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Surgery_Schwartz. which causes cessation of growth and, in most cases, actual regression of the lesions.103,104 Systemic corticosteroids and interferon-α can impede tumor progression, and laser therapy has been used as well. If tumors persist into adolescence leaving a cosmeti-cally undesirable defect, surgical resection may be considered. When surgical resection or debulking is considered, upfront selective embolization can help with planned resection.NeviNevi (singular, nevus) are areas of melanocytic hyperplasia or neoplasia. These collections can be found in the epidermis (junctional), partially in the dermis (compound), or completely within the dermis (dermal). They commonly develop in child-hood and young adulthood, and will sometimes spontaneously regress. Exposure to UV radiation is associated with increased density of these lesions.105 Nevi are typically symmetric and small. Congenital nevi are the result of abnormal development of melanocytes. The events leading to this abnormal develop-ment


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Surgery_Schwartz. increased density of these lesions.105 Nevi are typically symmetric and small. Congenital nevi are the result of abnormal development of melanocytes. The events leading to this abnormal develop-ment may also affect the surrounding cells, resulting in longer, darker hair. Congenital nevi are found in less than 1% of neo-nates, and when characterized as giant congenital nevi, they have up to a 5% chance of developing into a malignant mela-noma, and may do so even in the first years of childhood.106,107 Treatment, therefore, consists of surgical excision of the lesion as early as is feasible. For larger lesions, serial excision and tissue expansion may be required, with the goal of lesion exci-sion being maintenance of function and form while decreasing oncologic risk.Cystic LesionsCutaneous cysts are benign lesions that are characterized by overgrowth of epidermis towards the center of the lesion, resulting in keratin accumulation. Epidermoid cysts (often mistakenly referred to as


Surgery_Schwartz

Surgery_Schwartz. cysts are benign lesions that are characterized by overgrowth of epidermis towards the center of the lesion, resulting in keratin accumulation. Epidermoid cysts (often mistakenly referred to as sebaceous cysts) are classically the result of keratin-plugged pilosebaceous units. They commonly affect adult men and women, and present as a dermal or sub-cutaneous cyst with a single, keratin-plugged punctum at the skin surface, often at or above the upper chest and back. Epi-dermoid cysts are the most common cutaneous cyst and are histologically characterized by mature epidermis complete with granular layer. Another type of cystic lesion is known as a trichilemmal cyst. These cysts are derived from the outer sheath of hair follicles, and, in contrast to epidermoid cysts, lack a granular layer. They are almost always found on the scalp and more commonly in women. A third type of cutaneous cyst is a dermoid cyst. Dermoid cysts are congenital variants that occur as the result of persistent


Surgery_Schwartz

Surgery_Schwartz. They are almost always found on the scalp and more commonly in women. A third type of cutaneous cyst is a dermoid cyst. Dermoid cysts are congenital variants that occur as the result of persistent epithelium within embry-onic lines of fusion. They occur most commonly between the forehead and nose tip, and the most frequent site is the eye-brow. They can lie in the subcutaneous tissue or intracranially, and often communicate with the skin surface via a small fis-tula. These cystic structures contain epithelial tissue, hair, and a variety of epidermal appendages. Treatment for these cystic structures includes surgical excision with care taken to remove the cyst lining to prevent recurrence.7Brunicardi_Ch16_p0511-p0540.indd 52719/02/19 3:09 PM 528SPECIFIC CONSIDERATIONSPART IIKeratosisActinic Keratosis. Actinic keratoses are neoplasms of epi-dermal keratinocytes that represent a range in a spectrum of disease from sun damage to squamous cell carcinoma. They typically occur in


Surgery_Schwartz

Surgery_Schwartz. Keratosis. Actinic keratoses are neoplasms of epi-dermal keratinocytes that represent a range in a spectrum of disease from sun damage to squamous cell carcinoma. They typically occur in fair-skinned, elderly individuals in primarily sun-exposed areas, and UV radiation exposure is the greatest risk factor. There are multiple variants, and they can present as erythematous and scaly to hypertrophic, keratinized lesions. They can become symptomatic, causing bleeding, pruritis and pain. They can regress spontaneously, persist without change, and transform into invasive squamous cell carcinoma. It is estimated that approximately 10% of actinic keratoses will transform into invasive squamous cell carcinoma, and that pro-gression takes about 2 years on average.108 About 60% to 65% of squamous cell carcinomas are believed to originate from actinic keratoses. The presence of actinic keratoses also serves as a predictor of development of other squamous cell and basal cell carcinomas.109


Surgery_Schwartz

Surgery_Schwartz. cell carcinomas are believed to originate from actinic keratoses. The presence of actinic keratoses also serves as a predictor of development of other squamous cell and basal cell carcinomas.109 Treatment options are excision, fluorouracil, cautery and destruction, and dermabrasion.110,111Seborrheic Keratosis. Seborrheic keratoses are benign lesions of the epidermis that typically present as well-demarcated, “stuck on” appearing papules or plaques over elderly individu-als. Clonal expansion of keratinocytes and melanocytes make up the substance of these lesions. They carry no malignant potential and treatment is primarily for cosmetic purposes.Soft Tissue TumorsAcrochordons. Acrochordons, also known as skin tags, are benign, pedunculated lesions on the skin made up of epider-mal keratinocytes surrounding a collagenous core. Although they can become irritated or necrotic, their removal is generally cosmetic.Dermatofibromas. Dermatofibromas are benign cutaneous proliferations that


Surgery_Schwartz

Surgery_Schwartz. surrounding a collagenous core. Although they can become irritated or necrotic, their removal is generally cosmetic.Dermatofibromas. Dermatofibromas are benign cutaneous proliferations that appear most commonly on the lower extremi-ties of women. They appear as pink to brown papules that pucker or dimple in the center when the lesion is pinched. It remains unclear whether these lesions have a neoplastic etiology or if they are the result of minor trauma or infection.112 These lesions are typically asymptomatic, and treatment is only indicated for cosmetic concerns or when a histologic diagnosis is required. Surgical excision is the recommended treatment, although cryo-therapy and laser treatment may be used.113 In rare cases, a basal cell carcinoma may develop within a dermatofibroma.Lipomas. Lipomas are the most common subcutaneous neo-plasm and have no malignant potential.114 They present as a painless, slow-growing, mobile mass of the subcutaneous tissue. Usually less than 5 cm in


Surgery_Schwartz

Surgery_Schwartz. are the most common subcutaneous neo-plasm and have no malignant potential.114 They present as a painless, slow-growing, mobile mass of the subcutaneous tissue. Usually less than 5 cm in diameter, these neoplasms can reach much larger sizes. Lipomas are largely asymptomatic but may cause pain due to regional nerve deformation. Surgical resection is indicated in cases of local pain, mass effect, or cosmetically sensitive areas. The tumors are usually well circumscribed and amenable to surgical resection. Liposarcoma is a malignant fatty tumor that can mimic a lipoma, but is often deep-seated, rapidly growing, painful, and invasive. In these cases, cross-sectional imaging is recommended prior to any surgical resection.Neural TumorsNeuromas. Neuromas do not represent a true clonal prolifera-tion of neural tissue, but rather disordered growth of Schwann cells and nerve axons, often at the site of previous trauma. They can present within surgical scar lines or at the site of previous


Surgery_Schwartz

Surgery_Schwartz. of neural tissue, but rather disordered growth of Schwann cells and nerve axons, often at the site of previous trauma. They can present within surgical scar lines or at the site of previous trauma as flesh-colored papules or nodules and are typically painful.Schwannomas. A schwannoma is a benign proliferation of the Schwann cells of the peripheral nerve sheath, and can arise sporadically or in association with type 2 neurofibromatosis. It contains no axons, but may displace the affected nerve and cause pain along the distribution of the nerve.Neurofibromas. Neurofibromas, in contrast, are benign prolif-erations that are made up of all nerve elements, and arise as fleshy and nontender, sessile or pedunculated masses on the skin. They can arise sporadically or in association with type 1 neurofibroma-tosis, and in these cases, are associated with café-au-lait spots and Lisch nodules. They are often asymptomatic, but may be pruritic. The development of pain at the site of a previously


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Surgery_Schwartz. neurofibroma-tosis, and in these cases, are associated with café-au-lait spots and Lisch nodules. They are often asymptomatic, but may be pruritic. The development of pain at the site of a previously asymptomatic neurofibroma may indicate a rare malignant transformation and requires surgical excision and biopsy.MALIGNANT TUMORSBasal Cell CarcinomaBasal cell carcinoma (BCC) is the most common tumor diag-nosed in the United States, with an estimated one million new cases occurring each year. It represents 75% of non-melanoma skin cancers and 25% of all cancers diagnosed each year.115 BCC is seen slightly more commonly in males and indi-viduals over the age of 60, though the incidence in younger age groups is increasing. The primary risk factor for disease devel-opment is sun exposure (UVB rays more than UVA rays), par-ticularly during adolescence. The pathogenesis of BCC stems from mutations of genes involved in tumor suppression, often caused by ionizing radiation. The p53 tumor


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Surgery_Schwartz. (UVB rays more than UVA rays), par-ticularly during adolescence. The pathogenesis of BCC stems from mutations of genes involved in tumor suppression, often caused by ionizing radiation. The p53 tumor suppressor gene is defective in approximately 50% of cases.116 There is a latency period of 20 to 50 years.BCC tends to occur on sun-exposed areas of the skin, most commonly the nose and other parts of the face. A malignant lesion on the upper lip is almost always BCC, and BCC is the most common malignant eyelid tumor. Because of the photo-protective effect of melanin, dark-skinned individuals are far less commonly affected. Other risk factors for development of BCC include immune suppression, chemical exposure, and ion-izing radiation exposure. There are also genetic susceptibilities to development of BCC in conditions such as xeroderma pig-mentosa, unilateral basal cell nevus syndrome, and nevoid BCC syndrome.115 The natural history of BCC is typically one of local invasion rather than


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Surgery_Schwartz. of BCC in conditions such as xeroderma pig-mentosa, unilateral basal cell nevus syndrome, and nevoid BCC syndrome.115 The natural history of BCC is typically one of local invasion rather than distant metastasis, but untreated BCC can often result in significant morbidity.There are multiple variants of BCC, and presentation can range from red, flesh-colored, or white macule or papule, to nodules and ulcerated lesions. Growth patterns of these lesions can either be well-circumscribed or diffuse and the most com-mon types of BCC are nodular and micronodular, superficial spreading, and infiltrative.117 The most common subtype is the nodular variant, characterized by raised, pearly pink papules with telangiectasias and occasionally a depressed tumor center with raised borders giving the classic “rodent ulcer” appearance. Superficial spreading BCC is confined to the epidermis as a flat, pink, scaling or crusting lesion, often mistaken for eczema, actinic keratosis, fungal infection, or


Surgery_Schwartz

Surgery_Schwartz. “rodent ulcer” appearance. Superficial spreading BCC is confined to the epidermis as a flat, pink, scaling or crusting lesion, often mistaken for eczema, actinic keratosis, fungal infection, or psoriasis. This subtype typically appears on the trunk or extremities and the mean age of diagnosis is 57 years. The infiltrative form appears on the 8Brunicardi_Ch16_p0511-p0540.indd 52819/02/19 3:09 PM 529THE SKIN AND SUBCUTANEOUS TISSUECHAPTER 16head and neck in the late 60s, often at embryonic fusion lines,117 with an opaque yellow-white color that blends with surrounding skin and has no raised edges.118 The morpheaform subtype rep-resents 2% to 3% of all BCC and is the most aggressive subtype. It usually presents as an indurated macule or papule with the appearance of an enlarging scar. The clinical margins are often indistinct, and the rate of positive margins after excision is high. There is also a pigmented variant of BCC that can be difficult to distinguish from certain melanoma


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Surgery_Schwartz. The clinical margins are often indistinct, and the rate of positive margins after excision is high. There is also a pigmented variant of BCC that can be difficult to distinguish from certain melanoma subtypes.Treatment of BCC varies according to size, location, type, and highor low-risk. Treatment options include surgical exci-sion, medical, or destructive therapies. Surgical excision should include 4 mm margins for small, primary BCC on cosmetically sensitive areas, and 10 mm margins otherwise.119 Mohs micro-surgical excision is sequential horizontal excision and has been shown to be cost-effective and associated with low recurrence rates for BCC (1%).120,121 It is the treatment of choice for mor-pheaform or other BCC with aggressive features, poorly delin-eated margins, recurrent tumors, or cosmetically sensitive areas, especially in the midface. A common approach used by derma-tologists for very small (<2 mm) and low risk lesions is cau-tery and destruction, although it should be


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Surgery_Schwartz. or cosmetically sensitive areas, especially in the midface. A common approach used by derma-tologists for very small (<2 mm) and low risk lesions is cau-tery and destruction, although it should be kept in mind that the local cure rates can be operator and institution dependent. Other destructive techniques include cryosurgery and laser ablation. Radiation therapy can be used as adjuvant therapy following surgery, or as primary therapy in poor surgical candidates with low-risk lesions. The practitioner must be aware of the poten-tial consequences of radiation therapy, including poor cosmetic outcomes and future cancer risk.Superficial medical therapies are generally reserved for patients in whom surgical and radiation treatment is not an option. Topical imiquimod or 5-fluorouracil have been used for periods of 6 to 16 weeks for small, superficial BCC of the neck, trunk or extremities.122-126 Lastly, topical photodynamic therapy has shown some benefit in treatment of premalignant or


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Surgery_Schwartz. been used for periods of 6 to 16 weeks for small, superficial BCC of the neck, trunk or extremities.122-126 Lastly, topical photodynamic therapy has shown some benefit in treatment of premalignant or super-ficial low-risk lesions as well.Patients with BCC need to have regular follow-up with full skin examinations every 6 to 12 months. Sixty-six percent of recurrences develop within 3 years, and with a few excep-tions occurring decades after initial treatment, the remaining recur within 5 years of initial treatment.121,127 A second primary BCC may develop after treatment and, in 40% of cases, presents within the first 3 years after treatment.Squamous Cell CarcinomaSquamous cell carcinoma (SCC) is the second most common skin cancer and accounts for approximately 100,000 cases each year. The primary risk factor for the development of SCC is UV radiation exposure128; however, other risks include light Fitzpatrick skin type (I or II), environmental factors such as chemical agents, physical


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Surgery_Schwartz. primary risk factor for the development of SCC is UV radiation exposure128; however, other risks include light Fitzpatrick skin type (I or II), environmental factors such as chemical agents, physical agents (ionizing radiation), pso-ralen, HPV-16 and -18 infections, immunosuppression, smok-ing, chronic wounds, burn scars, and chronic dermatoses. Heritable risk factors include xeroderma pigmentosum, epider-molysis bullosa, and oculocutaneous albinism.SCC classically appears as a scaly or ulcerated papule or plaque, and bleeding of the lesion with minimal trauma is not uncommon, but pain is rare. It can exhibit in situ (confined to the epidermis) or invasive subtypes. The most common in situ variant of SCC is actinic keratosis, described previously in this chapter. Invasive squamous cell carcinomas may arise de novo, but more commonly evolve from these precursors. Another in 9Figure 16-9. Squamous cell carcinoma forming in a chronic wound.situ variant is known as Bowen disease. This is


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Surgery_Schwartz. may arise de novo, but more commonly evolve from these precursors. Another in 9Figure 16-9. Squamous cell carcinoma forming in a chronic wound.situ variant is known as Bowen disease. This is characterized by full-thickness epidermal dysplasia and clinically appears as a scaly, erythematous patch often with pigmentation and fis-suring. When it occurs on the glans penis, it is known as eryth-roplasia of Queyrat. Ten percent of these cases will eventually become invasive.129 Outside of these instances, most in situ cases grow slowly and do not progress to invasive disease.Invasive SCC is characterized by invasion through the basement membrane into the dermis of the skin. It usually arises from an actinic keratosis precursor, but de novo varieties do occur and are higher risk. De novo invasive SCC commonly occurs in organ transplant and immunocompromised patients, and has a metastatic rate as high as 14%.130 De novo invasive SCC arising in areas of chronic wounds or burn scars are known


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Surgery_Schwartz. SCC commonly occurs in organ transplant and immunocompromised patients, and has a metastatic rate as high as 14%.130 De novo invasive SCC arising in areas of chronic wounds or burn scars are known as Marjolin’s ulcers, and have a higher metastatic potential (Fig. 16-9). Keratoacanthoma is now being accepted as a sub-type of SCC that is characterized by a rapidly growing nodule with a central keratin plug.131 The natural history of invasive disease depends on location and inherent tumor characteristics. Clinical risk factors for recurrence include presentation with neurologic symptoms, immunosuppression, tumor with poorly defined borders, and tumor that arises at a site of prior radiation. Perineural involvement also has a poorer survival with increased local recurrence and lymph node metastasis. Grades of differen-tiation are based on the ratio of differentiated to undifferentiated cells, with a lower ratio associated with a greater metastatic and recurrent potential. Large (>2 cm)


Surgery_Schwartz

Surgery_Schwartz. Grades of differen-tiation are based on the ratio of differentiated to undifferentiated cells, with a lower ratio associated with a greater metastatic and recurrent potential. Large (>2 cm) lesions, depth of invasion >4 mm, rapid growth, and location on the ear, lips, nose, scalp, or genitals are all also indicators of worse prognosis.When feasible, wide surgical excision including subcuta-neous fat is the treatment of choice for SCC. Margins of 4 mm are recommended for low-risk lesions and 6 mm for high-risk lesions.128 Mohs microsurgical excision is indicated for posi-tive margins, recurrent tumors, sites where cosmesis or function preservation is critical, poorly differentiated tumors, invasive lesions, and verrucous tumors. Using this modality often results in lower recurrence rates.127,130 It has also found use in nail bed lesions and in those arising in a background of osteomyelitis. The role of lymph node dissection in the setting of SCC contin-ues to evolve. Lymphadenectomy is


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Surgery_Schwartz. It has also found use in nail bed lesions and in those arising in a background of osteomyelitis. The role of lymph node dissection in the setting of SCC contin-ues to evolve. Lymphadenectomy is indicated following fine-needle aspiration or core biopsy for clinically palpable lymph nodes or nodes detected on cross-sectional imaging. Nodes Brunicardi_Ch16_p0511-p0540.indd 52919/02/19 3:09 PM 530SPECIFIC CONSIDERATIONSPART IIshould also be removed from susceptible regional lymph node basins in patients with SCC in the setting of chronic wounds. Patients with parotid disease benefit from a superficial or total parotidectomy (with facial nerve preservation) and adjuvant radiotherapy. Sentinel lymph node dissection may be used in high risk cases with clinically negative nodal disease. Radiation therapy is typically reserved as primary therapy for those who are poor surgical candidates, and as adjuvant therapy after surgi-cal resection for large, high-risk tumors. When used as primary


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Surgery_Schwartz. therapy is typically reserved as primary therapy for those who are poor surgical candidates, and as adjuvant therapy after surgi-cal resection for large, high-risk tumors. When used as primary therapy, cure rates may approach 90%.121MelanomaBackground. In 2017, an estimated 87,110 new cases of melanoma were diagnosed, as well as 9730 melanoma-related deaths. The incidence of melanoma is rising faster than most other solid malignancies, and these numbers likely represent an underestimation given the many in situ and thin melanoma cases that are underreported. These tumors primarily arise from mela-nocytes at the epidermal-dermal junction but may also originate from mucosal surfaces of the oropharynx, nasopharynx, eyes, proximal esophagus, anorectum, and female genitalia. Mela-noma characteristically metastasizes quite often, and can travel to most other tissues in the body. This metastasis confers a poor prognosis in patients, with a median life span of 6 to 8 months after


Surgery_Schwartz

Surgery_Schwartz. characteristically metastasizes quite often, and can travel to most other tissues in the body. This metastasis confers a poor prognosis in patients, with a median life span of 6 to 8 months after diagnosis.132The most important risk factor for the development of melanoma is exposure to UV radiation. It was recently reported that greater than 10 tanning bed sessions by adolescents and young adults increased their relative risk of developing mela-noma twofold,133 and there is a positive association with inter-mittent childhood sunburns and melanoma development.134 There is also an association with residence at high altitudes or in close proximity to the equator. Both personal and family history of melanomas increase the risk of primary melanoma develop-ment. Individuals with dysplastic nevi have a 6% to10% overall lifetime risk of melanoma, with tumors arising from preexisting nevi or de novo. Individuals with familial atypical multiple-mole melanoma syndrome have numerous melanocytic


Surgery_Schwartz

Surgery_Schwartz. have a 6% to10% overall lifetime risk of melanoma, with tumors arising from preexisting nevi or de novo. Individuals with familial atypical multiple-mole melanoma syndrome have numerous melanocytic nevi and a greatly increased risk of cutaneous melanoma. Congenital nevi increase the risk for melanoma proportionally with size, and giant congenital nevi (generally considered >20 cm in diameter) are associated with a 5% to 8% lifetime risk. Melanoma development is strongly associated with the p16/CDK4,6/Rb and p14ARF/HMD2/p53 tumor suppressor pathways and the RAF-MEK-ERK and PI3K-Akt oncogenic pathways.135Clinical Presentation. The presentation of melanoma is com-monly used to determine subtype but often starts as a localized, radial growth phase followed by a more aggressive, vertical growth phase. Approximately 30% of melanoma lesions arise from a preexisting melanocytic nevus. The most common sub-type of melanoma is superficial spreading (Fig. 16-10). This accounts for 50% to 70% of


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Surgery_Schwartz. phase. Approximately 30% of melanoma lesions arise from a preexisting melanocytic nevus. The most common sub-type of melanoma is superficial spreading (Fig. 16-10). This accounts for 50% to 70% of melanomas and typically arises from a precursor melanocytic nevus. Nodular subtype accounts for 15% to 30% of melanomas, and typically arises de novo, most commonly in men and on the trunk (Figs. 16-11 and 16-12). This subtype is aggressive with an early vertical growth pat-tern and is often diagnosed at a later stage. Up to 5% of these lesions will lack melanin and can be mistaken for other cutane-ous lesions. Lentigo maligna represents 10% of melanoma cases and is a less aggressive subtype of melanoma in situ that typi-cally arises on sun-exposed areas of the head and neck. Acral Figure 16-10. Primary cutaneous melanoma seen in the scalp of a 61-year-old male.Figure 16-11. Nodular melanoma seen in the leg of a 55-year-old male.lentiginous melanoma accounts for 29% to 72% of melanomas in


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Surgery_Schwartz. cutaneous melanoma seen in the scalp of a 61-year-old male.Figure 16-11. Nodular melanoma seen in the leg of a 55-year-old male.lentiginous melanoma accounts for 29% to 72% of melanomas in dark-skinned individuals, is occasionally seen in Caucasians, and is found on palmar, plantar, and subungual surfaces. This subtype is not thought to be due to sun exposure.Melanoma most commonly manifests as cutaneous dis-ease, and clinical characteristics of malignant transformation are often remembered by the initialism ABCDE. These lesions are typically Asymmetric with irregular Borders, Color variations, a Diameter greater than 6 mm, and are undergoing some sort of Evolution or change. Other key clinical characteristics include a pigmented lesion that has enlarged, ulcerated, or bled. Amela-notic lesions appear as raised pink, purple, or flesh-colored skin papules and are often diagnosed late.Diagnosis and Staging. Workup should begin with a his-tory and physical exam. The entire skin should be


Surgery_Schwartz

Surgery_Schwartz. appear as raised pink, purple, or flesh-colored skin papules and are often diagnosed late.Diagnosis and Staging. Workup should begin with a his-tory and physical exam. The entire skin should be checked for synchronous primaries, satellite lesions, and in-transit metas-tases, and all nodal basins should be examined for lymphade-nopathy. Suspicious lesions should undergo excisional biopsy with 1to 3-mm margins; however, tumors that are large or are in a cosmetically or anatomically challenging area can be approached by incisional biopsy, including punch biopsy.136 Brunicardi_Ch16_p0511-p0540.indd 53019/02/19 3:09 PM 531THE SKIN AND SUBCUTANEOUS TISSUECHAPTER 16ABCFigure 16-12. A. AP view of advanced melanoma in a 59-year-old male. B. Lateral view C. After resection and reconstruction with skin grafting.Tissue specimen should include full thickness of the lesion and a small section of normal adjacent skin to aid the pathologist in diagnosis. Clinically suspicious lymph nodes should


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Surgery_Schwartz. skin grafting.Tissue specimen should include full thickness of the lesion and a small section of normal adjacent skin to aid the pathologist in diagnosis. Clinically suspicious lymph nodes should undergo fine-needle aspiration (FNA), as this has been shown to have a high sensitivity and specificity for detection of melanoma in large lymph nodes.136-139Melanoma is characterized according to the American Joint Committee on Cancer (AJCC) as localized disease (stage I and II), regional disease (stage III), or distant metastatic disease (stage IV). The Breslow tumor thickness replaced the Clark’s level as the most important prognostic indicator for melanoma stag-ing.132,140 The Breslow tumor thickness measures the depth of penetration of the lesions from the top of the granular layer of the epidermis into the dermal layer and is directly related to the risk of disease progression. Tumor ulceration, mitotic rate ≥1 per mm2, and metastasis are all also associated with worse prognosis. In the


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Surgery_Schwartz. into the dermal layer and is directly related to the risk of disease progression. Tumor ulceration, mitotic rate ≥1 per mm2, and metastasis are all also associated with worse prognosis. In the presence of regional node metastasis, the num-ber of nodes affected is the most important prognostic indicator. For stage IV disease, the site of metastasis is strongly associated with prognosis, and elevated lactate dehydrogenase (LDH) is associated with a worse prognosis.141There is no supportive evidence for chest X-ray or com-puted tomography (CT) in the staging of patients unless there is positive regional lymph node disease, although it can be used to work up specific signs and symptoms when metastatic disease is suspected.136 In patients with stage III or greater disease, there is a high risk for distant metastasis, and imaging is recommended for baseline staging. These patients should receive additional imaging that includes CT of the chest, abdomen, and pelvis; whole-body positon


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Surgery_Schwartz. risk for distant metastasis, and imaging is recommended for baseline staging. These patients should receive additional imaging that includes CT of the chest, abdomen, and pelvis; whole-body positon emission tomography (PET)-CT; or brain magnetic resonance imaging (MRI).136The sentinel lymph node biopsy (SLNB) technique for melanoma was introduced in 1992 and has become a corner-stone in the management of melanoma, although its role in man-agement continues to be refined. SLNB is a standard staging procedure to evaluate the regional nodes for patients with clini-cally node-negative malignant melanoma. Detecting subclinical nodal metastasis in may benefit from lymphadenectomy or adju-vant therapy. This technique identifies the first draining lymph node from the primary lesion and has shown excellent accuracy and significantly less morbidity compared to complete resection of nodal basins. It is almost always performed at the time of initial wide excision, as SLN mapping after lymphatic


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Surgery_Schwartz. excellent accuracy and significantly less morbidity compared to complete resection of nodal basins. It is almost always performed at the time of initial wide excision, as SLN mapping after lymphatic violation from surgical excision could decrease the accuracy of the test. Recently, the results of MSLT-1, an international, multicenter, phase III trial were published. This study randomized clinically node negative patients to either SLNB at the time of primary melanoma excision (and completion lymphadenectomy if posi-tive) or nodal basin monitoring (and delayed complete lymph-adenectomy for recurrent lymph node disease).142 The results of this study demonstrated that SLNB, with immediate lymphad-enectomy if positive, improved disease-free survival by 7% and 10% in patients with intermediate thickness (1.2–3.5 mm) and thick (>3.5 mm) lesions respectively. The use of SLNB in lesions <1.2 mm thick did not affect disease-free survival. SLNB should also be offered to thin lesions with


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Surgery_Schwartz. thickness (1.2–3.5 mm) and thick (>3.5 mm) lesions respectively. The use of SLNB in lesions <1.2 mm thick did not affect disease-free survival. SLNB should also be offered to thin lesions with high-risk features (thickness >0.75, ulceration, mitoses ≥1 per mm2.136 The SLNB involves preoperative lymphoscintigraphy with intradermal injections of technetium-sulfur colloid to delineate lymphatic drainage and intraoperative intradermal injection of 1 mL of isosulfan or methylene blue dye near the tumor or biopsy site. (Figs. 16-13 and 16-14). The radioactive tracer-dye combination allows the sentinel node to be identified in 98% of cases. An incision over the lymph node basin of interest allows nodes to be excised and studied with hematoxylin and eosin and immunohistochemistry (S100, HMB45, and MART-1/Melan-A) staining (Fig. 16-15). 10Brunicardi_Ch16_p0511-p0540.indd 53119/02/19 3:09 PM 532SPECIFIC CONSIDERATIONSPART IIABSentinellymph nodeInjection siteSurgical exposure of sentinel


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Surgery_Schwartz. and MART-1/Melan-A) staining (Fig. 16-15). 10Brunicardi_Ch16_p0511-p0540.indd 53119/02/19 3:09 PM 532SPECIFIC CONSIDERATIONSPART IIABSentinellymph nodeInjection siteSurgical exposure of sentinel lymph nodeAfferent lymphaticchannelsSentinellymph nodePrimary melanomaSentinellymphnodeInguinal nodesABCFLOWINJ SITEAxillaryNODEANTFLOWPOSTTymphoMelanoma Primary Injection SiteSubmanibular Lymph nodesPopliteal nodesFigure 16-13. After injection of radioactive technetium-99–labeled sulfur colloid tracer at the primary cutaneous melanoma site, sentinel lymph node basins are identified. A. Lymphoscintig-raphy of 67-year-old male with a malignant melanoma of the right heel; sentinel lymph nodes in both the right popliteal fossa and inguinal region. B. Lymphoscintigraphy of 52-year-old male with a malignant melanoma of the posterior right upper arm; sentinel lymph node in the right axillary region. C. Lymphoscintigraphy of 69-year-old male with a facial melanoma; sentinel lymph nodes in the


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Surgery_Schwartz. a malignant melanoma of the posterior right upper arm; sentinel lymph node in the right axillary region. C. Lymphoscintigraphy of 69-year-old male with a facial melanoma; sentinel lymph nodes in the submandibular region. ANT = anterior; INJ = injection; POST = posterior.Risks of this technique are uncommon but include skin necrosis near the site of injection, anaphylactic shock, lymphedema, sur-gical site infections, seromas, and hematomas.Surgical Management of the Primary Tumors and Lymph Nodes. The appropriate excision margin is based on primary tumor thickness. Several retrospective studies suggest that for melanoma in situ, 0.5 to 1 cm margins are sufficient.143-145 We believe that 1-cm margins should be obtained in anatomically fea-sible areas given the possibility of an incidental finding of a small invasive component in permanent sections. Several studies com-pared 1to 3-cm margins and 2to 5-cm margins in melanoma <2 mm thick, and 2to 4-cm margins in melanoma lesions 1 to


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Surgery_Schwartz. finding of a small invasive component in permanent sections. Several studies com-pared 1to 3-cm margins and 2to 5-cm margins in melanoma <2 mm thick, and 2to 4-cm margins in melanoma lesions 1 to 4 mm thick and found no difference. 146-149 A British trial suggested that there is a limit to how narrow margins can be for melanomas >2 mm thick by showing that 1-cm margins provide worse outcomes compared to 3-cm margins.150 Tumors <1 mm thick require 0.5 to 1 cm margins. Tumors 1 to 2 mm thick require 1 to 2 cm margins, and tumors >2 mm thick require 2-cm margins.Completion lymphadenectomy is commonly performed in cases of sentinel nodes with metastatic disease, but it has been shown that most of these nodal basins do not have addi-tional disease. Thus, many surgeons do not perform routine completion lymphadenectomy for positive nodes, and data from the MSLT-2 may provide guidance. It has been shown that those patients with nonsentinel lymph node positivity found on completion lymph


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Surgery_Schwartz. completion lymphadenectomy for positive nodes, and data from the MSLT-2 may provide guidance. It has been shown that those patients with nonsentinel lymph node positivity found on completion lymph node dissection after a positive SLN have higher rates of recurrence and lower rates of sur-vival. The therapeutic value, however, has not been clearly demonstrated. In patients with clinically positive lymph nodes but absent signs of distant metastasis on PET-CT, therapeu-tic lymph node dissection is associated with 5-year survival rates of 30% to 50%. In these cases, resection of the primary melanoma lesion and a completion lymphadenectomy should be performed.Individuals with face, anterior scalp, and ear prima-ries who have a positive SLNB should undergo a superficial parotidectomy in addition to a modified radical neck dissection. Figure 16-14. Technique of sentinel lymph node biopsy for cutaneous melanoma. A. After injection of radioactive technetium-99–labeled sulfur colloid tracer at


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Surgery_Schwartz. to a modified radical neck dissection. Figure 16-14. Technique of sentinel lymph node biopsy for cutaneous melanoma. A. After injection of radioactive technetium-99–labeled sulfur colloid tracer at a lower abdominal wall primary cutaneous melanoma site, B. sentinel lymph node basins are identified. (Reproduced with permission from Gershenwald JE, Ross MI: Sentinel-lymph-node biopsy for cutane-ous melanoma, N Engl J Med. 2011 May 5;364(18):1738-1745.)Brunicardi_Ch16_p0511-p0540.indd 53219/02/19 3:09 PM 533THE SKIN AND SUBCUTANEOUS TISSUECHAPTER 16ABFigure 16-15. Operation of sentinel lymph node biopsy for cutaneous melanoma. After preoperative injection of radioactive technetium-99–labeled sulfur colloid tracer and intraoperative injection of Lymphazurin blue dye around the primary melanoma excision site, the nodal basin of interest is identified. An incision is made directly overlying the lymph node basin in the posterior axillary space. The sentinel lymph nodes are identified and


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Surgery_Schwartz. excision site, the nodal basin of interest is identified. An incision is made directly overlying the lymph node basin in the posterior axillary space. The sentinel lymph nodes are identified and excised.Patients with positive sentinel nodes in the inguino-femoral nodal basin should undergo an inguino-femoral lymphadenec-tomy that includes removal of Cloquet’s node. If Cloquet’s node is positive or the patient has three or more nodes that contain melanoma metastases the probability of clinically occult posi-tive pelvic nodes is increased. The effect of ileo-obturator lymph node dissection on the survival of these patients is unknown.Surgery for Regional and Distant Metastasis. Nonmeta-static, in-transit disease should undergo excision to clear mar-gins when feasible. However, disease not amenable to complete excision derives benefit from isolated limb perfusion (ILP) and isolated limb infusion (ILI) (Fig. 16-16). These two modali-ties are used to treat regional disease, and their


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Surgery_Schwartz. not amenable to complete excision derives benefit from isolated limb perfusion (ILP) and isolated limb infusion (ILI) (Fig. 16-16). These two modali-ties are used to treat regional disease, and their purpose is to administer high doses of chemotherapy, commonly melphalan, to an affected limb while avoiding systemic drug toxicity. ILI was shown to provide a 31% response rate in one study, while hyperthermic ILP provided a 63% complete response rate in an independent study.151-154The most common sites of metastasis of melanoma are the lung and liver. These are followed by the brain, gastroin-testinal tract, distant skin, and subcutaneous tissue. A limited subset of patients with small-volume, limited distant metastases to the brain, gastrointestinal tract, or distant skin can be treated with surgical resection or directed radiation. Liver metastases are better dealt without surgical resection unless they arise from an ocular primary. Adjuvant therapy after resection of meta-static


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Surgery_Schwartz. with surgical resection or directed radiation. Liver metastases are better dealt without surgical resection unless they arise from an ocular primary. Adjuvant therapy after resection of meta-static lesions is not standard of care. However, there are ongo-ing clinical trials addressing whether drugs and vaccines will be beneficial in this setting.115 Surgery may provide palliation for patients with gastrointestinal obstruction, gastrointestinal hem-orrhage, and nongastrointestinal hemorrhage. Radiotherapy for symptomatic bony or brain metastases provides palliation in dif-fuse disease.Adjuvant and Palliative Therapies. Eastern Cooperative Oncology Group (ECOG) Trials 1684, 1690, and 1694 were prospective randomized controlled trials that demonstrated Overhead heaterHot air blanketVenouscatheterArterialcatheterPneumatictourniquetPumpchamber25cc SyringeWarmingcoilEsmarchbandageDrug inpre-warmedsalineFigure 16-16. Isolated limb infusion. Schematic of isolated limb infusion of lower


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Surgery_Schwartz. SyringeWarmingcoilEsmarchbandageDrug inpre-warmedsalineFigure 16-16. Isolated limb infusion. Schematic of isolated limb infusion of lower extremity. (Adapted with permis-sion from Testori A, Verhoef C, Kroon HM, et al: Treatment of melanoma metas-tases in a limb by isolated limb perfusion and isolated limb infusion, J Surg Oncol. 2011 Sep;104(4):397-404.)Brunicardi_Ch16_p0511-p0540.indd 53319/02/19 3:09 PM 534SPECIFIC CONSIDERATIONSPART IIdisease-free survival advantages in patients with melanoma >4 mm in thickness with or without lymph node involvement if they received adjuvant treatment with high-dose interferon (IFN).155-157 A European Organization for Research and Treat-ment of Cancer (EORTC) trial also showed recurrence-free survival benefit with pegylated IFN.158 It is important to note that IFN therapy is not well tolerated and the pooled analysis of these trials did not show an improvement in overall survival benefit.Most patients with melanoma will not be surgical


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Surgery_Schwartz. to note that IFN therapy is not well tolerated and the pooled analysis of these trials did not show an improvement in overall survival benefit.Most patients with melanoma will not be surgical candi-dates. Although medical options for melanoma have historically been poor, several recent studies have shown promise in drug therapy for metastatic melanoma. BRAF inhibitors (sorafenib), anti-PD1 antibodies, CTLA antibodies (ipilimumab), and high-dose interleukin-2 (IL-2) with and without vaccines have been shown in randomized studies to provide survival benefit in metastatic disease.159-165 Despite the excitement of recent drugs, surgery will likely play an adjunct role in treating individuals who develop resistance to these drugs over time.Special Circumstances. Special circumstances of note are melanoma in pregnant women, melanoma of unknown prima-ries, and noncutaneous melanomas. The prognosis of pregnant patients is similar to women who are not pregnant. Extrapo-lation of studies


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Surgery_Schwartz. note are melanoma in pregnant women, melanoma of unknown prima-ries, and noncutaneous melanomas. The prognosis of pregnant patients is similar to women who are not pregnant. Extrapo-lation of studies examining the SLNB technique in pregnant women with breast cancer suggests lymphoscintigraphy may be done safely during pregnancy without risk to the fetus (blue dye is contraindicated). General anesthesia should be avoided during the first trimester, and local anesthetics should be used during this time. It has been suggested by some that after excising the primary tumor during pregnancy, the SLNB may be performed after delivery.Unknown primary melanoma occurs in 2% to 5% of cases and most commonly occurs in the lymph nodes. In these cases, a thorough search for the primary lesion should be sought, includ-ing eliciting a history about prior skin lesions, skin procedures (e.g., curettage and electrodessication, excision, laser), and review of any prior “benign” pathology. The surgeon


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Surgery_Schwartz. be sought, includ-ing eliciting a history about prior skin lesions, skin procedures (e.g., curettage and electrodessication, excision, laser), and review of any prior “benign” pathology. The surgeon should be aware that melanoma is known to spontaneously regress because of an immune response. Melanoma of unknown pri-mary has survival rates comparable to melanoma diagnosed with a known primary of the same stage.The most common noncutaneous disease site is ocular melanoma, and treatment of this condition includes photocoag-ulation, partial resection, radiation, or enucleation.166-168 Ocular melanomas exclusively metastasize to the liver and not regional lymph nodes, and some patients benefit from liver resection. Melanoma of the mucous membranes most commonly presents in the oral cavity, oropharynx, nasopharynx, paranasal sinus, anus, rectum, and female genitalia. Patients with this presenta-tion have a worse prognosis (10% 5-year survival) than patients with cutaneous melanomas.


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Surgery_Schwartz. oropharynx, nasopharynx, paranasal sinus, anus, rectum, and female genitalia. Patients with this presenta-tion have a worse prognosis (10% 5-year survival) than patients with cutaneous melanomas. Management should be excision to negative margins, and radical resections should be avoided because the role of surgery is locoregional control, not cure. Generally speaking, lymph node dissection should be avoided because the benefit is unclear.Merkel Cell CarcinomaMerkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin whose incidence has been rapidly increas-ing. Although it is a much rarer malignancy than melanoma, the prognosis is much worse, with a 5-year survival of 46%.169 Merkel cells are epidermal appendages involved in the sensation Figure 16-17. Merkel cell carcinoma seen just above the left knee in a 44-year-old female.of light touch, and along with Merkel cell carcinoma, are cyto-keratin-20 positive. This stain is now used to confirm the diag-nosis. Other


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Surgery_Schwartz. seen just above the left knee in a 44-year-old female.of light touch, and along with Merkel cell carcinoma, are cyto-keratin-20 positive. This stain is now used to confirm the diag-nosis. Other risk factors include age >65 years (the median age of diagnosis is 70 years), UV exposure, Merkel cell polyoma virus, and immunosuppression. MCC typically presents as a rapidly growing, flesh-colored to red or purple papule or plaque (Fig. 16-17). Regional nodes are involved in 30% of patients at diagnosis, and 50% will develop systemic disease (skin, lymph nodes, liver, lung, bone, and brain).170,171 There are no standard-ized diagnostic imaging studies for staging, but CT of the chest, abdomen, pelvis and octreotide scans may provide useful infor-mation when clinically indicated.After a thorough skin examination, treatment should begin by evaluating nodal basins. Patients without clinical nodal dis-ease should undergo an SLNB prior to wide local excision because studies suggest a benefit.172


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Surgery_Schwartz. skin examination, treatment should begin by evaluating nodal basins. Patients without clinical nodal dis-ease should undergo an SLNB prior to wide local excision because studies suggest a benefit.172 In patients with sentinel lymph nodes with metastatic disease, completion lymphad-enectomy and/or radiation therapy may follow, and in patients with node-negative disease, observation or radiation therapy should be considered.172 SLNB is important for staging and treatment, and the literature suggests that it predicts recurrenceand relapse-free survival. Elective lymph node dissection may decrease regional nodal recurrence and in-transit metastases. Patients with clinically positive nodes should have an FNA to confirm disease. If positive, a metastatic staging workup should follow, and, if negative, treatment of the primary and nodal basin as managed for sentinel lymph node-positive disease should be considered. A negative FNA and open biopsy-negative disease should be managed by


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Surgery_Schwartz. if negative, treatment of the primary and nodal basin as managed for sentinel lymph node-positive disease should be considered. A negative FNA and open biopsy-negative disease should be managed by treatment of the primary disease alone. Brunicardi_Ch16_p0511-p0540.indd 53419/02/19 3:09 PM 535THE SKIN AND SUBCUTANEOUS TISSUECHAPTER 16Patients with metastatic disease should be managed according to consensus from a multidisciplinary tumor board.Important surgical principles for excision of the primary lesion are to excise with wide margins down to fascia and com-plete circumferential and peripheral deep-margin assessment. Recommended management for margins is 1 to 3 cm, but there are no randomized trials defining these margins. Chemotherapy and adjuvant radiation are commonly used, but there are no data to support a specific regimen or that demonstrate a definitive survival benefit.Recurrence of MCC is common. One study of 95 patients showed a 47% recurrence, with 80% of recurrences


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Surgery_Schwartz. are no data to support a specific regimen or that demonstrate a definitive survival benefit.Recurrence of MCC is common. One study of 95 patients showed a 47% recurrence, with 80% of recurrences occurring within 2 years and 96% occurring within 5 years.173,174 Regional lymph node disease is common, and 70% of patients will have nodal spread within 2 years of disease presentation. Five-year overall survival of head and neck disease in surgically treated patients is between 40% and 68%.Kaposi’s SarcomaKaposi’s sarcoma is characterized by the proliferation and inflammation of endothelial-derived spindle cell lesions. There are five major forms of this angioproliferative disorder: classic (Mediterranean), African endemic, HIV-negative men having sex with men (MSM)-associated, and immunosuppression-associated. They are all driven by the human herpesvirus (HHV-8).175 Kaposi’s sarcoma is diagnosed after the fifth decade of life and predominantly found on the skin but can occur anywhere in


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Surgery_Schwartz. They are all driven by the human herpesvirus (HHV-8).175 Kaposi’s sarcoma is diagnosed after the fifth decade of life and predominantly found on the skin but can occur anywhere in the body. In North America, the Kaposi’s sarcoma herpes virus is transmitted via sexual and nonsexual routes and predominantly affects individuals with compromised immune systems such as those with HIV and transplant recipients on immune-suppressing medications. Clinically, Kaposi’s sarcoma appears as multifocal, rubbery blue-red nodules. Treatment of AIDS-associated Kaposi’s sarcoma is with antiviral therapy, and many patients experience a dramatic treatment response.176,177 Those individuals who do not respond and have limited muco-cutaneous disease may benefit from cryotherapy, photodynamic therapy, radiation therapy, intralesional injections, and topical therapy. Surgical biopsy is important for disease diagnosis, but given the high local recurrence and the fact that Kaposi’s sar-coma represents more


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Surgery_Schwartz. therapy, intralesional injections, and topical therapy. Surgical biopsy is important for disease diagnosis, but given the high local recurrence and the fact that Kaposi’s sar-coma represents more of a systemic rather than local disease, the benefit of surgery is limited and generally should not be pursued except for palliation.Dermatofibrosarcoma ProtuberansThis rare, low-grade sarcoma of fibroblast origin commonly afflicts individuals during their third decade of life. It has low distant metastatic potential, but it behaves aggressively locally with finger-like extensions. Tumor depth is the most important prognostic variable. Presentation is characteristically a slow-growing, asymptomatic, violaceous plaque involving the trunk, head, neck, or extremities (Fig. 16-18). Nearly all cases are posi-tive for CD34 and negative for factor XIIIa.178,179 Treatment is wide local excision with 3-cm margins down to deep underly-ing fascia or Mohs microsurgery in cosmetically sensitive areas


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Surgery_Schwartz. are posi-tive for CD34 and negative for factor XIIIa.178,179 Treatment is wide local excision with 3-cm margins down to deep underly-ing fascia or Mohs microsurgery in cosmetically sensitive areas where maximum tissue preservation will benefit.180 No nodal dissection is needed, and both approaches provide similar local control.181 Some clinicians have used radiation therapy and bio-logic agents (imatinib) as adjuvant therapy with some success in patients with advanced disease. Local recurrence occurs in 50% to 75% of cases, usually within 3 years of treatment. Thus, clini-cal follow-up is important. Recurrent tumors should be resected whenever possible.Figure 16-18. Dermatofibrosarcoma protuberans of the left flank.Malignant Fibrous Histiocytoma (Undifferentiated Pleomorphic Sarcoma and Myxofibrosarcoma)This uncommon, cutaneous, spindle-cell, soft tissue sarcoma occurs in the extremities, head, and neck of elderly patients. They present as solitary, soft to firm, skin-colored


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Surgery_Schwartz. and Myxofibrosarcoma)This uncommon, cutaneous, spindle-cell, soft tissue sarcoma occurs in the extremities, head, and neck of elderly patients. They present as solitary, soft to firm, skin-colored subcutane-ous nodules. Complete surgical resection is the treatment of choice, and adjuvant radiation therapy provides local control; patients with positive margins benefit most from this combina-tion. Nevertheless, patients undergoing complete gross resection will experience recurrence in 30% to 35% of cases.135 Up to 50% of patients may present with distant metastasis, and this is a contraindication to surgical resection.AngiosarcomaAngiosarcoma is an uncommon, aggressive cancer that arises from vascular endothelial cells and occurs in four variants, all of which have a poor prognosis.182 The 5-year survival estimate is 15%.183 The head and neck variant presents in individuals older than 40 years as an ill-defined red patch on the face or scalp, often with satellite lesions and distant


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Surgery_Schwartz. 5-year survival estimate is 15%.183 The head and neck variant presents in individuals older than 40 years as an ill-defined red patch on the face or scalp, often with satellite lesions and distant metastasis, and has a median survival of 18 to 28 months. Lymphedema-associated angiosarcoma (Stewart-Treves) develops on an extremity ipsi-lateral to an axillary lymphadenectomy. It appears on the upper, medial arm as a violaceous plaque in an individual with nonpit-ting edema and has a poor survival. Radiation-induced angio-sarcoma occurs 4 to 25 years after radiation therapy for benign and malignant conditions. Finally, the epithelioid variant of angiosarcoma involves the lower extremities and also has a poor prognosis. Surgical excision with wide margins is the treatment Brunicardi_Ch16_p0511-p0540.indd 53519/02/19 3:09 PM 536SPECIFIC CONSIDERATIONSPART IIof choice for localized disease, but the rate of recurrence is high. Adjuvant radiation therapy can be considered in a


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Surgery_Schwartz. 53519/02/19 3:09 PM 536SPECIFIC CONSIDERATIONSPART IIof choice for localized disease, but the rate of recurrence is high. Adjuvant radiation therapy can be considered in a multidisci-plinary fashion. Cases of extremity disease can be considered for amputation. For widely metastatic disease, chemotherapy and radiation may provide palliation, but these modalities do not prolong overall survival.115Extramammary Paget’s DiseaseThis rare adenocarcinoma of apocrine glands arises in axillary, perianal, and genital regions of men and women.184 Clinical pre-sentation is that of erythematous or nonpigmented plaques with an eczema-like appearance that often persist after failed treat-ment from other therapies. An important characteristic and one that the surgeon must be acutely aware of is the high incidence of concomitant other malignancies with this cutaneous disease. Forty percent of cases are associated with primary gastrointesti-nal and genitourinary malignancies, and a diligent search


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Surgery_Schwartz. incidence of concomitant other malignancies with this cutaneous disease. Forty percent of cases are associated with primary gastrointesti-nal and genitourinary malignancies, and a diligent search should be made after a diagnosis of extramammary Paget’s disease is made. Treatment is surgical resection with negative microscopic margins, and adjuvant radiation may provide additional locore-gional control.CONCLUSIONThe skin is the largest organ in the human body and is com-posed of three organized layers that are the source of numer-ous pathologies. Recognition and management of cutaneous and subcutaneous diseases require an astute clinician to opti-mize clinical outcomes. Improvements in drugs, therapies, and healthcare practices have helped recovery from skin injuries. Skin and subcutaneous diseases are often managed medically, although surgery frequently complements treatment. Benign tumors are surgical diseases, while malignant tumors are pri-marily treated surgically, and additional


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Surgery_Schwartz. diseases are often managed medically, although surgery frequently complements treatment. Benign tumors are surgical diseases, while malignant tumors are pri-marily treated surgically, and additional modalities including chemotherapy and radiation therapy are sometimes required. The management of melanoma is at an exciting phase, requiring the coordinated multidisciplinary care of medical oncologists, surgical oncologists, radiation oncologists, der-matopathologists, and plastic and reconstructive surgeons. The advent of new drug therapies will redefine the role of surgery in this disease in the coming years.REFERENCESEntries highlighted in bright blue are key references. 1. Kanitakis J. Anatomy, histology and immunohistochemistry of normal human skin. Eur J Dermatology. 2002;12(4):390-401. 2. Chug D, Hake A, Holbrook K. The structure and development of skin. In: Freedberg I, Eisen A, Wolff K, eds. Fitzpatrick’s Dermatology in General Medicine. 6th ed. New York: McGraw-Hill;


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Surgery_Schwartz. D, Hake A, Holbrook K. The structure and development of skin. In: Freedberg I, Eisen A, Wolff K, eds. Fitzpatrick’s Dermatology in General Medicine. 6th ed. New York: McGraw-Hill; 2003:47-88. 3. Michael Weitz, Brian Kearns, eds. Skin. In: Junqueira’s Basic Histology. 14th ed. New York: McGraw-Hill Education; 2016. 4. Segre JA. Epidermal barrier formation and recovery in skin disorders. J Clin Invest. 2006;116(5):1150-1158. 5. Elias PM. Stratum corneum defensive functions: an integrated view. J Invest Dermatol. 2005;125(2):183-200. 6. Girolomoni G, Caux C, Dezutter-Dambuyant C, Dezutter-Dambuyant C, Ricciardi-Castagnoli P. Langerhans cells: still a fundamental paradigm for studying the immunobiology of dendritic cells. Trends Immunol. 2002;23(1):6-8. 7. Mutyambizi K, Berger CL, Edelson RL. The balance between immunity and tolerance: the role of Langerhans cells. Cell Mol Life Sci. 2009;66(5):831-840. 8. Lori F, Kelly LM, Lisziewicz J. APC-targeted immuniza-tion for the treatment of


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Surgery_Schwartz. RL. The balance between immunity and tolerance: the role of Langerhans cells. Cell Mol Life Sci. 2009;66(5):831-840. 8. Lori F, Kelly LM, Lisziewicz J. APC-targeted immuniza-tion for the treatment of HIV-1. Expert Rev Vaccines. 2004;3 (4 suppl):S189-S198. 9. Yu SH, Bordeaux JS, Baron ED. The immune system and skin cancer. Adv Exp Med Biol. 2014;810:182-191. 10. Lens MB, Dawes M. Global perspectives of contemporary epi-demiological trends of cutaneous malignant melanoma. Br J Dermatol. 2004;150(2):179-185. 11. Lock-Andersen J, Drzewiecki KT, Wulf HC. Eye and hair colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma. A Danish case-control study. Acta Derm Venereol. 1999;79(1):74-80. 12. Tachibana T. The Merkel cell: recent findings and unresolved problems. Arch Histol Cytol. 1995;58(4):379-396. 13. Munde PB, Khandekar SP, Dive AM, Aparna Sharmal. Pathophysiology of merkel cell. J Oral Maxillofac Pathol.


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Surgery_Schwartz. cell: recent findings and unresolved problems. Arch Histol Cytol. 1995;58(4):379-396. 13. Munde PB, Khandekar SP, Dive AM, Aparna Sharmal. Pathophysiology of merkel cell. J Oral Maxillofac Pathol. 2013;17(3):408-412. 14. Ogawa H. The Merkel cell as a possible mechanoreceptor cell. Prog Neurobiol. 1996;49(4):317-334. 15. Bos JD, Zonneveld I, Das PK, Krieg SR, van der Loos CM, Kapsenberg ML. The skin immune system (SIS): distribution and immunophenotype of lymphocyte subpopulations in nor-mal human skin. J Invest Dermatol. 1987;88(5):569-573. 16. Spetz AL, Strominger J, Groh-Spies V. T cell subsets in normal human epidermis. Am J Pathol. 1996;149(2):665-674. 17. Toker C. Clear cells of the nipple epidermis. Cancer. 1970;25(3):601-610. 18. Garijo MF, Val D, Val-Bernal JF. An overview of the pale and clear cells of the nipple epidermis. Histol Histopathol. 2009;24(3):367-376. 19. Dillon DA, Lester SC. Lesions of the nipple. Surg Pathol Clin. 2009;2(2):391-412. 20. Lundquist K, Kohler S,


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Surgery_Schwartz. pale and clear cells of the nipple epidermis. Histol Histopathol. 2009;24(3):367-376. 19. Dillon DA, Lester SC. Lesions of the nipple. Surg Pathol Clin. 2009;2(2):391-412. 20. Lundquist K, Kohler S, Rouse R V. Intraepidermal cytoker-atin 7 expression is not restricted to Paget cells but is also seen in Toker cells and Merkel cells. Am J Surg Pathol. 1999;23(2):212-219. 21. Sato K, Leidal R, Sato F. Morphology and development of an apoeccrine sweat gland in human axillae. Am J Physiol. 1987;252(1 Pt 2):R166-80. 22. Burgeson RE, Nimni ME. Collagen types. Molecular structure and tissue distribution. Clin Orthop Relat Res. 1992;(282):250-272. 23. Eyden B. The myofibroblast: an assessment of controversial issues and a definition useful in diagnosis and research. Ultra-struct Pathol. 25(1):39-50. 24. Braverman IM. The cutaneous microcirculation. J Investig Dermatology Symp Proc. 2000;5:3-9. 25. Johansson O. The innervation of the human epidermis. J Neurol Sci. 1995;130(2):228. 26. Avram


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Surgery_Schwartz. IM. The cutaneous microcirculation. J Investig Dermatology Symp Proc. 2000;5:3-9. 25. Johansson O. The innervation of the human epidermis. J Neurol Sci. 1995;130(2):228. 26. Avram AS, Avram MM, James WD. Subcutaneous fat in normal and diseased states: 2. Anatomy and physiology of white and brown adipose tissue. J Am Acad Dermatol. 2005;53(4):671-683. 27. König A, Lehmann C, Rompel R, Happle R. Cigarette smok-ing as a triggering factor of hidradenitis suppurativa. Derma-tology. 1999;198(3):261-264. 28. Pink AE, Simpson MA, Desai N, Trembath RC, Barker JNW. γ-Secretase mutations in hidradenitis suppurativa: new insights into disease pathogenesis. J Invest Dermatol. 2013;133(3):601-607. 29. Jemec GBE. Clinical practice. Hidradenitis suppurativa. N Engl J Med. 2012;366(2):158-164. 30. Matusiak L, Bieniek A, Szepietowski JC. Increased serum tumour necrosis factor-alpha in hidradenitis sup-purativa patients: is there a basis for treatment with anti-tumour necrosis factor-alpha agents?


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Surgery_Schwartz. L, Bieniek A, Szepietowski JC. Increased serum tumour necrosis factor-alpha in hidradenitis sup-purativa patients: is there a basis for treatment with anti-tumour necrosis factor-alpha agents? Acta Derm Venereol. 2009;89(6):601-603.Brunicardi_Ch16_p0511-p0540.indd 53619/02/19 3:09 PM 537THE SKIN AND SUBCUTANEOUS TISSUECHAPTER 16 31. Schlapbach C, Hänni T, Yawalkar N, Hunger RE. Expression of the IL-23/Th17 pathway in lesions of hidradenitis suppura-tiva. J Am Acad Dermatol. 2011;65(4):790-798. 32. Clemmensen OJ. Topical treatment of hidradenitis suppurativa with clindamycin. Int J Dermatol. 1983;22(5):325-328. 33. Mandal A, Watson J. Experience with different treatment mod-ules in hidradenitis suppuritiva: a study of 106 cases. Surgeon. 2005;3(1):23-26. 34. Tierney E, Mahmoud BH, Hexsel C, Ozog ND, Hamzavi I. Randomized control trial for the treatment of hidradenitis sup-purativa with a neodymium-doped yttrium aluminium garnet laser. Dermatologic Surg.


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Surgery_Schwartz. E, Mahmoud BH, Hexsel C, Ozog ND, Hamzavi I. Randomized control trial for the treatment of hidradenitis sup-purativa with a neodymium-doped yttrium aluminium garnet laser. Dermatologic Surg. 2009;35(8):1188-1198. 35. Shuja F, Chan CS, Rosen T. Biologic drugs for the treatment of hidradenitis suppurativa: an evidence-based review. Dermatol Clin. 2010;28(3):511-521, 523-524. 36. Falola RA, DeFazio MV, Anghel EL, Mitnick CD, Attinger CE, Evans KK. What heals hidradenitis suppurativa: surgery, immunosuppression, or both? Plast Reconstr Surg. 2016;138 (3 suppl):219S-229S. 37. Marzano A V, Cugno M, Trevisan V, et al. Role of inflam-matory cells, cytokines and matrix metalloproteinases in neutrophil-mediated skin diseases. Clin Exp Immunol. 2010;162(1):100-107. 38. Bister V, Mäkitalo L, Jeskanen L, Saarialho-Kere U. Expres-sion of MMP-9, MMP-10 and TNF-alpha and lack of epithelial MMP-1 and MMP-26 characterize pyoderma gangrenosum. J Cutan Pathol. 2007;34(12):889-898. 39. Shore RN. Pyoderma


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