Journal of Dermatology 2014; 41: 1102–1105
doi: 10.1111/1346-8138.12679
CONCISE COMMUNICATION
Comparison of facial predilection sites for cutaneous squamous cell carcinoma and actinic keratosis in Japanese patients Yoshitsugu SHIBAYAMA, Shinichi IMAFUKU Department of Dermatology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
ABSTRACT Cutaneous squamous cell carcinoma (cSCC) and actinic keratosis (AK) occur most often on the face. Ultraviolet light is apparently their most common cause. As AK is considered to be a precursor of cSCC, their distribution on the face should be similar. However, cSCC often occurs on the temple or mandibular area, whereas AK arises on the central forehead, cheek or nose. We retrospectively evaluated differences in affected site distribution for cSCC (n = 54) and AK (n = 95). We found AK to occur preferentially on the central facial area (63/95, 66%), which is the most sun-exposed area, and cSCC to occur preferentially on peripheral areas such as the temple and mandibular area (24/54, 44%). Those distributions were significantly different (P = 0.011, Fisher’s exact test). This result suggests that cSCC occurs preferentially in the peripheral area compared with the central facial area, which further implies that either other factors are needed to make AK progress to cSCC in peripheral areas, or that peripheral cSCC can occur without preceding AK. This is the first report to focus on geographic assessment of cSCC and AK in detail. Further studies are needed to elucidate the mechanism of our finding.
Key words:
actinic keratosis, carcinogenesis, cutaneous squamous cell carcinoma, predilection site, ultraviolet.
INTRODUCTION Cutaneous squamous cell carcinoma (cSCC) is one of the most common malignancies, found on sun-damaged skin, burn scars and/or traumatic scars. As cSCC occurs most on sunexposed areas such as the face, ultraviolet light is considered its most common cause.1 Actinic keratosis (AK) also occurs on the sun-exposed areas (face, auricle and dorsum of hand) and is widely regarded as a neoplastic precursor of cSCC.2–5 If we assume that all AK on the face progress to cSCC with the same percentage, the distribution of sites for both lesions should accord. However, in our clinical experience in Japan, cSCC often occurs on the temple or mandibular area, whereas AK arises on the central forehead, cheeks or nose. To prove the distribution of these two neoplasms, we retrospectively evaluated differences in their predilection sites among our patients.
METHODS
atypical cells into the dermis. We excluded patients whose photographs did not offer sufficient details on their tumors’ locations. We also excluded cSCC on the lips and adnexal cancer, as their risk factors differ from those of most facial cSCC.
Patients with AK From the same database of our institution, we identified patients diagnosed pathologically with facial AK after incisional biopsy or excisional resection between January 2009 and March 2013. We included any histopathological type of AK (e.g. bowenoid, basal only). We excluded patients whose photographs did not offer sufficient details on their lesions’ locations.
Geographic distribution of facial lesions We divided the facial area into eight parts: (a) zygomatic arch; (b) buccal area; (c) mandibular area (from preauricular area to chin); (d) temple; (e) central forehead; (f) nose; (g) auricle; and (h) scalp (Fig. 1).
Patients with cSCC From the database of the Department of Dermatology at Fukuoka University Hospital, we identified patients who were pathologically diagnosed with facial cSCC after incisional or excisional resection between January 1998 and March 2013. We defined cSCC as when there was any clear microinvasion of
Statistical analysis Statistical analyses were performed with SPSS II for Windows (SPSS, Chicago, IL, USA). Student’s t-test, v2-test and Fisher’s exact test were used to determine statistical significance. P < 0.05 was considered statistically significant. When multiple
Correspondence: Yoshitsugu Shibayama, M.D., Department of Dermatology, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0133, Japan. Email: [email protected] Received 23 June 2014; accepted 15 September 2014.
1102
© 2014 Japanese Dermatological Association
Most likely facial sites for cSCC and AK
Figure 1. Geographic distribution of facial lesions. (a) Zygomatic arch, (b) buccal area, (c) mandibular area (from preauricular area to chin), (d) temple, (e) central forehead, (f) nose, (g) auricle and (h) scalp. comparison (n = 11) was performed, Bonferroni’s correction was employed and significant P-value level was set P < 0.05/ 11 = 0.0045.
RESULTS A total of 54 patients with 54 facial cSCC lesions and 91 patients with 95 facial AK lesions were identified (Table 1). Some patients had histopathologically established cSCC and clinically suspicious AK (without biopsy) at the same time.
Such patients were included in the cSCC group only and not in the AK group because AK is not established histopathologically by skin biopsy or resection. Three patients were included in both groups. Three of two patients had cSCC and AK on different areas at different times and another one was the only case of AK on the temple and was confirmed to have progressed to cSCC pathologically in 4 months. Of the 54 patients with cSCC, 26 were men and 28 were women; of the 91 patients with AK, 25 were men and 66 were women (P = 0.012). Mean ages were 80.6 years (range, 34–98) for cSCC and 78.6 years (range, 42–96) for AK (P = 0.086). Percentages of lesions on the left side, right side and central area, respectively, were 46%, 35% and 19% for cSCC, and 43%, 47% and 10% for AK (P = 0.173). Facial cSCC occurred most often on the temple (d, 24%), mandibular area (c, 20.3%), zygomatic arch (a, 12.9%), nose (f, 11.1%), buccal area (b, 9.2%), central forehead (e, 7.4%), auricle (g, 7.4%) and scalp (h, 7.4%). Facial AK occurred most often on the zygomatic arch (a, 26.3%), nose (f, 23.1%), buccal area (b, 16.8%), temple (d, 11.5%), central forehead (e, 8.4%), mandibular area (c, 7.3%), auricle (g, 3.1%) and scalp (h, 3.1%) (Table 1). These distribution patterns differed significantly (P = 0.011; Fisher’s exact test). The ratio of frequency of cSCC and AK was the largest in the mandibular area (2.78) and the smallest in the nose (0.48) and zygomatic arch (0.49) (Fig. 2a). Furthermore, 44% of cSCC occurred significantly more on the facial periphery (mandibular area + temple, [c] + [d]) compared with AK (18.9%) (P = 0.001 < 0.05/11 = 0.0045, a corrected significant P-value level for 11 comparisons). Of 95 AK cases, 47 (49.4%) occurred at the zygomatic arch + nose ([a] + [f]) (usually the heavily sun-exposed part) compared with
Table 1. Tumor characteristics of 145 patients with cSCC or AK cSCC n No. of patients (cases) Average age, years (range) Sex Male Female Left or right Left Right Central Site on the face (a) Zygomatic arch (b) Buccal area (c) Mandibular area (d) Temple (e) Central forehead (f) Nose (g) Auricle (h) Scalp
AK %
54 (54) 80.6 (34–98)
n
%
91 (95) 78.6 (42–96)
Statistics n.s. (P = 0.086)*
26 28
48 52
25 66
27 73
P = 0.012**
25 19 10
46 35 19
41 45 9
43 47 10
n.s. (P = 0.173)**
7 5 11 13 4 6 4 4
12.9 9.2 20.3 24.07 7.4 11.1 7.4 7.4
25 16 7 11 8 22 3 3
26.3 16.8 7.3 11.5 8.4 23.1 3.1 3.1
P = 0.011***
*Student’s t-test; **v2-test; ***Fisher’s exact test. n.s., not significant.
© 2014 Japanese Dermatological Association
1103
Y. Shibayama and S. Imafuku
(a)
(b)
Figure 2. Comparison of facial distribution of cutaneous squamous cell carcinoma (cSCC) and actinic keratosis (AK). (a) Distribution of each of the eight parts in Fig. 1 and the ratio of frequency of cSCC and AK (SCC-to-AK ratio). The ratio was the largest in the mandibular area (2.78) and the smallest in the nose (0.48) and zygomatic arch (0.49). (b) cSCC tended to occur on the facial periphery (mandibular area + temple, [c] + [d]) (P = 0.001). AK tended to occur on the area of the zygomatic arch + nose ([a] + [f]) (P = 0.003), and zygomatic arch + buccal area + nose ([a] + [b] + [f]) (P < 0.001). In this multiple comparison, a corrected P-value of
doi: 10.1111/1346-8138.12679
CONCISE COMMUNICATION
Comparison of facial predilection sites for cutaneous squamous cell carcinoma and actinic keratosis in Japanese patients Yoshitsugu SHIBAYAMA, Shinichi IMAFUKU Department of Dermatology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
ABSTRACT Cutaneous squamous cell carcinoma (cSCC) and actinic keratosis (AK) occur most often on the face. Ultraviolet light is apparently their most common cause. As AK is considered to be a precursor of cSCC, their distribution on the face should be similar. However, cSCC often occurs on the temple or mandibular area, whereas AK arises on the central forehead, cheek or nose. We retrospectively evaluated differences in affected site distribution for cSCC (n = 54) and AK (n = 95). We found AK to occur preferentially on the central facial area (63/95, 66%), which is the most sun-exposed area, and cSCC to occur preferentially on peripheral areas such as the temple and mandibular area (24/54, 44%). Those distributions were significantly different (P = 0.011, Fisher’s exact test). This result suggests that cSCC occurs preferentially in the peripheral area compared with the central facial area, which further implies that either other factors are needed to make AK progress to cSCC in peripheral areas, or that peripheral cSCC can occur without preceding AK. This is the first report to focus on geographic assessment of cSCC and AK in detail. Further studies are needed to elucidate the mechanism of our finding.
Key words:
actinic keratosis, carcinogenesis, cutaneous squamous cell carcinoma, predilection site, ultraviolet.
INTRODUCTION Cutaneous squamous cell carcinoma (cSCC) is one of the most common malignancies, found on sun-damaged skin, burn scars and/or traumatic scars. As cSCC occurs most on sunexposed areas such as the face, ultraviolet light is considered its most common cause.1 Actinic keratosis (AK) also occurs on the sun-exposed areas (face, auricle and dorsum of hand) and is widely regarded as a neoplastic precursor of cSCC.2–5 If we assume that all AK on the face progress to cSCC with the same percentage, the distribution of sites for both lesions should accord. However, in our clinical experience in Japan, cSCC often occurs on the temple or mandibular area, whereas AK arises on the central forehead, cheeks or nose. To prove the distribution of these two neoplasms, we retrospectively evaluated differences in their predilection sites among our patients.
METHODS
atypical cells into the dermis. We excluded patients whose photographs did not offer sufficient details on their tumors’ locations. We also excluded cSCC on the lips and adnexal cancer, as their risk factors differ from those of most facial cSCC.
Patients with AK From the same database of our institution, we identified patients diagnosed pathologically with facial AK after incisional biopsy or excisional resection between January 2009 and March 2013. We included any histopathological type of AK (e.g. bowenoid, basal only). We excluded patients whose photographs did not offer sufficient details on their lesions’ locations.
Geographic distribution of facial lesions We divided the facial area into eight parts: (a) zygomatic arch; (b) buccal area; (c) mandibular area (from preauricular area to chin); (d) temple; (e) central forehead; (f) nose; (g) auricle; and (h) scalp (Fig. 1).
Patients with cSCC From the database of the Department of Dermatology at Fukuoka University Hospital, we identified patients who were pathologically diagnosed with facial cSCC after incisional or excisional resection between January 1998 and March 2013. We defined cSCC as when there was any clear microinvasion of
Statistical analysis Statistical analyses were performed with SPSS II for Windows (SPSS, Chicago, IL, USA). Student’s t-test, v2-test and Fisher’s exact test were used to determine statistical significance. P < 0.05 was considered statistically significant. When multiple
Correspondence: Yoshitsugu Shibayama, M.D., Department of Dermatology, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0133, Japan. Email: [email protected] Received 23 June 2014; accepted 15 September 2014.
1102
© 2014 Japanese Dermatological Association
Most likely facial sites for cSCC and AK
Figure 1. Geographic distribution of facial lesions. (a) Zygomatic arch, (b) buccal area, (c) mandibular area (from preauricular area to chin), (d) temple, (e) central forehead, (f) nose, (g) auricle and (h) scalp. comparison (n = 11) was performed, Bonferroni’s correction was employed and significant P-value level was set P < 0.05/ 11 = 0.0045.
RESULTS A total of 54 patients with 54 facial cSCC lesions and 91 patients with 95 facial AK lesions were identified (Table 1). Some patients had histopathologically established cSCC and clinically suspicious AK (without biopsy) at the same time.
Such patients were included in the cSCC group only and not in the AK group because AK is not established histopathologically by skin biopsy or resection. Three patients were included in both groups. Three of two patients had cSCC and AK on different areas at different times and another one was the only case of AK on the temple and was confirmed to have progressed to cSCC pathologically in 4 months. Of the 54 patients with cSCC, 26 were men and 28 were women; of the 91 patients with AK, 25 were men and 66 were women (P = 0.012). Mean ages were 80.6 years (range, 34–98) for cSCC and 78.6 years (range, 42–96) for AK (P = 0.086). Percentages of lesions on the left side, right side and central area, respectively, were 46%, 35% and 19% for cSCC, and 43%, 47% and 10% for AK (P = 0.173). Facial cSCC occurred most often on the temple (d, 24%), mandibular area (c, 20.3%), zygomatic arch (a, 12.9%), nose (f, 11.1%), buccal area (b, 9.2%), central forehead (e, 7.4%), auricle (g, 7.4%) and scalp (h, 7.4%). Facial AK occurred most often on the zygomatic arch (a, 26.3%), nose (f, 23.1%), buccal area (b, 16.8%), temple (d, 11.5%), central forehead (e, 8.4%), mandibular area (c, 7.3%), auricle (g, 3.1%) and scalp (h, 3.1%) (Table 1). These distribution patterns differed significantly (P = 0.011; Fisher’s exact test). The ratio of frequency of cSCC and AK was the largest in the mandibular area (2.78) and the smallest in the nose (0.48) and zygomatic arch (0.49) (Fig. 2a). Furthermore, 44% of cSCC occurred significantly more on the facial periphery (mandibular area + temple, [c] + [d]) compared with AK (18.9%) (P = 0.001 < 0.05/11 = 0.0045, a corrected significant P-value level for 11 comparisons). Of 95 AK cases, 47 (49.4%) occurred at the zygomatic arch + nose ([a] + [f]) (usually the heavily sun-exposed part) compared with
Table 1. Tumor characteristics of 145 patients with cSCC or AK cSCC n No. of patients (cases) Average age, years (range) Sex Male Female Left or right Left Right Central Site on the face (a) Zygomatic arch (b) Buccal area (c) Mandibular area (d) Temple (e) Central forehead (f) Nose (g) Auricle (h) Scalp
AK %
54 (54) 80.6 (34–98)
n
%
91 (95) 78.6 (42–96)
Statistics n.s. (P = 0.086)*
26 28
48 52
25 66
27 73
P = 0.012**
25 19 10
46 35 19
41 45 9
43 47 10
n.s. (P = 0.173)**
7 5 11 13 4 6 4 4
12.9 9.2 20.3 24.07 7.4 11.1 7.4 7.4
25 16 7 11 8 22 3 3
26.3 16.8 7.3 11.5 8.4 23.1 3.1 3.1
P = 0.011***
*Student’s t-test; **v2-test; ***Fisher’s exact test. n.s., not significant.
© 2014 Japanese Dermatological Association
1103
Y. Shibayama and S. Imafuku
(a)
(b)
Figure 2. Comparison of facial distribution of cutaneous squamous cell carcinoma (cSCC) and actinic keratosis (AK). (a) Distribution of each of the eight parts in Fig. 1 and the ratio of frequency of cSCC and AK (SCC-to-AK ratio). The ratio was the largest in the mandibular area (2.78) and the smallest in the nose (0.48) and zygomatic arch (0.49). (b) cSCC tended to occur on the facial periphery (mandibular area + temple, [c] + [d]) (P = 0.001). AK tended to occur on the area of the zygomatic arch + nose ([a] + [f]) (P = 0.003), and zygomatic arch + buccal area + nose ([a] + [b] + [f]) (P < 0.001). In this multiple comparison, a corrected P-value of
