Skin and Soft Tissues

528 M.N. Prieto and P.D. Wey

Case 2

A 60-year-old man with a long history of sun exposure presents for evaluation of a nonhealing wound of the forehead of approximately 18 months’ duration. Physical examination reveals widespread actinic sun damage to the skin, with multiple scaly patches measuring 2 to 3 mm. Facial skin is deeply wrinkled, with a few small tan macules 3 to 4 mm in diameter. On the forehead is a 15-mm erythematous, indurated, slightly raised plaque with distinct borders and central ulceration.

Case 3

A 25-year-old woman presents with multiple pigmented lesions of the arms and trunk. She states that they have been present nearly all her life and have not changed in appearance. She is concerned because a distant family member recently was diagnosed with melanoma. Exam reveals multiple discrete 2- to 4-mm homogeneously colored brown to black lesions, some of which are slightly raised.

Case 4

Further examination of the patient described in Case 3 reveals an 8-mm homogeneously pigmented, dark brown lesion on her abdomen. It is asymmetric in shape with scalloped borders and is slightly raised with a variegated surface texture.

Case 5

A 45-year-old man presents with a pigmented lesion on his shoulder. It first appeared in his thirties and slowly enlarged over many years before nearly doubling in size and becoming more raised and nodular over the past year. He is fair-skinned, and his natural hair color is sandy blond. He is an avid outdoorsman, but he does not wear sunscreen. His father has been diagnosed with melanoma. Examination reveals an 18-mm raised, nodular, darkly pigmented lesion with variegated color and surface texture with scalloped borders. There is no palpable lymphadenopathy.

Case 6

A 37-year-old man presents with painless swelling of the right thigh, with rapid progression over the past 4 to 6 months. Physical exam reveals a poorly circumscribed mass measuring 10 ¥ 8 cm over the proximal anterior right thigh. It is deep and firm on palpation, nonfluctuant, and immobile.

Skin Lesions

Introduction

Most skin lesions are benign and can be diagnosed on examination based solely on physical characteristics. The identification and diag-

30. Skin and Soft Tissues 529

nosis of malignant skin lesions, however, is critical given their morbidity, mortality, and frequency. It is estimated that nearly half of all persons who live to the age of 65 will have one or more skin cancers in their lifetime. Well over one million new cases of skin cancer were identified in 2001, and that number was expected to rise slightly in 2002, accounting for approximately half of all new cancer diagnoses and making the skin the most common site of human malignancy.

When distinguishing malignant from benign lesions, the patient’s history, ethnicity, and genetic predisposition, as well as the physical characteristics of the lesion on exam, may serve to raise or lower the clinician’s index of suspicion. The distinction often is still difficult to make, and, ultimately, biopsy of the lesion and pathologic assessment are necessary for diagnosis when there is concern of malignancy.

General Evaluation

Elements of the patient’s history that should raise suspicion of malignancy include changes in color, surface texture, shape or elevation of a lesion, appearance of a new lesion with suspicious characteristics, family or personal history of skin cancer, and history of sun or toxic exposure. Focused examination of the presenting lesion should follow. In addition, the physician should perform a thorough examination of the entire skin surface, including scalp, palms, soles, and nail beds, noting any atypical lesions and documenting their size and appearance for future comparison.

While close observation of a lesion may be appropriate in some instances, biopsy of suspicious lesions is highly recommended. One also should understand approaches to precancerous lesions, since biopsy is indicated in some but not in others. Small lesions may be biopsied by full excision, while large lesions may be approached with full-thickness incisional biopsy or punch biopsy. Techniques that compromise pathologic evaluation, such as shave biopsy, which often is used in the treatment of benign lesions, are contraindicated in the workup of potentially malignant lesions.

Basal Cell Carcinoma

The patient described in Case 1 exhibits a facial lesion that fits the classic description of basal cell carcinoma (BCC) of the nodular type, the most commonly occurring of the four clinical subtypes of BCC described in Table 30.1. Basal cell carcinoma is the most common

Table 30.1. Four clinical subtypes of basal cell carcinoma.

530 M.N. Prieto and P.D. Wey

malignancy in the general population, usually occurring on the head and neck. Sun exposure is considered to be a primary causative factor, similar to other skin cancers, and patients almost always are fairskinned Caucasians. Tumors of the nasolabial fold (as in this patient), medial and lateral canthi, and postauricular regions often are associated with worse outcomes. Skin biopsy of suspected BCC is mandatory to confirm diagnosis and would be an appropriate next step in the management of this patient.

Since this is the patient’s first presentation, the physician should elicit the patient’s history of sun exposure and history of predisposing medical conditions, including such rare conditions as xeroderma pigmentosum and basal cell nevus syndrome. Since patients with BCC may develop multiple tumors over time and since recurrent disease is not uncommon, personal history of BCC and other skin cancers should be obtained. Physical examination should be performed meticulously, since different types of BCC may mimic scar tissue or dermatitis, and should include examination of local lymph node basins.

Basal cell carcinoma expands locally over long periods of time, and the tendency for metastasis is low: only 2% of cases involve regional lymph nodes. As a result of its indolent and nonaggressive behavior, excisional biopsy of localized primary BCC with 2- to 3-mm margins is curative in 95% of cases. Pathologic assessment of frozen sections intraoperatively can provide preliminary confirmation of complete excision of the tumor. Alternatively, Mohs’ micrographic excision, usually performed by a dermatologist, is highly effective as well, with a similar cure rate. This technique involves progressive excision and mapping of the tumor bed by microscopic examination of tissue as it is excised until a clear margin is identified. It commonly is reserved for lesions in anatomically sensitive areas such as the lip, nasal rim, and eyelid. Using Mohs’ technique, the amount of normal tissue removed in the course of excision is minimized. Other methods also have been used to treat BCC; these typically are reserved for patients with contraindications to surgery or for patients with multiple tumors in whom numerous excisions would be unfeasible. Electrodesiccation and curettage is one such method, used for ablation of a lesion <2 cm in diameter. Radiation therapy also is acceptable if tissue preservation is important. Both of these techniques are associated with a lower cure rate and accordingly are not appropriate as first-line treatment.

Squamous Cell Carcinoma

The patient described in Case 2 exhibits several manifestations of significant sun damage to the skin, including solar lentigo (tan macules), deep wrinkling, and actinic keratosis (scaly patches and plaques). Actinic keratoses are the result of ultraviolet damage to epidermal cells, and, while they may persist in a benign state for long periods of time, they may progress to squamous cell carcinoma (SCC). Alternatively, they may regress with cessation of sun exposure. The physician should monitor this patient closely and consider treatment of extensive actinic keratoses with topical fluorouracil, cryosurgery, electrodesicca-

30. Skin and Soft Tissues 531

tion and curettage, dermabrasion, or laser therapy. Biopsy should be performed if actinic lesions exhibit suspicious changes, including increasing erythema or induration, enlargement, ulceration, or bleeding. In this patient, whose nonhealing wound likely represents SCC, malignancy may have developed from a preexisting site of actinic keratosis.

A nonhealing wound or ulcer is a classic presentation of SCC. But SCC also may appear as an indurated, erythematous papule or plaque, which can be hyperkeratotic, as in this case, or smooth, with or without ulceration. Invasive SCC has a 5-year metastasis rate of 5%, although the likelihood of metastasis is two to three times greater with lesions >2 cm and location on the lip or ear. Similarly at high risk of recurrence and metastasis are lesions of mucous membranes, nose, scalp, forehead, and eyelid. Malignant transformation to SCC can occur within nonhealing wounds of various etiologies, as in scar tissue following burn or trauma (Marjolin’s ulcer), tissue damaged by radiation therapy, or at sites of chronic infection or draining sinus tracts; these tumors also tend to be particularly aggressive. Table 30.2 summarizes characteristics of SCC that confer high risk of metastasis and poor outcome.

As in other skin cancers, sun exposure is a primary causative factor in SCC. Other risk factors include toxic exposure to arsenic, nitrates, or hydrocarbons, as well as immunosuppression, particularly in organ transplant patients. Premalignant lesions that may degenerate into SCC include actinic keratosis, as described in the patient in Case 2, Bowen’s

Table 30.2. Features of cutaneous squamous cell carcinoma (SCC) associated with increased risk of recurrence and metastasis.

a Relative risk of 1 is defined as the likelihood of recurrence or metastasis of a small primary SCC.

b Tumor invasion to Clark level IV involves the reticular dermis, to Clark V involves the subcutaneous fat.

+ Indicates association with increased risk, but lacking sufficient data to calculate relative risk.

Source: Reprinted from Alam M, Ratner D. Primary care: cutaneous squamous cell carcinoma. N Engl J Med 2001;344(13):975–983, with permission. Copyright © 1994 Massachusetts Medical Society. All rights reserved.

532 M.N. Prieto and P.D. Wey

disease (SCC in situ), and keratoacanthoma. There also is a significant association between cutaneous SCC and human papillovirus infection, particularly types 6 and 11 in SCC of the genital region and type 16 in periungual tumors.

Early detection of SCC is critical, since early disease is largely curable and late disease has a dismal prognosis. The physician should perform a thorough history of potential predisposing conditions, including sun or other radiation exposure, exposure to carcinogens, immunosuppression, and family and personal history of skin cancer. Patients with a positive skin cancer history or extensive actinic skin damage should undergo regular screening examinations for new or changing lesions.

Physical examination of the patient in Case 2 should include examination of the entire skin surface and palpation of regional nodal basins surrounding questionable lesions. Given this patient’s history of sun exposure and evidence of extensive sun damage and because of the suspicious size and characteristics of the presenting lesion, a full-thickness biopsy is warranted. Radiologic and laboratory tests are not indicated unless there are symptoms of or reason to suspect metastasis.

Treatment of this patient’s low-risk lesion would involve surgical resection with 4-mm margins, with frozen section to confirm clear margins. This approach is associated with a 95% chance of a cure. As in BCC, Mohs’ excision also would be an appropriate first-line treatment and is, in fact, the procedure with the highest rate of cure for highrisk primary or recurrent lesions. Acceptable alternative therapies for limited low-risk SCC include electrodesiccation and curettage, cryosurgery, and radiation. Indications may include inoperable tumors, large lesions in cosmetically sensitive areas, or patient contraindications to surgery.

Nevi (Moles)

Many patients present for evaluation of nevi (melanocytic nevocellular nevi or moles). Moles are extremely common in all races, and it is not uncommon to find several dozen on a single individual. While most such lesions are entirely benign, the incidence of and mortality from malignant melanoma has increased markedly over recent years, bringing to the forefront the importance of the physician’s ability to recognize suspicious lesions.

Freckles (ephelides) should be distinguished from nevi. These tan to light brown, small macules with irregular borders are lesions of the basal and upper dermis that result from increased melanin production by nonneoplastic melanocytes. They are benign and require no treatment.

The common nevi seen in the patient presented in Case 3 are made up of benign neoplastic melanocytes, called nevus cells, and are classified according to the site of nevocellular proliferation. They are typically small, well-circumscribed macules or papules that, with the exception of the dermal nevus described below, regress spontaneously

30. Skin and Soft Tissues 533

by the sixth decade of life. History of childhood sunburn may increase the likelihood of developing a greater number of nevi, and those with numerous nevi (more than 40) have a greater likelihood of developing melanoma and should be monitored closely. The vast majority of nevi do not undergo malignant transformation.

All three of the common benign nevus types are represented among the many lesions of this patient. In junctional nevi, nevus cells are clustered at the dermal–epidermal junction above the basement membrane. These are dark brown to black, macular to slightly raised lesions that appear in young children after age 2. They are round to oval, with smooth regular borders. Compound nevi are composed of nevus cells both at the dermal–epidermal junction and within the dermis. They also are brown to black in color, are usually slightly raised, and are frequently hairy, with sharply defined but often irregular borders and smooth to slightly papillary surfaces. A compound nevus surrounded by an area of hypopigmentation is called a halo nevus. Intradermal nevi are made up of nevus cells primarily occupying the dermis, sometimes extending into subcutaneous fat. These are fleshcolored to brown, raised, fleshy papules that distort normal skin anatomy, with hairs and dark flecks sometimes present on the surface. The occasional presence of telangiectasia may make differentiation from BCC difficult. Malignant transformation of any of these nevi is rare when they are small in size (<6 mm), stable in appearance over time, and lacking suspicious characteristics, including ulceration, bleeding, or pruritis. No intervention is indicated for this patient’s lesions at this time, although she should be instructed to monitor their appearance and to follow up with her physician for periodic screening exams.

Atypical and Dysplastic Nevi

Case 4 describes a specific lesion on the same young woman as in Case 3. Unlike the many pigmented lesions on her arms and trunk that easily are classified as benign, this particular lesion should come to the physician’s attention because of its size and irregular shape and surface texture. This lesion is termed atypical on the basis of its gross clinical characteristics. Any nevus is classified as clinically atypical if relatively large in size, i.e., >6 mm, asymmetric, or having an irregular, raised surface or color variegation. While often referred to as dysplastic nevi, atypical nevi may or may not demonstrate histologic dysplasia.

A single atypical nevus can be found in 5% of whites in the United States, and, in the absence of family history of melanoma, this finding is associated with a 6% lifetime risk of developing melanoma. In persons with one or more atypical nevi and a strong family history, the risk of developing melanoma may be as high as 80%. In these persons, the atypical nevus itself may undergo malignant transformation, or disease may develop de novo elsewhere; hence, annual skin screening exams by a physician strongly are recommended. In all patients with a single atypical nevus or nevi, education regarding melanoma risk and self-examination is essential. Because atypical nevi

534 M.N. Prieto and P.D. Wey

Table 30.3. Elements of history to consider in evaluation for melanoma.

Intermittent but intense exposure to sunlight Blistering sunburns in childhood

Tendency to sunburn rather than tan

Living in sunny climates close to the equator Positive family history of melanoma

Positive personal history of melanoma or other skin cancer

History of atypical nevi Recent changes in mole(s)

are associated with increased risk of developing melanoma, fullthickness biopsy of this patient’s lesion should be performed.

Melanoma

The lesion of the patient described in Case 5 is worrisome for several reasons. He has a significant history of sun exposure and sunburn, which is a strong risk factor in fair-complexioned individuals. Intermittent but intense sunlight exposure in particular appears to increase risk. Additionally, melanoma in a first-degree relative, in this case his father, increases risk by at least eight times. The patient also reports a recent history of rapid change in the size and texture of the lesion, which should alert the physician to the likelihood of a malignant process. Other suspicious changes not seen in this patient include changes in color, ulceration, bleeding, or pruritis. Given the high likelihood of malignant melanoma in this patient, one also should question him about recent weight loss or other constitutional symptoms that may be indicative of metastatic disease. Table 30.3 summarizes elements of a patient history that should be considered significant in the evaluation of a possible melanoma.

On exam, this patient’s lesion possesses many characteristics typical of malignant melanoma, including heterogeneous color and nodularity and relatively large (1.8 cm) diameter. The mnemonic ABCDE as described in Table 30.4 summarizes key characteristics of pigmented lesions that should raise suspicion of malignancy. Table 30.5 lists other physical findings that the physician also should take into con-

Table 30.4. The ABCDE of melanoma: characteristics of pigmented lesions suggestive of melanoma.

A:Asymmetry

B:Border irregularity

C:Color variation or variegation

D:Diameter greater than 6 mm

E:Elevated area or palpable nodule within a

formerly flat lesion

Also: ulceration, inflammation, bleeding, satellite nodules, local lymphadenopathy

30. Skin and Soft Tissues 535

Table 30.5. Elements of physical examination to consider in evaluation for melanoma.

Caucasian, fair skin with freckles

Red or blond hair, blue eyes

Presence of atypical nevi

Evidence of sun-induced skin damage

The ABCDE (see Table 30.4)

sideration. The ABCDE mnemonic is a useful guideline, and the diagnosis of melanoma based on history and physical exam alone is highly sensitive when made by an experienced physician. Nonetheless, not all melanomas are clinically obvious, as different histologic types present very differently. Amelanotic melanoma, for instance, is a dangerous, albeit rare entity, because of its tendency to go unrecognized, and hence, it tends to be diagnosed at a later stage when therapy becomes more problematic.

Besides a complete history and examination of the suspect lesion, a thorough examination of the skin over the entire body is essential to the initial evaluation and follow-up of this high-risk patient.

While 60% of melanomas arise de novo from epidermal melanocytes, 40% arise from malignant degeneration of a preexisting atypical or dysplastic nevus. Identification and monitoring of atypical nevi permits early detection and intervention, which are critical, since the depth of melanoma invasion at the time of diagnosis is the most accurate predictor of survival. Regional lymph node basins also should be palpated for clinical evidence of nodal involvement.

Given the highly suggestive appearance and suspect history of the presenting lesion, further evaluation is mandatory. The management of this patient would begin with excisional biopsy, to include a 1- to 2-mm margin of grossly normal skin and subcutaneous tissue. Incisional or punch biopsy also would be an acceptable approach and would be indicated for larger lesions or those in cosmetically sensitive areas. Full-thickness biopsy techniques are absolutely necessary to provide adequate tissue for pathologic assessment and staging, while allowing for reexcision at the site should the malignancy be confirmed.

Shave biopsy, cryosurgery, and electrodesiccation should not be used, since they compromise histologic assessment and primary staging of disease, which are the cornerstones of establishing prognosis and defining treatment.

An excisional biopsy of the patient’s shoulder lesion in Case 5 was performed. The biopsy results showed superficial spreading melanoma of intermediate thickness at 2.8 mm.

Superficial spreading melanoma is the most common type of melanoma, accounting for approximately 70% of all cases. It begins as a brown, slightly elevated lesion, progressing to have irregular, raised borders, a variegated brown to black color pattern, and a diameter of 2 to 3 cm, sometimes with central pigment loss. It exhibits a prolonged radial growth phase, with lateral extension confined to the epidermis and papillary dermis. This noninvasive growth pattern can

536 M.N. Prieto and P.D. Wey

last as long as a decade, and, as a result, it generally is associated with a good prognosis. In this patient’s case, however, increasing nodularity may be indicative of vertical growth into deeper layers of skin and increased likelihood of metastasis.

There are three other distinct histologic types of melanoma, each exhibiting its own characteristic features, growth patterns, and prognoses. Nodular melanoma represents 8% to 10% of all melanomas, with characteristically uniform gray-blue to brown or black color, although they also can be nonpigmented. These demonstrate almost immediate vertical growth, and hence, they are associated with early metastasis and poor prognosis. Lentigo maligna melanoma accounts for approximately 10% of cutaneous melanomas. They are typically flat, tan macules of up to 3 cm or more in diameter that grow slowly and radially within the upper dermis. Elevated nodules and irregular areas of dark brown or black pigmentation arising within these lesions may represent invasive melanoma. The precursor lesion is known as lentigo maligna (Hutchinson’s freckle). Acral-lentiginous melanoma represents only 1% of melanoma cases and occurs exclusively on the palms, soles, and nail beds. Its prognosis ranges from good to poor. Unlike the other subtypes, it occurs with equal frequency among Caucasians and dark-skinned persons. Lesions generally are flat with irregular borders, variably pigmented brown-black to black, but they also may be amelanotic.

As in other forms of cancer, disease staging of melanoma using a TNM (tumor-node-metastasis) classification scheme is ideally predictive of prognosis and useful in guiding therapy. The most recent TNM classification and staging system for melanoma of the American Joint Committee on Cancer (AJCC) was published in 2002 and is shown in

Tables 30.6 and 30.7.

Depth of tumor invasion as measured in millimeters (Breslow depth) is the defining variable in determining the next appropriate step in this patient’s management. Lesion thickness has been found to be inversely related to survival, and it is a good predictor of prognosis in node-negative patients. Melanomas are referred to as thin (less than 1 mm thick), intermediate (1.0 to 4.0 mm thick), and thick (greater than 4 mm) with regard to prognosis and management. The Clark level (Table 30.8) describes the level of invasion relative to the histologic layers of the skin. While these levels correlate reasonably well with Breslow depth, the basis of the Clark system is flawed, in that no true barriers to tumor invasion exist in the subepidermal layers and, in that dermal thickness varies greatly in different parts of the body. It is, however, an independent prognostic feature of thin (T1, i.e., <1.0 mm) melanomas. Chest x-ray, serum alkaline phosphatase, and lactate dehydrogenase are recommended as screening measures for pulmonary and liver metastasis in patients with melanoma greater than 1 mm thick.

Treatment of Melanoma

Definitive treatment of melanoma is surgical control of both local and metastatic disease. The recommended surgical approach to the

538 M.N. Prieto and P.D. Wey

Table 30.7. Proposed stage groupings for cutaneous melanoma.

a Clinical staging includes microstaging of the primary melanoma and clinical/radiologic evaluation for metastases. By convention, it should be used after complete excision of the primary melanoma with clinical assessment for regional and distant metastases. b Pathologic staging includes microstaging of the primary melanoma and pathologic information about the regional lymph nodes after partial or complete lymphadenectomy. Pathologic stage 0 or stage 1A patients are the exception; they do not require pathologic evaluation of their lymph nodes.

c There are no stage III subgroups for clinical staging.

Source: Reprinted from Balch CM, Buzaid AC, Soong SJ, et al. Final version of the American Joint Committee on Cancer staging system. J Clin Oncol 2001;19(16):3635–3648. Review. With permission from the American Society of Clinical Oncology.

the technique of sentinel node biopsy (SNB) described below can be used to identify patients with positive nodes who would benefit from full lymph node dissection. Prior to or at the same time as wide excision of the primary lesion, isosulfan blue and radioactive tracer are injected into the lesion or biopsy site. These are allowed time to drain to the node or nodes that provide primary lymphatic drainage to the

Table 30.8. Clark’s classification of melanoma tumor depth

Level I: Confined to the epidermis (melanoma in situ)

Level II: Invades papillary dermis

Level III: Penetrates up to junction of papillary and reticular dermis

Level IV: Invades the reticular dermis Level V: Extends into subcutaneous fat

540 M.N. Prieto and P.D. Wey

disease-affected region, called the “sentinel” nodes, of which there is at least one but sometimes as many as four. These sentinel nodes then are identified easily by the presence of radioactivity and dye and are removed selectively. If the sentinel node is free of melanoma, the remainder of the regional lymph basin will be disease-free in more than 95% of cases, and full lymph node dissection usually is not indicated. Full lymph node dissection is reserved for patients with positive sentinel nodes and, in the absence of distant metastases, may be therapeutic, although therapeutic efficacy is unproven to date. Nonetheless,

SNB is widely used in clinical practice in the treatment of interme- diate-thickness melanomas (1–4 mm) and in selection of patients for adjuvant therapy. For the patient in Case 5, then, excision and simultaneous SNB with possible lymph node dissection would be the next step in management.

For the patient with clinically appreciable lymphadenopathy, fineneedle aspiration (FNA) of regional lymph glands also is an appropriate means of evaluating the nodal basin. As with SNB, identification of a positive node is indication for full nodal basin dissection in melanoma of intermediate thickness.

In a melanoma thicker than 4 mm, full lymph node dissection after positive SNB or FNA usually is not indicated, as metastasis to distant sites is highly likely, eliminating any advantage of lymph node dissection in preventing disease progression. Thick melanomas should be excised with 2- to 3-cm margins (M.D. Anderson and Moffitt Cancer Centers, level II evidence).2

Thin melanomas (<1 mm), on the other hand, have a very low likelihood (<5%) of nodal involvement, and SNB typically does not play a role, since excision of thin melanoma lesions with 1-cm margins has been shown to be largely curative (World Health Organization Melanoma Trial, level I evidence).3

Staging and Treatment of Metastatic Disease

Sentinel node biopsy or fine-needle aspiration of clinically involved nodes is necessary for disease staging in melanomas >1 mm thick and has implications for outcome and future management. Chest x-ray, serum alkaline phosphatase, and lactate dehydrogenase, which, as stated previously, are recommended for melanomas >1 mm thick, also contribute to the metastatic workup for melanoma. A number of chemotherapeutic and immunotherapeutic agents have been tested for use as adjuvant therapy in the treatment of metastatic melanoma. Only interferon-alpha-2b has shown demonstrated efficacy and was approved for use by the Food and Drug Administration (FDA) in 1996 in therapy of resected high-risk melanoma. A high-dose regimen was demonstrated in randomized controlled studies (Eastern Cooper-

2 Heaton KM, Sussman JJ, Gershenwald JE, et al. Surgical margins and prognostic factors in patients with thick (>4 mm) primary melanoma. Ann Surg Oncol 1998;5: 322–328.

3 Veronesi U, Cascinelli N. Narrow excision (1-cm margin). A safe procedure for thin cutaneous melanoma. Arch Surg 1991;126:438–441.

542 M.N. Prieto and P.D. Wey

(26%)

(24%)

(26%)

Figure 30.1. Anatomic distribution and site-specific histologic subtypes of 1182 consecutive patients with soft tissue sarcomas seen at the University of Texas M.D. Anderson Cancer Center (University of Texas M.D. Anderson Cancer Center Sarcoma Database, June 1996–December 1998). MFH, malignant fibrous histiocytoma; ERMS, embryonal rhabdomyosarcoma; MPNT, malignant peripheral nerve sheath tumor. (Reprinted from Pisters PWT. Soft tissue sarcoma. In: Norton JA, Bollinger RR, Chang AE, et al, eds. Surgery: Basic Science and Clinical Practice. New York: Springer-Verlag, 2001, with permission.

to elucidate the extent and compartmentalization of the tumor and to clarify the involvement of neurovascular and other surrounding structures. These studies often can rule out a benign process such as a lipoma and provide anatomic information that may help determine the best biopsy approach. Magnetic resonance imaging has been regarded as the study of choice because of its ability potentially to differentiate tumor and muscle, while providing clear definition of fascial planes and neurovascular structures. The advantage of MRI over CT, however, remains controversial. Computed tomography is indeed a cost-effective option and has been reported to provide as much clinically useful information as MRI in the diagnosis and staging of soft tissue tumors.

Because of its large size, suspicious history, and deep location, this patient’s lesion should be biopsied by percutaneous core needle

Table 30.10. Indications for biopsy of a soft tissue lesion.

Noticeable enlargement

Size >5 cm

Persistence beyond 4–6 weeks

Deep location on exam

30. Skin and Soft Tissues 543

biopsy, a widely used method of biopsy that usually provides adequate tissue for diagnosis while being minimally invasive. Fine-needle aspiration is used by some, but tissue obtained using this method can be difficult to assess, and this technique typically is reserved for diagnosis of suspected recurrence. Many surgeons performing these biopsies tattoo the biopsy site for later excision, since tumor recurrence within the biopsy needle tract has been reported. The position of the biopsy site for these and other techniques is of significance, since sarcomas exhibit regional morphologic variation, and, as a result, multiple samples may be required for diagnosis.

Incisional or excisional biopsy of a suspicious soft tissue mass may be performed when definitive diagnosis cannot be achieved by less invasive means. Small, superficial lesions lend themselves to excisional biopsy, if not located nearby critical anatomic structures that would compromise appropriate surgical margins or in turn be compromised by such excision. For both excisional and incisional biopsy, incisions should be placed over the most superficial point of the tumor and should be oriented longitudinally along the axis of the extremity to facilitate wide local excision of the biopsy site and remaining tumor at a later time. Local hemostasis is critical to prevent seeding of tumor cells into adjacent tissues by hematoma.

With more than 30 histologic subtypes and with the anatomic heterogeneity and rarity of soft tissue sarcomas, a meaningful staging system that accurately describes all forms of the disease is in evolution. The American Joint Committee on Cancer–International Union

Against Cancer (AJCC-UICC) system is used widely and incorporates the standard tumor-node-metastasis (TNM) classification as well as histologic grading ranging from well-differentiated to undifferentiated and substaging based on tumor location relative to fascia (Table 30.11).5 It is important to note that, although node status is included in this classification scheme, sarcomas metastasize hematogenously, and, as such, node involvement has no specific prognostic significance except as a site of distant metastasis.

Tissue biopsy of the patient’s lesion in Case 6 revealed a grade 2, moderately differentiated liposarcoma. Staging of this patient’s disease calls for detailed imaging studies if not performed prior to biopsy: CT or MRI of the affected extremity to look for skip metastases or local bone involvement and plain film or CT of the chest.

Spread hematogenously, sarcomas of the extremities metastasize most frequently to the lungs. The grade of a sarcoma as determined by biopsy is related to the likelihood of metastasis. Generally, low-grade lesions are an indication for chest x-ray, while chest CT usually is indicated in high-grade lesions. Bone metastases are the second most common type of distant disease associated with soft tissue sarcoma; accordingly, technetium bone scanning also might be used by some in staging disease.

Treatment of extremity sarcoma has centered on surgical resection, which, until 10 to 20 years ago, entailed amputation of the affected

5 Greene FL, Page DL, Fleming ID, et al, eds. AJCC Cancer Staging Manual, 6th ed. New York: Springer-Verlag, 2002.

544 M.N. Prieto and P.D. Wey

Table 30.11. American Joint Committee on Cancer staging system for soft tissue sarcomas.

Source: Reprinted from Greene FL, Balch CM, Fleming ID, et al, eds. American Joint Committee on Cancer AJCC Cancer Staging Manual, 6th ed. New York: Springer-Verlag, 2002, with permission.

limb. Prospective randomized studies have shown, however, that limbsparing surgery with postoperative radiation therapy yields overall survival rates comparable to those achieved with amputation

(National Cancer Institute, level I evidence),6 and that this approach results in superior local control of disease compared to surgical resection alone (Table 30.12). Limb-sparing surgery requires full excision of the mass with wide margins rather than enucleation of the tumor pseudocapsule, which is associated with very high local recurrence rates. No studies to date have defined the ideal margin of resection, but 2 cm is an arbitrary and commonly used margin. It also should be noted that there is evidence that primary soft tissue sarcomas <5 cm may be treated with resection alone without radiotherapy.

Other therapies used in the treatment of localized soft tissue sarcoma of the extremities include chemotherapy, whose role remains controversial despite decades of randomized trials, combined chemotherapy and radiotherapy protocols, and hyperthermic isolated limb perfusion, which has shown usefulness in some settings and is currently in clinical trials.

The most effective treatment to date of soft tissue sarcoma metastasis, which occurs most frequently in the lungs, is surgical resection of pulmonary lesions. Unfortunately, metstatectomy benefits only a

6 Rosenberg SA, Tepper J, Glatstein E, et al. The treatment of soft tissue sarcoma of the extremities: prospective randomized evaluations of (1) limb sparing surgery plus radiation therapy compared with amputation and (2) the role of adjuvant chemotherapy. Ann Surg 1982;196:305–315.

546 M.N. Prieto and P.D. Wey

Algorithm 30.2. Management of nonmelanoma skin cancer. EDC, electrodesiccation and curettage.

small fraction of such patients (<15%), and hence it is critical that patient selection for pulmonary resection be conducted in an extremely cautious manner. The following commonly are accepted as criteria for patient selection: (1) the primary tumor is controlled or controllable, (2) there is no extrathoracic disease, (3) the patient is an appropriate medical candidate for thoracotomy and pulmonary resection, and (4) complete resection of all metastatic disease seems possible. In this way, the morbidity of thoracotomy can be limited to the few patients most likely to benefit from this aggressive procedure.

Retroperitoneal sarcomas are relatively rare, accounting for approximately 15% of all sarcomas. Their diagnosis, treatment, and management are beyond the scope of this chapter.

Summary

Given the extremely common presentation of skin lesions by patients to surgeons and general practitioners alike, it is vital that all physicians be comfortable differentiating those lesions that are thoroughly benign, those that are somewhat questionable, and those that are most likely malignant. Given the rise in incidence of all forms of skin cancer and

30. Skin and Soft Tissues 547

given the dismal outcomes associated with late diagnosis of squamous cell carcinoma and melanoma, recognizing the “red flags” of malignant skin lesions and knowing when to refer to a specialist for biopsy are essential skills. The general approach to the management of skin lesions is summarized in Algorithms 30.1 and 30.2.

Patient presents with extremity mass