- Email: [email protected]
Acral lentiginous melanoma – Is inflammation the missing link?
Accepted Manuscript Acral Lentiginous Melanoma - is inflammation the missing link? F. Al-Hassani, C. Chang, H. Peach PII:
S2352-5878(17)30046-3
DOI:
10.1016/j.jpra.2017.06.002
Reference:
JPRA 130
To appear in:
JPRAS Open
Received Date: 21 January 2017 Revised Date:
16 June 2017
Accepted Date: 29 June 2017
Please cite this article as: Al-Hassani F, Chang C, Peach H, Acral Lentiginous Melanoma - is inflammation the missing link?, JPRAS Open (2017), doi: 10.1016/j.jpra.2017.06.002. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Acral Lentiginous Melanoma - is inflammation the missing link?
F Al-Hassani; C Chang; H Peach
RI PT
Department of Plastic and Reconstructive Surgery; Leeds General Infirmary
SC
Summary
We propose that repetitive chronic microtrauma, in susceptible individuals, is a significant causative
M AN U
factor in the development of ALM. This observational study documents a possible correlation between anatomical site of ALM and recognised high pressure sites on the plantar foot. The pattern of distribution not only matches the gait analysis pattern, but the concentration of cases correlate with the zones of highest pressure. The surface area distribution also highlights a discrepancy between surface area affected and incidence of ALM for a purely direct causal link, suggesting
TE D
another causative factor. This hypothesis is consistent with other known features of ALM, particularly age of onset in the sparing of glabrous skin, which is not subjected to repetitive shearing
AC C
EP
or direct pressure forces.
1
ACCEPTED MANUSCRIPT
Introduction
Acral Lentiginous melanoma (ALM) was first described as a separate histological variant from other melanomas by Reed (1) in 1972 and represents only about 1-3% of all melanomas. “Acral “ due to its predilection for acral sites,” lentiginous” due to characteristic radial or lentiginous growth pattern.
accounts for up to 70% of all melanomas found in dark individuals (2).
RI PT
The frequency of occurrence is the same regardless of skin colour, white, brown or black, but
Patients with ALM have key demographic and lifestyle differences when compared to patients with
SC
melanomas of other subtypes: it occurs in an older patient population, and is associated with a lower number of common and atypical nevi, a lower incidence of familial melanoma, and a lower
M AN U
incidence of sunburn but a higher personal and family history of non-cutaneous cancers. ALM, unlike the commoner sub-types of melanoma found in white Caucasian skin, does not appear to be associated with sun exposure and the pathogenesis of ALM remains poorly understood. Green (3) associated risk factors to ALM including trauma (penetrative injury) and exposure to agriculture
TE D
chemicals. Briggs (4) noted this finding, but concluded the initial injury only draws the patient’s attention to the lesion rather than causing the lesion. Kaskel (5) surmised that an increased incidence of trauma in acral sites was to be expected but found no association between trauma and
EP
the development of ALM.
There are no published papers suggesting an association between trauma and the aetiology of acral
AC C
lentiginous melanoma. We hypothesise a link between the development of melanoma with repeated micro-trauma by analysing barefoot gait pressure pattern, the distribution of plantar ALM and examining the ratio of incidence of ALM to body surface area.
Material and Method A retrospective clinical analysis from a single tertiary melanoma centre (Leeds Teaching Hospitals Trust) was completed. We identified fifty-seven cases of plantar acral lentiginous melanoma treated over a period of 11 years (January 2005 and January 2016). Patients were identified using the
2
ACCEPTED MANUSCRIPT
hospital pathology database. All samples were reviewed to ensure only melanomas that occurred on the plantar surface of the feet were included. The location of the lesion was confirmed through reviewing of patient records, operation notes and the hospital patient medical image system (Medical Image Manager, MIM). The following exclusion criteria were applied: ALM to the nail (sub-
RI PT
ungual melanoma), dorsum of foot or other non-plantar locations.
Histology and clinical images of all confirmed cases of plantar ALM were reviewed and baseline demographic and histological data recorded, these include age at diagnosis, location, Breslow
SC
thickness, lesion dimension, mitotic count, ulceration and regression status. Baseline histological data from the initial excisional biopsy were used for this study. However, in cases where the initial
M AN U
biopsy was incisional or punch biopsy, the histology data are taken from the wide local excision sample instead to allow for completeness of dataset. The foot was graphically divided into 12 quadrants; (medial, central and lateral horizontally; heel, midfoot, forefoot and toes vertically) .The distribution of the acral melanoma was mapped within these quadrants ( Figure 1).
Results
EP
normal walking.
TE D
A literature search was carried out to identify the known pressure mapping of the foot during
57 patients were included in the study, with a higher prevalence of females compared to males
AC C
(35:22) and an average age of 66.21 (range 35-86). The average Breslow thickness was 3.23mm (range 0.5 – 15.5mm). The histology did not record mitotic rate in 11 cases, the presence or absence of ulceration in 11 cases and macroscopic size of the lesion in 46 cases. In those cases of ALM in which the histological dataset was complete, the average diameter and mitotic rate were 22.62mm (range 4 - 64mm) and 6.28/mm2 (0-35) respectively. Ulceration was evident in 19 out of 46 cases At the point of lesion mapping, 8 cases were omitted (N=49) due to insufficient information in the case notes for precise location of the tumour. The locations of the 49 cases of ALM are represented by circles as seen in Figure 1. This illustrates that 83.5% of the cases of ALM presented in this study
3
ACCEPTED MANUSCRIPT
were concentrated around three areas of the foot; the lateral heel (37%), medial heel (20%) and across the metatarsal heads (26.5%). We found no cases that involved the instep of the foot and only a few cases, which arose on the lateral aspect of the mid foot or the pulp of the toes Gait analysis pressure map represents the magnitude and pattern of pressure applied to the foot
RI PT
during walking . The spectrum of colours represents the pressure applied to the different anatomical sites of the foot. The highest pressure (red) to the lowest pressure (green), with colours distributed according to the area over which the pressure is applied. The pressure map is presented alongside
SC
the image showing the distribution of ALM in our study.
Discussion
M AN U
There are several risk factors thought to be linked to the development of certain melanoma subtypes. Superficial Spreading, Nodular and Lentigo Maligna subtypes appear to be associated with fair skin (Fitzpatrick type I and II), excessive sunlight and ultraviolet light exposure along. In addition there may be a genetic susceptibility presenting as part of a family history or an atypical naevus
TE D
phenotype. The aetiology of ALM appears not to be associated with any of these factors, as specifically plantar skin is amelanotic and rarely experiences excessive ultraviolet light exposure.
EP
Most clinicians with an interest in melanoma, will remember cases where individual patients will have associated the development of their melanoma at ‘exactly the point where they injured
AC C
themselves several years previously. Phan et al (9) described the possible role of trauma as an aetiological factor for developing ALM but pointed it out as a frequency of only 13% in their series. Mohrle and Hafner (10) suggested a link between a history of trauma and developing subungual melanoma – most commonly seen on the thumb or hallux, postulating that due to their relative sizes, both digits would be subject to more frequent trauma compared to other digits. In a German study, ALM occurred on the feet in about 87%, and on the hands in 13% of the cases (11), whilst in our study we only found cases of ALM on the plantar aspect of the foot. However both studies confirm a significant predilection for developing ALM on the foot, an area, which is subjected to
4
ACCEPTED MANUSCRIPT
repeated and persistent microtrauma. These papers and others, have raised the possibility of trauma being an aetiological factor in the development of ALM, however these are often limited, retrospective small case series with poor recollection of ‘where the trauma occurred’. There has also been frequent discussion as to whether the trauma itself just highlighted a pre-existing lesion.
RI PT
This study examined the question from a different perspective, namely to assess whether the location of known ALM on the foot correlated to known pressure data from gait analysis. The hypothesis examining whether recurrent microtrauma on the plantar aspect of the foot could be an
SC
aetiological factor in the development of Acral Lentiginous Melanoma
The pressure gait maps define the areas of peak pressure applied to the foot during normal walking.
M AN U
What is remarkable is the direct correlation of these pressure areas with the anatomical distribution of the ALM in this series. The pattern of distribution correlates not only to the anatomical subregions of the foot as per the pressure map, but the highest density of ALM also correlates with the zones of peak pressure applied to the foot whilst walking. In addition it is noticeable that in this
TE D
study, ALM occurred neither within the instep area of the foot, nor the palmar aspect of the hand, both regions not normally associated with excessive shear or pressure forces. The dermatopathology of skin from the plantar instep and palmar skin demonstrate them to have the same characteristics
EP
as the skin from weight-bearing areas of the foot albeit with a thinner keratin layer. Therefore if there is a genetic or systemic explanation as to the aetiology of ALM, one would expect
AC C
a relatively even anatomical distribution of cases of ALM. The common subtypes of melanoma, appear most frequently on sun exposed sites and even demonstrate an intersex distribution appropriate for different skin exposure – female legs, male trunk. ALM appears to be associated with weight-bearing areas of plantar skin and within that a concentration of cases directly proportional to differential pressures applied to those areas
The relative incidence of ALM varies according to ethnic origin. In the Afro-Caribbean population, ALM account for up to 80% of all melanomas, however in the white Caucasian group, which is
5
ACCEPTED MANUSCRIPT
representative of our study group, the incidence has been reported at around 7% (11). The surface area of the foot represents about 1.75% of the total body surface area, however the evaluated surface area of the contact part of the foot is less than 1 %. Therefore the contact element of both feet represents about 2% of the total body surface area. However the incidence of ALM within this
RI PT
site is 3-4 times greater than this. If the aetiological factors associated with the development of ALM were the same as those of other melanoma subgroups then one would expect the frequency of occurrence of ALM to match the percentage body surface occupied by glabrous skin, namely 1.75%. In practice the exact opposite is found, where ALM of the foot, has been reported, to have a
SC
prevalence 5 to 16 times higher than any other anatomical location. (6, 7, 8). This suggests ALM to
M AN U
have different aetiological factors when compared to the other more common melanoma subtypes.
The epidemiology data of this series also agrees with previous reports of the relative later onset of ALM. This would also support our proposal of an aetiological effect relating to microtrauma. It is not the acute injury in which we see ALM develop; otherwise ALM would be expected to correlate with
TE D
people who have undergone foot surgery. The question is whether chronic microtrauma is a significant causative factor, our data suggests a strong possibility.
AC C
Funding: nil
EP
Conflict of Interest: nil
6
ACCEPTED MANUSCRIPT
Average
Range
66.21
(35-86)
Male
Female
22
35
Average
Range
3.23
(0.5 - 15.5)
Yes
No
19
27
Mitotic Rate (no/mm2) (n = 46)
Average
Range
6.28
(0-35)
Size (mm) (n = 46)
Average
Range
22.62
(4-64)
Sex (n = 57) Tumour Thickness (mm) (n = 57) Ulceration (n = 46)
SC
Age (years) (n = 57)
RI PT
Table 1 –Tumour demographics for ALM Histology
Table 2 –ALM distribution per quadrant
5
Midfoot
0
Forefoot
4 1
Central
Lateral
9
14
1
4
5
4
0
2
AC C
Toes
EP
Heel
TE D
Medial
M AN U
Table 1: Patient Demographics and Tumour Histology Breakdown
7
ACCEPTED MANUSCRIPT
References
1. Reed RJ. New concepts in surgical pathology of the skin. John Wiley & Sons; 1976. 73-96. 2. Krementz ET, Feed RJ, Coleman WP, 3rd, Sutherland CM, Carter RD, et al. Acral lentiginous melanoma. A clinicopathologic entity. Ann Surg. Lippincott, Williams, and Wilkins; 1982 May
RI PT
1;195(5):632–1185. 3. Green A, McCredie M, MacKie R, Giles G, Young P, Morton C, et al. A case-control study of melanomas of the soles and palms (Australia and Scotland). Cancer Causes Control. 1999 Feb;10(1):21–5.
SC
4. Briggs JC. The role of trauma in the aetiology of malignant melanoma: a review article. Br J Plast Surg. 1984 Oct;37(4):514–6.
M AN U
5. Kaskel P, Kind P, Sander S, Peter RU, Krähn G. Trauma and melanoma formation: a true association? Br J Dermatol. 2000 Oct;143(4):749–53.
6. Ridgeway CA, Hieken TJ, Ronan SG, Kim DK, Gupta Das TK. Acral lentiginous melanoma. Arch Surg. 1995 Jan;130(1):88–92.
TE D
7. Paladugu RR, Winberg CD, Yonemoto RH. Acral lentiginous melanoma. A clinicopathologic study of 36 patients. Cancer. 1983 Jul 1;52(1):161–8. 8. Sutherland CM, Mather FJ, Muchmore JH, Carter RD, Reed RJ, Krementz ET. Acral lentiginous
EP
melanoma. Am J Surg. 1993 Jul;166(1):64–7.
9. Phan A, Touzet S, Dalle S, Ronger-Savlé S, Balme B, Thomas L. Acral lentiginous melanoma: a
AC C
clinicoprognostic study of 126 cases. Br J Dermatol. 2006 Sep;155(3):561–9. 10. Möhrle M, Häfner HM. Is subungual melanoma related to trauma? Dermatology (Basel). 2002;204(4):259–61.
11. Kuchelmeister C, Schaumburg-Lever G, Garbe C. Acral cutaneous melanoma in caucasians: clinical features, histopathology and prognosis in 112 patients. Br J Dermatol 2000;143(2):275– 80.
8
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
S2352-5878(17)30046-3
DOI:
10.1016/j.jpra.2017.06.002
Reference:
JPRA 130
To appear in:
JPRAS Open
Received Date: 21 January 2017 Revised Date:
16 June 2017
Accepted Date: 29 June 2017
Please cite this article as: Al-Hassani F, Chang C, Peach H, Acral Lentiginous Melanoma - is inflammation the missing link?, JPRAS Open (2017), doi: 10.1016/j.jpra.2017.06.002. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Acral Lentiginous Melanoma - is inflammation the missing link?
F Al-Hassani; C Chang; H Peach
RI PT
Department of Plastic and Reconstructive Surgery; Leeds General Infirmary
SC
Summary
We propose that repetitive chronic microtrauma, in susceptible individuals, is a significant causative
M AN U
factor in the development of ALM. This observational study documents a possible correlation between anatomical site of ALM and recognised high pressure sites on the plantar foot. The pattern of distribution not only matches the gait analysis pattern, but the concentration of cases correlate with the zones of highest pressure. The surface area distribution also highlights a discrepancy between surface area affected and incidence of ALM for a purely direct causal link, suggesting
TE D
another causative factor. This hypothesis is consistent with other known features of ALM, particularly age of onset in the sparing of glabrous skin, which is not subjected to repetitive shearing
AC C
EP
or direct pressure forces.
1
ACCEPTED MANUSCRIPT
Introduction
Acral Lentiginous melanoma (ALM) was first described as a separate histological variant from other melanomas by Reed (1) in 1972 and represents only about 1-3% of all melanomas. “Acral “ due to its predilection for acral sites,” lentiginous” due to characteristic radial or lentiginous growth pattern.
accounts for up to 70% of all melanomas found in dark individuals (2).
RI PT
The frequency of occurrence is the same regardless of skin colour, white, brown or black, but
Patients with ALM have key demographic and lifestyle differences when compared to patients with
SC
melanomas of other subtypes: it occurs in an older patient population, and is associated with a lower number of common and atypical nevi, a lower incidence of familial melanoma, and a lower
M AN U
incidence of sunburn but a higher personal and family history of non-cutaneous cancers. ALM, unlike the commoner sub-types of melanoma found in white Caucasian skin, does not appear to be associated with sun exposure and the pathogenesis of ALM remains poorly understood. Green (3) associated risk factors to ALM including trauma (penetrative injury) and exposure to agriculture
TE D
chemicals. Briggs (4) noted this finding, but concluded the initial injury only draws the patient’s attention to the lesion rather than causing the lesion. Kaskel (5) surmised that an increased incidence of trauma in acral sites was to be expected but found no association between trauma and
EP
the development of ALM.
There are no published papers suggesting an association between trauma and the aetiology of acral
AC C
lentiginous melanoma. We hypothesise a link between the development of melanoma with repeated micro-trauma by analysing barefoot gait pressure pattern, the distribution of plantar ALM and examining the ratio of incidence of ALM to body surface area.
Material and Method A retrospective clinical analysis from a single tertiary melanoma centre (Leeds Teaching Hospitals Trust) was completed. We identified fifty-seven cases of plantar acral lentiginous melanoma treated over a period of 11 years (January 2005 and January 2016). Patients were identified using the
2
ACCEPTED MANUSCRIPT
hospital pathology database. All samples were reviewed to ensure only melanomas that occurred on the plantar surface of the feet were included. The location of the lesion was confirmed through reviewing of patient records, operation notes and the hospital patient medical image system (Medical Image Manager, MIM). The following exclusion criteria were applied: ALM to the nail (sub-
RI PT
ungual melanoma), dorsum of foot or other non-plantar locations.
Histology and clinical images of all confirmed cases of plantar ALM were reviewed and baseline demographic and histological data recorded, these include age at diagnosis, location, Breslow
SC
thickness, lesion dimension, mitotic count, ulceration and regression status. Baseline histological data from the initial excisional biopsy were used for this study. However, in cases where the initial
M AN U
biopsy was incisional or punch biopsy, the histology data are taken from the wide local excision sample instead to allow for completeness of dataset. The foot was graphically divided into 12 quadrants; (medial, central and lateral horizontally; heel, midfoot, forefoot and toes vertically) .The distribution of the acral melanoma was mapped within these quadrants ( Figure 1).
Results
EP
normal walking.
TE D
A literature search was carried out to identify the known pressure mapping of the foot during
57 patients were included in the study, with a higher prevalence of females compared to males
AC C
(35:22) and an average age of 66.21 (range 35-86). The average Breslow thickness was 3.23mm (range 0.5 – 15.5mm). The histology did not record mitotic rate in 11 cases, the presence or absence of ulceration in 11 cases and macroscopic size of the lesion in 46 cases. In those cases of ALM in which the histological dataset was complete, the average diameter and mitotic rate were 22.62mm (range 4 - 64mm) and 6.28/mm2 (0-35) respectively. Ulceration was evident in 19 out of 46 cases At the point of lesion mapping, 8 cases were omitted (N=49) due to insufficient information in the case notes for precise location of the tumour. The locations of the 49 cases of ALM are represented by circles as seen in Figure 1. This illustrates that 83.5% of the cases of ALM presented in this study
3
ACCEPTED MANUSCRIPT
were concentrated around three areas of the foot; the lateral heel (37%), medial heel (20%) and across the metatarsal heads (26.5%). We found no cases that involved the instep of the foot and only a few cases, which arose on the lateral aspect of the mid foot or the pulp of the toes Gait analysis pressure map represents the magnitude and pattern of pressure applied to the foot
RI PT
during walking . The spectrum of colours represents the pressure applied to the different anatomical sites of the foot. The highest pressure (red) to the lowest pressure (green), with colours distributed according to the area over which the pressure is applied. The pressure map is presented alongside
SC
the image showing the distribution of ALM in our study.
Discussion
M AN U
There are several risk factors thought to be linked to the development of certain melanoma subtypes. Superficial Spreading, Nodular and Lentigo Maligna subtypes appear to be associated with fair skin (Fitzpatrick type I and II), excessive sunlight and ultraviolet light exposure along. In addition there may be a genetic susceptibility presenting as part of a family history or an atypical naevus
TE D
phenotype. The aetiology of ALM appears not to be associated with any of these factors, as specifically plantar skin is amelanotic and rarely experiences excessive ultraviolet light exposure.
EP
Most clinicians with an interest in melanoma, will remember cases where individual patients will have associated the development of their melanoma at ‘exactly the point where they injured
AC C
themselves several years previously. Phan et al (9) described the possible role of trauma as an aetiological factor for developing ALM but pointed it out as a frequency of only 13% in their series. Mohrle and Hafner (10) suggested a link between a history of trauma and developing subungual melanoma – most commonly seen on the thumb or hallux, postulating that due to their relative sizes, both digits would be subject to more frequent trauma compared to other digits. In a German study, ALM occurred on the feet in about 87%, and on the hands in 13% of the cases (11), whilst in our study we only found cases of ALM on the plantar aspect of the foot. However both studies confirm a significant predilection for developing ALM on the foot, an area, which is subjected to
4
ACCEPTED MANUSCRIPT
repeated and persistent microtrauma. These papers and others, have raised the possibility of trauma being an aetiological factor in the development of ALM, however these are often limited, retrospective small case series with poor recollection of ‘where the trauma occurred’. There has also been frequent discussion as to whether the trauma itself just highlighted a pre-existing lesion.
RI PT
This study examined the question from a different perspective, namely to assess whether the location of known ALM on the foot correlated to known pressure data from gait analysis. The hypothesis examining whether recurrent microtrauma on the plantar aspect of the foot could be an
SC
aetiological factor in the development of Acral Lentiginous Melanoma
The pressure gait maps define the areas of peak pressure applied to the foot during normal walking.
M AN U
What is remarkable is the direct correlation of these pressure areas with the anatomical distribution of the ALM in this series. The pattern of distribution correlates not only to the anatomical subregions of the foot as per the pressure map, but the highest density of ALM also correlates with the zones of peak pressure applied to the foot whilst walking. In addition it is noticeable that in this
TE D
study, ALM occurred neither within the instep area of the foot, nor the palmar aspect of the hand, both regions not normally associated with excessive shear or pressure forces. The dermatopathology of skin from the plantar instep and palmar skin demonstrate them to have the same characteristics
EP
as the skin from weight-bearing areas of the foot albeit with a thinner keratin layer. Therefore if there is a genetic or systemic explanation as to the aetiology of ALM, one would expect
AC C
a relatively even anatomical distribution of cases of ALM. The common subtypes of melanoma, appear most frequently on sun exposed sites and even demonstrate an intersex distribution appropriate for different skin exposure – female legs, male trunk. ALM appears to be associated with weight-bearing areas of plantar skin and within that a concentration of cases directly proportional to differential pressures applied to those areas
The relative incidence of ALM varies according to ethnic origin. In the Afro-Caribbean population, ALM account for up to 80% of all melanomas, however in the white Caucasian group, which is
5
ACCEPTED MANUSCRIPT
representative of our study group, the incidence has been reported at around 7% (11). The surface area of the foot represents about 1.75% of the total body surface area, however the evaluated surface area of the contact part of the foot is less than 1 %. Therefore the contact element of both feet represents about 2% of the total body surface area. However the incidence of ALM within this
RI PT
site is 3-4 times greater than this. If the aetiological factors associated with the development of ALM were the same as those of other melanoma subgroups then one would expect the frequency of occurrence of ALM to match the percentage body surface occupied by glabrous skin, namely 1.75%. In practice the exact opposite is found, where ALM of the foot, has been reported, to have a
SC
prevalence 5 to 16 times higher than any other anatomical location. (6, 7, 8). This suggests ALM to
M AN U
have different aetiological factors when compared to the other more common melanoma subtypes.
The epidemiology data of this series also agrees with previous reports of the relative later onset of ALM. This would also support our proposal of an aetiological effect relating to microtrauma. It is not the acute injury in which we see ALM develop; otherwise ALM would be expected to correlate with
TE D
people who have undergone foot surgery. The question is whether chronic microtrauma is a significant causative factor, our data suggests a strong possibility.
AC C
Funding: nil
EP
Conflict of Interest: nil
6
ACCEPTED MANUSCRIPT
Average
Range
66.21
(35-86)
Male
Female
22
35
Average
Range
3.23
(0.5 - 15.5)
Yes
No
19
27
Mitotic Rate (no/mm2) (n = 46)
Average
Range
6.28
(0-35)
Size (mm) (n = 46)
Average
Range
22.62
(4-64)
Sex (n = 57) Tumour Thickness (mm) (n = 57) Ulceration (n = 46)
SC
Age (years) (n = 57)
RI PT
Table 1 –Tumour demographics for ALM Histology
Table 2 –ALM distribution per quadrant
5
Midfoot
0
Forefoot
4 1
Central
Lateral
9
14
1
4
5
4
0
2
AC C
Toes
EP
Heel
TE D
Medial
M AN U
Table 1: Patient Demographics and Tumour Histology Breakdown
7
ACCEPTED MANUSCRIPT
References
1. Reed RJ. New concepts in surgical pathology of the skin. John Wiley & Sons; 1976. 73-96. 2. Krementz ET, Feed RJ, Coleman WP, 3rd, Sutherland CM, Carter RD, et al. Acral lentiginous melanoma. A clinicopathologic entity. Ann Surg. Lippincott, Williams, and Wilkins; 1982 May
RI PT
1;195(5):632–1185. 3. Green A, McCredie M, MacKie R, Giles G, Young P, Morton C, et al. A case-control study of melanomas of the soles and palms (Australia and Scotland). Cancer Causes Control. 1999 Feb;10(1):21–5.
SC
4. Briggs JC. The role of trauma in the aetiology of malignant melanoma: a review article. Br J Plast Surg. 1984 Oct;37(4):514–6.
M AN U
5. Kaskel P, Kind P, Sander S, Peter RU, Krähn G. Trauma and melanoma formation: a true association? Br J Dermatol. 2000 Oct;143(4):749–53.
6. Ridgeway CA, Hieken TJ, Ronan SG, Kim DK, Gupta Das TK. Acral lentiginous melanoma. Arch Surg. 1995 Jan;130(1):88–92.
TE D
7. Paladugu RR, Winberg CD, Yonemoto RH. Acral lentiginous melanoma. A clinicopathologic study of 36 patients. Cancer. 1983 Jul 1;52(1):161–8. 8. Sutherland CM, Mather FJ, Muchmore JH, Carter RD, Reed RJ, Krementz ET. Acral lentiginous
EP
melanoma. Am J Surg. 1993 Jul;166(1):64–7.
9. Phan A, Touzet S, Dalle S, Ronger-Savlé S, Balme B, Thomas L. Acral lentiginous melanoma: a
AC C
clinicoprognostic study of 126 cases. Br J Dermatol. 2006 Sep;155(3):561–9. 10. Möhrle M, Häfner HM. Is subungual melanoma related to trauma? Dermatology (Basel). 2002;204(4):259–61.
11. Kuchelmeister C, Schaumburg-Lever G, Garbe C. Acral cutaneous melanoma in caucasians: clinical features, histopathology and prognosis in 112 patients. Br J Dermatol 2000;143(2):275– 80.
8
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT