SOFT TISSUE TUMORS

OF UNCERTAIN HISTOTYPE
PGI PAULINE BALUIS
1. SYNOVIAL SARCOMA
(Malignant Synovioma)

Definition:
 Malignant soft tissue tumor of uncertain
histogenesis with variable epithelial differentiation
 Typically arises near the knee and ankle joints of
children and young adults
 May also occur around and close to other joints,
such as the tendon sheaths and bursae

 Extremely rare for it to actually invade the joint space and

synovial membrane.
Etiology:
 Unclear
 May arise from a multipotent mesenchymal stem
cell OR satellite cells (immature myoblasts) as a
potential source

 Despite the name, the cells of origin are not synovial cells.
Epidemiology:
 5 - 10% of all soft tissue sarcomas
 Age range: 0 to 85
 Median age: 35 years
 Slight male predominance (1.2:1)
 Children and young adults (17.6%)
Location:
 Can occur anywhere in the body

Primary site distribution:

 Extremities: 68.7%
 Trunk: 15.7%
 Head and neck: 6.3%
 Intra-thoracic: 5.3%
 Intra-abdominal: 1.8%
 Other: 2.2%
Pathophysiology:
 (90%) t(X;18)(p11;q11)  fusion of the SS18 gene
on chromosome 18  SSX1 (66%) or SSX2 (33%)
 This results to multiple effects on oncogenetic
pathways:
 SWI/SNF chromatin remodeling complex;
 Polycomb repressor complex;
 WNT pathway
Clinical features:
 Very rarely associated with prior radiation therapy
 Not classically known to be associated with any
syndromes

Subtypes:
 Biphasic and Monophasic spindle cell
 Rarer subtypes: Poorly differentiated (round cell),
Calcifying / ossifying and myxoid
PHYSICAL EXAMINATION:
GROSS APPEARANCE:

Grossly, it tends to be
well circumscribed,
firm, and grayish pink.

Focal calcification is
frequent.
GROSS APPEARANCE:

Arm Shoulder Elbow

1. BIPHASIC TUMOR

 Typical biphasic tumor: epithelial (gland-like spaces

lined by cuboidal or columnar cells) and
sarcomatous components (spindle cells with a
fibroblast-like appearance.)
 Hypercellular nuclei, focally whorled pattern,
distinct fasciculations, a focal hemangiopericytoma-
like vascular pattern, and prominent mast cells.
 Hyalinization, calcification, and osseous
metaplasia can be present.
MICROSCOPIC APPEARANCE:
MICROSCOPIC APPEARANCE:

Biphasic tumor composed

of sharply segregated
epithelial (gland-like
spaces) and sarcomatous
components (spindle cells
with a fibroblast-like
appearance.)
2. MONOPHASIC SYNOVIAL SARCOMA

 Composed of only one component: the spindle cell

sarcomatous component (spindle cells with a
fibroblast-like appearance).
 Misdiagnosed as fibrosarcoma or other spindle cell
neoplasm
MICROSCOPIC APPEARANCE:

Monotonous cells with

scant amphophilic
cytoplasm, ovoid to
spindled vesicular nuclei
with evenly dispersed
chromatin.
3. POORLY DIFFERENTIATED

 Characterized by a greater degree of cellularity,

atypia, and mitotic activity.
 The tumor cells may be round, spindled, or large
and clear.
MICROSCOPIC APPEARANCE:

Highly cellular round cells

with hyperchromatic
nuclei, frequent mitotic
activity and necrosis.

Has an adenocarcinoma-
like appearance of the
epithelial component.
4. CALCIFYING SYNOVIAL SARCOMA

 This results hen the calcification from the biphasic

subtype is particularly heavy.
 Rarely can be extensive enough to obscure the true
nature of the tumor.
MICROSCOPIC APPEARANCE:
RADIOLOGY:

 Most present as round to oval, lobulated mass

 Ossifying synovial sarcomas have characteristic
spotty radio-opacities caused by focal calcifications
MRI:
MANAGEMENT:

 Primarily surgical
 Radiotherapy and adjuvant chemotherapy
 High risk (Tumors > 5 cm or difficult to resect)
 Radiation therapy:
 adjuvant use has shown improvement in
oncologic outcome and overall survival
PROGNOSIS:

Poor prognostic factors:

 SS18-SSX1 translocation
 Monophasic and poorly differentiated subtypes
 Male
 Older age at diagnosis
 Size ≥ 5 cm
 Non-extremity location
 Deep seated tumors
 Higher percentage of tumor necrosis
 Mitotic activity ≥ 10/HPF
 Immunohistochemical expression of CXCR4 and IGF-1R
 Positive surgical margins
Grading:
 In adults: Fédération Nationale des Centres de Lutte
Contre le Cancer (FNCLCC)
 In children: new grading system by the Pediatric
Oncology Group (POG)
2. MYXOMA

Definition:
 Rare, benign, gelatinous lesion resembling fetal
umbilical cord
 Often intramuscular or juxta-articular
 May derive from modified fibroblasts

Etiology:
 (61%) GNAS1 mutations (intramuscular
myxomas)   activation of the cellular oncogene
protein c-Fos
Epidemiology:
 Adults ages 40 - 70 years
 Female predominance
 Multiple myxomas associated with fibrous dysplasia
of the bones of the same extremity:
 Carney Complex
 Mazabraud Syndrome
PHYSICAL EXAMINATION:
DIFFERENTIAL DIAGNOSES:

1st group:
 Myxoid change can be a prominent secondary
feature.
 Liposarcoma, myxofibrosarcoma, chondrosarcoma, leiomyosarcoma,
embryonal rhabdomyosarcoma, neurofibroma, nerve sheath
myxoma, and aggressive angiomyxoma.

2nd group:
 Variety of non-neoplastic disorders resulting in focal
mucinous degeneration of the skin or soft tissues.
 Nodular fasciitis, localized myxedema, mucous (myxoid) cyst,
ganglion, follicular mucinosis, papular mucinosis, and cutaneous focal
mucinosis.
GROSS APPEARANCE:

Mucoid / gelatinous,
often poorly circumscribed,
may have infiltrative borders.

May grow up to 13 cm.

MICROSCOPIC APPEARANCE:

Hypocellular,
composed of
bland cells,
no lipoblasts,
scant blood
vessels; may have
focal histiocytes.

May have areas of

increased
vascularity or be
hypercellular.
MICROSCOPIC APPEARANCE:

Slightly basophilic
matrix with few spindle
cells and oval nuclei.
MICROSCOPIC APPEARANCE:

Cardiac

Thigh
MANAGEMENT:

 Surgical excision

Prognosis:
 Good prognosis
 Rarely recurs if adequately excised
3. ALVEOLAR SOFT PART SARCOMA

Definition:
 Rare tumor of deep soft tissue characterized by well
defined nests of cells separated by fibrous stroma.

Etiology:
 Unbalanced t(X;17)(p11.2;q25)  fusion of the
TFE3 transcription factor gene to ASPSCR1 gene
Epidemiology:
 <1% of all soft tissue tumors
 Most often arises in the deep soft tissue of thigh
and leg
 Less common: Oral cavity, pharynx, tongue,
mediastinum, retroperitoneum, orbit, bladder,
uterus, and vagina.
 Young female predominance (60%)
Clinical features:
 Usually presents as a deeply seated mass in the
lower limbs or limb girdle
 Vein invasion is common
PHYSICAL EXAMINATION:
PHYSICAL EXAMINATION:
GROSS APPEARANCE:

Tumors are
well circumscribed,
usually large,
moderately firm, and
gray or yellowish.
MICROSCOPIC APPEARANCE:

Large polygonal cells

with granular cytoplasm,
vesicular nuclei,
prominent nucleoli.

Vascular invasion is
common.

Characteristic rod-
shaped crystalloids.

No / rare mitotic figures,

minimal pleomorphism.
MICROSCOPIC APPEARANCE:

Prominent
nested growth pattern.
DIAGNOSIS:

Cytoplasmic vacuolation.

Large, rounded, polygonal

cells with abundant
acidophilic granular
cytoplasm.
DIAGNOSIS:
PAS (+):
Diastase resistant needle-like structures.
MANAGEMENT:

 Surgical removal
 Radiation therapy
PROGNOSIS:

 Highly malignant, despite its deceptively slow and

indolent
 Metastasis in the lung or another organ is the first
manifestation of the disease
4. CLEAR CELL SARCOMA
(Melanoma Of Soft Parts)

Definition:
 Rare aggressive tumor, slowly progressive, that arises
chiefly in association with large tendons and
aponeuroses of the extremities.
 Most common site affected: feet

Etiology (Genetic classification):

 t(12;22)(q13;q12)  EWSR1-ATF1 gene fusion  MiTF
transcript (melanocyte-specific splice form)
 GI tract cases: t(2;22)  EWSR1-CREB1 fusion
Epidemiology
 Male predominance (60%)
 Median age 30 years

Subtypes based on site of origin:

 Typical clear cell sarcoma of tendons and aponeuroses
(layers of flat broad tendons)
 Gastrointestinal clear cell sarcoma
 Cutaneous clear cell sarcoma

Clinical features:
 Initially asymptomatic, slow-growing lump
PHYSICAL EXAMINATION:

An erythematous,
dome-shaped,
nodular lesion,
1.3 cm in diameter
with a
serohemorragic crust
on its surface.
PHYSICAL EXAMINATION:
GROSS APPEARANCE:

Firm, well circumscribed,

gray - white,
gritty sensation
when cutting.
Ranges 1 - 15 cm.
Variable necrosis.
MICROSCOPIC APPEARANCE:

Distinct
nested growth
pattern with mixture
of spindle, epithelioid
and tumor giant cells.
MICROSCOPIC APPEARANCE:

Melanin pigment in
2 / 3.
May have floret-
like multinucleated
giant cells.

Often rhabdoid
cells, bizarre
pleomorphic cells.
Usually necrosis.

Mean:
4 MF / 10 HPF.
DIAGNOSIS:

FNAB
Positive stains:

• S-100 protein
• HMB 45
• Micropthalmic
transcription factor
(75%)
RADIOLOGY:

Soft tissue
swelling

 Ill defined, osteolytic lesion

at the calcaneal bone,
indicating cortical thinning.
MANAGEMENT:

 Radiation therapy: When given before surgery,

radiation therapy may shrink a tumor and make the
surgical procedure smaller.
 Standard chemotherapies: Ifosfamide and
Doxorubicin
 Targeted therapies: designed to target specific
features of cancer cells.
PROGNOSIS:

 Slow but relentless progression

 Frequent local recurrences
 Nodal and distant metastases
 Large tumor size and necrosis are significant
predictors of poor prognosis.
5. EPITHELIOID SARCOMA

Definition:
 Rare, malignant mesenchymal neoplasm that exhibits
epithelioid cytomorphology and a predominantly
epithelial phenotype, occurring in both pediatric and
adult populations

Etiology:
 Prior trauma at the site of the tumor (27%)
 Loss of INI1/SMARCB1 expression  deletion of
chromosome 22q11.2
 Proximal type: Dysadherin expression
 Two typical morphologies:
1. Classic / Conventional type (Distal type) with
epithelioid to spindled cells with central
pseudogranulomatous architecture.
2. Proximal type (Large cell type) with predominant
epithelioid and rhabdoid cells.
Epidemiology:
 < 1% of all adult soft tissue sarcomas
 4 - 8% of pediatric non-rhabdomyoblastic sarcomas
 Classic type: Most common ages 10 and 40 years;
M:F = 1.9:1
 Proximal type: More common ages of 20 and 65
years; M:F = 1.6:1
Location:
 Either type may arise anywhere
 Classic type: distal upper extremity; >60% arising in
the fingers and hand
 Proximal type: deep soft tissue, truncal tissue
(including pelvic peritoneal, genital and inguinal)
and buttock / hip
Pathophysiology:
 Structural and immunohistochemical studies
suggest a multidirectional differentiation, including
epithelial, histiocytic, fibroblastic, myofibroblastic,
endothelial and perineural.
Clinical features:
 Solitary or multiple, slowly growing, usually
painless, firm nodules
 Lesion often results in non-healing skin ulcers
 Tumor spreads to non-contiguous areas of skin, soft
tissue, fascia, and bone, as well as by direct
extension along fascial planes
PHYSICAL EXAMINATION:
PHYSICAL EXAMINATION:
GROSS APPEARANCE:

One or more
indurated, ill
defined, dermal or
subcutaneous
nodules.

Deep seated tumors

are multinodular
masses and involve
tendons or fascia.

Cut surface is gray-

white or gray-tan
color and with
multiple areas of
hemorrhage and
necrosis.
MICROSCOPIC APPEARANCE:

Most characteristic
features of this lesion is
the striking acidophilia
of the tumor, which is
due to the combined
effect of the staining
characteristics of the
cytoplasm and the
extensive desmoplasia.
MICROSCOPIC APPEARANCE:

The necrosis often

seen in the center of
the nodules.

The epithelioid
appearance of the
tumor cells may result
in a misdiagnosis of
infectious granuloma
or necrobiotic
granulomatous
inflammation.
DIAGNOSIS:

 Percentage expression of cytokeratins:

 CK8 (94%)
 CK19 (72%)
 CK14 (48%)
 CK7 (22%)
 CK20 (15%)
 CK5/6 (30%)
BIOPSY:
BIOPSY:
RADIOLOGY:

Calcification occurs within
the lesion in 10-20%.

Erosion of adjacent bone is

sometimes found.
MRI:

Tendon sheath nodule

may be visualized
MANAGEMENT:

 Core needle biopsy for deep tumors

 Punch biopsy for dermal tumors
 Wide excision with adjuvant radiotherapy
▪ all operable tumor
▪ high rate of multiple recurrences if mistaken for a benign lesion and
inadequately excised
▪ re-excision of the tumor bed is recommended for inadequate initial
resection 
 Amputation
 indications
▪ may be necessary to prevent spread of disease in cases of multiple
recurrences
PROGNOSIS:

 Local recurrence may take years to develop.

 Lymph node metastases is the first clinical
manifestation of the disease
 Proximal or axial tumor: more aggressive due to
location, increased size and depth, hemorrhage,
mitotic figures, necrosis, rhabdoid features, and
vascular invasion.