In terms of clinical and pathologic entities, soft tissue refers

to non-epithelial tissue excluding the skeleton, joints,

central nervous system, hematopoietic and lymphoid
tissues.

Most of the soft tissue is derived embryologically from mesoderm, with a

neuroectodermal contribution corresponding to the peripheral nerves, and
presumably to some of the soft tissues of the head and neck region

Fibrous tissue consists primarily of fibroblasts and an extracellular matrix that

contains fibrillary structures (collagen and elastin) and nonfibrillary extracellular
matrix (‘ground substance’). Fibrous tissue is classified according to its texture into
loose (most locations) and dense (tendons, aponeuroses, and ligaments). Fibroblasts
are responsible for the production of the various extracellular materials, including the
many types of collagen. Their shape varies from spindle (especially when stretched
along bundles of collagen fibers) to stellate (in myxoid areas). Immunohistochemically,
they are reactive for vimentin and focally for actin. Fibrocytes represent the quiescent
stage of fibroblasts. Myofibroblasts are modified fibroblasts that show features
intermediate between fibroblasts and smooth muscle cells.[25–27]
Adipose tissue is divided into two major types: white fat, mainly located in the
subcutaneous tissue, mediastinum, abdomen, and retroperitoneum; and brown fat,
which is concentrated in the interscapular region, neck, mediastinum, axillae, and
retroperitoneum (especially perirenal region).[3] Brown fat, whose main function is
heat production, is much more conspicuous in infants and children. White fat consists
of lipocytes. These are round or oval cells having most of the cytoplasm occupied by a
single large lipid droplet that pushes the crescent-shaped nucleus to the periphery. 2
Brown fat cells are smaller, with an acidophilic multivacuolated cytoplasm and a
Although nonneoplastic conditions can involve
soft tissue, they are seldom confined to this compartment
so the area of soft tissue pathology is restricted to neoplasms.
With the exception of skeletal muscle neoplasms,
benign soft tissue tumors outnumber their malignant counterparts,
the sarcomas, by 100 fold.
In the United States, the
incidence of soft tissue sarcomas is approximately 12,000
per year, which is less than 1% of all cancers. Sarcomas,
however, cause 2% of all cancer mortality, reflecting their
aggressive behavior.
Most soft tissue tumors arise in the
extremities, especially the thigh. Approximately 15% arise
in children but the incidence increases with age.

Soft tissue tumor comprises of wide variety of lesions with

different architectural patterns. It is often difficult to assess
the exact histological type of soft tissue lesions on fine needle
aspiration cytology (FNAC). The primary diagnosis of soft
tissue tumor with the help of FNAC is not well-accepted and it
is still a controversial issue. In fact, there is a negative attitude
of surgeons, oncologist and even histopathologists regarding
FNAC diagnosis of soft tissue lesions.

3
Few areas in cytology arouse such passionate discourse as fine-needle aspiration (FNA)
cytogenetic analysis has emerged as a promising diagnostic adjunct in soft tissue
tumour diagnosis. Karyotyping, fluorescent in situ hybridization (FlSH) and molecular
genetic analysis can be performed on FNA from musculoskeltal tumours [64-68] (fig.
6). FISH or reverse Fine needle Aspiration of Soft Tissue Tumours transcriptase-
polymerase chain reaction (RT-PCR; when the gene involved in a diagnostic
chromosomal aberration, most often a translocation, are known) are easier to
perform on FNA, because the number of cell necessary for these analyses are far Iess
than for conventional karyotyping, and dividing cell are not necessary. The hitherto
known diagnostic chromosomal aberrations are listed in table 3.

4
Purpose of classification is to link
similar tumors in order to understand
their behavior, determine the most
appropriate treatment, and investigate
their biology.
  Soft tissue tumors are classified
according to the cell type they
resemble.

In this atlas we use the classification proposed by Kemp on et al. and Weis and
Goldblum, respectively. Since knowledge of the histotype of a sarcoma alone is not
always sufficient to predict clinical course and choice of therapy a number of grading
systems, based on a variety of parameters have been suggested and debated. The
most frequent parameter used are cellularity, differentiation, cellular and nuclear
pleomorphism mitotic rate, necrosis and vascular invasion. The number of grades
varies; two, three and four grade have been proposed. However the histotype in itseIf
may indicate tumour grade. For example, the extraskeletal
Ewing's sarcoma (ES)/primitive neuroectodermal tumour (PNET) family of tumour,
rhabdomyosarcoma and pleomorphic liposarcoma are all high-grade malignant, while
well-differentiated liposarcoma, paucicellular myxoid liposarcoma, infantile
fibrosarcoma and dermatofibrosarcoma protuberans are low grade. Provided that a A
smear from a sarcoma is technically satisfactory and moderately cellular it impossible
to grade most sarcomas into low grade or high-grade categories

The diagnostic workup of a soft tissue tumour before surgery include site, type
diagnosis and location in relation to the surrounding tissues, especially major nerves 5
and vessels. Magnetic resonance imaging is usually best for this evaluation. For
still unknown but recognized causes include:
various physical and chemical factors,
exposure to ionizing radiation, and
inherited or acquired immunologic defects.
Sarcomas originating from benign tumors rare
except for MPNS arising in neurofibromas in von Recklinghausen
GIST, an adjacent nodule has absolutely bland histology.
Etiology
- Radiation
- Trauma????
- Foreign body
- Chemicals
- Viruses (HHV8, EBV)

Environmental Factors
Trauma
calls attention to underlying neoplasm.
But occasionally, a causal relation found
Rare soft tissue sarcomas arising in
scar tissue
following surgical procedures or thermal or acid burns
fracture sites, and
in vicinity of plastic or metal implants,
Environmental carcinogens
Certain herbicides (Phenoxyacetic acid, chlorophenols, and dioxin)
have been linked to sixfold increased risk sarcomagenesis. 6
Vinyl chloride
Lipoma, a benign tumor of fat, is the most common soft tissue tumor of adulthood.
These tumors are subclassified according to morphologic and/or characteristic
molecular features as conventional lipoma, fibrolipoma, angiolipoma, spindle cell
lipoma and myelolipoma.
Lipomas are soft, mobile, and painless (except angiolipoma) and are usually cured by
simple excision.

7
MORPHOLOGY
The conventional lipoma, the most common subtype, is a wellencapsulated mass of
mature adipocytes. It usually arises in the subcutis of the proximal extremities and
trunk, most frequently during middle adulthood. Infrequently, lipomas are large,
intramuscular, and poorly circumscribed.

9
Liposarcoma is one of the most common sarcomas of adulthood. It occurs mainly in
people in their 50s to 60s in the deep soft tissues of the proximal extremities and in
the retroperitoneum. Amplification of 12q13-q15 and t(12;16) are characteristic of
well-differentiated and myxoid liposarcomas, respectively. One of the key genes in the
amplified region of chromosome 12q is MDM2, which you will recall encodes a
potent inhibitor of p53. Pleomorphic liposarcomas contain complex karyotypes
without reproducible genetic abnormalities.

12
All types of liposarcoma recur locally and often repeatedly unless adequately excised.
The well-differentiated variant is relatively indolent, the myxoid/round cell type is
intermediate in its malignant behavior, while the pleomorphic variant usually is
aggressive and frequently metastasizes.

13
All types of liposarcoma recur locally and often repeatedly unless adequately excised.
The well-differentiated variant is relatively indolent, the myxoid/round cell type is
intermediate in its malignant behavior, while the pleomorphic variant usually is
aggressive and frequently metastasizes.

15
Due to the clinical history most nodular fasciitis lesions are needled in an early
phase.
The vast majority regress spontaneously and conservative follow-up is the
appropriate management
if the combined evaluation of clinical data and cytological features is typical

Nodular fasciitis is a self-limited fibroblastic and myofibroblastic

proliferation that typically occurs in young
adults in the upper extremity. A history of trauma is present
in approximately 25% of cases and the tumors grow rapidly
over a period of several weeks or months, typically no larger
than 5 cm. Whereas nodular fasciitis was historically considered
a reactive inflammatory lesion, identification of
t(17;22) that produces a MYH9-USP6 fusion gene indicates
that it is a clonal, but self-limited, proliferation.
It appears that the proliferating cells lack some key hallmark of cancer, perhaps the
ability to avoid senescence.
Intriguingly, ABC(discussed earlier), another tumor that sits in a gray zone between
reactive and neoplastic proliferations, also contains USP6 fusion genes.
Nodular fasciitis typically spontaneously regresses and if excised, it rarely recurs

The pseudosarcomatous lesions are an important target for needling in this

histogenetic group of tumors/lesions.
Nodular fasciitis is among the commonest and the most frequently needled. Dahl and
Åkerman reported 13 cases with cytology 1981;12 at present, our material comprises 17
more than 70 cases, all with remarkably similar cytomorphology.
Grossly the lesion is less than 5 cm, circumscribed, or slightly infiltrative

18
Nodular fasciitis arises in the deep dermis, subcutis, or muscle. Grossly the lesion is
less than 5 cm, circumscribed, or slightly infiltrative. The lesion is richly cellular and
contains plump, immature-appearing fibroblasts and myofibroblasts arranged
randomly or in short fascicles reminiscent of tissue culture fibroblasts. A gradient of
maturation (zonation) from cellular, loose, and myxoid to organized and fibrous is
typical.
The cells vary in size and shape (spindle to stellate) and have conspicuous nucleoli;
mitotic figures are abundant. Lymphocytes and extravasated red blood cells are
common but neutrophils are unusual.

20
Fibromatoses
Superficial Fibromatosis
Superficial fibromatosis is an infiltrative fibroblastic proliferation that can cause local
deformity but has an innocuous clinical course. All forms of superficial fibromatosis
affect males more frequently than females. They are characterized by nodular or
poorly defined broad fascicles of fibroblasts in long, sweeping fascicles, surrounded
by abundant dense collagen. Several clinical subtypes have been identified:

Clonal fibroblastic proliferation of deep soft tissue with infiltrative growth

"Desmos" (Greek) means tendon-like
Locally aggressive (local recurrence, but no metastases)
Epidemiology
Incidence of 2 - 4 per million population, less common than superficial fibromatosis
May be familial (associated with Gardner syndrome / FAP syndrome, or familial
desmoid syndrome, or related to trauma

22
Palmar (Dupuytren contracture): Irregular or nodular thickening of the palmar fascia
either unilaterally or bilaterally (50%). Over a span of years, attachment to the
overlying skin causes puckering and dimpling. At the same time a slowly progressive
flexion contracture develops that mainly affects the fourth and fifth fingers of the
hand.
Plantar: Common in young patients, unilateral and without contractures.
Penile (Peyronie disease): Palpable induration or mass on the dorsolateral aspect of
the penis. Eventually, it may cause abnormal curvature of the shaft, constriction of
the urethra, or both.
In about 20% to 25% of cases, the palmar and plantar fibromatoses stabilize and do
not progress, in some instances resolving spontaneously. Some recur after excision,
particularly the plantar variant.
Deep Fibromatosis (Desmoid Tumors)
Deep fibromatoses are large, infiltrative masses that frequently recur but do not
metastasize. They are most frequent in the teens to 30s, predominantly in women.
Abdominal fibromatosis generally arises in the musculoaponeurotic structures of the
anterior abdominal wall but tumors can arise in the limb girdles or the mesentery.
Deep fibromatoses contain mutations in the APC or β-catenin genes, both of which
lead to increased Wnt signaling. The majority of tumors are sporadic, but individuals
with familial adenomatous polyposis (Gardner syndrome, Chapter 17) who have
germline APC mutations are predisposed to deep fibromatosis.
In addition to possibly being disfiguring or disabling, deep-seated fibromatosis is
occasionally painful. Because of the extensively infiltrative nature, complete excision
is often difficult. Recent efforts have concentrated on medical therapy with
cyclooxygenase 2 inhibitors, tyrosine kinase inhibitors, or hormonal blockade
(tamoxifen). 23
Fibrosarcoma
Fibrosarcoma is a malignant tumor of fibroblasts, lacking any other specific
differentiation.
Fibrosarcomas are rare.
When considering spindle cell tumors, fibrosarcoma is often in the differential
diagnosis, but seldom is the final diagnosis.
Several other spindle cell sarcomas, including malignant fibrous histiocytoma (MFH),
synovial sarcoma, liposarcoma, rhabdomyosarcoma, and malignant schwannoma may
have fibrosarcoma-like growth and are more common. Also, fibromatoses,
fibrohistiocytic tumors, and nodular fasciitis may have a similar appearance, although
these tumors never grow in a herringbone pattern [I14.20].
Fibrosarcomas are slow-growing and may be deceptively circumscribed, especially
when small.
The tumor is usually painless (in contrast with synovial sarcoma or malignant
schwannoma, which may be painful).
Fibrosarcoma can occur at any age, including infants, but usually affects middle-aged
adults.
Women are slightly more commonly affected than men.
Infantile and congenital subtypes are less aggressive; boys are slightly more
commonly affected than girls.
Fibrosarcoma can occur anywhere there is fibrous tissue.
However, the tumor is not associated with nerve, neurofibroma, or von
Recklinghausen's disease (unlike malignant schwannoma).
Superficial fibrosarcomas occur, but are extremely rare in the palm or sole (unlike
fibromatosis).
Deep fibrosarcomas are more common, particularly in the extremities and trunk, and 27
are more aggressive.
Microscopic (histologic) description
Highly cellular fibroblastic proliferation in herringbone pattern (cells in columns of
short parallel lines with all the lines in one column sloping one way and lines in
adjacent columns sloping the other way)
Cells have scant cytoplasm, tapering elongated dark nuclei with increased granular
chromatin, variable nucleoli
Mitotic activity present, often with abnormal forms
Variable collagen
Usually no giant cells
No pleomorphism (or call pleomorphic MFH), no other distinct cell types
Patterns:
Keloid-like (thick hyalinized collagen fibers), loose fascicular, focally myxoid

29
Rhabdomyosarcoma
Rhabdomyosarcoma is a malignant mesenchymal tumor with skeletal muscle
differentiation. Three subtypes are recognized: alveolar (20%), embryonal (60%) and
pleomorphic (20%). Rhabdomyosarcoma (alveolar and embryonal) is the most
common soft tissue sarcoma of childhood and adolescence, usually appearing before
age 20. Pleomorphic rhabdomyosarcoma is seen predominantly in adults. The
pediatric forms often arise in the sinuses, head and neck and genitourinary tract,
locations that do not normally contain much skeletal muscle, underscoring the notion
that sarcomas do not arise from mature, terminally differentiated muscle cells. The
embryonal and pleomorphic subtypes are genetically heterogeneous. Alveolar
rhabdomyosarcoma frequently contains fusions of the FOXO1 gene to either the PAX3
or the PAX7 gene, rearrangements marked by the presence of (2;13) or(1;13)
translocations, respectively. PAX3 is a transcription factor that initiates skeletal muscle
differentiation, and it appears that the chimeric PAX3-FOXO1 fusion protein interferes
with the gene expression program that drives differentiation, a mechanism similar to
many of the transcription factor fusion proteins that are found in various forms of
acute leukemia

31
Leiomyoma
Leiomyoma, a benign tumor of smooth muscle, often arises in the uterus; in fact,
uterine leiomyomas are the most common neoplasm in women. They develop in 77%
of women and, depending on their number, size, and location, may cause a variety of
symptoms including infertility. Leiomyomas may also arise from the erector pili
muscles (pilar leiomyomas) found in the skin, nipples, scrotum, and labia and rarely in
the deep soft tissues and the muscularis of the gut. Pilar leiomyomas may be multiple
and painful. The phenotype of multiple cutaneous leiomyomas may be transmitted as
an autosomal dominant trait that is also associated with uterine leiomyomas and
renal cell carcinoma—hereditary leiomyomatosis and renal cell cancer syndrome. This
disorder is associated with a germline loss-of-function mutation in the fumarate
hydratase gene located on chromosome 1q42.3. Fumarate hydratase is an enzyme
that participates in the Krebs cycle, and this association thus constitutes another
intriguing example of the link between metabolic abnormalities and certain forms of
neoplasia.

Soft tissue leiomyomas are usually 1 to 2 cm and are composed of fascicles of densely
eosinophilic spindle cells that tend to intersect each other at right angles. The tumor
cells have blunt-ended, elongated nuclei and show minimal atypia and few mitotic
figures. Solitary lesions are easily cured. However, multiple tumors may be so
numerous that complete surgical removal is impractical.

36
Microscopic (histologic) description
Whorled (fascicular) pattern of smooth muscle bundles separated by well
vascularized connective tissue
Smooth muscle cells are elongated with eosinophilic or occasional fibrillar cytoplasm
and distinct cell membranes
May develop areas of degeneration if large including hyaline or mucoid change,
calcification, cystic change or fatty metamorphosis
Usually noninfiltrative, thick walled arteries throughout and cleft-like spaces
May have extensive hyaline necrosis if protrudes into endometrial cavity
Variable lymphocytes and mast cells
Usually less than 5 mitotic figures per 10 high power fields in most mitotically active
area, no significant atypia
Rarely has focal skeletal muscle differentiation (Hum Pathol 1999;30:356) or tubules /
glands
Post lupron treatment: initially edema and necrosis, then hyalinization and mild
lymphocytic infiltrate

Smooth muscle proliferations with unusual growth patterns: disseminated

peritoneal leiomyomatosis; benign metastasizing leiomyoma; intravenous
leiomyomatosis; lymphangioleiomyomatosis

39
Leiomyosarcoma accounts for 10% to 20% of soft tissue sarcomas. They occur in
adults and afflict women more frequently than men. Most develop in the deep soft
tissues of the extremities and retroperitoneum. A particularly deadly form arises from
the great vessels, especially the inferior vena cava. Leiomyosarcomas have complex
genotypes that stem from underlying defects that lead to profound genomic
instability

40
Treatment depends on tumor size, location, and grade. Superficial or cutaneous
leiomyosarcomas are usually small and have a good prognosis, whereas those of the
retroperitoneum are large, cannot be entirely excised, and cause death by both local
extension and metastatic spread, especially to the lungs.

44
Synovial Sarcoma
Synovial sarcoma was so-named because the first described cases arose in the soft
tissues near the knee joint and a morphologic relationship to synovium was
postulated. However, this name is a misnomer, as these tumors can present in
locations (chest wall, head and neck) that lack synovium and their morphologic
features are inconsistent with an origin from synoviocytes. Synovial sarcomas account
for approximately 10% of all soft tissue sarcomas and rank as the fourth most
common sarcoma. Most occur in people in their 20s to 40s. Patients usually present
with a deep-seated mass that has been present for several years. Most synovial
sarcomas show a characteristic chromosomal translocation t(x;18)(p11;q11)
producing SS18-SSX1, -SSX2, or -SSX4 fusion genes that encode chimeric transcription
factors.
Synovial sarcomas are treated aggressively with limbsparing surgery and frequently
chemotherapy. The 5-year survival varies from 25% to 62%, related to stage and
patient age. Common sites of metastases are the lung and occasionally the regional
lymph nodes.

45
MORPHOLOGY
Synovial sarcomas are morphologically monophasic or biphasic. Monophasic synovial
sarcoma consists of uniform spindle cells with scant cytoplasm and dense chromatin
growing in short, tightly packed fascicles. Many tumors historically classified as
fibrosarcoma likely would be classified as synovial sarcoma today. The tumors may
calcify. The biphasic type contains, in addition to the spindle cell component above,
gland-like structures composed of cuboidal to columnar epithelioid cells.
Immunohistochemistry is helpful in identifying these tumors, since the tumor cells,
especially in the biphasic type, are positive for epithelial markers (e.g.,
keratins),differentiating them from most other sarcomas.

47
Microscopic (histologic) description
General (Ann Diagn Pathol 2014;18:369):
Two main subtypes: biphasic and monophasic spindle cell
Rarer subtypes: poorly differentiated (round cell), monophasic epithelial,
calcifying / ossifying and myxoid
Biphasic:
Architecture:
Two components, spindle cells and gland-like epithelial structures
Glandular lumina contain mucin
Cytologic features:
Epithelial component has moderate, distinct amphophilic cytoplasm
with round to ovoid nuclei
Rarely squamous metaplasia can occur
Monophasic:
Architecture:
Infiltrative borders
Hypercellular fascicular architecture with little intervening stroma
Can rarely show hyalinization or myxoid change
Ill defined nuclear palisading may be seen
Cytologic features:
Monotonous cells with scant amphophilic cytoplasm, ovoid to spindled
vesicular nuclei with evenly dispersed chromatin and inconspicuous
nucleoli
Nuclei often close enough to overlap with adjacent nuclei
Poorly differentiated: highly cellular round cells with hyperchromatic nuclei and
frequent mitotic activity and necrosis 48
Additional features:
Malignant Fibrous Histiocytoma
Malignant fibrous histiocytoma (MFH) has been considered the most common soft-
tissue sarcoma of mid to late adult life. The cytogenesis is disputed: is it a tumor of
fibroblasts, histiocytes, both, neither? Perhaps more likely, MFH may be the final
common pathway of dedifferentiation of a variety of malignant tumors [Swanson
1991]. On careful and thorough examination, including the use of increasingly
sophisticated ancillary studies, many so-called MFHs can be classified as a specific
type of pleomorphic sarcoma, but many are found to be nonmesenchymal [Fletcher
1992]. In fact, some cases of "MFH" have been shown to express epithelial markers
such as keratin and epithelial membrane antigen [Litzky 1990, A Rosenberg 1993],
raising the possibility that at least some of these tumors are pleomorphic carcinomas.
In addition, some cases of MFH follow previously documented carcinomas of a type
known to be capable of manifesting a sarcomatous appearance. On the other hand,
some cases of pleomorphic MFH recur after therapy with a more mature morphologic
appearance, eg, as osteosarcoma or leiomyosarcoma [M Costa 1994]. In summary,
although recognition of broad categories (such as melanoma, lymphoma, and
carcinoma) is therapeutically important, there is no evidence that subclassification of
pleomorphic sarcomas is of any significant benefit to the patient at the present time
[Fletcher 1992]. In this section, MFH will be considered as a distinct diagnostic entity
usually presents as a painless mass, often in an extremity, sometimes accompanied by
systemic symptoms (particularly when located in the retroperitoneum) such as
anorexia, weight loss, or fatigue. Inflammatory MFH may present with fever,
leukocytosis, neutrophilia, and eosinophilia. MFH is sometimes associated with
lymphoreticular malignancies, eg, lymphoma (Hodgkin's, non-Hodgkin's), leukemia,
multiple myeloma, malignant histiocytosis.
MFH is usually of less than 6 months' duration and shows slow, then rapid, growth. 49
The patients are usually older adults (50 to 70 years and up); therefore, diagnose
MORPHOLOGY
UPS are usually large, grey-white fleshy masses and can grow quite large (10 to 20 cm)
depending on the anatomic compartment. Necrosis and hemorrhage are common.
They consist of sheets of large, anaplastic spindled to polygonal cells with
hyperchromatic irregular, sometimes bizarre nuclei. Mitotic figures, including atypical
non-symmetric forms, are abundant as is coagulative necrosis. By definition, tumor
cells lack differentiation along recognized lineages.

Soft Tissue Tumors

■ The category of soft tissue neoplasia describes tumors
that do not fall into categories of epithelial, skeletal, central
nervous system, hematopoietic or lymphoid tissues. A
sarcoma is a malignant mesenchymal tumor.
■ Although all soft tissue tumors probably arise from pluripotent
mesenchymal stem cells, rather than mature cells,
tumors can be classified into:
■ Tumors that recapitulate a mature mesenchymal tissue
(e.g., skeletal muscle) can be further subdivided into
benign and malignant forms.
■ Tumors composed of cells for which there is no normal
counterpart (e.g., synovial sarcoma, undifferentiated
pleomorphic sarcoma)
■ Sarcomas with simple karyotypes demonstrate reproducible,
chromosomal and molecular abnormalities which
contribute to pathogenesis and are sufficiently specific to
have diagnostic utility. 53
Most adult sarcomas have complex karyotypes, tend to be