BENIGN TUMORS OF THE SKIN AND SUBCUTANEOUS TISSUE

Cysts (Epidermal, Dermoid, Trichilemmal)

Although surgeons often refer to cutaneous cysts as sebaceous cysts because

they appear to contain sebum, this is a misnomer and the substance is actually keratin.
Epidermal cysts are the most common type of cutaneous cyst, and may present as a
single, firm nodule anywhere on the body.

Dermoid cysts are congenital lesions that result when epithelium is trapped
during fetal midline closure. Although the eyebrow is the most frequent site of
presentation, dermoid cysts are common anywhere from the nasal tip to the forehead.

Trichilemmal (pilar) cysts, the second most common cutaneous cyst, occur
more often on the scalp of females. When ruptured, these cysts have an intense,
characteristic odor.

On clinical examination, it is difficult to distinguish one type of cyst from

another: Each cyst presents as a subcutaneous, thin-walled nodule containing a white,
creamy material. Histologic examination reveals several key features. Cyst walls
consist of an epidermal layer oriented with the basal layer superficial, and the more
mature layers deep (i.e., with the epidermis growing into the center of the cyst). The
desquamated cells (keratin) collect in the center to form the cyst.

Epidermal cysts have a mature epidermis complete with granular layer.

Dermoid cysts demonstrate squamous epithelium, eccrine glands, and pilosebaceous
units. In addition, these particular cysts may develop bone, tooth, or nerve tissue on
occasion. Trichilemmal cyst walls do not contain a granular layer; however, these
cysts contain a distinctive outer layer resembling the root sheath of a hair follicle
(trichilemmoma). Each of these cysts typically remain unnoticed and asymptomatic
until they rupture, cause local inflammation, or become infected. Once infected, these
cysts behave similar to abscesses, and incision and drainage is recommended. After
resolution of inflammation, the cyst wall must be removed in its entirety or the cyst
will recur.

Keratoses (Seborrheic, Solar (Actinic))

Actinic keratoses, also known as solar keratoses, are common premalignant

tumors of the epidermis, which occur in sun-exposed skin. Lesions are typically
multiple, and may be so numerous as to alter most of the sun-exposed portion of the
cutaneous surface. Most commonly, actinic keratoses are poorly defined papules with
a surface scale, which may be more easily felt than seen. Their color ranges from pink
to dark brown. Most notable in the older age groups, lesions appear light brown or
yellow and have a velvety, greasy texture. Solar keratoses are considered
premalignant lesions, and squamous cell carcinoma (SCC) may develop over time.

Interestingly, sudden eruptions of multiple lesions may be associated with

internal malignancies. However, Solar keratoses are rarely mistaken for other lesions,
so biopsy and treatment are seldom required. Histologically, these lesions contain
atypical-appearing keratinocytes and evidence of dermal solar damage. Although
malignancies that do develop rarely metastasize, lesion destruction is the treatment of
choice.

Treatments often include application of topical 5-fluorouracil, surgical

excision, electrodesiccation, liquid nitrogen cryosurgery, and dermabrasion.

The patient's skin should be protected from further ultraviolet damage by

chemical or opaque sunscreens and physical protection such as hats and long-sleeved
shirts. Patient education regarding sun protection is essential.

Cutaneous horns

Cutaneous horns are elongated, keratinous projections from the skin, ranging
in size from a few millimeters to many centimeters. Because they are suggestive of
underlying anaplasia, biopsy examination is warranted. Most cutaneous horns arise
from actinic keratoses but they may also result from seborrheic keratoses, warts,
keratoacanthomas, squamous cell carcinomas, and basal cell carcinomas.

Nevi (Acquired and Congenital)

Depending on the location of nevus cells, acquired melanocytic nevi are

classified as junctional, compound, or dermal. This classification does not represent
different types of nevi, but rather different stages in nevus maturation. Initially, nevus
cells accumulate in the epidermis (junctional). As they mature, nevus cells migrate
partially into the dermis (compound) and finally rest completely within dermal tissues
(dermal). Eventually most lesions undergo involution. Congenital nevi are relatively
rare, and may be found in less than 1% of neonates. These lesions are larger and often
contain hair.

Histologically, congenital and acquired nevi appear similar. Giant congenital

lesions (giant hairy nevi) most often occur in a swim trunk distribution, chest, or back.
Not only are these lesions cosmetically unpleasant, but congenital nevi may develop
into malignant melanoma in 1 to 5% of cases.

Total excision of the nevus is the treatment of choice; however, the lesion is
often so large that inadequate tissue for wound closure precludes complete resection.
Instead, serial excisions with local tissue expansion/advancement are frequently
required over several years.

Although the giant nevus may be aesthetically concerning, these lesions

present a roughly 5% risk of malignant transformation over one's lifetime.

Vascular Tumors of the Skin and Subcutaneous Tissue

Hemangiomas are benign vascular neoplasms that present soon after birth.
They initially undergo rapid cellular proliferation over the first year of life, then
undergo slow involution throughout childhood. In contrast to neoplasms, vascular
malformations are a result of structural abnormalities formed during fetal
development. Unlike hemangiomas, vascular malformations grow in proportion to the
body and never involute.
 Histologically, hemangiomas are composed of mitotically active endothelial
cells surroundings several, confluent blood-filled spaces. Although these lesions may
enlarge significantly in the first year of life, approximately 90% involute over time.

Acute treatment is limited to hemangiomata that interfere with function, such

as airway, vision, and feeding or imposes psychological harm to a preschool age
child. In addition, lesions resulting in systemic problems, such as thrombocytopenia
or high-output cardiac failure, should prompt resection. The growth of rapidly
enlarging lesions also can be halted with systemic prednisone or interferon alpha-2a
treatment use. In the absence of acute surgical indications or significant patient/parent
concern, many lesions are allowed to spontaneously involute. However,
hemangiomata that remain into adolescence or involute to leave an unsightly
telangiectasia typically require surgical excision for optimal resolution.

Therapy consists of surgical resection or laser ablation. Even when complete

lesion resection is not possible, significant debulking may greatly diminish
symptomatology. In addition, angiography with selective embolization just before
surgery greatly facilitates operative removal.
 The capillary malformation, or port-wine stain, is a flat, dull-red lesion often
located on the trigeminal (cranial nerve V) distribution on the face, trunk, or
extremities. Presentation within the V1 or V2 facial regions should prompt concern of
a possible link to more systemic syndromes such as Sturge-Weber syndrome
(leptomeningeal angiomatosis, epilepsy, and glaucoma).

Glomus tumor is an uncommon, benign neoplasm of the extremity.

Representing less than 1.5% of all benign, soft-tissue extremity tumors, these lesions
arise from dermal neuromyoarterial apparatus (glomus bodies). Glomus tumor more
commonly affects the hand, and presentation within the subungual region of the toe is
rare. Diagnosis is traditionally delayed, and atypical presentation on the foot or toes
often leads to even greater diagnostic challenges. In addition to the severe pain, point
tenderness and cold sensitivity are associated with these lesions and subungual
glomus tumors typically appear as blue, subungual discolorations of 1 to 2 mm.
Tumor excision is the treatment of choice.
 Soft-Tissue Tumors (Acrochordons, Dermatofibromas, Lipomas)

Lipomas are the most common subcutaneous neoplasm. Although they are
found most frequently on the trunk, these lesions may appear anywhere. Typically
soft and fleshy on palpation, lipomas may grow to a large size and become
substantially deforming. Histologic examination reveals a lobulated tumor composed
of normal fat cells. It is not premalignant.

Although observation is an option, surgical excision is required for tumor

removal.

Acrochordons (skin tags) are fleshy, pedunculated masses located on the

preauricular areas, axillae, trunk, and eyelids. They are composed of

hyperplastic epidermis over a fibrous connective tissue stalk. These lesions are
usually small, and are frequently treated via "tying off" or with resection in the clinic.

Dermatofibromas are solitary, soft-tissue nodules usually approximating 1 to

2 cm in diameter, and are found primarily on the legs and flanks. Histologically, these
lesions are composed of unencapsulated connective tissue whorls containing
fibroblasts. Although a majority of dermatofibromas can be diagnosed clinically,
atypical presentation or course should prompt excisional biopsy to assess for
malignancy. Although these tumors may be managed conservatively, operative
removal is the treatment of choice.

Neural Tumors (Neurofibromas, Neurilemomas, Granular Cell Tumors)

Benign, cutaneous neural tumors such as neurofibromas, neurilemomas, and

granular cell tumors primarily arise from the nerve sheath. Neurofibromas can be
sporadic and solitary. However, a majority are associated with café au lait patches,
Lisch nodules, and an autosomal dominant inheritance (von Recklinghausen's
disease). These lesions are firm, discrete nodules attached to a nerve. Histologically,
proliferation of perineurial and endoneurial fibroblasts with Schwann cells embedded
in collagen are noted. In contrast to direct nerve attachment as seen with
neurofibromas, neurilemomas are solitary tumors arising from cells of the peripheral
nerve sheath. These lesions are discrete nodules that may induce local or radiating
pain along the distribution of the nerve. Microscopically, the tumor contains Schwann
cells with nuclei packed in palisading rows. Surgical resection is the management
option of choice.
 Granular cell tumors are usually solitary lesions of the skin or, more
commonly, the tongue. They consist of granular cells derived from Schwann cells that
often infiltrate the surrounding striated muscle. Based on the severity of
symptomatology, operative resection is the primary therapy of choice.

MALIGNANT TUMORS OF THE SKIN

Although malignancies arising from cells of the dermis or adnexal structures

are relatively uncommon, the skin is frequently subject to epidermal tumors, such as
basal cell carcinoma (BCC), SCC, and melanoma.

Etiology:

Perhaps of greatest significance is that increased exposure to UV radiation is

associated with an increased development of all skin cancer. Clinical studies reveal
that persons with outdoor occupations are at greater risk, as are those with fair
complexions and people living in regions receiving higher per capita sunlight. In
addition, albino individuals of dark-skinned races are prone to develop cutaneous
neoplasms that are typically rare in nonalbino members of the same group. This
observation suggests that melanin, and its ability to limit UV radiation tissue
penetration, plays a large role in carcinogenesis protection.

Skin cancer development also has been strongly linked to chemical

carcinogens such as tar, arsenic, and nitrogen mustard.

Radiation therapy directed at skin lesions increases the risk for local BCC and
SCC. As an ongoing area of intense research interest, certain subtypes of HPV have
been linked to SCC. Additionally, chronically irritated or nonhealing areas such as
burn scars, sites of repeated bullous skin sloughing, and decubitus ulcers present an
elevated risk of developing SCC. Systemic immunologic dysfunction is also related to
an increase in cutaneous malignancies. Immunosuppressed patients receiving
chemotherapy, those with advanced HIV/AIDS, and immunosuppressed transplant
recipients have an increased incidence of BCC, SCC, and melanoma.

Basal Cell Carcinoma

Arising from the basal cell layer of the epidermis, BCC is the most common
type of skin cancer.

Types: Based on gross and histologic morphology

 nodular,

superficial spreading,

micronodular,

infiltrative,

pigmented, and

morpheaform.

Nodulocystic or noduloulcerative type accounts for 70% of BCC tumors.

Waxy and frequently cream colored, these lesions present with rolled, pearly borders
surrounding a central ulcer. Although superficial basal cell tumors commonly occur
on the trunk and form a red, scaling lesion, pigmented BCC lesions are tan to black in
color. Morpheaform BCC often appears as a flat, plaque-like lesion. This particular
variant is considered relatively aggressive and should prompt early excision. A rare
form of BCC is the basosquamous type, which contains elements of both basal cell
and squamous cell cancer. These lesions may metastasize similar to SCC, and should
be treated aggressively.

BCCs are slow growing, and metastasis is extremely rare. Due to this slow
developmental progression, patients often neglect these lesions for years and
presentation with extensive local tissue destruction is common.

Treatment: The majority of small (less than 2 mm), nodular lesions may be
treated via curettage, electrodesiccation, or laser vaporization.

Although effective, these techniques destroy any potential tissue sample for
confirmatory pathology diagnosis and tumor margin analysis. Surgical excision may
be used to both effect complete tumor removal as well as allow proper laboratory
evaluation. Basal cell tumors located at areas of great aesthetic value, such as the
cheek, nose, or lip, may be best approached with Mohs' surgery. Typically completed
by specialized dermatology surgeons, Mohs' surgery uses minimal tissue resection
and immediate microscopic analysis to confirm appropriate resection. Large tumors,
those that invade surrounding structures, and aggressive histologic types
(morpheaform, infiltrative, and basosquamous) are best treated by surgical excision
with 0.5-cm to 1-cm safety margins.

Squamous Cell Carcinoma

 SCCs arise from epidermal keratinocytes. While less common than BCC, SCC
is more devastating due to an increased invasiveness and tendency to metastasize.
Before local invasion, in situ SCC lesions are termed Bowen's disease. In situ SCC
tumors specific to the penis are referred to as erythroplasia of Queyrat. Following
tissue invasion, tumor thickness correlates well with malignant behavior. Tumor
recurrence is more prevalent once SCC tumors grow more than 4 mm in thickness,
and lesions that metastasize are typically at least 10 mm in diameter. Tumor location
is also of great prognostic importance. Although SCC tumors in areas with cumulative
solar damage are less aggressive, and respond well to local excision, lesions arising in
burn scars (Marjolin's ulcer), areas of chronic osteomyelitis, and areas of previous
injury metastasize early.

Although basal cell carcinoma is the most common tumor involving the head
and neck, squamous cell carcinoma occurs with high frequency on the nose, ears, and
lower lip.

Treatment: Although small lesions can be treated with laser and

electrodesiccation, most surgeons recommend surgical excision.
 Lesions should be excised with a 1-cm margin, and histologic confirmation of
tumor-free borders is mandatory. Tumors within areas of great aesthetic value, such as
the cheek, nose, or lip, may be best approached with Mohs' surgery. This precise,
specialized surgical technique uses minimal tissue resection and immediate
microscopic analysis to confirm appropriate resection yet limit removal of valuable
anatomy.

The need for lymph node (LN) dissection in the setting of SCC remains a topic
of debate. Regional LN excision is indicated for clinically palpable nodes. However,
SCC lesions arising in chronic wounds are more aggressive and regional lymph node
metastases are observed more frequently. In this instance, lymphadenectomy before
development of palpable nodes (prophylactic LN dissection) is indicated. Metastatic
disease is a poor prognostic sign, and only 13% of patients typically survive 10 years.

Mohs' Surgery for Squamous and Basal Cell Carcinomas

Basal and squamous cell lesions often present on sun-exposed portions of the
body such as the head and face.

Unfortunately, these areas are of great aesthetic value and significant tissue
loss may significantly alter facial symmetry, contour, and continuity. Developed in
1936, Mohs' technique uses serial excision in small increments coupled with
immediate microscopic analysis to ensure tumor removal, yet limit resection of
aesthetically valuable tissue. One distinct advantage of Mohs' technique is that all
specimen margins are evaluated. In contrast, traditional histologic examination
surveys selected portions on surgical margin. The major benefit of Mohs' technique is
the ability to remove a tumor with minimal sacrifice of uninvolved tissue. Although
this procedure is of particular value when managing tumors of the eyelid, nose, or
cheek, one major drawback is procedure length. Total lesion excision may require
multiple attempts at resection, and many procedures may be carried out over several
days. Recurrence and metastases rates are comparable to those of wide local excision.

Malignant melanoma

The increasing rate of melanoma diagnoses

The pathogenesis of melanoma is complex and remains poorly understood to

date. Melanoma may arise from transformed melanocytes anywhere that these cells
have migrated during normal embryogenesis. Dysplastic nevi contain a histologically
identifiable focus of atypical melanocytes. These lesions are thought to represent an
intermediate stage between benign nevus and true malignant melanoma. A strong
genetic component has been described (Up to 14% of malignant melanomas occur in
a familial pattern).

Sites: Although the eye and anus are notable sites, over 90% of melanomas
are found on the skin. 4% of tumors are discovered as metastases without any
identifiable primary site. Suspicious features suggestive of malignant transformation
include any pigmented lesion with recent irregular border, darkening coloration,
ulceration, and raised surface. 5 to 10% of melanomas are nonpigmented.

Four types of melanoma are

Superficial spreading (70%): anywhere on the skin except the hands and feet.
They are typically flat and measure 1 to 2 cm in diameter at diagnosis.

Nodular (15-30%)

Lentigo maligna (4-15%): occurs most frequently on the neck,

face, and hands of the elderly.

Acral lentiginous (2-8%): on the palms, soles, and subungual regions..

Significant prognostic indicators:

Histologic type

Depth of invasion

Lesions of the extremities have a better prognosis than patients with

melanomas of the

Head, neck, or trunk (10-year survival rate of 82% for localized disease of the
extremity compared to a 68% survival rate with a lesion of the face).

Lesion ulceration carries a worse prognosis.

Females have an improved survival compared to males.

Regional LNs metastasis is a poor prognostic sign

Distant metastasis is the worst prognostic sign

The most current staging system (AJCC)

 Historically, the vertical thickness of the primary tumor (Breslow thickness) &

Anatomic depth of invasion (Clark level) have represented the dominant

factors in the T classification.

The T classification of lesions (prognosis is directly related to the level of

invasion of the skin by the melanoma).

Clark histologic level [I, superficial to basement membrane (in situ); II,
papillary dermis; III, papillary/reticular dermal junction; IV, reticular dermis; and V,
subcutaneous fat].

Breslow measured lesions from the granular layer of the epidermis or the base
of the ulcer to the greatest depth of the tumor (I, 0.75 mm or less; II, 0.76 to 1.5 mm;
III, 1.51 to 4.0 mm; IV, 4.0 mm or more).

These levels of invasion have been subsequently modified and incorporated in

the AJCC staging system.

Stage III: regional LNs metastasis

Stage IV: distant metastasis

Diagnosis of melanoma typically requires excisional biopsy

Treatment

Surgical excision is the management of choice.

Lesions 1 mm or less in thickness can be treated with a 1-cm margin.

For lesions 1 mm to 4 mm thick, a 2-cm margin is recommended.

Lesions of greater than 4 mm may be treated with 3-cm margins.

The surrounding tissue should be removed down to the fascia to remove all
lymphatic channels. If the deep fascia is not involved by the tumor, removing it does
not affect recurrence or survival rates, so the fascia is left intact.

Treatment of regional LNs:

Elective LN dissection on clinically negative nodes

Thin lesions (less than 1 mm), the tumor cells are still localized in the
surrounding tissue, and the cure rate is excellent with wide excision of the primary
lesion; therefore treatment of regional LNs is not beneficial.
 Lesions deeper than 4 mm, it is highly likely that the tumor cells already have
spread to the regional LNs and distant sites. Removal of the melanomatous LNs has
no effect on survival. Most of these patients die of metastatic disease before
developing problems in regional nodes.

In patients with intermediate-thickness tumors (T2 and T3, 1 to 4.0 mm) and
no clinical evidence of nodal or metastatic disease, the use of prophylactic dissection
(elective LN dissection on clinically negative nodes) is controversial. To date, no
prospective, randomized studies have demonstrated that elective LN dissection
improves survival in patients with intermediate-thickness melanomas. However, 25 to
50% of LN specimens contain micrometastases in these cases and recurrence may be
decreased with LN dissection.

Sentinel lymphadenectomy for malignant melanoma is gaining acceptance.

The sentinel node may be preoperatively located with the use of a gamma camera,
which identifies the radioisotope injected into the primary lesion. Whereas
preoperative identification may provide the surgeon greater reliability in localizing the
LN, intraoperative mapping with 1% isosulfan blue dye injection may be equally
effective.

If micrometastasis is identified in the removed node by frozen-section

examination, a complete LN dissection is performed. This method may be used to
identify patients who would benefit from LN dissection, while sparing others an
unnecessary operation.

All microscopically or clinically positive LNs should be removed by regional

nodal dissection. When groin LNs are removed, the deep (iliac) nodes must be
removed along with the superficial (inguinal) nodes, or disease will recur in that
region. For axillary dissections, the nodes medial to the pectoralis minor muscle also
must be resected. For lesions on the face, anterior scalp, and ear, a superficial
parotidectomy to remove parotid nodes and a modified neck dissection is
recommended.

Metasxtasis:

Solitary lesions in the brain, GI tract, or skin that are symptomatic should be
excised when possible. Although cure is extremely rare, the degree of palliation can
be high and asymptomatic survival prolonged
 Hyperthermic regional perfusion with a chemotherapeutic agent (e.g.,
melphalan) is presently the treatment of choice. The goal of regional perfusion
therapy is to increase the dosage of the chemotherapeutic agent to maximize tumor
response while limiting systemic toxic effects. Melphalan generally is heated to an
elevated temperature [up to 41.5°C, (106.7°F)] and perfused for 60 to 90 minutes.
Although difficult to perform and associated with complications (neutropenia,
amputation, death), it does produce a high response rate (greater than 50%). The
introduction of tumor necrosis factor alpha or interferon- with melphalan results in the
regression of more than 90% of cutaneous in-transit metastases.

Although initially thought to be ineffective in the treatment of melanoma, the

use of radiation therapy, regional and systemic chemotherapy, and immunotherapy are
all under investigation.

ADDITIONAL MALIGNANCIES OF THE SKIN

Merkel Cell Carcinoma (Primary Neuroendocrine Carcinoma of the Skin)

Once thought to be a variant of SCC, Merkel cell carcinomas are actually of

neuroepithelial differentiation. These tumors are associated with a synchronous or
metasynchronous SCC 25% of the time. Due to their aggressive nature, wide local
resection with 3-cm margins is recommended. Local recurrence rates are high, and
distant metastases occur in one third of patients. Prophylactic regional LN dissection
and adjuvant radiation therapy are recommended. Overall, the prognosis is worse than
for malignant melanoma.

Kaposi's Sarcoma

Kaposi's sarcoma (KS) appears as rubbery bluish nodules that occur primarily
on the extremities but may appear anywhere on the skin and viscera. These lesions are
usually multifocal rather than metastatic. Histologically, the lesions are composed of
capillaries lined by atypical endothelial cells. Early lesions may resemble
hemangiomas, while older lesions contain more spindle cells and resemble sarcomas.
Classically, KS is seen in people of Eastern Europe or sub-Saharan Africa. The
lesions are locally aggressive but undergo periods of remission. A different variety of
KS has been described for people with AIDS or with immunosuppression from
chemotherapy. For reasons not yet understood, AIDS-related KS occurs primarily in
male homosexuals and not in IV drug abusers or hemophiliacs. In this form of the
disease, the lesions spread rapidly to the nodes, and the GI and respiratory tract often
are involved. Development of AIDS-related KS is associated with concurrent
infection with a herpes-like virus. Treatment for all types of KS consists of radiation
to the lesions. Combination chemotherapy is effective in controlling the disease,
although most patients develop an opportunistic infection during or shortly after
treatment. Surgical treatment is reserved for lesions that interfere with vital functions,
such as bowel obstruction or airway compromise.

Extramammary Paget's Disease

This tumor is histologically similar to the mammary type. It is a cutaneous

lesion that appears as a pruritic red patch that does not resolve. Biopsy demonstrates
classic Paget's cells. Paget's disease is thought to be a cutaneous extension of an
underlying adenocarcinoma, although an associated tumor cannot always be
demonstrated.

Angiosarcoma

Angiosarcomas may arise spontaneously, mostly on the scalp, face, and neck.
They usually appear as a bruise that spontaneously bleeds or enlarges without trauma.
Tumors also may arise in areas of prior radiation therapy or in the setting of chronic
lymphedema of the arm, such as after mastectomy (Stewart-Treves syndrome). The
angiosarcomas that arise in these areas of chronic change occur decades later. The
tumors consist of anaplastic endothelial cells surrounding vascular channels. Although
total excision of early lesions can provide occasional cure, the prognosis usually is
poor, with 5-year survival rates of less than 20%. Chemotherapy and radiation therapy
are used for palliation.

Dermatofibrosarcoma Protuberans

Dermatofibrosarcoma protuberans (DFSP) accounts for 1 to 2% of all soft-

tissue sarcomas, occurs most frequently in persons aged 20 to 50 years, and is more
common in males. The most common presenting location is on the trunk (50 to 60%),
although the proximal extremities (20 to 30% of cases), as well as head and neck also
are frequently affected (10 to 15%). DFSP often appears as a pink, nodular lesion that
may ulcerate and become infected. Histologically, the lesions contain atypical spindle
cells, probably of fibroblast origin, located around a core of collagen tissue. Despite
what appears to be complete lesion excision, local recurrence remains frequent and
mortality associated with metastasis relatively high.

To date, the minimum resection margin needed to achieve local control

remains undefined. Local recurrence rates of up to 50% have been reported after
simple excision, and wide local excision with 3-cm margins is linked to a 20%
recurrence rate.

Most authorities seem to advocate a three-dimensional margin of 2 to 3 cm

with resection of skin, subcutaneous tissue, and the underlying investing fascia. The
periosteum and a portion of the bone may also need to be resected to achieve negative
deep surgical margins. In addition to achieving wide macroscopic resection,
conformation of negative microscopic margins is especially critical. DFSP is
considered to be a radiosensitive tumor, and radiotherapy following wide local
excision has reached local control rates approximating 95% at 10 years. Continued
study of chemotherapy efficacy on DFSP also has produced optimistic results.
Imatinib, a selective inhibitor of platelet-derived growth factor (PDGF) -chain alpha
and PDGF receptor beta protein-tyrosine kinase activity, alters the biologic effects of
deregulated PDGF receptor signaling. Clinical trials have shown activity against
localized and metastatic DFSP containing the t(17:22) translocation, suggesting that
targeting the PDGF receptors may become a new therapeutic option for DFSP. Phase
II clinical trials are underway.

Fibrosarcoma

Fibrosarcomas are hard, irregular masses found in the subcutaneous fat. The
fibroblasts appear markedly anaplastic with disorganized growth. If they are not
excised completely, metastases usually develop. The 5-year survival rate after
excision is approximately 60%.

Liposarcoma

Liposarcomas arise in the deep muscle planes, and, rarely, from the
subcutaneous tissue. They occur most commonly on the thigh. An enlarging lipoma
should be excised and inspected to distinguish it from a liposarcoma. Wide excision is
the treatment of choice, with radiation therapy reserved for metastatic disease.
 SYNDROMIC SKIN MALIGNANCIES

Several genetic syndromes are associated with an increased incidence of skin

malignancy. Although many are related to development of a specific lesion, others
appear to produce a more generic prevalence for neoplastic formation. Based on their
respective genetic defects, syndromes associated with BCC, SCC, and melanoma
have all been identified and well described.

Diseases linked with BCC include the basal cell nevus (Gorlin's) syndrome
and nevus sebaceus of Jadassohn. Basal cell nevus syndrome is an autosomal
dominant disorder characterized by the growth of hundreds of BCCs during young
adulthood. Palmar and plantar pits are a common physical finding and represent foci
of neoplasms. Treatment is limited to excision of only aggressive and symptomatic
lesions. Nevus sebaceus of Jadassohn is a lesion containing several cutaneous tissue
elements that develops during childhood. This lesion is associated with a variety of
neoplasms of the epidermis, but most commonly BCC.

Diseases associated with SCC may have a causative role in the development
of carcinoma. Skin diseases that cause chronic wounds, such as epidermolysis
bullosus and lupus erythematosus, are associated with a high incidence of SCC.
Epidermodysplasia verruciformis is a rare autosomal recessive disease associated with
infection with HPV. Large verrucous lesions develop early in life and often progress
to invasive SCC in middle age. Xeroderma pigmentosum is an autosomal recessive
disease associated with a defect in cellular repair of DNA damage. The inability of the
skin to correct DNA damage from UV radiation leaves these patients prone to
cutaneous malignancies. SCCs are most frequent, but BCCs, melanomas, and even
acute leukemias are seen.

Dysplastic nevi are considered precursors to melanoma. Familial dysplastic

nevus syndrome is an autosomal dominant disorder. Patients develop multiple
dysplastic nevi, and longitudinal studies have demonstrated an almost 100% incidence
of melanoma. Gene mapping of the defects found in familial dysplastic nevus
syndrome has identified several candidate "melanoma" genes.

It remains to be determined whether these germline mutations also are found in

sporadic cases of melanoma. Much like other familial malignancy syndromes, genetic
analysis of the hereditary defect may shed much needed light on the molecular
mechanisms that lead to malignant transformation. Much like familial polyposis coli
and the association with colon cancer, familial dysplastic nevus syndrome is treated
by close surveillance and frequent biopsy of all suspicious lesions. Similarly, the
development of colon cancer can be arrested with total proctocolectomy;
unfortunately, a similar solution is not possible in patients with familial dysplastic
.nevi