Paediatric Flashcards
What is the typical microscopic appearance of classical medulloblastoma
Small round blue cells. Scanty cytoplasm
Homer wright rosettes (rings of Neuroblasts surrounding eosinophilic neutrophil)
What are the histological subtypes of medulloblastoma, and what are their prognosis
Desmoplastic/nodular: good
Extensive nodularity : Good (significant overlap with desmoplastic/nodular: both SSH associated)
Classical: intermediate
Anaplastic/large cell (marked nuclear pleomorphism, numerous mitosis and apoptosis): poor
What are the molecular subtypes of medulloblastoma
Wingless (WnT)
Sonic hedgehog (SHH)
Group 4
Group 3
Groups 3 and 4 have worse prognosis
What does PNET stand for
Primitive neuroectodermal tumour
What are the 4 categories of brain stem glioma
Diffusely infiltrating (typically pontine; diffusely infiltrating pontine glioma)
Focal (well circumscribed, <2cm diameter, wihthout infiltration or oedema
Dorsally exophytic
Cervicomedullary
What is the difference in survival outcome between low grade and high grade brain stem gliomas
There is no difference. Possibly high tendency to transformation, or heterogeneity within tumour
Which subset of brain stem glioma tend to be indolent and can be observed
Focal tectal tumours
Where does craniopharyngioma arise, and what is its malignant potential
Arises in the remnant of Rathkes pouch/ hypophyseal duct. Usually supresellar
Benign
What are the two main subtypes of craniopharyngioma
Adamantinomatous (most common)
Papillary
What is the typical microscopic appearance of adamantinomatous craniopharyngioma
Adherence to surrounding structures
Wet keratin nodules
Rosenthal fibres
Pallisading basal layers of cells with intense gliosis
What are the common genetic abnormalities in the two subtypes of craniopharyngioma
Adamantinomatous: WNT pathway abnormalities. B-catenin gene mutation
Papillary: BRAF V600E mutation.
Which gene fusion is significantly prognostic in rhabdomyosarcoma
PAX/FOX01.
FOX01 on chromosome 13
Most common in alveolar rhabdomyosarcoma
Several different PAX genes can be involved (on different chromosomes)
Associated with unfavourable prognosis
What is the microscopic appearance of alveolar rhabdomyosarcoma
Small round blue cells
Alveolar growth pattern with appearance similar to lung alveolar
What is the appearance of embryonal rhabdomyosarcoma
Small cells with round nuclei on a background myeloid stroma
Organic architecture eg nests
What age group is favourable in rhabdomyosarcoma
2-10
What two chromosomal translocations are common in Ewing sarcoma
t(11:22) (90%) t(21:22)
But many many others
Histologically what is thought to be the relationship between histological origin of ewings sarcoma and neuroblastoma
Ewings: thought to arise from parasympathetic postganglionic cells
Neuroblastoma: thought to arise from sympathetic cells
What is the microscopic appearance of Ewing sarcoma
Small round blue cells
Extensive necrosis
What are the histological subtypes of Ewing sarcoma
Typical: classical
Atypical: lobular, alveolar, organoid
What does the pneumonic EG-MODE stand for
Bone tumours
-Epiphysis: Giant cell tumour
-Metaphysis: Oesteosarcoma
-Diaphysis: Ewing
What does the mnemonic LEMONS stand for
Small round blue cell tumours
Lymphoma
Ewings
Medulloblastoma
Other (rhabdomyosarcoma, pineoblastoma, ependymoblastoma, etc)
Neuroblastoma
Small cell carcinoma
What are the prognostic factors for Ewing sarcoma
MASSSive LDH Response
Male gender
Age >17
Site (pelvic/axial)
Size >8cm
Stage (metastasis)
LDH
Response to chemo (>90% favourable)
What are common genetic abnormalities is neuroblastoma
Key point: MANY genetic anomalies common
N-MYC over expression (due to 1p loss)
11q deletion
17q gain
TERT rearrangements
ATRX deletion
ALK mutation
What are the microscopic features of favourable wilms tumour
Triphasic. Ie, three different tissue elements
-epithelial (tubules/glomeruli)
-stromal (immature spindled cells)
-blastemal (small round blue cell component)
What are microscopic features of unfavourable histology wilms tumour
Anaplastic features: enlarged nuclei, hyperchromatism of nuclei, abnormal mitotic figures (must have all 3)
Sarcomatous features
What are the 5 pathological types of paediatric renal tumours
Favourable histology wilms tumour
Unfavourable histology wilms tumour
Rhabdoid tumour of kidney (RTK) (associated with ATRT): treated as wilms
Clear cell sarcoma of kidney (CCSK): treated as wilms
Renal cell carcinoma
What genetic abnormality has prognostic significance in Wilma tumour
1q gain
1p and/or 16q loss (worse if both)
What is a syndrome associated with medulloblastoma, what pathway is affects
Gorlin syndrome. Mutation in receptor for SHH pathway
What are the different types of rosettes found in paediatric malignancies and the associated malignancies
Homer wright rosettes (cells surround central neuropil; collection of neural projections): medulloblastoma, pineoblastoma, neuroblastoma
Perivascular pseudorosettes(areas without nuclei around central blood vessel): ependymoma, glioblastoma
What is Turcot syndrome
Mutation of APC gene, which means B-catenin is not regulated (as part of Wnt pathway and pro proliferative.
Wingless variant of medulloblastoma, polyposis, colorectal cancer, gliomas.
Translocation of what gene defines Ewing sarcoma
EWSR1
Usually either t(11:22) or t(21:22)
What IHC is diffusely staining in most Ewing sarcoma
CD99 (indicates translocation of EWS1
Which neuroendocrine IHC marker is most commonly positive in paediatric “blastoma” small round blue cell tumours
Synaptophysin
(See blue book page 20)
What does AT/RT stand for
Atypical teratoma/rhabdoid tumour
In basic terms what are the microscopic components of an AT/RT tumour
Rhabdoid cells: eccentric nuclei. Abundant eosinophilic cytoplasm. Abundant mitosis. Geographic necrosis.
Teratoid: other poorly differentiated elements including small cell embryonal, spindle cell, neuroectodermal, epithelial, mesenchymal (ie like teratoma)
What is the WHO grade of AT/RT
Grade 4
What molecular/IHC abnormalities are required for diagnosis of AT/RT
SMARCB1 (INI1)
Or more rarely:
SMARCA4 (BRG1)
What is the pattern of B-catenin staining in wingless medulloblastoma
Nuclear staining (as well as normal cytoplasmic/membranous staining)
Due to the issue being APC not breaking down B-catenin
What is the microscopic appearance of pineoblastoma
Resembles medulloblastoma
Can have homer wright rosettes
High N:C ratio, hyperchromatic
Frequent mitosis
WHO grade 4
What is the IHC profile of rhabdomyosarcoma
The same for embryonal and alveolar
MAD
Myogenin, MyoD1
Actin (muscle specific actin)
Desmin
Vimentin (non specific)
What are the two special variants of embryonal rhabdomyosarcoma, and what is their prognosis in comparison to standard embryonal rhabdomyosarcoma
Botyroid (abundant myxoid stroma): best prognosis
Spindle variant (spindle cells present): also better than standard
What are the favourable sub sites of rhabdomyosarcoma
Orbit
Non parameningeal H+N
GU tract (excluding bladder/prostate)
Biliary tract
Which sub sites of rhabdomyosarcoma are more likely to have LN involvement
Extremities, paratesticular
Orbit, H+N, trunk, female genital rarely have LN involvement
What are rates of distant Mets at presentation of rhabdomyosarcoma. What are the most common sites
20%
Bone and lung
Bone marrow
What are the histological variants of rhabdomyosarcoma
Embryonal
-botyroid
-spindle
Alveolar
Undifferentiated
What are the components of pre op IRSG staging for rhabdomyosarcoma
Stage 1-4
Favourable vs unfavourable site
Node status
Tumour size (5cm)
M status
Stage 1: favourable sites as long as there is no metastatic disease
Stage 4: metastatic disease
What are the components of the rhabdomyosarcoma IRSG Risk Categories
Low, intermediate and high risk
IRSG stage (initial clinical stage)
IRSG clinical group (surgical outcome of primary and nodes)
Histological subtype (alveolar vs embryonal)
What are the pattern as of spread of rhabdomyosarcoma
Local invasion (fascial or muscle planes)
Lymphatic (extremity, paratesticular, GU)
Haematogenous (lung, bone, marrow)
Leptomeningeal
What are the three main ways that rhabdomyosarcoma can be divided up prognositcally
Disease site
Histological subtype
IRSG risk group
What percentage of wilms tumours are sporadic vs familial vs genetic syndromes
90% sporadic
1% familial
9% genetic syndrome
What is one syndrome associated with Wilma’s tumour. What is the underlying genetic abnormality
WAGR syndrome
Wilms
Aniridia (no irises)
GU tract anomalies
Retardation
Due to loss of part of chromosome 11 containing several genes including WT1
What is the role of WT1
Normal kidney development
What is the microscopic appearance of neuroblastoma
Small round blue cell tumour
Homer wright pseudorosettes
Where does neuroblastoma most commonly arise
Adrenals
Paraspinal ganglia
What is the macroscopic appearance of wilms tumour
Destruction of renal parenchyma, but well demarcated
Pseudocapsule of compressed atrophic renal tissue
Lacks calcification
What genes are commonly mutated to cause loss of function in wilms tumour
WTX: 30%. On X chromosome, only need to loose single copy to develop wilms
WT1: chromosome 11. 5-10%. Need to loose both copies
Are the standard neuroendocrine IHC markers positive in paediatric non-CNS neuroendocrine tumours
Generally not.
Positive in neuroblastoma (PNS)
+/- in wilms
Negative in Ewings
What are the 3 features that must be present for a diagnosis of anaplastic wilms tumour
Abnormal mitoses
Nuclear Hyperchromasia
Nuclear enlargement (>3x)
What defines favourable vs unfavourable histology in wilms tumour
The presence of anaplastic.
FH: no anaplastic or sarcomatoid histology present
UH: extreme anaplastic
-focal anaplasia 4yr OS 90-100%
-diffuse anaplastia 4yr OS 4-55%
What cytogenetics in Wilms are associated with increased risk of relapse and death
1p and/or 16q loss (worse with both)
1q gain
Why might patients with Wilms tumour present with anaemia and hypertension
Anaemia: reduced EPO production
Hypertension: increased renin production
What are the three tumours on the spectrum of neuroblastic tumours
Ganglioneuroma: well differentiated ganglion cells; benign
Ganglio -neuroblastoma
Neuroblastoma: immature cells
What is the result of chromosome 1p deletion (loss of heterogeneity)
Loss of suppressor of N-MYC.
Therefore results in N-MYC over expression, which is pro proliferative
Can occur in: oligodendroglioma, neuroblastoma, wilms. Probably others (haven’t gone searching)
What are the factors used to classify neuroblastoma as favourable histology or unfavourable histology in the Shimada histpathological classification
SAD-MiND
Stromal pattern: stroma rich with more fibrillary material is favourable
Age: <1 favourable, >5 worse
Differentiation
Mitotic-karyorrhexis index
Nodularity (nodular bad vs diffuse better)
What is the natural history of neuroblastoma
Can spontaneously regress/ mature into benign ganglioneuroma
More commonly present with symptoms from metastatic disease rather than local symptoms
Age <1 60% have localised disease
Age >1 70% have metastatic disease
Most common sites of Mets: bone marrow, bone( skull/orbit: raccoon eyes, liver, skin (blueberry muffin)
Why would neuroblastoma present with horners syndrome
Due to the malignancy arising in the cervical ganglion
What oncological emergencies can occur in neuroblastoma
Cord compression: from growth of paraspinal primary into spinal canal
Pepper syndrome: massive liver Mets causing respiratory compression and breathing difficulty. RT 4.5Gy/3#
What are the criteria for stage 4S in neuroblastoma, what is its relevance
Age <1
Metastases limited to skin and liver
<10% bone marrow involvement, MIBG negative in bone marrow if performed
80% of cases regress spontaneously, associated with good prognosis
What are the prognostic factors for neuroblastoma -SANDS SAD-MiND
Stage, site of primary, site of Mets
Age (<1 favourable, >5 unfavourable)
N-MYC amplification (unfavourable)
DNA hypo/hyperdiploid
Stromal pattern
Age (as above)
Differentiated
Mitotic-karryhorrexis index
Nodularity- diffuse vs nodular
What are the four most common posterior paediatric tumours in paediatrics
BEAM
Brain stem glioma
Ependymoma
Astrocytoma
Medulloblastoma
