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Subungual melanoma: a clinico-pathological study of 24 cases
Elrrrrrh Jozend ofP/usri< surge,? , 1992). 45. 275.-278 6
1992 The British Association of Plastx Surgconr
PLASTIC
Subungual melanoma
:
a clinico-pathological
SURGERY
study of 24 cases
H. S. Rigby and J. C. Briggs Department
of Histopathology,
Frenchay Hospital.
Frencha)‘, Bristol
SUMMARY. Twenty-four patients with subungual melanoma (13 women and 11 men) had a mean age of 61.6 years. Twenty-two lesions arose either on the thumb or hallux. The mean delay before diagnosis was 30 months. Two patients presented with stage two melanoma and three of the melanomas were in situ lesions (Clark level 1). Nineteen melanomas were Clark level 4 or 5 and the mean thickness of the invasive melanomas was 4.7 mm. Seven patients died of metastatic disease (mean survival 10 months, range 6-50 months). Clark level, thickness and mitotic activity of the melanomas correlated with poor clinical outcome. Delay in presentation and the presence of advanced disease contribute to the poor prognosis of this tumour.
In 1886, Sir Jonathan Hutchinson gave the first detailed description of subungual melanoma in which he called the lesion a “melanotic whitlow” (Hutchinson, 1886). He recognised both the malignant nature of the condition and that the only effective treatment was radical surgery. In western countries the lesion is rare, with incidences varying from less than 2 % up to 3.5% of cutaneous melanomas (Das Gupta and Brasfield, 1965 ; Shaw and Koea. 1988). However, in non-whites the subungual site is one of the most prevalent (Gutman et al., 1985). and in one series, 31% of cutaneous melanomas in Japanese persons were in the subungual region (Saida and Oshima, 1989). Although over a century has passed since it was first reported. subungual melanoma is still frequently mistaken for benign conditions and is thus improperly treated (Gibson et al., 1957 ; Das Gupta and Brasfield, 1965 ; Pack and Oropeza, 1967). The close resemblance of this tumour to traumatic. inflammatory or benign lesions of the nail beds leads to diagnostic delay, which contributes to the poor prognosis (Patterson and Helwig, 1980; Feibleman et al., 1980). The prognosis of patients with subungual melanoma is generally poor compared with melanoma of other sites. with 5-year survival figures ranging from 16-50 % (Graham, 1973 ; Patterson and Helwig, 1980). There is evidence that subungual melanoma has special clinical and pathological characteristics (Klausner et al., 1987) even though in many studies subungual melanomas are grouped with other melanomas of the extremities (Krementz et al., 1982). The clinical and pathological features which may influence prognosis have not been elucidated (Das Gupta and Brasfield, 1965; Patterson and Helwig, 1980; Feibleman et al., 1980). This study analyses these features and the results of treatment of 24 subungual melanomas at a major referral centre from 1967 until mid- 199 1. Materials and methods Frenchay
Hospital
is a major
centre
for the man-
agement of cutaneous melanoma. Details of all melanoma cases are inserted into a computer based Melanoma Registry (Briggs et al., 1984) and up to 50 items of information are available for each case. The clinical details came from the case notes and microfilm records. During the period from 1967 to June 1991 2323 patients with primary cutaneous melanoma were treated, with 282 melanomas located on the hands and feet, of which 24 were subungual. The clinical data included patient age and sex, duration of lesion before diagnosis, history of lesion, stage and surgical management, clinical course and survival. Histological details of the primary lesions include melanoma subtype, Clark level, thickness, mitotic activity. cell type, amount of pigment production. lymphocytic infiltrate, vascular and/or lymphatic invasion and regression. Results ClinicalJkatures Thirteen patients were women and 11 were men. The average age at presentation was 61.6 years (range 16-96). Fourteen of the lesions were on the upper limb, of which 13 were on the thumb and one on a middle finger. Of the lower limb lesions, 9 were on the hallux and one on a middle toe nail. In 7 cases there was a definite history of preceding trauma. In a further 7 patients there was a history of a pigmented area on the nail of mean duration 2.5 years (0.5-7 years). Ten lesions arose de nova in the nail bed. The length of history ranged from 3 months to 12 years. Thirteen patients underwent biopsy prior to dehnitive surgery. All lesions were treated by amputation. In the upper limb the digits were amputated through, or just proximal to, the distal interphalangeal joint. The great toes were amputated at the metatarsophalangeal joint. The other toe was amputated through the proximal phalanx. Three patients presented with enlarged groin nodes and synchronous node dissection showed metastatic melanoma (i.e. Stage IT). In three patients there was in situ melanoma (Clark level 1) and
216
British Journal of Plastic Surgery
Table 1 Numbers of invasive subungual melanomas graded (O-3) for pigment production. lymphocytic infiltration and regression
Pigment Lymphoid Regression
infiltrate
0
I
4 3 I
11 12 13
Grade 2 5 4 0
3 1 2 1
Table 2 Pathological parameters of invasive subungual melanomas in 9 patients, 7 dead and 2 with recurrence, and of 6 patients alive with no recurrence Patients dead or with recurrence
Patients alive with no recurrence
Superficial spreading Acral lentiginous Nodular Unclassified
3 3 0 3
2 3 1 0
Clark level 4 5
1 8
4 2
Thickness (mean)
5.9 (SD = 2.3)
3.3 (SD = 1.5)
4.4 (SD = 2.8)
2.2 (SD = 1.6)
Melanoma
type
in mm
Mitotic figures/ 5 HPF (mean) Cell type Round Spindle Bizarre Round and spindle Round and bizarre
melanomas was a mixture of round and spindle cells (38 %). Round cell tumours alone accounted for 24 % of cases, while spindle cells, round and bizarre cells and bizarre cells accounted for 19 %, 10 % and 9 % of cases respectively. The mitotic figures per 5 high power fields (1 sq.mm) ranged from O-10 with a mean of 3.1. Seven cases showed a mitotic activity of 5 or more mitotic figures per 5 high power fields. Six of the lesions showed evidence of vessel invasion. The degree of pigment production, amount of host lymphoid infiltration and degree of regression were all graded from O-3. The results are shown in Table 1. The pathological features in the melanomas of patients who had died of metastatic melanoma or were alive with recurrence were compared with those of patients who were alive and recurrence free. The results are shown in Table 2 on the 15 patients with invasive subungual melanoma and excludes those with level 1 lesions (3) and those who died of unrelated causes (6). No statistically significant difference was demonstrated between the two groups in respect of melanoma type, degree of pigmentation, degree of lymphocytic infiltration or degree of regression. However, a statistically significant difference between the two groups was demonstrated for Clark levels (Fisher’s exact probability test p = 0.047), thickness, and number of mitoses per 5 high power fields (p = 0.034 and 0.039) respectively (Mann-Whitney U Test).
Discussion
Pigment 0
3 5 1 0
2 Vascular
invasion
Lymphocyte (mean)
infiltrate
1 2 3 0
4
1
1.4 (SD = 0.7)
1.O (SD = 0.9)
4 = Grade 5 = Grade
2 = Grade 4 = Grade
0 1
0 1
of the 21 patients with invasive disease, 19 (90 %) had lesions that were of either Clark level 4 or 5. Seven of the patients had nodal recurrence following primary surgery (mean time to recurrence 19 months). Seven patients (29 %) died from metastatic melanoma with a mean survival of 10.7 months (range 650 months). Six patients died from unrelated causes and all had been clinically free of melanoma at the followup prior to death (mean follow-up 71 months). Eleven patients are alive with follow-up from 3 months to 18 years.
Pathological features Ten of the patients had superficial spreading melanomas ; 9 were of acral lentiginous type, 3 cases were unclassifiable and 2 cases proved to be nodular variants. The range of thickness in mm for the invasive melanomas was l-1 1 mm with a mean of 4.7 mm. The commonest cell type in the invasive subungual
Only rarely does melanoma affect the nail bed in Caucasians. In this series an incidence of 1% of all primary cutaneous melanomas is less than that of other series (Das Gupta and Brasfield, 1965 ; Pack and Oropeza, 1967). There is a relatively high incidence in blacks (Petersen et al., 1962) when one considers the relative rarity of melanoma in that race. In a Japanese series, 19 % of all diagnosed melanomas involved the nail bed (Takematsu et al., 1984). The majority of the patients with subungual melanoma are middle aged or elderly (in this series 83 % were aged 50 or over). This is in contrast to melanomas in other cutaneous sites. Cutaneous melanomas are more common in women, whereas the incidence of subungual melanomas is similar in men and women. The frequency of distribution of lesions between the fingers and toes is equal in Caucasians. In this series, 92% of the melanomas were located on either the thumbs or the great toes. Although this pattern is well described (Feibleman et al., 1980) in the Japanese there is a higher proportion of upper limb lesions (Takematsu et al., 1984). The higher distribution of lesions on the thumbs and great toes was noted by Hertzler (1922) and is intriguing. In the foot 90% of subungual melanomas involve the hallux and there is no doubt that this the most commonly injured toe. The area of the thumb nail is 50-100% larger than for any one finger and the area of the hallux nail is 80-250 % larger than any other toe (Roberts, 1984). These area differences, however, probably do not account for the preponderance of subungual melanomas on these
Subungual
Melanoma : a Clinico-Pathological
Study
digits. While the thumb nail is generally held exposed to the sunlight when in normal posture, this obviously does not apply to the usually covered hallux nail. This distribution remains an enigma. Most subungual melanomas present due to the appearance of the digit rather than discomfort (Briggs, 1985). Delay in presentation is not uncommon and in this series the length of history was a mean of 2.5 years (range 3 months to 12 years). A clinical misdiagnosis in favour of pyogenic granuloma, paronychia, subungual haematoma. vascular tumours and junctional naevi (Patterson and Helwig, 1980; Papachristou and Fortner, 1982) is often seen. Gibson et al. (1957) reported that of their patients, two thirds had some form of minor surgery before the condition was correctly diagnosed. In this series, 42 % of cases presented because of the appearance of a nail lesion de now. It is possible that some patients were unaware of the existence of a pigmented lesion at this site and became conscious of the condition following local trauma. The relatively common history of preceding trauma in this series (29%) is less than in others (Patterson and Helwig, 1980; Takematsu et al., 1984). Malignant change in the skin is well known to occur in old burn scars and at other sites of chronic trauma. Ewing in 1935 postulated minimal criteria for a causal relationship between trauma and malignancy. After the 1930’s, papers concerning subungual melanoma either do not mention trauma (Nordlund and Lerner, 1977) or mention it only to dismiss it. However, there are case reports demonstrating the relationship between trauma and cutaneous melanoma (Nancarrow, 1979 ; Stillwell and Sclare, 1980). Nevertheless, subungual trauma is common and subungual melanoma rare and, as trauma has not been proven at any site as a cause of melanoma, it is highly unlikely that injury plays any significant role (Briggs, 1984). The role of the biopsy in cutaneous melanoma has been controversial (Griffiths and Briggs, 1985; Lederman and Sober, 1986). However, there now appears to be no adverse effect on prognosis from the performing of a biopsy (Lees and Briggs, 1991). In this series 13 out of the 24 patients underwent biopsy and there was no demonstrable effect on prognosis. The biopsy procedure may require excision of the entire nail and should extend down to near the periosteum. The entire nail must be carefully embedded and the inclusion of skin immediately adjacent to the main lesion is important, since it is in this adjacent skin that clues as to whether the melanoma is nodular, superficial spreading or acral lentiginous are found. Early biopsy and clinical awareness are essential whether the lesion is pigmented or not. Biopsies may be reported as benign because the histological impression is bland. Kopf et al. ( 1979) state that, in Caucasians, an acquired subungual melanocytic lesion is more likely to be a malignant melanoma than a benign naevus. The only effective means of treatment is surgery . In the Frenchay unit, the treatment of the primary lesion is by amputation, through or proximal to the interphalangeal joint for the thumb, fingers and toes and through or proximal to the metatarsophalangeal joint for the hallux. Therapeutic lymph node dissection is required in patients with clinically palpable nodes
217 (Feibleman et al., 1980). The value of elective lymph node dissection and isolated limb perfusion is not firmly established. Clark et al. (1979) state that they perform prophylactic lymph node dissection if there is stage 2 disease, the lesion extends to levels 4 or 5 and in all tumours greater than 1.5 mm thick. The local micro-anatomy of the lesions and the fact that the dermis of the nail bed is thick and hard and adherent to the periosteum means that the assessment of levels and, to a lesser degree. lesional thickness can be difficult. In this series 79 % of the lesions invaded to Clark level 4 or 5. It should be emphasised that the radial growth phase of a malignant melanoma in the subungual region is easily confused histologically with a junctional naevus (Briggs, 1985). Most series report a preponderance of acral lentiginous melanoma (Feibleman et al., 1980; Hudson et al., 1990). However, in this series the classical acral lentiginous pattern was not always recognised and the picture was one of superficial spreading, nodular or unclassifiable variant. The pathological parameters of these subungual melanomas have been analysed to ascertain any relationship to prognosis. Patterson and Helwig (1980) found that the biological behaviour of subungual melanomas was similar for lentiginous and nodular varieties and indicated that depth of invasion is the most important indicator of prognosis. No difference was demonstrated in the melanoma type in our group between the 9 patients dead or with recurrence and in the 6 who were alive and recurrence free. The histogenetic type of subungual melanoma did not influence clinical outcome. This is similar to findings in other cutaneous sites. It would appear that one a melanoma has become invasive, then it is the depth of invasion that is of prognostic significance and the actual melanoma type is not important (Bonett et al.. 1986). In Patterson and Helwig’s series there was no correlation between thickness in mm and numbers of mitotic figures per 5 high power fields in the group of patients alive and recurrence free and those either dead from melanoma or with recurrence. Other series have shown the mitotic rate to correlate well with survival and this may be the best differential factor in determining prognosis (Feibleman et al.. 1980). No significant difference could be demonstrated between the 2 groups when the degree of host lymphoid response and degree of pigmentation were analysed. The lack of host response has been described as a poor prognostic sign (Huvos et al., 1974) but in this series no correlation with outcome can be made. The vascular invasion between the two groups was not statistically significant, although 4 out of 9 of the patients dead or with recurrence demonstrated it and it was present in only one of the six survivors. Subungual melanoma has a generally poor prognosis and aggressive behaviour. The lesions tend to be seen early by the patient and diagnosed late by the clinician. The majority of the melanomas are deep when diagnosed and early metastasis is common. Amputation is the treatment of choice. A variety of histological features can be observed which do not appear to influence the clinical outcome. In this study
British Journal
278
Clark level, thickness and mitotic figures correlated with a poor outcome. The overall 5 year survival figures range from 1650 % (Graham, 1973 ; Patterson and Helwig, 1980). Once the diagnosis is confirmed then Hutchinson’s advice given all those years ago is still relevant-“ Early amputation is demanded “.
Acknowledgement The authors are grateful to the Plastic Surgeons at Frenchay Hospital, whose patients form this study, and to Mr A. 0. Hughes, Senior Lecturer in Medical Statistics, University of Bristol, for statistical help.
References
Huvos, A. G., Shah, J. P. and Mike, V. (1974). Prognostic factors in cutaneous melanomas. A comparative study of long term and short term survivors. Human Pathology, 5, 347. Klausner, J. M., Inbar, M. and Gutman, M. (1987). Nail bed melanoma. Journal of Surgical Oncology, 34, 208. Kopf, A. W., Bart, R. S., Rodriguez-Sains, R. S. and Ackerman, A. B. (1979). Malignant melanoma. New York, Masson Publishing USA Inc., p. 161. Krementz, E. T., Reed, R. J., Coleman, W. P., Sutherland, C. M., Carter, R. D. and Campbell, M. (1982). Acral lentiginous melanoma: a clinico-pathologic entity. Annals of Surgery, 195, 632. Lederman, J. S. and Sober, A. J. (1986). Does wide excision as the initial diagnostic procedure improve prognosis in patients with cutaneous melanoma? Journal qf Dermutological Surger_v and Oncology, 12, 697. Lees, V. C. and Briggs, J. C. (199 1). Effect of initial biopsy procedure
on prognosis in stage 1 invasive cutaneous melanoma; review of 1086 patients. British Journul of Surgery, 78, 1108. Nancarrow, J. D. (1979). Malignant melanoma arising in an unstable burn scar. British Journal of Plastic Surger?, 32, 135. Nordlund, J. J. and Lemer, A. B. (1977). On the cause of melanomas. American Journal qf Pathology, 89. 443.
Bone& A., Roder, D. and Esterman, A. (1986). Melanoma case survival rates in South Australia by histological type, thickness and level of tumour at diagnosis. The Medical Journal of Australia, 144,680. Briggs, J. C. (1984). The role of trauma in the aetiology of malignant melanoma. British Journal of Plastic Surgery, 37, 5 14. Briggs, J. C. (1985). Subungual malignant melanoma: a review article. British Journal of Plastic Surgery, 38. 174. Briggs, J. C., Ibrahim, N. B. N., Wickremaratehi, T., Mackintosh, I., Norris, D. and Griffiths, R. W. (1984). A melanoma registry based on a computer run word and data processing system. Computers in Biological Medicine, 14, 245.
Clark, W. H., Goldman, L. I. and Mastrangelo, M. J. (1979). Human malignant melanoma. New York, Grune Stratton. p. 121. Das Gupta, T. and Brasfield, R. (1965). Subungual melanoma. Annals of Surgery, 161. 545.
Ewing, J. (1935). Modern attitude toward traumatic cancer. Archives of Pathology, 19, 690.
Feibleman, C. E., StoU, H. and Maize, J. C. (1980). Melanomas of the palm, sole and nail bed. A clinicopathological study. Cancer, 46. 2492.
Gibson, J., Montgomery, H., Woolner, L. B. and Brunsting, L. A. (1957). Melanotic whitlow (subungual melanoma). Journal oj imesfigatizle Dermatology, 29,
of Plastic Surgery
119.
Graham, W. P. (1973). Subungual melanoma. Pennsylvania Medicine, 76, 56. Griffiths, R. W. and Briggs; J. C. (1985). Biopsy procedures, primary
wide excisional surgery and long term prognosis in primary clinical stage 1 invasive cutaneous malignant melanomas. Annuls of rhe RoJlal College of Surgeons of England, 67,15.
Gutman, M., Klausner, J. M., Inbar, M., Skornick, Y., Baratz, M. and Rozin, R. R. (1985). Acral (volar-subungual) melanoma. British Journal of Surgery, 72, 610.
Hertzler, A. E. (1922). Melanoblastoma
of the nail bed. Architles of
Dermatology and Syphilology. 6, 701.
Hudson, D. A., Krige, J. E. J., Stover, R. M. and King, H. S. ( 1990). Subungual melanoma of the hand. Journal of Hand Surgeq,, 15B, 288. Hutchinson, J. (1886). Melanosis not often black: melanotic whitlow. British Medical Journal. 1, 491.
Pack, G. T. and Oropeza, R. (1967). Subungual melanoma. Surger) Gynaecology and Obstetrics, 124, 571. Papachristou, D. N. and Fortner, J. G. (1982). Melanoma arising under the nail. Journal of Surgical Oncology, 21,219. Patterson, R. H. and Helwig, E. B. (1980). Subungual malignant melanoma : a clinical pathological study. Cancer, 46, 2074. Petersen, N. C., Bodenham, D. C. and Lloyd, 0. C. (1962). Malignant melanomas of the skin. A study of the origin, development, aetiology. spread, treatment and prognosis. Brirish Journal c$ Plastic Surgery. 15. 49. Roberts, A. H. N. (1984). Subungual melanoma following a single injury. Journal of Hund Surgery, 9B. 328. Saida, T. and Oshima, Y. (1989). Clinical and histopathological characteristics of the early lesions of subungual malignant melanoma. Cancer, 63, 556. Shaw, J. H. F. and Koea, J. B. (1988). Acral (volar-subungual) melanoma in Auckland New Zealand. British Journal qfsurgery, 75. 69.
Stillwell, J. H. and Sclare, G. (1980). Malignancy following a single injury to the skin. British Journal of Plastic Surgery,. 43. 74. Takematsu, H., Obata, M., Tomita, Y., Kato, T., Takahashi, M. and Ahe, R. (1984). Subungual melanoma. A clinicopathologic study of 16 Japanese cases. Cancer, 55. 2725.
Addendum Blessing, K., Kernohan, N. M. and Park, K. G. M. (1991). Subungual melanoma: clinicopathological features of 100 cases. Histopathology, 19. 425.
The Authors H. S. Rigby, DM, FRCS, MRCPath, Senior Registrar in Histopathology. J. C. Briggs, MBBS, DPath, FRCPath, Consultant Histopathologist. Department of Histopathology, Frenchay Hospital. Frenchay, Bristol BSI 6 1LE. Requests for reprints to Dr H. S. Rigby. Paper received 15 November 1991. Accepted 25 November 1991.
1992 The British Association of Plastx Surgconr
PLASTIC
Subungual melanoma
:
a clinico-pathological
SURGERY
study of 24 cases
H. S. Rigby and J. C. Briggs Department
of Histopathology,
Frenchay Hospital.
Frencha)‘, Bristol
SUMMARY. Twenty-four patients with subungual melanoma (13 women and 11 men) had a mean age of 61.6 years. Twenty-two lesions arose either on the thumb or hallux. The mean delay before diagnosis was 30 months. Two patients presented with stage two melanoma and three of the melanomas were in situ lesions (Clark level 1). Nineteen melanomas were Clark level 4 or 5 and the mean thickness of the invasive melanomas was 4.7 mm. Seven patients died of metastatic disease (mean survival 10 months, range 6-50 months). Clark level, thickness and mitotic activity of the melanomas correlated with poor clinical outcome. Delay in presentation and the presence of advanced disease contribute to the poor prognosis of this tumour.
In 1886, Sir Jonathan Hutchinson gave the first detailed description of subungual melanoma in which he called the lesion a “melanotic whitlow” (Hutchinson, 1886). He recognised both the malignant nature of the condition and that the only effective treatment was radical surgery. In western countries the lesion is rare, with incidences varying from less than 2 % up to 3.5% of cutaneous melanomas (Das Gupta and Brasfield, 1965 ; Shaw and Koea. 1988). However, in non-whites the subungual site is one of the most prevalent (Gutman et al., 1985). and in one series, 31% of cutaneous melanomas in Japanese persons were in the subungual region (Saida and Oshima, 1989). Although over a century has passed since it was first reported. subungual melanoma is still frequently mistaken for benign conditions and is thus improperly treated (Gibson et al., 1957 ; Das Gupta and Brasfield, 1965 ; Pack and Oropeza, 1967). The close resemblance of this tumour to traumatic. inflammatory or benign lesions of the nail beds leads to diagnostic delay, which contributes to the poor prognosis (Patterson and Helwig, 1980; Feibleman et al., 1980). The prognosis of patients with subungual melanoma is generally poor compared with melanoma of other sites. with 5-year survival figures ranging from 16-50 % (Graham, 1973 ; Patterson and Helwig, 1980). There is evidence that subungual melanoma has special clinical and pathological characteristics (Klausner et al., 1987) even though in many studies subungual melanomas are grouped with other melanomas of the extremities (Krementz et al., 1982). The clinical and pathological features which may influence prognosis have not been elucidated (Das Gupta and Brasfield, 1965; Patterson and Helwig, 1980; Feibleman et al., 1980). This study analyses these features and the results of treatment of 24 subungual melanomas at a major referral centre from 1967 until mid- 199 1. Materials and methods Frenchay
Hospital
is a major
centre
for the man-
agement of cutaneous melanoma. Details of all melanoma cases are inserted into a computer based Melanoma Registry (Briggs et al., 1984) and up to 50 items of information are available for each case. The clinical details came from the case notes and microfilm records. During the period from 1967 to June 1991 2323 patients with primary cutaneous melanoma were treated, with 282 melanomas located on the hands and feet, of which 24 were subungual. The clinical data included patient age and sex, duration of lesion before diagnosis, history of lesion, stage and surgical management, clinical course and survival. Histological details of the primary lesions include melanoma subtype, Clark level, thickness, mitotic activity. cell type, amount of pigment production. lymphocytic infiltrate, vascular and/or lymphatic invasion and regression. Results ClinicalJkatures Thirteen patients were women and 11 were men. The average age at presentation was 61.6 years (range 16-96). Fourteen of the lesions were on the upper limb, of which 13 were on the thumb and one on a middle finger. Of the lower limb lesions, 9 were on the hallux and one on a middle toe nail. In 7 cases there was a definite history of preceding trauma. In a further 7 patients there was a history of a pigmented area on the nail of mean duration 2.5 years (0.5-7 years). Ten lesions arose de nova in the nail bed. The length of history ranged from 3 months to 12 years. Thirteen patients underwent biopsy prior to dehnitive surgery. All lesions were treated by amputation. In the upper limb the digits were amputated through, or just proximal to, the distal interphalangeal joint. The great toes were amputated at the metatarsophalangeal joint. The other toe was amputated through the proximal phalanx. Three patients presented with enlarged groin nodes and synchronous node dissection showed metastatic melanoma (i.e. Stage IT). In three patients there was in situ melanoma (Clark level 1) and
216
British Journal of Plastic Surgery
Table 1 Numbers of invasive subungual melanomas graded (O-3) for pigment production. lymphocytic infiltration and regression
Pigment Lymphoid Regression
infiltrate
0
I
4 3 I
11 12 13
Grade 2 5 4 0
3 1 2 1
Table 2 Pathological parameters of invasive subungual melanomas in 9 patients, 7 dead and 2 with recurrence, and of 6 patients alive with no recurrence Patients dead or with recurrence
Patients alive with no recurrence
Superficial spreading Acral lentiginous Nodular Unclassified
3 3 0 3
2 3 1 0
Clark level 4 5
1 8
4 2
Thickness (mean)
5.9 (SD = 2.3)
3.3 (SD = 1.5)
4.4 (SD = 2.8)
2.2 (SD = 1.6)
Melanoma
type
in mm
Mitotic figures/ 5 HPF (mean) Cell type Round Spindle Bizarre Round and spindle Round and bizarre
melanomas was a mixture of round and spindle cells (38 %). Round cell tumours alone accounted for 24 % of cases, while spindle cells, round and bizarre cells and bizarre cells accounted for 19 %, 10 % and 9 % of cases respectively. The mitotic figures per 5 high power fields (1 sq.mm) ranged from O-10 with a mean of 3.1. Seven cases showed a mitotic activity of 5 or more mitotic figures per 5 high power fields. Six of the lesions showed evidence of vessel invasion. The degree of pigment production, amount of host lymphoid infiltration and degree of regression were all graded from O-3. The results are shown in Table 1. The pathological features in the melanomas of patients who had died of metastatic melanoma or were alive with recurrence were compared with those of patients who were alive and recurrence free. The results are shown in Table 2 on the 15 patients with invasive subungual melanoma and excludes those with level 1 lesions (3) and those who died of unrelated causes (6). No statistically significant difference was demonstrated between the two groups in respect of melanoma type, degree of pigmentation, degree of lymphocytic infiltration or degree of regression. However, a statistically significant difference between the two groups was demonstrated for Clark levels (Fisher’s exact probability test p = 0.047), thickness, and number of mitoses per 5 high power fields (p = 0.034 and 0.039) respectively (Mann-Whitney U Test).
Discussion
Pigment 0
3 5 1 0
2 Vascular
invasion
Lymphocyte (mean)
infiltrate
1 2 3 0
4
1
1.4 (SD = 0.7)
1.O (SD = 0.9)
4 = Grade 5 = Grade
2 = Grade 4 = Grade
0 1
0 1
of the 21 patients with invasive disease, 19 (90 %) had lesions that were of either Clark level 4 or 5. Seven of the patients had nodal recurrence following primary surgery (mean time to recurrence 19 months). Seven patients (29 %) died from metastatic melanoma with a mean survival of 10.7 months (range 650 months). Six patients died from unrelated causes and all had been clinically free of melanoma at the followup prior to death (mean follow-up 71 months). Eleven patients are alive with follow-up from 3 months to 18 years.
Pathological features Ten of the patients had superficial spreading melanomas ; 9 were of acral lentiginous type, 3 cases were unclassifiable and 2 cases proved to be nodular variants. The range of thickness in mm for the invasive melanomas was l-1 1 mm with a mean of 4.7 mm. The commonest cell type in the invasive subungual
Only rarely does melanoma affect the nail bed in Caucasians. In this series an incidence of 1% of all primary cutaneous melanomas is less than that of other series (Das Gupta and Brasfield, 1965 ; Pack and Oropeza, 1967). There is a relatively high incidence in blacks (Petersen et al., 1962) when one considers the relative rarity of melanoma in that race. In a Japanese series, 19 % of all diagnosed melanomas involved the nail bed (Takematsu et al., 1984). The majority of the patients with subungual melanoma are middle aged or elderly (in this series 83 % were aged 50 or over). This is in contrast to melanomas in other cutaneous sites. Cutaneous melanomas are more common in women, whereas the incidence of subungual melanomas is similar in men and women. The frequency of distribution of lesions between the fingers and toes is equal in Caucasians. In this series, 92% of the melanomas were located on either the thumbs or the great toes. Although this pattern is well described (Feibleman et al., 1980) in the Japanese there is a higher proportion of upper limb lesions (Takematsu et al., 1984). The higher distribution of lesions on the thumbs and great toes was noted by Hertzler (1922) and is intriguing. In the foot 90% of subungual melanomas involve the hallux and there is no doubt that this the most commonly injured toe. The area of the thumb nail is 50-100% larger than for any one finger and the area of the hallux nail is 80-250 % larger than any other toe (Roberts, 1984). These area differences, however, probably do not account for the preponderance of subungual melanomas on these
Subungual
Melanoma : a Clinico-Pathological
Study
digits. While the thumb nail is generally held exposed to the sunlight when in normal posture, this obviously does not apply to the usually covered hallux nail. This distribution remains an enigma. Most subungual melanomas present due to the appearance of the digit rather than discomfort (Briggs, 1985). Delay in presentation is not uncommon and in this series the length of history was a mean of 2.5 years (range 3 months to 12 years). A clinical misdiagnosis in favour of pyogenic granuloma, paronychia, subungual haematoma. vascular tumours and junctional naevi (Patterson and Helwig, 1980; Papachristou and Fortner, 1982) is often seen. Gibson et al. (1957) reported that of their patients, two thirds had some form of minor surgery before the condition was correctly diagnosed. In this series, 42 % of cases presented because of the appearance of a nail lesion de now. It is possible that some patients were unaware of the existence of a pigmented lesion at this site and became conscious of the condition following local trauma. The relatively common history of preceding trauma in this series (29%) is less than in others (Patterson and Helwig, 1980; Takematsu et al., 1984). Malignant change in the skin is well known to occur in old burn scars and at other sites of chronic trauma. Ewing in 1935 postulated minimal criteria for a causal relationship between trauma and malignancy. After the 1930’s, papers concerning subungual melanoma either do not mention trauma (Nordlund and Lerner, 1977) or mention it only to dismiss it. However, there are case reports demonstrating the relationship between trauma and cutaneous melanoma (Nancarrow, 1979 ; Stillwell and Sclare, 1980). Nevertheless, subungual trauma is common and subungual melanoma rare and, as trauma has not been proven at any site as a cause of melanoma, it is highly unlikely that injury plays any significant role (Briggs, 1984). The role of the biopsy in cutaneous melanoma has been controversial (Griffiths and Briggs, 1985; Lederman and Sober, 1986). However, there now appears to be no adverse effect on prognosis from the performing of a biopsy (Lees and Briggs, 1991). In this series 13 out of the 24 patients underwent biopsy and there was no demonstrable effect on prognosis. The biopsy procedure may require excision of the entire nail and should extend down to near the periosteum. The entire nail must be carefully embedded and the inclusion of skin immediately adjacent to the main lesion is important, since it is in this adjacent skin that clues as to whether the melanoma is nodular, superficial spreading or acral lentiginous are found. Early biopsy and clinical awareness are essential whether the lesion is pigmented or not. Biopsies may be reported as benign because the histological impression is bland. Kopf et al. ( 1979) state that, in Caucasians, an acquired subungual melanocytic lesion is more likely to be a malignant melanoma than a benign naevus. The only effective means of treatment is surgery . In the Frenchay unit, the treatment of the primary lesion is by amputation, through or proximal to the interphalangeal joint for the thumb, fingers and toes and through or proximal to the metatarsophalangeal joint for the hallux. Therapeutic lymph node dissection is required in patients with clinically palpable nodes
217 (Feibleman et al., 1980). The value of elective lymph node dissection and isolated limb perfusion is not firmly established. Clark et al. (1979) state that they perform prophylactic lymph node dissection if there is stage 2 disease, the lesion extends to levels 4 or 5 and in all tumours greater than 1.5 mm thick. The local micro-anatomy of the lesions and the fact that the dermis of the nail bed is thick and hard and adherent to the periosteum means that the assessment of levels and, to a lesser degree. lesional thickness can be difficult. In this series 79 % of the lesions invaded to Clark level 4 or 5. It should be emphasised that the radial growth phase of a malignant melanoma in the subungual region is easily confused histologically with a junctional naevus (Briggs, 1985). Most series report a preponderance of acral lentiginous melanoma (Feibleman et al., 1980; Hudson et al., 1990). However, in this series the classical acral lentiginous pattern was not always recognised and the picture was one of superficial spreading, nodular or unclassifiable variant. The pathological parameters of these subungual melanomas have been analysed to ascertain any relationship to prognosis. Patterson and Helwig (1980) found that the biological behaviour of subungual melanomas was similar for lentiginous and nodular varieties and indicated that depth of invasion is the most important indicator of prognosis. No difference was demonstrated in the melanoma type in our group between the 9 patients dead or with recurrence and in the 6 who were alive and recurrence free. The histogenetic type of subungual melanoma did not influence clinical outcome. This is similar to findings in other cutaneous sites. It would appear that one a melanoma has become invasive, then it is the depth of invasion that is of prognostic significance and the actual melanoma type is not important (Bonett et al.. 1986). In Patterson and Helwig’s series there was no correlation between thickness in mm and numbers of mitotic figures per 5 high power fields in the group of patients alive and recurrence free and those either dead from melanoma or with recurrence. Other series have shown the mitotic rate to correlate well with survival and this may be the best differential factor in determining prognosis (Feibleman et al.. 1980). No significant difference could be demonstrated between the 2 groups when the degree of host lymphoid response and degree of pigmentation were analysed. The lack of host response has been described as a poor prognostic sign (Huvos et al., 1974) but in this series no correlation with outcome can be made. The vascular invasion between the two groups was not statistically significant, although 4 out of 9 of the patients dead or with recurrence demonstrated it and it was present in only one of the six survivors. Subungual melanoma has a generally poor prognosis and aggressive behaviour. The lesions tend to be seen early by the patient and diagnosed late by the clinician. The majority of the melanomas are deep when diagnosed and early metastasis is common. Amputation is the treatment of choice. A variety of histological features can be observed which do not appear to influence the clinical outcome. In this study
British Journal
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Clark level, thickness and mitotic figures correlated with a poor outcome. The overall 5 year survival figures range from 1650 % (Graham, 1973 ; Patterson and Helwig, 1980). Once the diagnosis is confirmed then Hutchinson’s advice given all those years ago is still relevant-“ Early amputation is demanded “.
Acknowledgement The authors are grateful to the Plastic Surgeons at Frenchay Hospital, whose patients form this study, and to Mr A. 0. Hughes, Senior Lecturer in Medical Statistics, University of Bristol, for statistical help.
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Addendum Blessing, K., Kernohan, N. M. and Park, K. G. M. (1991). Subungual melanoma: clinicopathological features of 100 cases. Histopathology, 19. 425.
The Authors H. S. Rigby, DM, FRCS, MRCPath, Senior Registrar in Histopathology. J. C. Briggs, MBBS, DPath, FRCPath, Consultant Histopathologist. Department of Histopathology, Frenchay Hospital. Frenchay, Bristol BSI 6 1LE. Requests for reprints to Dr H. S. Rigby. Paper received 15 November 1991. Accepted 25 November 1991.