Copyright © 2012 OA Publishing London
Competing interests: none declared. Conflict of interests: none declared.
All authors contributed to conception and design, manuscript preparation, read and approved the final manuscript.
All authors abide by the Association for Medical Ethics (AME) ethical rules of disclosure.
Hamdoon Z, Jerjes W, Upile T, McKenzie G, Jay A, Hopper C. Structural
validation of facial skin using optical coherence tomography. Head
Neck Oncol. 2012 Oct 15;4(3):67.
Structural validation of facial skin using optical
coherence tomography
Zaid Hamdoon1,2,3,4
Waseem Jerjes1,5,6
Tahwinder Upile4
Gordon McKenzie4
Amrita Jay4
Colin Hopper2,4,5
(1) Department of Oral and Maxillofacial Surgery, School of Dentistry, ALYarmouk University College, Baghdad, Iraq
(2) Unit of Oral and Maxillofacial Surgery, UCL Eastman Dental Institute,
London, UK
(3) Department of Oral and Maxillofacial Surgery, University of Mosul, Mosul,
Iraq
(4) Head and Neck Centre, University College London Hospitals, London, UK
(5) Department of Surgery, UCL Medical School, London, UK
(6) Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK
Corresponding authors
U
Zaid Hamdoon
Department of Oral and Maxillofacial Surgery,
University of Mosul,
Mosul,
Iraq
ZH: zaid19772000@yahoo.com
WJ: waseem_wk1@yahoo.co.uk
GM: gordon.mckenzie@md-ltd.co.uk
TU: mrtupile@yahoo.com
AJ: amritajk@msn.com
CH: c.hopper@ucl.ac.uk
2TU
U2T
Abstract
Background
Skin cancer is the most common malignancy in the Western world. Optical
coherence tomography (OCT), an optical imaging modality, offers real-time
imaging with micrometer resolution and has great potential for mapping skin
pathologies.
Objectives
In this immediate ex-vivo skin-OCT study we aimed to (1) identify the cellular
structures of normal facial skin using OCT and compare them to the gold
standard histopathology, (2) differentiate between normal and pathological
facial skin, and (3) create an optical (OCT) diagnostic criterion for the
detection of suspicious facial skin lesions.
Material and Methods
A total of 53 patients, with 57 suspicious facial lesions, participated in this
clinical study. Each patient had the skin lesion fully excised. The tissue was
then subjected to OCT in the immediate ex-vivo phase. Histopathological
evaluation revealed that 26 patients had basal cell carcinoma (BCC), 12 had
squamous cell carcinoma (SCC), 9 had actinic keratosis (AK), 7 had invasive
malignant melanoma (MM) and 3 had lentigo maligna (LM). The normal
microanatomical structures were identified and studied on optical biopsy.
Then the common architectural changes on OCT and histopathology paraffin
slides were correlated.
Results
Analysis of the OCT images facilitated the identification of normal architecture
of the facial skin. In this study, the stratum corneum, epidermis and papillary
dermis could be easily identified in macroscopically normal areas.
Pathologically, OCT could differentiate between BCC subtypes due to
different manifestations of backscattering. Morphological and light-scattering
changes were visible in the stratum corneum layer in actinic keratosis. OCT
features in SCC had more of a snowstorm appearance than BCC, but were
still distinguishable. Malignant melanoma and lentigo maligna were potentially
diagnosable using OCT.
According to the pathology criteria, there was overall 87% OCT suspicious
features of melanoma. Multicomponent specific OCT patterns were observed
in 93% of all types of BCC and in 95% for the nodular type. With SCC, 92%
OCT patterns were the most commonly observed and 73% and 95% for
lentigo maligna and actinic keratosis, respectively.
Conclusion
This study proved the success of OCT in identifying structural changes in
healthy and pathological facial skin. Further studies to prove its usefulness in
vivo are required.
Introduction
Skin cancer is the most frequent cancer in the western world. It encompasses
basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and malignant
melanoma (MM) (1). The incidence of skin cancer is still increasing globally,
which introduces a huge health and financial burden on health systems (2,3).
This trend can be counteracted by means of primary prevention (avoidance of
risk factors) and secondary prevention (early diagnosis and intervention).
Early diagnosis is usually achieved by regular visual inspection and a surgical
biopsy when required. It is clearly impractical to biopsy everyone, and there
are no consistent guidelines for taking a biopsy.
Screening efforts using non-invasive real-time diagnostic tools are evolving.
However, the lack of evidence for the efficacy of these tools remains a real
obstacle to adequate skin cancer screening and may account for delayed
diagnosis in some cases (4). In order to increase the sensitivity and specificity
of early detection and monitoring, strong evidence-based studies are required
before any tool can be introduced into the clinical setting.
The development of optical diagnostics is a current necessity. The goal is to
provide real-time non-invasive diagnoses of suspect tissues. This will help
reduce tissue trauma, reduce the work load on pathology departments and
reduce the time the anxious patient has to wait for a diagnosis (5,6).
A light of a specific wavelength is fired into tissue and the reflected light is
measured in such a way that a specific optical signature can be generated
(i.e. cellular and subcellular changes in elastic scattering spectroscopy,
molecular vibration in Raman spectroscopy, surface morphology by
microendoscopy and biochemical changes from tissue fluorescence).
The main aim of these optical techniques is, eventually, to act as an adjunct to
histopathology to provide immediate diagnosis of lesions and aid in monitoring
lesions with risk of malignant transformation in the clinical setting (7).
Optical coherence tomography (OCT), first applied in 1991 by Huang et al., is
a non-invasive interferometric (superimposing or interfering waves)
tomographic imaging modality that allows millimetre penetration with
micrometre-scale axial and lateral resolution, and provides morphological
information similar to pathology.
OCT is an optical technique that uses a low-coherence interferometer to
develop a two dimensional image of optical scattering from internal tissue
microstructures. OCT also allows non-invasive monitoring of morphologic
changes in skin diseases and may have a particular role in the monitoring of
medical treatment of non-melanoma skin cancer. Several technical
modifications are being implemented to further improve the quality of images
of this technology.
For OCT to become clinically interpretable and relevant, the structures
visualised must be correlated with the corresponding tissue microstructures.
To date, the interpretation of OCT images has been largely intuitive and
empirical (8).
We designed this immediate ex-vivo study to (1) identify cellular structures in
normal facial skin using OCT and compare them to the gold standard
histology, (2) differentiate between structural changes in normal and
pathological facial skin, and (3) build on a diagnostic criterion in the use of
OCT for the detection of suspicious facial skin lesions using a commercially
approved machine.
Material and methods
Fifty-seven facial lesions from 53 patients who presented with suspicious
lesions to the UCLH Head & Neck Centre, London, were recruited for this
study.
The study protocol was approved by the local committees of ethics for human
research. The protocol was devised in cooperation with the Departments of
Pathology at University College London and Imperial College.
Informed consent was obtained from each patient explaining the nature of the
study. Inclusion criteria included a minimum age of 18 years and no prior skin
cancer in the same area or any skin procedures (i.e., electrosurgical excision,
PDT, cryotherapy…etc.).
In this study we used a swept-source frequency-domain optical coherence
tomography microscope (Michelson Diagnostics EX1301 OCT Microscope
V1.0), the components of which are illustrated in Figure 1. The light source
used was a Santec HSL-2000, with an imaging wavelength of 1310nm, axial
optical resolution of <10µm, and lateral optical resolution of <10µm. The
system provides an image resolution of 5.3µmpixels with a maximum image
width of 6mm, a sub-surface imaging depth of 1.5mm, and a focal depth of
1mm. Samples can be manipulated to see full quality results on the screen
instantly, with an image capture time of <100ms and refresh rate of >1Hz.
The multi-beam swept source OCT EX1301 (Michelson Diagnostics Ltd.,
Orpington, UK) utilises a novel optical set-up involving multiple optical
channels which does not suffer from loss of sensitivity or other serious
drawbacks. The idea is to partition the depth of field into sub-fields, and
provide a separately focused beam for each sub-field.
The laser beam in the SS-OCT EX1301 is split into 5 ‘beamlets’ using an
etalon-type ‘rattle plate’ prior to the interferometer beam splitter. Four of these
beams are used to scan the specimens and are relayed back to an array of
photodiodes where they interfere with four reference beams in the
conventional manner. The fifth beam is imaged onto a 5th photodiode to
generate a balance signal.
Each patient underwent full excision followed by OCT of the excised lesion in
the immediate ex-vivo phase. The specimens were kept in saline until being
transferred for scanning. The OCT instrument captured b-mode scans of the
tissue.
Digital pictures and diagrams were produced to ensure that the
histopathologist would be able to identify the scanned planes accurately and
provide an exact histopathological image. Our co-registration method was
enhanced by using dyes and sutures for better orientation.
A histopathological diagnosis was then achieved after several steps, including
embedding in paraffin wax, staining with haematoxylin and eosin, and
examination by light microscopy. Close attention was paid to tissue shrinkage
in formalin when comparing microanatomical structures of immediate ex-vivo
OCT images and paraffin wax slides.
Each whole skin specimen was placed under the OCT imaging beam and
imaged ex vivo as the transverse virtual line between the two landmarks
(Figure 2). To provide a linear focal trough, a series of images were taken
from edge to edge along the whole length of the specimen. All the pathology
slides were examined and the most obvious architectural changes were
recorded.
Several variables were studied on the OCT images to assess microanatomical structures of normal facial skin and architectural changes in these
areas. These included visibility of the stratum corneum, epidermis and
papillary dermis and other micro-anatomical structures. Controlled OCT
measurements were taken from the edges of the macroscopically normal
facial skin of the surgical biopsy; this was compared to OCT images of the
suspect area taken from the centre of the lesion.
These variables were compared between OCT and pathology by a senior
clinician and a senior pathologist who were trained to read OCT images and
not blind to the diagnosis. Descriptive diagnostic criteria were then extracted
from each OCT image and its corresponding pathology according to
agreement between the two assessors.
Results
All data were entered and stored in a computerized database designed with
Microsoft Excel 2000. The statistical analysis was performed using the
statistical software package SPSS 13.0 (SPSS, Chicago, Ill).
Fifty–seven clinical and pathologically different skin lesions were obtained
from 53 patients. The lesions were obtained from 34 women (64.1%) and 19
men (35.9%) ranging in age from 38 to 84 years (median age: 48.4 years).
Twenty-nine (53%) were located on the cheek, 16 (28%) on the nose, 6
(10.5%) on the ear, 3 (5.0%) on the forehead and 3 (5.0%) on the lower lip.
Histo-pathological evaluation revealed that 26 (45.5%) patients had basal cell
carcinoma (BCC), 12 (21%) had squamous cell carcinoma (SCC), 9 (15.9%)
had actinic keratosis (AK), 7 (12.3%) had invasive malignant melanoma (MM)
and 3 (5.3%) were diagnosed with lentigo maligna (LM).
The most common histological subtypes for the BCC were nodular (53.5%),
major cystic (21.5%), and microcystic (17.8%) and the least common type
was superficial (7.2%) BCC. The majority of SCCs were located on the ear,
followed by cheek and forehead (Table1).
OCT and histology correlation (normal margins)
OCT was able to visualise and differentiate skin layers and structures such as
stratum corneum, epidermis, and papillary dermis. Only a few large and
prominent epidermal papilla has been correlated in 50% with gold standard
histology. Describing features in normal facial skin was straightforward for the
assessors (Figure 3). The dermal-epidermal junction, the epidermal layer and
the stratum corneum could all be identified in 100% of the specimens (Table2).
OCT and histopathology correlation
With respect to actinic keratosis, correlation was achieved in 60% of the
specimens by identifying thickening in the DEJ, in 100% by identifying
destruction in the corneum layer and in 89% by identifying thickening in this
layer.
With regard to basal cell carcinoma, correlation was achieved in 100% of the
specimens by identifying the dermal-epidermal junction, and in 100% by
identifying the epidermal, keratin cell layer. With nodular BCC, areas beyond
the dermal-epidermal junction exhibited a solid nest or honeycomb form in
93% of cases, while major or microcystic BCC showed small multiple empty
spaces in 100% of cases. Superficial spreading BCC were mainly represented
by cords or small buds protruding from the epidermis into the superficial
dermis in 100% of cases.
With regard to squamous cell carcinoma, correlation was achieved in 91% of
the specimens by identifying the dermal-epidermal junction as damaged, 83%
by identifying the epidermal layer as increased in thickness, and 100% by
description of the stratum corneum layer and its changes. Other features
included small bright clusters (nonhomogenous) within the papillary dermis
(80%).
With regards to lentigo maligna, correlation was achieved in 30% of the
specimens by identifying the rete ridges as elongated, and in 30% by
identifying nests or lobules within the epidermal layer near the DEJ.
With regards to malignant melanoma, correlation was achieved in 85% of the
specimens by identifying abnormal signals within the papillary dermis layer,
which exhibited diffuse or patchy reflectivity and loss of the typical bright
horizontal linear structures, and in 57% the dermal-epidermal junction was
described as intact with prominent junctional densities (Tables 3,4).
Qualitative OCT analysis for different pathologies
In normal skin, the majority of the top layer (stratum corneum (SC)) shows
more signal reflection than the lower layer that represents the epidermis. The
SC was fissured and wrinkled in areas on the face. The epidermis, the second
layer below the SC layer, appears significantly darker (low signal reflection)
until the transition with the dermis. The signal intensity at the lower boundary
of the epidermis represents the dermo-epidermal junction. There is no
boundary for the dermo-epidermal junction except the smooth or undulated
demarcation between the less reflective/backscattering layer of the epidermis
to the highly reflective/backscattering papillary dermal layer.
Description of stratum corneum layer (SC)
In AK, the SC layer demonstrates hyper-reflective features (bright) due to a
water/SC refractive index difference, with mostly focal areas of damage. The
damaged area appears as a punched out depression, with or without lifting of
the stub from the epidermal layer (Figure 4). In nodular and infiltrating BCCs,
this layer has normal-reflective features because the tumour infiltrates the
deeper tissue, dissimilar to the ulcerative type. In LM and MM this layer either
disappears or presents very thin hypo-reflective features.
Description of epidermal layer (EL)
Epidermal thickness is of considerable significance in AK, with homogeneity
similar to the surrounding normal margins. The situation is similar in BCCs
with dark spaces (solid or empty) of different sizes within the epidermal layer
(Figures 5,6). Unlike with AK, BCCs have EP layer thicknesses that vary
significantly for different histologic sub-types.
In LM, the EP layer usually becomes atrophied in the active areas, with some
hypoecoic areas that represent junctional activity in the rete ridges (Figure 7).
With MM, elongated rete ridges are mainly seen (Figure 8).
Description of dermal layer
In AK, the dermal layer is completely normal with signal-poor snail-track like
cavities corresponding to blood vessels, hair follicles and some sweat glands.
Some BCC tumours aggregate as signal-poor round spots surrounded by
hyporeflective bands.
For SCCs and MMs, these non-homogenous areas are signal-free globules,
and represent concentrations of melanin or keratin pearl in spherical or
elliptical arrangements below breached areas in the dermo-epidermal
junction, usually extending from the EL so there is no band surrounding the
spaces.
Description of dermal-epidermal junction (DEJ)
The dermo-epidermal junction is rather flat with an intact border between the
epidermis and dermis, as in the case of AK and BCC. Breaches in cases of
SCC (Figures 9, 10) may disappear in infiltrative growing melanoma or display
a typical saw tooth appearance from damage to the junction which pushes the
rete ridges in early stage cases. These appear as echo-poor, low scattering
projections sharply demarcated from the echo-rich homogeneous dermis.
Diagnostic criteria
In the case of the stratum corneum (SC), OCT images were assessed with
regard to reflectivity as hyper-reflective (thick), normal-reflective or hyporeflective. Surface damage confined within the stratum corneum is one of the
most important diagnostic criteria. Epidermal layer thickness, whether
increased, decreased or no change according to normal margins was also
assessed. The epidermal layer may show nonhomogeneous lobules with
active single or multiple tumour nest collection lobules inside. DEJ may be
demarcated without protrusion toward the dermis, demarcated with protrusion
or non-demarcated (breach).
Signs within the papillary dermis include homogenous or non-homogenous
signal indicating connective tissue invasion. The presence of solid or empty
spaces surrounded with hyper-reflective band within the dermal layer was
found in BCCs. The main architectural feature for AC was hyper-reflectivity
and/or disruption of the stratum corneum and demarcated DEJ. For
squamous cell skin cancer, the DEJ lost its integrity; other features included
disintegration of superficial epidermal layers (honeycombing and
cobblestoning) with small bright clusters within the papillary dermis.
With melanoma, non-edged papillae, cerebriform clusters infiltrating dermal
papillae, diffuse or patchy reflectivity, loss of the typical bright horizontal linear
structures were diagnostic. Lentigo maligna was characterised by
predominantly uniformly elongated rete ridges as well as uniform nests within
the epidermis (Table 5).
Discussion
This study reports on the morphologic features observed in OCT imaging
performed ex-vivo on fresh facial skin tissue specimens. Although the sample
size is small, it represents the range of relevant morphologies needed for their
future use for in-vivo diagnosis, and the results indicate that morphological
changes on OCT images match histopathology.
To interpret OCT images of abnormal skin, it is necessary to be familiar with
normal skin architecture. In normal skin histology, the epidermis is comprised
primarily of keratinocytes and a smaller population of dendritic cells, which are
the melanocytes and Langerhans cells. The dermis is comprised of blood
vessels, nerves, inflammatory cells and fibroblasts enmeshed with collagen
fibres and elastin. The papillary dermis comprises projections into the
epidermis, called dermal papillae. The meeting point between the epidermis
and the dermis is called the dermal-epidermal junction. In the epidermis, the
keratinocytes are differentiated to form four different layers. The stratum
corneal is the most superficial layer of the epidermis, which is comprised of
flat anucleated keratinocytes.
Histopathologically, there are many histological variants of BCC, including
nodular, superficial, morpheaform (or sclerosing), infiltrative and micronodular
(9). A typical BCC lesion has a pearly or waxy appearance. The shape of the
lesion is flat or slightly raised, white or light pink, flesh-coloured or brown, with
visible blood vessels in the lesion or adjacent skin. It usually has a central
ulceration and a well-defined border. It may also appear as a scar-like lesion
without a history of injury to the skin in that area. The less common infiltrative
type can be seen as poorly defined, lightly pigmented, indurated, flat skin
lesions, occasionally with overlying telangiectasia.
Squamous cell carcinoma is the second most common skin cancer,
representing 20% of all cutaneous malignancies (10). The histologic spectrum
of squamous cell carcinoma begins with actinic keratosis (AK). Actinic
keratoses (AK) are the most common pre-malignant skin pathology (11).
Histologically, the difference between AK, SCC in situ and frank SCC is
described as such; AK involves only part of the epidermis, SCC in situ
occupies the full thickness of the epidermis, and invasive SCC penetrates the
basement membrane of the epidermis.
In the current study, the results showed that traditional normal histological
landmarks such as the stratum corneum, dermo-epidermal junction and
papillary dermal layer can be clearly identified using OCT. This study
indicates that the characteristic layering of normal skin is lost both in BCCs
and SCCs, and this is identifiable on OCT.
The depth of the OCT in this study was limited to a maximum of only 2mm.
which is satisfactory to visualise the epidermis and dermis layers where most
of the pathological changes occur. The axial resolution of 10µm would not
allow detection of single cells. However, the investigation of single cells or
subcellular structural changes is a part of ongoing research. Unlike other
imaging modalities, reflectance confocal microscopy enables identification of
these layers based on architecture and cytological characteristics.
This layer varies in depth depending on anatomical site and sun exposure.
Under confocal microscopy, it produces a bright image. Large polygonal
anucleated korneocytes (25–50µm) can be seen. Dermatoglyphs appear as
dark linear valleys amidst the korneocyte groups. In comparison with OCT,
conofocal microscopy has higher resolution than OCT. However, the depth of
detection is less than OCT.
One of the great advantages of OCT, which cannot be seen by confocal
microscopy, is the possibility of analysing micro-anatomical structures up to a
depth of 1500µm. This means any abnormalities extending from the papillary
dermis to the reticular dermis are diagnosable. For this reason, tumours that
invade the depths can be more properly assessed. This includes areas where
the epidermis has a shallow thickness, and part of the reticular epidermis can
also be assessed (12)
Further technical development of OCT, such as polarization-sensitive OCT
(PS-OCT) or speckle-reduced OCT may increase the diagnostic accuracy.
Finally, the introduction of image analysis, machine learning algorithms or
neural networks may provide a more precise classification of AK and BCC
lesions than relying on the human eye alone.
In the case of nodular BCC, a single significant feature (i.e. the formation of
tumour aggregates in the upper dermis) was found to be characteristic of the
investigated lesions. This study revealed that the diagnostic ability of OCT is
ideally valuable in detecting sub-types and early stages of BCC; however,
partial loss of normal OCT architecture may not be seen in various pre-BCC
lesions.
With regard to AK lesions, focal changes and thickening of the epidermis,
OCT investigation of the AC showed another diagnostic feature in the form of
buds and irregular proliferation of tumour tissue attached to the undersurface
of the epidermis or in the form of a very distinct thickening of the dermoepidermal layer. The dermo-epidermal junction appeared less well
demarcated compared to healthy skin, which is probably due to cellular
aggregates of this lesion. OCT’s ability to detect cell aggregation at the
dermo-epidermal junction, at the pre-invasion stage, is a very profound finding
in detecting the early invasive phase of skin cancer.
Korde and colleagues (13) studied OCT images of sun damaged skin and AK
and described characteristic dark elongated bands in the epidermis for
accurate diagnosis of AK. These bands correspond to keratin deposits in a
thickened stratum corneum. The main problem in AK diagnosis is the
thickening of the stratum corneum layer, which reduces the penetration depth
of OCT; this is attributed to the optical properties of hyperkeratosis in AK.
Features of SCC are distinct by OCT. However, this study did not evaluate the
sensitivity and specificity of the OCT. Both BCCs and SCCs in the current
study demonstrated very reliable diagnostic features, contrary to the finding of
Mogensen et al (14), who concluded that the naked eye is superior to OCT for
diagnosis of non-melanoma skin cancer.
Other researchers have performed OCT studies on BCC. They found that the
epidermis and associated basal cell carcinoma had identifiable structural
features that were apparent in both the OCT images and histologic pictures.
The lobules, islands, and infiltrating strands of basal cell
carcinoma appeared similar in OCT images and histologic sections regardless
of the type of tumour (15).
Interestingly, this study demonstrated that OCT is capable of distinguishing
malignant melanoma, with the ability to differentiate the early stage of lentigo
maligna. Furthermore, OCT was still helpful in identifying the late stage of
lentigo maligna. In malignant melanoma, OCT images show irregular
structures in the lower epidermis with the dermo-epidermal junction.
De Giorgi et al (16) recently performed a pilot study imaging nine dysplastic
nevi and one superficial spreading melanoma by OCT in vivo. The authors
reported that in selected cases OCT allows for an in vivo correlation to be
established between surface dermatoscopic parameters and histopathological correlates, in particular the pigment network and brown globules.
Another study conducted on melanoma skin lesions failed to detect any
definitive features in OCT images enabling differentiation of tumour subtypes
(i.e. junctional nevi, compound nevi) but demonstrated useful discriminating
parameters between benign nevi and malignant melanoma (17).
Our methodology of histological serial slices could play an important role in
correlating the OCT scanning lane with the histological section. However,
deformation by histological processing and slightly different sectioning levels
are unavoidable and can make direct comparisons of histological pictures and
OCT images appear difficult. Nevertheless, this happened in only four cases,
in which it was still possible to demonstrate the same morphological
structures with OCT imaging and by histological investigation.
However, this is one of the limitations of this study. Precise control of the
histological plane is difficult, and combined with processing artifacts in
histology, this makes precise one-to-one registration of histology to OCT/
OCM images challenging. Therefore, the assessments of image and
histological data are based on correspondences in feature information.
Another limitation in the current study is the relatively small sample size,
which prevents us from determining OCT’s sensitivity and specificity for
assessment of skin malignancy.
There are three basic differences in OCT in relation to the conventional
histology routine. In OCT, images are obtained horizontally from the lesion,
whereas in conventional histology the sections are made vertically. The
images are obtained in gray scale, similar to what happens in radiographs.
Moreover, OCT imaging can provide instantaneous dynamic images of the
skin and may in the case of in vivo OCT show events such as blood flow, in
poor agreement with routine histology using formalin-fixed and paraffinembedded cut sections.
Our observations in this descriptive study indicate that despite the ex vivo
nature of the specimens, the level of resolution of OCT seems adequate for
clinical practice. Moreover, it suggests that in the future resolution using in
vivo OCT systems will improve due to tissue perfusion, which may also further
improve the diagnostic potential of the method for all skin cancers. OCT might
also be a promising tool for the characterisation of melanoma skin lesions.
Conclusion
This study proved the success of OCT in identifying structural changes in
healthy and pathological facial skin. Further studies to prove its usefulness in
vivo are required.
Competing interests
Mr Colin Hopper is an Advisory Board Member at Michelson Diagnostics,
Kent, UK. Dr Gordon McKenzie is a Medical Applications Director at
Michelson Diagnostics, Kent, UK.
Authors’ contributions
All authors designed and performed the study, carried out the literature
research and manuscript preparation. All authors were responsible for critical
revision of the scientific content and manuscript review. All authors approved
the final version of the manuscript.
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Tables
Table 1: Patient demographic information
No. (%)
Gender
Male
Female
19 (35,9)
34 (64.1)
Anatomical location
Cheek
Nose
Ear
Forehead
Lower lip
29 (53)
16 ( 28)
6 (10.5)
3 (5)
3 (5)
Lesion colour
Mixed
Red
Brown
Black
White
Non-specific
30 (52.6)
11 (19.2)
7 (12.2)
4 (7)
3 (5.2)
6 (10.5)
Skin type
Type II
Type III
Type VI
21 (39.6)
18 (33.9)
14 (26.4)
No. (%)
Signs and symptoms
Itchiness
Symptomless
Scaly
Lumpy
Bleeding
15 (28.3)
13 (24.5)
10 (18.8)
10 (18.8)
5 (9.4)
Clinical features
Papule
Erosion
Ulcer
Nodule
Others
17 (29.8)
15 (26.3)
12 (21)
10 (17.5)
3 (5.2)
Histopathological diagnosis
BCC
26 (45.5)
SCC
12 (21)
AK
9 (15.9)
LM
3 (5.3)
MM
7 (12.3)
Table 2: Correlation between OCT and normal histology
Normal resection margins
OCT
Histology
Total
Identification of the stratum corneum
Yes
No
30
0
30
0
60
0
Identification of the epidermis
Yes
No
30
0
30
0
60
0
Identification of epidermal papilla
15
30
Identification of (DEJ)
Yes
No
28
2
30
0
58
2
Homogenous papillary dermal layer
Yes
No
30
0
30
0
60
0
Table 3: Common descriptive features between OCT and pathology from skin
lesions agreed by two observers (I)
SCC
OCT
Pathology
Total
11
1
12
0
23
1
5
7
6
6
11
13
4
8
5
7
9
15
Yes
12
12
24
No
0
0
0
OCT
14
12
Pathology
15
11
Total
29
23
8
18
8
18
16
36
6
20
6
20
12
40
2
24
2
24
4
48
Dermal–epidermal junction (DEJ) lost integrity
Yes
No
Superficial epidermal layers (honeycombed)
Yes
No
Small bright cluster at the papillary dermis
Yes
No
Stratum corneum disruption or thickening
BCC
Solid nest or honeycomb beyond (DEJ)
Yes
No
Small multiple empty spaces
Yes
No
Cystic BCC, large one or two empty space
Yes
No
Cords or small buds protruding from
epidermis
Yes
No
Table 4: Common descriptive features between OCT and pathology from skin
lesions agreed by two observers (II)
AK
Parakeratosis/hyperkeratosis
Yes
No
Stratum corneum disruption
Yes
No
Dermal–epidermal junction thickening
Yes
No
Total
Yes
No
OCT
Pathology
Total
8
1
9
0
17
1
9
0
9
0
18
0
3
6
5
4
8
10
20
7
23
4
OCT
Pathology
Total
4
3
7
0
11
3
6
1
7
0
13
1
7
0
7
0
14
0
OCT
Pathology
Total
1
2
3
0
4
2
1
2
3
0
4
2
MM
Non-edged rete ridges with clusters infiltrating
papillary dermal layer
Yes
No
Loss of typical bright horizontal linear
structures
Yes
No
Intact dermo–epidermal junction
Yes
No
LM
Elongated rete ridges
Yes
No
Uniform nest within the epidermis
Yes
No
SC hyperreflective
SC hyporeflective
SC
normoreflective
damaged
EL ↑
EL ↓
EL ↔
nest or lobule in
EL
homogenous EL
DEJ demarcated
without protrusion
toward D
DEJ demarcated
with protrusion
toward D
DEJ not
demarcated
empty space in D
solid space in D
non-homogenous
D
Table 5: Descriptive interpretation of OCT image changes
BCC (n= 26)
10
5
8
3
7
3
16
17
9
18
2
0
16
9
1
SCC (n=12)
8
0
2
2
10
0
2
0
12
0
1
11
6
0
6
AK (n=9)
8
0
0
1
3
0
6
1
8
9
0
0
0
0
0
LM (n=3)
0
0
3
0
1
1
1
3
0
1
2
0
0
0
0
MM (n=7)
2
0
5
0
2
3
2
1
6
1
4
2
4
1
2
Normal resection margins
(n=30)
0
0
30
0
0
0
30
0
30
30
0
0
0
0
0
Pathology entity
SC=stratum corneum layer, EL=epidermis layer, DEJ=dermo-epidermal junction ↑=increase, ↓=decrease, ↔=no change, D=
dermis.
Figures
Figure 1: Schmatic view of the lab based OCT machine
Figure 2: Specimen with orientation suture under OCT scanning arm with
laser guiding beam. The scanned area is between the two reference sutures
Figure 3: Histology versus OCT scan for normal skin margin of the cheek
showing three distinctive layers. A: representing the stratum corneum, B:
epidermis, C: DEJ, D: Dermis, E: papilla. Correlation was good for the stratum
corneum, epidermis while few large and prominent papilla has been
correlated
Figure 4: AK showing damage to stratum corneum layer (A) with thick
epidermis (B) but intact dermo-epidermal junction
Figure 5: Mixed cystic solid BCC
Figure 6: Giant cystic BCC showing lobular hypo-ecoic OCT feature
occupying large portion of dermis layer
Figure 7: Lentigo maligna, characterized by a predominantly uniformly
elongated rete ridges (Arrow). Uniform nests within the epidermis (circle)
Figure 8: Malignant melanoma, non-edged papillae (arrow), cerebriform
clusters infiltrating dermal papillae (circle), diffuse or patchy reflectivity, partial
loss of the typical bright horizontal linear structures
Figure 9: SCC in situ (Bowen's disease) from temple showing thick stratum
corenum ,hyperkeratosis (arrow), thickening of the epidermal layer with
broadening of DEJ as early sign of papillary dermal layer invasion (circle)
Figure 10: SCC showing the transitional area between intact and damaged
DEJ (red arrow)