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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2915_Библиотеки_им_академика_М_И_Перельмана.pdf
Section - I. Skin and Soft
Tissue Cancer
Nonmelanoma Skin Cancer
More than 1 million new cases occur annually including 80% basal cell
carcinomas (BCCs) and 20% squamous cell carcinomas (SCCs).
Sun exposure is the major risk factor with ultraviolet radiation causing
mutations in key genes.
Immunosuppressed patients, mainly organ-transplanted patients, have a SCC
incidence up to 36-fold higher than non transplanted.
BCC and SCC appear mainly on sun-exposed skin.
Classic BCC is a pearly, telangiectatic, with ulcerated nodule or a pale, sclerotic
plaque.
Classic SCC is a flesh-tone or red, with keratotic, variably ulcerated nodule.
BCCs that are large, deep, or infiltrative may be locally aggressive but
metastasize only rarely (<1%).
SCCs have a greater metastatic rate, especially those that are large, deep, have
perineural invasion.
Primary treatment for both BCCs and SCCs is surgical.
Mohs’ surgery is the preferred surgical technique for ill-defined or aggressive
lesions because it allows microscopic control of tumor margins.
Alternative therapies include radiation therapy or physical destruction. The
choice among different options of alternative therapies will depend of location,
size and depth of lesion.
Interferons and inducers of interferons (e.g., imiquimod) are proving useful in
selected cases.
Combinations of surgery, radiation therapy, and chemotherapy can be used for
metastatic disease.
Chapter 1
Abstract
Introduction
Nonmelanoma skin cancers (Basal and squamous cell carcinomas) are the most
commonly diagnosed malignancies in the world. Basal cell carcinoma accounts for
approximately 80% and squamous cell carcinoma for 20% of all nonmelanoma skin cancers.
Gustavo Arruda Viani
4
Factor
Description
UV light exposure
Excessive UV light exposure is the main risk factor.
NMSC are >50 times less common in nonwhite population than in white persons.
Of these cancers, 90% develop in sun-exposed areas of the body.
Blue-eyed, fair-skinned, blond and red-haired people, and those who are easily
sunburned are at increased risk
Exposure to ionizing
radiation
Individuals who were exposed to ionizing radiation (uranium miners, individuals
treated with radiation, cancer survivors) have a higher risk of NMSC.
Both tumors are most commonly treated with surgery, radiation therapy, or a combination of
both. Selection of therapy is based on preservation of function and cosmesis, and patient
preference. In this chapter we will examine the role of radiotherapy for treating these tumors.
1. Epidemiology
• Nonmelanoma skin cancer (NMSC) is the most common cancer as women as men in
the world, with an estimated annual incidence of >3 million cases.
• Basal cell carcinomas (BCCs) account for 70–80% of NMSCs, while squamous cell
carcinomas (SCCs) represent about 20% of NMSCs.
• In terms of the frequency, when we compared both tumors, we observe that BCC is
four times more frequent than SCC, and BCCs tend to be more indolent and rarely
metastasize. In the last decades, the incidence rates have risen dramatically compared
with the past decade.
• Currently, they account for most of the 2400 deaths annually. Together, these two
carcinomas account for most (95%) patients with nonmelanoma skin cancer
(NMSC), with malignant melanomas account for only 5% of all skin malignancies.
• In general, BCCs and SCCs occur in individuals older than 50 years old, mainly on
the sun-exposed head and neck or extremities.
Reference
American Cancer Society Cancer Facts and Figures 2012. http://www.cancer.org/acs
/groups/content/@epidemiologysurveilance/documents/document/acspc-026238.pdf
(Accessed on january 04, 2012).
2. Risk factors
The risk factors for developing BCC and SCC are multifactorial. Cumulative exposure to
sunlight is the most significant risk factor. Table-1 describes the main risk factors for BCC
and SCC.
Table 1. Several risk factors associated with developing of skin cancer
Nonmelanoma Skin Cancer
5
Factor
Description
Chronic
immunosuppression
Organ transplant recipients have 60 to 250 higher risk of development of SCC than
the general population.
BCC occurs in this population only 10 times more commonly.
Chronic
inflammation
SCC can occasionally originate from the site of chronic ulcers or scars, sites of
thermal burns, chronic draining osteomyelitis, and sinus tracts.
Hereditary factors
Basal cell nevus syndrome (Gorlin syndrome) is a rare autosomal-dominant
disorder caused by mutations in the human patched gene (PTCH).
Xeroderma pigmentosum is a multigenic, autosomal-recessive disorder in which
DNA repair ability is impaired. Homozygotes have severe skin and eye sensitivity
to sunshine. They develop SCC, BCC, and melanomas in the early childhood.
Infection
Verrucous carcinoma (Buschke-Lowenstein tumor) is typically a slow-growing,
HPV-associated (usually serotypes 6 and 11) neoplasm of the anogenital region that
may deeply invade underlying structures. Periungual SCC is associated with HPV
type 16.
References
van Dam RM, Huang Z, Rimm EB et al. Risk factors for basal cell carcinoma of the skin in
men: results from the health professionals follow-up study. Am J Epidemiol.
1999;150(5):459.
Zanetti R, Rosso S, Martinez C et al. Comparison of risk patterns in carcinoma and melanoma
of the skin in men: a multi-centre case-case-control study. Br J Cancer. 2006;94(5):743.
3. Anatomy
Three layers (epidermis, dermis, and subcutis) constitute the skin. Figure-1 describes
these three layers.
• The epidermis is a squamous epithelium layer that includes keratinocytes. This layer
has no blood vessels, so nutrition and excretion products are achieved through
diffusion.
• The epidermis has other cells such as melanocytes, langerhans cells and Merkel cells.
Melanocytes are cells originated from neural crest cells and produce the pigment
melanin. Langerhans cells originate from bone marrow and are located in the basal
and granular layers of epidermis. Merkel cells originate from the mesoderm, and are
associated with light touch sensation
• The dermis consists of two layers, the superficial papillary layer and the deeper
reticular dermis layer. Capillaries feed the papillary dermis, which is composed of
elastic leaves, reticular leaves and collagen, as well as the avascular epidermis via
diffusion.
• The hypodermis is located under the dermis, and includes subcutaneous adipose and
connective tissues. (figure-1)
Gustavo Arruda Viani
6
Figure 1. Layers of skin.
4. Clinical Features
• The BCC is a tumor with slow growing over months to years. It is usually
asymptomatic unless ulceration occurs, and then can exist pain and bleeding. BCC
occurs on sun-exposed areas such as the face and upper trunk, and is rare on the
palms and soles.
• The initial lesions are round-to-oval papules or nodules, often with an umbilicated
center that may be ulcerated. The color is pink to red and often has a translucent or
pearly quality (Figure-2C).
• BCCs are firm to palpation. When untreated, the lesion enlarges slowly and is
destructive to neighboring structures by direct invasion.
• There are often telangiectasias in the surrounding skin, which also shows other
evidence of solar damage, such as actinic keratosis, atrophy, dryness, and irregular
pigmentation.
• The SCC often arises in damaged skin or skin that has been subjected to chronic
irritation.
• SCC usually evolves faster than BCC, but not as rapidly as keratoacanthoma.
• The initial lesion, the so-called intraepidermal SCC or carcinoma in situ, typically
appears as a scaly, erythematous plaque on sun-exposed areas. The lesion often has a
sharply demarcated but irregular outline.
• Invasive SCC (Figure1A,B) almost always arises from a preexisting premalignant
lesion or from an in situ carcinoma, although de novo squamous cell carcinoma has
been reported.
• The lesion is typically an erythematous, indurated papule, plaque, or nodule. The
shape of the lesion may be polygonal, oval, round, or verrucous .
Nonmelanoma Skin Cancer
7
• The tumor tends to increase both in elevation and diameter with time. The late lesion
is often eroded, crusted, and ulcerated with an indurated margin.
• The ulcer is often covered with a purulent exudate and bleeds easily (Figure-2 A,B).
Figure 2. A,B,C BCC and SCC lesions in an arm, lips and ear.
• Regional lymphadenopathy may be present either as a response to infection of the
ulcer or from metastases. The risk of developing lymph nodal metastases, usually is
higher in SCC than in BCC.
• However, immunocompetent patients with small (<2 cm), thin (<4 to 5 mm thick),
no recurrent lesions are at low (<5%) risk of developing nodal metastases.
• Patients without these criteria can be considered high-risk patients (>10% risk), and
appropriate management is required. Lesions in close proximity (forehead, temple,
ear, cheek) to the parotid gland increase the risk to develop lymphonodal metastases
(figure-3).
• Also, tumor thickness greater than 6mm has been appointed as a powerful indepen-
dent predictor for regional metastases.
• The most frequent sites for the development of metastatic cutaneous SCC are the
parotid gland, the cervical lymph nodes, or both. The development of distant
metastases (e.g., lung, liver) rarely occurs as a first site of relapse.
Figure 3. Lesion on parotid topograph with nodal involvement.
Gustavo Arruda Viani
8
Variable
Decription
Clinical findings
Patients with suspicious lesions are offered a complete skin examination.
Clinical evaluation of skin cancers consists of inspection and palpation of the
involved area and the regional lymph nodes.
All suspicious lesions must be biopsied.
Imaging studies
Chest radiography, computed tomography [CT], or magnetic resonance imagings
[MRI], generally, are not required in most patients with NMSC.
Lymph node metastasis and bone involvement are best assessed with contrast-
enhanced CT scan acquired with soft tissue and bone windows (figure-3).
Reference
Sariya D, Ruth K, Adams-McDonnell R, Cusack C et al. Clinicopathologic correlation of
cutaneous metastases: experience from a cancer center. Arch Dermatol. 2007;143(5):613.
5. Diagnostic and Evaluation
Tumour diagnosis must be confirmed by scrapings, punch biopsy, or excisional biopsy.
Large or fixed tumours may require assessment of deeper involvement with X-ray and/or CT
scans (table-2).
Table 2. Diagnostic and evaluation of skin cancer
Reference
Sariya D, Ruth K, Adams-McDonnell R, Cusack C et al. Clinicopathologic correlation of
cutaneous metastases: experience from a cancer center. Arch Dermatol. 2007;143(5):613.
6. Pathology
Basal cell carcinoma of the skin is the most common histological type of skin cancer. It is
a nonkeratinizing neoplasm arising from the basal layer of the epidermis.
Basal cell carcinoma has a low metastatic potential with predilection for local invasion.
Histological sub-types of basal cell carcinoma include:
• Nodular: raised nodule with telangiectasia in sun-exposed areas
• Superficial: erythematous or eroded macule, which mimic eczema or psoriasis
• Morpheaform: flat, firm lesion without well defi ned margins
Squamous cell carcinoma of the skin is the second most common histological type of skin
cancer. Squamous cell carcinoma is a neoplasm of keratinizing malignant cells, and arises
from keratinocytes of the epidermis, and actinic keratosis is a precancerous condition of
squamous cell carcinoma of the skin. Pathologic grading of squamous cell carcinoma of the
Nonmelanoma Skin Cancer
9
Primary Tumor (T)
TX
Primary tumor cannot be assessed
T0
No evidence of primary tumor
Tis
Carcinoma in situ
T1
Tumor 2 cm or less in greatest dimension with less than two high-risk features (see list of
high-risk features below)
T2
Tumor greater than 2 cm in greatest dimension OR
Tumor any size with two or more high-risk features
T3
Tumor with invasion of maxilla, mandible, orbit, or temporal bone
T4
Tumor with invasion of skeleton (axial or appendicular) or perineural invasion of skull
base
High-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
Regional lymph nodes (N)
NX
Regional lymph nodes cannot be assessed
N0
No regional lymph node metastases
N1
Metastasis in a single ipsilateral lymph node, 3 cm or less 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
Distant metastasis (M)
M0
No distant metastases
MI
Distant metastases
skin depends on the magnitude of polymorphism, mitosis, and keratinization, and classifies
the disease to poorly, moderately, or well differentiated categories.
Reference
Yanofsky VR, Mercer SE, Phelps RG. Histopathological variants of cutaneous squamous cell
carcinoma: a review. J Skin Cancer. 2011;2011:210813.
7. Staging
Nonmelanoma skin cancers are staged clinically, and the American Joint Committee on
Cancer (AJCC) TNM Staging System is used (table-3).
Table 3. TNM staging system for nonmelanoma skin cancer
Gustavo Arruda Viani
10
Perineural invasion. Perineural invasion is an indicator for local and/ or regional recurrence or distant
metastasis.
Recurrent disease. Locally recurrent squamous cell carcinoma of the skin has an overall metastatic rate
of 30%
Histological subtype. Recurrences are seen most commonly with morpheaform and nodular.
Location and size. Location and size are recognized prognostic factors for local recurrence of SCC,
mainly, tumors located in the head and neck, genitalia, mucosal surfaces, and ear are at higher risk of
metastasizing. For BCC tumors in the head and neck area are more likely to recur and carry a worse
prognosis. Tumor size of larger than 2 cm in diameter carries an increased risk or local recurrence.
Tumor staging. The presenting staging of the disease, including overall invasiveness and depth of the
primary disease, as well as regional nodal involvement status, is the most important prognostic factor for
SCC. Tumors of at least 4 mm deep or invading the reticular dermis and subcutis have a high recurrence
rate or nodal involvement.
Degree of differentiation. Degree of cellular differentiation is of prognostic signifi cance. Poorly
differentiated tumors are more likely to metastasize.
Reference
American Joint Committee on Cancer Staging Manual, 7th, Edge SB, Byrd DR, Compton
CC, et al (Eds), Springer, New York 2010.
8. Routes of Spread
• SCC can spread by three major routes: local extension, regional (lymphatic), and
distant (hematogenous). On the other hand, BCC of the skin rarely metastasizes but
they have a high potential for local invasion. In general, for BCC nodal and distant
metastases occur in less than 10% of cases.
• Pattern of lymphatic spread in SCC of the skin depends on the location of the
primary tumor. For example, the most commonly involved lymph nodes in SCC of
the skin of the head and neck are the intraparotid lymph nodes, followed by the
lymph nodes in the submandibular triangle and upper jugulodigastric regions.
Reference
Miller SJ, Alam M, Andersen J et al.Basal cell and squamous cell skin cancers. J Natl Compr
Canc Netw. 2010;8(8):836.
9. Prognostic Factors
Several prognostic factors have been associated with a higher risk of recurrence for both
tumors SCC and BCC (table-4) shows principal prognostic factors.
Table 4. Prognostic factors associated with local control and distant metastases