- Email: [email protected]
Number of acquired melanocytic nevi in renal transplant recipients as a risk factor for melanoma
Number of Acquired Melanocytic Nevi in Renal Transplant Recipients as a Risk Factor for Melanoma A.T. Gu¨lec¸, D. Sec¸kin, Y. Saray, E. Sarıfakıog˘lu, G. Moray, and T. C¸olak
R
ENAL transplant recipients (RTRs) are at increased risk for malignant tumors due to long-term immunosuppression.1–5 Skin cancers are the most frequent malignancies in these patients, accounting for 37% of all de novo neoplasms.6 The cutaneous malignant rate is high, with a relative risk ranging from 3 to 9 times that in the general population.1 The presence of large numbers of melanocytic nevi is the best known risk factor for melanoma.7–9 A few investigations have documented higher than normal numbers of melanocytic nevi in RTRs.3,10,11 This case-controlled study was undertaken to investigate the numbers of acquired benign melanocytic nevi in adult RTRs. PATIENTS AND METHODS The study included 115 consecutive renal allograft recipients (78 males and 37 females) who attended the Renal Transplantation Unit at Baskent University for routine check-up examinations between March and October 2001. The mean patient age was 32.8 ⫾ 10.8 years (range, 18 to 61 years), and the mean time since transplantation was 55.4 ⫾ 54.6 months (range, 2 months to 24 years). Because the number of melanocytic nevi can be influenced by duration of immunosuppression, we divided the patients into 3 groups: group A (n ⫽ 30) had undergone transplantation within the year; group B (n ⫽ 47), 1–5 years survival; and group C (n ⫽ 38), more than 5 years survival. Thirty-six (31.3%) patients were taking prednisolone (P), cyclosporine (CyA), and mycophenolate mofetil; 33 (28.7%) were taking P, CyA, and azathioprine (Aza); 21 (18.3%) were taking P and CyA; 15 (13%) were taking P, mycophenolate mofetil, and tacrolimus; and 10 (8.7%) were taking other combinations of these 4 drugs. One hundred and one age- and sex-matched immunocompetent individuals (70 males and 31 females) randomly selected from patients in the dermatology department and hospital personnel served as controls. The mean age of the controls was 32.5 ⫾ 11.2 (range, 18 to 64 years). The RTR and control groups were also matched for skin type according to the phototype classification system proposed by Fitzpatrick:12 (1) always burns, never tans; (2) usually burns, tans with difficulty; (3) rarely burns, tans easily; (4) never burns, tans easily. The same dermatologist investigated each patient according to a set protocol. Interviews were conducted with a standardized questionnaire that surveyed other well-known risk factors for melanoma, namely, outdoor activities for leisure and vacation, a history of severe sunburn with blistering, family history of melanoma, and use of tanning salons. Dates of first and subsequent transplantation and the type and duration of immunosuppression were also noted in the RTRs. Acquired nevi of all sizes were counted on all parts of 0041-1345/02/$–see front matter PII S0041-1345(02)02881-6 2136
the body except the scalp and genitals. A lesion was regarded as a benign melanocytic nevus if it was a focal, brown, pigmented lesion with a well-defined edge that was not obviously a freckle, seborrheic keratosis, a solar lentigo, a pigmented basal cell carcinoma, or pigmented actinic keratosis. Because there are no specific criteria to distinguish lentigo simplex from junctional nevus, the former could not be excluded from the nevus count. All lesions that were clinically suspicious for melanoma were evaluated using epiluminescence microscopy (dermatoscopy) and the ABCD rule.13,14 Regional nevus counts were performed as follows: face/neck, arms/forearms/dorsum of the hands, chest/abdomen, back/buttocks, thighs/lower legs/dorsum of the feet, and palms/soles. The ratio of the mean number of melanocytic nevi in RTRs/mean number of nevi in controls was calculated for each area. For statistical analysis, the Student’s t test was used to compare mean nevi counts, and P values ⬍0.05 were considered significant. Pearson correlation analysis was used to assess the effects of the following variables on mean total nevi counts in all groups of RTRs: age, sex, skin type, donor type (cadaver or living-related), history of a severe sunburn with blistering, duration of immunosuppression, and use of CyA and/or Aza for immunosuppression in the past or present. Because mycophenolate mofetil and tacrolimus have only been included in our center’s treatment protocol for the last 2 years, we decided that it would not be appropriate to evaluate the effects of these drugs on nevi counts.
RESULTS
Table 1 lists the clinical details for the RTRs. None of the patients had any personal or family history of melanoma. None of the patients’ melanocytic nevi were suspicious for melanoma, so no excisional biopsies were needed. The questionnaire revealed that 7.8% of the RTR group and 35% of the control group had had episodes of sunburn with blistering and that none of the RTRs had been treated with ultraviolet (UV) light therapy for uremic pruritus. Due to the small number of subjects with skin types 1 and 4, the RTRs and controls were divided into 2 groups, as skin types 1 and 2 and skin types 3 and 4. Although we collected data on outdoor activities for leisure and vacation, we decided not to use these. During the course of the study, we realized From the Dermatology Department, Faculty of Medicine, Baskent University, Ankara, Turkey. Address reprint requests to Dr A.T. Gu¨lec¸, Dermatalogy Department, Faculty of Medicine, Baskent University, 06490 Bahcelievler, Ankara, Turkey. E-mail: [email protected] © 2002 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010 Transplantation Proceedings, 34, 2136 –2138 (2002)
ACQUIRED MELANOCYTIC NEVI
2137
Table 1. Clinical Information on the 115 Renal Transplant Recipients Studied Age (y, mean ⫾ SD) Sex Skin type History of melanoma History of severe sunburn Number of transplants Donor type Duration of immunosuppression (years, mean ⫾ SD)
32.8 ⫾ 10.8 (range, 18 – 61) 78 M, 37 F 29 (skin types 1 and 2), 86 (skin types 3 and 4) 0 9 positive, 106 negative 111 (1), 4 (2) 24 (cadaver), 91 (living-related) 4.6 ⫾ 4.5 (range, 2 mo-24 y)
that the relevance of self-assessment of lifetime exposure to UV radiation was debatable. We viewed this as a subjective assessment that provided no information about actual doses of UV received; thus, the data for lifetime sun exposure are not shown. There was no significant difference in the mean total acquired nevi counts for the RTRs and immunocompetent controls (25.2 ⫾ 28.8 and 22.7 ⫾ 18.9, respectively; P ⫽ 0.445). Most of the mean regional nevi counts were also similar in the 2 groups; however, the chest/abdomen results were significantly different. Interestingly, the control group had a significantly higher number of melanocytic nevi in this area than RTRs (5.5 ⫾ 3.3 and 3.9 ⫾ 5.9, respectively; P ⫽ 0.026) (Table 2). Correlation analysis showed no significant effect of age, skin type, donor type, duration of immunosuppression, treatment with CyA, or treatment with Aza on nevi counts in the RTRs. The male recipients had significantly higher total nevi counts than their female counterparts (29.6 ⫾ 32.5 and 16.1 ⫾ 15.2, respectively; P ⫽ .003). RTRs with history of a severe sunburn with blistering (7.9%) tended to have more nevi than those without this history (92.1%) (56 ⫾ 49.9 and 22.6 ⫾ 24.9, respectively; P ⫽ .081), but the difference was not statistically significant. DISCUSSION
Immunosuppression is a well-demonstrated pathogenetic mechanism for skin cancer, including melanoma.15,16 Immunodeficiency due to various causes (drug-induced or cancer-induced, eg) is associated with increased incidence
of melanoma.16 Clinically atypical nevi and large numbers of acquired melanocytic nevi are the most important risk factors for melanoma. Young age, male gender, and fair skin with light-colored hair and eyes are the major host factors, while solar UV radiation is considered the most significant environmental risk factor in the etiopathogenesis of large numbers of nevi.17 In recent years, it has been proposed that immunosuppression may constitute an additional risk factor for increased number of acquired benign melanocytic nevi.10,18 In 1988, Barker and Macdonald noted eruptive dysplastic nevi in a 12-year-old boy after renal transplantation.18 Similarly, 2 years later, a case was reported in which an identical twin developed excess numbers of melanocytic nevi after renal transplantation, while no such increase was observed in his sibling.4 These observations inspired the investigators to conduct case-controlled studies to determine whether these were isolated chance findings or a true increased incidence due to immunosuppression.3,10,11 However, only a few such investigations have been done, and the results are controversial. Some research has shown that adult RTRs have higher than normal numbers of benign melanocytic nevi.3,11 In pediatric kidney recipients, 1 study found no significant difference in numbers,19 whereas another showed a marked increase in total melanocytic nevi count.10 Our study confirmed the former finding in children: our adult RTRs did not have increased numbers of benign melanocytic nevi. The data showed that male kidney recipients were more likely to have increased nevi, as has been observed in the immunocompetent population.17 Two previous reports have indicated that the number of nevi increases in parallel with duration of immunosuppression.10,11 In contrast, work by Bouwes Bavinck et al, which focused on RTRs who had had their grafts for at least 8 years, revealed no associations between the total number of nevi and duration or cumulative dose of immunosuppression.20 The results of another study confirmed this finding.3 Some immunosuppressive agents are thought to have specific effects on nevi counts. Azathioprine may cause an increase in nevi,11 whereas CyA is suggested to have a protective effect.10 Our results are in line with previous findings3,20 that indicate that duration of immunosuppression and type of immunosuppressive drugs have no significant effect on nevi count.
Table 2. Total and Regional Numbers of Benign Melanocytic Nevi in the Renal Transplant Recipients (RTRs) and Controls Mean value (mean ⫾ SD) Skin area
Face/neck Arms/dorsum of the hands Chest/abdomen Back/buttocks Legs/dorsum of the feet Palms/soles Total
RTRs
4.79 ⫾ 5.54 7.74 ⫾ 11.19 3.97 ⫾ 5.92 4.25 ⫾ 6.33 4.14 ⫾ 5.22 0.40 ⫾ 0.75 25.23 ⫾ 28.78
RTR: renal transplant recipients; NS: not significant.
Controls
3.87 ⫾ 4.28 7.66 ⫾ 6.93 5.52 ⫾ 3.31 4.04 ⫾ 4.41 4.75 ⫾ 6.70 0.62 ⫾ 4.77 22.65 ⫾ 18.93
Significance
RTR/Controls
NS NS P ⫽ .026 NS NS NS NS
1.23 1.01 0.71 1.05 0.87 0.64 1.11
2138
Although there is a correlation between large numbers of benign melanocytic nevi and higher risk of melanoma, the pathogenetic mechanisms that underlie this relationship remain unclear. It is well known that there is a weak correlation between site of highest nevi count and melanoma. For instance, although several studies have found that the largest numbers of nevi in women occur on the arms,21,22 the most common site for melanoma is the lower legs.21 Also, despite the fact that a large proportion of melanoma patients report a preexisting nevus at the site of their melanoma, histologic examinations have confirmed this in less than 10% of cases.23 Considering these findings, it would be more appropriate to view large numbers of nevi as an indicator of high risk for melanoma rather than a direct cause. Genetic tendency and environmental factors such as sun exposure might independently cause both large numbers of nevi and melanoma. In conclusion, our results do not support the hypothesis that the total number of benign melanocytic nevi is increased in RTRs. We believe that immunosuppression may enhance the risk of melanoma by mechanisms other than increasing the nevi count. Nevertheless, in order to clarify whether these counts are a meaningful predictor of melanoma risk in these patients, a nevi count should be done at the time of renal transplantation. It would be most appropriate to follow these patients yearly to determine the actual increase in their nevi counts.
REFERENCES 1. Greene MH, Young TI, Clark WH: Lancet 1:1196, 1981
GU¨ LEC¸ , SEC¸ KIN, SARAY ET AL 2. Liddington M, Richardson AJ, Higgins RM, et al: Br J Surg 76:1002, 1989 3. Grob JJ, Bastuji-Garin S, Vaillant Loic, et al: J Invest Dermatol 107:694, 1996 4. McGregor JM, Barker JNWN, Macdonald DM: Clin Exp Dermatol 16:131, 1991 5. Sec¸kin D, Gu ¨lec¸ TO, Demirag A, et al: Transplant Proc 30:802, 1998 6. Penn I: Surg Clin North Am 74:1247, 1994 7. Holly EA, Kelly JW, Shpall SN, et al: J Am Acad Dermatol 17:459, 1987 8. Swerdlow AJ, English J, Mackie RM, et al: Br Med J 292:1555, 1989 9. Grob JJ, Gouvernet J, Aymar D, et al: Cancer 66:387, 1990 10. Smith CH, McGregor JM, Barker JNWN, et al: J Am Acad Dermatol 28:51, 1993 11. Szepietowski J, Wasik F, Szepietowski T, et al: Dermatology 194:17, 1997 12. Fitzpatrick TB: Arch Dermatol 124:869, 1988 13. Cohen D, Sangueza O, Fass E, et al: Int J Dermatol 32:257, 1993 14. Stolz W, Riemann A, Cognetta AB, et al: Eur J Dermatol 4:521, 1994 15. Fisher MS, Kripke ML: Science 216:1133, 1982 16. Ross PM: J Am Acad Dermatol 21:529, 1989 17. Green A, Swedlow AJ: Epidemiol Rev 11:204, 1989 18. Barker JNWN, Macdonald DM: Clin Exp Dermatol 13:123, 1988 19. Abdel-Hamid IA, Sobh M, Wafa E, et al: J Eur Acad Dermatol Venereol 5(suppl 1):S128, 1995 20. Bouwes Bavinck JN, Crijns M, Vermeer BJ, et al: J Invest Dermatol 106:1036, 1996 21. Mackie RM, English J, Aitchison TC, et al: Br J Dermatol 113:167, 1985 22. Pack GT, Lenson N, Gerber M: Arch Surg 65:862, 1952 23. Elder DE, Greene MH, Clark WH: In Ackerman AB (ed): Pathology of Malignant Melanoma. New York: Masson; 1981, p 185
R
ENAL transplant recipients (RTRs) are at increased risk for malignant tumors due to long-term immunosuppression.1–5 Skin cancers are the most frequent malignancies in these patients, accounting for 37% of all de novo neoplasms.6 The cutaneous malignant rate is high, with a relative risk ranging from 3 to 9 times that in the general population.1 The presence of large numbers of melanocytic nevi is the best known risk factor for melanoma.7–9 A few investigations have documented higher than normal numbers of melanocytic nevi in RTRs.3,10,11 This case-controlled study was undertaken to investigate the numbers of acquired benign melanocytic nevi in adult RTRs. PATIENTS AND METHODS The study included 115 consecutive renal allograft recipients (78 males and 37 females) who attended the Renal Transplantation Unit at Baskent University for routine check-up examinations between March and October 2001. The mean patient age was 32.8 ⫾ 10.8 years (range, 18 to 61 years), and the mean time since transplantation was 55.4 ⫾ 54.6 months (range, 2 months to 24 years). Because the number of melanocytic nevi can be influenced by duration of immunosuppression, we divided the patients into 3 groups: group A (n ⫽ 30) had undergone transplantation within the year; group B (n ⫽ 47), 1–5 years survival; and group C (n ⫽ 38), more than 5 years survival. Thirty-six (31.3%) patients were taking prednisolone (P), cyclosporine (CyA), and mycophenolate mofetil; 33 (28.7%) were taking P, CyA, and azathioprine (Aza); 21 (18.3%) were taking P and CyA; 15 (13%) were taking P, mycophenolate mofetil, and tacrolimus; and 10 (8.7%) were taking other combinations of these 4 drugs. One hundred and one age- and sex-matched immunocompetent individuals (70 males and 31 females) randomly selected from patients in the dermatology department and hospital personnel served as controls. The mean age of the controls was 32.5 ⫾ 11.2 (range, 18 to 64 years). The RTR and control groups were also matched for skin type according to the phototype classification system proposed by Fitzpatrick:12 (1) always burns, never tans; (2) usually burns, tans with difficulty; (3) rarely burns, tans easily; (4) never burns, tans easily. The same dermatologist investigated each patient according to a set protocol. Interviews were conducted with a standardized questionnaire that surveyed other well-known risk factors for melanoma, namely, outdoor activities for leisure and vacation, a history of severe sunburn with blistering, family history of melanoma, and use of tanning salons. Dates of first and subsequent transplantation and the type and duration of immunosuppression were also noted in the RTRs. Acquired nevi of all sizes were counted on all parts of 0041-1345/02/$–see front matter PII S0041-1345(02)02881-6 2136
the body except the scalp and genitals. A lesion was regarded as a benign melanocytic nevus if it was a focal, brown, pigmented lesion with a well-defined edge that was not obviously a freckle, seborrheic keratosis, a solar lentigo, a pigmented basal cell carcinoma, or pigmented actinic keratosis. Because there are no specific criteria to distinguish lentigo simplex from junctional nevus, the former could not be excluded from the nevus count. All lesions that were clinically suspicious for melanoma were evaluated using epiluminescence microscopy (dermatoscopy) and the ABCD rule.13,14 Regional nevus counts were performed as follows: face/neck, arms/forearms/dorsum of the hands, chest/abdomen, back/buttocks, thighs/lower legs/dorsum of the feet, and palms/soles. The ratio of the mean number of melanocytic nevi in RTRs/mean number of nevi in controls was calculated for each area. For statistical analysis, the Student’s t test was used to compare mean nevi counts, and P values ⬍0.05 were considered significant. Pearson correlation analysis was used to assess the effects of the following variables on mean total nevi counts in all groups of RTRs: age, sex, skin type, donor type (cadaver or living-related), history of a severe sunburn with blistering, duration of immunosuppression, and use of CyA and/or Aza for immunosuppression in the past or present. Because mycophenolate mofetil and tacrolimus have only been included in our center’s treatment protocol for the last 2 years, we decided that it would not be appropriate to evaluate the effects of these drugs on nevi counts.
RESULTS
Table 1 lists the clinical details for the RTRs. None of the patients had any personal or family history of melanoma. None of the patients’ melanocytic nevi were suspicious for melanoma, so no excisional biopsies were needed. The questionnaire revealed that 7.8% of the RTR group and 35% of the control group had had episodes of sunburn with blistering and that none of the RTRs had been treated with ultraviolet (UV) light therapy for uremic pruritus. Due to the small number of subjects with skin types 1 and 4, the RTRs and controls were divided into 2 groups, as skin types 1 and 2 and skin types 3 and 4. Although we collected data on outdoor activities for leisure and vacation, we decided not to use these. During the course of the study, we realized From the Dermatology Department, Faculty of Medicine, Baskent University, Ankara, Turkey. Address reprint requests to Dr A.T. Gu¨lec¸, Dermatalogy Department, Faculty of Medicine, Baskent University, 06490 Bahcelievler, Ankara, Turkey. E-mail: [email protected] © 2002 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010 Transplantation Proceedings, 34, 2136 –2138 (2002)
ACQUIRED MELANOCYTIC NEVI
2137
Table 1. Clinical Information on the 115 Renal Transplant Recipients Studied Age (y, mean ⫾ SD) Sex Skin type History of melanoma History of severe sunburn Number of transplants Donor type Duration of immunosuppression (years, mean ⫾ SD)
32.8 ⫾ 10.8 (range, 18 – 61) 78 M, 37 F 29 (skin types 1 and 2), 86 (skin types 3 and 4) 0 9 positive, 106 negative 111 (1), 4 (2) 24 (cadaver), 91 (living-related) 4.6 ⫾ 4.5 (range, 2 mo-24 y)
that the relevance of self-assessment of lifetime exposure to UV radiation was debatable. We viewed this as a subjective assessment that provided no information about actual doses of UV received; thus, the data for lifetime sun exposure are not shown. There was no significant difference in the mean total acquired nevi counts for the RTRs and immunocompetent controls (25.2 ⫾ 28.8 and 22.7 ⫾ 18.9, respectively; P ⫽ 0.445). Most of the mean regional nevi counts were also similar in the 2 groups; however, the chest/abdomen results were significantly different. Interestingly, the control group had a significantly higher number of melanocytic nevi in this area than RTRs (5.5 ⫾ 3.3 and 3.9 ⫾ 5.9, respectively; P ⫽ 0.026) (Table 2). Correlation analysis showed no significant effect of age, skin type, donor type, duration of immunosuppression, treatment with CyA, or treatment with Aza on nevi counts in the RTRs. The male recipients had significantly higher total nevi counts than their female counterparts (29.6 ⫾ 32.5 and 16.1 ⫾ 15.2, respectively; P ⫽ .003). RTRs with history of a severe sunburn with blistering (7.9%) tended to have more nevi than those without this history (92.1%) (56 ⫾ 49.9 and 22.6 ⫾ 24.9, respectively; P ⫽ .081), but the difference was not statistically significant. DISCUSSION
Immunosuppression is a well-demonstrated pathogenetic mechanism for skin cancer, including melanoma.15,16 Immunodeficiency due to various causes (drug-induced or cancer-induced, eg) is associated with increased incidence
of melanoma.16 Clinically atypical nevi and large numbers of acquired melanocytic nevi are the most important risk factors for melanoma. Young age, male gender, and fair skin with light-colored hair and eyes are the major host factors, while solar UV radiation is considered the most significant environmental risk factor in the etiopathogenesis of large numbers of nevi.17 In recent years, it has been proposed that immunosuppression may constitute an additional risk factor for increased number of acquired benign melanocytic nevi.10,18 In 1988, Barker and Macdonald noted eruptive dysplastic nevi in a 12-year-old boy after renal transplantation.18 Similarly, 2 years later, a case was reported in which an identical twin developed excess numbers of melanocytic nevi after renal transplantation, while no such increase was observed in his sibling.4 These observations inspired the investigators to conduct case-controlled studies to determine whether these were isolated chance findings or a true increased incidence due to immunosuppression.3,10,11 However, only a few such investigations have been done, and the results are controversial. Some research has shown that adult RTRs have higher than normal numbers of benign melanocytic nevi.3,11 In pediatric kidney recipients, 1 study found no significant difference in numbers,19 whereas another showed a marked increase in total melanocytic nevi count.10 Our study confirmed the former finding in children: our adult RTRs did not have increased numbers of benign melanocytic nevi. The data showed that male kidney recipients were more likely to have increased nevi, as has been observed in the immunocompetent population.17 Two previous reports have indicated that the number of nevi increases in parallel with duration of immunosuppression.10,11 In contrast, work by Bouwes Bavinck et al, which focused on RTRs who had had their grafts for at least 8 years, revealed no associations between the total number of nevi and duration or cumulative dose of immunosuppression.20 The results of another study confirmed this finding.3 Some immunosuppressive agents are thought to have specific effects on nevi counts. Azathioprine may cause an increase in nevi,11 whereas CyA is suggested to have a protective effect.10 Our results are in line with previous findings3,20 that indicate that duration of immunosuppression and type of immunosuppressive drugs have no significant effect on nevi count.
Table 2. Total and Regional Numbers of Benign Melanocytic Nevi in the Renal Transplant Recipients (RTRs) and Controls Mean value (mean ⫾ SD) Skin area
Face/neck Arms/dorsum of the hands Chest/abdomen Back/buttocks Legs/dorsum of the feet Palms/soles Total
RTRs
4.79 ⫾ 5.54 7.74 ⫾ 11.19 3.97 ⫾ 5.92 4.25 ⫾ 6.33 4.14 ⫾ 5.22 0.40 ⫾ 0.75 25.23 ⫾ 28.78
RTR: renal transplant recipients; NS: not significant.
Controls
3.87 ⫾ 4.28 7.66 ⫾ 6.93 5.52 ⫾ 3.31 4.04 ⫾ 4.41 4.75 ⫾ 6.70 0.62 ⫾ 4.77 22.65 ⫾ 18.93
Significance
RTR/Controls
NS NS P ⫽ .026 NS NS NS NS
1.23 1.01 0.71 1.05 0.87 0.64 1.11
2138
Although there is a correlation between large numbers of benign melanocytic nevi and higher risk of melanoma, the pathogenetic mechanisms that underlie this relationship remain unclear. It is well known that there is a weak correlation between site of highest nevi count and melanoma. For instance, although several studies have found that the largest numbers of nevi in women occur on the arms,21,22 the most common site for melanoma is the lower legs.21 Also, despite the fact that a large proportion of melanoma patients report a preexisting nevus at the site of their melanoma, histologic examinations have confirmed this in less than 10% of cases.23 Considering these findings, it would be more appropriate to view large numbers of nevi as an indicator of high risk for melanoma rather than a direct cause. Genetic tendency and environmental factors such as sun exposure might independently cause both large numbers of nevi and melanoma. In conclusion, our results do not support the hypothesis that the total number of benign melanocytic nevi is increased in RTRs. We believe that immunosuppression may enhance the risk of melanoma by mechanisms other than increasing the nevi count. Nevertheless, in order to clarify whether these counts are a meaningful predictor of melanoma risk in these patients, a nevi count should be done at the time of renal transplantation. It would be most appropriate to follow these patients yearly to determine the actual increase in their nevi counts.
REFERENCES 1. Greene MH, Young TI, Clark WH: Lancet 1:1196, 1981
GU¨ LEC¸ , SEC¸ KIN, SARAY ET AL 2. Liddington M, Richardson AJ, Higgins RM, et al: Br J Surg 76:1002, 1989 3. Grob JJ, Bastuji-Garin S, Vaillant Loic, et al: J Invest Dermatol 107:694, 1996 4. McGregor JM, Barker JNWN, Macdonald DM: Clin Exp Dermatol 16:131, 1991 5. Sec¸kin D, Gu ¨lec¸ TO, Demirag A, et al: Transplant Proc 30:802, 1998 6. Penn I: Surg Clin North Am 74:1247, 1994 7. Holly EA, Kelly JW, Shpall SN, et al: J Am Acad Dermatol 17:459, 1987 8. Swerdlow AJ, English J, Mackie RM, et al: Br Med J 292:1555, 1989 9. Grob JJ, Gouvernet J, Aymar D, et al: Cancer 66:387, 1990 10. Smith CH, McGregor JM, Barker JNWN, et al: J Am Acad Dermatol 28:51, 1993 11. Szepietowski J, Wasik F, Szepietowski T, et al: Dermatology 194:17, 1997 12. Fitzpatrick TB: Arch Dermatol 124:869, 1988 13. Cohen D, Sangueza O, Fass E, et al: Int J Dermatol 32:257, 1993 14. Stolz W, Riemann A, Cognetta AB, et al: Eur J Dermatol 4:521, 1994 15. Fisher MS, Kripke ML: Science 216:1133, 1982 16. Ross PM: J Am Acad Dermatol 21:529, 1989 17. Green A, Swedlow AJ: Epidemiol Rev 11:204, 1989 18. Barker JNWN, Macdonald DM: Clin Exp Dermatol 13:123, 1988 19. Abdel-Hamid IA, Sobh M, Wafa E, et al: J Eur Acad Dermatol Venereol 5(suppl 1):S128, 1995 20. Bouwes Bavinck JN, Crijns M, Vermeer BJ, et al: J Invest Dermatol 106:1036, 1996 21. Mackie RM, English J, Aitchison TC, et al: Br J Dermatol 113:167, 1985 22. Pack GT, Lenson N, Gerber M: Arch Surg 65:862, 1952 23. Elder DE, Greene MH, Clark WH: In Ackerman AB (ed): Pathology of Malignant Melanoma. New York: Masson; 1981, p 185