Gu: Who Gu - Nephroblastic Tumors P 48-55

Front 1

Nephroblastoma is a ___ embryonal neoplasm derived from __

Back 1

- malignant
- nephrogenic blastemal cells
- replicates histology of developing kidney and often shows divergent patterns of differentiation

Front 2

Prevalence of Wilms tumor

Age at diagnosis

Back 2

1/8-10,000

90% < 6yo
98% < 10yo
mean age 3-4yo
uncommon in adulthood

Front 3

Most common renal tumor of chilhood is __

Back 3

nephroblastoma

Front 4

Wilms tumor presents with __

Back 4

- palpable mass (felt by parent)
- abd pain (maybe acute abd due to traumatic rupture)
- hematuria
- HTN

Front 5

Wilms tumors are treated following two protocols (most cases)

Back 5

International Society of Pediatric Oncology (SIOP)
- advocate preop therapy followed by resection

Children's Oncology Group (COG)
- advocate primary resection followed by therapy determined by classification into "favorable" and "unfavorable" histology categories

NOTE: both show similar outcomes despite divergent philosophies

Front 6

nephroblastoma (gross)

Back 6

- most are solitary
- rounded, well-demarcated with a fibrous pseudocapsule
- may be cystic
- rarely occur in extrarenal locations

Front 7

Wilms tumor metastases typically spread to __, __, and __; metastatic tumor to other sites like bone or brain should suggest __

Back 7

resitricted pattern of metastasis
- regional lymph nodes
- lung
- liver

-- suggest alternate dx

Front 8

Wilms tumor staging in general involves

Back 8

- identification of renal capsule penetration
- renal sinus vessel involvement
- margin status
- region lymph node status

Front 9

Bilateral Wilms tumors are classified as stage __, however__

Back 9

Stage V

- But, the prognosis is based on the stage of the most advanced tumor and the presence or absence of anaplasia (each tumor is separately staged)

Front 10

Wilms tumor blastemal cells

Back 10

- small, closely-packed, mitotically active, round to oval cells with scant cytoplasm, small nucleoli

Front 11

Patterns of blastemal cells in Wilms tumor

Back 11

Diffuse pattern
- LACK cellular cohesion (contrast to other patterns)
- aggressive pattern of invasiveness (contrast to typical circumscribed, pushing invasion of most tumors)

Nodular or Serpentine pattern
- round or undulating, sharply defined cords and nests of blastemal cells in a loose fibromyxoid stroma

Front 12

Epithelial component of Wilms tumor can consist of

Back 12

- primitive rosette-like structures
- tubular or papillary elements (recapitulating normal nephrogenesis)

Heterologous epithelial elements!
- most commonly mucinous and squamous epithelium

NOTE: DDX metanephric adenoma vs. epithelial Wilms tumor
- in Wilms the tumor cells are mitotically active and much larger than those of metanephric adenoma; metanephric adenoma is seen mainly in adult females (avg age 41)
- IMPORTANT NOTE: some epithelial Wilms tumors in adults and children can have areas identical to metanephric adenoma, so extensive sampling is required
- Metanephric adenomas are often positive for WT-1 too!!

Front 13

Stromal component of Wilms tumor

Back 13

- smooth muscle
- fibroblastic

Heterologous stromal components
- skeletal muscle (most common)

- adipose
- cartilage
- bone
- ganglion cells
- neuroglial tissue

Front 14

Post-chemotherapy changes in Wilms tumor

Back 14

- necrosis
- xanthomatous histocytic foci
- hemosiderin deposits
- fibrosis
- maturation of blastema, epithelial, and stromal components (striated muscle is most frequent)

Front 15

In Wilms tumor, anaplasia correlates with ___ rather than __

Back 15

responsiveness to therapy rather than aggressiveness

Front 16

In Wilms tumor, histologic diagnosis of anaplasia requires

Back 16

- multipolar, polypoid mitotic figures
-- abn metaphase must be as larger or larger than a nml metaphase

- marked nuclear enlargement and hyperchromasia
-- at least 3 times the size of a non-anaplastic nucleus in another area of the specimen

Front 17

Focal vs. Diffuse anaplasia

Back 17

- anaplasia is more consistently associated with poor px when diffuse

Focal anaplasia:
- one or a few sharply localized regions of anaplasia within a primary tumor, confined to the kidney
- majority of tumor has NO nuclear atypia
- Anaplasia must NOT be within vascular spaces
- Anaplasia must be confined to renal parenchyma

Tumors not meeting these critieria are classified as diffuse anaplasia

Front 18

Wilms tumor IHC

Back 18

blastemal cells
- vimentin +
- +/- focal CK, desmin, NSE

WT-1
- not + in all Wilms tumors!
- correlates with histology
-- blastemal cells and areas of early epithelial differentiation are strongly WT-1+
-- stromal areas and areas of terminal epithelial differentiation are negative to weakly WT-1+

Front 19

Pediatric renal maligancies include

Back 19

- Nephroblastoma (80%)
- Nephroblastoma, anaplastic (5%)
- mesoblastic nephroma (5%)
- clear cell sarcoma
- Rhabdoid tumor
Misc:
- neuroblastoma
- PNET
- synovial sarcoma
- RCC
- angiomyolipoma
- lymphoma
- other

Front 20

Syndromes with highest risk of nephroblastoma

Back 20

- Denys-Drash syn (90% risk)
- WAGR syn (30%)
- Beckwith-Wiedemann syn
- hemihypertrophy
- familial nephroblastoma

Front 21

patients with WAGR syn have ___ of WT1 gene, while patients with Denys-Drash syn have __

Back 21

WAGR syn: deletions of WT1 gene

DD syn: point mutation in one copy of WT1 gene with tumors showing loss of other nml allele

Front 22

Nephrogenic rests

Back 22

abnormally persistent foci of embryonal cells capable of developing into nephroblastomas

Front 23

Neophroblastomatosis

Back 23

diffuse or multifocal nephrogenic rests

Front 24

Nephrogenic rests are found in 25-40% of pts with __ and 1% of __

Back 24

- nephroblastomas
- infant autopsies

Front 25

nephrogenic rests can be divided into __ and __

Back 25

PLNR (perilobar nephrogenic rests) and ILNR (intralobar NR)

Front 26

PLNR can remain ___ or __

Back 26

- dormant
- (most commonly) regress
- hyperplastic nephrogenic rest (almost impossible to distinguish from a nephroblastoma)

Front 27

nephroblastoma developing in a PLNR is recognized by __

Back 27

- spherical expansile growth with peritumoral fibrous pseudocapsule formation (similar for tumors arising in ILNR)

Front 28

Diffuse hyperplastic nephroblastomatosis has a high risk of developing __

Back 28

- nephroblastomas
- more likely to be multiple and exhibit anaplasia

Front 29

cystic partially differentiated nephroblastoma is a __

Back 29

- rare, multilocular cystic neoplasm of very young children
- composed of epithelial and stromal elements with nephroblastomatous tissue

Front 30

cystic partially differentiated nephroblastoma is a Wilms tumor composed entirely of __

Back 30

- cysts with delicate septa
- within septa are small foci of blastema, immature-appearing stromal cells, and primitive or immature epithelium

Front 31

cystic partially differentiated nephroblastoma without nephroblastomatous elements is called __

Back 31

- cystic nephroma, although this is NOT the same thing as teh morphologically similar cystic nephromas that occur in adults

Front 32

cystic partially differentiated nephroblastoma occurs in __

Back 32

- boys > girls
- most before 2yo

Front 33

cystic partially differentiated nephroblastoma entirely made up of ___ and lack __

Back 33

- cysts
- lack expansile nodules to alter the rounded cyst contour

Front 34

Cysts in cystic partially differentiated nephroblastoma are lined by

Back 34

- flattened, cuboidal, or hobnail epithelial cells
- may LACK an epithelial linig too

Front 35

Septa in cystic partially differentiated nephroblastoma contain

Back 35

- variably celullar differentiated and undifferentiated mesenchymal cells
- blastema
- nephroblastomatous epithelial elements
- skeletal muscle and myxoid mesenchyme are present in most tumors
- may see cartilage and fat