Paediatric tumours Flashcards
1yr M, arm lesion
Dx:
Key features:
Presentation:
Syndromic associations:
Mutation:
IHC:
Fibrous haemartoma of infancy.
Triphasic organoid pattern: Mature adipose tissue, myxoid nodules containing primitive mesenchymal cells with rounded to stellate nuclei, fascicles of bland fibroblasts/myofibroblastic cells. Mitosis/necrosis infrequent/absent respectively. Interspersed inflammaotry cells.
bundles of bland fibroblastic/myofibroblastic cells, nodules of primitive mesenchyme, and mature adipose tissue.
Painless, solitary s/c mass. Multiple tumours in same pt can be encountered. Dx < 2 yrs, male predominance.
Tuberous sclerosis and William syndrome.
Recurrent EGFR exon 20 insertion/duplication.
IHC: SMA(+) fibroblastic areas/primitve mesenchyme; S100 adipocytic component; CD34(+) in primitive mesenchyme. EGFR expression desireable.
Below: bundles of fibroblastic spindle cells, mature adipose tissue, and nodules of primitive mesenchyme.
Dx:
Clin presentation:
Genetic mutation:
Histo:
Px:
Lipoblastoma (localised) vs lipoblastomatosis (diffuse).
Trunk/extremities. 75–90% of cases occur before the age of 3 years).
Rearrangement of PLAG1
lobulated tumour comprising sheets of adipocytes showing a spectrum of maturation, separated by fibrovascular septa. Myxoid areas display a plexiform vascular pattern with primitive mesenchymal cells. Zonal pattern of maturation, with more immature myxoid cells at the periphery (adjacent to fibrous septa) and mature adipocytes in the centre of the lobule.
IHC: S100, CD34, CD56 in lipoblasts. PLAG1 nuclear immunohistochemical staining can be useful, especially in less differentiated tumours, but its concordance with molecular studies is < 60% and sensitivity is about 50%
Tendency to recurrence if incompletely excised.
Image: The tumour shows predominant lipoblasts, with evidence of a spectrum of maturation.
2M leg mass
Dx?
Key features demonstrated by this image.
DDX?
Px:
Lipoblastoma.
A spectrum of adipocyte maturity, myxoid matrix, and fibrovascular septa constitute this classic lipoblastoma.
DDx:
Lipofibromatosis (no lipoblasts)
FHI: ((no lipoblasts; EGFR(+) by IHC)
Myxoid liposarcoma (rare in childre, usu 3-6th decage)
Primitive myxoid mesenchymal tumour of infancy (predominant round cell component, curvilinear plexiform vascular pattern, )
Complete excison is curative.
Below image: A spectrum of adipocyte maturity, myxoid matrix, and fibrovascular septa constitute this classic lipoblastoma.
4M ankle lesion
Dx:
Presentation:
Key features:
DDx:
Px:
Lipofibromatosis
Distinctive admixture of mature fat, fascicles of bland spindled cells, and lipoblast-like cells.
typically presents as a slowly growing s/c mass.
Male predilection, from birth to 14 yrs.
Histo: fascicles of mature fibrous tissue with bland, uniform, elongated nuclei and eosinophilic cytoplasm traversing mature adipose tissue. In newborn patients, the fat lobules may have an immature appearance with a myxoid matrix. Small collections of univacuolated cells may be present in the fibroblastic component. LPF entraps skeletal muscle and subcutaneous structures. Mitoses are rare and necrosis is absent.
IHC: fibroblasts show variable expression of CD34 and SMA, and the fat is S100-positive.
DDx:
Fibromatosis
FHI (has immature mesenchymal component)
Fibrolipoma: fibrous component is perilobular, no intersecting fascicles
Lipoblastoma (lobular architecture; myxoid areas, immature lipoblasts, PLAG1 rearrang)
Lipofibromatosis-like neural toumours: cyto atypia, CD34(+), S100(+), NTRK1 gene fusion
Calcifying aponeurotic fibroma, infantile fibrosarcoma (if early and no prominent calcs can mimic LPF; recurrent FN1::EGF gene fusion)
High rate of recurrence if incompletely excised. No metastatic potential.
Image: Mature adipose tissue is traversed by cellular fascicles of spindle cells with uniform fibroblasts.
In other image, entrapped skeletal m.
5M pelvic abscess
Dx?
CD99(-), desmin(+), MyoD1(+), Myogenin (patchy +)
Embryonal rhabdomyosarcoma.
Primitive mesencyhmal cells in various stages of myogenesis.
Mha have prominent spindel cell morphology.
Heterologous cartilage may be seen, esp in tumours a/w DICER1 syndrome.
Embryonal rhabdomyosarcoma
Arises most commonly in which sites?
Head and neck region, orbit and genitourinary.
alveolar rhabdomyosarcoma
Arises most commonly in which sites?
extremities
rhabdomyosarcoma
subtypes
Embryonal
Alveolar
Pleomorphic
Spindle cell sclerosing
Anaplastic + botryoid (?only embryonal?)
alveolar Rhabdomyosarcoma
Genetic mutations
ARMS is characterized by a t(2;13)(q36;q14) translocation in 70–80% of cases, or a t(1;13)(p36;q14) translocation in 20–25% of cases { 8098985 ; 8187070 ; 8275086 ; 22447499 ; 28521080 }. These translocations juxtapose PAX3 (2q36.1) or PAX7 (1p36.13) with FOXO1 (13q14.11). PAX7::FOXO1 fusions are associated with amplification of the PAX7 locus
6M desmin(+), myogenin(+), INI1(+), CD99/NKX2.2/CD45/PHOX2B/WT1 (-)
Dx?
Botryoid rhabdomyosarcoma.
Low-power examination of a mucosal-based botryoid embryonal rhabdomyosarcoma shows hypocellular polypoid masses with tumour condensation beneath the epithelial lining (cambium layer).
spindle cell sclerosing rhabdomyosarcoma
mutation?
SCSRMS may harbour MYOD1 p.L122R mutations or VGLL2::NCOA2 rearrangements
rhabdomyosarcoma subtypes
Essential and desireable dx features as per the WHO
Essential: for ERMS: primitive spindle to round cell morphology with differentiating rhabdomyoblasts; heterogeneous nuclear staining for myogenin; for ARMS: monomorphic round cells; homogeneous strong nuclear staining for myogenin; presence of PAX3, PAX7, or FOXO1 rearrangement; for SCSRMS: purely spindled morphology with intersecting fascicles or admixed sclerosing patterns with round cells and abundant collagenous/hyalinized matrix.
Desirable (in selected cases): MYOD1 mutations or VGLL2::NCOA2 gene rearrangements in SCSRMS; diffuse nuclear staining for MYOD1 in SCSRMS.
rhabdomyosarcoma
Which IHC can be used to distinguish ERMS vs ARMS vs SCSRMS? Describe the pattern of staining.
ARMS with FOXO1 rearrangements shows strong diffuse nuclear staining for myogenin, whereas ERMS shows variable myogenin expression (10–80% of tumour nuclei) { 23765537 }. SCSRMS may have little to absent desmin or myogenin expression but show strong and diffuse nuclear staining for MYOD1
Px rhabdomyosarcoma
Prognosis?
rhabdomyosarcoma, subtypes
Morphology, genetic mutations and px
17F, lumbar paraspinal tumour
AE1/AE3/desmin/synapto (-); INI retained; S100 patchy +; CD99 strong membraneous +; NKX2.2+, ERG+
Dx?
Genetic mutions?
Ewing sarcoma is a small round cell sarcoma with gene fusions involving a FET-family gene (usually EWSR1) and a member of the ETS family of transcription factors.
Gene fusion involving a FET gene (FUS, EWSR1, or TAF15) and an ETS gene. The most common gene fusion is EWSR1::FLI1, resulting from a t(11;22)(q24;q12) translocation, present in about 85% of cases. The second most common gene fusion is EWSR1::ERG, resulting from a t(21;22)(q22;q12) translocation, seen in about 10% of Ewing sarcomas
Ewing sarcoma
IHC?
CD99 immunohistochemistry typically shows strong diffuse membranous reactivity, but this is not specific for Ewing sarcoma. NKX2-2, likewise, is a highly sensitive but only moderately specific marker for Ewing sarcoma. FLI1 and ERG are often expressed in cases with the corresponding gene fusions. Cytokeratins are expressed in a minority of Ewing sarcomas. Other markers that may be positive include neuroendocrine antigens, S100, and TRK proteins.
Below: tumour showing neuroectodermal differentiation with pseudorosettes.
4M cervical paraspinal tumour (extradural)
AE1/AE3 patchy +; EMA(+) desmin (-); CD99 (+); NKX2.2(-); INI1 (LOST)
Dx?
Histo features:
Genetic mutation:
Locations:
IHC:
Extrarenal rhabdoid tumour
rhabdoid cells with large vesicular rounded to bean-shaped nuclei, prominent nucleoli, and abundant cytoplasm, arranged in sheets or in a solid trabecular pattern. Many tumour cells have juxtanuclear eosinophilic, PAS-positive, diastase-resistant hyaline inclusions or globules. Infiltrate periphery. Nuclear pleomorphism (-) but mitoses frequent.
Mainly affects infants and small children.
Biallelic alterations of the SMARCB1 gene.
Axial region/paraspinal
IHC: keratins/EMA(+); The expression of neural or neuroectodermal markers such as CD99/synaptophysin frequently +.
Characteristically, rhabdoid tumours show a loss of SMARCB1 (INI1, BAF47) expression { 15489652 ; 21934399 } or, alternatively, a loss of SMARCA4 (BRG1) { 31403913 }.
3 week old female, paraorbital tumour
Vimentin strongly +; Desmin, myogenin, S100, EMA, Glut 1 all negative; BCL2 patchy cytoplasmic staining; CD45 highlights lymphocytes
FISH: ETV6 gene rearrangement detected…
Dx:
Px:
Mutation:
Analogous tumours in the kidney called….
IHC:
Essential dx criteria
DDX?
Infantile fibrosarcoma
Locally aggressive/infrequently metastasises
Fibroblastic tumour
characterised by an ETV6::NTRK3 fusion -> leading to oncogenic tyrosine kinase signaling.
Analogous tumours in the kidney called cellular congenital mesoblastic nephroma.
1/3 cases congenital; mediate age of pts is 3-4 months, majority int eh 1st year of life.
IHC: Variable expression of SMA, S100, CD34, and (rarely) desmin { 22420727 ; 30585824 }. Those tumours harbouring NTRK gene rearrangements typically show expression for pan-TRK antibodies
Essential: a primitive ovoid/round cell or spindle cell tumour, often arranged in sheets or fascicles; haemangiopericytoma-like vessels and/or mixed chronic inflammation.
Desirable: ETV6::NTRK3 or other reported fusions or activating alterations of receptor tyrosine kinase pathway genes (e.g. NTRK1, NTRK2, NTRK3, RET, MET, BRAF).
DDx: adult type fibrosarcoma; infantile fibromatosis; monophasic synovial sarcoma; embryonal rhabdomyosarcoma.
below: characteristic Herring bone pattern
12M thigh mass
Desmin/AE1/AE3/S100(-)
EMA patchy +; H3K27me3 +; CD34+; CD99+; BCL2+; TLE1+
Dx:
What is it?
demographic:
Sites:
Histo:
Localisation:
Mutation:
IHC:
Essential + desireable WHO criteria
Synovial sarcoma
Malignant mesenchymal neoplasm showing variable epithelial differentiation and characterized by a specific SS18::SSX fusion gene.
Most common in adolescents 10-18 yrs
70% deep soft tissues of the extremities, often near large joints.
3 main histological patterns of SS: monophasic (most common), biphasic (second most common, accounting for as many as a third of cases), and poorly differentiated.
Monophasice = dense cellular sheets and fascicles of uniform spindle cells.
Chromosomal translocation resulting in the formation of an oncogenic SS18::SSX fusion gene.
IHC: Immunohistochemistry: novel antibody for SS18::SSX fusion protein { 32141887 } allows a sensitive and specific diagnosis of SS.
TLE1 shows diffuse nuclear staining in most cases of SS, (not specific and is also expressed in histological mimics such as malignant peripheral nerve sheath tumour and solitary fibrous tumour.
Epithelial differentiation can be demonstrated with EMA and cytokeratins. In most cases of SS there is expression of BCL2 and CD99 (which may be perimembranous).
S100 and SMA are variably expressed, whereas desmin and CD34 staining is exceptional. SMARCB1 (INI1) staining may be partially or completely lost in a subset of SS.
Essential: monomorphic spindle cell sarcoma with or without gland formation, showing variable histological and/or immunohistochemical epithelial differentiation; diffuse and strong nuclear immunostaining for TLE1.
Desirable: diffuse and strong nuclear immunostaining for SS18::SSX fusion protein or demonstration of an SS18::SSX gene fusion.
Synovial sarcoma
IHC and molecular
3F palm lesion. CD68 patchy +; SMA +
SMA
Dx:
Sites:
Histo:
IHC:
DDx:
Px:
Plexiform fibrous histiocytoma
Dermal + s/c neoplasm; biphasic nodules of histiocytoid cells and spindled myofibroblasts arranged in plexiform achitecture.
Upper extremiteis > lower extremities
Histo: infiltrates s/c adipose tissue + sk m. plexiform + multinodular arrangement of histiocytoid cells w/ variable number of admixed multinucleated, osteoclastic-like giant cells, connected by fascicles of spindled fibroblastic/myofibroblastic cells. Low mitotic rate/pleomorphism/LVSI is rare.
IHC: SMA+ in myofibroblastic cells;
DDx:
- (plexiform) plexiform myofibroblastoma, plexiform neurofibroma;
- (Fibroblastic): fibromatosis; FHI
- Primiennt fibrohistiocytic pattern: DF
Dx criteria: Nodules of histiocytoid cells and often osteoclastic-like giant cells; fascicles fo (myo)fibroblastic spindle cells; plexiform architecture.
Distant mets rare. lcoal recurrence (12-38%)
1yr abdominal mass
Dx?
Key features?
IHC:
Favorable and unfavourable prognostic factors
Neuroblastoma.
Primitive small round blue cells forming Homer-Wright pseudo rosettes around neuropil.
(+) staining for PHOX2B (also Syn, CD56, chromo)
Favourable: low stage, age < 18 months, MYCN not amplified. presence of > 50% schwannian stroma and also presence of gangliocytic differentiation; Hyperdipoloid, low mitosis-karyorrhexis index; no loss of chromosome 1p and 11q (inverse true for unfavourable)
3M retroperitoneal mass
Dx?
Histo features?
Genetic mutation?
Wt tumour
Essential: presence of ≥ 2 of the following components: blastemal, epithelial, and/or stromal.
Desirable: for monophasic nephroblastoma: immunohistochemistry or molecular testing to distinguish it from other tumours with similar histological features.
This image: his example is composed of closely mixed blastemal and epithelial components.
11M gingival mass
Peripheral giant cell granuloma
Non-encapsulated aggregates of foreign body giant cell s+ fibroangiomatous stroma w/ haemorrhage, haemosideron, acute and chronic inflammatory cells.
2M cerebellar lesion
Dx?
Subtypes & key features
Medullablastoma (classic subtype)
Classic medulloblastoma:
Small, blue, round cell tumor
Syncytial arrangement of densely packed undifferentiated cells
(embryonal cells)
Mitosis with apoptotic bodies
Homer Wright rosettes
Desmoplastic / nodular medulloblastoma:
Densely packed, undifferentiated cells with hyperchromatic and
pleomorphic nuclei that produce dense intercellular reticulin fiber
network with nodular reticulin free zones
Medulloblastoma with extensive nodularity:
Expanded lobular architecture due to reticulin free nodular zones
becoming enlarged and rich in neuropil-like tissue.
Large cell / anaplastic medulloblastoma:
Anaplasia with marked nuclear pleomorphism, high mitotic count
and high apoptotic count
Nuclear molding and cell wrapping
Medulloblastomas with melanotic or myogenic differentiations
2M posterior fossa lesion
Dx?
What key feature is image showing?
Medulloblastoma
Myogenic differentiation
4F nephrectomy
Dx?
Key features?
IHC:
Metanephric adenofibroma
Biphasic tumour composed of epithelial and stromal components.
Typically solitary, unencapsulated. No nuclear atypia in both compartments. Epithelial component is similar to epithelial component in metanephric adenoma and stromal component similar to stromal component in metanephric stromal tumor
Epithelial: AE1/A3; WT1; BRAF (+)
Stromal: CD34; WT1(nucl) (+)
neonate. Cardiac arythmia.
Dx
key histo features?
Px:
habdomyoma is the most common heart neoplasm in children, accounting for > 60% of cardiac tumours. It is also the most common heart tumour diagnosed prenatally
> 50% of children with tuberous sclerosis are diagnosed with a cardiac rhabdomyoma by echocardiography
Histopath: Well-demarcated but unencapsulated nodules, easily distinguished from the surrounding myocardium, with enlarged vacuolated cells. Characteristic spider-cell feature is the consequence of radial sarcoplasmic extensions emanating from the centrally located nucleus to the sarcoplasmic membrane. Positive expression of markers of striated muscle cells (myoglobin, desmin, actin, and vimentin) is detected by immunohistochemistry
Px: cardiac rhabdomyomas are peculiar in that they have a propensity to resolve spontaneously with age.
2M nephrectomy
Dx?
Demographic?
Key histo features of subtypes
Cytogenetics:
IHC
Mesoblastic nephroma,
Demographic: Most common renal tumour in the first 3 months of life. In 90% of cases it occurs in the first year of life, and it virtually never arises after the age of 3 years.
Classic/cellular and mixed subtypes
Key features:
Most cases arise in the medial renal sinus.
Classic MN (25%) characterized by intermingling fascicles of spindle cells; collagen deposition; low mitotic activity; and often prominent, dilated, thin-walled vascular spaces. There is no capsule, and the tumour–kidney border is irregular, with many finger-like protrusions of the tumour into the renal parenchyma, resulting in numerous islands of entrapped renal elements, which may undergo metaplastic changes. Islands of hyaline cartilage may be found at the tumour–kidney interface. Foci of extramedullary haematopoiesis are common.
Cellular MN (~65%) is characterized by increased cellularity of plump cells with vesicular nuclei and a moderate amount of cytoplasm, growing in a sheet-like pattern. The tumour subtly infiltrates the kidney. Mixed-type MN (~10% of cases) shows features of both types.
SMA and cyclin D1 immunostains are positive in MN { 25556515 }. Desmin is usually negative. Nuclear staining with a pan-TRK antibody is supportive of a diagnosis of cellular MN with ETV6::NTRK3 gene fusion.
Molecular: A specific chromosomal translocation, t(12;15)(p13;q25), which results in the fusion of ETV6 and NTRK3, has been found in about 70% of cases of cellular MN. EGFR internal tandem duplication (ITD) is a consistent and recurrent genetic event in classic MN, whereas mixed MN may have either EGFR ITD or ETV6::NTRK3 gene fusion
1M head lesion
Dx?
Key features?
IHC?
DDx?
Dx: infantile myofibroma/myopericytoma
Location: head and neck
Any age but frequently up to 2 years
Features:
MF has a nodular growth pattern and is characterized by a biphasic zonation appearance associated with a biphasic cell population
haemangiopericytoma-like vascular pattern.
cells often form nodules bulging into vascular lumina. There is no marked atypia, and the rate of mitosis is variable.
MF and MP cells express SMA and may stain for desmin and h-caldesmon.
The main differential diagnoses of MF are infantile fibrosarcoma, infantile spindle cell rhabdomyosarcoma, vascular tumours, solitary fibrous tumour, desmoid tumour, and nodular fasciitis.
abdominal mass 5 M
dx
key histo features
Wilm’s tumour
Triphasic tumour composed of blastemal,epithelial and stromal elements.
6M distal femur lesion
dx
key features
IHC
Molecular
Ewings sarcoma
Key features:
Image shows monotonous proliferation of round blue cells with vacuolated cytoplasm secondary to the deposition of glycogen is shown.
Medulloblastoma
Molecular classification and IHC staining
