Skin Cancer, Acquired Immunodeficiency Syndrome Related Malignancies, and Kaposi’s Sarcoma

SKIN

Anatomy

The integumentary system comprises the skin and the appendageal structures traversing the skin.
The epidermis is composed of two layers: The outermost layer is the stratum corneum, and the basal layer rests on the basement membrane that separates the epidermis from the dermis. Melanocytes, which are pigment-producing cells, are located between the basal cells of the epidermis.
The dermis consists of spindle-shaped fibroblasts that produce collagen, giving the skin much of its strength. It contains two vascular plexuses as well as sensory and autonomic nerves.
The skin contains smooth muscles in the form of the musculi arrectores pilorum, which attach to the hair shaft and are responsive to cold and sweat.
Appendageal structures of the skin include the sebaceous, eccrine, and apocrine glands. Sebaceous glands are found throughout the skin, except on the palms and soles. The apocrine glands are found mainly in the anal and genital areas.

Epidemiology

Carcinomas of the skin account for nearly one third of all cancers diagnosed in the United States each year. The incidence is estimated to be over 800,000 new cases per year.
Exposure to (ultraviolet) solar radiation, especially ultraviolet B, is the most common cause of skin cancer.
Other etiologic factors include ionizing radiation, genetic predisposition (xeroderma pigmentosa, albinism), arsenic exposure, preexisting chronic skin ulcers related to syphilis or burns, and human papillomavirus.

Diagnostic Workup

The diagnosis of skin cancer requires a detailed clinical history.
Physical examination should focus on appreciation of changes in the normal appearance of the skin.
The size, diameter, depth of invasion, and multifocality of the tumor must be precisely defined.
Regional lymph nodes must be assessed.
Various tools to assess the skin, including Wood’s light and potassium hydroxide preparations, fungal cultures, skin biopsies, Tzanck smears, and patch testing, should be used.

Staging

The staging system for skin cancer is shown in Table 9-1, which shows the AJCC designations for cutaneous T-cell lymphoma, melanoma and Merkel cell carcinoma (MCC) (1).

TABLE 9-1 American Joint Committee Staging System for Skin Cancer

*Primary Tumor (T)^a*
TX	Primary tumor cannot be assessed
T0	No evidence of primary tumor
Tis	In situ primary tumor
	*Cutaneous Squamous cell/other Cutaneous Carcinoma*
T1	Tumor 2 cm or less in greatest dimension with <2 high risk features^b
T2	Tumor >2 cm in greatest dimension or
	Tumor any size with two or more high risk features^c
T3	Tumor with invasion of maxilla, orbit, or temporal bone
T4	Tumor with invasion of skeleton (axial or appendicular) or perineural invasion of skull base
	*Merkel Cell Carcinoma*
T1	≤2 cm maximum tumor dimension
T2	>2 cm but not more than 5 cm maximum tumor dimension
T3	Over 5 cm maximum tumor dimension
T4	Primary tumor invades bone, muscle, fascia, or cartilage
	*Melanoma of the Skin*
T1	Melanomas <1.0 mm in thickness
T1a	without ulceration and mitosis <1/mm²
T1b	with ulceration or mitoses >1/mm²
T2^d	Melanomas 1.01-2.00 mm
T3^d	Melanomas 2.01-4.00 mm
T4^d	Melanomas >4.0 mm
*Regional Lymph Nodes (N)*
NX	Regional lymph nodes cannot be assessed
N0	No regional lymph node metastasis
	*Cutaneous Squamous cell/other Cutaneous Carcinoma*
N1	Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension
N2	Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension; or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension; or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension
N2a	Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension
N2b	Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension
N2c	Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension
N3	Metastasis in a lymph node, more than 6 cm in greatest dimension
	*Melanoma of the Skin*
N1	1 node with micrometastasis^e or macrometastasis^f
	2-3 nodes with micrometastasis^e or macrometastasis^f
N2c	2-3 nodes, in transit met(s)/satellite(s) without metastatic nodes
N3	Clinical: >1 node with in transit met(s)/satellite(s); pathologic: 4 or more metastatic nodes, or matted nodes, or in transit met(s)/satellite(s) with metastatic node(s)
	*Merkel Cell Carcinoma*
N1	Metastasis in regional lymph node(s)
	Micrometastasis^g
	Macrometastasis^h
N2	In transit metastasisⁱ
*Distant Metastasis (M)*
M0	No distant metastasis
M1	Distant metastasis
	Melanoma divides M1 M1a: Metastases to skin, subcutaneous tissues, or distant lymph nodes; M1b: Metastases to lung; and M1c: Metastases to all other visceral sites or distant metastases to any site combined with an elevated serum LDH
	Merkel Cell Carcinoma divides M1 M1a: Metastasis to skin, subcutaneous tissues or distant lymph nodes; M1b: Metastasis to lung; and M1c: Metastasis to all other visceral sites
^aIn the case of multiple simultaneous tumors, the tumor with the highest T category will be classified, and the number of separate tumors will be indicated in parentheses, for example, T2 (5). ^bHigh risk features for the primary tumor (T) staging: Depth/invasion: >2 mm thickness, Clark level > IV, perineural invasion Anatomic location: primary site ear, primary site hair-bearing lip Differentiation: poorly differentiated or undifferentiated ^cExcludes cSCC of the eyelid. ^dT2 to T4 have substages a and b, which indicate without ulceration or with ulceration, respectively ^eMicrometastases are diagnosed after SLN biopsy and completion lymphadenectomy (if performed). ^fMacrometastases are defined as clinically detectable nodal metastases confirmed by therapeutic lymphadenectomy or when nodal metastasis exhibits gross extracapsular extension.^gMicrometastases are diagnosed after sentinel or elective lymphadenectomy. ^hMacrometastases are defined as clinically detectable nodal metastases confirmed by therapeutic lymphadenectomy or needle biopsy. ⁱIn transit metastasis: a tumor distinct from the primary lesion and located either (a) between the primary lesion and the draining regional lymph nodes or (b) distal to the primary lesion
Source: Staging from Edge SB, Byrd DR, Compton CC, et al., eds. AJCC cancer staging manual, 7th ed. New York, NY: Springer Verlag, 2009, with permission.

Clinicopathologic Manifestations

Basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) are the most common, and melanomas are the most serious.
Malignant tumors of the skin include BCC, SCC, melanoma, MCC, adnexal tumors, connective tissue tumors, malignant lymphomas, mycosis fungoides, Kaposi’s sarcoma, keratoacanthoma (acute epithelial cancer), and metastases.
Keratoacanthomas are treated with 2.5 to 3 Gy fractions for large lesions and 4 to 5 Gy fractions for smaller lesions to total doses of 40 to 60 Gy.
BCCs occur most often on hair-bearing skin of the head and neck; they rarely metastasize.
SCCs frequently are preceded by premalignant lesions, most commonly actinic keratosis. They also can arise from old burn scars or areas of chronic inflammation or radiation dermatitis. Lesions that arise from areas of chronic inflammation or develop de novo are more aggressive and metastasize in 10% of cases. See Ref. 24.

General Management

Surgical excision and radiation therapy offer equivalent, excellent cure rates. The treatment modality selected should offer the greatest potential for cure with the most acceptable cosmetic and functional results.
Factors that influence treatment decisions include size and anatomic location of the lesion, involvement of adjacent cartilage or bone, depth of invasion, tumor grade, previous treatment, and the general medical condition of the patient (16).
Computed tomography scans should be done for lesions around the eye to determine the magnitude of the tumor, particularly for recurrent tumors after surgery.

Surgery

Small BCCs and SCCs may be surgically excised.
Curettage and electrodesiccation is used for small nodular BCCs (less than 1.5 cm) with distinct margins. The cure rate is approximately 90% in properly selected cases. This technique is contraindicated for diffusely infiltrating tumors, recurrent tumors, and lesions in areas where significant tissue trauma may result from the procedure (24).
Mohs’ microsurgery involves fixation of the tumor and adjacent scar with zinc chloride, followed by mapping and surgical excision. Frozen-section samples are taken to locate areas of residual tumor; these are further excised until negative margins are obtained. Treatment is indicated for BCCs and SCCs. It is contraindicated for Merkel cell tumor, because of its noncontiguous growth pattern. The literature reports a 5-year cure rate of 95% or better.
Cryotherapy consists of the application of liquid nitrogen to skin neoplasms, which causes necrosis of malignant cells by destruction of the microvasculature. The indications and contraindications are similar to those for curettage and electrodesiccation. It can result in cure rates of 90% or higher.

Radiation Therapy

For small lesions of the lip, eyelid, ear, or nose, irradiation may offer an advantage over surgical techniques with respect to cosmesis and function. For a study on sebaceous carcinoma, see (20).
Radiation therapy is indicated for lesions larger than 2 cm, lesions with deep fixation, and lesions with involvement of adjacent structures, in which surgery may result in poor cosmetic or functional outcome.
Radiation therapy is beneficial for the treatment of multiple lesions or lesions that involve regional lymph nodes.
Postoperative irradiation is indicated for patients with incomplete resection of squamous cell tumors. In this group of patients, irradiation improves local tumor control and survival, if it is delivered immediately after surgical excision (24).

TABLE 9-2 Malignant Conditions of the Skin for which Radiation Therapy is Indicated

*Highly Indicated*	*Often Indicated*
Kaposi’s sarcoma	BCC and SCC of head, trunk, vulva, or perineum
Mycosis fungoides	Keratoacanthoma
Lymphoma cutis	Melanoma
	Merkel Cell Carcinoma
	Angiosarcoma
	Bowen’s disease

Perez (21) reported 87% tumor control and 10% to 15% nodal metastases in initially treated patients, compared with 65% control and 39% nodal metastases in patients treated for salvage after observation.
Table 9-2 lists various malignant lesions of the skin that can be treated with radiation therapy.

Chemotherapy