Soft tissue is loosely defined as the complex of nonepithelial extraskeletal structures of the body exclusive of the

supportive tissue of the various organs and the hematopoietic/lymphoid tissue. It is composed of fibrous (connective)
tissue, adipose tissue, skeletal muscle, blood and lymph vessels, and peripheral nervous system. 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. Soft tissue involvement by infectious
processes usually is the result of direct extension from cutaneous, visceral, or osseous foci or the complication of
trauma or surgery. Rarely, the process has a hematogenous source. The severity of the inflammatory reaction and the
type of tissue response observed pathologically depend on the type, dose, and virulence of the infecting organism; the
resistance of the host tissues; the presence or absence of necrotic tissue, hematoma, or foreign body; and the anatomic
features of the infected area. Clinical types of infectious processes, such as hemolytic streptococcal gangrene,
necrotizing fasciitis, and Meleney synergistic gangrene, must be diagnosed by clinical appearance and bacteriologic
study. In necrotizing fasciitis the process is accompanied by severe systemic toxicity; it is usually caused by group A
streptococci, but other bacteria and fungi may be involved, including zygomycosis. [36,40] All of the pyogenic and
necrotizing infections result in acute inflammatory tissue reactions indistinguishable microscopically.
Granulomatous inflammations of soft tissue include tuberculosis, atypical mycobacteriosis, actinomycosis,
blastomycosis, coccidioidomycosis, sporotrichosis, cryptococcosis, and dirofilariasis.[35,38,39] A proper search for
microorganisms should be made with special stains and cultures. Hematoma, if deep and encysted, can simulate
clinically and radiographically a malignant soft tissue tumor. They occur most commonly in and around the tensor
fasciae latae and have been variously referred to as ancient hematoma, calcifying myonecrosis, chronic expanding
hematoma, and post-traumatic cyst of soft tissues.Tumors Classification Soft tissue tumors constitute a large and
heterogeneous group of neoplasms. This chapter deals primarily with tumors located in the somatic soft tissues; it
excludes those arising from the soft tissues of the mediastinum, retroperitoneum, and visceral organs and those
primarily involving the dermis, such as Kaposi sarcoma and dermatofibrosarcoma protuberans. Traditionally, soft
tissue sarcomas have been classified according to a histogenetic concept (e.g., fibrosarcoma as a tumor arising from
fibroblasts, osteosarcoma as a tumor arising from osteoblasts, and so on). However, morphologic,
immunohistochemical, and data from experimental animals suggest that most if not all sarcomas arise from primitive
multipotential mesenchymal cells, which in the course of neoplastic transformation undergo differentiation along one
or more lines.[42] The acceptance of this alternative scheme does not require a change in terminology: a liposarcoma
remains as such but is now viewed not as a tumor arising from a lipoblast but as a tumor exhibiting lipoblastic
differentiation. At a practical level, the importance of this classification based on histogenesis and/or differentiation is
that it correlates with a variety of clinical parameters, such as location, pattern of growth, multiplicity, likelihood of
recurrence, incidence and distribution of metastases, therapeutic response (such as the good response to ifosfamide-
based regimens in synovial sarcoma and the greater resistance to chemotherapeutic agents in leiomyosarcoma),
prognosis, and patient's ageClinical features A definite relationship exists between soft tissue tumor type and the age
of presentation.[46,47] For instance, embryonal rhabdomyosarcoma is typically a tumor of infants and children, synovial
sarcoma mainly affects adolescents and young adults, and liposarcomas and so-called malignant fibrous histiocytomas
are usually seen in middle-aged and elderly patients. Some of the pediatric cases are congenital. It is interesting that
congenital soft tissue tumors rarely behave in a malignant fashion, even if an aggressive behavior might have been
expected from their microscopic appearance. [45]Most soft tissue sarcomas are solitary. Synchronous or metachronous
multiple sarcomas represent only 0.2% of all cases. [44] Liposarcomas account for a high percentage of these cases.
Normal anatomy SKINThe skin or integument is a complex organ with many functions and with three main anatomic
components: epidermis and skin adnexa, melanocytic system, and dermis and subcutis. [18,19,23,24]The epidermis is a
stratified squamous epithelium that differentiates to form the outer protective layer of keratin. It is composed of
keratinocytes arranged in four layers: basal, squamous (prickle, malpighian), granular, and cornified (horny). The
basal cells are the mitotically active cells that give rise to all other keratinocytes; they contain low molecular weight
keratin and are separated from the dermis by a continuous basal layer, to which they are attached by
hemidesmosomes. The basal membrane is a complex antigenic structure that plays an important role in many
cutaneous diseases.[15] The dermoepidermal junction is thrown into undulating folds of interlocking ridges of
epidermis (rete ridges) and dermal papillae. Thus the undersurface of the epidermis seen in whole mounts presents an
anastomosing and reticulated pattern of ridges and valleys. The pattern and size of these ridges vary from area to area.
With age, they diminish in size, and the dermoepidermal junction becomes flattened. The squamous layer is composed
of several layers of cells, which become larger, more flattened, and more eosinophilic as they approach the surface.
This correlates with the intracytoplasmic accumulation of filaments, which are the precursors of keratin, and a
diminution of ribosomes. Some cells in the squamous layer exhibit a clear, vacuolated cytoplasm (sometimes resulting
in nuclear indentation), which should not be confused with that of melanocytes or Paget cells. When the cells are
separated, as a result of fixation and dehydration or intercellular edema, these areas of attachment are seen via the
light microscope as fine spiny (‘intercellular’) bridges, with a dot-like structure at their center (Bizzozero nodule),
representing the desmosome. The epidermal cells are not a syncytium, and true intercellular bridges do not exist.
Destruction of these attachments causes the cells to lose their cohesiveness. This process, termed acantholysis, is seen
in pemphigus vulgaris and related diseases. The granular layer is composed of one to three layers of flattened cells
containing keratohyaline granules. These coarse, intensely basophilic granules are rich in histidine and represent the
precursors of the protein filaggrin, which is responsible for the aggregation of keratin filaments. The cornified layer
contains multiple layers of polyhedral cells that have lost their nuclei and that are arranged in a basket-weave pattern
(except for the acral regions, in which this layer is thick and compact). The skin from the palms and soles features an
additional layer – the stratum lucidum – located between the granular and the cornified layers and appearing as a
homogeneous eosinophilic zone. The major proteins of basal keratinocytes are keratins 5 and 14, which form an
extensive network of 10 nm cytoskeletal filaments. As keratinocytes differentiate, they downregulate this pair of
keratins and switch on expression of other pairs, the nature of which is dependent on the site. In the epidermis,
terminally differentiated keratinocytes express keratins 1 and 10. The keratinization cycle usually takes 30–45 days.
Many dermatoses result in alterations in the pattern and speed of this process. Abnormal keratinization may be
manifest by hyperkeratosis, in which the stratum corneum is thickened, usually in association with a more prominent
granular layer, or by parakeratosis, in which the cells of the stratum corneum retain their nuclei and the granular layer
is diminished or absent. Certain descriptive terms are applied to alterations in the pattern of the epidermis. It may
become atrophic or thinned with age or disease. It may be thickened, and as it proliferates the rete ridges extend
deeper into the dermis, a process known as acanthosis. Outward overgrowth of the epidermis accompanied by
elongation of the dermal papillae is papillomatosis. A degenerative process in which the basal cells become
vacuolated, separated, and disorganized is called liquefactive or hydropic degeneration. Various combinations of these
changes are seen in the dermatoses, and this descriptive jargon allows succinct communication. In addition to
keratinocytes, the normal epidermis contains melanocytes, Langerhans cells, and Merkel cells. Melanocytes are
described on page 151. Langerhans cells are bone marrow-derived dendritic cells whose function is to present antigens
to immunologically competent T cells. They are scattered throughout the upper part of the squamous layer and are
difficult to identify in routinely stained sections. Ultrastructurally, they have a characteristic organelle – the Birbeck
granule – a rod-shaped structure with zipper-like striations and sometimes a bulbous end. Immunohistochemically,
they express CD1a, langherin, and S-100 protein; they have receptor sites for the Fc portion of the IgG molecule and
the third component of complement. [19]Merkel cells, also extremely difficult to identify in hematoxylin and eosin
(H&E) sections and even with special stains, are concentrated in the glabrous skin of the digits, lips, outer root sheath
of hair follicles, and tactile hair disks. Ultrastructurally, they contain cytoplasmic dense core (neurosecretory-type)
granules, often arranged beneath the cell membrane or located within unmyelinated neurites. Spinous processes
projecting from the cytoplasm anchor these cells to adjacent keratinocytes. Immunohistochemically, Merkel cells are
reactive for neuron-specific enolase (NSE), neurofilaments, keratin (including CK20) and a variety of peptide
hormones.[17,22]

The skin adnexa are represented by the hair follicles, sebaceous glands, sweat (eccrine) glands, and apocrine glands.
The hair follicle, sebaceous gland, erector pili muscle, and (in certain regions) the apocrine gland constitute a
functional complex known as the pilar unit. The hair follicle is responsible for the formation of hair, a cyclic process
that proceeds in three phases: anagen or growing phase, catagen or involuting phase, and telogen or resting phase.
The mitotically active cells of the hair follicles lining the dermal papilla are the matrix (generative) cells. These cells
give rise to the hair shaft and the inner root sheath. The outer layer of the latter structure is surrounded by a layer of
large clear (glycogen-rich) cells known as the outer root sheath. At the level of the isthmus, these cells undergo an
abrupt type of keratinization, which occurs without the interposition of a granular layer; this is referred to as
trichilemmal keratinization and, by extension, the layer itself is known as the trichilemmal sheath. By contrast, the
keratinization in the infundibular portion of the follicle is similar to that of the adjacent epidermis. It is not unusual to
find Demodex folliculorum mites, clumps of Staphylococcus epidermidis, and yeasts of Pityrosporum inside the pilar
infundibulum. The sebaceous glands are lobulated structures containing an outer layer of germinative cells that, as
they differentiate, move toward the inside and accumulate intracytoplasmic lipid droplets. These result in a typical
multivacuolated appearance, with multiple indentations of the centrally located nucleus. The excretory duct of the
sebaceous glands opens into the infundibulum of the hair follicle. Sweat glands are of three types: eccrine (responsible
for thermoregulation and, therefore, the only ‘true’ sweat glands), apocrine, and mixed (apoeccrine glands). Eccrine
sweat glands are tubular structures with a secretory and an excretory portion. The secretory coil, located in the deep
dermis or sometimes in the subcutis, is composed of secretory cells (further divided into clear and dark cells) and
myoepithelial cells. The excretory portion is composed of a dermal (straight) and an intraepidermal (spiral) portion,
the latter also known as the acrosyringium. Although the apocrine glands are concentrated in the axillae, groin, and
perineum, they also occur in small numbers on the face and elsewhere. Like eccrine glands, they have a secretory and
an excretory component. It is the former that gives them their highly characteristic appearance. The cells have an
abundant acidophilic cytoplasm, which may contain lipid, iron, and lipofuscin.Dermatosis is defined as a disorder
involving lesions or eruptions of the skin that are acute (lasting days to weeks) or chronic (lasting months to years).
Acute lesions are relatively common and exhibit a wide range of clinical conditions. Usually, these conditions are
triggered by local or systemic immunologic factors (e.g., allergic reaction); however, the exact etiology remains
unclear Seborrheic keratoses are common, benign, pigmented, predominantly basal keratinocytic proliferations
occurring chiefly on the trunk of adults. They may be single or multiple. The sudden appearance of, or increase in the
number and size of, seborrheic keratoses in association with internal malignant disease is known as the Leser–Trélat
sign.[4]Grossly, the lesions of seborrheic keratosis protrude above the surface of the skin, are soft, and vary in color
from tan to black. The single, heavily pigmented seborrheic keratosis may be confused clinically with malignant
melanoma. Microscopically, the number of epidermal basal cells is greatly increased, presumably as a result of a
maturation defect. The acanthotic pattern is the most frequent, in which a thick layer of basal cells is seen interspersed
with pseudohorny cysts (Fig. 4.50). Some of these cells contain melanin, as the result of transfer from neighboring
melanocytes (see p. 151). Other microscopic variants of seborrheic keratosis are the hyperkeratotic, adenoid,
acantholytic,[2] and desmoplastic. The latter may simulate invasive squamous cell carcinoma. [6] Psoriasiform keratosis
is a recently described condition combining features of seborrheic keratosis and psoriasis, the true nature of which still
needs to be determined. Keratoacanthoma is a skin lesion that erupts in sun-damaged skin, rather like a little
volcano. It grows for a few months; then it may shrink and resolve by itself. Keratoacanthoma is considered to be a
variant of the keratinocyte or non-melanoma skin cancer, squamous cell carcinoma (SCC). As it cannot be clinically
reliably distinguished from more severe forms of skin cancer, keratoacanthomas are usually treated
surgically.Keratoacanthoma may start at the site of a minor injury to sun-damaged and hair-bearing skin. At first, it
may appear as a small pimple or boil and may be squeezed but is found to have a  solid core filled with keratin (scale).
It then proliferates, and it may be up to 2cm in diameter by the time it is brought to the attention of the doctorActinic
keratosis

In that portion of the epidermis exposed to sunlight, chiefly that of the near ultraviolet spectrum, a sequence of
atrophic, hyperplastic, and eventually dysplastic changes known as actinic keratosis may develop. [18] The term ‘senile’
keratosis, often used as a synonym, is inappropriate. An increased incidence of these changes has been found in renal
transplant recipients, particularly in the lip region. [20] Histologically, actinic keratoses involve the interfollicular
epidermis, sparing the follicular apparatus and the intraepidermal portion of the sweat duct, as demonstrated in the
classic article by Pinkus. [26] The stratum corneum is replaced by a parakeratotic scale. Excessive production and
accumulation of this scale lead to the formation of cutaneous horns. The granular layer is generally absent except at
and about the follicular orifices. The malpighian layer shows disorderly maturation as well as individually dysplastic
and dyskeratotic cells (Fig. 4.51). Morphologic variations on the theme of actinic keratosis include basaloid
proliferations resembling early basal cell carcinomas, changes along the dermoepidermal junction resembling lichen
planus (benign lichenoid keratosis or lichen planus-like keratosis [23]), suprabasal acantholysis producing vesicles
similar to those of pemphigus vulgaris, a marked degree of keratinocytic atypia throughout the malpighian layer
(bowenoid actinic keratosis), and the presence of large atypical clear cells (pagetoid actinic keratosis). [22] Not
infrequently, the basal melanocytes participate in the proliferation and atypia, resulting in a combination of actinic
keratosis and actinic melanosis. Such cases appear clinically as heavily pigmented lesions Squamous cell carcinoma
General features The large majority of squamous cell (epidermoid) carcinomas of the skin are actinic induced, [46,64,68]
one of the postulated pathogenetic mechanisms being the induction of TP53 mutations by ultraviolet light[49] (Fig.
4.54). The incidence of this tumor is directly related to the amount of exposure to the sun and the lack of pigmentation
of the skin. Blond, blue-eyed, fair-skinned people living in Texas have a higher incidence of skin cancer than do their
counterparts in Minnesota. Squamous cell carcinoma in black people is a very rare disease. In urban populations,
frankly invasive squamous cell carcinoma is uncommon, whereas in rural populations it is common. [77] Nearly all of
these actinic-induced tumors are preceded and accompanied by lesions of actinic keratosis. Microscopic features Over
80% of squamous cell carcinomas are well differentiated and, as such, produce large amounts of keratin (Fig. 4.55).
Some of this is seen in the form of horn pearls, particularly in the better differentiated tumors; characteristically,
keratohyaline granules within these pearls are sparse or absent. So-called intercellular bridges can be found with ease
in most cases. The pattern of growth may be polypoid or even papillary, [85] or may have a deep penetrating quality.
Sometimes the tumors are cup-shaped in the manner of keratoacanthomas. Melanocytes Melanocytes are neural crest-
derived cells located in the basal layer of skin, hair follicles, most squamous-covered mucosal membranes,
leptomeninges, and several other sites. Their function is to produce an insoluble pigment known as melanin, using
tyrosine as a substrate, and to transfer this product through the process of cytocrinia to the adjacent epithelial cells.
The neuroectodermal origin of melanocytes, proposed many years ago by Masson and others, [628] has been supported
by a variety of techniques, among which the chick–quail chimera of Le Douarin is the most elegant and convincing, at
least for this particular cell typeNevi The word nevus (L. naevus, birthmark) can be properly applied to any
circumscribed growth of the skin of congenital nature. However, in common practice it is usually used as a synonym
for mole (L. moles, a shapeless mass) to designate a localized benign abnormality of the melanocytic system. The
adjectives melanocytic (which we prefer), nevocellular, and pigmented refer specifically to this type of nevus.
Junctional nevus is defined as a nevus in which the melanocytic proliferation is restricted to the basal portion of the
epidermis (‘junctional’ area). Nevi of the palms and soles are nearly always of the junctional type, [661] with most of the
intraepidermal melanocytes concentrated in the skin furrows. [673] Grossly, junctional nevus is flat or slightly elevated,
nonhairy, and fawn colored. Microscopically, it is characterized by the presence of melanocytic nests ('theques’) on
the epidermal side of the dermoepidermal junction (Fig. 4.100). Malignant melanomas may arise from this lesion.
Intradermal nevus is the term given to a nevus in which all the melanocytes are in the dermis. This is the common
adult type of nevus. It may be papillomatous, pedunculated, or flat, and it is often hairy. Microscopically, small nests
or bundles of melanocytes are seen in the upper dermis, with a tendency to concentrate around pilosebaceous units. [674]
The degree of pigmentation and cellularity varies widely. The lower half of the lesion tends to be less cellular and less
pigmented, and is composed of spindle cells with fibrillary cytoplasm arranged in bundles Compound nevus
combines the features of the junctional and intradermal types, i.e., it has both an epidermal and a dermal component.
The percentage of nevi with junctional changes decreases as the age of the patient increases. [675] As for the other types
of nevi, the amount of melanin deposition is highly variable and sometimes very abundant ( hypermelanotic nevus);[657]
as a general rule, it is concentrated in the superficial half of the lesion, particularly the intraepidermal portion. As with
other nevi, lymphocytes and other mononuclear cells may be seen at the base of the lesion; [655] they tend to be in
clusters rather than exhibiting the bandlike quality more commonly seen in melanoma. Osteosarcomas are
malignant bone-forming tumors. They are the second most common primary bone tumor after multiple myeloma,
accounting for ~20% of all primary bone tumors. They can be classified into primary and secondary forms, as well as
histologic types, of which conventional osteosarcoma is the most common Osteoid osteomas are benign bone-
forming tumors that typically occur in children (particularly adolescents). They have a characteristic lucent nidus less
than 1.5 or 2 cm and surrounding osteosclerotic reaction, which classically causes night pain that is relieved by the use
of salicylate analgesia, e.g. aspirin. An osteoid osteoma is composed of three concentric parts 1:1 nidus, representing
the neoplastic process

o meshwork of dilated vessels, osteoblasts, osteoid, and woven bone

o may have a central region of mineralization 2
2. fibrovascular rim
3. surrounding reactive sclerosis
The nidus releases prostaglandins (via the enzymes cyclo-oxygenase-1 and cyclo-oxygenase-2) which in turn result in
pain. Chondrosarcomas are malignant cartilaginous tumors that account for ~25% of all primary malignant bone
tumors. They are most commonly found in older patients within the long bones and can arise de novo or secondary
from an existing benign cartilaginous neoplasm. On imaging, these tumors have ring-and-arc chondroid matrix
mineralization with aggressive features such as lytic pattern, deep endosteal scalloping and soft-tissue extension. Soft
tissue chondromas or extraskeletal chondromas are benign soft tissue tumors of hyaline or myxoid cartilage
originating in extraosseous and extrasynovial locations commonly found in the hands and feet. Soft tissue chondromas
are soft tissue tumors with a chondroid matrix composed of hyaline or myxoid cartilage which sometimes calcifies .
Pleomorphic liposarcomas are high-grade malignant neoplasms arising from adipocytic tissues characterized by a
variable number of pleomorphic lipoblasts and the absence of areas of well-differentiated liposarcoma and other lines
of differentiation. Pleomorphic liposarcomas are highly malignant neoplasms characterized by pleomorphic lipoblasts
with features of pleomorphic spindle cell sarcoma or myxofibrosarcoma and in the case of the epithelioid subtype with
sheets of carcinoma-like epithelioid cells 1. They commonly have necrotic and myxoid changes Lipomas are benign
tumors composed of mature adipocytes. They are the most common soft tissue tumor, seen in ~2% of the population.
Benign lipomas are circumscribed soft masses, usually encapsulated, and composed almost entirely of fat. A small
amount of non-adipose components are often present, representing fibrous septa, areas of fat necrosis, blood vessels,
and interposed muscle fibers. Any non-adipose components must be carefully assessed to exclude a more aggressive
component. Histology demonstrates mature adipocytes with no cellular atypia or pleomorphism 4.A minority of
lipomas are found in deeper locations and include intramuscular, intermuscular, intrathoracic, and retroperitoneal
lipomas. These deep lipomatous masses should be assessed carefully, as they are more likely to be malignant. In fact,
lesions in retroperitoneal location should be considered a well-differentiated liposarcoma until proven
otherwise 5.Intramuscular lipomas have nearly identical histology to superficial lipomas; however, intramuscular
lesions tend to invade the adjacent musculature and commonly lack a capsule. Thus, these are sometimes known
as infiltrating lipoma. In contradistinction, intermuscular lipomas do not exhibit local invasion and tend to be lobular
or dumbbell-shaped, easily separated from adjacent soft tissues during surgical resection 6,7.In 5-15% of patients,
lipomas are multiple, and approximately a third of these will be familial. Pleomorphic rhabdomyosarcoma is a type
of rhabdomyosarcoma, and is the least common, accounting for only 5% of all rhabdomyosarcomas. Unlike
embryonal and pleomorphic types, these tumors occur in adults over the age of 40 years 1, and are difficult to
distinguish from other pleomorphic sarcomas such as malignant fibrous histiocytomas. Some publications divide into
3 specific types

 classic: predominantly atypical  pleomorphic polygonal rhabdomyoblasts (PRMB) in sheets

 round cell: clusters of PRMB throughout the tumor with a background of slightly atypical, medium-sized,
round, blue RMB
 spindle cell: scattered PRMB in a predominance of atypical spindled RMB arranged in a storiform growth
pattern
Rhabdomyomas are rare benign mesenchymal tumors,

Capillary hemangiomas are believed to be hamartomatous proliferations of vascular endothelial cells. They are now
thought to be of placental origin due to a unique microvascular phenotype shared by juvenile hemangiomas and
human placenta. Periorbital capillary hemangiomas follow a similar course to hemangiomas on other parts of the
body. They generally exhibit 2 phases of growth, a proliferative phase and an involutional phase. The proliferative
phase of rapid growth typically occurs from 8-18 months. Pathologically, it is characterized by an increased number of
endothelial and mast cells, the latter being a stimulus for vessel growth. Endothelial cell proliferation returns to
normal following the proliferation phase.
The involutional phase is characterized by slow regression of the hemangiomas. One half of all lesions will involute
by age 5 years, and 75% will involute by age 7 years. During this phase, mast cell numbers decrease to normal and
there is a decrease in endothelial and mast cell activity. These vascular spaces become lined with endothelial cells
without muscular support