Keloid scarring is a reactive fibrous proliferation that almost invariably follows local trauma or surgery. It commonly affects young people of African descent; there may be a familial tendency to developing keloid scars

Any anatomic location may be affected, but the head and neck region is most commonly involved

Management is difficult as up to 50% of patients have local recurrence after excision

Keloid scarring appears as raised firm cutaneous tissue extending beyond the boundaries of the site of initial tissue damage

Keloid scar consists of hypocellular thick, hyalinized, eosinophilic collagen bundles, haphazardly arranged into broad bands or nodules, sometimes with associated calcifications

Hypertrophic scar, less common than keloid scarring, is confined to the original site of tissue damage and is more cellular with a nodular growth pattern and less prone to local recurrence

Nodular fasciitis is a common, self-limiting, benign neoplasm composed of fibroblastic and myofibroblastic cells

Histologically, nodular fasciitis is often mistaken for sarcoma

Typically presents as a rapidly growing, often painful or tender subcutaneous nodule – most lesions are present for less than 12 weeks prior to presentation

Most commonly arises in young adults but may occur at any age; no apparent gender predilection

Common sites of involvement include subcutaneous tissue and fascial surfaces of the upper extremities and trunk and head and neck in children

A small percentage of lesions develop in intravascular, intramuscular, and intra-articular sites; dermal involvement is rare

Cranial fasciitis occurs predominantly in infants and involves soft tissues of the scalp and underlying skull bone, often resulting in bone erosion

Nodular fasciitis is a self-limiting neoplasm and shows spontaneous regression if untreated; less than 2% recur locally after incomplete excision

Grossly, nodular fasciitis is unencapsulated and either well-circumscribed or infiltrative, usually measuring <3 cm in diameter

The cut surface may have a myxoid, cystic, or fibrous appearance

Nodular fasciitis consists of a cellular proliferation of spindled myofibroblastic and fibroblastic cells in short intersecting fascicles or whorls

T he stroma is variably loose, myxoid, or collagenous with a feathery appearance and contains delicate thin-walled vessels, resembling granulation tissue

Neoplastic cells have plump spindled nuclei with occasional prominent nucleoli and palely eosinophilic cytoplasm; tumor cells lack nuclear atypia and pleomorphism

Mitotic forms may be numerous, but atypical forms are not seen

Additional features include extravasated red blood cells, osteoclast-like multinucleated giant cells, scattered inflammatory cells, keloidal hyalinization, and, rarely, reactive new bone formation

Tumor cells express muscle-specific actin and smooth muscle actin, consistent with myofibroblastic differentiation, and are negative for desmin, keratin, and S-100 protein

CD68 expression may be seen in the osteoclast-like giant cells

Fasciitis ossificans: usually periosteal in location and contains prominent reactive bone formation; it has features of both nodular fasciitis and myositis ossificans

Sarcoma : Some sarcomas may fall into the differential diagnosis with nodular fasciitis, such as myxofibrosarcoma or myxoinflammatory fibroblastic sarcoma. In general, sarcomas rarely grow as rapidly as nodular fasciitis and, depending on the specific sarcoma type, are typically more cellular and show greater nuclear atypia and hyperchromasia. Additionally, myxofibrosarcoma also shows curvilinear vessels and pseudolipoblasts, while myxoinflammatory fibroblastic sarcoma contains Reed–Sternberg-like cells

Desmoid fibromatosis: Fasciitis-like areas are often seen in intra-abdominal and breast tumors, mimicking nodular fasciitis. Fibromatosis is usually larger with a more infiltrative growth pattern, often with skeletal muscle involvement, but occasional cases can be nodular. Histologically, the fascicles of desmoid fibromatosis are longer than those in nodular fasciitis. Tumor cells are also spindled with bland nuclei, but mitoses are usually rare. 80% of desmoid fibromatoses show nuclear expression of β-catenin, which helps in the distinction from nodular fasciitis

Benign fibrous histiocytoma: Usually dermal, with a mixed storiform and fascicular growth pattern with a more polymorphous population of spindled and histiocytoid tumor cells, foamy macrophages, and chronic inflammatory cells. Lateral entrapment of collagen is frequent

The most common presentation of proliferative fasciitis is a rapidly growing subcutaneous mass on the extremities (usually forearm and thigh), in patients between the ages of 40 and 70 years and without gender predilection

Lesions rarely recur after excision

Poorly circumscribed, subcutaneous, gray-white mass, usually measuring 1–5 cm

Histologically, this proliferation is similar to nodular fasciitis but contains numerous large ganglion-like cells, which have abundant basophilic cytoplasm and one or more round nuclei with prominent nucleoli

Proliferative myositis: intramuscular location

Nodular fasciitis: lacks ganglion-like cells; intramuscular location is unusual

Proliferative myositis typically presents as a solitary, rapidly growing lesion of less than 4 weeks’ duration, involving the muscles of trunk and shoulder girdle of middle-aged adults, with no gender predilection. Recurrence of the lesion is rare after excision

Grossly proliferative myositis is poorly demarcated and usually measures 1–6 cm in diameter. There is often scar-like induration involving muscle and overlying fascia

The histologic appearance is similar to proliferative fasciitis, but growth between individual muscle fibers results in a classic “checkerboard-like” appearance with slight atrophy, but preservation, of muscle fibers

Foci of metaplastic bone or cartilage may be present (approximately 10% of cases)

Proliferative fasciitis: subcutaneous location

Nodular fasciitis: lacks ganglion-like cells; intramuscular location is unusual

This lesion occurs in debilitated, immobilized, or bedridden patients as the result of prolonged pressure and impaired circulation

It produces a painless soft tissue mass, often mistaken for a neoplasm, in the subcutaneous areas over bony prominences such as at the shoulder, sacrum, and hip

There is a slight female predilection, and the peak age is between 70 and 90 years

Local recurrence after excision may occur, usually due to ongoing pressure

Ischemic fasciitis forms a poorly circumscribed mass in the deep subcutis, which may extend into underlying skeletal muscle

Lobular or zonal proliferation of prominent vessels and inflamed granulation tissue with admixed plump, atypical-appearing fibroblasts

Prominent myxoid stroma with cystic change, diffuse fibrinoid necrosis, and variable fibrosis (especially in older lesions)

Elastofibroma is an uncommon lesion believed to be reactive; however, reports of clonal abnormalities raise the possibility that this is a true neoplasm; clustering of cases suggests a genetic predisposition

Patients are usually elderly, and there is a marked female predilection

Presentation is that of a slow-growing, ill-defined mass attached to the periosteum of ribs

Elastofibroma usually arises in the subscapular region and is rarely bilateral; occasional cases occur at other parts of the thoracic cavity

There is no tendency for local recurrence or metastatic potential; surgery is curative

Elastofibroma has ill-defined lesional margins that typically measure between 5 and 10 cm

The cut surface has a dense fibrous or rubbery texture with infiltration of surrounding adipose tissue

Elastofibroma is composed of irregular bands of dense, hypocellular collagenous fibrous tissues, with characteristically thick, eosinophilic elastic fibers with a beaded or globular appearance

There are often entrapped mature adipose tissue and a variably myxoid matrix

Gardner fibroma: lacks beaded elastic fibers; tumor cells express SMA and β-catenin

Scar: lacks beaded elastic fibers, with history of prior trauma/surgery

This benign tumor is relatively common in adults and presents as a slow-growing, painless, hard nodule attached to the tendons of hands and feet (usually on the fingers)

There is a peak age between 20 and 50 years, and males are affected twice as commonly as females

Up to 25% of cases recur after incomplete excision

Well-circumscribed, firm, and rubbery nodules attached to tendons, 1–2 cm in size

Well-circumscribed, vaguely lobulated, and variably cellular proliferation of bland-appearing fibroblasts/myofibroblasts within dense collagenous stroma

Thin, slit-like vessels are characteristic and usually more prominent at the edges of the lesion

Cellularity and mitosis vary with the duration of the lesion, with earlier lesions being more cellular and mitotically active

Myxoid change and chondro-osseous metaplasia may occur

Tumor cells can show SMA expression, consistent with fibroblastic differentiation

Giant cell tumor of tendon sheath: more cellular, scattered multinucleate giant cells and less hyalinized stroma

Nodular fasciitis: usually not attached to tendons, more cellular, less hyalinized, and lacks slit-like vessels

Fibromatosis: usually infiltrative, long sweeping fascicles of bland spindled cells; lacks slit-like vessels

Desmoplastic fibroblastoma is an uncommon benign neoplasm affecting mainly middle-aged males, with a male/female ratio of approximately 3:1

Patient usually presents with a painless subcutaneous nodule on the upper or lower extremities or back

Tumors are typically hypocellular and composed of bland spindled- and stellate-shaped fibroblasts embedded in a collagenous and/or myxoid stroma – the lesion is usually well circumscribed but unencapsulated, although infiltration into fat is often seen

Tumor cells may show expression of SMA and are negative for desmin, S100, EMA, and CD34 – scattered AE1-/AE3 positive cells may be seen

Surgical excision is curative

This is a benign myofibroblastic proliferation arising in lymph nodes, in particular inguinal nodes

The lesion often resembles schwannoma due to the presence of palisading but contains distinctive amianthoid fibers or thick collagen bundles, and the lesional cells express SMA but not S-100

Mammary-type myofibroblastoma is histologically identical to myofibroblastoma of the breast but occurs in sites (mostly subcutaneous) outside the breast, most commonly along the putative “milk line,” mainly inguinal and groin areas

Arises mainly in middle-aged or elderly adults and shows a male predominance

Local excision is usually curative

Mammary-type myofibroblastoma is well circumscribed and unencapsulated

Composed of small ovoid–spindled cells, resembling those in spindle cell lipoma, arranged in short fascicles

Collagenous stroma with prominent hyalinized collagen bundles and admixed mast cells

Adipose tissue is usually present in variable amounts

Tumor cells express desmin and CD34 and show loss of expression of retinoblastoma (Rb) protein

Spindle cell lipoma: virtually always arises on the posterior neck/upper back as an ill-defined, dermal, or subcutaneous mass; tumor cells are negative for desmin

Cellular angiofibroma: prominent round or branching vessels, often with hyalinization; tumor cells are negative for desmin

Fat-forming solitary fibrous tumors: branching hemangiopericytoma-like vessels; positive for STAT6 and CD34, and negative for desmin

Angiomyofibroblastoma arises almost exclusively in the subcutaneous tissue of the pelviperineal region, mostly in the vulva of premenopausal adult females and less commonly in scrotal or paratesticular soft tissue in males

Presentation is usually as a painless, circumscribed mass

Angiomyofibroblastoma is a begin neoplasm, and simple excision is curative

Angiomyofibroblastoma is well-circumscribed with a thin fibrous pseudocapsule and prominent small thin-walled vessels throughout a loose edematous stroma

This neoplasm is variably cellular, consisting of small round to spindled cells, which are concentrated around vessels

Scattered binucleate and multinucleated tumor cells are usually present

Epithelioid change or degenerative nuclear atypia may be seen

Mature adipose tissue is present in approximately 10% of cases

Desmin is positive in all cases; however, expression of this marker may be decreased in tumors arising in postmenopausal women – actin is usually negative

Tumor cells also commonly express estrogen and progesterone receptors

Cellular angiofibroma is a rare benign neoplasm that affects mainly middle-aged adults with no gender predilection and usually arises in the superficial vulvovaginal and inguinoscrotal soft tissues

Patients present with a painless mass or hydrocele (males)

Simple excision is curative; local recurrence occurs in rare cases

Cellular angiofibroma is usually well circumscribed and may have a thin fibrous pseudocapsule

Variably cellular neoplasm composed of small spindle cells with oval nuclei, closely resembling the cells in spindle cell lipoma, which are distributed somewhat haphazardly or in short fascicles

Characteristic prominent vasculature consisting of medium-sized thick-walled vessels with round lumina, and some variations in size are present; hyalinization of vessel walls is common

Tumor stroma is variably hyalinized, myxoid, and/or edematous; scattered mast cells are usually present

Intratumoral adipose tissue is present in 50% of cases

Cellular angiofibroma is variably positive for CD34 and almost always negative for desmin

Tumor cells show loss of expression of Rb

Mammary-type myofibroblastoma: inconspicuous vessels and bundles of hyalinized collagen; positive for desmin and CD34

Angiomyofibroblastoma: small thin-walled vessels and round to ovoid tumor cells; retains Rb expression

Aggressive angiomyxoma: deeper location; prominent myxoid stroma; small, thin-walled vessels with bundles of myoid cells radiating from vessel walls

Nuchal-type fibroma is a rare, benign fibroblastic proliferation that affects mainly young and middle-aged males and may be associated with diabetes mellitus

Marked preference for the posterior neck area; however, it may arise at other anatomic sites

Nuchal-type fibroma often recurs but does not metastasize

Nuchal-type fibroma is an ill-circumscribed mass involving dermal and subcutaneous tissue, composed of dense hypocellular, haphazardly arranged collagen, often with entrapment of adnexa and adipocytes and occasionally skeletal muscle

Many cases show proliferation of small nerve bundles

Spindled cells are usually positive for CD34

Gardner fibroma: in many cases, nuchal-type fibroma can appear histologically indistinguishable from Gardner fibroma. Features that favor the latter diagnosis include younger patient age, relatively less cellularity, relatively thicker collagen bundles, and expression of β-catenin in the majority of cases

Calcifying fibrous tumor is a benign fibrous neoplasm predominantly affecting children but also less commonly arising in adults. There is no gender predilection

Most patients seek medical attention due to a painless mass in the subcutaneous and deep soft tissues of the extremities, trunk, and neck. Rarely, visceral locations and in particular peritoneal surfaces may be affected

An association with inflammatory myofibroblastic tumor (IMT) has been suggested; however, this association is still controversial

Calcifying fibrous tumor is a well-circumscribed hypocellular fibroblastic lesion characterized by a dense sclerosis, a variably prominent chronic inflammatory component with lymphoid follicles, and variable amounts of calcifications, both dystrophic and psammomatous types

Examples without calcifications exist

The spindle cells are positive for CD34 and negative for ALK

Fibrous hamartoma of infancy presents in the first 2 years of life (patients are usually younger than 1 year of age) as a solitary freely movable, poorly circumscribed soft tissue mass (3–5 cm) involving the dermis and subcutis

Most common in the anterior or posterior axillary area, upper arm, and shoulder regions and show a marked male predilection

Local excision is usually curative and recurrences are rare

Fibrous hamartoma of infancy has an organoid growth pattern and is composed of three components in varying proportions: (1) myxoid foci with small round nests of undifferentiated spindle cells; (2) fascicles of myofibroblasts with wavy, tapering nuclei resembling fibromatosis; and (3) mature adipose tissue

Lipofibromatosis: lacks the myxoid nodules of primitive cells, which are characteristic of fibrous hamartoma of infancy

Myofibroma and myopericytoma are benign tumors on a morphologic continuum, along with other perivascular tumors such as glomus tumor and angioleiomyoma

Myopericytoma is most commonly seen in adults, arises in the dermis or subcutis of distal extremities (>proximal extremities and head and neck), and is usually solitary but may present with multiple lesions

Myofibroma occurs over a wide age range, but infants and young children (less than 2 years of age) are more commonly affected than for myopericytoma, with many cases being congenital; there is a male predominance

Myofibromas may be solitary lesions or present as multicentric lesions – i.e., myofibromatosis

Solitary myofibroma usually arises in the dermis or subcutis of the head and neck region, followed by trunk and extremities, and rarely in the bones of the skull

Myofibromatosis may involve the soft tissue and bone, as well as visceral locations such as the gastrointestinal tract, lungs, and kidneys

Although the etiology of myofibroma/myopericytoma is unknown, the occurrence of familial cases is highly suggestive of a genetic component

Patients are usually cured with simple excision; recurrence is uncommon and likely represents regrowth of residual disease in multicentric or poorly circumscribed tumors. Tumors at visceral locations may have a poor outcome

Most lesions are less than 3 cm, well-circumscribed, and unencapsulated with a lobulated or multinodular pattern. Lesions arising in deep locations and visceral sites tend to have less well-defined edges. Necrosis or cystic degenerations are common

Myopericytoma is composed of ovoid to spindled cells that show concentric growth around small blood vessels and medium-sized branching hemangiopericytoma-like vessels

Blood vessels near the lesion may also show a proliferation of perivascular cells

Some myopericytomas show areas of conventional glomus tumor and are referred to as glomangiopericytoma

Myofibroma is composed of whorls and short fascicles of bland spindled fibroblasts and myofibroblasts and plumper ovoid tumor cells, intimately associated with prominent hemangiopericytoma-like vessels

The stroma is often hyalinized and may have a pseudochondroid appearance with a light blue hue

Infantile myofibromatosis is often hypercellular and may mimic infantile fibrosarcoma

There is often a prominent subendothelial proliferation of spindle cells with projection into vessels, which may mimic lymphovascular invasion; however, there is no association with metastasis. Mitotic activity is usually low

Myopericytoma is positive for SMA and caldesmon

Myofibroma is positive for SMA but usually negative for caldesmon

Both are negative for desmin, S-100 protein, EMA, and keratins

Glomus tumor: rounder cells with prominent cell membranes, which are highlighted by SMA and caldesmon

Fibroma of tendon sheath: slit-like vessels are more prominent at the periphery of the lesion; lacks the pseudochondroid appearance of myofibroma and striking perivascular growth pattern

Infantile fibrosarcoma : some cases of infantile myofibromatosis may mimic infantile fibrosarcoma; FISH or RT-PCR to detect the ETV6–NTRK3 fusion gene characteristic of the latter tumor may be needed to resolve this differential

Fibromatosis colli is a fusiform, scar-like fibrous replacement of the distal sternocleidomastoid muscle that is seen in neonates usually by 2–4 weeks of age, resulting in cervicofacial asymmetry (torticollis)

It is often associated with abnormal positioning in utero and traumatic delivery, as well as with other musculoskeletal abnormalities

Microscopically, fibromatosis colli is characterized by a variably cellular fibroblastic/myofibroblastic proliferation with a myxoid to collagenous stroma

Entrapment of skeletal muscle, evidenced by the presence of scattered multinucleated muscle fibers, is invariably present

Most lesions will resolve with nonsurgical approaches, such as physical therapy and stretching exercises; however, approximately 10% of cases require surgical intervention. Most patients achieve complete cure if treated before 1 year of age

Juvenile hyaline fibromatosis is an exceedingly rare, hereditary disorder of infants and children with an autosomal recessive pattern of inheritance

This disorder is characterized by cutaneous, tumorlike lesions involving the head and neck, gingiva, and periarticular soft tissue (leading to contractures) and bone, especially the skull, long bones, and phalanges

Morphologically, lesions are composed of plump fibroblasts embedded in a hyaline nonfibrillary material

Mutations of the gene encoding capillary morphogenesis protein 2 (CMG2) on chromosome 4q21 are implicated in the pathogenesis of this disorder

Local recurrence is common; prognosis is dependent on the number, size, and location of nodules

This is a distinct fibrous tumor that occurs on the dorsal aspect of fingers and toes of infants as a small nodule (usually measuring <2 cm) in the dermis and subcutis

Patients are usually less than 1 year of age, and there is no gender predilection

Histologically, inclusion body fibromatosis consists of an ill-defined nodule of fascicles of myofibroblasts with characteristic scattered intracytoplasmic perinuclear round eosinophilic inclusions (trichrome and actin positive). There is no cytologic atypia and mitoses are scarce

Surgery is the main treatment. Recurrence is seen in approximately 60% of cases and is directly correlated with the adequacy of excision

Lipofibromatosis affects mainly infants and young children, with a male predominance

Patients present with an ill-defined, slowly growing mass involving hands and feet

Lipofibromatosis is composed of two main components in varying amounts: (1) adipose tissue and (2) spindle cells arranged in long fascicles traversing the adipocytic component

The major differential diagnosis is with fibrous hamartoma of infancy. Lipofibromatosis does not contain the myxoid nodules of primitive ovoid cells, which are characteristic of fibrous hamartoma of infancy

Calcifying aponeurotic fibroma is a rare, slowly growing fibroblastic proliferation that occurs in the distal extremities (palms and soles, wrist, and ankle) of children and adolescents (median age 9 years), with a slight male predominance

Clinical presentation is with a solitary, poorly defined, painless mass arising close to or involving aponeuroses and tendons

Local recurrence occurs in approximately 50% of patients

Tumors are usually less than 3 cm and have an infiltrative growth pattern, with entrapment of adjacent normal structures

Histologically, islands of central calcification are surrounded by small, round cells arranged in a linear pattern. Fascicles of fibroblasts/myofibroblasts are present between these islands

Osteoclast-like giant cells and cartilaginous differentiation may be present

Gardner fibroma is an uncommon benign fibroblastic proliferation arising in infants, children, and teenagers, with no sex predilection. It affects mainly the paraspinal area, chest wall, flank, head and neck, and extremities

Gardner fibroma is frequently associated with the development of desmoid-type fibromatosis and familial adenomatous polyposis

It usually presents as an asymptomatic plaque-like thickening in superficial and/or deep soft tissue locations

Gardner fibroma is hypocellular and composed of haphazardly arranged thick collagen bundles with cleft-like spaces

Tumor cells express CD34 and β-catenin in approximately 65% of cases

Nuchal-type fibroma: can be very difficult to distinguish histologically from Gardner fibroma. Nuchal-type fibroma occurs in older patients (adults) and compared to Gardner fibroma is relatively more cellular, the collagen bundles are less thick, and β-catenin is negative in lesional cells

Solitary fibrous tumor (SFT) was originally described as a neoplasm of the pleura; however, it is now well known that SFT can arise at any anatomic location, including the visceral locations, peritoneum, retroperitoneum, mediastinum, and head and neck regions

SFT arises virtually exclusively in adults, with no gender predilection, and presents as a slowly enlarging mass located in deep soft tissues

Rarely associated with systemic symptoms such as hypoglycemia and finger clubbing

Clinical course is variable, ranging from benign (most commonly) to malignant forms

Characterized by recurrent intrachromosomal (ch12q13) translocation resulting in the formation of NAB2–STAT6 fusion gene

SFT is usually large, well circumscribed, and vaguely lobulated

A characteristic “patternless” proliferation of relatively uniform spindled tumor cells is seen, with variably prominent intervening collagen bundles

There is usually marked variation in cellularity within the lesion

The stroma may show marked fibrosis, especially pleural lesions, and the neoplasm has a characteristic hemangiopericytoma-like branching vascular pattern

The neoplastic cells have ovoid nuclei, vesicular chromatin, inconspicuous nucleoli, and small to moderate amounts of palely eosinophilic cytoplasm

Variant: lipomatous SFT is characterized by a variable adipocytic component. Most components of this variant are benign

Occasionally, cases of SFT demonstrate atypical features such as diffuse hypercellularity, marked nuclear pleomorphism, or necrosis; the diagnosis of “malignant SFT” is made in the presence of four or more mitoses/10 high-power fields

Tumor cells express STAT6 in >95% of cases, in a diffuse nuclear pattern, and show CD34 positivity in >90%

Nonspecific markers CD99 and bcl2 may be positive but are nondiscriminatory from histologic mimics

Negative for S-100 protein, desmin, and keratin

Desmoid fibromatosis arises in three clinical settings: sporadic, associated with familial adenomatous polyposis (FAP), and multicentric or familial types

They are described on the basis of their anatomic location as follows: extra-abdominal (60%), abdominal wall (25%), or intra-abdominal (15%)

The sporadic group of tumors are usually extra-abdominal, commonly involving limb girdles and proximal extremities, as well as the head and neck. Abdominal wall tumors usually occur on the anterior abdominal wall in women in the peripartum period but may also arise in a preceding scar (e.g., cesarean section). Patients with FAP tend to have intra-abdominal tumors, particularly involving the mesentery (Gardner syndrome)

Peak incidence is between 15 and 40 years of age, with females more commonly affected than males

In most cases, desmoid tumors are completely excised. However, in some cases, often due to anatomic location or tumor size, patients undergo conservative management, radiation therapy, or chemotherapy to attempt to shrink the tumor prior to excision.

Grossly, desmoid tumors are usually large (>5 cm), poorly circumscribed, and infiltrative with a pale, whorled, and fibrous cut surface; intra-abdominal tumors are often well circumscribed

Desmoid tumors are composed of long sweeping fascicles of bland fibroblasts and myofibroblasts

Cellularity and mitotic activity are variable but usually low

The stroma is variably collagenous with elongated, compressed blood vessels; keloidal hyalinization may also be present

Some tumors may show prominent myxoid change resembling nodular fasciitis, especially tumors arising in the pelvis and mesentery

Cartilaginous or osseous metaplasia occurs rarely

Tumor edges are often ill defined and entrapment of, or invasion into, adjacent structures is common

Tumor cells express actin in most cases, and nuclear β-catenin positivity is present in approximately 80% of cases

Nodular fasciitis: looser stromal arrangement with microcystic degeneration; negative for β-catenin

Palmar/plantar fibromatosis : involves palmar or plantar surfaces; multinodular growth pattern, otherwise histologically very similar to desmoid fibromatosis. SMA positive in most; 50% show nuclear expression of β-catenin. Likely genetic component to these lesions as patients often have a family history; arises in aponeuroses and results in nodules and flexion contractures of fingers. Local recurrence after surgery is common

Dermatofibrosarcoma protuberance (DFSP) involves the dermis and subcutaneous tissue of adults, between 20 and 50 years of age, without any sex or racial predilection. The most common sites of involvement are the trunk, groin, and lower extremities. They are slow-growing tumors

Local recurrences are very common (30–60%), and therefore, complete local excision is required. Metastasis is uncommon and only occurs in tumors showing fibrosarcomatous transformation

Grossly DFSP may appear as a plaque-like lesion, nodule, or multinodular mass

Cut surface is ill defined, white-gray firm mass, with an average size of 5 cm

DFSP is a dermal-based neoplasm with diffusely infiltrative margins and extension into the subcutaneous tissue, resulting in infiltration and isolation of fat lobules, so-called “honeycombing” growth pattern

The tumor is usually separated from the overlying epidermis by a narrow Grenz zone and contains entrapped adnexal structures

DFSP is composed of a uniform population of fibroblast-like spindle cells arranged in a storiform growth pattern; tumor cells have plump hyperchromatic nuclei and small amounts of cytoplasm; there is minimal cytologic atypia or pleomorphism, and mitotic activity is usually low

Areas of giant cell fibroblastoma may be present, usually in pediatric or young adult patients

Fibrosarcomatous variant: transition to cellular fascicular growth pattern, with an increased mitotic rate and greater cytologic atypia; confers metastatic potential (15%)

Bednar tumor (<5% of cases): DFSP with heavy melanin-pigmented dendritic spindle cells

Myxoid variant: may mimic other myxoid neoplasms

The neoplastic cells are positive for CD34 and negative for desmin, SMA, and S-100

Supernumerary ring chromosomes derived from portions of chromosomes 17 and 22 are frequently present in adult cases of DFSP; unbalanced translocation t(17;22)(q21.3;q13.1) is present in most pediatric cases

Cellular benign fibrous histiocytoma: composed of a more heterogeneous cell population (negative for CD34), often with lipid and hemosiderin deposition; shows entrapment of collagen at the edges; but lacks honeycomb pattern of infiltration of subcutaneous fat

IMT is most common in childhood and adolescence; however, the age range is wide

The most common sites of involvement are the lung and abdominal cavity (mesentery and omentum), but IMT has been described at nearly all anatomic sites

Clinical presentation is quite variable with symptoms relating to the site of origin of the tumor – occasionally, systemic symptoms such as weight loss, fever, and hematologic abnormalities are present

Local recurrence occurs in approximately 25% of patients, which is usually related to location and extent of resection; metastasis is rare, occurring in less than 5%

Rearrangement of ALK gene on chromosome 2p is present in approximately 50% of tumors and of ROS1 in <5%

IMT is a fascicular spindle cell neoplasm composed of plump fibroblasts and myofibroblasts, associated with a prominent inflammatory infiltrate rich in mainly plasma cells and lymphocytes

The stroma is variably myxoid and collagenous, and the tumor is often poorly circumscribed

The tumor cells of IMT show variable positivity for actin, desmin, and occasionally keratin

Nodular fasciitis: looser storiform growth pattern, microcystic degeneration, well circumscribed, and negative for ALK

Smooth muscle tumors: tumor cells have cigar-shaped nuclei and brightly eosinophilic cytoplasm and usually less inflammatory cells; SMA, desmin, and caldesmon positive and negative for ALK and ROS1

Inflammatory well-differentiated/dedifferentiated liposarcoma: occurs in the retroperitoneum and may have greater cytologic atypia; tumor cells show nuclear positivity for MDM2 and CDK4

Low-grade myofibroblastic sarcoma occurs predominantly in young to middle-aged adults, with a slight male predilection

Tumors most commonly arise in the head and neck region (tongue) but can arise at other somatic soft tissue sites, where they are usually deep seated

Local recurrence is common; however, metastases are rare and tend to occur after long periods from the initial diagnosis

Histologically, tumors are composed of hypercellular fascicles of spindled myofibroblasts with mild to moderate nuclear atypia and usually diffuse infiltration of skeletal muscle

Tumors are variably positive for desmin and smooth muscle actin and are negative for S-100 protein, keratin, and caldesmon

Infantile fibrosarcoma is characterized by a t(12;15)(p13;q25), juxtaposing the ETV6 gene on chromosome 12 with the NTRK3 gene on chromosome 15. This is the same abnormality encountered in congenital mesoblastic nephroma and mammary analogue secretory carcinomas of the salivary gland

Almost all cases of infantile fibrosarcoma arise within the first year of life and are frequently congenital; there is a slight male predominance

The most commonly affected sites include the distal extremities, trunk, and head and neck regions, and presentation is with a rapidly growing soft tissue mass

Recurrence rate after surgery is between 5 and 50%, and metastases are rare; the mortality rate is now less than 5%. Infantile fibrosarcoma may rarely show spontaneous regression

While infantile fibrosarcoma is a clinically, histologically, and biologically distinct entity, adult fibrosarcoma is now known to actually represent/encompass several different tumor types that show a uniform fascicular growth pattern, such as malignant peripheral nerve sheath tumor (MPNST), synovial sarcoma, fibrosarcomatous component of DFSP, and low-grade myofibroblastic sarcoma

A diagnosis of fibrosarcoma in adults is therefore rarely made and should be done only with caution and after excluding the above-listed tumor types – in most such cases where a line of differentiation is not identified histologically or with ancillary studies, a diagnosis of unclassified spindle cell sarcoma is more appropriate

Infantile fibrosarcoma is usually a large poorly defined, lobulated mass with infiltrative edges

The cut surface is tan and soft with areas of myxoid and cystic degeneration, hemorrhage, and necrosis

Infantile fibrosarcoma is a highly cellular neoplasm composed of intersecting fascicles of primitive-appearing spindle or ovoid cells forming a characteristic herringbone growth pattern

There is minimal pleomorphism, with the tumor cells having a monomorphic appearance, but the mitotic rate is high

Stromal collagen is variable. Necrosis, hemorrhage, and dystrophic calcifications may be present

As mentioned, areas similar to fibrosarcoma may be encountered in several different tumors in adults, such as dermatofibrosarcoma protuberans and MPNST; however, areas of typical morphology are often present and help in the differential diagnosis

Immunohistochemistry is helpful in adult tumors with a morphologic appearance of “fibrosarcoma,” e.g., CD34 for DFSP, TLE1/EMA/AE1/3 for synovial sarcoma, and S100/GFAP/SOX10 for MPNST

The tumor types that may have a fibrosarcomatous appearance in adults are listed above – in addition to IHC/molecular studies, the identification of conventional areas of a given tumor type clearly helps distinguish these tumors, e.g., DFSP

Myxoinflammatory fibroblastic sarcoma is a rare sarcoma associated with a translocation t(1;10)(p22:q24) that occurs in middle-aged males and females and usually involves the distal extremities, in particular hands and feet

Patients present with a slowly growing, painless mass in the dermis and subcutaneous tissue

Morphologically, the neoplasm shows alternating hypocellular, myxoid areas and hypercellular collagenized areas with a prominent mixed inflammatory infiltrate, and often resembles granulation tissue. Admixed atypical cells that have large nuclei and prominent eosinophilic nucleoli, resembling Reed–Sternberg (RS) cells, are key features. Areas containing macrophages filled with mucin are also present. The vascularity of myxoinflammatory fibroblastic sarcoma is inconspicuous

The large RS-like cells do not show any specific immunophenotypic profile and are negative for CD30 and CD15, as well as for keratins, desmin, and S-100 protein

The rate of local recurrence is as high as 70%; however, metastases are very rare (<2% of cases)

Myxofibrosarcoma is the most common sarcoma of the extremities of older adults (>60 year of age) and shows a slight male predominance

Presentation is with a subcutaneous (67% cases) or deep, slowly growing and usually painless mass

The rate of local recurrence (50–60%) is directly related to the completeness of resection, while distant metastasis (20–35%) correlates with tumor depth and histologic grade

Surgery is the main treatment of myxofibrosarcoma – neoadjuvant radiotherapy is often used for high-grade tumor, and adjuvant radiotherapy may be considered for positive or close margins after surgery to prevent local recurrence

The most common metastatic sites are the lung and bone

Ill-defined, lobulated mass with poorly defined margins and variable myxoid areas

Necrosis and hemorrhage are common

Myxofibrosarcoma shows a lobulated architecture and is a variably cellular tumor: low-grade tumors are hypocellular with predominant myxoid matrix, but atypical cells can usually be readily appreciated at low-power magnification, while high-grade tumors are hypercellular with marked nuclear atypia and necrosis

Curvilinear vessels are typically present and readily identified within the myxoid areas and are a helpful clue to the diagnosis

Neoplastic cells tend to converge and accumulate around these vessels

Nuclear pleomorphism is characteristically present as well as frequent mitoses, including atypical forms and necrosis

Within the myxoid areas, pseudolipoblasts may be present and are characterized by macrophages containing mucin in the cytoplasm, without the scalloping of nuclei seen in true lipoblasts

Epithelioid change may be seen and in some cases is the dominant morphology and may mimic carcinoma or melanoma; epithelioid myxofibrosarcoma is generally high grade

IHC is generally not helpful, and its role is limited to excluding histologic mimics: tumor cells may show positivity for SMA and CD34, whereas desmin, S-100, caldesmon, and keratins are negative

Myxofibrosarcoma has a complex karyotype

Pleomorphic liposarcoma: characterized by marked pleomorphism and often mimics myxofibrosarcoma: the identification of “true” lipoblasts with atypical, hyperchromatic, indented nuclei and sharply punched-out cytoplasmic vacuoles confirms the diagnosis

Pleomorphic leiomyosarcoma : composed of fascicles of spindled cells with marked pleomorphism and brightly eosinophilic cytoplasm; lacks myxoid areas and curvilinear vessels; neoplastic cells are positive for SMA, desmin, and caldesmon

Pleomorphic rhabdomyosarcoma : characterized by scattered large pleomorphic tumor cells, which are positive for desmin, MYOD1 and myogenin/MYF4

Low-grade fibromyxoid sarcoma (LGFMS) is a rare translocations-associated sarcoma that occurs mostly in young adults with a peak age between 30 and 50 years

Most neoplasms are deeply seated, well circumscribed, and painless and occur in limbs and limb girdles

The most common translocation t(7;16)(q33;p11) results in the formation of FUS–CREB3L2 fusion gene; less commonly FUS–CREB3L1 or EWSR1–CREBL1 fusion genes are present

Recurrence (60%) and metastasis (6–50%) may occur many years after initial diagnosis, and patients require long clinical follow-up; metastases are commonly seen in the lungs

The tumor is composed of swirling fascicles of bland, uniform spindled fibroblasts within abruptly alternating fibrous and myxoid areas

The tumor cells are small with minimal nuclear pleomorphism and rare mitoses and may mimic benign tumors such as soft tissue perineurioma and cellular myxoma, but histologic mimics are negative for MUC4 by IHC

Some cases may have large hyalinized rosettes (formerly known as hyalinizing spindle cell tumor with giant rosettes)

MUC4 is a newly described immunohistochemical marker for LGFMS and shows diffuse cytoplasmic staining in approximately 99% of cases

Tumor cells also show expression of EMA in 75% and are negative for actin, desmin, CD34, and S-100

Sclerosing epithelioid fibrosarcoma is a rare fibroblastic sarcoma, which in some cases shares morphologic and molecular features of low-grade fibromyxoid sarcoma

This high-grade tumor occurs in older adults, usually as a deep-seated mass in the extremities, and up to 50% of patients develop distant metastases

The characteristic morphologic appearance is one of cords and nests of polygonal epithelioid cells with clear or palely eosinophilic cytoplasm embedded in a dense sclerotic stroma – in some cases, areas with the classic appearance of LGFMS are present

This tumor may mimic carcinoma but is negative for keratins; similar to LGFMS, diffuse strong expression of MUC4 is seen in >90% of cases

The most common fusion gene in sclerosing epithelioid fibrosarcoma is EWSR1–CREB3L1; a small percentage of cases have FUS–CREB3L2 fusion gene

Benign fibrous histiocytoma may be subdivided into two main types depending on anatomic location:

Deep fibrous histiocytoma mainly arise in adults between 20 and 40 years of age, with a slight male predominance

The most common sites of involvement are the lower limb and head and neck regions; approximately 10% of cases arise in the retroperitoneum or mediastinum

Local recurrence occurs in approximately 20% of cases; distant metastasis is very rare

Tumors are well circumscribed and pseudoencapsulated and usually measure greater than 2–3 cm; central hemorrhage or cystic change is occasionally present

Deep fibrous histiocytoma is well circumscribed and lacks the entrapment of peripheral collagen usually seen in dermal tumors

Cellular with a storiform or short fascicular growth pattern, consisting of polymorphous spindle cells with elongated or plump vesicular nuclei and indistinct cytoplasm, scattered foamy macrophages and giant cells

Branching hemangiopericytoma-like vessels are common