Soft tissue Flashcards
Name this tumour.
Line of differentiation?
Site predilection?
Explain appearance of cytoplasm?
Stains:
Describe any genetic exceptions
Granular cell tumour
Neuroectodermal differentiation
Predilection for the tongue
Granular cytoplasm caused by inactivating mutations in ATP6AP1 or 2 (so can’t break down lysosomes) -> granular ppearance.
Stains: S100 (+), CD68, inhibin, calretinin.
Genetic exceptions: congenital (ginival) granular cell tumour (congenital epulis) - looks simlar, located on gingiva at birth, S100-
Molecular mutation in myxoid liposarcoma:
FUS-DDIT3 t(12;16) OR
EWSR-DDIT3 t(12;22)
FUS rearrangements seen in which soft tissue tumours?
myxoid lipoidsarcoma
Low-grade fibromyxosarcoma
Angiomatoid fibrous histiocytoma
name the 4 types of Kaposi sarcoma
Causative agent?
Associations
1) classic (older males 90%; indolent)
2) Endemic/African (NOT a/w HIV, aggressive)
3) Iatrogenic (usu immunosuppressed; variable behaviour)
4) Aids-associated (coinfection with HIV and HHV8; most aggressive type)
HHV-8
Classic often a/w underlying malignancy (haematologic)
Kaposi sarcoma
What are the three stages of the disease?
- Patch stage
- Plaque stage
- Tumor stage
Kaposi sarcoma
Patch stage, key histological features?
Increased “jagged” interconnected vascular channels in reticular dermis
Dissecting/wrapping around collagen bundles
Growing around adnexa
Growing into normal vessels (promontory sign is characteristic but uncommon finding)
Lined by uniform endothelial cells with minimal atypia
Scattered plasma cells (very useful clue) and lymphocytes
Extravasated erythrocytes and hemosiderin deposits
Kaposi sarcoma
Plaque stage, key histological features
More extensive vascular proliferation
Increased inflammatory infiltrate with plasma cells
Spindle cell proliferation infiltrating dermis and invading/destroying eccrine glands
Kaposi sarcoma
Tumour stage, key histological features
Nodules of spindle cells arranged in intersecting fascicles
Blood-filled slit- and sieve-like spaces between spindle cells
When blood-filled spaces absent, may be difficult to recognize as vascular tumor
Mitoses often prominent, but nuclear atypia is usually only mild to moderate
If severe atypia, consider spindled angiosarcoma
In AIDS, KS may have more atypical areas similar to angiosarcoma
Intracytoplasmic hyaline globules in spindle cells
Some suggest these are degenerated erythrocytes
Inflammatory infiltrate with plasma cells usually present
IHC kaposi sarcoma
CD31, CD34, ERG, D2-D40 positive.
HHV-8 Punctate, speckled, or granular pattern of nuclear staining is classic. All other vascular tumours negative for HHV-8
DDx Kaposi sarcoma
Angiosarcoma: different clinical context, HHV-8(-)
Acroangiodermatitis (i.e. venous stasis): Dermal spindle cells are fibroblasts (not spindled endothelial cells as in KS) so negative for vasc markers.
Painful, well circumscirbed skin lesion. Higher power magnification:
Dx:
Key histological features:
Angioleiomyoma
Well-circumscribed tumour.
Bundles of cytologically bland smooth muscle cells growing concentrically around blood vessels of varying calibre.
angioleiomyoma
Subtypes (3)
Three subtypes of angioleiomyoma have been described based on predominant vascular morphology; solid, venous and cavernous.
The solid subtype is composed of compact bundles of smooth muscle surrounding compressed, slit-like vessels.
Venous subtype tumours are made up of thick-walled vessels with smooth muscle from blood vessel walls blending with intervascular smooth muscle bundles.
Cavernous subtype lesions are composed of dilated vascular channels with a proliferation of smooth muscle within intervascular spaces.
IgG4 related disease
Histologically, what features are highly suggestive of the disease?
2 out of 3…
1) Dense lymphoplasmacytic infiltrate
2) Fibrosis, usually storiform in character
3) Obliterative phlebitis
AND
> 40% IgG4/IgG plasma cell ratio IgG4+ plasma cells/high power field > 30 in surgical specimen or > 10 in biopsy specimen
Synovial sarcoma
IHC
Key molecular alterations
TLE1(+; 80-90%, specific + sens)
Cytokeratins: ~90% (depending on epithelial vs spindled component. CK7 ~(+) for both)
EMA: 29-90% +, variable
BCL2: 29-90% +
CD99(+): 91%
CD56(+) 100%
Molecular: t(X;18)(p11.2;q11): SYT-SSX1 fusion in 90% can detect via RT-PCR
Paediatric small round blue cell tumours
DDx?
IHC to distinguish them:
Neuroblastoma
Rhabdomyosarcoma
Ewing sarcoma
Lymphoblastic lymphoma
WT
Malignant rhabdoid tumour
IHC: PHOX2B, desmin, myogenin, MyoD1, CD99, NKX2.2, CD45, TdT, INI1, WT1
Rhabdomyosarcoma
What is myogenin?
Discuss myogenin staining in alveolar vs embryonal subtypes:
A transcriptional regulatory protein expressed early in skeletal muscle differentiation (therefore nuclear).*
ERMS is patchy
ARMS is diffuse (nuclear) staining
*Positive normal staining in fetal muscle, negative in adult muscle
What is MyoD1?
What does it stand for?
MYOD1 encodes a nuclear protein that promotes transcription of muscle specific target genes and regulates muscle cell differentiation.
myogenic differentiation 1 gene
More intense staining in ARMS than in ERMS
Excision foot
Dx?
Key features?
Traumatic (Morton’s) neuroma
Perineural, epineural, endoneural fibrosis, hyalinisation, fibrosis and thickening of vessel walls, fibrosis within adipose tissue.
37F thigh lesion
Dx?
IHC?
Desmoid fibromatosis
Essential: long, sweeping fascicles of bland fibroblasts and myofibroblasts without substantial cytological atypia; infiltrative growth.
Desirable: nuclear β-catenin expression; characteristic CTNNB1 mutation (in challenging cases or small biopsies).
SFT
Genetic mutation?
paracentric inversion involving chromosome 12q, resulting in the fusion of the NAB2 and STAT6 genes
SFT
Sub-types
IHC
Fat-forming; giant-cell rich; dedifferentiated
IHC: CD34(+); STAT6 nuclear (+)
Dx:
Essential and desireable dx features:
SFT
Essential: spindled to ovoid cells arranged around a branching and hyalinized vasculature; variable stromal collagen deposition; CD34 and/or STAT6 expression by immunohistochemistry.
Desirable (in selected cases): demonstration of NAB2-STAT6 gene fusion.
Below: Tumour cells typically display scant to moderate amounts of indistinct, palely eosinophilic cytoplasm and bland nuclei with fine pale chromatin and inconspicuous nucleoli.
DFSP
Molecular/genetic alteration?
COL1A1::PDGFB [t(17;22)(q21.33;q13.1)} fusion
34M slow growing thigh mass
Dx?
IHC:
Molecular:
Px:
Low-grade fibromyxoid sarcoma
Low to moderately cellular, bland fusiform or spindled cells with focal to diffuse whirling in heavily collagenized stroma with abrupt transition to myxoid areas
45% have epithelioid areas
40% contain poorly formed but large collagen rosettes
Often infiltrates adjacent skeletal muscle
Occasionally has areas of increased cellularity, atypia, necrosis or mitotic activity characteristic of intermediate to high grade sarcoma
IHC: MUC4(+) highly sensitive (100%) and specific; CD99 (+)(90%) and BCL2(+) (90%)
CD34(-) c.f. intramuscular myxoma (which also MUC4(-))
Molecular: t(7;16)(q32-34;p11) FUS-CREB3L2 fusion in 90% or more
DDx: Intramuscular myxoma; myxofibrosarcoma (more pleomorphism/hyperchromasia and more developed vasc network); desmoid type fibromatosis (lacks myxoid areas); myxoid neurofibroma (wavy nuclei, thick collagen bundles in b/g)
px: requires long-term f/u as can metastasise years later
Image: abrupt transition to myxoid area
solitary fibrous tumour
IHC:
CD34: diffuse to focal but nonspecific, present in 85 - 95% of cases, may be lost in malignant or dedifferentiated cases.
STAT6 (nuclear): highly sensitive and specific marker (close to 100%) but could be lost in dedifferentiated cases
May have focal EMA (30%) and actin (20%)
BCL2 (30%) and CD99 (70%): nonspecific and not diagnostically useful
25F skin lesion scapula
Dx?
essential and desireable dx features
IHC:
Molecular
Nodular fasciitis
Essential: bland, typically cellular myofibroblastic proliferation with a tissue culture–like growth pattern; variably myxoid stroma with microcystic changes; extravasated red blood cells.
Desirable: assessment of USP6 rearrangement can be helpful in selected cases.
IHC: neoplastic cells express SMA and MSA in a typical myofibroblastic (tram-track) pattern; desmin positivity is occasionally found, usually focally { 1928550 }. Nuclear β-catenin may be seen in cranial fasciitis
Molecular: in challenging cases, break-apart USP6 FISH or next-generation sequencing techniques may be used to confirm the diagnosis
scapula lesion 60M
dx
Key diagnostic features
elastofibroma
Essential: a bland-appearing, hypocellular fibrofatty tumour with excessive abnormal elastic fibres.
palm lesion 10 yr boy
dx
Key features
IHC
calcifying aponeurotic fibroma
Essential: infiltrative lesion composed of bland, evenly spaced spindle cells lying in parallel within a collagenous matrix; islands or geographical areas of calcified matrix often surrounded by palisading epithelioid fibroblasts.
Desirable: FN1-EGF gene fusion (as needed in unusual cases).
IHC: lesional cells react with SMA, MSA, CD99, and (in the chondroid areas) S100. Nuclear staining for β-catenin is not seen.
4yr hand lesion
dx
key features
IHC
Lipofibromatosis
Admixture of mature fat, short fascicles of bland spindle cells, and lipoblast-like cells in the interface between the spindle cell and lipomatous components. Lipofibromatosis entraps subcutaneous tissue and sometimes skeletal muscle.
IHC: fibroblasts show variable expression of CD34 and SMA. The spindle cells are negative for desmin, in contrast to the spindle cells in lipoblastoma.
35F arm mass
dx
key features
IHC
desmoid fibromatosis
Essential: long, sweeping fascicles of bland fibroblasts and myofibroblasts without substantial cytological atypia; infiltrative growth.
Desirable: nuclear β-catenin expression; characteristic CTNNB1 mutation (in challenging cases or small biopsies).
IHC: lesional cells are positive for SMA and MSA. The majority of tumours (~80%) show nuclear β-catenin expression, although definite nuclear reactivity can be difficult to appreciate
20F finger lesion
dx
key features
fibroma of tendon sheath
Essential: benign firm nodule most often on the finger tendons; usually a paucicellular (bland spindled cells) collagen-rich lesion with slit-like vessels.
Image: Low-power view showing the highly sclerotic and hypocellular appearances. Note the small vessels and clefts.
35M thumb lesion
dx
key features
fibroma of tendon sheath.
The tumour is well circumscribed and is composed of bland spindle cells with a prominent collagenous stroma and slit-like, thin-walled blood vessels. Can have increased cellularity usu evident around the periphery
1M thigh mass
dx
key features
fibrous hamartoma of infancy
Classic organoid growth pattern
3 distinct components in widely variable proportions
Intersecting bands and sheets of mature fibroblasts/myofibroblasts
Nests of immature ovoid to spindled mesenchymal cells in loose basophilic, myxoid stroma
May contain subtle chronic inflammatory infiltrate
Mature adipose tissue
1M trunk lesion
dx
key features
Fibrous hamartoma of infancy
Classic organoid growth pattern
3 distinct components in widely variable proportions
Intersecting bands and sheets of mature fibroblasts/myofibroblasts
Nests of immature ovoid to spindled mesenchymal cells in loose basophilic, myxoid stroma
May contain subtle chronic inflammatory infiltrate
Mature adipose tissue
10month male axilla lesion
dx
key features
FHI
Medium-power view showing the triphasic organoid pattern with bundles of fibroblastic spindle cells, mature adipose tissue, and nodules of primitive mesenchyme.
mesenteric mass
dx
Dx criteria
IHC
Inflammatory myofibroblastic tumour
Essential: loose or compact fascicles of spindle cells with a prominent inflammatory infiltrate and a variable fibrous or myxoid stroma; expression of ALK (seen in as many as 60% of cases).
Desirable: ALK or other gene rearrangements (in selected cases).
IHC: variable (+) for SMA, calponin, desmin, focal CK(+)in 30%; ALK IHC correlates with ALK rearrangements; ROS1
plantar lesion
dx
key features
Plantar fibromatosis
Essential: bland, variably cellular proliferation of spindled fibroblasts/myofibroblasts; collagenous stroma; involvement of aponeurosis and variably subcutis and dermis.
dorsal aspect 3rd toe newborn infant
dx
key features
Inclusion body fibromatosis
Essential: dermal-based and cytologically bland myofibroblastic proliferation; eosinophilic intracytoplasmic and paranuclear inclusions.
High-power view demonstrates spindle cells with elongated, cytologically bland nuclei and rounded, eosinophilic, intracytoplasmic inclusions, some indenting the nucleus.
55F slow growing mass in arm
dx?
Desmoplastic fibroblastoma
Essential: hypocellular with abundant collagenous or myxocollagenous matrix; stellate, bipolar, and spindle cells with small nucleoli.
60 M forearm lesion
dx
Key dx features
Proliferative fasciitis and myositis
Essential: myofibroblastic/fibroblastic proliferation with ganglion-like cells; variable collagenous/myxoid stroma; subcutaneous/fascial involvement (proliferative fasciitis); intramuscular checkerboard growth pattern (proliferative myositis).
thigh lesion 6/52 post trauma
dx
key features
Ischaemic fasciitis
Essential: mass-forming lesion mainly in the deep subcutis; zonal appearance with central fibrinoid degeneration/necrosis and cystic changes; periphery with granulation tissue–like vascular component; admixed plump activated fibroblasts/myofibroblasts (ganglion-like cells).
nodular lesion shoulder
dx
IHC
dx molecular
DFSP
IHC: CD34(+); +/- EMA, NB: fibrosarcomatous DFSP can show loss of CD34 expression in about half of the cases
Molecular: etection of COL1A1-PDGFB can be used to confirm the diagnosis
below image: DFSP with characteristic storiform pattern
2nd finger lesion
dx
IHC
tenosynovial giant cell tumour, localised type
IHC: histiocyte-like cells are positive for CD68, CD163, and CD45.
right arm lesion 18 yr
dx
key features
Plexiform fibrohistiocytic tumor
Essential: plexiform architecture; involvement of dermis and/or subcutaneous adipose tissue; nodules composed of histiocytoid epithelioid cells and osteoclast-like giant cells; fascicles of myofibroblastic spindle cells.
16F left forearm lesion
dx
key features
Plexiform fibrohistiocytic tumor
Essential: plexiform architecture; involvement of dermis and/or subcutaneous adipose tissue; nodules composed of histiocytoid epithelioid cells and osteoclast-like giant cells; fascicles of myofibroblastic spindle cells.
Image: The distinctive nodules are distributed within adipose tissue in a plexiform distribution.
6M trunk lesion
dx
key features
giant cell fibroblastoma
mean age 6
Juvenile version of DFSP
Essential: infiltrative margins within dermis and subcutis; hypocellular lesion with myxoid or collagenous stroma; bland spindled and stellate cells and scattered multinucleated giant cells, often lining pseudovascular spaces.
Desirable: COL1A1-PDGFB fusion (in selected cases).
Image shows ectatic pseudovascular spaces lined by multinucleate giant cells.
38M subcutaneous trunk mass
dx
Key features
Hibernoma
Rich capillary network
Polygonal, multivacuolated, granular, brown fat cells, with a variable component of univacuolated white fat. The nuclei of the brown fat cells are small, round, and centrally located, with small nucleoli.
Nuclear atypia/mitotic activity are absent
2M subcutaneous trunk ? lipoma
dx
key features
IHC
molecular
Lipoblastoma
Essential: lobulated mass formed of sheets of adipocytes with variable maturation separated by fibrovascular septa; The fat lobule itself can occasionally exhibit a zonal pattern of maturation, with more immature myxoid cells at the periphery and adjacent to fibrous septa, with mature adipocytes in the centre of the lobule
IHC: adipocytes S100+, CD56+ CD34+;
Molecular: PLAG1 rearrangements / copy-number gain can support the diagnosis
tender nodule forearm excisional bx
dx?
Essential criteria
angiolipoma
Essential: tender, often multiple subcutaneous nodules; mature fat with a variable amount of capillary vessels; fibrin microthrombi.
ALT/WD LS
subtypes and essential and desireable dx criteria including molecular
Essential: lipoma-like ALT/WDLPS: variation in adipocytic size associated with nuclear atypia in stromal and/or adipocytic cells; sclerosing ALT/WDLPS: hyperchromatic bizarre stromal cells set in a fibrillary sclerotic background; inflammatory ALT/WDLPS: scattered atypical stromal cells scattered in a chronic inflammatory background; lipoblasts are not required for diagnosis.
Desirable (in selected or challenging cases): MDM2 and/or CDK4 nuclear expression or evidence of MDM2 and/or CDK4 gene amplification.
50M retroperitoneum
Dx
Key features
DDx:
Molecular:
Dedifferentiated liposarcoma
Essential: transition (abrupt or gradual) from WDLPS (of any type) to spindle cell and pleomorphic non-lipogenic (rarely lipogenic) tumour (of low grade or high grade).
Desirable (in selected cases): expression of MDM2 or demonstration of MDM2 gene amplification.
DDx: Undifferentiated pleomorphic sarcoma (dediff component resembles this
molecular: Detection of MDM2 amplification by FISH is helpful to distinguish DDLPS from other undifferentiated sarcomas in the appropriate clinical context. (?also CKD4 amplification?)
thigh lesion
dx
Key features exemplied from image.
Molecular
Pleomorphic liposaromca
Note that most of the lesion shows spindle cells and such foci cannot be diagnosed as pleomorphic liposarcoma. Pleomorphic liposarcoma is diagnosed on H&E staining by identifying pleomorphic lipoblasts, as in the upper left of the image, in which lipid droplets crisply indent the pleomorphic nucleus. Sometimes examination of multiple tissue blocks is required to identify the diagnostic areas, which can be missed on needle biopsies.
Molecular: Absence of amplification of MDM2 can help distinguish pleomorphic liposarcoma from dedifferentiated liposarcoma.
50M thigh mass
dx
Key dx criteria
molecular
key px factor
Myxoid liposarcoma
Essential: myxoid matrix containing delicately arborizing capillaries; bland round to ovoid cells; variable number of small non-pleomorphic lipoblasts, often adjacent to capillaries; hypercellularity, diminished myxoid matrix, obscured capillaries, and elevated nuclear grade and mitotic activity in high-grade MLPS.
Desirable: demonstration of DDIT3 rearrangement (FUS-DDIT3 or EWSR1-DDIT3 fusion genes).
Px: The presence of > 5% hypercellularity is associated with significantly poorer prognosis. The presence and percentage of hypercellular areas should be recorded.
digit lesion
dx
Key features
IHC
Glomus tumour
Monomorphic round to epithelioid cells with centrally placed, round nuclei and well-defined cell borders, arranged in perivascular nests.
IHC: SMA/MSA/h-caldesmon (+); CD34-/f+
1cm nodule wrist
dx
Key features
IHC
glomangioma
Glomangioma, composed of dilated vascular spaces lined by several layers of glomus cells. Glomus cells have (monomorphic round to epithelioid cells with centrally placed, round nuclei and well-defined cell borders, arranged in perivascular nests).
IHC: SMA/MSA/h-caldesmon (+); CD34 -/F+
solitary nodule wrist
dx
key features
Myopericytoma
Well circumscribed/encapsulated lesion composed of land, myoid-appearing spindled cells growing in a concentric pattern around numerous small vessels;
IHC: SMA/h-caldsmon (+); CD34/desmin f+
bladder mass 4M
dx
Key features
molecular
Embryonal rhabdomyosarcoma
Essential: primitive round and spindle cell morphology with scattered differentiated rhabdomyoblasts; positivity for desmin and heterogeneous nuclear staining for myogenin and/or MYOD1.
Desirable (in selected cases): lack of FOXO1 gene rearrangements to distinguish poorly differentiated ERMS from solid ARMS.
50M thigh lesion
Dx:
Key features
IHC:
Molecular:
Multinodular architecture defined by fibrous septa that divide the tumour into hypocellular lobules with abundant pale-blue myxoid or chondromyxoid matrix. Well-formed hyaline cartilage is virtually never seen.
The cells characteristically interconnect with one another to form cords, small clusters, and complex trabecular or cribriform arrays. The cells have a modest amount of deeply eosinophilic to vacuolated cytoplasm.
Essential: generally bland cells with eosinophilic cytoplasm disposed in strands or cords in a predominantly myxoid stroma.
Desirable: NR4A3 rearrangement (in selected cases).
IHC: S100 (+, 20%); KIT (+, 30%), keratin/GFAP (-)
30M shoulder mass
dx
key features
IHC
Molecular
Low-grade fibromyxoid sarcoma
composed of collagenous hypocellular areas and more-cellular myxoid nodules. An abrupt transition between these two areas is typical. The tumour cells are bland, spindled, and sometimes plump, and they grow in short fascicles or in a whorling pattern. Mitotic activity is generally inconspicuous.
IHC: MUC4 (+); EMA (+, 80%)
If MUC4 is negative or not available to confirm the diagnosis, identification of FUS-CREB3L2 (or other rare variants) offers molecular genetic support for the diagnosis.
Image: The tumour cells are spindled and cytologically bland and grow in short fascicles or in a storiform pattern.
30F ankle palpable mass
dx
demographic
key histo features
IHC
dx molecular:
clear cell sarcoma of soft tissues
young adults 3rd to 4th decade; palpable mass distal extremities
Characteristic nested or fascicular architecture with epithelioid to plump spindled cells partitioned by thin fibrous septa. Infiltrative growth through dense fibrous tissue. Despite its name, CCS typically has tumour cells with palely eosinophilic cytoplasm and vesicular nuclei with macronucleoli, with only rare examples showing true cytoplasmic clearing. Substantial nuclear pleomorphism is generally absent, although scattered wreath-like multinucleated giant cells are relatively common. Melanin pigment is present in more than half of cases.
The mitotic count of CCS is frequently low and necrosis is identified in roughly one third of cases.
CCS shows consistent expression of S100, SOX10, melan-A, HMB45, and MITF
below image: wreath like giant cells.
Molecular: The genetic hallmark of CCS is the reciprocal translocation t(12;22)(q13;q12), present in 70–90% of cases, which fuses EWSR1 with ATF1
Nodular fasciitis
Key features/definition
Key features:
Sites
Molecular
IHC
Self-limiting mesenchymal neoplasm that usually occurs in subcutaneous tissue. It is composed of plump, uniform fibroblastic/myofibroblastic cells displaying a tissue culture–like architectural pattern, and it usually harbours USP6 rearrangement.
Key features: plump spindled cells lacking hyperchromasia/infiltrative growth; tissue culture; extravasated RBCs, osteoclast giant cells occasionally seen; can have mitoses but no atypical forms:;
Sites: typically develops on the surface of fascia and extends into subcutis, although occasional cases are intramuscular { 153036 }. Any anatomical site can be involved, but the upper extremities, trunk, and head and neck are most frequently affected.
Molecular: Virtually all cases contain recurrent gene fusions; MYH9::USP6 is the most common fusion product, although many other USP6 partners have been identified in nodular fasciitis and related entities (e.g., cranial fasciitis, fibroma of tendon sheath, myositis ossificans, aneurysmal bone cyst)
IHC: SMA and MSA (+) in a typical myofibroblastic (tram-track) pattern; desmin positivity is occasionally found, usually focally { 1928550 }. Nuclear β-catenin may be seen in cranial fasciitis. CD34(-)
Image, below: the characteristic tissue culture–like appearance and cystic myxoid changes are virtually diagnostic.
64F big toe
dx
key features
Consistent with a rheumatoid nodule
Key features:
Central area of fibrinoid necrosis surrounded by palisading macrophages and lymphocytes
Necrobiosis, with fibrin deposition and palisading epithelioid histiocytes
Leukocytoclastic vasculitis (with associated immunoglobulin [Ig], fibrin deposition and complement activation) can be found in 33% of all rheumatoid nodules
Granulomas are typically identified in the subcutis but occasionally may involve the dermis
Above: Palisading granulomas surrounding fibrinoid necrosis
Below: Abundant fibrin with neutrophils surrounded by a palisade of epithelioid histiocytes
lobular capillary hemangioma
key features
Essential: Polypoid tumour with epithelial collarette and lobules of capillaries associated with an oedematous stroma.
a/W frequent ulceration with prominent inflammation consisting of neutrophils, usually restricted to the superficial aspect of the lesion.
small round blue cell tumour
ddx
D desmoplastic small round cell tumour
R Rhabdomyosarcoma (alveolar)
L Lymphoma (lymphoblastic type, TdT)
E Ewing’s sarcoma
M Melanoma (small cell type)
O Other (mesenchymal chondrosarcoma, small cell osteosarcoma)
N Neuroblastoma
S Small cell carcinoma/synovial sarcoma (small cell type not biphasic or epithelioid)
Other organ specific SRBCT e.g. orbit = RB, posterior cranial cavity (medulloblastoma)
14M retroperitoneal/intraabdominal small round blue cell tumour
Likely dx based on clinical
Desmoplastic small round cell tumour
(commonly occurs in adolescent males retroperitoneal/intrabdominal)
20M SRBCT in upper arm/head/neck
likely dx based on clincal
Alveolar rhabdomyosarcoma
(Occurs commonly in adolescents/young adults in the extremities/head + neck)
4yr posterior mediastinal mass
Likely dx based on clinical
Neuroblastoma
(commonly occurs in children < 5 yrs in posterior mediastinum/retroperitoneum
posterior knee mass. 20M
dx
Localisation
Epi
Key histo features
IHC:
Molecular
Dx: Monophasic synovial sarcoma (most common)
Localisation: Juxta-articular location on extremities is common.
Epi: 77% of cases occur before the age of 50 years
Key histo features:
dense, cellular sheets/vague fascicles of UNIFORM spindle cels, scanty cytopalsm.
Variable mitotic rate
Variable collagenous stroma
STROMAL CALCS 30% (diagnostic clue)
+/- metaplsatic bone/osteoid formation
Stromal vasculature can be prominent (focally staghorn/haemangiopericytoma-like)
Mast cells are a feature
Necrosis is UNCOMMON
IHC:
Keratin/EMA can be F+ (if D+, consider different entity). Can be D+ in epithelial component of biophasic SS.
TLE1 S+D+ nuclear (NB: focal and weak is non-specific & can be present in histological mimics e.g. SFT, MPNST and biphenotypic sinonasal sarcoma)
SS18:SSX (sensitive/specific)
S100/SOX10 F+ in 40%; CD56/CD99 (+) (DDx: neuroendocrine carcinoma/Ewing sarcoma)
CD43/SMA/desmin/myogenein/PAX3/NKX2.2 (-)
Molecular: SS harbours a unique t(X;18)(p11;q11) translocation { 11782370 }, by which SS18 on chromosome 18 is fused to one of the SSX genes (SSX1, SSX2, or SSX4) on the X chromosome
Below: Monophasic SS showing wiry collagen.
epithelioid haemangioendothelioma
Molecular alteration? (x2)
characterized by the presence of a WWTR1-CAMTA1 gene fusion. A small subset of tumours show distinct morphology, with well-formed vessels lined by epithelioid endothelial cells with abundant eosinophilic cytoplasm, and are characterized by a YAP1-TFE3 fusion.
Dx
Key features
IHC:
Key features:
Angiocentric tumour inducing a sclerotic stromal response
Myxohyaline stroma
+/-Infiltrative growth
Intracytoplasmic vacuoles sometimes present +/- RBCs
Minimal atypia
stroma variably hyaline/myxoid
Epithelioid haemangioendothelioma with YAP1-TFE3 fusion shows distinctive histological features. The tumour cells usually have brightly eosinophilic cytoplasm and are more likely to show solid growth and often form vascular spaces;
IHC: Epithelioid haemangioendothelioma with WWTR1-CAMTA1 typically shows diffuse strong nuclear expression of CAMTA1, which is a surrogate for the WWTR1-CAMTA1 fusion protein. Tumours with YAP1-TFE3 fusion show diffuse nuclear TFE3 expression; however, TFE3 is less specific in this regard, because expression can be seen in tumours with WWTR1-CAMTA1 fusion
Essential: classic epithelioid haemangioendothelioma is composed of cords or nests of epithelioid cells with cytoplasmic vacuolization within a myxochondroid or hyaline stroma; epithelioid haemangioendothelioma with YAP1-TFE3 fusion shows either solid growth or well-formed vascular channels lined by epithelioid endothelial cells with moderate nuclear atypia and abundant pale cytoplasm.
Desirable (in selected cases): CAMTA1 expression by immunohistochemistry and/or WWTR1-CAMTA1 fusion; TFE3 overexpression by immunohistochemistry and/or TFE3 gene rearrangement (YAP1-TFE3 gene fusion).
epithelioid haemangioendothelioma
Localisation:
Molecular alteration:
Most commonly involves somatic soft tissue, lung, and liver, but any site or organ can be affected.
Identification of the WWTR1-CAMTA1 or YAP1-TFE3 fusion transcripts helps distinguish epithelioid haemangioendothelioma from other tumours.
Forearm lesion, well-circumscribed
Dx?
Localisation?
Demographic?
Key histo features?
Molecular?
IHC?
DDX
Nodular fasciitis
Localisation: upper extremities, trunk, head and neck
Demo: More commonly in young adults
Histo:
Low-power: characteristic zonation effect (the center is hypocellular and the periphery is more hypercellular)
plump spindle-shaped cells lacking nuclear hyperchromasia or pleomorphism
Loose myxoidstroma
Arrangement of cells in “tissue-culture like manner”, typically it is partly discohesive and myxoid
Scattered osteoclast-like giant cells+ extravasated RBCs often seen
Mitotic activity may be prominent
Microcysts
IHC: SMA S&D (+) myofibroblastic (tram-track) pattern; , desmin (-); nuclear beta-catenina (+)
Molecular: USP6 rearrangements
DDx: (other myofibroblastic/fibroblastic tumors) i.e. desmoid fibromatosis, myofibroma, cellular dermatofibroma (benign fibrous histiocytoma) and spindle cell sarcoma or UPS
Image: the characteristic tissue culture–like appearance and cystic myxoid changes are virtually diagnostic.
vulval lump
dx?
IHC?
ddx?
Cellular angiofibroma
Usually arises in the superficial soft tissues of the vulva or inguinoscrotal regions.
Histologically uniform spindle cells, myxoid / collagenous stroma, network of thin walled, branching blood vessels; Alternating myxoid and collagenous areas; regional variation in cellularity, Perivascular lymphoid aggregates may be present. Mast cells are frequent. Small aggregates or individual adipocytes are observed in close to 50% of cases.
IHC: CD34 expression has been documented in 30–60% of tumours. Variable expression of SMA and desmin is identified in a minority of cases. ER and PR are expressed in many cases. RB1 loss is frequently detected.
6month old male neck mass
dx?
IHC?
Poorly differentiated neuroblastoma
Image showing thin septae of shwannian stroma (black arrows) & pale eosinophilic neuropil (blue arrows)
32M jaw mass
dx
Essential and desireable dx features
Diagnostic molecular
Mesenchyma chondrosarcoma.
Location: 50% intraosseus occur in jaw.
Median age 30 years.
Essential: undifferentiated tumour cells with a high N:C ratio; islands of cartilage.
Desirable: staghorn vascular pattern; HEY1-NCOA2 fusion.
aggressive angiomyxoma
genetic alteration
HMGA2 rearrangement identified in a small subset (33%)
NB: IHC staining does not equate to gene rearrangement as approx. 90% of tumours can be positive by IHC
SFT
factors used in risk assessment of these tumours
SDH deficient GISTs are associated with…(2)
- Carney triad (syndromic but not heritable), SDHC hypermethylation. (Multiple gastric GISTs, paragangliomas/phaoes and pulmonary chondromas)
- Germline SDH mutation syndrome (heritable SDHA/B/C/D mutations. Paragangliomas, GISTs, SDH-definicent RCC, pit adenoma
GIST risk assessment
describe
21 Male ulcer lesion sole of foot
Dx
Key dx features
IHC
Epithelioid sarcoma
Classic type usually on distal extremities young adults/adolescents. Also has a pseudogranulomatous pattern.
Essential: tumour presenting as a soft tissue mass (so-called distal or proximal presentations); epithelioid to spindled cytomorphology with infiltrative growth; diffuse loss of SMARCB1 (INI1, BAF47) and staining for EMA and keratin.
IHC: LMWCK/HMWCK/EMA + loss of INI1 (SMARCB1) nuclear staining.
desmoplastic small round cell tumour
Localisation:
Diagnostic molecular:
Localisation: abdominal cavity; retroperitoneum; ommentum; mesentery, pelvis.
Molecular: EWSR1 and WT1 gene rearrangements
Carney triad?
Gastric GIST, pulmonary chondroma and extra-adrenal paraganglioma
DFSP
mutation?
IHC?
COL1A1::PDGFB is the most common fusion product
IHC: CD34+
(-) S100, HMB45, desmin, SMA
48M PIPJ mass
Dx?
Dx: tumoral calcinosis
Lobular to irregular deposits of amorphous calcium crystals (hydroxyapatite crystals) within cystic spaces, surrounded by foreign body giant cell reaction
Nonneoplastic condition, mimics osteocartilaginous tumors
Can be primary (familial or sporadic) or secondary (tumoral calcinosis-like lesions)
Painless periarticular subcutaneous masses involving large joints and occurring in the first 2 decades
upper extremity well circumscribed skin nodule
Dx:
Dx: collagenous fibroma
Rare paucicellular tumor consisting of dense collagen fibers with scattered stellate and spindled fibroblasts involving the subcutis or skeletal muscles.
Most frequently found in the subcutis, with up to 25% found in the skeletal muscles
molecular alteration in Low -grade fibromyxoid sarcoma
FUS-CREB3L1 or FUS-CREBL2 gene fusion
molecular alteration in SFT?
NAB2-STAT6 fusion
Molecular alteration in LG fibromyxoid sarcoma?
t(7;16)(q34;p11), producing an FUS-CREBL2
What is Carney triad?
Gastrointestinal stromal tumours, pulmonary chondromas, paragangliomas
Name the soft tissue tumours of which mitotic rate determines malignancy? (4)
SFT
Smooth muscle tumors
Nerve sheath tumors
Granular cell tumors
dx molecular in nodular fasciitis?
rearrangements of USP6 moat odrwn ewaulrinf in n MYH9-UAP6 gene fusion.
55M right posterior shoulder nodule
Dx:
IHC:
Pleomorphic lipoma
(histologic variant of spindle cell lipoma)
IHC: CD34+, nuclear loss of RB1
dx molecular in lipoblastoma?
PLAG1 rearrangement
gene rearrangement in DFSP
DFSP (including the fibrosarcomatous component) harbors COL1A1-PDGFB rearrangement
What are the three most common pleomorphic sarcomas?
UPS
Myxofibrosarcoma
DD-LPS
Name lipoma variants (8)
Aside from lipoblastoma, spindle cell lipoma and pleomorphic lipoma
angioliopma
Intramuscular angiomas
Angiomyolipomas
Intramuscular lipoma
Hibernoma
epithelioid hemangioma
key features and molecular
predilection for head and neck
lobular proliferation of capillaries with plump epithelioid endothelial cells and prominent inflammatory infiltrate of lymphocytes and eosinophils
FOS or FOSB are detected in around half cases
molecular alteration in tenosynovial giant cell tumour (both localised and diffuse types)
COL6A3-CSF1 gene fusion
Synovial sarcoma dx molecular?
IHC
SS harbours a unique t(X;18)(p11;q11) translocation, by which SS18 on chromosome 18 is fused to one of the SSX genes (SSX1, SSX2, or SSX4) on the X chromosome
IHC: strong nuclear immunostaining for TLE1. TLE1 staining is not specific for SS, because it may also occur in histological mimics of SS, in particular malignant peripheral nerve sheath tumour and SFT.
Desmin/h-caldesmon always -
alveolar soft part sarcoma IHC and dx molecular
Characteristically have an unbalanced translocation der(17)t(X;17) with a corresponding ASPSCR1-TFE3 fusion.
TFE3 immunoreactivity is useful in the dx of alveolar soft part sarcoma.
list round cell sarcomas (8)
Ewing sarcoma
CIC-rearranged sarcoma
Sarcoma with BCOR alterations
PD synovial sarcoma
Alveolar RMS
HG myxoid (“round cell”) LPS
Desmoplasstic SRCT
Neuroblastoma
Plexiform schwannoma is associated with which syndrome?
NF2 and schwannomatosis
31F chest wall mass
Dx:
Key features
Molecular:
Mesenchymal chondrosarcoma
occurs in bone or soft tissue.
histo:
Solid sheets of undifferentiated small blue cells with a hemangiopericytoma-like vascular pattern mixed with islands of mature appearing, well differentiated hyaline cartilage
molecular: HEY1-NCOA2 gene fusion
Dx + histo key features
epidemiology - sk mature vs immature?
Imaging
Molecular
Imaging: multiloculated lesion with fluid-fluid levels, best appreciated on MRI
Skeletally immature
Histology: cyst walls composed of fibroblasts, woven bone and osteoclastic giant cells
Molecular: rearrangement of USP6 gene (primary form only)
extraskeletal myxoid chondrosarcoma, histo key features + mutation?
fibrous septa imparting multi lobular architecture
myxoid matrix
uniform cells in cords/clusters
NR4A3 rearrangement (sometimes with EWSR1). So use FISH
low grade fibromyxoid sarcoma mutation?
FUS-CREB3L2
Grading sarcomas in trunk/extremities?
pseudogout
Pathogenesis
polarized light findings
Calcium pyrophosphate dihydrate deposition disease
Classic rhomboid shaped crystals with positive birefringence under polarized light
EWSR1 translocation tumours (soft tissue)
Ewing sarcoma
Clear cell sarcoma (of soft tissue)
desmoplastic small round cell tumour
Angiomatoid fibrous histiocytoma
extraskeletal myxoid chondrosarcoma
ewing sarcoma
two most common translocations
(most common) EWSR1-FLI-1
EWSR1-ERG
epithelioid hemangioendothelioma
common molecular events (2)
- WTR1-CAMTA1 fusion (majority)
- YAP1-TFE3 fusion (minority)
How to distinguish angiomyofibroblastoma from deep aggressive angiomyxoma?
Angiomyofibroblastoma: variable cellularity, small round to spindle cells; more vascular and displays less larger open vessels instead displaying more numerous smaller vessels.
Deep aggressive angiomyxoma: infiltrative border, thick rounded (“medial hypertrophy”) vessels; hypocellular. HMGA2 overexpressed immunohistochemically > 90%
Both entities (+) for desmin; (-) for SMA/MSA
extraskeletal chondromyxoid sarcoma, desireable molecular criteria?
NR4A3 rearrangement (in selected cases). (FISH)
molecular alteration in alveolar soft part sarcoma
unbalanced translocation der(17)t(X;17) with a corresponding ASPSCR1-TFE3 fusion.
mesenchymal chondrosarcoma, key features and molecular?
SRBCT
Cartilage
Staghorn vessels.
HEY1-NCOA2
CD99+; Fli1/myogenin/LCA -
Adolescents/young adults
