Fibroblastic and myofibroblastic tumors of the skin

Most commonly occurs in the second decade of life

Incidence after surgery from 40% to 70%, after burns from 30% to 90%

Lesions developing in the background of burns have a higher incidence in children

Familial predisposition common

No racial predilection

Predilection for chest, back, shoulders, buttocks, and knees

Slightly raised lesion of reddish discoloration

Generally not thicker than 2 mm

Remains confined within the boundaries of the wound

Occurs shortly after injury, generally within week(s), and usually flattens spontaneously within 1 to 2 years

Occasionally associated with pruritus and/or pain

Extensive lesions associated with limited mobility and possibly also contractions

Shows tendency to flatten and regresses over time

Recurrences after simple excision in up to 10%

Fascicles, whorls, and/or nodules composed of spindle-shaped fibroblasts/myofibroblasts

• Frequently arranged parallel to the epidermis

• Generally more cellular than keloids

By definition no wiry (keloidal) collagen

Increased amounts of small blood vessels with frequent perpendicular orientation to the epidermis

The epidermis can be atrophic

A foreign body granulomatous reaction occasionally present

Early lesions characterized by (opposite features typical for late lesions)

• Increased cellularity

• Increased amount of inflammatory cell infiltrate

• Numerous capillaries

Distinction from keloids can be difficult. In the latter, however, wiry collagen is present

Desmoid or superficial fibromatosis (on small biopsy)

Highest incidence in the second decade of life

More common in certain ethnic groups, including Asian, black, and Hispanic populations, with the incidence in these groups as high as 15% (in other races the incidence varies from 0.2% to 1%)

Familial predisposition common

Both autosomal-dominant and -recessive modes of inheritance reported

Raised lesion, frequently associated with reddish discoloration

Painful and/or pruritic

Predilection for earlobes, shoulders, anterior chest (in particular presternal area), upper arm, and cheeks

Typically grows beyond the confines of the original wound

Develops months or even years after the initial injury, most commonly from 3 months to 1 year

Multiple lesions not uncommon

Does not regress over time

Resistant to various forms of treatment

High recurrence rate after simple surgical excision (50%–80%)

Thick, eosinophilic, or “glassy” wiry hyalinized collagen bundles (e.g., keloidal collagen) arranged in a haphazard pattern represent the hallmark of the entity, but prominent in only up to 55% of cases

Keloidal collagen admixed with spindle-shaped fibroblasts forming whorls, nodules, or fascicles

Fibroblasts generally represent a minor component of the lesion

Mucinous degeneration can be seen

Additional discriminative features from hypertrophic scar

• No flattening of the overlying epidermis

• No fibrosis of the papillary dermis

• Absence of vertically oriented blood vessels

• Prominent disarray of fascicles/nodules

• Presence of tonguelike advancing edge

• Prominent fascialike hypocellular fibrous band in parallel with the epidermis, usually in the deeper aspects of the lesion

Distinction from hypertrophic scar may be difficult on histological grounds alone and in small biopsies

Desmoid or superficial fibromatosis (on small biopsy)

Rare disorder with about 200 patients reported in Europe and North America

More common in males

Onset of skin lesions

• Congenital or neonatal onset

  • Usually stable lesions with no or little expansion in the postnatal period

  • Epidermal nevus and vascular malformations

• Delayed onset

  • Progressive growth in the postnatal period

  • Cerebriform connective tissue nevus and lipomas

Cerebriform connective tissue nevus

• Well-demarcated plaque with rugged cerebriform appearance

• Firm consistency

• Predilection for soles (can be bilateral) and palms

• Other locations much more uncommon, including chest, abdomen, and back

• Lesions may be inapparent before the age of 2 years

Epidermal nevus

• Flat-topped, brown, hyperkeratotic papules in linear arrangements along Blaschko lines

• Soft consistency

• Asymmetrical distribution with predilection for trunk and neck

Vascular malformation

• Violaceous compressible masses

• Predilection for trunk and lower extremities

Lipomas

• Soft skin-colored nodules

• Predilection for head, abdomen, groin, and legs

Partial lipohypoplasia

• Generally presents as areas with reduced fat content, thus displaying accentuated bony contours

• Usually restricted to one-half of the trunk or extremities

Dermal hypoplasia

• Depressed reddish plaques

• Usually associated with decreased subcutaneous fat and absence of hair

• Lower extremities

Skin lesions associated with significant morbidity and can be disfiguring

Conservative treatment is preferable for nontumorous proliferations

Connective tissue nevus

• Highly collagenized connective tissue

Epidermal nevus

• Hyper(ortho)keratosis, acanthosis, and papillomatosis

• No adnexal hyperplasia

Vascular malformation

• See corresponding chapter

Lipoma

• See corresponding chapter

Noncontributory

Klippel–Trénaunay syndrome

Epidermal nevus syndrome

Bannayan–Riley–Ruvalcaba syndrome

Hemihyperplasia multiple lipomatosis syndrome

Young to middle-aged adults from 20 to 40 years of age

No gender predilection

About 10% of lesions develop in children, with male predominance

Solitary, rapidly growing swelling or nodule, developing in the course of a few weeks (up to 8 weeks)

Tenderness over the affected area, lesions can also be asymptomatic

Size usually less than 3 cm (ranges from 0.4 cm to 10 cm)

Predilection for the subcutaneous tissue, fascial planes, or, less often, skeletal muscle of the upper extremities, particularly volar aspects of the forearm, trunk, and head and neck (most common site in children)

Rare sites include intraarticular, visceral, oral cavity, maxillary sinus, and within a nerve

History of previous trauma in up to 20%

Benign self-limiting proliferation

Recurrences after simple excision most unusual

Spontaneous regression common (in a large study, almost 90% of lesions regressed spontaneously after fine needle aspiration biopsy was performed for diagnostic purposes)

Well-delineated and nonencapsulated, margins occasionally more infiltrative

Bland myofibroblastic proliferation

• Short, irregular, and intersecting bundles or fascicles

• Less often loose storiform or haphazard pattern

• Plump vesicular nuclei, a single small nucleolus

• Eosinophilic cytoplasm

• No or limited nuclear pleomorphism

• Mitoses common (from 1 to 10 per 10 high-power fields)

• Atypical mitoses absent

Myxoid or fibrous stroma with feathery microcystic appearance (“tissue culture–like”)

• Variably abundant

• Extravasated red blood cells

• Focal frank hemorrhagic areas with hemosiderin deposition (more prominent in intraarticular locations)

• Chronic inflammatory cell infiltrate, predominantly composed of lymphocytes, especially at the periphery of the lesion

• Metaplastic bone rarely present

• Stromal hyalinization (more prominent in intraarticular locations)

• Thin, small blood vessels, frequently lined by prominent endothelial cells

• Multinucleated giant cells

Early lesions

• More cellular proliferation

• Loose myxoid matrix

Older lesions

• Less cellular, especially toward the center of the lesion with cystic degeneration

• Collagenized and hyalinized matrix, occasionally with keloidal appearance

Not contributive, merely confirm fibroblastic/myofibroblastic differentiation

Strongly and diffusely positive for smooth muscle actin and often calponin

Variable positivity for muscle specific actin, and much more infrequently for desmin

Consistently negative for cytokeratins, S100 protein, and CD34

Genomic rearrangement of the USP6 locus on chromosome 17p13 detected in over 90% of cases

• t(17;22)(p13;q13) resulting in the fusion gene MYH9-USP6 most common

Desmoid fibromatosis

Leiomyosarcoma

Sarcoma, not otherwise specified (NOS)

No gender predominance

Third decade of life

Solitary painless mass, rapidly growing

Rare superficial ulceration and bleeding

Size ranging from 0.5 cm to 5.5 cm (mean 1.3 cm)

Predilection for limbs and trunk, followed by the head and neck

Benign clinical course

No recurrences after complete excision

Well-circumscribed, nonencapsulated proliferation in the dermis, with possible limited extension into the subcutis

Bland uniform spindle cells

• Short intersecting bundles, focal storiform pattern

• Elongated tapering nuclei, vesicular chromatin, small nucleoli

• No significant cytological atypia or pleomorphism

• Mitoses not uncommon (mean number of 2.5 mitoses per 10 high-power fields)

Myxoid to collagenous stroma

• Prominent stromal hyalinization with keloid-like areas

• Extravasation of red blood cells and hemosiderin deposition

• Metaplastic ossification and calcification

• Osteoclast-like multinucleated giant cells

• Slitlike capillary network

• Inflammatory cell infiltrate, usually composed of lymphocytes

Overlying epidermis frequently ulcerated

Smooth muscle actin diffusely and strongly positive

Negative for CD34, desmin, h-Caldesmon, S100 protein, and cytokeratins

HSPle (17p13) rearrangement in most cases

Cellular fibrous histiocytoma

Myofibroma

Superficial angiomyxoma

No gender predilection

Young adults between 20 and 30 years of age

Solitary lesion, well-circumscribed mainly in the superficial soft tissues

Predilection for upper and lower extremities

History of previous local trauma in up to 15% of cases

Benign clinical course

Complete excision curative

Background features of nodular fasciitis (see earlier)

Trabeculae of osteoid and mature woven bone arranged in irregular pattern, lined by bland osteoblasts

Areas of chondroid differentiation and calcifications occasionally present

See nodular fasciitis

HSPle (17p13) rearrangement in most cases

Myositis ossificans

Osteosarcoma

Male predominance (M : F = 2 : 1), with reversal of the ratio and female predominance with increasing age

Almost exclusively in children, particularly infants

Mean age at presentation about 20 months

Congenital occurrence rare

Rapidly growing firm mass of typically short duration (few weeks)

Involves the deep soft tissues of the scalp, including deep fascia, galea capitis, cranial periosteum, or fibromembranous covers of the sutures with occasional erosion of the underlying bone

Mean size of 2.5 to 3 cm

Extension into or through the skull bone with/without dural involvement possible

Pure intracranial lesions localized to dura mater rare, and as a rule do not involve brain

Association with previous trauma (5%–15%), irradiation or surgical procedure, causative relationship uncertain

A single case associated with familial adenomatous polyposis displaying germline APC mutation with additional acquired somatic nonsense APC mutation reported recently

Benign self-limiting proliferation

Spontaneous regression possible

Simple excision is the treatment of choice

Local recurrence in about 1%

Well-circumscribed proliferation composed of spindle- and stellate-shaped cells in the background of variably myxoid stroma

Myofibroblastic proliferation

• Short intersecting bundles or fascicles, focal storiform pattern

• Normal mitoses not infrequent, atypical mitoses distinctly uncommon

• Minimal nuclear atypia

• Cellularity varies, can be prominent

Intervening stroma

• Myxoid with typical “tissue culture–like” appearance or collagenous

• Thick hyalinized collagen bundles can be prominent

• Delicate capillary network

• Areas of hemorrhage and/or hemosiderin deposition

• Inflammatory cell infiltrate, usually at the periphery

• Multinucleated giant cells absent or rare

• Focal osseous metaplasia, exceptional

Smooth muscle actin and muscle specific actin positive

Negative for S100 protein, cytokeratins, desmin, CD34

A subsets of lesions display nuclear β-catenin positivity

Relationship to nodular fasciitis is uncertain as HSPle (17p13) rearrangement is not routinely present

Activating mutation to CTNNB1 , the gene encoding β-catenin, has also been noted

Desmoid fibromatosis

Infantile fibrosarcoma

No gender predilection

Predilection for middle-aged adults in the sixth decade of life (mean age about 50 years)

Occurrence in children exceptional

Solitary poorly demarcated mass or nodule in the subcutis

Metachronous appearance in the orbit and forearm recently reported

Rapid growth typical, with the majority of the lesions developing in 2 to 6 weeks

Firm on palpation, movable, and not attached to the overlying skin

Painful in 50% to 75%

Predilection for the upper extremities, particularly volar side of the forearm, followed by the lower extremities, trunk, and head and neck

The majority of lesions less than 3 cm in diameter

Association with previous local trauma in less than 20%, causative relationship uncertain

Benign self-limiting clinical course

Spontaneous regression possible

Conservative complete excision

Recurrences exceptional

Poorly delineated proliferation in the superficial fascia, with frequent multifocal extension into the connective septa of the subcutis and, less frequently, into the underlying skeletal muscle

Exclusive intradermal occurrence recently reported

Two main components are spindle cells (myofibroblasts) and ganglion-like cells embedded in a variably myxoid or collagenous stroma

Spindle cell proliferation

• Short intersecting bundles or fascicles, focal storiform pattern

• Normal mitoses not infrequent, atypical mitoses distinctly uncommon

Ganglion-like cells

• One or two large vesicular nuclei, multinucleated forms much more infrequent

• Prominent nucleoli

• Abundant basophilic cytoplasm, fibrillary to granular

• Loosely arranged or forming small groups

Intervening stroma

• Myxoid or collagenous with typical tissue culture appearance

• Delicate capillary network

• Areas of hemorrhage and/or hemosiderin deposition

• Inflammatory cell infiltrate, usually at the periphery

• Focal osseous metaplasia, exceptional

Unusual features of lesions developing in children

• More circumscribed and less infiltrative growth

• Increased cellularity

• Predominance of ganglion-like giant cells

Spindle cells

• Smooth muscle actin and muscle specific actin positive

• Negative for S100 protein, cytokeratins, desmin, CD34

Ganglion-like cells

• Variable positivity for CD68

Diploid pattern of DNA flow cytometry

Relationship to nodular fasciitis is uncertain as HSPle (17p13) is not routinely rearranged

Proliferative myositis

Rhabdomyosarcoma

Sarcoma, not otherwise specified (NOS)

Slight male predominance (M : F = 1.4 : 1)

Age distribution wide (from 6 months to 66 years)

The majority occur from the first to the third decade of life

Solitary, slowly growing nodule or mass, occasionally sausage shaped and multilobular

Rapid growth in 2 to 3 weeks reported in rare cases

Nonpainful, associated with discomfort, tender or painful

Multiple lesions within the single area also reported

Size from 0.6 cm to 5 cm

Predilection for head and neck and upper extremity, followed by lower extremity and trunk

Additional sites include oral cavity and periocular soft tissue

Association with previous trauma and/or thrombosis exceptionally reported, causative relationship not clear

An exceptional case developing in a pregnant woman also reported

Benign clinical course

Complete excision curative

Recurrence possible, but unlikely

Typical features of nodular fasciitis (for detailed description see corresponding chapter), featuring plump spindle cells arranged in short intersecting fascicles, focal storiform pattern, or exhibiting a more haphazard growth in the background of variably myxoid stroma

Small to medium-sized arteries and veins, larger vessels can also be affected

• Localized within the subcutaneous tissue

• Involvement of dermis and deeper soft tissue more infrequent

Intraluminal, intramural, or with possible extramural extension

Infiltrative borders with entrapment of neighboring structures, like perivascular connective tissue, skeletal muscle, and fascia, also rarely reported

Extension from the main vessel into smaller vessels at some distance, creating “satellite” lesions or nodules occasionally present

Multinucleated cells less frequent than in classical nodular fasciitis

Smooth muscle actin positive

Negative for S100 protein, cytokeratins, desmin, CD34, and CD31

Given the rarity of this lesion, HSPle (17p13) rearrangement status, is not well studied

Intravascular pyogenic granuloma

Fibromuscular dysplasia

Sarcoma, not otherwise specified (NOS)

Adult patients between 40 and 50 years of age

Occurrence in children very rare

Equal gender distribution

Rapidly growing soft tissue mass

Asymptomatic, discomfort, pain

Predilection for the shoulder area, followed by the trunk, proximal extremities, and head and neck

Intraoral occurrence exceptional

Spontaneous regression without particular treatment possible

Recurrences after marginal/incomplete excision distinctly uncommon

Poor circumscription at the periphery

Proliferation of spindle cells and ganglion-like cells within the skeletal muscle, growing in horizontal and vertical planes, resulting in a checkerboard growth pattern

Regular mitoses not uncommon in either component, atypical mitoses absent

Ganglion-like cells

• Typically contain large nuclei, one or more prominent nucleoli, and abundant basophilic cytoplasm

• Evenly or randomly distributed within the lesion

Degenerative changes of skeletal muscle cells

Myxoid to collagenous stroma, occasionally with areas of osseous or chondroid metaplasia and focal aggregates of mononuclear inflammatory cells

Lesions in children usually more cellular, with predominance of spindle cells, display nodular rather infiltrative growth, better delineation of the lesion, and can contain foci of necrosis

Spindle cells

• Smooth muscle actin positive

• Variable positivity for CD68

Ganglion-like cells

• Variable positivity for CD68 and smooth muscle actin

• Negative for neural markers

S100 protein and desmin negative

Cytogenetic analysis of two cases revealed trisomy 2 and translocation t(6;14)

HSPle (17p13) rearrangement not documented in this lesion

Distinction from sarcoma can be difficult in small biopsies

Elderly patients in the eighth and ninth decades of life predominantly affected

Rare under the age of 50 years

Rare in children

Male predominance

Solitary, painless, ill-defined mass, slowly growing

Surface ulceration generally lacking

Duration usually less than 6 months

Size varies from 1.3 to 10 cm (median size 4.7 cm)

Predilection for soft tissues overlying bony prominences or for sites of increased pressure points, most frequently areas over the sacrum, greater trochanter, shoulder area, buttocks, and posterior chest wall

An unusual location includes the vulvovaginal area

Deep subcutaneous tissue, with possible involvement of the dermis, or deeper structures including skeletal muscles, tendons, and fascia

Exclusive involvement of skeletal muscle exceptional

Simple excision usually curative

Recurrences uncommon, generally related to the persistence of the underlying cause (e.g., pressure-related local ischemia)

Zonal pattern of proliferation

The central area consists of fibrinoid degeneration or necrosis with subsequent formation of pseudocystic spaces

The peripheral area is composed of granulation tissue, representing an admixture of

• Spindled and more epithelioid cells with irregular hyperchromatic smudged nuclei, prominent basophilic nucleoli, rare normal mitoses, and variably abundant amphophilic (basophilic) cytoplasm

• Large polygonal ganglion-like cells containing round, oval, or reniform hyperchromatic nuclei with prominent nucleoli, similar to the ones present in proliferative fasciitis

• Vascular proliferation, frequently containing thrombosed vascular spaces

• Mixed inflammatory cell infiltrate

Additional changes include edema, hemorrhage, deposition of hemosiderin, areas of myxoid degeneration, chondroid metaplasia, and fat necrosis/infarction

Generally noncontributory

Variable positivity for smooth muscle actin, desmin, and calponin

Consistently negative for cytokeratins and S100 protein

HSPle (17p13) is not rearranged

Proliferative fasciitis

Proliferative myositis

Nodular fasciitis

Sarcomas of different histogenesis

Female predominance (F : M = 4 : 1)

Elderly patients, usually in their sixth to seventh decade of life, or after

Rare in children

Familial occurrence possible, but rare

An autopsy study detected the presence of subclinical elastofibromatous changes in nearly 25% of women and in about 10% of men after the age of 55 years

Poorly demarcated, slowly growing swelling or mass

Asymptomatic, but can also be associated with discomfort, pain, stiffness, limited mobility, and/or snapping of the scapula

Predilection for the infrascapular region (over 95%), in particular, the area between the thoracic wall, the serratus anterior, and the latissimus dorsi muscle

Often attached to the periosteum of the bones of the thoracic wall

Infrequent sites include oral cavity, gastrointestinal tract, orbit, intraspinal space, intraarticular location, neural foramen, ligamentum flavum, ischial tuberosity, greater trochanter, olecranon, chest wall, axilla, inguinal area, deltoid muscle, foot, and greater omentum

Bilateral occurrence in up to two-thirds of cases, either synchronous or metachronous

Multiple lesions at distant locations rare

Size from 5 to 10 cm

Checkerboard white-and-yellow pattern on cut surface due to entrapment of fat

Complete excision curative

Recurrences after incomplete or marginal excision in up to 10%

Hypocellular proliferation of spindled or stellate-shaped fibroblasts

• Lack of mitotic activity

• Lack of cytological atypia

Broad bands of collagenized stroma

Enlarged, fragmented, and branched elastic fibers resulting in a beaded, globular/discoid or irregularly grained appearance represent the hallmark of the lesion

Interspersed streaks of mature fat in variable proportions

Inflammatory cell infiltrate generally absent

Myxoid degeneration

Formation of pseudocystic spaces

Fibroblasts CD34 and factor XIIIa positive

Elastic fibers can be highlighted by van Gieson stain

Clonal and nonclonal abnormalities mainly affecting chromosome 1 and 3, translocations involving chromosome 8 and 12, and gains of Xq detected in limited number of cases

Not usually relevant due to typical histological features, but nuchal fibroma or desmoplastic fibroblastoma might be considered

Female predominance, but pediatric occurrence appears to have nearly equal gender distribution

Most common in the fourth decade of life (mean age 30 years)

Presentation in infancy or early childhood rare

Solitary, slowly growing, indurated plaque or nodule; however, linear and annular variants also described

Multiple lesions exceptionally present

Hypopigmented, skin-colored, or brown-red discoloration

Asymptomatic, occasionally painful

Size from 1.0 to 2.0 cm, giant variants larger than 10 cm also reported

Predilection for shoulder area, upper arm, axillary region, neck, and upper trunk

Pediatric lesion shows predilection for the neck area

Simple excision curative

No recurrences reported even after marginal or incomplete excision

Involvement of the reticular dermis and/or subcutis, whereas the papillary dermis and occasionally also superficial parts of the reticular dermis are usually spared

Ill-defined, plaquelike proliferation with occasional formation of nodules

Cellularity can vary

Bundles and fascicles of bland spindle cells running in parallel to the epidermis, frequently associated with perpendicular growth into the subcutis along the septa

• Uniform vesicular nuclei with tapering ends

• Absence of cytological atypia

• Mitoses absent or rare

• Bland eosinophilic cytoplasm

Adnexal structures preserved

Elastic fibers may be increased and fragmented

Additional features

• Extravasation of erythrocytes

• Proliferation of capillaries

• Formation of sievelike and slitlike spaces

• Mild inflammatory cell infiltrate

Overlying epidermis normal, but can also be hyperplastic or, rarely, atrophic

Variable positivity for smooth muscle actin, calponin, and muscle specific actin

In some cases smooth muscle actin can be negative

Focal positivity for CD34 not uncommon, but never diffuse

Desmin, h-Caldesmon, S100 protein, β-catenin, EMA, and markers of epithelial differentiation consistently negative

Dermatofibroma

Pilar leiomyoma

Neurofibroma

Dermatofibrosarcoma protuberans

Male predominance (M : F = about 2 : 1)

Adult patients, most commonly around 50 years of age

Solitary

Slowly growing mass

The majority of lesions are smaller than 2 cm in greatest diameter

Asymptomatic (about 50%), tender, or painful

Destruction of nail plate not uncommon

Striking predilection for fingers, particularly subungual or periungual area of the hands and feet

Occurrence outside acral locations an exception

Previous local trauma in a minority of cases, pathogenetic role not clear

Complete excision curative

Recurrences after marginal or incomplete excision in up to 25%

Centered predominantly in the dermis, with possible extension into subcutis

Involvement of deeper structures, including fascia, periosteal surface, and bone, rare

Margins infiltrative and poorly delineated or expansile and well circumscribed

Spindled and stellate cells arranged in haphazard, loose storiform or vague fascicular growth pattern

• No or mild nuclear atypia in the majority of cases

• Focal areas or scattered cells with moderate to severe nuclear atypia and pleomorphism found in rare cases, thought to be degenerative in nature (enlarged nuclei with irregular contours, hyperchromasia, clumped chromatin, and indistinct nucleoli)

• Mitoses rare (fewer than 1 per 10 high-power fields), absence of atypical mitoses

• Pale eosinophilic cytoplasm

Multinucleated giant cells (present in about 50%)

Predominantly myxoid, myxocollagenous, or predominantly collagenous stroma/matrix

Vascular proliferation and increased number of mast cells, particularly in myxoid areas

Chondroid and osseous metaplasia rare

CD34 positive

Variable positivity for EMA

Generally negative for cytokeratins, S100 protein, desmin, glial fibrilary acid protein, MUC4, claudin-1

Loss of RB1 (13q14)

Spindle cell lipoma, pleomorphic lipoma, mammary-type myofibroblastoma, and cellular angiofibroma also show RB1 loss

Acquired digital fibrokeratoma

Periungual/subungual fibroma

Cellular myxoma

Superficial angiomyxoma

Low-grade fibromyxoid sarcoma

Dermatofibrosarcoma protuberans

Adult patients

Female predominance

Multiple lesions can be associated with pregnancy, obesity, diabetes, and Birt–Hogg–Dube syndrome

Lesions in children extremely rare, and when present can signify association with nevoid basal cell carcinoma syndrome

Polypoid or pedunculated lesion

Skin colored or hyperpigmented

Size from 0.2 to 5 cm (on average less than 1 cm)

Multiple lesions frequent, developing either synchronously or metachronously

Predilection for skin folds of the neck, axilla and groins, and perianal and genital area; other locations much more infrequent

Benign proliferation

Simple excision generally curative, most commonly performed due to cosmetic reasons

Isolated cases of basal cell carcinoma, squamous cell carcinoma in situ, and invasive squamous cell carcinoma described histologically in the background of a clinically banal fibroepithelial polyp

Lesion generally covered by normal or hyperplastic epidermis

Fibrovascular core containing loose or dense collagen fibers

Lack of skin adnexa within the lesion

Mature fat occasionally abundant

• Overlapping features with nevus lipomatosus superficialis

Lesions containing scattered cells with bizarre hyperchromatic nuclei and multinucleated giant cells also referred to as pleomorphic fibromas (see p. 82 )

Not contributory

The bizarre cells in pleomorphic fibroma may be smooth muscle actin positive

Polypoid seborrheic keratosis

Intradermal lipoma

No gender predominance

All age groups can be affected, including children

Slow-growing, skin-colored or erythematous papule or nodule

Firm on palpation, asymptomatic

Solitary lesion or multiple occurrence

Size up to 1 cm

No site predilection

Complete excision curative

Recurrences distinctly uncommon

Papillary dermis frequently unaffected

Well-circumscribed, nonencapsulated hypocellular proliferation in the dermis

Thick collagen bundles arranged in a storiform or whorled pattern

Collagen bundles separated by prominent artifactual clefts

Cleftlike spaces may contain copious amounts of mucin

Scattered spindled or stellate-shaped fibroblasts among collagen bundles, with no or with mild nuclear pleomorphism and absence of mitotic activity

Multinucleated giant cells occasionally present, dispersed among collagen bundles

• Defining feature of giant cell collagenoma (regarded as a subtype of sclerotic fibroma)

• Foreign body type, Touton type, Langhans type, and/or floretlike

• Bizarre-shaped, crowded vesicular nuclei, frequently overlapping

• Small prominent nucleoli

• Mitoses generally absent

• Pale cytoplasm

Absence of elastic fibers and adnexal structures within the lesion

Epidermis overlying the lesion usually atrophic

CD34 and CD99 positive

Consistently negative for smooth muscle actin, desmin, calponin, S100 protein, and EMA

Sclerotic fibroma-like pattern in inflammatory lesions, for example, folliculitis, chronic fibrosing vasculopathy (erythema elevatum diutinum)

Sclerotic fibroma-like pattern in various neoplastic lesions, including dermatofibroma, neurofibroma, melanocytic nevus, lipoma, fibroma of tendon sheath, angiofibroma

Middle-aged and older adults (sixth decade of life)

Male predominance

Solitary

Polypoid or dome-shaped papule

Predilection for extremities and trunk, followed by the head and neck area

Complete excision curative

Recurrences after incomplete excision very rare

Well-circumscribed, nonencapsulated, hypocellular dermal proliferation

Spindle-shaped, stellate, epithelioid, and multinucleated (often floretlike) giant cells with degenerative atypia

• Large pleomorphic hyperchromatic nuclei and small nucleoli

• Mitotic activity absent or infrequent, yet atypical mitoses occasionally seen

Thick and haphazardly arranged collagen bundles with slitlike spaces

Additional features

• Mature adipose tissue, likely the results of metaplastic change

• Stroma with areas of hyalinization, sclerosis, and/or myxoid degeneration

• Inflammatory cell infiltrate, composed of lymphocytes and histiocytes

• Dilated blood vessels with or without areas of hemorrhage

Inconsistent positivity for smooth muscle actin, muscle specific actin, factor XIIIa, and CD34

Sclerotic fibroma (likely represents part of a spectrum)

Giant cell collagenoma

Atypical fibrous histiocytoma

Giant cell fibroblastoma

Male predominance

Nuchal fibromas generally occur in adult patients (mean age about 40 years)

Extranuchal fibromas tend to develop at younger age (mean age 25 years)

Occurrence in children should raise the suspicion of Gardner fibroma in the background of Gardner syndrome

Solitary, poorly circumscribed, ill-defined mass

Multiple lesions exceptionally present, either within the same topographical area or at distant sites

Asymptomatic, mild discomfort or pain

Nuchal fibromas tend to be smaller (mean diameter about 4 cm) than extranuchal fibromas (mean diameter 6 cm)

Predilection for posterior neck, interscapular, and paraspinal areas

Extranuchal locations in about one-third, including back, shoulder, face, buttock, and extremities

Associated conditions include diabetes mellitus (up to 50%), previous local trauma, and much more infrequently scleroderma and scleredema

Collision with dermatofibrosarcoma protuberans reported in an exceptional case, likely coincidental

Generally not associated with familial adenomatous polyposis or desmoids tumors (in contrast to Gardner fibroma)

Complete excision curative

Nondestructive recurrences in over 40% at extranuchal sites

Predominantly centered in the subcutaneous fatty tissue

Extension into the dermis not uncommon, whereas involvement of skeletal muscle(s) or deeper structures rare

Paucicellular proliferation

Thick collagen bundles arranged in haphazard pattern, but vague lobular arrangement can be appreciated toward the center of the lesion

Cracking artifacts between collagen bundles

Scattered fibroblasts between collagen bundles

Entrapment of lobules of mature fat and nerve endings typical for the entity, but skin adnexa can also be entrapped

Traumatic neuroma-like proliferation of small nerves frequently present

Perineural fibrosis occasionally present

Number of elastic fibers within the lesion typically reduced

Mild inflammatory cell infiltrate, composed of lymphocytes, occasionally present

CD34 (up to 80%) and CD99 positive

Negative for smooth muscle actin, β-catenin, desmin, S100 protein

Gardner fibroma

Connective tissue nevus

Desmoid-type fibromatosis

Children and young adults

About 30% diagnosed in the first year, almost 80% in the first decade, 15% in the second decade, and less than 10% after the third decade

Slightly more common in males (M : F = 1.2 : 1)

Slowly growing, ill-defined plaque of rubbery consistency

Solitary lesions more common than multifocal tumors (concurrent or subsequent)

Size from 0.3 to 12 cm (mean size 3.9 cm)

Most frequently on the back and paraspinal region (78%), followed by the head and neck area (14%), extremities (14%), and chest/abdomen (11%)

Benign behavior

Concurrent or subsequent development of desmoid fibromatosis with or without prior precipitating factor (trauma and/or surgery) in about 20% of cases

Poorly circumscribed proliferation in the superficial (subcutis/dermis) and/or deep soft tissue (deeper to the fascia with skeletal muscle involvement)

Hypocellular proliferation

Haphazardly arranged thick collagen bundles often associated with cracking artifact

Spindled or fusiform fibroblasts scattered between collagen bundles

Small capillary-sized blood vessels between collagen bundles, frequently compressed

Entrapment of fat lobules and peripheral nerve fibers, especially at the periphery

Lack of nodularity and fascicular growth

Increased number of small nerve twigs/bundles (traumatic neuroma-like), as in nuchal fibroma, usually not present

Can be associated with desmoid fibromatosis, characterized by fascicular growth and more prominent cellularity (see corresponding chapter)

Positive for CD34, cyclin D1, and c-Myc

Variable β-catenin nuclear positivity (in about 70% of cases)

Negative for smooth muscle actin, desmin

Nuchal fibroma

Desmoid fibromatosis

Equal gender distribution

Adult patients in the third to fifth decade of life

Lesions in children extremely rare, generally trauma related

Slowly growing mass or nodule

Poorly delineated

Asymptomatic, associated with stiffness or painful

Size generally less than 3 cm in greatest diameter

Localized within the nuchal ligament; surrounding structures can also be affected

Predilection for the deep soft tissue of the lower cervical spine at the junction of nuchal ligament and deep cervical fascia at the level of C4–5 and C5–6

Complete excision curative

No recurrences reported after complete excision

Poorly delineated and moderately cellular proliferation of fibroblasts and chondroblasts forming a nodule

Both cellular components fairly uniform, lacking cytological atypia(s), nucleoli, and mitotic activity

Chondroblasts frequently arranged in short cords or strands, binucleated cells within lacunae generally absent

Fibroblastic component often paucicellular

Disorganization of collagen and fragmentation of elastic fibers within the lesion

Inflammation, hemorrhage, or deposition of hemosiderin generally absent

Degenerative changes of the nuchal ligament surrounding the central area of fibrochondrous metaplasia with fragmentation of elastic fibers

CD34 positivity in both fibroblastic and chondroblastic component

Chondroid areas display S100 protein positivity

Negative for desmin and CD99

Soft tissue chondroma

Nuchal fibroma

Myositis ossificans

Incidence of 0.4% live births

Slight male predominance (M : F = 1.5 : 1)

Over 90% of the lesions present before the age of 3 months, usually between first and eighth week of life

Delayed presentation in adults has been reported

Familial occurrence in less than 5% with possible autosomal-dominant pattern of inheritance

Nontender, firm, fusiform swelling within the sternocleidomastoid muscle

Initial rapid growth for several weeks, followed by stabilization of the lesion with lack of additional growth lasting for several months, with subsequent spontaneous diminution or complete regression of the lesion within the first year of life

Nodular proliferation can be associated with ipsilateral tilting of the head and contralateral head rotation (e.g., torticollis) in about 20% to 25%

The lesion typically measures between 1 and 3 cm in diameter

The majority of the lesions are solitary, bilateral occurrence being exceptional

Overlying skin generally normal; hyperpigmentation and hypertrichosis reported in a single case

Spontaneous resolution in 50% to 80%, usually within the first year

Initial treatment should be conservative, including physical therapy, heat, and massage

Surgical therapy (usually in less than 10%) restricted for lesions nonresponsive to conservative treatment

Late complications include delayed torticollis and craniofacial asymmetry

Proliferation of bland spindled fibroblasts associated with variable amount of collagenous matrix between skeletal muscles with replacement of skeletal muscles resulting in the formation of predominantly hypocellular collagenous mass

Skeletal muscles frequently atrophic with accompanying degenerative changes

Inflammatory cell infiltrate generally absent