma tumors divided histologically?
stroma-rich vs. stroma poor.
stroma rich is schwannian stroma- ganglioneuroblastoma and ganglioneuroma; stroma poor is neuropil pericellular matrix- undifferentiated, poorly differentiated cells
What are six factors that make for an unfavorable histology for a neuroblastoma?
kid is older than 5, has a high MKI, diploid DNA ploidy, 1p deletion, 17q gain, or N-myc amplification
What is wilms’ tumor
kidney tumor of ppl under the age of 10.
triphasic: blastemal, epithelial, and stromal/mesenchymal elements.
What makes a Wilms’ tumor have unfavorable histology (3 features)
- Nuclei 3X the size of their neighbors
- hyperchromasia (incr. intensity of nuclear staining
- abnormal mitoses (multipolar)
What is heterologous differentiation?
areas that have differentiated from blastemal cells but are not native to the kidney (ie. skeletal muscle)
Ewings sarcoma/Askin tumor/primitive neuroectodermal tumor: what is the translocation common to them all?
TET family gene and an ETS-related gene translocation.
EWS/FLI1 translocation
What are important markers for the diagnosis of ES/PNET?
IHC:CD99- high sensitivity but low specificity
FISH: look for the translocation
histochemistry: PAS with and without diastase. ES/PNET cells have PAS positiveglycogen that dissolves when pretreated with diastase
EM: can elucidate intracytoplasmic organelles
What is osteosarcoma? Who is affected, where, and how does it present?
malignant neoplasm of osteoblasts that occurs during adolescence at sites of growing bones in the metaphysis of long bones near jts like the knee and hip. presents with pain and pathologic fracture
destroys cortical bone with periosteal reaction: codman triangle
What is a histologic feature required for diagnosis of osteosarcoma?
osteoid production by neoplastic osteoblasts
What are the four types of rhabdomyosarcoma? What kind of tumor is it?
soft tissue tumor embryonal RMS botryoid spindle cell alveolar
What is embryonal rhabdomyosarcoma? type, prognosis, sites, key cells
varied type
intermediate prognosis
various sites
contains strap cells- immature muscle cell called a rhabdomyoblast
What is Botryoid RMS? type, prognosis, body location
subset of embryonal RMS
good prognosis
occurs in mucosal surfaces, esp. in the GU region or head and neck region.
Spindle cell RMS: prognosis
best prognosis of RMS
What is alveolar RMS? prognosis? translocation?
worst prognosis
translocation btw FOXO1a and PAX3 or PAX7.
What are small round blue cell tumors of childhood? What distinguishes them?
poorly differentiated tumors occuring in viscera and soft tissue
distinguished by site, morphology, immunhohistochemical staining, genetic aberrations
Where might you see a teratoma?
head and neck, sacrococcygeal, mediastinum
What is an important histological feature of neuroblastoma?
homer-ritght rosettes (neuropil in the center)
What is neuroblastoma?
arises from neural crest cells. adrenal is from the adrenal medulla and extra-adrenal is from the sympathetic ganglion
What are clinical features of neuroblastoma?
most common tumor of embryonic origin. may present with metastatic disease, commonly to regional lymph nodes.
What are the three neuroblastoma tumors?
neuroblastoma, ganglioneuroblastoma, ganglioneuroma. neuroblastoma is the least mature
4 microscopic features of neuroblastoma:
- composed of neuroblasts: primitive small round cells with hyperchromatic nuclei
- formation of neuropil= extracellular eosinophilc fibrillary matrix
- intermixed with larger immature cells differentiating in the direction of ganglion cells
- homer-wright rosettes (central core of fibrillary material)
What is the mitosis-karyorrhexis index for neuroblastoma?
number of karyorrhectic cells and mitotic figures based on 5000 cells in random fields
What are some gross features of a Wilms tumor?
usually unilateral, encapsulated, well-circumscribed. cut surface is pale tan to light grey. hemorrhage, necrosis and cysts often seen
Describe the metanephric blastema of a wilms tumor.
most primitive cell type- densely packed small round oval cells with scanty cytoplasm
Describe the epithelial compoent of a wilms tumor
ranges from true rosettes to embryonic tumular structures
describe the stromal compentn of a wilms tumor
loose, immature spindle cells resembling fibroblasts that may differentiate toward skeletal muscle
What are three syndromes associated with Wilms tumors?
beckwith wiedemann (WT2 deletion) WAGRO (wilms aniridia, gu anomalies, retardation, obesity); denys drash (WT1 point mutation)
what are the most common sites for rhabdomyosarcoma?
head and neck, GU, extremities
