Pediatric Tumors Flashcards
under the SIOP protocol, a history of wedge biopsy prior to chemotherapy or surgery with upstage the post-chemotherapy pediatric renal tumor to Stage__
Stage III
In the SIOP protocol, history of these biopsies does not upstage post-chemotherapy pediatric renal tumor but the size of the needle gauge should be mentioned to the pathologist.
- Fine needle aspiration biopsy; or
- percutaneous core needle (“tru-cut”) biopsy
In the SIOP protocol, what tumor histologic types needs to subtyped (4)?
- Wilms Tumor (nephroblastoma)
- Mesoblastic nephroma
- Clear cell sarcoma of the Kidney
- Rhabdoid tumor of the Kidney
SIOP protocol
Categorize the risk (Low, Intermediate, or High) of these tumor subtypes:
- Mesoblastic nephroma
- Cystic partially differentiated nephroblastoma
- Nephroblastoma-completely necrotic
Low-risk
MCN
SIOP protocol
Categorize the risk (Low, Intermediate, or High) of these tumor subtypes:
- Nephroblastoma-blastemal type
- Nephroblastoma-diffuse anaplasia type
- Clear Cell Sarcoma of the kidney
- Rhabdoid tumor of the kidney
High-risk
SIOP protocol
Categorize the risk (Low, Intermediate, or High) of these tumor subtypes:
- Nephroblastoma-epithelial type
- Nephroblastoma-stromal type
- Nephroblastoma-mixed type
- Nephroblastoma-regressive type
- Nephroblastoma-focal anaplasia type
Intermediate-risk
SIOP protocol
Only Nephroblastoma subtype that is Low-risk
Nephroblastoma-completely necrotic
SIOP protocol
Two Nephroblastoma subtypes that are high-risk
- Nephroblastoma-blastemal type
- Nephroblastoma-diffuse anaplasia type
SIOP protocol
Nephroblastoma-anaplasia type that has Intermediate-risk
-Nephroblastoma-focal anaplasia type
SIOP protocol
Nephroblastoma-anaplasia type that has High-risk
-Nephroblastoma-diffuse anaplasia type
SIOP protocol
Criteria for anaplasia in a RESECTION specimen (3):
- atypical (tri/multipolar) mitotic figures
- marked nuclear enlargement (defined as diameters 3X of adjacent cells)
- hyperchromatic tumor cell nuclei.
SIOP protocol
In a RESECTION specimen, Anaplasia is defined as presence of _ three of these criteria.
ALL
SIOP protocol
For BIOPSY specimens, anaplasia can be mentioned if the tumor meets at least _ of these criteria.
ONE
SIOP protocol
Criteria for anaplasia in a BIOPSY specimen (2):
(1) atypical (tri/multipolar) mitotic figures; OR
2) marked nuclear enlargement (defined as diameters 3X of adjacent cells
SIOP protocol
__ do NOT qualify as anaplasia and should not be included in the assessment of nuclear enlargement.
rhabdoymyoblastic foci
SIOP protocol
defined as anaplasia involving a clearly defined focus within the primary intrarenal tumor
Focal anaplasia
SIOP protocol
The criteria for focal anaplasia must meet _ of the following criteria
ALL
SIOP protocol
Criteria for focal anaplasia (5):
- anaplasia present in less than five foci in the intrarenal tumor;
- absence of anaplasia in the renal vessels;
- absence of anaplasia outside the kidney,
- anaplastic focus should be completely surrounded by non-anaplastic tissue; AND
- the rest of the non-anaplastic tumor must NOT show severe nuclear unrest
SIOP protocol
In focal anaplasia, this is defined as enlarged nuclei with no atypical mitosis
Severe nuclear unrest
SIOP protocol
TRUE / FALSE:
For multifocal tumors, specify dimension of each additional tumor in the gross, but not necessarily in the final diagnosis
TRUE
SIOP protocol
Lymph nodes with “involvement by tumor” includes (3):
- viable tumor cells
- nonviable tumor cells
- chemotherapy-induced changes in the lymph nodes
SIOP protocol
STAGE:
The tumor is limited to kidney or surrounded with a fibrous (pseudo)capsule if outside of the normal contours of the kidney. The renal capsule or pseudocapsule may be infiltrated by the tumor but it does not reach the outer surface.
Stage I
SIOP protocol
STAGE:
The tumor may be protruding (“bulging”) into the pelvic system and “dipping” into the ureter
but it is not infiltrating their walls.
Stage I
SIOP protocol
STAGE:
The vessels or the soft tissues of the renal sinus are not involved.
Stage I
SIOP protocol
STAGE:
Intrarenal vessel involvement may be present.
Stage I
SIOP protocol
STAGE:
Viable tumor penetrates through the renal capsule and/or fibrous pseudocapsule into perirenal fat but is completely resected (resection margins “clear”).
Stage II
SIOP protocol
STAGE:
Viable tumor infiltrates the soft tissues of the renal sinus.
Stage II
SIOP protocol
STAGE:
Viable tumor infiltrates blood and lymphatic vessels of the renal sinus or in the perirenal
tissue but it is completely resected.
Stage II
SIOP protocol
STAGE:
Viable tumor infiltrates the renal pelvic or ureter’s wall.
Stage II
SIOP protocol
STAGE:
Viable tumor infiltrates adjacent organs or vena cava but is completely resected.
Stage II
SIOP protocol
STAGE:
Viable or non-viable tumor extends beyond resection margins.
Stage III
SIOP protocol
STAGE:
Any abdominal lymph nodes are involved.
Stage III
SIOP protocol
STAGE:
Tumor rupture before or intraoperatively (irrespective of other criteria for staging).
Stage III
SIOP protocol
STAGE:
The tumor has penetrated through the peritoneal surface.
Stage III
SIOP protocol
STAGE:
Tumor implants are found on the peritoneal surface.
Stage III
SIOP protocol
STAGE:
The tumor thrombi present at resection margins of vessels or ureter, are transsected or
removed piecemeal by surgeon.
Stage III
SIOP protocol
STAGE:
The tumor has been surgically biopsied (wedge biopsy) prior to preoperative chemotherapy or surgery.
Stage III
SIOP protocol
STAGE: Hematogenous metastases (lung, liver, bone, brain, etc) or lymph node metastases outside the abdomino-pelvic region.
Stage IV
SIOP protocol
STAGE:
Bilateral renal tumors at diagnosis. Each side should be sub-staged according to the above criteria.
Stage V
Typical demographics of Lymphoma
Children and Adolescents
Typical demographics of Ewing Sarcoma
- 5yo to 30s
- Caucasians
Typical demographics of Alveolar Rhabdomyosarcoma
Adolescents
Typical demographics of Neuroblastoma
Birth to 5yo
Typical demographics of Synovial Sarcoma
Teens to 30s
Typical demographics of Wilms Tumor
Infants to 6yo
Typical demographics of Rhabdoid Tumor
Birth to 3yo
Typical demographics of MPNST
- Teens to 50s
- 50% also NF1
Typical demographics of Melanoma
increasing incidence with age
Typical demographics of Desmoplastic Small Round Cell Tumor
- Teens to 30s
- Males
Typical Locations of Lymphoma (3)
- Bone Marrow
- Nodes
- Thymus
Typical Locations of Ewing Sarcoma (2)
- Diaphyseal bone
- Soft tissue
Typical Locations of Alveolar Rhabdomyosarcoma (3)
- Head and Neck
- Extremities
- Genitourinary
Typical Locations of Neuroblastoma (2)
- Adrenal gland
- Paraspinal
Typical Locations of Synovial Sarcoma (2)
- Extremities
- Head and Neck
Typical Location of Wilms Tumor
Kidney
Typical Locations of Rhabdoid tumor (2)
- Kidney
- Soft tissue
Typical Locations of of MPNST (2)
- Proximal limbs
- Trunk
Typical Locations of Melanoma (2)
- Skin
- Metastatic
Typical Locations of DSRCT
-Diffuse abdominal disease “Carcinomatosis”
Key histologic features of Lymphoma (2)
- Discohesive
- Lymphoglandular
Key histologic feature of Ewing Sarcoma
-Foamy cytoplasm
Key histologic features of Alveolar Rhabdomyosarcoma
- Discohesive
- liner “picket fence” of cells at edges of nests
Key histologic features of Neuroblastoma (2)
- Neuropil
- Neural differentiation
Key histologic features of Synovial sarcoma (2)
- HPC-vessels
- Variable features
Key histologic features of Wilms Tumor (2)
- Triphasic
- Glomeruloid differentiation
Key histologic feature of Rhabdoid tumor
-Prominent rhabdoid cytology
Key histologic features of MPNST (2)
- Spindled
- relative pleomorphism
Key histologic feature of Melanoma
-Variable
Key histologic features of DSRCT (2):
- Desmoplastic stroma
- Ewing-like cytology
Key Test for Lymphoma
CBC
Key Tests for Ewing Sarcoma
- CD99+
- Nkx2.2+
- EWSR1 fusions
Key Tests for Alveolar Rhabdomyosarcoma
- Myogenin
- MyoD1
- Desmin
Key Test for Neuroblastoma
PHOX2B
Key Test for Synovial Sarcoma
SS18 rearranged
Key Tests for Wilms Tumor
- WT1 (N-term+, C-term+)
- Desmin +/-
- Keratin +/-
Key Test for Rhabdoid Tumor
INI-1 negative
Key Tests for MPNST
- focal S100
- SOX9/SOX10
Key Tests for Melanoma
- S100
- MART-1
Key Tests for DSRCT
- Desmin
- Keratin
- EWSR1-WT1 translocation
- WT1 (N-term-, C-term+)
Key Molecular Feature of Lymphoblastic Lymphoma
Hyperdiploid
Favorable / Unfavorable:
The hyperdiploid molecular feature in Lymphoblastic Lymphoma
Favorable
Key Molecular Features of Burkitt Lymphoma (3):
- t(8;14) - MYC-IgH
- t(2;8) - Kappa-MYC
- t(8;22) - MYC-Lambda
Key Molecular Features of Ewing Sarcoma (2):
- t(11;22) - EWSR1-FLI1
- t(21;22) - EWSR1-ERG
Key Molecular Features of Alveolar Rhabdomyosarcoma (2)
- t(1;13) - PAX7-FOXO1
- t(2;13) - PAX3-FOXO1
Key Molecular Feature of Neuroblastoma:
MYCN amplification (high risk)
Key Molecular Features of Synovial Sarcoma
t(X;18) SS18-SSX1, 2, 4
Key Molecular Feature of DSRCT:
t(11;22) EWSR1-WT1
Key Molecular Feature of Rhabdoid Tumor
INI-1 (SMARCB1) deletion
SIOP protocol
Three tumor interfaces needed to block:
- Tumor-kidney interface
- Tumor-capsule interface
- Tumor-renal sinus interface
SIOP protocol
In subtyping of post-treated Wilms Tumor, percentage of WHAT needs to be assessed? (2)
- Necrosis
- Different components of the tumor (blastemal, epithelial, stromal)
SIOP protocol
TRUE/FALSE:
Tumors with focal anaplasia should still be subtyped on the basis of other components
True
SIOP protocol
post-treated Wilms Tumor:
Assessed Necrosis = 100%
Completely Necrotic
SIOP protocol
post-treated Wilms Tumor:
Assessed Necrosis >66%
Regressive type
SIOP protocol
post-treated Wilms Tumor:
Assessed Necrosis <66%
-Assess Blastemal Component in Viable tumor
SIOP protocol
post-treated Wilms Tumor:
Assessed Blastemal component >66%
Blastemal type
SIOP protocol
post-treated Wilms Tumor:
Assessed Blastemal component 10%-66%
Mixed type
SIOP protocol
post-treated Wilms Tumor:
Assessed Blastemal component <10%
-Assess other components in Viable tumor
SIOP protocol
post-treated Wilms Tumor:
Assessed other components (Epithelial >66%)
Epithelial type
SIOP protocol
post-treated Wilms Tumor:
Assessed other components (Stromal >66%)
Stromal type
SIOP protocol
post-treated Wilms Tumor:
Assessed other components (No predominant)
Mixed type
SIOP protocol
Renal sinus vascular involvement is easy to confirm when (2):
- Tumor fills the lumen; OR
- Tumor invades the vascular wall
SIOP protocol
Displacement artifact is also readily identified when (3)
- present in arterial lumina
- accompanied by abundant displacement artifact elsewhere
- ink is present within the aggregates
The protocol for pediatric extragonadal germ cell tumors is only applied to tumors located in the: (5)
- Mediastinum
- Sacrococcygeal area
- Retroperitoneum
- Neck
- Intracranial sites
Pediatric EGGCT protocol
Congenital/neonatal age group
Birth to 6 months
Pediatric EGGCT protocol
Childhood/prepubertal age group
7 months to 11 years old
Pediatric EGGCT protocol
Postpubertal/adult
greater than or equal to 12 years old
Pediatric EGGCT protocol
Head and Neck region tumor site INCLUDES
-Thyroid
Pediatric EGGCT protocol
Head and Neck region tumor site EXCLUDES
-Intracranial
Pediatric EGGCT protocol
Mediastinum tumor site includes (4):
- Pericardium
- Heart
- Thymus
- Lung
Pediatric EGGCT protocol
Histologic (Norris) Grade:
Neoplasms with some immaturity (of any cell type), but with immature neuroepithelium absent or limited to collectively occupying no more than one 4x objective, on a single slide, ≤1 LPF.
Grade 1
Pediatric EGGCT protocol
Histologic (Norris) Grade:
Neoplasms with more immaturity and primitive neuroepithelium greater than 1 and not exceeding 3 low-power (4x objective) fields per slide, between 1-3 LPF’s.
Grade 2
Pediatric EGGCT protocol
Histologic (Norris) Grade:
Neoplasms in which immaturity and primitive neuroepithelium are prominent, primitive neuroepithelium present in >3 low-power (4x objective) fields per slide, >3 LPFs.
Grade 3
Pediatric EGGCT protocol
Which type of resection specimen does Microscopic Tumor Extension needs to be reported?
Sacrococcygeal resections ONLY
Pediatric EGGCT protocol
Which of the elements that needs to be reported is optional but still needed to be indicated if present? (2)
- LVI
- PNI
Pediatric EGGCT protocol
This staging for any Malignant EGGCT is based on the pretreatment tumor characteristics
Children’s Oncology Group (COG) staging
Pediatric EGGCT protocol
COG stage:
- Complete resection at any site;
- coccygectomy for sacrococcygeal site;
- negative tumor margins
Stage I
Pediatric EGGCT protocol
COG stage:
- Microscopic residual;
- lymph nodes negative
Stage II
Pediatric EGGCT protocol
COG stage:
-Lymph nodes involved by metastatic disease.
-Gross residual or biopsy only, retroperitoneal
nodes negative or positive
Stage III
Pediatric EGGCT protocol
COG stage:
-Distant metastases, including liver
Stage IV
Pediatric EGGCT protocol
What serologic markers are needed?
- alpha-fetoprotein (AFP)
- human chorionic gonadotropin (HCG)
Pediatric EGGCT protocol
What are needed to be identified when grossing sacrococcygeal tumors?
- Coccyx
- Soft tissue margins
Pediatric EGGCT protocol
At least _ section per centimeter of the tumor’s greatest dimension.
one
Pediatric EGGCT protocol
Within the pediatric age range, prognosis is worse with _ age.
increasing
Pediatric EGGCT protocol
For _ age group, immaturity is not predictive of malignant behavior
congenital/neonatal
Pediatric EGGCT protocol
For congenital/neonatal age group, completeness of resection is more associated with recurrences of a _ tumor
pure yolk sac tumor
Pediatric EGGCT protocol
For prepubertal/child age group, grade 2 to 3 immaturity are more frequently associated with _ tumor
admixed yolk sac tumor
Pediatric EGGCT protocol
For the _ age group, no grading schema for extragonadal immature teratomas is used at present, however, it is reasonable to report the percentage of immature elements
postpubertal
Pediatric EGGCT protocol
In specimens treated with chemotherapy prior resection, the tissue usually shows (4):
- Necrosis
- Fibrosis
- Mixed inflammatory infiltrates
- Xanthogranulomatous inflammation
Pediatric EGGCT protocol
Less than _% viable tumor cells are a good prognostic factor as defined by the International Germ Cell Consensus Classification Group (IGCCCG)
10%
RB protocol
All measurements are in _
Millimeters
RB protocol
Histologic Grade:
Tumor with areas of retinocytoma (fleurettes or neuronal differentiation)
G1
RB protocol
Histologic Grade:
Tumor with many rosettes (Flexner-Wintersteiner or Homer Wright)
G2
RB protocol
Histologic Grade:
Tumor with occasional rosettes (Flexner-Wintersteiner or Homer Wright)
G3
RB protocol
Histologic Grade:
Tumor with poorly differentiated cells without rosettes and/or with extensive areas (more
than half of tumor) of anaplasia
G4
RB protocol
Histologic Grade:
Grade cannot be assessed
GX
RB protocol
Choroid extension of solid tumor is less than 3 mm in maximum diameter (width or thickness)
Minimal
RB protocol
Choroid extension of solid tumor is more than 3 mm in maximum diameter (width or thickness)
Massive
RB protocol
What part of the eye should be mentioned if the tumor involves less than or more than two-thirds?
Sclera
RB protocol
The depth of the tumor invasion into the optic nerve should be measured from the (3):
- Limiting membrane of the optic disc
- Exit of the large central vessels
- level of the Bruch membrane
* in decreasing order
RB protocol
Primary Tumor (pT):
Unknown evidence of intraocular tumor
pTX
RB protocol
Primary Tumor (pT):
No evidence of intraocular tumor
pT0
RB protocol
Primary Tumor (pT):
Intraocular tumor(s) without any local invasion, focal choroidal invasion, or pre- or intralaminar involvement of the optic nerve head
pT1
RB protocol
Primary Tumor (pT):
Intraocular tumor(s) with local invasion
pT2
RB protocol
Primary Tumor (pT):
Concomitant focal choroidal invasion and pre- or intralaminar involvement of the optic nerve head
pT2a
RB protocol
Primary Tumor (pT):
Tumor invasion of stroma of iris and/or trabecular meshwork and/or Schlemm’s canal
pT2b
RB protocol
Primary Tumor (pT):
Intraocular tumor(s) with significant local invasion
pT3
RB protocol
Primary Tumor (pT):
Massive choroidal invasion (>3 mm in largest diameter, or multiple foci of focal choroidal involvement totaling >3 mm, or any full-thickness choroidal involvement)
pT3a
RB protocol
Primary Tumor (pT):
Retrolaminar invasion of the optic nerve head, not involving the transected end of the optic nerve
pT3b
RB protocol
Primary Tumor (pT):
Any partial-thickness involvement of the sclera within the inner two thirds
pT3c
RB protocol
Primary Tumor (pT):
Full-thickness invasion into the outer third of the sclera and/or invasion into or around emissary channels
pT3d
RB protocol
Primary Tumor (pT):
Evidence of extraocular tumor:
- tumor at the transected end of the optic nerve
- tumor in the meningeal spaces around the optic nerve
- full-thickness invasion of the sclera with invasion of the episclera, adjacent adipose tissue, extraocular muscle, bone, conjunctiva, or eyelids
pT4
RB protocol
Regional Lymph Nodes (pN):
Regional lymph nodes cannot be assessed
pNX
RB protocol
Regional Lymph Nodes (pN):
No regional lymph node involvement
pN0
RB protocol
Regional Lymph Nodes (pN):
Regional lymph node involvement
pN1
RB protocol
Distant Metastasis (pM) (required only if confirmed pathologically in this case):
Distant metastasis with histopathologic confirmation
pM1
RB protocol
Distant Metastasis (pM) (required only if confirmed pathologically in this case):
Histopathologic confirmation of tumor at any distant site (eg. bone marrow, liver, or
other)
pM1a
RB protocol
Distant Metastasis (pM) (required only if confirmed pathologically in this case):
Histopathologic confirmation of tumor in the cerebrospinal fluid or CNS parenchyma
pM1b
RB protocol
Definition of Heritable Trait (H):
Unknown or insufficient evidence of a constitutional RB1 gene mutation.
HX
RB protocol
Definition of Heritable Trait (H):
Normal RB1 alleles in blood tested with demonstrated high-sensitivity assays
H0
RB protocol
Definition of Heritable Trait (H):
Bilateral retinoblastoma, any retinoblastoma with an intracranial primitive neuroectodermal tumor (ie, trilateral retinoblastoma), patient with family history of retinoblastoma, or molecular definition of a constitutional RB1 gene mutation
H1
RB protocol
Pathologic stage group: pT - pT1, pT2, pT3 pN - pN0 M - cM0 pH - any
I
RB protocol
Pathologic stage group: pT - pT4 pN - pN0 M - cM0 pH - any
II
RB protocol
Pathologic stage group: pT - any pN - pN1 M - cM0 pH - any
III
RB protocol
Pathologic stage group: pT - any pN - any M - cM1 or pM1 pH - any
IV
RB protocol
What should be sampled first if fresh tumor samples are needed for genetic studies?
Optic nerve margin
RB protocol
Fix the specimen for _ hours in buffered formalin in a _ ratio
- 48 hours
- 10:1
RB protocol
The cornea is:
Wider than taller
RB protocol
The optic nerve attachment is:
skewed nasally (medially)
RB protocol
Superior oblique muscle insertion is at the:
-UO quadrant (superotemporal) behind superior rectus insertion
RB protocol
The tendon and muscle fibers of superior oblique muscle run towards the:
superonasal aspect
RB protocol
Inferior oblique muscle wide insertion is at the:
inferotemporal (inferolateral) quadrant of sclera
RB protocol
Inferior oblique muscle wide insertion is _ to the optic nerve
temporal (lateral)
RB protocol
What structure marks the equatorial (horizontal) plane?
Long posterior ciliary arteries
RB protocol
What structure exits at 45 degrees from the sagittal (vertical) and equatorial planes?
Vortex veins
RB protocol
This invasion is identified when there are groups of tumor cells present in the open spaces between intraocular structures, extraocular tissues and/or subarachnoid space.
Artifactual invasion
RB protocol
This invasion is defined as 1 or more solid nests of tumor cells that fills or replaces the choroid and has pushing borders
True invasion
RB protocol
Invasion of this is not a form of choroidal invasion
sub-retinal pigment epithelium (RPE) space
-where tumor cells are present under the RPE (but not beyond Bruch’s membrane into the choroid)
RB protocol
This invasion is defined as a solid nest of tumor that measures less than 3 mm in maximum diameter (width or thickness)
Focal choroidal invasion
RB protocol
This invasion is defined as a solid tumor nest 3 mm or more in maximum diameter (width or thickness) in contact with the underlying sclera.
Massive choroidal invasion
Histologic features:
- No schwannian stroma / No Neuropil
- Requires adjunctive diagnostic tests
Diagnosis?
Neuroblastoma, undifferentiated
Histologic features:
- Schwannian stroma poor
- Presence of neuropil allows for H&E diagnosis
- Less than 5% differentiating neuroblasts
Neuroblastoma, Poorly differentiated
Histologic features:
- Schwannian stroma poor
- More abundant neuropil
- > 5% differentiating neuroblasts
Neuroblastoma, Differentiating
Histologic features:
- Schwannian stroma comprises >50% of the tumor
- Microscopic foci of neuropil contain neuroblastic cells at varying stages of maturation
- No macroscopic nodules present
Ganglioneuroblastoma, intermixed
Histologic features:
- Schwannian stroma is the predominant element of the tumor
- Scattered ganglion cells are mature or maturing
- No neuropil is present
Ganglioneuroma, maturing
Histologic features:
- Schwannian stroma is the predominant element of the tumor
- Scattered ganglion cells are mature with surrounding satellite cells
- No neuropil is present
Ganglioneuroma, mature
Histologic features:
- Composite stroma rich/dominant and stroma poor
- Grossly visible nodule consists of any type of stroma poor neuroblastoma
- Background of ganglioneuroblastoma or ganglioneuroma
- Nodular component should also be classified
Ganglioneuroblastoma, Nodular
INPC:
Any age with Favorable Histology (2)
- Ganglioneuroblastoma, intermixed
- Ganglioneuroma, mature or maturing
INPC:
<18 months with Favorable Histology (2)
- Neuroblastoma, poorly differentiated, with low or intermediate MKI
- Neuroblastoma, differentiating, with low or intermediate MKI
INPC:
18-60 months with Favorable Histology (1)
Neuroblastoma, differentiating, with low MKI
INPC:
Any age with Unfavorable histology (2)
- Neuroblastoma, undifferentiated
- Neuroblastoma, of any subtype, with high MKI
INPC:
18-60 months with Unfavorable histology (2):
- Neuroblastoma, poorly differentiated
- Neuroblastoma, differentiating, with intermediate MKI
INPC:
> 60 months with Unfavorable histology
Neuroblastoma of any subtype
INPC
Count of all mitotic and karyorrhectic figures present per 5000 neuroblasts
Mitosis-karyorrhexis index (MKI)
INPC
Category of MKI:
- <100/5000
- 2%
Low
INPC
Category of MKI:
- 100-200/5000
- 2%-4%
Intermediate
INPC
Category of MKI:
> 200/5000
->4%
High
Tumors of the neuroblastoma group are defined as embryonal tumors of the sympathetic nervous system derived from the __
Neural crest
Tumors of the neuroblastoma group arise in the (3):
- Adrenal medulla
- Paravertebral sympathetic ganglia
- Sympathetic paraganglia, such as the Organ of Zuckerkandl
Most common solid neoplasm in childhood other than CNS tumors accounting for approximately 15% of all neoplasms encountered in the first 4 years of life
Neuroblastic tumors
The neural crest is known to give rise to (6):
- cells of the future Adrenal medulla
- neuronal cells of the autonomic NS
- Schwannian cells
- Melanocytes
- some types of NEC
- mesenchymal-type tissue in the H and N region
Types of unique biologic behaviors of Neuroblastic tumors (3)
- Involution / Spontaneous regression
- Maturation
- Aggressive proliferation
Type of Biologic behavior of NTs:
characterized by massive cellular death of still-immature neuroblasts before complete differentiation.
Involution / Spontaneous regression
Aggregates of immature neural crest cells
Neuroblastic nodules
Two main cell populations of Neuroblastic tumors:
- Neuroblastic / Ganglionic cells
- Schwann cells
Microscopically, these are composed of neuroblastic cells that form groups or nests separated by delicate, often in- complete stromal septa without or with limited Schwannian proliferation
Schwannian stroma-poor tumors
characterized by a ganglioneuromatous appearance with mature and/or maturing ganglion cells individually scattered in a background of highly developed Schwannian stroma (2)
- Schwannian stroma-rich tumors
- Schwannian stroma-dominant tumors
The INPC has restricted the term ganglioneuroblastoma to those tumors with two distinctive components:
1) a mature Schwannian stromal component with individually scattered mature and/or maturing ganglion cells (i.e., ganglioneuromatous tissue); AND
2) a neuroblastic component
This term refers to the ganglioneuromatous component of the tumor
Ganglio-
The neuroblastic component can be seen (2):
1) as multiple microscopic foci (ganglioneuroblastoma, intermixed subtype); or
2) in distinct macroscopic and commonly hemorrhagic nodule(s) (ganglioneuroblastoma, nodular subtype)
In neuroblastic tumors, this is defined as the number of tumor cells in mitosis and in the process of karyorrhexis
Mitosis karyorrhexis index (MKI)
in MKI, high cellularity is
700-900 cells per HPF
in MKI, moderate cellularity is
400-600 tumor cells
in MKI, low cellularity with extensive neuropil
100-300 cells per HPF
In highly cellular tumors, the MKI can be determined in:
6-8 HPFs (x400)
in tumors with a low cellularity with a prominent neuropil, MKI can be determined in:
20 or more HPFs
in MKI, these are characterized by more or less rod-shaped condensations of chromatin with spiked projections and the absence of a nuclear membrane
Mitotic figures
in MKI, these show condensed and fragmented nuclear material usually accompanied by condensed eosinophilic cytoplasm
Karyorrhectic cells
This is determined by counting of 10 contiguous HPFs at x400 magnification
Mitotic rate (MR)
Low MR class
less than or equal to 10 mitoses in 10 HPFs
a characteristic feature of embryonal tissues and some solid neoplasms of infancy, without the connotation that the latter are overtly malignant or aggressive tumors
Higher mitotic rate
in NTs, this appears as dense basophilic clumps or amorphous granular material in areas of viable or necrotic tumor
Calcification
defines tumors that show an unequivocal categorization, although the subtype cannot be determined be- cause of poor quality of the sections, extensive hemorrhage, cystic degeneration, necrosis, crush artifact, and/or diffuse calcification
Neuroblastoma (Schwannian stroma-poor), NOS
refers to the rare, but observed, tumor with a stroma-rich appearance containing area(s) of extensive calcification that may obscure a stroma-poor neuroblastic nodule.
Ganglioneuroblastoma, NOS
INSS Stage:
Localized tumor with complete gross excision
Stage I
INSS Stage:
Ipsilateral “non-adherent” lymph node negative
microscopically
Stage I
INSS Stage:
May include positive margins (microscopic residual disease)
Stage I
INSS Stage:
May include positive lymph node if adherent to
resected tumor
Stage I
INSS Stage:
Localized tumor with incomplete gross excision
Stage II
INSS Stage:
Ipsilateral “non-adherent” lymph node negative
microscopically
Stage IIA
INSS Stage:
Ipsilateral “non-adherent” lymph node positive
microscopically
Stage IIB
INSS Stage:
Any enlarged contralateral lymph node
confirmed microscopically negative
Stage IIB
INSS Stage:
Unresectable unilateral tumor crossing vertebral column with or without regional lymph node involvement
Stage III
INSS Stage:
Localized unilateral tumor with contralateral lymph node involvement
Stage III
INSS Stage:
Unresectable midline tumor with bilateral tumor infiltration or lymph node involvement
Stage III
INSS Stage:
Any primary tumor with distant metastasis to lymph node, bone, bone marrow, liver, skin or other organs not defined as stage IVS
Stage IV
INSS Stage:
Infant younger than 12 months
Stage IVS
INSS Stage:
Localized primary tumor (stage I, IIA, or IIB) with dissemination limited to skin, liver, and/or bone marrow
Stage IVS
INSS Stage:
Bone marrow involvement must have <10% cellularity
Stage IVS
INSS Stage:
Bone marrow must be metaiodobenzyl guanidine scan negative
Stage IVS
Most common neoplasm of childhood, typically presenting as a leukemia
Lymphoblastic leukemia/lymphoma
Lymphoblastic leukemia/lymphoma are most often
B-cell (>80%)
40% of all childhood lymphomas
Burkitt lymphoma
Histologic features of Burkitt Lymphoma:
- Cytoplasmic vacuoles
- Starry sky of tingible body macrophages
IHC of lymphoblastic lymphoma targets:
Immature lymphocyte, most often B-cell
POSITIVE/NEGATIVE IHCs for
Lymphoblastic Lymphoma:
- CD20
- CD19
- CD10
- TdT
- CD34
- CD99
Positive
-CD10 (+/-)
POSITIVE/NEGATIVE IHCs for Lymphoblastic Lymphoma:
- surface Ig
- myeloid markers
Negative
IHC for Burkitt Lymphoma targets:
Mature germinal center B-cell
POSITIVE/NEGATIVE IHCs for Burkitt Lymphoma:
- CD20
- CD19
- CD10
- BCL-6
- Ki-67
- surface Ig
Positive
-Ki-67 (>90%)
POSITIVE/NEGATIVE IHCs for Burkitt Lymphoma:
- TdT
- BCL2
- CD34
Negative
ENDEMIC / SPORADIC
Burkitt Lymphoma:
- Males
- Africa and Papua New Guinea
Endemic
ENDEMIC / SPORADIC
Burkitt Lymphoma:
-Jaw or facial bones
Endemic
ENDEMIC / SPORADIC
Burkitt Lymphoma:
-EBV+ (98%)
Endemic
ENDEMIC / SPORADIC
Burkitt Lymphoma:
- Males
- Caucasians
Sporadic
ENDEMIC / SPORADIC
Burkitt Lymphoma:
-Abdominal mass
Sporadic
ENDEMIC / SPORADIC
Burkitt Lymphoma:
-Less often EBV+ (20-30%)
Sporadic
B- or T- LL:
Young child with anterior mediastinal mass
T-Lymphoblastic Lymphoma
can present as “blueberry muffin” babies
Neuroblastoma
Classify:
- At least 50% schwannian stroma
- Gross nodule that is microscopically neuroblastoma
Ganglioneuroblastoma, nodular
Classify:
- At least 50% schwannian stroma
- No nodule identified
Assess location of Neuroblasts
Classify:
- At least 50% schwannian stroma
- No nodule identified
- Neuroblasts all in Schwannian stroma
Ganglioneuroma
Classify:
- At least 50% schwannian stroma
- No nodule identified
- Neuroblasts any in Neuropil
Ganglioneuroblastoma, intermixed
Classify:
- Less than 50% Schwannian stroma
- No neuropil
Neuroblastoma, undifferentiated
Classify:
- Less than 50% Schwannian stroma
- with neuropil
-Assess degree of differentiation
Classify:
- Less than 50% Schwannian stroma
- with neuropil
- at least 5% degree of differentiation
Neuroblastoma, differentiating
Classify:
- Less than 50% Schwannian stroma
- with neuropil
- less than 5% degree of differentiation
Neuroblastoma, poorly differentiated
INRG Pretreatment risk group:
- <18 months
- NA MYCN
- with Hyperdiploidy
Low risk
INRG Pretreatment risk group:
- <12 months
- NA MYCN
- with diploidy
Intermediate risk
INRG Pretreatment risk group:
- 12 to <18 months
- NA MYCN
- with diploidy
Intermediate risk
Type of Synovial Sarcoma:
Histology - round/oval cells, short fascicles
Poorly differentiated
Type of Synovial Sarcoma:
Histology - spindle cells with long fascicles
Monophasic
Type of Synovial Sarcoma:
Histology - spindle cells with epithelial elements
Biphasic
IHC: -TLE1+ -CD99+ CK7+ -decreased INI-1
Diagnosis?
Synovial Sarcoma
associated with WAGR and Beckwith-Wiedemann syndrome
Wilms Tumor
Renal tumor to be expected in <1 yo (3)
- Congenital mesoblastic nephroma
- Wilms Tumor
- Rhabdoid tumor
Renal tumor to be expected in 1-4 yo (3)
- Wilms tumor
- Rhabdoid tumor of kidney
- Clear cell sarcoma
Renal tumor to be expected in >4-5 yo
Wilms tumor
Renal tumor to be expected in >5-10 yo (3)
- Wilms tumor
- Clear cell sarcoma
- Renal cell carcinoma
Renal tumor to be expected in >10-19 yo (2)
- Renal cell carcinoma
- PNET/Ewing sarcoma
INI-1 loss tumors (9):
- Malignant rhabdoid tumor
- ATRT (CNS)
- Renal medullary carcinoma
- Epithelioid sarcoma
- Rhabdoid GI carcinomas
- PD Sinonasal carcinomas
- Epithelioid MPNST (subset)
- Myoepithelial carcinoma (subset)
- Extraskeletal myxoid chondrosarcoma (subset)
Predisposition for germline heterozygous loss
Malignant Rhabdoid tumor
Has prominent eosinophilic cytoplasmic inclusions
Malignant Rhabdoid tumor
