Biomedical Engineering Reference
In-Depth Information
clinical applications
Introduction: Actinic Keratoses
Background and Epidemiology
AKs are a premalignant skin condition, comprising the third
most common reason and 14% of all dermatology offi ce vis-
its (48,49). Approximately 4 million Americans are diag-
nosed with AKs annually (50), with a prevalence of AKs
within the US population ranging from 11% to 26% and the
highest incidence in southern regions and older Caucasian
patients (51).
The concern for untreated AKs is their rate of transforma-
tion to cutaneous squamous cell carcinoma (SCC). A small
percentage of SCC metastasizes (52), and this is more likely in
higher risk areas, such as mucous membranes (e.g., lips) (53).
The reported conversion rate of AK to SCC varies widely, esti-
mated as 0.025-16% per lesion per year (54-58). AKs may be
considered an SCC-in situ (59,60), with AK resting on the pre-
cancerous end of a spectrum that leads toward invasive SCC.
It has been suggested that the AK/SCC continuum be graded
as “cutaneous intraepithelial neoplasia,” in a manner analo-
gous to cervical malignancy. Further histopathologic evidence
supports the link between AKs and SCC. Both lesions express
tumor markers, including the tumor suppressor gene p53 (61),
and over 90% of biopsied SCCs have adjacent AKs within the
examined histopathologic fi eld (62).
1.2
1.0
0.8
0.6
0.4
0.2
0.0
350
400
450
500
550
600 650 700
750
Figure 10.1
Porphyrin absorption curve displays maximum absorption in the
Soret band (360-400 nm) followed by four smaller peaks between 500 and
635 nm (Q bands).
lamps, LEDs, and intense pulsed light (IPL) systems. Non-
coherent light sources are easy to use, affordable, easily
obtained, and portable due to their compact size (45). The ear-
liest uses in PDT were fi ltered slide projectors that emitted
white light (17). Metal halogen lamps such as the Curelight
(Photocure, Oslo, Norway, 570-680 nm) are often employed
in PDT as they provide an effective light source in a time,
power, and cost-effective manner (17,46). In Europe, the PDT
1200 lamp (Waldmann Medizintechnik, VS-Schwennigen,
Germany) gained in popularity, providing a unit with high
power density emitting a circular fi eld of light radiation from
600 to 800 nm (40,46). Short arc, tunable xenon lamps have
also been used, emitting light radiation from 400 to 1200 nm
(40). The only widely available fl uorescent lamp used in con-
junction with PDT is the Blu-U (DUSA Pharmaceuticals, Inc.)
with a peak emittance at 417 ± 5 nm. LEDs provide a narrower
spectrum of light irradiation, usually in a 20-50 nm band-
width that matches the absorption spectrum of porphyrins via
a compact, solid, but powerful semiconductor (17,47). LEDs
are simple to operate, emitting light from the ultraviolet (UV)
to infrared (IR) portion of the electromagnetic spectrum (47),
and are relatively inexpensive compared with lasers. In addi-
tion, they can also provide wide area illumination fi elds. IPL is
yet another source of incoherent light, emitting a radiation
spectrum from approximately 500 to 1200 nm (47). Cutoff fi l-
ters allow customization of the delivered wavelengths. This
light source is particularly useful in photorejuvenation, target-
ing pigment, blood vessels, and even collagen.
Lasers provide precise doses of light radiation. As a collimated
light source, lasers deliver energy to target tissues at specifi c wave-
lengths chosen to mimic absorption peaks along the porphyrin
curve. Lasers used in PDT include the tunable argon dye laser
(blue-green light, 450-530 nm) (40), the copper vapor laser-
pumped dye laser (510-578 nm), pulsed dye laser (PDL, LPDL)
(585-595 nm), the neodymium-doped yttrium aluminum gar-
net potassium-titanyl-phosphate dye laser (532 nm), the gold
vapor laser (628 nm), and solid-state diode lasers (630 nm) (46).
Although laser sources allow the physician to deliver light with
exact specifi cations in terms of wavelength and fl uence, the fl u-
ence rate should be kept in the range of 150-200 mW/cm
2
to
avoid hyperthermic effects on the tissue (17,42). In fact, there is
evidence to support that cumulative light doses of greater than
40 J/cm
2
can deplete all available oxygen sources during the
oxidation reaction, making higher doses of energy during PDT
unnecessary (19).
Clinical Presentation and Diagnosis
AKs typically appear as 1-3 mm, slightly scaly plaques on an
erythematous base, often on a background of solar damage.
They are often detected more easily through palpation than
visual detection (63), due to their hyperkeratotic nature. The
surrounding skin often shows signs of moderate-to-severe
photodamage, including dyspigmentation, telangiectasias, and
sallow coloration due to solar elastosis (Fig. 10.2). Individual
AK lesions may converge, creating larger contiguous lesions.
Most AKs are subclincial and not readily apparent to visual or
palpable examination. The evidence for subclinical AKs is
their fl uorescence when exposed to ALA + Wood's lamp or a
specialized charge-coupled device (CCD) camera (64).
Although often asymptomatic, AKs may have accompanying
burning, pruritus, tenderness, or bleeding (49). Several vari-
ants of AK exist, including nonhyperkeratotic (thin), hyper-
keratotic, atrophic, lichenoid, verrucous, horn-like (cutaneous
horn), and pigmented variants (51). AKs on the lip, most
often occurring on the lower lip, are designated as actinic
cheilitis (53). As AKs often result from a long history of
UV exposure, the lesions usually arise in heavily sun-exposed
areas, including the scalp, face, ears, lips, chest, dorsal hands, and
extensor forearms (65). Risk factors for AKs include fair skin
(Fitzpatrick skin type I-III), history of extensive, cumulative sun
exposure, increasing age, elderly males (due to UV exposure),
history of arsenic exposure, and immunosuppression (48,49).
Histopathology
Histopathologic examination of AKs is characterized by atypi-
cal keratinocytes and architectural disorder (49). Early lesions
demonstrate focal keratinocyte atypia originating at the basal
layer of the epidermis and extending variably upward within
the epidermis (66). Hyperchromatic and pleomorphic nuclei
and nuclear crowding characterize the cellular fi ndings while
architectural disorder is comprised of alternating ortho- and
