nonacral melanomas
Soo Hyeon Bae, MD,aHyun Ju Seon, MD, PhD,bYoo Duk Choi, MD, PhD,c Hyun-Jeong Shim, MD, PhD,dJee-Bum Lee, MD, PhD,aand Sook Jung Yun, MD, PhDa
Gwangju, Korea
Background: Although other primary systemic cancers in patients with melanoma have been studied, there have been few focusing on acral melanomas.
Objectives: We assessed other primary systemic cancers in patients with acral and nonacral melanomas.
Methods: We analyzed other primary cancers in 452 patients with melanoma from 1994 to 2013.
Metachronous cancers were defined as those given a diagnosis more than 2 months after diagnosis of melanoma. The others were considered prechronous or synchronous cancers.
Results: Among 51 cases of other primary cancers, gastrointestinal cancer (35.3%, n = 18/51) was the most common, followed by thyroid (17.6%), lung (11.8%), and breast (5.9%). Those were more prevalent in the acral melanoma group (12.8%, n = 31/243) compared with the nonacral melanoma group (9.6%, n = 20/209). Of 23 cases of metachronous cancer, the risk was the highest in bone marrow, followed by oral cavity, bladder, colon, lung, and thyroid. Among 28 cases of prechronous or synchronous cancers, gastrointestinal tract (35.7%, n = 10/28) was the most common site, followed by thyroid (17.9%), breast (10.7%), and lung (7.1%).
Limitations: The study is limited by a small number of patients.
Conclusion: Careful follow-up and imaging studies are necessary for early detection of other primary cancers and metastatic lesions in patients with melanoma. ( J Am Acad Dermatol 2016;74:333-40.) Key words: acral melanoma; metachronous cancer; nonacral melanoma; other primary systemic cancer;
prechronous or synchronous.
M
elanoma is associated with the highest fatality rate among skin cancers.Unfortunately, several studies have shown an extra susceptibility for other primary systemic cancers in patients with melanoma, which also in- crease mortality and reduces the overall life quality of patients.1-3Crocetti and Carli4showed an increased
From the Departments of Dermatology,aRadiology,bPathology,c and Oncology,dChonnam National University Medical School.
Drs Soo Hyeon Bae and Hyun Ju Seon contributed equally to all aspects of this article.
This study was supported by a grant (HCRI 15 016-21) from Chonnam National University Hwasun Hospital Institute for Biomedical Science and by Leading Foreign Research Institute Recruitment Program through the National Research Founda- tion of Korea funded by the Ministry of Education, Science, and Technology (2011-0030034).
Conflicts of interest: None declared.
Accepted for publication September 22, 2015.
Reprint requests: Sook Jung Yun, MD, PhD, Department of Dermatology, Chonnam National University Medical School, 160 Baekseo-ro, Dong-gu, Gwangju 501-746, Korea (South).
E-mail:sjyun@chonnam.ac.kr.
Published online November 15, 2015.
0190-9622/$36.00
Ó 2015 by the American Academy of Dermatology, Inc.
http://dx.doi.org/10.1016/j.jaad.2015.09.047 Abbreviations used:
ALM: acral lentiginous melanoma CI: confidence interval NMSC: nonmelanoma skin cancer SIR: standardized incidence ratio SSM: superficial spreading melanoma
333
risk of second primary cancers in patients with melanoma, especially in those aged 60 years or younger. Several studies have reported the prevalence of specific cancers in patients with melanoma: non- Hodgkin lymphoma,1chronic lymphocytic leukemia,5 female breast,1,6 ovary,6 endometrium,7 testis,8 prostate,1kidney,9bladder,10brain,11and colon.7
Acral melanomas, which involve the acral sites such as palm, sole, and subungual areas, are common in Asian countries, comprising up to 71.4% of all patients with melanoma.12-14 In Caucasians, on the other hand, nonacral melanomae primarily, superficial sprea- ding melanoma (SSM)eis the prevalent type.15Interestingly, Asian Americans who share the same environmental back- ground with non-Hispanic white Americans nevertheless showed different anatomical sites, subtypes, and stages of melanoma.16Also, it was sug- gested that the development of cancer can differ among each subtype of melanoma.
Nagore et al17revealed a strong relation between acral lentiginous melanoma (ALM) and personal/familial nonskin cancer history, as compared with other sub- types, which suggests a different genetic and/or environmental cause relative to different melanoma subtypes.
The first aim of this study was to evaluate an association of melanoma with other primary systemic cancers, diagnosed both before and after melanoma, in patients with melanoma. Although previous reports only focused on the risk of second primary cancers (diagnosed after melanoma) in patients with melanoma,1,2,4,7 we analyzed the whole history of other primary cancers in patients with melanoma. We reasoned that the genetic and/or environmental cause shared in both melanoma and nonmelanoma cancers should be emphasized. Also, the temporal ordering between melanoma and nonmelanoma cancer can be questionable because delayed diagnosis of melanoma in clinical fields is frequent, especially in the case of acral mela- nomas.18,19 Secondly, we sought to examine the pattern of other primary cancers between patients with acral and nonacral melanoma. Most previous studies focused on nonacral melanoma rather than acral melanoma.15 In this study, however, the
prevalence of both acral and nonacral melanoma was similar (53.8% and 46.3%, respectively). We think that comparing both types of melanoma with a balanced number of patients within the same ethnicity allows for a more precise analysis of clinicopathologic and etiologic features. This study not only represents the overall risk of other primary cancers in patients with mel- anoma, but also a balanced analysis between acral and nonacral melanoma.
METHODS Patients
A total of 468 patients with melanoma were identified from Chonnam National University Hospital, Gwangju and Chonnam National University Hwasun Hospital, Hwasun, in Korea (between January 1, 1994, and December 31, 2013). The medical records and histo- pathological reports, including demographics, clinical pre- sentation, histologic features, and follow-up data, were systematically reviewed. The histologic subtypes of melanoma are as follows: ALM, SSM, nodular melanoma, lentigo maligna melanoma, and mucosal melanoma. Otherwise, 13 patients with unclassified melanomas or less frequent variants (eg, desmoplastic) and 3 non-Korean patients were excluded. The patients were divided into acral and nonacral groups, to evaluate the influence of melanoma location on the development of nonmela- noma primary cancers. The institutional review boards of the hospitals approved this retrospective study.
Other primary systemic cancer
The data for other primary systemic cancers were obtained from Gwangju-Jeonnam Cancer Registry and clinicohistopathological diagnoses made in the pathology department of above hospitals (until December 31, 2013). Histopathological diagnosis of primary cancer was confirmed by excluding the probability that one is a metastatic lesion originating from the other. To avoid potential selection bias, metachronous (second or tertiary) primary cancer was defined as those cancers diagnosed more than 2 months apart after diagnosis of melanoma.4 In our study, second primary melanomas4 and non- melanoma skin cancer (NMSC) were excluded.
The others were considered prechronous or CAPSULE SUMMARY
d Other primary systemic cancers occurred in patients with acral and nonacral melanomas.
d Gastrointestinal cancer was the most frequent other primary systemic cancer combined with melanoma, followed by thyroid, lung, and breast. Those cancers were more prevalent in the acral melanoma group than in the nonacral melanoma group.
d Careful follow-up examinations and imaging studies are necessary for early detection of other primary systemic cancers and metastatic lesions to improve survival in patients with melanomas.
synchronous primary cancers, which were diag- nosed before or within 2 months of the diagnosis of melanoma, respectively.
Statistical method
Statistical analyses were performed using soft- ware (SPSS, IBM Corp, Armonk, NY). We used t test and analysis of variance to determine significant differences between group means. Epidemiologic, clinical, and histopathological data were analyzed usingx2and Fisher exact tests.
Standardized incidence ratio (SIR), a ratio of observed/expected number of cancers, was used as a relative measure of the risk that a patient with melanoma will develop a metachronous primary cancer. To obtain the expected number of each systemic cancer, we multiplied the number of person-years by the national age- and sex-specific incidence rates for each year separately for these cancer sites. Person-years at risk were calculated from the date of diagnosis of melanoma to the date of death (death certificate database of statistics in Korea ending December 31, 2012), the date last known alive, or December 31, 2013. A 95% confidence interval (CI) was calculated by assuming a Poisson distribution of the observed number of cases. Thex2 and Fisher exact tests were used to analyze prechro- nous and synchronous primary cancers.
RESULTS
Patient characteristics: Acral and nonacral melanomas
Among 452 patients with melanoma, the average age at diagnosis was 64.4 years (median age 67 years). There were 208 male and 244 female patients with a male-to-female ratio of 0.9:1. The acral area was the most common lesion site, accounting for 53.8% of all cases (n = 243/452, 163 volar and 80 subungual), followed by head and neck (24.8%, n = 112), extremities (9.3%, n = 42), trunk (6.6%, n = 30), and other sites (5.5%, n = 25). The mean duration to diagnosis of melanoma was 92.5 months (median 36 months). ALM was the most common subtype, comprising 48.5%
(n = 219/452) of all patients, followed by mucosal (19.9%, n = 90), SSM (13.5%, n = 61), nodular melanoma (10.6%, n = 48), and lentigo maligna melanoma (7.5%, n = 34) (Table I).
The number of patients with acral and nonacral melanoma was 243 and 209, respectively. The average age at diagnosis of both groups was 63.4 and 61.3 years, respectively. The male-to-female ratios were 1.0:1 and 0.7:1, respectively. Although ALM (90.1%) was the most prevalent histopathologic subtype of the acral melanoma group, mucosal
(43.1%) and SSM (28.2%) subtypes were the most prevalent in the nonacral melanoma group (Table II).
Other primary systemic cancers in patients with melanoma
Within all 452 patients with melanoma, 48 patients had 1 other primary systemic cancer (51 other primary cancers; 3 patients had triple primary cancers). Gastrointestinal cancer was the most common comprising 35.3% (n = 18/51) of all other primary cancers, followed by thyroid (17.6%, n = 9), lung (11.8%, n = 6), breast (5.9%, n = 3), and others (49.0%, n = 25).
Table I. Demographics of patients with melanoma
Characteristic
Patients with melanoma
Total patients, n 452
Age at diagnosis, y (mean6 SD) 64.46 12.8 Gender
Male 208 (46.0)
Female 244 (54.0)
Site of lesion
Head and neck 112 (24.8)
Trunk 30 (6.6)
Extremities 42 (9.3)
Acral 243 (53.8)
Volar 163 (36.1)
Palm 8 (1.8)
Sole 155 (34.3)
Subungual 80 (17.7)
Fingernail 41 (9.1)
Toenail 39 (8.6)
Others 25 (5.5)
Duration to diagnosis, mo (mean6 SD) 92.56 139.3 Histologic subtype
ALM 219 (48.5)
SSM 61 (13.5)
NM 48 (10.6)
LMM 34 (7.5)
Mucosal 90 (19.9)
Pre/synchronous primary cancer*
Gastrointestinal 10 (35.7)
Thyroid 5 (17.9)
Lung 2 (7.1)
Breast 3 (10.7)
Othery 8 (25.6)
Total 28 (100)
Data are given as number (percentage) of participants unless otherwise indicated.
ALM, Acral lentiginous melanoma; LMM, lentigo maligna melanoma;
NM, nodular melanoma; SSM, superficial spreading melanoma.
*Second primary melanoma and nonmelanoma skin cancers were excluded.
yIncludes bladder, bone marrow, brain, kidney, and prostate cancer.
Other primary systemic cancers were more prevalent in the acral melanoma group (12.8%, n = 31/243) compared with the nonacral melanoma group (9.6%, n = 20/209) without a statistically significant difference. Gastrointestinal (n = 11), lung (n = 5), bone marrow (n = 4), and kidney (n = 3) cancers were more common in the acral melanoma group compared with the nonacral group. On the other hand, thyroid (n = 7) and breast (n = 3) cancers were more common in the nonacral melanoma group compared with the acral mela- noma group (Table III).
Metachronous primary cancer (>2 months after melanoma)
Among 452 patients with melanoma, 23 meta- chronous primary cancers were diagnosed in 20
patients (3 patients had triple primary cancers).
Overall, 23 cancers were observed versus 10.7 expected, corresponding to a SIR of 2.2 (95% CI 1.4-3.2). The SIR was 2-fold higher in men (SIR 3.4, 95% CI 1.9-5.6) compared with women (SIR 1.3, 95%
CI 0.6-2.5). The risk was significantly increased among subjects aged 60 years and older (SIR 2.3, 95% CI 1.4-3.6), especially in men (SIR 4.2, 95% CI 2.4-6.9) (Table IV).
When comparing risks of each metachronous primary cancer, the SIR was significantly elevated for the development of bone marrow (SIR 100, 95%
CI 2.5-557.2), oral cavity (SIR 50, 95% CI 1.3-278.6), bladder (SIR 16.7, 95% CI 2.0-60.2), colon (SIR 13.89, 95% CI 4.5-32.4), lung (SIR 5.19, 95% CI 1.4-13.3), and thyroid (SIR 4.08, 95% CI 1.1-10.5) cancer. The risks were also higher in other sites, including the cervix (SIR 7.14, 95% CI 0.2-39.8), pancreas (SIR 2.63, 95% CI 0.1-14.7), and stomach (SIR 1.92, 95% CI 0.2-6.9) without the difference amounting to statistical significance. Among 9 male patients with metachronous primary cancer, who were aged 60 years or older, the most common site of cancer was the colon (44.4%), followed by lung (33.3%).
Difference in the risk of metachronous primary cancer was not statistically significant between patients with acral melanoma (5.3%, n = 13/243) and nonacral melanoma (4.8%, n = 10/209). Within the acral melanoma group, the risk was increased in the volar group compared with the subungual group, without a statistically significant difference. Among patients with nonacral melanoma, there was no notable difference among the 4 subtypes (Table V).
Prechronous and synchronous primary cancers (before and within 2 months from melanoma)
The most common site of prechronous and syn- chronous primary cancers was the gastrointestinal tract (35.7%, n = 10/28), followed by thyroid (17.9%, n = 5), breast (10.7%, n = 3), lung (7.1%, n = 2), and others (25.6%, n = 8) (Table I).
Prechronous and synchronous primary cancers were more prevalent in the acral melanoma group (7.4%, n = 18/243) compared with the nonacral melanoma group (4.8%, n = 10/209), without a statistically significant difference. Gastrointestinal (n = 7) and lung (n = 2) cancers were more common in the acral melanoma group compared with the nonacral group. On the other hand, breast (n = 3) cancer was more common in the nonacral melanoma group compared with the acral melanoma group (Table II). However, a statistically significant differ- ence was not shown in all cases, perhaps because of the relatively small sample size.
Table II. Differential characteristics between patients with acral and nonacral melanoma
Characteristic
Acral melanoma
Nonacral
melanoma P value
Total patients, n 243 209
Age, y (mean6 SD) 63.4 6 12.7 61.3 6 14.8 .108 Age distribution
at diagnosis, y
.018
\30 0 (0) 6 (2.9)
30-59 83 (34.2) 76 (36.4)
$60 160 (65.8) 127 (60.8)
Gender .034
Male 123 (50.6) 85 (40.7)
Female 120 (49.4) 124 (59.3) Duration to
diagnosis, mo (mean6 SD)
59.56 98.3 71.3 6 141.2 .356
Histologic subtype \.001
ALM 219 (90.1) 0 (0)
SSM 2 (0.8) 59 (28.2)
NM 22 (9.1) 26 (12.4)
LMM 0 (0) 34 (16.3)
Mucosal 0 (0) 90 (43.1)
Pre/synchronous primary cancer*
Gastrointestinal 7 (38.9) 3 (30)
Thyroid 2 (11.1) 3 (30)
Lung 2 (11.1) 0 (0)
Breast 0 (0) 3 (30)
Othery 7 (38.9) 1 (10)
Total 18 (100) 10 (100)
Data are given as number (percentage) of participants unless otherwise indicated.
ALM, Acral lentiginous melanoma; LMM, lentigo maligna melanoma; NM, nodular melanoma; SSM, superficial spreading melanoma.
*Second primary melanoma and nonmelanoma skin cancers were excluded.
yIncludes bladder, bone marrow, brain, kidney, and prostate cancer.
DISCUSSION
In our study, gastrointestinal tract, thyroid, and lung cancers were commonly detected in patients with melanoma. Although previous reports focusing
on Caucasians have shown significant associations between melanoma and different cancers/cancer sites, such as non-Hodgkin lymphoma,1 chronic lymphocytic leukemia,5 ovary,6 endometrium,7 testis,8and prostate,1none of these were observed in our patients. This result also raises the possibility of genetic and environmental disparity among ethnicities for the development of malignancies.
The risk of metachronous primary cancer was significantly higher for subjects 60 years of age and older (SIR 2.3), especially among the men in that group (SIR 4.2). This also differs from the results of Swerdlow et al11 and Wassberg et al7 regarding Caucasians, which showed significant increases of metachronous primary cancer in ages younger than 50 and 60 years, respectively. Considering the early onset of other primary cancer, genetic susceptibility can be relatively more important in metachronous primary cancer for Caucasians, whereas environ- mental factors can be relatively more important in Asians who show late onset of other primary cancer.
In our study, the risk of metachronous primary cancer was the highest in bone marrow, followed by oral cavity, bladder, colon, lung, and thyroid.
Although the type of metachronous primary cancers differs among studies, the representative cancers in previous studies on Caucasians were non-Hodgkin lymphoma,1,4female breast cancer,1,20and prostate cancer,1,21 with the exception of melanoma and NMSC. The trend of metachronous cancer in our study totally differed from those of previous studies.
Table IV. A comparison of expected versus observed incidences of metachronous primary cancers with different ages and gender
Group
No. of patients
Metachronous primary cancers
SIR (95% CI) Observed Expected
All patients
Total 452 23 10.71 2.15 (1.4-3.2)
Men 208 15 4.44 3.38 (1.9-5.6)
Women 244 8 6.27 1.28 (0.6-2.5)
Age\30 y
Total 6 1 0 NA
Men 0 0 0 -
Women 6 1 0 NA
30# Age \ 60 y
Total 159 6 2.41 2.49 (0.9-5.4)
Men 75 3 0.88 3.41 (0.7-9.7)
Women 84 3 1.53 1.96 (0.4-5.8)
Age$60 y
Total 287 19 8.30 2.29 (1.4-3.6)
Men 133 15 3.56 4.21 (2.4-6.9)
Women 154 6 4.74 1.27 (0.5-2.8)
Second primary melanoma and nonmelanoma skin cancers were excluded. Three patients had triple primary cancer.
CI, Confidence interval; NA, not assessed; SIR, standardized incidence ratio.
Table III. Histologic subtypes of other primary systemic cancers in patients with melanoma
Primary cancer
Acral melanoma Nonacral melanoma
Pre/synchronous Metachronous Pre/synchronous Metachronous
Site (n) Site (n) Site (n) Site (n) Site (n)
Bladder (4) Bladder (1) Bladder (1) Bladder (1) Bladder (1)
Bone marrow (4) Bone marrow (3) Bone marrow (1)
Brain (1) Brain (1)
Breast (3) Breast (3)
Cervix (1) Cervix (1)
Colon (10) Colon (4) Colon (2) Colon (1) Colon (3)
Kidney (2) Kidney (1) Kidney (1)
Liver (1) Liver (1)
Lung (6) Lung (2) Lung (3) Lung (1)
Oral cavity (1) Oral cavity (1)
Pancreas (1) Pancreas (1)
Periampullary (1) Periampullary (1) Prostate (1) Prostate (1)
Stomach (5) Stomach (2) Stomach (2) Stomach (1)
Thymus (1) Thymus (1)
Thyroid (9) Thyroid (2) Thyroid (3) Thyroid (4)
Total (51) Acral (31) Nonacral (20)
Data are given as number.
Second primary melanoma and nonmelanoma skin cancers were excluded. Three patients had triple primary cancers.
Table V. Incidences of each metachronous primary cancer between patients with acral and nonacral melanoma according to the different subtypes
Primary cancer
Acral melanoma Nonacral melanoma
Total (n = 243) Subungual (n = 80) Volar (n = 163) Total (n = 209)
Mucosal (n = 90)
SSM (n = 59)
LMM (n = 34)
NM (n = 26) No. (%) Interval*
ALM (n = 72)
NM (n = 8)
ALM (n = 147)
NM (n = 14)
SSM
(n = 2) No. (%) Interval*
All sites 13 (5.3) 30.96 35.4 2 (2.5) 10 (6.1) 10 (4.8) 28.86 44.3 4 (4.4) 3 (5.1) 2 (5.9) 1 (3.8)
Bladder 1 (0.4) 2.8 - - 1 (0.6) - - 1 (0.5) 17.6 1 (1.1)
Bone marrow 1 (0.4) 12.7 1 (1.3) - - - -
Brain - - - - -
Breast - - - - -
Cervix - - - 1 (0.5) 109.7 1 (1.1)
Colon 2 (0.8) 15.26 20.2 - - 2 (1.2) - - 3 (1.4) 3.96 1.1 2 (2.2) 1 (2.9)
Kidney 1 (0.4) 65.8 - - 1 (0.6) - -
Liver - - - - -
Lung 3 (1.2) 48.36 57.0 1 (1.3) - 2 (1.2) - - 1 (0.5) 38.6 1 (1.7)
Oral cavity 1 (0.4) 57.1 - - 1 (0.6) - -
Pancreas 1 (0.4) 72.3 - - 1 (0.6) - -
Periampullary - - - - -
Prostate - - - - -
Stomach 2 (0.8) 5.26 5.5 - - 2 (1.2) - -
Thymus 1 (0.4) 3 - - 1 (0.6) - -
Thyroid - - - 4 (1.9) 30.06 53.4 2 (3.4) 1 (2.9) 1 (3.8)
Data are given as number (percentage) of participants unless otherwise indicated.
Second primary melanoma and nonmelanoma skin cancers were excluded. Three patients had triple primary cancers.
ALM, Acral lentiginous melanoma; LMM, lentigo maligna melanoma; NM, nodular melanoma; SSM, superficial spreading melanoma.
*Time interval between diagnosis of melanoma and metachronous primary cancer, mo, mean (6SD). FEBRUARY2016 JAMACADDERMATOLetal
Although this may result from the small number of patients in our study, there is still a potential possibility for a difference between Asians and Caucasians relative to different genetic and environmental disparities in the development of melanoma. Therefore, there is a need for a balanced evaluation between different ethnicities and different melanoma groups, especially between acral and nonacral groups.
The incidence and histopathologic types of other primary systemic cancers differed between patients with acral and nonacral melanoma in our results. The acral melanoma group, which is the predominant subtype of melanoma in Asians,12-14 revealed a higher incidence of other primary cancers compared with the nonacral melanoma group. Thyroid (n = 7) and breast (n = 3) cancers were relatively common in the nonacral melanoma group, although only 2 cases of thyroid cancer and no cases of breast cancer were in the acral melanoma group. It is well known that both nonacral melanoma and thyroid papillary cancers have a strong relation with the BRAF mutation.22,23 Also, Hollestelle et al24reported that 10% of breast cancer cell lines were associated with the BRAF mutation. Along with these reports, our results also strongly suggest a genetic relevance among these cancers.
In our study, prechronous and synchronous cancers were also more prevalent in the acral melanoma group, compared with the nonacral melanoma group. On the other hand, the risks of metachronous cancer between patients with acral and nonacral melanoma showed no notable difference. This differed from results of Nagore et al17 with Caucasians, which revealed frequent metachronous primary cancer in patients with ALM compared with those of other histologic subtypes (22.2% vs 7.1%). However, patients without ALM outnumbered those with ALM (932 vs 46 patients) in that study, and the ethnicities of the patients differed from those of our study. Although the major type of metachronous primary cancer in patients with nonacral melanoma was thyroid cancer (44.4%), the acral melanoma group showed a diverse distribution, composed of single cases of bladder, oral cavity, pancreas, periampullary, and thymic cancer in our study. Colon and lung cancer were commonly observed in both the acral and nonacral melanoma groups (6 vs 4, and 5 vs 1) regardless of the time of diagnosis. For the early detection of those cancers, careful follow-up examinations and imaging studies are needed.
Ultraviolet light is a well-known risk factor to induce both nonacral melanoma and NMSC, whereas its relevance to acral melanoma is
weak.17,25,26 Considering that NMSC is strongly associated with ultraviolet, the extremely low prevalence of NMSC in our study (n = 1) suggests that sun exposure is a less important contributing factor in the development of melanoma in Asians.
Also, individual genetic predisposition and other environmental factors, rather than ultraviolet, can be considered more important in carcinogenesis of other primary cancers and melanoma in Asians. For example, Green et al27 suggested physical trauma and chemical exposure as major events predisposing acral melanoma. Jung et al28 also elucidated the importance of trauma by showing a higher prevalence of melanomas at pressure-susceptible sites, such as the center of the heels and the inner aspect of the foot, and at sites following the long axis along natural creases of the soles.
Because major limitations in this study include small number of patients, the short-term follow-up period, and retrospective studies, a further prospec- tive investigation of melanomas with a larger patient group and longer follow-up period is needed for better understanding the genetic and environmental relations between specific melanoma subtypes and the development of other primary systemic cancer.
In conclusion, the high risk of multiple primary cancers in patients with melanoma necessitates careful follow-ups and systemic evaluations.
Especially, internal organ cancers such as gastrointestinal, lung, breast, or thyroid cancer, which were relatively prevalent in our study, require a special imaging study, such as enhanced computed tomography or positron emission/computed tomography or ultrasonography for early detection.
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