Journal of Dermatology 2015; 42: 897–899
doi: 10.1111/1346-8138.12942
CONCISE COMMUNICATION
Xeroderma pigmentosum complementation group F: Report of a case and review of Japanese patients Yukari TOFUKU,1 Yoshimasa NOBEYAMA,1 Ryoichi KAMIDE,2 Shinichi MORIWAKI,3 Hidemi NAKAGAWA1 1
Department of Dermatology, The Jikei University School of Medicine, 2Hihuno Clinic Ningyocho, Tokyo,3Department of Dermatology, The Osaka Medical College, Osaka, Japan
ABSTRACT Xeroderma pigmentosum (XP) is an autosomal recessive genetic disorder characterized by extraordinary sensitivity to sunlight, resulting in cutaneous malignant tumors. Among XP, XP-F presents relatively uniquely in Japanese. To clarify the characteristics of this group, we describe a case of XP-F and review Japanese cases previously reported. A 50-year-old Japanese woman was referred to us with multiple, variously sized, light- or dark-brown macules on the face and sunlight-exposed extremities. She had experienced bulla formation with approximately 10 min of sunlight exposure during her elementary school years. Her parents had been first cousins, and her mother and sister had photosensitivity. She showed no neurological or developmental abnormalities. Ultraviolet (UV) irradiation testing revealed normal levels for minimal erythema dose with UV-A and UV-B. Sensitivity to UV-C and DNA repair ability in the patient’s fibroblasts were indicated between that in normal individuals and that in an XP-A patient. Complementation assay revealed that transfection of the XPF gene led most efficient DNA repair compared with the other XP genes. Therefore, the patient was diagnosed with XP-F. Twenty-three cases of Japanese patients (six males, 17 females) with XP-F have been reported, including the present case. Our review suggested a relatively high prevalence of 50% (11/22) for cutaneous malignant tumors. A significant difference was evident in the mean age at first medical consultation between patients with cutaneous malignant tumors (53.6 years) and patients without such tumors (30.8 years). This suggests that cutaneous malignant tumors could occur in the age range of 30–50 years in XP-F patients.
Key words: carcinogenesis, complementation group F, cutaneous malignant tumors, hypersensitivity to sunlight, xeroderma pigmentosum.
INTRODUCTION Xeroderma pigmentosum (XP) is an autosomal recessive genetic disorder characterized by extraordinary sensitivity to sunlight, resulting in cutaneous malignant tumors including squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and melanoma.1 XP is classified into seven genetic complementation groups, comprising groups A–G, and one variant form (XP-V).2 These genetic complementation groups are defined by impaired nucleotide excision repair (NER) due to mutations in the genes encoding the proteins associated with NER, including XPA, XPB, XPC, XPD, XPE, XPF and XPG,1 while XP-V is defined by normal NER and abnormal translesion synthesis due to mutations in the gene encoding the damagespecific polymerase hRAD30.3 The prevalence rate for all groups of XP is estimated as 1/ 1 million persons in the USA and 1/22 000 persons in Japan.4 In Japanese XP patients, approximately 50%, 25% and 7% belong to XP-A, XP-V and XP-F, respectively.5 In particular,
XP-F presents relatively uniquely in Japanese; relatively few non-Japanese patients have been reported to date.6,7 To clarify the characteristics of this group, including the involvement of cutaneous malignant tumors in XP-F, we describe a case of XP-F and review Japanese cases previously reported, because the Japanese are regarded as a population with a relatively homogeneous background in innate and acquired factors.
CASE REPORT A 50-year-old Japanese woman was referred to us with pigmentation on her face. Her parents had been first cousins. She had experienced bulla formation with approximately 10 min of sunlight exposure during outdoor swimming during her elementary school years. She had not belonged to an outdoor activity club during her junior high school and high school years because she had suffered from extraordinary sunburn on exposure to sunlight. During an approximate 10-year period, she had sometimes played tennis outside while protecting herself
Correspondence: Yoshimasa Nobeyama, M.D., Ph.D, Department of Dermatology, The Jikei University School of Medicine, 25-8 Nishi-shimbashi 3-chome, Minato-ku, Tokyo 105-8461, Japan. Email: [email protected] Received 31 January 2015; accepted 23 March 2015.
© 2015 Japanese Dermatological Association
897
Y. Tofuku et al.
from sunlight using sunscreen, long sleeves and long pants; however, she had still experienced erythema on the face and dorsal surfaces of the hands. She had suffered from pigmented macules on sunlight-exposed regions, including the face and extremities, from 10 years old, and symptoms began to increase from 15 years old. Her father, son and daughter had no photosensitivity, but her mother and sister had photosensitivity and developed multiple, small, red papules on the dorsal surfaces of the hands and on the face, especially in spring.
(a)
(b) 102 101 100 10–1 10–2 10–3
(c) 102
N25 N69 N33 N47 Pt2 Pt1 XPA
101 100 10–1 10–2
0
500 1000 1500
0
3
6
9
12 15
(d) 102
XPF XPG XPD XPC Mock XPB XPA
101 100 10–1 10–2
N47 N7 N1 N3 N24 Pt XPA
0
1500
Figure 1. (a) Clinical findings. The patient suffered from multiple, variously sized, light- and dark-brown macules on the face, but few pigmented macules in the submental region. (b) Ultraviolet (UV) sensitivity test to determine DNA repair ability. Survival rate is defined as the number of colonies of fibroblasts treated with UV-C divided by the number of colonies of untreated fibroblasts. N1, 3, 7, 24 and 47 indicate fibroblasts derived from normal individuals. Pt and XPA indicate fibroblasts derived from the patient and a patient with xeroderma pigmentosum (XP)-A, respectively. Vertical and horizontal axes indicate the survival rate (%) and level of UV-C irradiation (J/ m2). (c) Luciferase assay to determine DNA repair ability. Expression vectors developed with luciferase gene damaged by UV-C irradiation to 500, 1000 or 1500 J/m2 as a reporter gene were introduced into fibroblasts derived from the patient, normal individuals and a patient with XP-A. Vertical and horizontal axes indicate luciferase activity (%) and the level of UVC irradiation (J/m2), respectively. Pt1 and Pt2 indicate patient fibroblasts examined independently on two occasions. N25, N33, N47 and N69 indicate fibroblasts derived from normal individuals. XPA indicates fibroblasts derived from the XP-A patient. (d) Genetic complementation test. The expression vector developed with luciferase gene damaged by UV-C irradiation as a reporter gene was introduced into fibroblasts from the patient. Each XPA, XPB, XPC, XPD, XPF and XPG gene was transfected into fibroblasts with the damaged luciferase gene by plasmid vector of pcDNATM3.1(+) (Invitrogen, Carlsbad, CA, USA). Vertical and horizontal axes indicate the rate of luciferase activity (%) and the amount of UV-C irradiation (J/m2), respectively.
898
Table 1. Japanese XP-F patients No.
Age at first visit*
Sex
Malignancy†
Age at first tumor‡
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
49 42 73 42 40 18 73 65 62 62 64 45 29 8 11 8 5 44 61 54 50
F F F M F F F F F F M F M F F F M F F F F
BCC BCC BCC BCC BCC BCC BCC SCC SCC BCC, SCC BCC, SCC No No No No No No No No No No
49 40 70 42 41 18 72 64 62 53 71 NA NA NA NA NA NA NA NA NA NA
22 23
48 7
M M
No Unknown
NA NA
Reference #9 #9 #9 #9 #9 #10 #15 #9 #11 #12 #14 #9 #9 #9 #9 #9 #9 #9 #9 #13 Present case #15 #9
*Age at first medical consultation (years). †Type of malignant cutaneous tumor(s). ‡Age at first onset of malignant cutaneous tumor(s). BCC, basal cell carcinoma; SCC, squamous cell carcinoma; NA, not applicable; XP, xeroderma pigmentosum.
80
P = 0.016
60 40 20 0
–
+
Figure 2. Mean age at first medical consultation of the patients with cutaneous malignant tumors and without such tumors. Statistical analysis using Student’s t-test revealed a significant difference between these patients. Vertical and horizontal axes indicate the mean age (years), and patients with cutaneous malignant tumors (+) and patients without such tumor(s) ( ), respectively. Physical examination revealed multiple, variously sized, light- or dark-brown macules on the face and sunlight-exposed extremities, but few pigmented macules in the submental region (Fig. 1a). She showed no neurological or developmental abnormalities. Free erythrocyte-protoporphyrin, urinary coproporphyrin and urinary uroporphyrin levels were all within normal ranges. Ultraviolet (UV) irradiation testing revealed normal
© 2015 Japanese Dermatological Association
Xeroderma pigmentosum complementation group F
levels for minimal erythema dose with UV-A (≥6.93 J/cm2) and UV-B (≥66 mJ/cm2). UV sensitivity testing using fibroblasts derived from the patient, normal individuals and a patient with XP-A revealed that sensitivity to UV-C in the patient’s fibroblasts was significantly higher than that in fibroblasts from normal individuals, but not as high as that in a patient with XP-A (Fig. 1b). Luciferase assay using fibroblasts with luciferase gene damaged by UV-C irradiation revealed that DNA repair ability in fibroblasts from the patient was significantly lower than that in fibroblasts from normal individuals, but not as low as that in fibroblasts from the patient with XP-A (Fig. 1c). Complementation assay revealed that transfection of the XPF gene led most efficiently to recovery of luciferase activity compared with the other XP genes (Fig. 1d). These examinations using fibroblasts from patients and normal individuals were performed under the permission of the ethics committee at The Osaka Medical College. Based on the results, the patient was diagnosed with XP-F and provided with instruction in suitable protection from sunlight, including the use of sunscreen.
DISCUSSION Xeroderma pigmentosum-F has been clinically characterized by late onset, ease of sunburn from sunlight exposure, pigmentation on sunlight-exposed regions, low incidence of cutaneous malignant tumors and very low incidence of neurological involvement.8 Our patient was thus considered to have typical symptoms of XP-F, given the pigmentation on sunlightexposed regions, and absence of both cutaneous malignant tumors and neurological involvement. To the best of our knowledge, 23 cases of Japanese patients (six males, 17 females) with XP-F have been reported, including the present case (Table 1).9–15 The mean age at first medical consultation is 41.7 years (range, 5–73). Among the 22 patients for whom the involvement of cutaneous malignant tumors was previously described, 11 had cutaneous malignant tumors including BCC in nine of 11 patients and SCC in four of 11 patients. In contrast to previous descriptions of a low incidence of cutaneous malignancy,8 our review suggested a relatively high prevalence of 50% (11/22) for cutaneous malignant tumors; these may be novel findings regarding XP-F. A significant difference was evident in the mean age at first medical consultation between patients with cutaneous malignant tumors (53.6 years) and patients without such tumors (30.8 years) (Fig. 2). This fact suggests that early diagnosis is important to prevent onset of the tumor. In the present case, the patient was 50 years old, which was close to the mean age in the patient group with cutaneous malignant tumors. Nevertheless, this patient showed no cutaneous malignancy. This fact may be attributable to the
© 2015 Japanese Dermatological Association
relatively low level of exposure to sunlight; the patient had avoided sunlight exposure by not participating in outdoor activities during her student days and by protecting herself against sunlight, even when playing outdoor tennis through the years of her adult life. This suggests the possibility that an educational campaign to limit lifetime sunlight exposure may contribute to reducing the risk of developing cutaneous malignant tumors in individuals with XP-F who have not yet been diagnosed, as well as those patients who have been diagnosed.
CONFLICT OF INTEREST:
The authors have no conflicts
of interest.
REFERENCES 1 Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ. Fitzpatricks dermatology in general medicine, 7th edn. Mcgraw-hill, New York 2007; 1311–1320. 2 Yagi T, Katsuya A, Koyano A, Takabe H. Sensitivity of group F xeroderma pigmentosum cells to UV and mitomycin C relative to levels of XPF and ERCC1 overexpression. Mutagenesis 1998; 13: 595–599. 3 Johnson RE, Kondratick CM, Prakash S, Prakash L. hRAD30 mutations in the variant form of xeroderma pigmentosum. Science 1999; 285: 263–265. 4 Tamura D, DiGiovanna JJ, Kraemer KH. Founder mutations in xeroderma pigmentosum. J Invest Detmatol 2010; 130: 1491–1493. 5 Kraemer KH, DiGiovanna JJ. Xeroderma pigmentosum. Genereviews [internet]. University of Washington, Seattle 2014. 6 Moriwaki S, Nisigori C. Recent progress in the diagnosis of xeroderma pigmentosum (in Japanese). Clin Dermatol 1999; 53: 79–83. 7 Sethi M, Lehmann AR, Fawcett H et al. Patients with xeroderma pigmentosum complementation group C, E and V do not have abnormal sunburn reactions. Br J Dermatol 2013; 169: 1279–1287. 8 Moriwaki S, Nishigori C, Imamura S et al. A case of xeroderma pigmentosum complementation group F with neurological abnormalities. Br J Dermatol 1993; 128: 91–94. 9 Kondo S, Miyamoto C, Keong CH et al. Sib patients bearing basaliomas in xeroderma pigmentosum complementation group F (in Japanese). Nishinihon J Dermatol 1990; 52: 279–284. 10 Ito T, Watanabe H, Yamaizumi M, Ono T. A case of young XPF with basal cell carcinoma (in Japanese). Jpn J Dermatol 1995; 105: 424. 11 Yasue T, Hiraiwa A, Matsumoto Y et al. A case of xeroderma pigmentosum group F (in Japanese). Jpn J Dermatol 1998; 108: 883. 12 Kato Y, Muro Y, Yasue T, Matsumoto Y, Ohashi M, Yagi T. AntiCENP-F antibody in a patient with xeroderma pigmentosum (in Japanese). Jpn J Dermatol 2000; 110: 301–306. 13 Minamino Y, Fujisawa H, Imakado S, Otsuka F, Yamaizumi M. A case of xeroderma pigmentosum group F (in Japanese). Jpn J Dermatol 2002; 112: 866. 14 Asai M, Koike Y, Tomimura S, Takenaka M, Utani A. Long-term follow up of a case of xeroderma pigmentosum complementation group F (in Japanese). Nishinihon J Dermatol 2013; 75: 508–510. 15 Matsumura Y, Nishigori C, Yagi T, Imamura S, Takabe H. Characterization of molecular defects in xeroderma pigmentosum group F in relation to its clinically mild symptoms. Hum Mol Genet 1998; 7: 969–974.
899
doi: 10.1111/1346-8138.12942
CONCISE COMMUNICATION
Xeroderma pigmentosum complementation group F: Report of a case and review of Japanese patients Yukari TOFUKU,1 Yoshimasa NOBEYAMA,1 Ryoichi KAMIDE,2 Shinichi MORIWAKI,3 Hidemi NAKAGAWA1 1
Department of Dermatology, The Jikei University School of Medicine, 2Hihuno Clinic Ningyocho, Tokyo,3Department of Dermatology, The Osaka Medical College, Osaka, Japan
ABSTRACT Xeroderma pigmentosum (XP) is an autosomal recessive genetic disorder characterized by extraordinary sensitivity to sunlight, resulting in cutaneous malignant tumors. Among XP, XP-F presents relatively uniquely in Japanese. To clarify the characteristics of this group, we describe a case of XP-F and review Japanese cases previously reported. A 50-year-old Japanese woman was referred to us with multiple, variously sized, light- or dark-brown macules on the face and sunlight-exposed extremities. She had experienced bulla formation with approximately 10 min of sunlight exposure during her elementary school years. Her parents had been first cousins, and her mother and sister had photosensitivity. She showed no neurological or developmental abnormalities. Ultraviolet (UV) irradiation testing revealed normal levels for minimal erythema dose with UV-A and UV-B. Sensitivity to UV-C and DNA repair ability in the patient’s fibroblasts were indicated between that in normal individuals and that in an XP-A patient. Complementation assay revealed that transfection of the XPF gene led most efficient DNA repair compared with the other XP genes. Therefore, the patient was diagnosed with XP-F. Twenty-three cases of Japanese patients (six males, 17 females) with XP-F have been reported, including the present case. Our review suggested a relatively high prevalence of 50% (11/22) for cutaneous malignant tumors. A significant difference was evident in the mean age at first medical consultation between patients with cutaneous malignant tumors (53.6 years) and patients without such tumors (30.8 years). This suggests that cutaneous malignant tumors could occur in the age range of 30–50 years in XP-F patients.
Key words: carcinogenesis, complementation group F, cutaneous malignant tumors, hypersensitivity to sunlight, xeroderma pigmentosum.
INTRODUCTION Xeroderma pigmentosum (XP) is an autosomal recessive genetic disorder characterized by extraordinary sensitivity to sunlight, resulting in cutaneous malignant tumors including squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and melanoma.1 XP is classified into seven genetic complementation groups, comprising groups A–G, and one variant form (XP-V).2 These genetic complementation groups are defined by impaired nucleotide excision repair (NER) due to mutations in the genes encoding the proteins associated with NER, including XPA, XPB, XPC, XPD, XPE, XPF and XPG,1 while XP-V is defined by normal NER and abnormal translesion synthesis due to mutations in the gene encoding the damagespecific polymerase hRAD30.3 The prevalence rate for all groups of XP is estimated as 1/ 1 million persons in the USA and 1/22 000 persons in Japan.4 In Japanese XP patients, approximately 50%, 25% and 7% belong to XP-A, XP-V and XP-F, respectively.5 In particular,
XP-F presents relatively uniquely in Japanese; relatively few non-Japanese patients have been reported to date.6,7 To clarify the characteristics of this group, including the involvement of cutaneous malignant tumors in XP-F, we describe a case of XP-F and review Japanese cases previously reported, because the Japanese are regarded as a population with a relatively homogeneous background in innate and acquired factors.
CASE REPORT A 50-year-old Japanese woman was referred to us with pigmentation on her face. Her parents had been first cousins. She had experienced bulla formation with approximately 10 min of sunlight exposure during outdoor swimming during her elementary school years. She had not belonged to an outdoor activity club during her junior high school and high school years because she had suffered from extraordinary sunburn on exposure to sunlight. During an approximate 10-year period, she had sometimes played tennis outside while protecting herself
Correspondence: Yoshimasa Nobeyama, M.D., Ph.D, Department of Dermatology, The Jikei University School of Medicine, 25-8 Nishi-shimbashi 3-chome, Minato-ku, Tokyo 105-8461, Japan. Email: [email protected] Received 31 January 2015; accepted 23 March 2015.
© 2015 Japanese Dermatological Association
897
Y. Tofuku et al.
from sunlight using sunscreen, long sleeves and long pants; however, she had still experienced erythema on the face and dorsal surfaces of the hands. She had suffered from pigmented macules on sunlight-exposed regions, including the face and extremities, from 10 years old, and symptoms began to increase from 15 years old. Her father, son and daughter had no photosensitivity, but her mother and sister had photosensitivity and developed multiple, small, red papules on the dorsal surfaces of the hands and on the face, especially in spring.
(a)
(b) 102 101 100 10–1 10–2 10–3
(c) 102
N25 N69 N33 N47 Pt2 Pt1 XPA
101 100 10–1 10–2
0
500 1000 1500
0
3
6
9
12 15
(d) 102
XPF XPG XPD XPC Mock XPB XPA
101 100 10–1 10–2
N47 N7 N1 N3 N24 Pt XPA
0
1500
Figure 1. (a) Clinical findings. The patient suffered from multiple, variously sized, light- and dark-brown macules on the face, but few pigmented macules in the submental region. (b) Ultraviolet (UV) sensitivity test to determine DNA repair ability. Survival rate is defined as the number of colonies of fibroblasts treated with UV-C divided by the number of colonies of untreated fibroblasts. N1, 3, 7, 24 and 47 indicate fibroblasts derived from normal individuals. Pt and XPA indicate fibroblasts derived from the patient and a patient with xeroderma pigmentosum (XP)-A, respectively. Vertical and horizontal axes indicate the survival rate (%) and level of UV-C irradiation (J/ m2). (c) Luciferase assay to determine DNA repair ability. Expression vectors developed with luciferase gene damaged by UV-C irradiation to 500, 1000 or 1500 J/m2 as a reporter gene were introduced into fibroblasts derived from the patient, normal individuals and a patient with XP-A. Vertical and horizontal axes indicate luciferase activity (%) and the level of UVC irradiation (J/m2), respectively. Pt1 and Pt2 indicate patient fibroblasts examined independently on two occasions. N25, N33, N47 and N69 indicate fibroblasts derived from normal individuals. XPA indicates fibroblasts derived from the XP-A patient. (d) Genetic complementation test. The expression vector developed with luciferase gene damaged by UV-C irradiation as a reporter gene was introduced into fibroblasts from the patient. Each XPA, XPB, XPC, XPD, XPF and XPG gene was transfected into fibroblasts with the damaged luciferase gene by plasmid vector of pcDNATM3.1(+) (Invitrogen, Carlsbad, CA, USA). Vertical and horizontal axes indicate the rate of luciferase activity (%) and the amount of UV-C irradiation (J/m2), respectively.
898
Table 1. Japanese XP-F patients No.
Age at first visit*
Sex
Malignancy†
Age at first tumor‡
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
49 42 73 42 40 18 73 65 62 62 64 45 29 8 11 8 5 44 61 54 50
F F F M F F F F F F M F M F F F M F F F F
BCC BCC BCC BCC BCC BCC BCC SCC SCC BCC, SCC BCC, SCC No No No No No No No No No No
49 40 70 42 41 18 72 64 62 53 71 NA NA NA NA NA NA NA NA NA NA
22 23
48 7
M M
No Unknown
NA NA
Reference #9 #9 #9 #9 #9 #10 #15 #9 #11 #12 #14 #9 #9 #9 #9 #9 #9 #9 #9 #13 Present case #15 #9
*Age at first medical consultation (years). †Type of malignant cutaneous tumor(s). ‡Age at first onset of malignant cutaneous tumor(s). BCC, basal cell carcinoma; SCC, squamous cell carcinoma; NA, not applicable; XP, xeroderma pigmentosum.
80
P = 0.016
60 40 20 0
–
+
Figure 2. Mean age at first medical consultation of the patients with cutaneous malignant tumors and without such tumors. Statistical analysis using Student’s t-test revealed a significant difference between these patients. Vertical and horizontal axes indicate the mean age (years), and patients with cutaneous malignant tumors (+) and patients without such tumor(s) ( ), respectively. Physical examination revealed multiple, variously sized, light- or dark-brown macules on the face and sunlight-exposed extremities, but few pigmented macules in the submental region (Fig. 1a). She showed no neurological or developmental abnormalities. Free erythrocyte-protoporphyrin, urinary coproporphyrin and urinary uroporphyrin levels were all within normal ranges. Ultraviolet (UV) irradiation testing revealed normal
© 2015 Japanese Dermatological Association
Xeroderma pigmentosum complementation group F
levels for minimal erythema dose with UV-A (≥6.93 J/cm2) and UV-B (≥66 mJ/cm2). UV sensitivity testing using fibroblasts derived from the patient, normal individuals and a patient with XP-A revealed that sensitivity to UV-C in the patient’s fibroblasts was significantly higher than that in fibroblasts from normal individuals, but not as high as that in a patient with XP-A (Fig. 1b). Luciferase assay using fibroblasts with luciferase gene damaged by UV-C irradiation revealed that DNA repair ability in fibroblasts from the patient was significantly lower than that in fibroblasts from normal individuals, but not as low as that in fibroblasts from the patient with XP-A (Fig. 1c). Complementation assay revealed that transfection of the XPF gene led most efficiently to recovery of luciferase activity compared with the other XP genes (Fig. 1d). These examinations using fibroblasts from patients and normal individuals were performed under the permission of the ethics committee at The Osaka Medical College. Based on the results, the patient was diagnosed with XP-F and provided with instruction in suitable protection from sunlight, including the use of sunscreen.
DISCUSSION Xeroderma pigmentosum-F has been clinically characterized by late onset, ease of sunburn from sunlight exposure, pigmentation on sunlight-exposed regions, low incidence of cutaneous malignant tumors and very low incidence of neurological involvement.8 Our patient was thus considered to have typical symptoms of XP-F, given the pigmentation on sunlightexposed regions, and absence of both cutaneous malignant tumors and neurological involvement. To the best of our knowledge, 23 cases of Japanese patients (six males, 17 females) with XP-F have been reported, including the present case (Table 1).9–15 The mean age at first medical consultation is 41.7 years (range, 5–73). Among the 22 patients for whom the involvement of cutaneous malignant tumors was previously described, 11 had cutaneous malignant tumors including BCC in nine of 11 patients and SCC in four of 11 patients. In contrast to previous descriptions of a low incidence of cutaneous malignancy,8 our review suggested a relatively high prevalence of 50% (11/22) for cutaneous malignant tumors; these may be novel findings regarding XP-F. A significant difference was evident in the mean age at first medical consultation between patients with cutaneous malignant tumors (53.6 years) and patients without such tumors (30.8 years) (Fig. 2). This fact suggests that early diagnosis is important to prevent onset of the tumor. In the present case, the patient was 50 years old, which was close to the mean age in the patient group with cutaneous malignant tumors. Nevertheless, this patient showed no cutaneous malignancy. This fact may be attributable to the
© 2015 Japanese Dermatological Association
relatively low level of exposure to sunlight; the patient had avoided sunlight exposure by not participating in outdoor activities during her student days and by protecting herself against sunlight, even when playing outdoor tennis through the years of her adult life. This suggests the possibility that an educational campaign to limit lifetime sunlight exposure may contribute to reducing the risk of developing cutaneous malignant tumors in individuals with XP-F who have not yet been diagnosed, as well as those patients who have been diagnosed.
CONFLICT OF INTEREST:
The authors have no conflicts
of interest.
REFERENCES 1 Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ. Fitzpatricks dermatology in general medicine, 7th edn. Mcgraw-hill, New York 2007; 1311–1320. 2 Yagi T, Katsuya A, Koyano A, Takabe H. Sensitivity of group F xeroderma pigmentosum cells to UV and mitomycin C relative to levels of XPF and ERCC1 overexpression. Mutagenesis 1998; 13: 595–599. 3 Johnson RE, Kondratick CM, Prakash S, Prakash L. hRAD30 mutations in the variant form of xeroderma pigmentosum. Science 1999; 285: 263–265. 4 Tamura D, DiGiovanna JJ, Kraemer KH. Founder mutations in xeroderma pigmentosum. J Invest Detmatol 2010; 130: 1491–1493. 5 Kraemer KH, DiGiovanna JJ. Xeroderma pigmentosum. Genereviews [internet]. University of Washington, Seattle 2014. 6 Moriwaki S, Nisigori C. Recent progress in the diagnosis of xeroderma pigmentosum (in Japanese). Clin Dermatol 1999; 53: 79–83. 7 Sethi M, Lehmann AR, Fawcett H et al. Patients with xeroderma pigmentosum complementation group C, E and V do not have abnormal sunburn reactions. Br J Dermatol 2013; 169: 1279–1287. 8 Moriwaki S, Nishigori C, Imamura S et al. A case of xeroderma pigmentosum complementation group F with neurological abnormalities. Br J Dermatol 1993; 128: 91–94. 9 Kondo S, Miyamoto C, Keong CH et al. Sib patients bearing basaliomas in xeroderma pigmentosum complementation group F (in Japanese). Nishinihon J Dermatol 1990; 52: 279–284. 10 Ito T, Watanabe H, Yamaizumi M, Ono T. A case of young XPF with basal cell carcinoma (in Japanese). Jpn J Dermatol 1995; 105: 424. 11 Yasue T, Hiraiwa A, Matsumoto Y et al. A case of xeroderma pigmentosum group F (in Japanese). Jpn J Dermatol 1998; 108: 883. 12 Kato Y, Muro Y, Yasue T, Matsumoto Y, Ohashi M, Yagi T. AntiCENP-F antibody in a patient with xeroderma pigmentosum (in Japanese). Jpn J Dermatol 2000; 110: 301–306. 13 Minamino Y, Fujisawa H, Imakado S, Otsuka F, Yamaizumi M. A case of xeroderma pigmentosum group F (in Japanese). Jpn J Dermatol 2002; 112: 866. 14 Asai M, Koike Y, Tomimura S, Takenaka M, Utani A. Long-term follow up of a case of xeroderma pigmentosum complementation group F (in Japanese). Nishinihon J Dermatol 2013; 75: 508–510. 15 Matsumura Y, Nishigori C, Yagi T, Imamura S, Takabe H. Characterization of molecular defects in xeroderma pigmentosum group F in relation to its clinically mild symptoms. Hum Mol Genet 1998; 7: 969–974.
899
