Tumors of neuroectodermal origin

No gender predilection

No age predominance

Frequency varies according to the underlying causative event

• Less than 3% of patients after radical neck dissection

• As high as 26% of patients after bilateral limb amputation

Associated conditions, in addition to previous surgery, include burns, trauma, minor trauma (not readily apparent), human bite, arteriovenous aneurysm, nuchal- and extranuchal-type fibroma

Solitary firm nodule or a raised, occasionally erythematous area within a preexistent scar

Not fixed to the underlying tissue

Generally measures less than 1 cm in greatest diameter

Usually painful, but asymptomatic examples not uncommon

Other sensory abnormalities include paresthesia, anesthesia, tenderness, and hypersensitivity

Multiple lesions infrequent

• Genital locations

• May be associated with previous burns

Site of origin generally related to the site of previous trauma and most commonly includes extremities and the head and neck area

Mucosal surfaces (e.g., oral cavity) can also be affected

Uncommon sites include intraosseous occurrence, subungual area, and penis

Treatment options include nonsurgical methods (injections of steroids, sympathetic ganglion block, therapy by ultrasound) with variable success, as well as surgical excision

Complete surgical excision usually curative, but recurrences not uncommon, and multiple procedures may be needed

Disorganized/haphazard proliferation of all the elements of the nerve fascicle, including axons, Schwann cells, and perineural fibroblasts, in the dermis and/or subcutis

Variably cellular collagenous and hyalinized stroma in the background (scarring)

Cleft-like spaces between components of the lesion and stroma

Additional features

• Intraepithelial proliferation of axons overlying the lesion has been described at mucosal sites

• Granular cytoplasm of Schwann cells with centrally placed uniform nucleoli exceptionally reported in lesions developing in the breast

• Mature ganglion cells, occasionally in clusters, with accompanying satellite cells

• Dystrophic calcification

• Mast cells in variable proportions

• Chronic inflammation

• Mucinous change in the stroma

Perineural and intraneural infiltration of nerve bundles by neoplastic cells reported in an exceptional case of squamous cell carcinoma and microcystic adnexal carcinoma

Accessory digit

Mucosal neuroma

Schwannoma

Neurofibroma

Ganglioneuroma

No gender predilection

Middle-aged adults

Congenital occurrence in a single patient

About 50% of lesions associated with previous trauma

One lesion associated with Morton neuroma

Progressive, sometimes excruciating pain in the affected digit, radiating to the arm

Local tenderness

Localized swelling or small, palpable nodule

Solitary lesions predominate, but multifocal occurrence possible

Site of occurrence includes fingers and toes

Complete excision associated with immediate relief of symptoms

No recurrences reported

Main components of the lesion include Pacinian corpuscles, nerve fibers, and fibrosis

Pacinian corpuscles increased in numbers (hyperplasia) and size (hypertrophy)

• Composed of central axon surrounded by a discontinued single Schwann cell layer and lamellae of perineurial cells

• Pericorpuscular fibrosis generally present, but usually mild

Small nerve fibers increased in numbers

• In between Pacinian corpuscles

• Endoneural and perineural fibrosis

Additional histological features

• Foreign body granuloma

• Traumatic neuroma

• Mild inflammation

• Erosive changes of the proximal phalanx reported in a single case

Neurotized melanocytic nevus

Traumatic neuroma

Pacinian schwannoma

Pacinian neurofibroma

Striking female predominance (F:M = 5–10 : 1)

Different age groups can be affected, but most common between 40 and 60 years of age

Fullness with enlargement of the interdigitating space with subsequent thickening

Well-defined mass or nodule generally not seen

Forefoot pain, irritating and debilitating at the bottom of the foot, usually on walking

Tenderness and paresthesia

Size of the lesion from 0.7 to 2.0 cm (mean size 1.1 cm)

Predilection for third to fourth web interspace of the foot, followed by second to third web interspace, but distal sites to the metatarsal heads not uncommonly affected

Associated conditions can include rheumatoid nodules at the same site(s) in the setting of rheumatoid arthritis

Multiple lesions rare

Gradual onset, but slowly progressive if left untreated

Nonsurgical treatment options include activity modification, use of appropriate footwear, nonsteroidal anti-inflammatory drugs, sonography-guided alcohol injections, injection of local anesthetics, and corticosteroids

Radiofrequency ablation and surgical neurectomy

Thickening of the affected nerve

Degeneration and demyelinization of nerve fibers

Fibrosis/sclerosis of the epineurium, perineurium, and endoneurium

Proliferation, hyalinization, and sclerosis of endoneurial vessels

The diagnosis is generally made on clinical grounds

Equal gender distribution

Usually present at birth or develops shortly thereafter

Solitary mucosal or cutaneous lesions, not associated with MEN 2B, appear to develop in older patients

Dome-shaped papules or small nodules covered by normal mucosa

Size about 5 mm in largest diameter

Sites of predilection include oral mucosa (lips, buccal area, gingivae, palate, tongue), but also eyelids, conjunctiva, and sclera

Cutaneous involvement in MEN 2B much more infrequent

• Present as small papules or nodules, skin colored

• Diverse sites of origin, including perinasal area, pinna, and face, less often on trunk

• Widespread cutaneous neuromas (over 70) in association with macular amyloidosis on the back reported in a single patient

Dermal hyperneury consists of the presence of increased normal nerve bundles within the dermis

Solitary lesions not associated with MEN 2B also reported in the larynx, hard palate, and bronchial mucosa

Multiple intraosseous neural hyperplasia(s) in maxillary bone also reported and is thought to be highly suggestive for MEN 2B

No treatment generally required

Surgical treatment usually related to the location-induced functional impairment

Occurrence at particular location(s) (e.g., vocal cords) can be life threatening

Poorly circumscribed nodular or multinodular (plexiform) arrangement(s) of hyperplastic peripheral nerves in the subepithelial stroma or dermis

Haphazardly arranged, disorganized, interlacing fascicles of Schwann cells and axons

Nuclear palisading of Schwann cells can occasionally be seen and usually represents a focal phenomenon

Mitoses and nuclear pleomorphism absent

Hyperplastic nerves surrounded at the periphery of fascicles by a discontinuous layer of perineurial cells

Schwann cells strongly positive for S100 protein

Perineurial cells highlighted by EMA

Traumatic neuroma

Solitary circumscribed neuroma

No gender predilection

Wide age distribution (0–92 years), most common in the fourth decade of life

Asymptomatic, flesh-colored, dome-shaped, sometimes verrucous papule or groups of papules with occasional linear arrangement(s)

Solitary lesions predominate, multifocal occurrence exceptional

Size about 1 cm in greatest diameter in cases of a solitary papule

Predilection for the trunk, followed by extremities, head and neck, and acral locations

Diagnosis generally not suspected on clinical grounds

Excision usually performed due to other suspected pathology

Complete excision curative

Well-circumscribed, nonencapsulated proliferation

Composed of mature ganglion cells and fascicles of hyperplastic nerves with Schwann cells and axons

• Proportion of the component varies among the lesions

• Components usually intermingled, but can be separated

Ganglion cells characterized by

• Abundant eosinophilic to basophilic cytoplasm

• Vesicular, eccentrically placed nuclei

• Prominent nucleoli

• Oval to stellate-shaped morphology

• Retraction artifact between ganglion cells and surrounding stroma

Hyperplastic nerves characterized by proliferation of

• Spindle-shaped Schwann cells with elongated and slightly wavy nuclei forming bundles and fascicles

• Axons arranged in interweaving fascicles

Epidermal changes include acanthosis, papillomatosis, hypergranulosis, and hyperkeratosis

• Features indistinguishable from seborrheic keratosis can also be seen

Additional changes include

• Stromal desmoplasia

• Focal myxoid change

• Fatty metaplasia

• Chronic inflammatory cell infiltrate composed of lymphocytes and macrophages

Ganglion cells strongly positive for synaptophysin, c-kit (CD117), and CD56; nearly always positive for neuron-specific enolase (NSE) and neurofilament; and positive for S100 protein

Schwann cells positive for S100 protein

Ganglion cell choristoma

Entrapment of ganglion cells by neurofibroma

Skin metastasis of a well-differentiated neuroblastoma (maturation into ganglioneuroma)

Benign and malignant melanocytic proliferations

Reticulohistiocytoma

Epithelioid fibrous histiocytoma

Infancy and early childhood

Not distinctive

Benign

No treatment generally required

Dermal proliferation

Small capillaries

Background proliferation of bland, spindle-shaped cells

Spindle cells neuron specific enolase positive

Various nerve sheath tumors

Equal gender distribution

Most common in age groups between 30 and 60 years

Generally not associated with particular neurocutaneous syndrome(s), like neurofibromatosis, multiple endocrine neoplasia (MEN), Cowden syndrome, Bannayan–Riley–Ruvalcaba syndrome, or Gorlin syndrome

Solitary pink or flesh-colored papule or small nodule

• Slowly growing, dome shaped, and firm

• Asymptomatic or slightly painful

• Size between 0.2 and 0.6 cm

Multiple lesions an exception

• Synchronous occurrence of multiple lesions in a linear distribution on both hands (palms and fingers) reported recently

Loss of hair follicles and hairs in areas of skin overlying the lesion usually noted

Predilection for the face, especially areas close to the interface between skin and mucosal sites

Less frequent sites include neck, trunk, shoulders, proximal extremities, and acral sites

Mucosal surfaces can also be affected, including oral and nasal mucosa and glans penis

Complete excision curative

Recurrences after incomplete/marginal excision unlikely

Nodular and less commonly multinodular (plexiform) proliferation in the dermis with exceptional extension into the subcutaneous fatty tissue

Main components include Schwann cells, axons, and perineurial cells

Schwann cells forming broad intersecting elongated fascicles, nests, or whorls of bland spindle cells

• Nuclei pointed at ends, but also plump, fusiform, and wavy

• Palisading of nuclei with formation of Verocay bodies an exception; if present, generally a focal phenomenon

• Mitoses absent or exceptional

• Nuclear pleomorphism absent or mild and limited

• Cytoplasm poorly delineated, pale, and eosinophilic

• Fascicles separated by artifactual clefts, also present at the peripheral aspects of the proliferation

Axons

• Arranged in parallel to the orientation of the fascicles

• Usually evenly distributed and numerous

• Axon(s) to Schwann cells ratio usually does not exceed 1 : 2 (A:SC ≤1 : 2)

• In rare cases, their distribution can be focal and scarce

Perineurial cells

• Within the discontinuous capsule at the periphery of the lesion

• Not present in between Schwann cells within the lesion

Preexistent peripheral nerve can be identified in about 50% of the lesions

• Serial sections may be necessary to demonstrate this phenomenon

Histological variants include epithelioid, multinodular (plexiform), and vascular

• Epithelioid variant, as the name implies, features more epithelioid cells with round to oval nuclei and more prominent eosinophilic cytoplasm

• Multinodular (plexiform) variant essentially corresponds to multiple interconnecting nodules representing a single lesion sectioned at multiple planes throughout the dermis

• Vascular variant is characterized by an increase in cavernous-type blood vessels with possible thromboses and perivascular hyalinization (“ancient-like” changes)

Additional histological features

• Overlying epithelium normal, atrophic, or hyperplastic

• Myxoid change and stromal mucin, rarely extensive

• Limited inflammatory cell infiltrate composed of lymphocytes and, rarely, eosinophils

• Limited collagenized connective tissue stroma

Schwann cells positive for S100 protein and collagen type IV

Axons can be delineated by neurofilament stain

Perineurial cell population EMA, GLUT-1, and/or claudin-1 positive

GFAP staining consistently negative

(Multiple) mucosal neuroma(s)

Traumatic neuroma

Neurofibroma

Schwannoma

Fewer than 10 cases reported

Slight female predominance (F:M = 4 : 3)

Adult patients (from 43 to 86 years, mean age 63 years)

Solitary erythematous plaque, papule, or nodule

Size from 0.5 to 2 cm in greatest diameter

Asymptomatic, pruritic, or painful

Exclusively reported on the skin of the back so far

Simple excision curative

No recurrences reported

Proliferation restricted to the papillary and superficial reticular dermis

Numerous thickened peripheral nerves surrounded by perineural epithelial sheath

Peripheral nerves

• Disorganized proliferation

• Occasionally display parallel orientation to the surface epidermis

• May not be associated with perineural epithelial sheath, especially at the periphery of the lesion

Perineural epithelial sheath

• Composed of regular squamous epithelium, likely of infundibular derivation

• Cornification generally preserved with formation of dyskeratotic keratinocytes, presence of granular cell layer, and orthokeratotic basket-weave keratin

• Epithelial elements only can occasionally be seen, not associated with peripheral nerves, especially in the central parts of the lesion

• Epithelial sheath can be absent, especially at the peripheral aspects of the lesion, composed of thickened nerves only

Additional features

• Perineural inflammatory cell infiltrate composed of lymphocytes and plasma cells, variably prominent

• Minimal and delicate perineural fibroplasia

• Myxoid/mucinous perineural stromal degeneration

Overlying epidermis usually normal

No connection to the epidermis or adnexal structures

Nerve bundles

• Consistent positivity for S100 protein, neurofilament, CD57, and nerve growth factor receptor

Perineural epithelial sheath(s)

• Strong positivity for CK-MNF116 and less intense positivity for CK-AE1/AE3

• Negative for CAM5.2, EMA, and CEA

Traumatic neuroma

Idiopathic neuroma

Reactive neuroepithelial aggregates

Cutaneous hamartomas containing nerve fibers

• Neurofollicular hamartoma

• Congenital neural hamartoma

• Striated muscle hamartoma/rhabdomyomatous mesenchymal hamartoma

Reexcision perineural invasion by nonneoplastic squamous epithelium

Perineural infiltration by epithelial tumors (e.g., squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma) or keratoacanthoma

Dermal hyperneury

Equal gender distribution

Most common in the fourth and fifth decade of life

Slowly growing, painless swelling or nodule

Pain on percussion over the nerve (Tinel sign) present in over 90%

Multiple lesions can be associated with neurofibromatosis type 2

Multiple nonintradermal schwannomas in the absence of vestibular schwannomas can represent part of a schwannomatosis, an autosomal-dominant multiple neoplasia syndrome associated with a mutation in the SMARCB1 tumor suppressor gene located on chromosome 22q11

Benign tumor with very low malignant potential

Complete excision generally curative

Biphasic morphological pattern, designated as Antoni A and Antoni B areas, intermixed and in variable proportions

Antoni A areas

• Cellular component

• Closely packed spindle cells with wavy, elongated, and tapering nuclei

• Cytoplasm ill defined, eosinophilic

• Verocay bodies: two rows of nuclear palisading separated by Schwann cell processes

• Mitoses rare

• Degenerative nuclear pleomorphism

• Stroma frequently hyalinized or collagenized with focal dystrophic calcifications

• Small blood vessels with frequently hyalinized vessel walls

Antoni B areas

• Hypocellular component

• Irregularly distributed spindle and stellate cells

• Abundant myxoid stroma

• Scattered chronic inflammatory cell infiltrate

• Small blood vessels with frequently hyalinized vessel walls

• Degenerative changes not uncommon, including deposition of hemosiderin and microcystic change

Very rarely schwannoma can show Pacinian differentiation

• Such lesions were previously considered neurofibromas with Pacinian features

• These are not associated with neurofibromatosis, but have been associated in a few cases with vascular malformations

Strong nuclear and cytoplasmic S100 protein positivity

Capsule contains EMA-positive perineurial cells

Aberrations on chromosome 22 frequent (loss of 22q or monosomy of chromosome 22)

Solitary circumscribed neuroma

Neurofibroma

Leiomyoma

Represents about 5% of schwannomas

No sex predilection

Wide age distribution, but most common in young adults (fourth decade of life)

Congenital/childhood occurrence signifies possible association with neurofibromatosis type 2 or schwannomatosis, especially when lesions are multiple

Slowly growing, generally nonpainful nodule

Single lesions predominate

Size usually less than 2 cm, but giant variants also reported

Multiple lesions can develop within the single anatomical area, or are widely distributed

Most common at superficial locations (dermis/subcutis) (90%), with predilection for the head and neck, upper extremities, and trunk

Mucosal sites (e.g., oral cavity), deep soft tissues (about 50% develop in extremities, followed by pelvis), or visceral locations (gastrointestinal tract) affected less frequently (in about 10%)

Association with neurofibromatosis type 2 (NF2) (with multiple lesions in the dermis and subcutis) and, less often, with schwannomatosis, whereas occurrence in the setting of neurofibromatosis type 1 (NF1) much more uncommon

Plexiform schwannoma in the setting of NF1 and NF2 exceptionally associated with macrodactyly

Benign tumors with no malignant potential, but may cause severe nerve dysfunction

Recurrences rare, usually after incomplete excision

Complete excision curative

Tumors developing within plexiform schwannoma in exceptional cases

• Epithelioid angiosarcoma

• Intratumoral metastases, mainly from the breast

Antoni A elements (cellular) predominant/exclusive component of the lesions

Antoni B elements present focally or lacking altogether

Generally encapsulated by thin layer of perineurial cells, which may be discontinuous/lacking immediately beneath the surface, especially at the mucosal sites

Increased cellularity, mitotic activity, nuclear pleomorphism, and focal areas of necrosis (12% of deep-seated variants of plexiform schwannoma) do not have any biological significance

S100 protein positive

Chromosomal abnormalities appear to be different than in conventional schwannoma, with trisomy of chromosome 17 and 18, not associated with chromosome 22 aberrations

Plexiform neurofibroma

Malignant peripheral nerve sheath tumor

Elderly patients

Occurrence in pediatric population most unusual

Represents about 0.8% of soft tissue tumors

Generally a long-standing lesion

Predilection for deeper locations, particularly soft tissues of the head and neck, thorax, retroperitoneum, pelvis, and extremities

An exceptional case occurring within the lymph node has also been reported

Lesions generally follow a benign clinical course

Malignant transformation of ancient schwannoma an exceedingly rare phenomenon with fewer than 10 such cases reported (see malignant peripheral nerve sheath tumor)

Complete excision curative

Degenerative nuclear atypia characterized by nuclear hyperchromasia, pleomorphism, intranuclear cytoplasmic pseudoinclusions, and often multilobated nuclei

Mitotic activity absent or very low

Relative loss of cellular Antoni A areas with increase in the proportions of hypocellular areas

Recent/old hemorrhage with extravasation of erythrocytes or hemosiderin deposition

Pseudocystic areas

Calcification and osseous metaplasia

Xanthomatous change and/or formation of cholesterol clefts

Vascular thrombosis in different stages of organization

Perivascular hyalinization

Stromal edema, hyalinization, and fibrosis

Background changes of conventional schwannoma

See conventional schwannoma

See conventional schwannoma

Middle-aged adults

Plexiform variant of cellular schwannoma can be congenital and shows predilection for childhood

Represents about 5% of schwannomas

Association with neurofibromatosis rare

Slowly growing nodular proliferation

Predilection for paravertebral areas of the mediastinum and retroperitoneum

Neurological disturbances related to the site of origin; erosion of the bone occasionally present

Plexiform variant of cellular schwannoma

• Multinodular occurrence, occasionally associated with a rapid growth

• Predilection for extremities

• Generally lacks association with neurofibromatosis

An unusual collision of cellular schwannoma and plexiform neurofibroma in the absence of neurofibromatosis reported recently

Benign clinical course with lack of malignant alteration

Recurrences after incomplete excision common, with increased mitotic activity demonstrated to be predictive of possible recurrence

Complete excision curative, but might be difficult to achieve due to the site of origin

Predominance of highly cellular Antoni A areas with spindle cells growing in interlacing fascicles, but additional storiform or whorled pattern not uncommon

Mitotic activity

• Typically present and may be as high as 10 mitoses per 10 high-power fields

• Atypical mitoses absent

Isolated microfoci of necrosis not uncommon, but larger areas of necrosis or multifocal necrosis an exception

Mild to moderate nuclear pleomorphism associated with nuclear hyperchromasia

Absence of Verocay bodies, but vague nuclear palisading can be present at least focally

Additional features

• Foamy macrophages, may be particularly prominent

• Inflammatory cell infiltrate, usually composed of lymphocytes

Diffuse and strong S100 protein positivity

Malignant peripheral nerve sheath tumor

Leiomyosarcoma

Female predominance

Adult patients, most common in the fifth decade of life

Slowly growing, asymptomatic nodule

Lesions can also be painful

Generally less than 2 cm in greatest diameter

Predilection for the head and neck area, followed by the back

Rare sites include intracranial nerves and neck of the bladder

Benign lesion with no malignant potential

Recurrences rare, even after incomplete excision

Conservative excision generally curative

Highly cellular, multinodular proliferation surrounded by a thin capsule (may be absent in rare instances)

Lesional cells grow in small nests, trabeculae, cords, or strands (can be separated by artifactual clefts)

Epithelioid cells with round to oval nuclei containing small nucleoli and well-defined, abundant eosinophilic cytoplasm

Mitoses rare (usually up to 1 per 10 high-power fields), atypical mitoses absent

Necrosis absent

Focal symplastic change with nuclear pleomorphism and intranuclear cytoplasmic pseudoinclusions frequently present

Transitions to classic schwannoma can be seen focally in a proportion of cases

Medium-sized blood vessels with hyalinized walls

Myxoid matrix

Plexiform variant characterized by

• Multiple nodules composed of epithelioid Schwann cells in the dermis and subcutis

• Each nodule surrounded by a thin layer of perineurial cells

• Up to 5 mitoses per 10 high-power fields

Diffuse and strong nuclear and cytoplasmic S100 protein positivity

EMA, melan A, CD34, various cytokeratins negative

Proliferative activity (Ki-67) generally low

Epithelioid neurofibroma

Myoepithelial tumors

Epithelioid malignant peripheral nerve sheath tumor

Female predominance (F:M = 6 : 1)

Wide age distribution, most common in fourth decade of life

Not associated with neurofibromatosis

Solitary asymptomatic nodule, occasionally painful

Predilection for neck, followed by trunk and extremities

Unusual locations include vulva and orbit

Benign lesion

Complete excision curative

Well-circumscribed and encapsulated

Dermis and/or subcutis

Lesional cells small with round to oval nuclei, indistinct nucleoli, and scant cytoplasm

Epithelioid morphology not uncommon, either focally or more extensive

Formation of rosette-like structures around blood vessels or collagenous cores

Mild nuclear atypia occasionally present

Mitoses generally absent

Necrosis absent

Multinodular/plexiform growth pattern in a single case

Typical features of conventional schwannoma present at least focally in the majority of cases

Diffuse and strong S100 protein positivity

Occasional focal positivity for synaptophysin, GFAP, and neuron specific enolase

EMA delineates perineurial cells within the capsule

Neuroblastoma

Dendritic cell neurofibroma with pseudorosettes

Wide age distribution (11–93 years, median 63 years)

No gender predominance

Slowly growing solitary nodule

Multinodular growth reported in a single case, presented with facial swelling

Size from 0.4 to 23 cm (median size 4.3 cm)

Predilection for visceral sites, especially gastrointestinal tract (isolated cases reported also in adrenal gland, respiratory tract, pancreas, cervical spine)

Rare sites include subcutis and deep soft tissue

Benign clinical course

No recurrences after complete excision

Lesions at visceral sites generally well circumscribed but not encapsulated

Cutaneous tumors encapsulated

Spindle cells growing in anastomozing and interconnecting strands with formation of a microcystic/reticular and, less often, cribriform growth pattern

Nuclei round, oval, or tapered with inconspicuous small nucleoli

Nuclear atypia generally absent

Mitoses rare (usually fewer than 3 per 50 high-power fields)

Cytoplasm ill defined, eosinophilic

Myxoid material or fibrillary collagen occasionally present within microcystic/reticular structures

Intervening stroma myxoid, fibrillary, or sclerotic/collagenized

Areas resembling conventional schwannoma, foci with epithelioid morphology, and fascicular growth pattern occasionally present

Scattered inflammatory cell infiltrates composed of lymphocytes (aggregates or formation of germinal centers rare)

Strong and diffuse nuclear and cytoplasmic S100 protein positivity

Variable positivity for GFAP and CD117 (c-kit)

Negative for various cytokeratins, smooth muscle actin, desmin

Extraskeletal myxoid chondrosarcoma

Perineurioma

Myoepithelial tumors

Equal gender distribution

Most common in the fourth decade of life, although age distribution is quite broad (about 70% develop from second to fifth decade)

Association with neurofibromatosis type 1, neurofibromatosis type 2, and schwannomatosis appears to be more frequent than initially estimated, especially for multiple lesions

Solitary, slowly growing nodule

Generally asymptomatic, occasionally painful

Mean size about 3 cm

Predilection for limbs, head and neck, and trunk

Lesions can also develop at diverse sites, including visceral locations (gastrointestinal tract), mucosal sites (oral mucosa), lymph nodes, and external genital area

Two lesions reported recently, developed after previous irradiation, but the causative relationship uncertain

Benign proliferation

Local recurrence rare

Malignant alteration an exception (demonstrated in a single case)

Well-circumscribed (infiltrative growth rare) and unencapsulated proliferation in the dermis and/or subcutis

Growth patterns include storiform, whorled, fascicular, with nuclear palisading, plexiform, and lamellar

Two cell populations intimately admixed (may be difficult to separate on sections stained with hematoxylin and eosin [H&E])

• Schwann cells: nuclei more plump or tapering, eosinophilic cytoplasm with indistinct cell borders

• Perineurial cells: slender nuclei with bipolar cytoplasmic processes

Mitoses usually absent

Degenerative nuclear atypia present in about 25% of the lesions

Myxoid and/or hyalinized stroma

An exceptional example with triple hybrid components, including schwannomatous, neurofibromatous, and perineuriomatous differentiation, has recently been reported in the nasal cavity

S100 protein–positive Schwann cells usually comprise about 50% to 60% of the population

EMA-positive and frequently also claudin-1–positive perineurial cells represent about 30% to 40% of the tumor cell population

No tumor cells coexpressing S100 protein and EMA

CD34 usually diffusely positive

Variable positivity for GFAP

Neurofilament demonstrates entrapped axons in about one-third of the lesions

Congenital melanocytic nevus with areas of neurotization

Schwannoma

Low-grade malignant peripheral nerve sheath tumor

Female predominance

Wide age distribution, but most common in the fifth decade of life

Solitary, slowly growing papule or a superficial nodule

Cutaneous lesions generally smaller than soft tissue counterparts, with a median size of less than 1 cm

Most common on lower limbs and trunk, with the exception of sclerosing variant showing special predilection for fingers and palm

Complete excision curative

Recurrences distinctly uncommon