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Nonmelanoma Skin Cancer
11
Location
• high-risk areas (eg, central face, nose, lips, eyelids, eyebrows, periorbital skin, chin,
mandible, ears, preauricular and postauricular areas, temples, hands, feet)
Size
• Over 20 mm in diameter in all other areas (excluding hands and feet)
Recurrent lesions
Lesions in sites treated previously by radiation therapy
Lesions with poorly defined borders
Perineural invasion
References
Weinstock MA, Bogaars HA, Ashley M, Litle V, Bilodeau E, Kimmel S. Nonmelanoma skin
cancer mortality. A population-based study. Arch Dermatol. 1991;127(8):1194.
Joseph MG, Zulueta WP, Kennedy PJ. Squamous cell carcinoma of the skin of the trunk and
limbs: the incidence of metastases and their outcome. Aust N Z J Surg. 1992;62(9):697.
Rowe DE, Carroll RJ, Day CL Jr. Prognostic factors for local recurrence, metastasis, and
survival rates in squamous cell carcinoma of the skin, ear, and lip. Implications for
treatment modality selection. J Am Acad Dermatol. 1992;26(6):976.
10. Treatment
• Selection of therapy is based on preservation of function and cosmesis, location of
the lesion(s), patient preference and general health status.
• BCC and SCC lesions are divided in two groups. BCC/SCC with low or high risk of
recurrence. This division is done based on some clinical and pathological features.
The characteristics described in table 5 have been proposed as factors associated with
increased risk for tumor recurrence.
Table 5. Risk factors associated with a high risk of recurrence
• Mohs micrographic surgery is the standard and preferred treatment for BBC and SCC
lesions with high risk of recurrence.
• Mohs micrographic surgery (Mohs surgery) is a procedure that utilizes frozen tissue
sections to assess 100 % of excised tissue margins.
• Conventional surgical excision can be used for the treatment of low-risk BCC and,
also, can be used for the treatment of some high-risk lesions.
• Radiation therapy is effective for the treatment of BCCs at high risk for recurrence;
however, cure rates are lower than Mohs surgery and there is the potential for longterm local adverse effects. So, RT is a good treatment option for older patients with
high-risk lesions who are not candidates for surgical excision, as showed in table-6.
• Adjuvant radiotherapy is considered in lesions with positive margins, tumor more
than 3 cm, T4 lesions and with perineural invasion.
Gustavo Arruda Viani
12
Treatment
Description
Local control
Mohs’ surgery
It is indicated for sites that have a high initial treatment failure rate
when traditional methods are used and for recurrent tumours.
It is a technique that allows rapid examination of horizontal frozen-
section specimens, which are processed to include 100% of the
peripheral and deep surgical margins.
99%
Surgical
excision
Surgery is indicated for small tumours that can be excised and then
the defect closed directly so that the surgical procedure produces
good cosmetic and functional results with a high cure rate.
85 – 90%
Radiotherapy
Radiotherapy is an important treatment option for older patients
who don`t concerned with the cosmetic results.
It is preferred to surgery for large superficial or extensive tumours
and for multiple tumours where the cosmetic results are better.
Tumours that are in sites that make removal difficult or that are
unresectable should also be treated by radiotherapy. Radiotherapy
should be offered for patients who refuse surgery, who are unfit, or
who are on anticoagulant therapy.
91-93%
Electrodesiccat
ioncryosurgery
Electrodesiccation and curettage and cryosurgery are indicated for
small well-defined primary tumours with non-agressive features on
the neck, trunk, arms, and legs.
Variable
Topical 5-FU
Topical 5-fluorouracil is available in strengths of 2 or 5% and is
usually applied twice daily to the tumour and its margins
Variable
Photodynamic
therapy
Both systemic and topical porphyrins can be used but
photodynamic therapy is of value in treating superficial rather than
thick tumours.
Variable
• For BCC and SCC lesions considered as low risk (superficial, small, and located in
arms and trunk) alternative therapies (eletrodissection/5-FU/photodynamic
/imiquimod) are viable options (table-6).
Table 6. Treatment options for low and high risk lesion and the rates of local control
References
Smeets NW, Krekels GA, Ostertag JU, Essers BA, Dirksen CD, Nieman FH, Neumann HA.
Surgical excision vs Mohs' micrographic surgery for basal-cell carcinoma of the face:
randomised controlled trial. Lancet. 2004;364(9447):1766.
Lovett RD, Perez CA, Shapiro SJ, Garcia DM. External irradiation of epithelial skin cancer.
Int J Radiat Oncol Biol Phys. 1990;19(2):235.
Goette DK. Topical chemotherapy with 5-fluorouracil. A review. J Am Acad Dermatol.
1981;4(6):633.
Petsuksiri J, Frank SJ, Garden AS et al. Outcomes after radiotherapy for squamous cell
carcinoma of the eyelid. Cancer. 2008;112(1):111.
11. Treatment Technique
The treatment of skin lesions can be done with Orthovoltage X-rays (75–150 kVp
depending on the depth of tumor) or more commonly electron beams (6–12 MeV depending
on the depth of tumor), figure-4.
Nonmelanoma Skin Cancer
13
Figure 4. Superficial radiotherapy machine.
When the treatment is performed using electron-beams, the 90% isodose line of the
electron-beam should cover the entire depth of the tumor (including bolus) with a few
millimeters deeper than the base of the tumor. The size of the electron beams should be at
least 5 cm for reliable dosimetry. The patient should be positioned supine, prone or semiprone so that the tumour can be accessed by the superficial X-ray machine or electron
applicators. Several accessories such as pillows, head rests, and sandbags to aid in the
immobilization as necessary.
The gross tumor volume (GTV) is defined clinically and marked on the skin. The margin
added to the GTV to create the clinical target volume (CTV) depends on the clinicpathological type of lesion, the site and size of the lesion being treated, and closeness with
organs at risk. The field size is chosen to the PTV adequately receives 95% of prescribed dose
and will vary between superficial and electron beam radiotherapy.
For a low risk small BCC/SCC with a well-defined GTV < 2cm, a margin of 1 cm to
create the treatment field using superficial radiotherapy is appropriate. For high risk, larger or
poorly defined lesions, and a margin of 1.5 -2 cm may be necessary to create the treatment
field using superficial radiotherapy (figure- 5).
A: margins given to lesion less than 2cm. B: margins given to lesion higher than 2 cm.
Figure 5. Radiotherapy margins for skin lesions according to the size.
Gustavo Arruda Viani
14
Elective radiation to the lymph node is not recommended for both basal and squamous
cell carcinoma of the skin, except in patients with large infiltrative squamous cell carcinoma
(figure-6).
Figure 6. Superficial radiotherapy application in patients with SCC in the arm.
This margin needs to be increased when electron therapy is used to allow for the shape of
the isodoses. This will depend on the size of the lesion and the energy of the electron beam.
For a 6 MeV electron beam treating a 5 cm circle, an extra 1 cm should be added to the
margins above to define the field size with an electron applicator. Definitive radiation therapy
doses for BCC and SCC can be recommended as follows according to the size and pathology
of the primary disease:
For BCC lesions < 2 cm, 40 Gy
For BCC lesions 3 cm or SCC <1 cm, 45–50 Gy
For BCC >3 cm and SCC >1 cm, 60 Gy
All treatment is given in 1.8 – 2 Gy fractions per day, 5 days per week.
The use of standard fractionation (1.8–2 Gy per fraction) is expected to show an
improved cosmetic result when compared to higher dose per fraction (figure-7).
Figure 7. Cosmetic result of a nasal SCC, after superficial radiotherapy treatment with 60 Gy in 30
fractions.
Nonmelanoma Skin Cancer
15
Conclusion
• Basal cell carcinoma of the skin rarely metastasizes, but it has a predilection for local
invasion. On the other hand, squamous cell carcinoma can spread by local invasion
and lymph nodal drainage.
• Surgery, radiation therapy, or a combination of both is commonly used to treat both
tumors.
• Selection of therapy is based on preservation of function and cosmesis, and patient
preference.
• For both tumors, tumor stage at diagnosis is directly correlated with local control in
irradiated patients. In general, for early tumors (T1 and T2) local control is 95% and
80% respectively. For T3 tumors, however, the local control rates are as low as 50%.
Chapter 2
Melanoma
Abstract
The incidence of melanoma has risen dramatically over the past few decades.
Approximately 59,940 new cases of invasive melanoma are diagnosed each year in
the United States, and it is estimated that 1 in 49 men and 1 in 73 women in the
United States will be diagnosed with melanoma in their lifetime.
Risk of melanoma is strongly related to exposure to ultraviolet irradiation, and to a
susceptible host phenotype: fair hair and skin, a tendency to burn, and numerous
benign or atypical nevi.
Any suspicious lesion or questionable new or changing lesion should have a full-
thickness biopsy.
Staging categorization of the primary lesion relies on accurate determination of the
thickness of the lesion and determination of whether histologic ulceration is present.
All primary melanomas need wide local excision for local control. Margins of
excision are determined by the thickness of the primary lesion.
For patients presenting with a new primary melanoma >1 mm and a clinically
negative regional node basin, sentinel node biopsy is used to determine the node
status.
For patients with known metastatic nodes, regional node dissection is performed.
Adjuvant therapy should be offered to patients with high-risk, resected disease (e.g.,
nodal metastases or a primary tumor >4 mm), either with interferon-alfa or as part of
a clinical trial.
Although interferon has been approved by the U.S. Food and Drug Administration
(FDA) for high-risk patients, subsequent clinical trials of interferon have shown a
consistent disease-free survival (DFS) benefit, but failed to show a clear overall
survival benefit; thus its routine use remains controversial.
For advanced melanoma, dacarbazine (DTIC) and high-dose interleukin-2 (IL-2) are
the only FDA-approved agents.
Durable complete responses with high-dose IL-2 are possible, and this therapy
should be considered for all eligible patients.
A number of promising new molecular and immunologic agents are under active
investigation.
Gustavo Arruda Viani
18
Factor
Description
Familial factors
Up to 10% of melanomas are familial. The higher risk of melanoma in these families
is attributed to both shared susceptibility genes and shared environment.
CDKN2A and CDK4, are associated with high-penetrance susceptibility. Mutated
CDKN2A is the most prevalent gene in families with melanoma and it was found in
14% families with two cases of melanoma, in 67% families with six to seven cases,
and 100% families with seven to ten cases.
Nevi
Typical nevi are frequently precursors of melanoma, but more importantly they are
markers of increased risk.
Congenital nevi are benign neoplasms that are present at birth and composed of
nevomelanocytes. The malignant potential of giant congenital nevi varies between
different types. Pigmented giant nevi have especially high risk for malignant
transformation.
Nevus sebaceous is associated with the development of basal cell carcinoma.
Verrucous epidermal nevi and woolly hair nevi do not have malignant potential.
Previous
melanoma.
The rate of a second primary cutaneous melanoma is more than 10 times higher than
the first one. The 1-year, 5-year, and 10-year probability of developing the second
primary melanoma are 1% to 2%, 2.1% to 3.4%, and 3.2% to 5.3%, respectively.
1. Epidemiology
• Malignant melanoma represents about 4% of all skin cancers, being responsible for
80% of deaths.
• The incidence of melanoma in the United States is 16.9 cases per 100,000/year.
• Malignant melanoma is the sixth most common cancer among women and the fifth
most common cancer among men in the United States.
• The median age at the time of diagnosis is 58 years, and only 0.9% of cases are
diagnosed before the age of 20.
• The incidence of melanoma rose rapidly in the 1970s at about 6% per year; this rate
decreased in the 1980s to about 3% per year.
• In the past decade the death rate from melanoma has decreased.
• White people have a 17 to 25 times higher risk for development of melanoma than
blacks, but melanoma is diagnosed among all races.
Reference
Kohler BA, Ward E, McCarthy BJ, Schymura MJ, Ries LA, Eheman C, Jemal A, Anderson
RN, Ajani UA, Edwards BK. Annual report to the nation on the status of cancer, 1975-
2007, featuring tumors of the brain and other nervous system. J Natl Cancer Inst.
2011;103(9):714.
2. Risk Factors
The risk factors strongly asssociated with the development of melanoma are positive
family history, multiple benign or atypical nevi, and a previous melanoma (table-1).
Table 1. Risk factors associated with developing of MM
Melanoma
19
Factor
Description
Sun exposure
It is known that UV radiation causes genetic changes in the skin, impairs cutaneous
immune function, increases the local production of growth factors, and induces the
formation of DNA-damaging reactive oxygen species that affect keratinocytes and
melanocytes.
Immunosuppres
sion.
Among organ allograft recipients, melanoma constituted 5% of skin cancers and was
significantly higher than in the general population (2.7%).
References
Rivers JK.Melanoma. Lancet. 1996;347(9004):803.
Chaudru V, Chompret A, Bressac-de Paillerets B, Spatz A, Avril MF, Demenais F. Influence
of genes, nevi, and sun sensitivity on melanoma risk in a family sample unselected by
family history and in melanoma-prone families. J Natl Cancer Inst. 2004;96(10):785.
Bradford PT, Freedman DM, Goldstein AM, Tucker MA. Increased risk of second primary
cancers after a diagnosis of melanoma. Arch Dermatol. 2010;146(3):265.
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).
4. Clinical Features
• The most important clinical feature of a cutaneous melanoma is change in the color,
size, perimeter, or contour of a mole or pigmented skin lesion.
• Cutaneous melanoma can arise anywhere on the body. The most common site in
women is the lower extremity; On the other hand in men is the back.
Gustavo Arruda Viani
20
• MM has a variegated color, with irregular borders, or a history of a change in your
appearence.
• Symptoms and signs of warning for MM are called of “ABCDE” rule: Asymmetry,
Border irregularity, Color change/variegation, Diameter change, and Evolution
(change over time) of the lesion.
Figure 1. Skin anatomy.
• Some melanomas do not have these typical features; some are nonpigmented and
may resemble other dermatologic entities such as basal cell carcinoma, squamous
cell carcinoma, dermatofibroma, or seborrheic keratosis.
• Melanoma appears in five clinical growth patterns: superficial spreading melanoma
(SSM); nodular melanoma (NM); lentigo maligna melanoma (LMM); acral
lentiginous melanoma (ALM); and desmoplastic melanoma (DM), see figure-2.
• The clinical features, anatomic distribution, ethnic distribution, and etiology are
distinctive.
• SSM, the most common type of cutaneous melanoma among the white population. It
has a predominant radial growth phase, both clinically and histologically. These
lesions are more common on the legs in women and on the trunk in men, and
characteristically are large, asymmetric, with irregular borders, and multiple colors.
• NM is the second most common type of melanoma. The lesions usually are shiny,
smooth nodules, often with a single color, usually black, dark brown, or bluish. The
survival rates and prognosis for SSM and NM are virtually the same when matched
for thickness and ulceration.
• LMM occurs on chronically sun-exposed skin, especially the face and neck, in older
persons. The majority of patients with LMM (75%) are older than 60 years of age,
and they typically have a history of a slowly growing mole that has been present for a
decade or more.