1 Masterarbeit Dermatoscopic Study of Nonfacial Actinic Keratosis in a Group of Patients with FitzPatrick skin type I and a Proposed New Classification of Nonfacial Actinic Keratosis Results and Atlas Eingereicht von Dr med. Conor Brosnan zur Arlangung des akademischen Grades Master of Science (MSc) an der Medizinischen Universität Graz Univeritätsklinik für Dermatologie und Venerologie Unter der Betreuung von Professor Dr. Andreas Blum Dingle, Co Kerry, Ireland 1 February 2020
Transcript
1
Masterarbeit
Dermatoscopic Study of Nonfacial Actinic Keratosis in a Group of Patients with FitzPatrick skin
type I and a Proposed New Classification of Nonfacial Actinic Keratosis
Results and Atlas
Eingereicht von
Dr med. Conor Brosnan
zur Arlangung des akademischen Grades
Master of Science (MSc)
an der
Medizinischen Universität Graz
Univeritätsklinik für Dermatologie und Venerologie
Unter der Betreuung von
Professor Dr. Andreas Blum
Dingle, Co Kerry, Ireland
1 February 2020
2
Eidesstattliche Erklärung
Ich erkläre eherwörtlich, dass ich die vorliegende Arbeit selbständig und ohne fremde Hilfe
verfasst habe, andere als die angegebenen Quellen nicht verwendet habe und die den
benutzten Quellen wörtlich oder inhaltlich entnommenen Stellen als solche kenntlich gemacht
habe.
Dingle, Co. Kerry, Ireland, 1 February 2020 Conor Brosnan
3
Ar scáth a chéile a mhaireann na daoine
People depend on each other
(Irish proverb)
4
Acknowledgements to
Professor Dr. Andreas Blum, Public, Private and Teaching Practice of Dermatology, Konstanz
and the University of Tübingen, Germany who has patiently and expertly guided the
completion of this thesis
Grainne, Sadhbh, Sorcha and Ana who have understood and supported my journey into
dermatoscopy
Tom Fox for technical support and encouragement
The patients of West Kerry
5
Table of contents
Abstract 6
Zusammenfassung 7
Introduction 8
Methods 22
Results 23
Discussion 24
Atlas 29
References 49
6
Abstract
Background:
Actinic keratosis is the most common carcinoma in-situ in humans. This thesis is the first descriptive
dermatoscopic study of nonfacial actinic keratosis in a group of patients with FitzPatrick skin type I. It
proposes a new classification of nonfacial actinic keratoses.
Aim:
1. A dermatoscopic description of nonfacial actinic keratoses.
2. To propose a new classification of nonfacial actinic keratosis.
3. To establish if the classification of facial actinic keratosis by Zalaudek et al was applicable to
nonfacial sites.
Method:
This observational study was undertaken in the author’s General Practice in Dingle, Co Kerry, Ireland
between July 2017 and September 2019. 106 actinic keratoses from 43 patients were examined for
ten dermatoscopic features.
Results:
The 43 patients varied in age from 57 to 97 with an average age of 74 years. FitzPatrick skin type 1
was found in 93.1% of the patients and 6.9% had skin type 2. The lesions were found on the dorsum
of the hands in 87 (82%) of cases, 12 (11.3%) on arms, 5 (4.7%) on fingers and one each on shoulder
and chest. A previous history of 38 skin carcinomas – 19 basal cell carcinomas, 16 squamous cell
carcinomas, two melanomas and one adnexal cancer –were found in 21 (48.8%) of the patients – 20
men and one woman. Two of the patients had both basal cell carcinomas and squamous cell
carcinomas excised, one patient had an adnexal tumour and five basal cell carcinomas removed and
one had four basal cell carcinomas excised. The dermatoscopic findings reveal more than seven
times as many linear-irregular vessels and four times as many dotted vessels as a study on nonfacial
actinic keratosis in skin type ll and lll and ten times as many linear-irregular vessels and seven times
as many dotted vessels as a study of facial actinic keratosis in skin type ll. This study also found more
than three times as many white structureless areas, four times as many rosettes and more than
twice the incidence of erythema as the study on facial actinic keratoses. The study had one third the
incidence of brown pigmentation as the study on nonfacial actinic keratoses.
Conclusion:
The high frequency of blood vessels, white structureless areas, rosettes and erythema and low
incidence of brown pigmentation are the most common features of nonfacial actinic keratosis. This
study does not support the use of Zalaudek’s classification of facial actinic for nonfacial sites.
7
Abstrakt
Hintergrund:
Aktinische Keratosen sind das häufigste in-situ Karzinom des Menschen. Diese Masterarbeit ist die
erste deskriptive Studie von nicht-fazialen (extra-fazialen) aktinischen Keratosen bei einer
Patientengruppe mit FitzPatrick Hauttyp I.
Ziel:
1. Eine dermatoskopische Beschreibung der nicht-fazialen aktinischen Keratosen.
2. Vorschlag einer neuen dermatoskopischen Klassifikation der nicht-fazialen aktinischen Keratosen.
3. Überprüfung ob die dermatoskopische Klassifikation der fazialen aktinischen Keratosen nach
Zalaudek et al. für die nicht-fazialen aktinischen Keratosen anwendbar ist.
Methode:
Diese deskriptive Observationsstudie wurde durch den Verfasser in der General Practice in Dingle,
Co Kerry, Irland, zwischen Juli 2017 und September 2019 durchgeführt. 106 extrafazialen aktinischen
Keratosen von 43 Patienten wurde untersucht auf die Anamnese von Hautkrebs und den
dermatoskopischen Strukturen. Die Häufigkeiten der Strukturen wurden evaluiert.
Ergebnisse:
Die 43 Patienten waren durchschnittlich 74 Jahre alt (von 57-97 Jahren). FitzPatrick Hauttyp I fand
sich bei 93,1% und Hauttyp II bei 6,9% der Patienten. Von den 106 Läsionen fanden sich 87 (82%) an
den Handrücken, 12 (11,3%) an den Armen, fünf (4,7%) an den Fingern und jeweils eine (1%) an der
Schuler und Brust. In 21 (48,8%) der Patienten (20 Männer und eine Frau) fanden sich in der
Anamnese 38 Hautkrebse (19 Basalzellkarzinome, 16 Plattenepithelkarzinome, zwei Melanome und
ein Adnextumor). Bei den dermatoskopischen Strukturen fanden sich siebenmal häufiger lineare
irreguläre Gefäße und viermal häufiger punktförmige Gefäße verglichen zu einer Studie von nicht-
fazialen aktinischen Keratosen mit Hauttyp II und III; 10-mal häufiger ließen sich lineare irreguläre
Gefäße und siebenmal häufiger punktförmige Gefäße nachweisen verglichen zu der Studie von
fazialen aktinischen Keratosen mit Hauttyp II. Ebenso fanden sich in dieser Studie dreimal häufiger
weiße strukturlose Areale, viermal häufiger Rosetten und mehr als zweimal häufiger Erytheme
verglichen zu der Studie mit fazialen aktinischen Keratosen. Hingegen konnten nur in einem Drittel
der Fälle braune Pigmentierung gefunden werden verglichen zu der Studie mit nicht-fazialen
aktinischen Keratosen bei Hauttyp II und III.
Zusammenfasung:
Die hohe Anzahl der Blutgefäße, weißen strukturlosen Arealen, Rosetten sowie dem Erythem und
das geringere Auftreten der braunen Pigmentierung sind die häufigen dermatoskopischen
Strukturen der extrafazialen aktinischen Keratosen. Diese Studie konnte aufzeigen, dass die
dermatoskopische Klassifikation der fazialen aktinischen Keratosen nach Zalaudek et la. nicht für die
extrafazialen aktinischen Keratosen übernommen werden kann.
8
Introduction
This thesis is a descriptive dermatoscopic study of nonfacial actinic keratosis in a group of patients
with FitzPatrick skin type I in a General Practice in southwest Ireland and a proposed new
classification of nonfacial actinic keratosis. First described by the Parisian dermatologist Dubreuilh in
1896 (‘hyperkératoses circonscrites’)1 actinic keratoses are focal areas of keratinocytes proliferation
and differentiation exhibiting varying degrees of epithelial dysphasia found on sun exposed skin of
the head and upper extremities.2 The dermatoscopic features of facial actinic keratosis have been
well documented in many research papers whereas this is the first analysis of non-facial actinic
keratosis in FitzPatrick skin type I.
Actinic Keratosis
Actinic keratosis is the most common carcinoma in-situ in humans and, as life expectancy increases,
will become a greater burden for both patients and their physicians. It is estimated that they account
for at least 10% of all dermatological visits.3 The importance of actinic keratosis relates to their
cosmetic appearance, financial cost and the potential for malignant transformation to invasive
squamous cell carcinoma, the majority of which arise in actinic keratoses. €1.7 billion was spent on
treating actinic keratoses in the US in 2013.4 Actinic keratoses are either macules or patches and,
since 2007, have been classified as grade 1 if just visible or palpable, grade 2 if red and scaly and
grade 3 if keratotic.5 (Figures 1, 2 and 3). The malignant potential of actinic keratosis to become
squamous cell carcinoma varies from 0.025% to 16%.6
Figure 1: Actinic keratosis-Grade 1-feels better than seen
9
Figure 2: Actinic keratosis-Grade 2-easily felt and seen
Figure 3: Actinic keratosis-Grade 3-obvious
Pathogenesis
Actinic keratosis, also known as solar keratosis or keratinocyte intraepidermal neoplasia, is a
keratinocyte neoplasm that typically occurs on chronically sun-exposed surfaces of the face, ears,
balding scalp, dorsal hands and forearms in people over 50 years of age/elderly individuals. These
lesions occur in patients in their twenties and thirties who are fair skinned/red hair phenotype and
live in low latitudes.7 The other known risk factors include male sex, chronic immunosuppression,
arsenic exposure, psoralen ultraviolet A (PUVA) therapy, exposure to X –ray or radioisotopes and
chronic cutaneous inflammation. Organ-transplanted patients have a 250-fold higher risk of
developing actinic keratosis.8 The link between cutaneous HPV infection and actinic keratosis is
controversial.9
Genetics
Actinic keratoses have UV‐related alterations in the TP53, H‐Ras, bcl-2 and KNSTRN genes. UV
exposure has been shown to induce substitution of cystosine for adenine and has been found 19 %
of SCCs and 13 % of AKs. This substitution is not found in healthy skin10. A Dutch study of 3,194
people aged 51 to 99 found that actinic keratoses associated were with the IRF4, Mc1R and TYR
genes.11
10
Epidemiology
Actinic keratosis is the most common in-situ carcinoma found in humans. In Europe it is found in 34% of men and 18% of women older than 70 years of age, in 40-60% of Australians over 40 and in over 40 million Americans.12 Actinic keratoses are found in 2.7% of all Germans and in 11.5% of those aged 60-70 years. In the Netherlands in those over 45 actinic keratoses are found in 49% of men and 29% of women.13 In a study of 4,449 Austrians aged over 30 the overall actinic keratosis prevalence was 31% - 39.2 % in men and 24·3% in women.14
Histology
Since 2000 the classification proposed by Cockerell has been used to grade AK based on the
proportion of atypical keratinocytes throughout epidermal layers; with grade I, atypical
keratinocytes are found in the lower third of the epidermis; in grade II, in the lower two‐thirds; and
in grade III, throughout the entire epidermis. However, since many AK grade 1 progress directly to
squamous cell carcinoma a new histomorphological classification has been proposed based on the
basal growth pattern (PRO I–III) of atypical keratinocytes. Here, grade I corresponds to basal
crowding of atypical keratinocytes; grade II, to budding into the dermis; and grade III, to papillary
sprouting of atypical keratinocytes into the dermis (Figure 4).15
Figure 4: Normal appearance of epidermis and dermoepidermal junction and histological
classification of actinic keratoses defined by basal growth pattern. PRO I shows crowding of atypical
keratinocytes in basal and suprabasal layers; PRO II shows budding of atypical keratinocytes into the
upper papillary dermis; PRO III shows papillary sprouting of atypical keratinocytes into upper dermis
Normal epidermis &
dermoepidermal
junction
PRO I- crowding at
basal and suprabasal
layers
PRO II-budding into
upper papillary
dermis
PRO III-papillary
sprouting into upper
dermis
11
Clinical Presentation
Actinic keratosis usually presents as multiple, discrete, flat or elevated red, skin- coloured or
pigmented patches on sun-exposed surfaces. They can have telangiectasias within or surrounding
them. The lesions are most commonly found on the face, dorsum of hands, shoulders and balding
scalp. The surface may be scaly or have thick keratin, known as verrucous keratosis and the lesions
measure from 2-3mm to >2 cm in diameter. While actinic keratoses are usually asymptomatic some
patient complain of pruritis and/or burning. The differential diagnoses are Bowen’s disease,
superficial spread basal cell carcinoma, early lesions of chronic cutaneous lupus erythematosus,
erosive and pustular dermatosis of the scalp and pemphigus foliaceus.16 There are many types of
actinic keratosis – hypertrophic, atrophic, bowenoid, acantholytic, lichenoid, cheilitis and
pigmented.17 Pigmented actinic keratosis can pose a diagnostic challenge to physicians and a biopsy
is often needed to distinguish it from lentigo maligna. In both cases melanin is contained in
macrophages in upper dermis.18
Clinical Course
Actinic keratosis may regress spontaneously, remain stable or progress to invasive squamous cell
carcinoma.19 The rate of progression of actinic keratosis to squamous cell carcinoma varies from 0%
to 0.075% per lesion per year. In patients who have a history of NMSC this risk is 0.53% per lesion
per year. Regression rates of individual lesions per year ranges from 15% to 53%.20 In one study of
elderly patients with multiple actinic keratosis and previous keratinocytes carcinoma the annual rate
of progression was 0.6%. While the rate of regression was high at > 50% many of these lesions
reappear.21 Other studies report the risk of transformation between 0.025% to 16% with the overall
rate of progression to invasive squamous cell carcinoma at 8%. They report that the poorly
understood rate of regression is 26%.22 One of the most difficult treatment decisions for clinicians is
identifying which lesions may progress to invasive squamous cell carcinoma. In a study of 39 renal
transplant patients Zainab Jiyad and colleagues reported that the presence of an actinic keratosis
patch (defined as > 1 cm²) conferred an 18-fold increased risk of squamous cell carcinoma.23 Other
predictive findings include induration/inflammation, rapid enlargement, bleeding, erythema and
ulceration.24
Treatment
The treatment of actinic keratoses can be lesional- directed or field-directed. The former is treated with curettage, shave biopsy, excision, liquid nitrogen or laser and the latter by chemical peeling, topical photodynamic therapy, 5-fluorouracil cream diclofenac sodium gel, topical retinoids, imiquimod or ingenol mebutate (Table 1).25 There is no current agreement on the most efficacious of these treatments, but importantly 5-fluorouracil has been shown to both prevent and treat actinic keratoses, and imiquimod and photodynamic therapy may have the best cosmetic outcomes.26 In a study of 932 veterans in the US 5-fluorouracil resulted in a 75% reduction in the incidence of squamous cell carcinoma in one year. The authors suggest an annual course of it to the face and ears in those at high risk of squamous cell carcinoma.27 (
Table 1: Treatment options for actinic keratosis derived from de Berker et al,28 Haslim et al29 and Chetty et al30
13
Squamous cell carcinoma
Keratinocyte carcinoma (basal cell carcinoma and squamous cell carcinoma) is the most common cancer in the USA and accounts for about 75% of all cancers.31 The risk of squamous cell carcinoma is closed linked to actinic keratosis. Patients with more than 10 actinic keratoses have a 14% increased risk of developing squamous cell carcinoma within 5 years. The relative risk is 20% if there are more than 20 actinic keratoses. It has been shown that up to 82% of squamous cell carcinoma arise in or near actinic keratoses.32 This cancer has the potential to spread locally and distally. Sun-exposed areas have a five percent risk of metastatic spread while the risks with lesions of the ear and lip are 9 and 14 percent respectively.33 Surgically excised squamous cell carcinoma has a local and distal recurrence rate of 6.7% at 5 years.34 When squamous cell carcinoma metastasises the prognosis is poor with a 5-year survival rate of <25%.35
Organ transplantation and immunosuppression
The most common type of keratinocyte cancer among organ transplant recipients is squamous cell
carcinoma followed by basal cell carcinoma- a reversal of the general population. Metastatic
squamous cell carcinoma is more common and mortality is greater is this patient group.36 The risk of
invasive nonmelanoma skin cancer is related to duration of immunosuppression, varying from 5 %
after two years to 10–27 % after ten years and 40–60 % after 20 years. It is believed that the
increased rate of progression of up to 30% of actinic keratoses to invasive squamous cell carcinoma
is one of the reasons for this.37
Dermatoscopy
Dermatoscopy is a noninvasive diagnostic technique of illumination and magnification that allows
visualization of the colour, patterns and structure of the epidermis, dermoepidermal junction and
papillary dermis. Such visualization is not possible with the naked eye (Table 2). The term
“dermatoscopy” was coined in 1920 by the German dermatologist Johann Saphier. Dermatoscopy
has been shown to significantly increase the diagnosis of melanocytic, non- melanocytic, benign and
malignant lesions. In the case of melanoma it leads to a 10-27% improvement in its diagnosis.38
Dermatoscopy works through modifying the cutaneous air-tissue optical interface in two ways.
Nonpolarized dermatoscopy changes the interface through the use of a contact glass plate and liquid
(oil, water or alcohol) that approximates the refractive index of the stratum corneum resulting in less
reflected light from epidermis and more remitted light from deeper structures. Polarized
dermatoscopy uses the properties of a source polarizer and detector polarizer- the former emits
unidirectional light which is only received by the latter if it changes direction multiple times. There is
far more changes in light that passes through deep skin layers than light from the stratum corneum
and superficial skin layers. Nonpolarized dermatoscopy is better at visualizing superficial structures
such as milia-like cyst, comedo-like opening and blue-white veil, but as it uses skin contact is may
compress blood vessels. White shiny structures such as rosettes, white lines and clods are only seen
with polarized dermatoscopy. In addition bloods vessels are better seen with polarized
dermatoscopy. Modern dermatoscopes combine both settings (Figures 5-14 and Table 3).39
14
Figure 5: Normal conditions. The ability to detect light from epidermis and superficial dermis (black
arrows) is limited by reflected light from the stratum corneum
Figure 6: Nonpolarized dermatoscopy. By using a glass plate & liquid interface less reflected surface
light & more light from epidermis & superficial dermis is detected by the eye
15
Figure 7: Polarized dermatoscopy. Only light from source polarizer that has changed direction
multiple times (black arrows) is detected by cross polarized filter while light reflected from
superficial layers is less likely to be detected
Grade Clinical Dermatoscopic Histopathology
1 Slightly palpable AK Red pseudonetwork Atypical keratinocytes in lower one third of the epidermis
2 Moderately thick AK Background erythema intermingled with keratotic follicular openings
Atypical keratinocytes in lower two thirds of the epidermis
3 Very thick, hyperkeratotic AK
Structureless white-yellow areas
Atypical keratinocytes throughout entire epidermis; parakeratosis, acanthosis, papillomatosis, involvement of adnexal structures
Table 2: Dermatoscopic and histopathological features of actinic keratosis derived from Zalaudek et
al40 and Schmitz et al41
16
Figure 8: Actinic keratosis grade 1 - red pseudonetwork
Figure 9: Actinic keratosis grade 2 – strawberry pattern and distinct hyperkeratosis in the centre
Erythema Structureless pale red areas without any recognizable areas of hypopigmentation or morphology
Red pseudo-network
Structureless red areas, which intermingled with small roundish white areas, resemble network structure. The small white areas correspond to follicular openings of skin
Strawberry pattern
Structureless red areas in which are scattered targetoid inner yellow and outer white round structures not unlike the surface of a strawberry. The targetoid areas are keratin filled follicular openings
Dotted vessels Tiny pinpoint vessels
Coiled/glomerular vessels
Tightly coiled vessels resembling the glomerular structure of the kidney
Linear-irregular vessels
Liners or slightly curved vessels of various sizes and shaped and randomly distributed
Targetoid hair follicles
Round structures with yellow to light brown centre and white outer rim which represent keratotic plugs within a hair follicle
Rosettes Four bright white dots or clods arranged together as a square or a 4-leaf clover. Are believed to arise from the optical interaction of polarized light with the skin around follicular infundibulae
White structure area
White structureless area in the absence of any structure
Yellow to light brown opaque scales
Yellow to light brown opaque structureless areas with a scaly or keratotic that cover variable area of a lesion
Erosion Small and irregularly distributed structureless areas (orange/red/red-brown) which represent superficial haemorrhages
Table 3: Dermatoscopic criteria and their description used in this study derived from Lallas et
al,42 Zalaudek et al,43Scope et al,44 and Stolz et al45
19
Figure 11: Dotted vessels in a 75 year old man
20
Figure 12: Coiled vessels in a 73 year old man
21
Figure 13: Linear- irregular vessels in a 70 year old man
22
Figure 14: Rosettes in a 74 year old man
Aim of this study
The three aims of the study were
1. A dermatoscopic description of nonfacial actinic keratoses.
2. To propose a new classification of nonfacial actinic keratosis.
3. To establish if the classification of facial actinic keratosis by Zalaudek et al was applicable to
nonfacial sites.46
Method
This observational study was done between July 2017 and September 2019 in a General Practice in
Dingle, Co Kerry, Ireland. The contact polarized images were taken by the author using a Dermlite 3
dermatoscope (3Gen Inc, San Juan Capistrano, CA, USA) attached to a Samsung Galaxy S7
smartphone (Samsung, Samsung Town, Seoul, South Korea) and recorded in high-definition JPEG
format. All the lesions were subsequently treated with cryosurgery. The actinic keratoses were
analysed for history of skin carcinoma (squamous cell carcinoma, basal cell carcinoma, melanoma or
other skin cancer) and ten dermatoscopic features -keratin (white scale, moderate keratosis or thick
13), follicular openings/targetoid hair follicles, white structureless areas, erythema, red
pseudonetwork (Figure 8), strawberry pattern (Figure 9), rosettes (Figure 14) and brown
pigmentation. Twenty dermatoscopic images are listed in the atlas.
Results
Clinical features
The images of 106 nonfacial actinic keratoses were from 43 patients aged 57-97, average age 74
years. There were thirty-five men and eight women. FitzPatrick skin type I was found in 93.1% of the
patients and 6.9% had skin type II. The lesions were found on the dorsum of the hands in 87 (82%) of
cases, 12 (11.3%) on arms, 5 (4.7%) on fingers and one each on shoulder and chest (Table 4). A
previous history of 38 skin carcinomas – 19 basal cell carcinomas, 16 squamous cell carcinomas, two
melanomas and one adnexal cancer –were found in 21 (48.8%) of the patients – 20 men and one
woman. Two of the patients had both basal cell carcinomas and squamous cell carcinomas excised,
one patient had an adnexal tumour and five basal cell carcinomas removed and one had four basal
cell carcinomas excised.
Location Actinic keratoses (n = 106)
Dorsa of hands 87 (82%)
Arms 12 (11.3%)
Fingers 5 (4.7%)
Shoulder 1 (0.95%)
Chest 1 (0.95%)
Table 4: Location of actinic keratoses
Dermatoscopic features
101 (95.2%) of the lesions had some type of keratin (scale 13.2%, moderate keratosis 41.5% and
thick keratosis 40.5%) and 87.7% had blood vessels (dotted only 73.3%, coiled only 34.4%, linear
52.3% and mixed coiled and linear 17.1%). There were no vessels in 12.3% of the lesions. White
structureless areas were present in 56 (52.8%) of the lesions and erythema in 46 (43.4%).
White/yellow keratin dots/clods and their patterns were defined as follicular openings only (10.3%),
strawberry pattern (16%) or red pseudonetwork (2.8%). Erosions were seen in 24 (22.6%) of cases.
The other features found were brown pigmentation at 16 (15%) and rosettes in 16% of cases (Table
5).
24
Total n= 106
Total keratin 101 (95.2%)
White scale 14 (13.2%)
Moderate keratin 44 (41.5%)
Thick keratin 43 (40.5%)
Erosions 24 (22.6%)
Dotted vessels 78 (73.6%)
Linear-irregular vessels 58 (54.7%)
Coiled vessels 40 (37.7%).
Linear and/or coiled vessels only 27 (25.7%)
Follicular opening 11 (10.3%)
White structureless area 56 (52.8%)
Erythema 46 (43.4%)
Red pseudonetwork 3 (2.8%)
Brown pigmentation 16 (15%)
Strawberry pattern 17 (16%).
Rosettes 17 (16%)
Table 5: Dermatoscopic findings, numbers and per centages in Irish study of 106 actinic keratoses.
Based on the fact that actinic keratoses can present more than one dermatoscopic feature the sum of
numbers and percentage is higher than 106 or 100%
Discussion
This is the first study undertaken of the dermatoscopic features of nonfacial actinic keratoses in FitzPatrick skin type I skin. The principal findings from the 106 lesions were significantly more blood vessels (dotted, coiled and linear- irregular), white structureless areas and rosettes and less red pseudonetwork and brown pigmentation compared to previous studies on facial and nonfacial actinic keratoses. There was a similar incidence of erosions (Tables 6 & 7). Most of the previous studies have focussed on facial actinic keratosis, in particular pigmented actinic keratosis, in attempts to better differentiate them from lentigo maligna.47,48,49,50 Vascular patterns are important in differentiating actinic keratosis from other skin carcinomas. Squamous cell carcinoma is characterized by dotted, linear- irregular, glomerular and hairpin vessels often surrounded by a halo while basal cell carcinoma features arborizing or horizontal vessels- sharply focussed branching vessels. Seborrhoeic keratosis is distinguished from actinic keratosis by hairpin vessels. The hallmark of Bowen’s disease is the presence of coiled or glomerular vessels whereas dotted vessels arranged like pearls in a line are typical of clear cell acanthoma. The disordered pattern of linear- irregular, polymorphic and hairpins vessels are found in amelanotic /hypomelanotic melanoma. It is also important to distinguish actinic keratosis from the pink/red branched unfocussed vessels seen in sun-damaged atrophic skin.51 The most important finding from this study was the marked difference in the incidence of different vessel types when compared to other studies. In 2010 Iris Zalaudek and her colleagues reported surface scale, erythema and dotted vessels in extra-facial actinic keratoses without percentages reported, in observations that were not published.52 The only published study of nonfacial actinic keratoses was undertaken by Clarissa Reinehr and her colleagues in Brazil in 2015 involving 258 extra-facial actinic keratoses in patients with FitzPatrick skin types II or III.53 My study found dotted vessels in 78 (73.6%) of the lesions
25
which was more than four times the rate of their study which found them in 39 cases (15%). In addition, I noted linear-irregular vessels in 58 (54.7%) of cases whereas they found them in 18 (7%). When the combined total of dotted and coiled vessels in this Irish study is compared with one by Zalaudek and her colleagues54 on 70 facial actinic keratoses in FitzPatrick skin type II it was found that the Irish study had over seven times as many such vessels (81 (76.4%) v. 7 (10%)). In addition, my study found 58 (54.7%) linear-irregular vessels as against 4 (5.7%) in their paper. White structureless areas were found in 56 lesions (52.8%) in my study compared with 11 (15.7%) in that by Zalaudek and her colleagues. Rosettes, characterized by a 4 white points arranged as a 4-leaf clover (and thought to represent changes of orthokeratosis and parakeratosis) had an incidence of 16% in my study. This compares with 4.3% in that of Zalaudek and colleagues and an incidence of 46.3% in a study of 41 actinic keratoses by Liebman and colleagues.55 The incidence of red pseudonetwork was low with this study noting 3 cases (2.8%) and Reinehr and colleagues56 noting it in just 2 (0.8%) of cases. The incidence of brown pigmentation in their study was 93.1% compared with the Irish study finding of an incidence of 15%. This is not surprising as their patients had FitzPatrick skin type II and III. In my study I defined keratin dots/clods as follicular openings only (10.3%), strawberry pattern (16%) and red pseudonetwork (2.8%). In keeping with a study of facial actinic keratoses Zalaudek and colleagues57 found red pseudonetwork in 47 lesions (67.1%) in their study as against 3(2.8%) in mine. However, if I include the figures for red pseudonetwork and strawberry pattern (18.2%) the difference is less. Erythema was found in over half of the Brazilian study at 56.4%, in 39.6% in my study and in 17.1% of the lesions studies by Zalaudek et al. 58 Keratin/white scale is very common in actinic keratoses, both facial and nonfacial. While Reinehr et al59 reported “white scale” in 251 lesions (97.3%) I classified it as white scale, moderate keratin and thick keratin with the incidence of 13.3%, 41.5% and 40.5% respectively. Zalaudek and colleagues60 used the terms yellow-white opaque scales, diffuse/discrete scales and central scale and reported incidence of 32.8%, 24.3% and 18.5% (75.6% in total). The rate of erosions were similar to Zalaudek and her colleagues with my study having an incidence of 22.6% v. 24.3%. Of note is that they found an incidence of erosions of 29.5% in a study of 78 squamous cell carcinomas in the same paper suggesting that these findings are not helpful in distinguishing actinic keratosis from squamous cell carcinoma.
26
Table 6: Comparison of studies using bar chart format
The rate of previous skin carcinoma in this study was 48.8% in contrast to that of the hospital based studies of Reinehr et al at 77.9% and Zalaudek at el at 70.8%61,62. This could be related to the fact that patients with more significant skin pathology generally attend hospital dermatology clinics. The limitations of this study were that some of the patients had lived in low latitude countries earlier in their lives, most of the lesions were on the hands and 1.8% of the lesions were in a renal transplant patient.
Comparing studies
Brosnan C Zalaudek I Reinehr C
n=106 Non-facial n=70 Facial n=258 Non-facial
Hands-87 (82%) Hands-147 (56.9%)
White scales 14 (13.3%) 10 (24.3%) 251 (97.3%)
Yellow- white opaque scales
23 (32.8%) -
Moderate keratin 44 (41.5%) - -
Thick keratin 43 (40.5%) Total =101 (95.2%)
Diffuse/discrete scale 10 (24.3%) -
Erythema 42 (39.6%) 12 (17.1%) 147 (56.4%)
Dotted vessels 78 (73.6%) 39 (15%)
Dotted + coiled vessels
81 (76.4%) 7 (10%) -
Coiled vessels 40 (37.7%) - -
Linear-irregular vessels
56 (52.8%) 4 (5.7%) 18 (7%)
Red pseudonetwork 3 (2.8%) 47 (67.1%) 2 (0.8%)
Follicular opening 11 (10.3%) 18 (25.7%) -
Brown pigmentation 16 (15%) - 54 (93.1%)
Rosettes 17 (16%) 3 (4.3%) -
White structureless area
56 (52.8%) 11(15.7%) -
Erosions 24 (22.6%) 17 (24.3%) -
Table 7: Comparison of present study with one conducted by Zalaudek and colleagues on FitzPatrick skin type II63 and one by Reinehr and colleagues on skin types II and III 64
28
Conclusion
The findings of this study of nonfacial actinic keratosis in FitzPatrick skin type I are new. They reveal
more than seven times as many linear-irregular vessels and four times as many dotted vessels as a
study on nonfacial actinic keratosis in skin type ll and lll by Reinehr et al65 and ten times as many
linear-irregular vessels and seven times as many dotted vessels as a study of facial actinic keratosis
in skin type ll by Zalaudek et al66. This study also found more than three times as many white
structureless areas, four times as many rosettes and more than twice the incidence of erythema as
Zalaudek and colleagues. The study had one third the incidence of brown pigmentation as Reinehr
and her colleagues. I propose that high frequency of blood vessels, white structureless areas,
rosettes and erythema and low incidence of brown pigmentation are the most common features of
nonfacial actinic keratosis. This study does not support the use of Zalaudek’s classification of facial
actinic keratosis for nonfacial sites.
29
Atlas of nonfacial actinic keratoses
Fig. 1a: 85 year old man. Dorsum of hand
Fig 1b: Thick keratin, erosion, strawberry pattern and rosette
thick keratin
erosion
rosette
Strawberry pattern
30
Fig 2a: 73 year old male. Dorsum of hand
Fig 2b: Dotted, coiled and linear vessels
31
Fig 3a: 76 year old male. Dorsum of hand
Fig 3b: Dotted vessels, erosion and white structureless area
erosion
Dotted vessels
32
Fig 4a: 61 year old male. Upper arm
Fig 4b: Linear and dotted vessels, erosions and erythema
White structureless area
33
Fig 5a: 84 year old male. Upper arm
Fig 5b: Dotted and coiled vessels, scale and erythema
Dotted and coiled vessels
scale
34
Fig 6a: 60 year old male. Forearm
Fig 6b: Coiled and dotted vessels, moderate keratin, erosion and erythema
Erythema and erosion
Dotted vessels
Moderate keratin
Coiled vessels
35
Fig 7a: 71 year old male. Chest
Fig 7b: Coiled and linear-irregular vessels, moderate keratin and erythema
Coiled and
linear-irregular
vessels
Moderate keratin
36
Fig 8a: 81 year old man. Dorsum of hand
Fig 8b: Dotted, coiled and linear vessels, moderate keratin and strawberry pattern
Moderate keratin
Strawberry pattern
n
Dotted, coiled and
linear-irregular vessels
37
Fig 9a: 77 year male. Dorsum of hand
Fig 9b: moderately thick keratin, erosion and rosettes
rosetttes
erosion
Moderately thick
keratin
38
Fig 10a: 74 year old male. Dorsum of hand
Fig 10b: Dotted vessels, rosettes and moderately thick keratin
Dotted, coiled and
linear-irregular
vessels
rosettes
Moderately
thick keratin
Strawberry pattern
39
Fig 11a: 75 year old male. Dorsum of hand
Fig 11b: Dotted vessels, follicular openings and erythema
erythema
Dotted vessels
Follicular
openings
40
Fig 12a: 69 year old male. Dorsum of hand
Fig 12b: Dotted and coiled vessels, moderate keratin and white structureless area
Dotted, coiled
and linear vessels
White
structureless area
Moderate
keratin
41
Fig 13a: 70 year old male. Dorsum of hand
Fig 13b: Dotted, coiled and linear-irregular vessels
Linear-irregular
vessels
42
Fig 14a: 77 year old male. Dorsum of hand
Fig 14b: Erosion, rosettes and moderate keratin
rosettes
erosion
Moderate keratin
43
Fig 15a: 74 year old male. Dorsum of hand
Fig 15b: Brown pigmentation, thick keratin and follicular openings
Thick keratin
Brown pigmentation
Follicular openings
44
Fig 16a: 71 year old male. Dorsum of hand
Fig 16b: Brown pigmented lines and follicular openings
Brown
pigmented lines
Follicular
openings
45
Fig 17a: 76 year old female. Dorsum of hand
Fig17b: Dotted vessels, rosettes, strawberry pattern and brown pigmentation
Brown
pigmentation
Strawberry
pattern
rosettes
Dotted
vessels
46
Fig 18a 69 year old male. Dorsum of hand
Fig 18b: Dotted and linear-irregular vessels
Linear vessels
Dotted vessels
47
Fig 19a: 79 year old female. Dorsum of hand
Fig 19b: Linear-irregular and coiled vessels, rosettes, strawberry pattern and moderate keratin
Moderate keratin
Linear-irregular
and coiled vessels
rosette
Strawberry pattern
48
Fig 20a: 85 year female. Dorsum of hand
Fig 20b: Red pesudonetwork and thick keratin
Thick keratin
Red pseudonetwork
49
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Zalaudek I, Giacomel J, Schmid K, Bondino S, Rosendahl C, Cavicchini S, Tourlaki A, Gasparini S, Bourne P, Keir J, Kittler H, Eibenschutz L, Catricala C, Argenziano G. Dermatoscopy of facial actinic keratosis, intraepithelial carcinoma and invasive squamous cell carcinoma: A progressive model. Journal of the American Academy of Dermatology 2012;66:589-597. 58
Zalaudek I, Giacomel J, Schmid K, Bondino S, Rosendahl C, Cavicchini S, Tourlaki A, Gasparini S, Bourne P, Keir J, Kittler H, Eibenschutz L, Catricala C, Argenziano G. Dermatoscopy of facial actinic keratosis, intraepithelial
52
carcinoma and invasive squamous cell carcinoma: A progressive model. Journal of the American Academy of Dermatology 2012;66:589-597. 59
Reinehr CPH, Garbin GA,Bakos RM. Dermatoscopic Patterns of Nonfacial Actinic Keratosis: Characterization of Pigmented and Nonpigmented Lesions. American Society for Dermatologic Surgery 2017; 43:11:1385-1391. 60
Zalaudek I, Giacomel J, Schmid K, Bondino S, Rosendahl C, Cavicchini S, Tourlaki A, Gasparini S, Bourne P, Keir J, Kittler H, Eibenschutz L, Catricala C, Argenziano G. Dermatoscopy of facial actinic keratosis, intraepithelial carcinoma and invasive squamous cell carcinoma: A progressive model. Journal of the American Academy of Dermatology 2012;66:589-597. 61
Zalaudek I, Giacomel J, Schmid K, Bondino S, Rosendahl C, Cavicchini S, Tourlaki A, Gasparini S, Bourne P, Keir J, Kittler H, Eibenschutz L, Catricala C, Argenziano G. Dermatoscopy of facial actinic keratosis, intraepithelial carcinoma and invasive squamous cell carcinoma: A progressive model. Journal of the American Academy of Dermatology 2012;66:589-597. 62
Reinehr CPH, Garbin GA,Bakos RM. Dermatoscopic Patterns of Nonfacial Actinic Keratosis: Characterization of Pigmented and Nonpigmented Lesions. American Society for Dermatologic Surgery 2017; 43:11:1385-1391. 63
Zalaudek I, Giacomel J, Schmid K, Bondino S, Rosendahl C, Cavicchini S, Tourlaki A, Gasparini S, Bourne P, Keir J, Kittler H, Eibenschutz L, Catricala C, Argenziano G. Dermatoscopy of facial actinic keratosis, intraepidermal carcinoma, and invasive squamous cell carcinoma: A progressive model. Journal of the American Academy of Dermatology 2012; 66: 589-597. 64
Reinehr CPH, Garbin GA,Bakos RM. Dermatoscopic Patterns of Nonfacial Actinic Keratosis: Characterization of Pigmented and Nonpigmented Lesions. American Society for Dermatologic Surgery 2017; 43:11:1385-1391. 65 Reinehr CPH, Garbin GA,Bakos RM. Dermatoscopic Patterns of Nonfacial Actinic Keratosis: Characterization
of Pigmented and Nonpigmented Lesions. American Society for Dermatologic Surgery 2017; 43:11:1385-1391. 66 Zalaudek I, Giacomel J, Schmid K, Bondino S, Rosendahl C, Cavicchini S, Tourlaki A, Gasparini S, Bourne P,
Keir J, Kittler H, Eibenschutz L, Catricala C, Argenziano G. Dermatoscopy of facial actinic keratosis, intraepidermal carcinoma, and invasive squamous cell carcinoma: A progressive model. Journal of the American Academy of Dermatology 2012; 66: 589-597.
