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Pitfalls in diagnosis of soft tissue tumors of childhood
1. Pitfalls in diagnosis of soft tissue tumors of
childhood
Presenter: Dr. Sonic V.S
Moderator: Dr. Sumita Tripathy
Dept Of Pathology, MKCG Medical College, Berhampur, Odisha.
2. • Soft tissue is defined as nonepithelial extraskeletal tissue of the body
exclusive of the reticuloendothelial system, glia, and supporting tissue of
parenchymal organs.
• Represented by voluntary muscles, fat and fibrous tissue, along with
vessels serving the tissues.
• By convention peripheral nervous system is also included because
tumors arise from them also present as soft tissue masses and pose
similar problems in differential diagnosis and therapy.
3. Introduction
Soft tissue tumors are a heterogeneous group
Classified by line of differentiation, the adult tissue they form
Benign tumors: mostly resemble normal tissue
Malignant tumors: aggressive and invasive or destructive growth
Incidence varies in adults and children
4. WHO classification of STT 2013
Classified based on histologic category
Each category have benign and malignant tumors
Some have a borderline (low malignant potential) group
Adipocytic Vascular
Fibroblastic/Myofibroblastic Chondroosseous
So-called fibrohistiocytic Gastrointestinal stromal
Smooth muscle Nerve sheath
Pericytic Tumors of uncertain differentiation
Skeletal muscle
Undifferentiated/unclassified
sarcoma
5. Childhood Soft Tissue Sarcomas
Constitute 5-8% of all childhood tumors.
Pose significant diagnostic challenges due to:
histological diversity
Overlap in morphologic features
Some overlap with adult tumors, but unique.
Outcome increased dramatically over the last two decades.
Attention now directed to reduce the toxic effects of therapy
as it hampers growth and quality of life.
In the realization of clinical implications of misdiagnosis, we will be
discussing the potential pitfalls encountered in pediatric soft tissue
pathology.
6. International classification of childhood cancers 2005 –
Soft tissue and extraosseous sarcomas
(a) Rhabdomyosarcomas
(b) Fibrosarcomas, peripheral nerve sheath tumors, and other
fibrous neoplasms
(b.1) Fibroblastic and myofibroblastic tumors
(b.2) Nerve sheath tumors
(b.3) Other fibromatous neoplasms
(c) Kaposi sarcoma
(d) Other specified soft tissue sarcomas
(d.1) Ewing tumor and Askin tumor of soft tissue
(d.2) pPNET of soft tissue
(d.3) Extrarenal rhabdoid tumor
(d.4) Liposarcomas
(d.5) Fibrohistiocytic tumors
(d.6) Leiomyosarcomas
(d.7) Synovial sarcomas
(d.8) Blood vessel tumors
(d.9) Osseous and chondromatous neoplasms of soft tissue
(d.10) Alveolar soft parts sarcoma
(d.11) Miscellaneous soft tissue sarcomas
Embryonal
Rhabdomyosarcomas Alveolar
Pleomorphic
Botryoid
Embryonal NOS
Anaplastic
Spindle cell
Embryonal
7. Classification of sarcomas
According to major therapeutic significance, Pediatric soft tissue sarcomas are classified as:
Rhabdomyosarcomas (RMS)
Non-rhabdomyosarcomatous soft tissue sarcoma
(NRSTS)
Undifferentiated soft tissue sarcoma (USTS)*
*USTS indicates a high grade mesenchymal tumor which fails to demonstrate a specific line of differentiation
by pathological and molecular investigations.
8. Problems arising before reporting
Problems occur mainly with interpretation of small or crushed biopsies
or poorly fixed tissue.
Well prepared sections remain the gold standard for diagnosis.
Priority for triaging is fixation in 10% neutral buffered formalin.
There is overlap in histology and immunohistoprofile of many tumors.
So cytologic or molecular confirmation is valuable in such cases.
These studies are particularly helpful when presentation occurs at
unusual age group or location, when unusual morphologic variants or
aberrant immunoreactivity encountered.
9. With recent advance in technology, Fluorescence in situ
hybridization (FISH) and reverse transcriptase polymerase chain
reaction (RT-PCR) can be done in paraffin embedded tissue.
Tumor cells can also be retrieved from fixed tissue by laser
capture microdissection and subsequently analyzed by RT-PCR
for signature translocations.
This is particularly important when frozen tissue is not available
as in cases of small biopsies or outside referral cases.
10. Pitfalls in diagnosis
Pitfalls in diagnosis of STS can be divided into five main categories.
They include:
Misclassification of specific sarcomas
Benign lesions misdiagnosed as sarcomas
Sarcoma misdiagnosed as benign lesions
Misgrading of sarcomas
Non soft tissue tumors misdiagnosed as soft tissue sarcomas
11. Potential pitfalls Specific pitfalls
Misclassification of specific sarcomas
RMS versus non RMS
Alveolar versus Embryonal RMS
Synovial sarcoma versus other adult type NRSTS
Benign lesions misdiagnosed as sarcoma
Fetal Rhabdomyoma
Plexiform cellular schwannoma
Pseudosarcomatous myofibroblastic tumors
Infantile myofibroma/myofibromatosis
Sarcomas misdiagnosed as benign lesions
Embryonal RMS
Low grade fibromyxoid sarcoma
Myofibrosarcoma
Misgrading of sarcoma
IMT as embryonal RMS
Infantile fibrosarcoma as malignant spindle cell tumor
Angiomatoid fibrous histiocytoma as RMS, EFT or MFH
Non soft tissue tumors misdiagnosed as soft tissue
sarcomas
Deep juvenile xanthogranuloma
Non Hodgkin lymphoma
Granulocytic sarcoma
12. Misclassification of specific sarcomas
Benign lesions misdiagnosed as sarcomas
Sarcoma misdiagnosed as benign lesions
Misgrading of sarcomas
Non soft tissue tumors misdiagnosed as soft tissue sarcomas
13. Rhabdomyosarcomas
Most common pediatric STS (approximately 50%)
3.5% of all malignancies under age of 15
2% of all malignancies in 15-19 age group
90 % of all RMS in individuals < 25 years;
60-70% in <10 years
Peak age 2- 5 years
Male preponderance (1.4:1)
14. Embryonal RMS
Most common
60-70% of all childhood RMS
Usually children ages 3-10 years
Head and neck and GUT, nasal and oral
cavities, orbit, middle ear, prostate,
paratesticular region
Intermediate prognosis
Variants include:-
Embryonal NOS
Spindle cell
Botryoid
Anaplastic
Grossly
• well circumscribed, multinodular
• Gray white glistening, gelatinous
cut surface
15. Cells are primitive stellate or
fusiform to well differentiated
forms.
Extensive rhabdomyoblastic
differentiation
round, strap or tadpole shaped
eosinophilic cells in a myxoid stroma.
Cytoplasmic striations present (20
to 30% cases).
Hypercellular areas, typically
concentrated around blood vessels
with alternate mucoid matrix rich
hypocellular areas.
16. Spindle cell embryonal RMS
50% of more of tumor cells should be
spindled for this diagnosis
Low grade, fascicular or storiform pattern
Uniform, relatively differentiated elongated
spindle cells
Blunted central nuclei and tapered ends, pale
indistinct cytoplasm
Scattered rhabdomyoblasts present
Spindled or polygonal
Brightly eosinophilic cytoplasm
Pleomorphic nuclei
Cross-striations seen occasionally
Low mitotic activity
17. Botryoid embryonal RMS
Hypercellular zone beneath
epithelium (Nicholson's cambium
layer)
Cells are undifferentiated, round or
spindled
Minimal cytoplasm
Frequent mitotic figures
Less cellular in deeper layers
differentiating and undifferentiated
cells resembling embryonal NOS
Superior prognosis
18.
19. Alveolar RMS
20% of all rhabdomyosarcomas
More common in early to mid-
teens but all ages affected
Neonatal cases have poor
prognosis, are associated with skin
and brain metastases
Rapid growing, often high stage at
presentation.
Associated with t(2;13) and t(1;13)
20. Round cells with frequent mitoses
Hyperchromatic nuclei, coarse
chromatin, distinct nuclear membrane.
Classic variant consists of
Anastomosing fibrous septa
Aggregates of discohesive cells.
Solid variant – little fibrous septa
Reticulin stain is useful as it
encircles the variably sized solid
aggregates of tumor cells.
Single focus of alveolar
morphology is sufficient
21.
22. Immunoprofile
Express Myogenin/myf4, MyoD1/myf3
The extent and intensity of staining can
be used to differentiate between the two
main types of RMS.
Alveolar RMS display an extensive (>50%)
nuclear staining for myogenin
Embryonal RMS show a focal pattern of
staining
Other non specific markers include
desmin, CD99, ALK, CD56, smA,
cytokeratin, S100 and neurofilament
protein.
23. Myogenin and MyoD1 expression helps in differentiating
RMS from a variety of tumors like:
MPNST
Nodular fasciitis
Inflammatory myofibroblastic tumor
Benign and malignant smooth muscle and neural tumors
Problems with immunomarkers
Focal positivity for myogenin can be seen in
Blastemal component of Wilm’s tumor
Synovial sarcoma
Infantile fibrosarcoma
Non neoplastic entrapped or regenerating skeletal muscle fibres
especially at the infiltrative edges of a round or spindle cell tumor
24. Mimics of embryonal RMS and its variants
Embryonal RMS can be confused
with
Benign and malignant myxoid tumors
How to differentiate?
Immunohistochemistry is useful in such
situations.
Myogenin expression, focal in case of
embryonal RMS
MyoD1 expression
25. Spindle cell variant can be
confused with
Benign fibrous histiocytoma
Neurofibroma
Leiomyosarcoma
Inflammatory myofibroblastic
tumor (IMT)
How to differentiate?
Positive myogenin expression helps
to rule out BFH and NF.
Negative h-caldesmon rules out
leiomyosarcoma.
26. IMT overdiagnosed as RMS due to its
infiltrative growth pattern, high mitotic
count, moderate atypia and vascular
bulging
Mixture of growth patterns
Absence of atypical mitotic figures
Myogenin expression absent.
Botryoid variant is mimicked by
Fetal rhabdomyoma
How to resolve the issue?
Fetal rhabdomyoma is a benign tumor
Absence of cellular pleomorphism
Absence of cambium layer in submucosal
tumors
Very low mitotic count
27. Alveolar RMS
Diagnosis is difficult when
there is a small biopsy, as the
alveolar component may not
be appreciable.
Such cases necessitate
cytogenetic and molecular
studies.
t(2;13) and t(1;13)
IHC helps in differentiating
from other small round cell
tumors.
Myogenin
Desmin
28. Anaplastic RMS
Poor prognosis
Large hyperchromatic
nuclei with multipolar
mitotic figures
More common in
embryonal RMS
29. Sclerosing RMS
Recent inclusion by WHO
Now considered with spindle cell RMS
as a separate entity
Rare, usual location is head and neck
Abundant stroma
Obscures the small blue tumor cells
Micro alveolar architecture.
Can be confused with
Angiosarcoma
Carcinoma
Myogenin and myoD1 positivity helps
in differentiation
31. Ewing sarcoma family of tumors
This group include
Extra osseous Ewing tumor and its variants
Peripheral primitive neuroectodermal tumors (pPNET)
Second most common pediatric soft tissue tumors (20%)
Usual sites - chest wall, paraspinal tissues and abdominal wall.
Children more than 10years.
Chromosomal abnormality include t(11;22) and t(21,22).
32. Microscopic features depend on degree of
neural differentiation.
Ewing sarcoma - undifferentiated end
pPNET - varying degree of neural
differentiation.
Predominantly lobular or trabecular growth
pattern
with predominant ramifying capillary network.
Stroma is very little.
Undifferentiated lesions
Cells with scanty, pale cytoplasm
Round to ovoid open nuclei with fine chromatin
Variable nucleoli.
Differentiated end
Cells with eosinophilic cytoplasm
Coarse chromatin
Frequent nucleoli.
Presence of rosettes, usually Homer Wright type.
33. Diagnostic challenges
All the tumors of this family show positive
immunoreactivity for
CD99
FLI-1*
But not specific
Should be used along with a panel of
other markers to exclude tumors which
mimic same histology like
Haematolymphoid
Neuroblastic
Myogenic tumors
* Friend Leukemia Integration 1
34. Mimickers of EFT
Lymphoblastic lymphoma
Shows positivity for CD99 and FLI-1
Sometimes can be negative for CD45
(LCA)
A combination of haematolymphoid
markers are used in such cases
TdT, CD43, CD34, CD10 and CD79a.
Neuroblastomas
Usually negative for CD99
Neuroblastic marker NB84 is positive in
20% of EFT.
It is also important to note that EFT
can be positive for CD117, CK, CD31
and desmin.
35. How to resolve cases which pose difficulty
in routine and IHC studies?
Cytogenetic or molecular genetic confirmation required
t(11;22) and t(21,22) - EWS-FLI
This is useful especially in visceral location of the tumor.
FISH is useful in such instances to detect translocation.
36. Desmoplastic round cell tumor
Highly aggressive clinical entity primarily of
young adults.
Rare in children.
Displays striking diversity in location.
Wide histological spectrum with several
morphological variants
Polyphenotypic immunoreactivity.
37. Sharply demarcated nests of varying size
Small round or oval cells embedded in a
hypervascular desmoplastic stroma.
Large tumor cell nests often central
necrosis.
Neoplastic cells are undifferentiated
scant amount of eosinophilic cytoplasm
small hyperchromatic nuclei
inconspicuous nucleoli
Nuclei are relatively uniform in most cases
Some show increased nuclear atypia, and
Rare tumors show markedly atypical cells.
38. IHC profile of DRCT
Immunostaining for carboxy-terminus of WT1 is
most sensitive
Cytokeratins
EMA
Desmin
Vimentin
NSE
Synaptophysin
S100
Cytogenetic and molecular genetics
t(11;22) EWS-WT1
39. Diagnostic challenges
EFT
Alveolar rhabdomyosarcoma
Neuroblastoma
Lymphoma
Small cell carcinoma
Immunostaining with desmin is
characteristic – perinuclear
globular pattern of
immunoreactivity.
40. Malignant rhabdoid tumour
Aggressive neoplasm of infancy and
childhood
Propensity for wide-spread metastases.
Usual sites - kidney, CNS, extrarenal soft
tissue
Congenital disseminated form.
Abnormalities of 22q11 and mutations and
homozygous deletions of INI1(hSNF5) gene
characteristic
Presence of rhabdoid cell is the hallmark of
MRT.
41. Rhabdoid cells are large polygonal cells
eccentric vesicular nuclei
prominent nucleoli.
abundant cytoplasm containing juxtanuclear
eosinophilic PAS-positive hyaline inclusions or
globules.
These inclusions are paranuclear intracellular
aggregates of intermediate filaments
ultrastructurally.
Arranged in patternless sheets and cords.
Wide variety of cytologic and architectural
features
small, round cells and a myxoid collagenous
stroma.
42. Immunophenotype of MRT:
Vimentin
Cytokeratin
EMA
SMA
Lack of reactivity to INI1/BAF1
antibody
(Normal cells and rhabdoid cells
which lack INI1(hSNF5) deletion
express nuclear reactivity to
INI1/BAF1* antibody)
*Integrase interactor 1/Barrier to
autointegration factor1)
44. Adult type NRSTS in children
This is a heterogenous group which include entities that are
usually seen in adults. They are:
Synovial sarcoma
MPNST
Liposarcoma
Epithelioid sarcoma Constitute 70% of adult type NRSTS
Leiomyosarcoma
Adult type fibrosarcoma
GIST constitutes 2% of all soft tissue sarcomas.
45. Synovial sarcoma
Third most common sarcoma in
childhood
Second decade of life and also
newborns
Extremities common site
Visceral sites and mediastinum also
Gross – well circumscribed
round/multilobular
maybe cystic
occasional calcification
46. Biphasic
Monophasic
Poorly differentiated
Biphasic :
Large round/oval epithelial cells
having pale cytoplasm and vesicular nuclei
Arranged in solid cords, nests or glands
Surrounded by well oriented plump
uniform spindle cells – indistinct
cytoplasm and oval dark staining nuclei
Areas of hyalinization, myxoid change
and calcification maybe present
47. Monophasic type:
Mostly spindle cells
Plump fascicles with hyalinization
Accompanied by mast cells
Occasional osseous or cartilaginous
metaplasia
No particular pattern as in other
fibrous tumors
Monophasic epithelial type is rare
48. Poorly differentiated
Large cell or epithelioid pattern
having variably sized round nuclei
and prominent nucleoli
Small cell pattern with nuclear
features similar to other SRCTs
High grade spindle cell pattern
with high grade nuclear features
and high mitotic count with
necrosis
Highly vascular tumors
49. Mimickers of synovial
sarcoma
Biphasic type
MPNST as both the tumors show
glandular elements.
How to differentiate?
The glands of MPNST show intestinal type
epithelium
Presence of goblet cells and microvilli
Synovial sarcoma lack these features
IHC – SS is positive for CK and EMA
50. Monophasic type
MPNST
Fibrosarcoma
How to diagnose SS?
Thorough search for epithelial component
Foci of calcification
Above favors SS
Positivity for CK and EMA is confirmatory
Poorly differentiated
Small round cell tumors
MPNST
Embryonal RMS in case of myxoid variant
Infantile hemangipericytoma
How to differentiate?
Routine histology and IHC not helpful
Cytogenetic study for t(X;18) in SS
TLE 1 has emerged as a useful
marker for differentiating
difficult cases of synovial
sarcoma.
51. Malignant peripheral nerve sheath tumor
(MPNST)
15% of adult type sarcomas in
children
Usually infrequent in childhood
High grade tumors with poor
prognosis
Second decade
Occurs in children with NF1
Extremities, trunk, H&N
Gross:
Large fusiform mass >5cm
Tan white fleshy
Areas of hemorrhage and necrosis
52. Spindle cells in fascicular pattern
Branching hemangiopericytoma like
vascular pattern
Alternate hypo and hypercellular areas
Whorling or rarely palisading pattern
Geographic areas of necrosis
Hyperchromatic nuclei and pale
cytoplasm
Cells concentrate around blood vessels
MPNST in children shows prominent
neuro-epithelial foci and primitive cells
53. Epithelioid MPNST
Plump epithelioid cells
Abundant eosinophilic cytoplasm
Abundant extracellular myxoid matrix
Lobulated growth
• Malignant Triton tumor
• Skeletal muscle differentiation
• Glandular MPNST
• Glandular differentiation with or
without mucin production
54. Mimics of MPNST
Synovial sarcoma
Distinguished using neural marker Nestin
Plexiform cellular schwannoma
Commonly in first decade
Present as congenital tumors
No association with NF1
Uniform S100 positivity and lack of p53
expression
Electron microscopy well differentiated
Schwann cells
Leiomyosarcoma
Embryonal RMS
55. Leiomyosarcoma
Leiomyosarcoma in pediatric age group rare
Showed focally typical features of smooth muscle
differentiation
In the form of fascicles of eosinophilic spindle cells
With cigar-shaped nuclei.
Unusual whorled growth pattern maybe seen
Low grade lesions usually
Differential diagnosis include
Infantile myofibromatosis
Leiomyoma
Monophasic synovial sarcoma
Spindle cell rhabdomyosarcoma.
56. Liposarcoma (LPS)
Rare soft-tissue sarcoma of childhood
Presents in the second decade
Female predilection (2F:1M)
Preference for the lower extremity Myxoid LPS
accounts for 80% to 90% of cases
Usually myxoid-round cell types
Spindle cell and pleomorphic variants
Differential diagnosis include:
Lipoblastoma
Rhabdomyosarcoma
Lipoma
Cytogenetics:
t(12;16) (q13;p11) FUS-CHOP fusion
EWSR1-CHOP rearrangement
57. Misclassification of specific sarcomas
Benign lesions misdiagnosed as sarcomas
Sarcoma misdiagnosed as benign lesions
Misgrading of sarcomas
Non soft tissue tumors misdiagnosed as soft tissue sarcomas
59. Fetal rhabdomyoma
Rare tumor
Mean age in children 2years
25% cases are congenital
Head and neck region
Esp post auricular region
Intranasal or intraoral
Gross:
Circumscribed soft mass with glistening c/s
60. Irregular bundles of immature skeletal
muscle fibres
Myxoid background
Spindle cells with central oblong nuclei
and eosinophilic cytoplasm
Mitosis can be relatively frequent
Has to be distinguished from Embryonal
RMS – botryoid variant
Absence of cellular pleomorphism
Absence of cambium layer
Absence of nuclear atypia
Absence of atypical mitoses or necrosis
61. Plexiform schwannoma
Involve multiple nerve
fascicles or nerve plexus
Usually seen in childhood
or at birth
Arise from skin and
subcutaneous tissue
Grossly: encapsulated and
multinodular
62. Plexiform architecture
Lobules of tumor cells separated by
fibrous septa
Biphasic pattern may not be
prominent
Often cellular with hyperchromatic
nuclei and mitotic activity
No necrosis, no myxoid change
Has to be differentiated from
MPNST
Uniform positivity for S100
Lack of P53 positivity
63. Pseudosarcomatous
fibroblastic/myofibroblastic lesions
12% of STTs in childhood
Group of benign tumors
Due to rapid growth clinical suspicion of malignancy
Pathologically
Increased cellularity
Nuclear pleomorphism
Mitotic activity
Overlap with myogenic immunophenotype
64. Nodular fasciitis
Self limiting fibrous neoplasm of
subcutaneous tissue
Occurs in all ages
Rare in children (cranial fasciitis
occurs in infants)
Upper extremities, trunk, chest wall,
head and neck
In children arise as rapidly growing
mass in orbital, periorbital,
premaxillary areas
Grossly, <5cm, circumscribed,
nonencapsulated nodule with a
glistening mucoid appearance
65. Plump spindle shaped fibroblasts and
myofibroblasts forming short fascicles
Less cellular area of mucoid-myxoid
extracellular material (tissue culture
pattern)
Mitotic figures are plentiful
No nuclear hyperchromasia and
pleomorphism
Border is focally infiltrative
Presence of extravasated RBCs,
osteoclast like giant cells, lymphocytes
66. Overdiagnosis as malignancy:
Unusual extracranial locations
Erosion of bone
Invasion of skeletal muscle, nerves and
lymph nodes
Nuclear pleomorphism and mitosis in
cellular areas
In children it can mimic
Embryonal RMS
Synovial sarcoma
DFSP
Fibrosarcoma
• Can be differentiated by:
• Small size (<4cm)
• Absence of atypical mitotic figures
• Demonstration of myofibroblasts
• Vimentin
• Muscle specific actin
• SMA, Desmin
• Negative staining for
• Myogenin
• CK
• EMA
• CD34
67. Proliferative fasciitis
Rare in childhood
Subcutaneous lesions
Sites include upper extremities, head
and neck, trunk
Rapidly growing
Poorly circumscribed
discoid/elongated mass grossly
68. Bland tissue culture like fibroblastic
and myofibroblastic spindle cells
Variably myxoid and collagenous
stroma
Presence of large basophilic
ganglion like cells with vesicular
nuclei and prominent nucleoli
Pediatric lesions are usually more
cellular
Frequent mitosis
Acute inflammation and necrosis
Less collagenous matrix
69. Childhood proliferative fasciitis can mimic
Embryonal RMS
Ganglioneuroblastoma
Differentiated by
Demonstrating myofibroblastic immunotype
Negative staining for myogenin, NSE, GFAP and
neurofilament protein
70. Infantile myofibroma/myofibromatosis
20% of fibroblastic
myofibroblastic lesions
Age <2 years, 60% at birth
Solitary, multicentric and
generalized forms.
Usually superficial lesions
Grossly rubbery/firm lesions
C/s red or yellow soft centre
surrounded by white areas
71. Nodular or multinodular pattern
Biphasic light and dark staining areas
Light areas show plump myoid spindle
cells with eosinophilic cytoplasm
Arranged in whorls or short fascicles with
cigar shaped nuclei
Dark staining areas show round to
polygonal cells with hyperchromatic
nuclei
Arranged around vascular spaces
72. Features responsible for misdiagnosis as infantile fibrosarcoma
Increased cellularity
Mitotic activity
Infiltration of myofibroblasts into adjacent tissues
Intravascular growth simulating vascular invasion
Multicentric occurrence mistaken as metastasis
Differentiation is usually difficult in routine sections and IHC
Genetic studies to exclude fibrosarcoma is indicated
t(12;15)(p13;q25)
73. Misclassification of specific sarcomas
Benign lesions misdiagnosed as sarcomas
Sarcoma misdiagnosed as benign lesions
Misgrading of sarcomas
Non soft tissue tumors misdiagnosed as soft tissue sarcomas
74. Sarcomas misdiagnosed as benign lesions
Myxoid tumors
Treacherous group accounting for misdiagnosis
Clinical spectrum ranges from reactive, benign to high grade sarcomas
This include:
Embryonal RMS
Myofibrosarcoma
Low grade fibromyxoid sarcoma/hyalinising spindle cell tumor with giant
rosettes
75. Myofibrosarcoma
Rare in children
Arise in bone and soft tissue
Head and neck predilection
Grossly:
Firm
Pale fibrous cut surface
Ill defined margins
76. Histology:
Spindle to stellate shaped cells
Intersecting fascicles, sheets or
storiform
Collagenous/myxoid stroma
Cells have pale eosinophilic
cytoplasm
Fusiform nuclei
Evenly dispersed chromatin
Low mitosis
Necrosis absent
Infiltration to surrounding tissues
77. Low cellularity
Low mitotic activity can lead to a diagnosis of benign lesion
Absent necrosis
IHC can be helpful in such situations
SMA
Muscle specific actin
Calponin
78. Low grade fibromyxoid sarcoma/hyalinising
spindle cell tumor with giant rosettes
Morphologic spectrum of same entity
Majority in young adults
20% cases occur in <18years
Deep soft tissue mass in adults
Superficial form in children
No metastases
Grossly:
Well circumscribed
Fibrous, focally mucoid
1cm to >20cm
79. Low to moderate cellularity
Bland spindle cells with
hyperchromatic oval nuclei
Finely clumped chromatin
One to several small nucleoli
Cells are seen in fibrous and
myxoid stroma
Low mitotic activity
Whorled or random pattern
Curvilinear blood vessels
Collagen rosettes can be found
81. Misclassification of specific sarcomas
Benign lesions misdiagnosed as sarcomas
Sarcoma misdiagnosed as benign lesions
Misgrading of sarcomas
Non soft tissue tumors misdiagnosed as soft tissue sarcomas
82. Misgrading of sarcomas
Borderline neoplasms overdiagnosed as malignant
lesions
Two of the fibroblastic/myofibroblastic lesions:
Inflammatory myofibroblastic tumor
Infantile fibrosarcoma
These two lesions are of intermediate biologic potential
Recur locally
Rarely metastasize
83. Inflammatory myofibroblastic tumor
Borderline tumor
Occurs in first two decades
90% occur in respiratory tract, abdomen &
genitourinary tract
Associated with systemic symptoms and
polyclonal hyperglobulinemia
Grossly:
2 to 20cm
Lobular, multinodular/bosselated
Hard/rubbery gray white cut surface
84. Predominantly bland spindle
cells
In a myxoid or hyaline stroma
Lymphoplasmacytic infiltrate
Three patterns identified:
Nodular fasciitis
Fibrous histiocytoma
Scar like
Mitotic figures are variable, not
atypical
Large ganglion like cells can be
seen in first two
85. The fibrous histiocytoma like pattern can be misdiagnosed
as high grade spindle cell sarcomas
IHC is helpful in ruling out these lesions
ALK positivity is seen in IMT, but not specific.
Other mimics include:
Leiomyosarcoma
GIST
Both are rare in childhood
H-caldesmon and CD117 negativity
Cytogenetics
There is rearrangement of 2p23 and ALK gene in about 50%.
FISH is useful.
86. Infantile/congenital fibrosarcoma
Rare tumor
Presents in first year of life
Superficial and deep soft tissue of distal
extremities, head&neck
Rapidly enlarging mass
Grossly:
Poorly circumscribed lobulated
Pseudocapsule
Fleshy tan c/s
Cystic/mucoid areas with
hemorrhage/necrosis
87. Densely cellular
Intersecting fascicles of primitive,
round, ovoid and spindle cells
Focal herringbone pattern
Nuclear pleomorphism is little
Mitotic activity is prominent
Tumors with abundant collagen
resemble adult fibrosarcoma
Lymphocytic infiltration is common
88. Mimics
Solid growth pattern with high mitosis:
Spindle cell sarcomas of childhood
Infantile fibromatosis – difficult
Predominantly myxoid pattern:
Myxoid mesenchymal tumor of infancy
Multinodular
Primitive tumor cells are embedded in uniform myxoid
stroma
Branching blood vessels
Focal interlacing fascicles
Locally aggressive
IFS does not have specific immunotype
t(12;15)(p13;q25) ETV6-NTRK3 fusion
89. Misclassification of specific sarcomas
Benign lesions misdiagnosed as sarcomas
Sarcoma misdiagnosed as benign lesions
Misgrading of sarcomas
Non soft tissue tumors misdiagnosed
as soft tissue sarcomas
90. Non soft tissue tumors misdiagnosed as
STS
Atypical presentations of certain non soft tissue
tumors can be misinterpreted as soft tissue sarcomas
They include Histiocytic and haematolymphoid
tumors
Usual culprits include:
Deep juvenile xanthogranuloma
Extranodal Non Hodgkin’s lymphoma
Extramedullary myeloid tumors
91. Deep Juvenile Xanthogranuloma
Most common non-Langerhan’s
histiocytic disorder
Occurs in neonates and young
children
Solitary or multiple skin lesions
Head and neck region usually
Benign self limited lesion
92. Dense dermal infiltrate of lymphocytes
eosinophils and neutrophils, which
may extend into subcutis
Touton giant cells (usually),
Lipid laden macrophages and
histiocytes
0-2 mitotic figures per 10 HPF, rarely
numerous
Epidermis thins out, rete ridges
become elongated
93. Diagnostic difficulty arise in deep JXG
Esp in deep soft tissues and skeletal muscles
Poorly circumscribed
Rapid growth
Mistaken for sarcoma
Composed of non lipidised mononuclear
histiocyte like cells
Touton giant cells +/-
Histiocytes show atypia and mitotic activity
This picture will confuse with sarcoma
IHC is helpful in difficult cases
CD68 and FXIIIa is positive
94. Extranodal NHL in soft tissue
Very rare presentation
Usually subcutaneous masses
Association with HIV
Lymph node involvement maybe absent
Can be misdiagnosed as small round cell
tumors
IHC is mandated in such cases
95. Myeloid sarcoma in soft tissue
Rare presentation
May precede or coincide with AML
Pose a potential pitfall in diagnosis
Can be mistaken for soft tissue
sarcoma esp small round cell tumor
group
Immunotyping is advocated along
with hematological evaluation
CD117, CD43, MPO, CD68 & CD34 are
useful
96. IHC panel for Soft tissue sarcomas
IHC panel for small round cell tumors
CD45 NB84 CD99 Myogenin WT1 CK/EMA INI 1
Rhabdomyosarcom
a
- - - + - +, <10% +
EFT - + (20%) + - - +, <7% +
DRCT - + (50%) - - + + +
MRT - NK + - NK + -
NHL/ALL + - + - - + NK
Neuroblastoma - + - - - - NK
Blastemal
component of
Wilm’s tumor
- - - - + + +
97. Immunohistochemical reactivity for spindle cell sarcomas
– percentage positivity
Myogen
in
CK7 EMA S100 Nestin
RMS 95 <10 <1 <10 NK
SS 10 60 90 48 0
MPNST 0 0
13,
weak
55 78
FS 20 0 0 <5 NK
99. Summary
Soft tissue tumors in childhood pose great challenges in accurate
diagnosis
Pitfalls in diagnosis include
Misclassification
Benign tumors misdiagnosed as sarcomas
Sarcomas interpreted as benign tumors
Misgrading of sarcomas
Non STS presenting as soft tissue tumors
Rhabdomyosarcoma is the most common soft tissue sarcoma in
childhood.
Diagnosing the types and variants have therapeutic significance
Benign myofibroblastic tumors are the largest group involving misdiagnosis.
100. Extensive IHC may be necessary for accurate identification of
round cell and spindle cell tumors, but none of the antibodies
are specific.
Extrarenal soft tissue malignant rhabdoid tumor shows
morphological and immunophenotypic variability.
It can be diagnosed easily by the recent availability of commercial antibody to
the INI1/BAF gene product.
Genetic studies provide valuable support to pathological
diagnosis
Particularly for tumors having no specific histological features.
Critical in STTs presenting in unusual clinical settings or when rare
morphological variants or aberrant immunoreactivity is encountered.